Fluorescence Turn-on Enantioselective Recognition of both Chiral Acidic Compounds and α-Amino Acids by a Chiral Tetraphenylethylene Macrocycle Amine.

PubMed

Feng, Hai-Tao; Zhang, Xing; Zheng, Yan-Song

2015-08-21

New chiral tetraphenylethylene (TPE) macrocycles bearing optically pure amine groups were synthesized and found to have a discriminating ability between the two enantiomers of not only chiral acidic compounds but also α-amino acids by enantioselective aggregation and aggregation-induced emission (AIE) effects. NMR spectra, including 2D-NOESY, disclosed that the host-guest interaction of the macrocycle receptor played a key role in addition to the acid-base interactions.

A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds.

PubMed

Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R J D; Giacomini, Elisa; Hansen, Mette R; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F; Spring, David R

2015-04-21

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity.

Structures and properties of naturally occurring polyether antibiotics.

PubMed

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

Structures and Properties of Naturally Occurring Polyether Antibiotics

PubMed Central

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties. PMID:23586016

Can a proton be encapsulated in tetraamido/diamino quaternized macrocycles in aqueous solution and electric field?

PubMed

Jiang, Nan; Ma, Jing

2011-09-12

The proton-binding behavior of solvated tetraamido/diamino quaternized macrocyclic compounds with rigid phenyl and flexible phenyl bridges in the absence or presence of an external electric field is investigated by molecular dynamics simulation. The proton can be held through H-bonding interactions with the two carbonyl oxygen atoms in macrocycles containing rigid (phenyl) and flexible (propyl) bridges. The solute-solvent H-bonding interactions cause the macrocyclic backbones to twist to different extents, depending on the different bridges. The macrocycle with the rigid phenyl linkages folds into a cuplike shape due to π-π interaction, while the propyl analogue still maintains the ellipsoidal ringlike shape with just a slight distortion. The potential energy required for proton transfer is larger in the phenyl-containing macrocycle than in the compound with propyl units. When an external electric field with a strength of 2.5 V nm(-1) is exerted along the carbonyl oxygen atoms, a difference in proton encircling is exhibited for macrocycles with rigid and flexible bridges. In contrast to encapsulation of a proton in the propyl analogue, the intermolecular solute-solvent H-bonding and intramolecular π-π stacking between the two rigid phenyl spacers leads to loss of the proton from the highly distorted cuplike macrocycle with phenyl bridges. The competition between intra- and intermolecular interactions governs the behavior of proton encircling in macrocycles. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of Strained 1,3-Diene Macrocycles via Copper-Mediated Castro-Stephens Coupling/Alkyne Reduction Tandem Reactions.

PubMed

Li, Wei; Schneider, Christopher M; Georg, Gunda I

2015-08-07

A copper-mediated macrocyclization involving the reaction of a vinyl iodide and a terminal alkyne followed by an in situ reduction of the enyne intermediate is reported. The reaction generates a conjugated Z-double bond within a strained medium-size lactone, lactam, or ether macrocycle. A variety of macrocyclic compounds bearing different ring sizes and functionalities were synthesized. A complementary stepwise procedure was also developed for less strained ring systems.

Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors.

PubMed

Tang, Jun; Jones, Stacey A; Jeffery, Jerry L; Miranda, Sonia R; Galardi, Cristin M; Irlbeck, David M; Brown, Kevin W; McDanal, Charlene B; Han, Nianhe; Gao, Daxin; Wu, Yongyong; Shen, Bin; Liu, Chunyu; Xi, Caiming; Yang, Heping; Li, Rui; Yu, Yajun; Sun, Yufei; Jin, Zhimin; Wang, Erjuan; Johns, Brian A

2014-01-01

A macrocycle provides diverse functionality and stereochemical complexity in a conformationally preorganized ring structure, and it occupies a unique chemical space in drug discovery. However, the synthetic challenge to access this structural class is high and hinders the exploration of macrocycles. In this study, efficient synthetic routes to macrocyclized betulin derivatives have been established. The macrocycle containing compounds showed equal potency compared to bevirimat in multiple HIV-1 antiviral assays. The synthesis and biological evaluation of this novel series of HIV-1 maturation inhibitors will be discussed.

One-Bead-Two-Compound Thioether Bridged Macrocyclic γ-AApeptide Screening Library against EphA2.

PubMed

Shi, Yan; Challa, Sridevi; Sang, Peng; She, Fengyu; Li, Chunpu; Gray, Geoffrey M; Nimmagadda, Alekhya; Teng, Peng; Odom, Timothy; Wang, Yan; van der Vaart, Arjan; Li, Qi; Cai, Jianfeng

2017-11-22

Identification of molecular ligands that recognize peptides or proteins is significant but poses a fundamental challenge in chemical biology and biomedical sciences. Development of cyclic peptidomimetic library is scarce, and thus discovery of cyclic peptidomimetic ligands for protein targets is rare. Herein we report the unprecedented one-bead-two-compound (OBTC) combinatorial library based on a novel class of the macrocyclic peptidomimetics γ-AApeptides. In the library, we utilized the coding peptide tags synthesized with Dde-protected α-amino acids, which were orthogonal to solid phase synthesis of γ-AApeptides. Employing the thioether linkage, the desired macrocyclic γ-AApeptides were found to be effective for ligand identification. Screening the library against the receptor tyrosine kinase EphA2 led to the discovery of one lead compound that tightly bound to EphA2 (K d = 81 nM) and potently antagonized EphA2-mediated signaling. This new approach of macrocyclic peptidomimetic library may lead to a novel platform for biomacromolecular surface recognition and function modulation.

MacroEvoLution: A New Method for the Rapid Generation of Novel Scaffold-Diverse Macrocyclic Libraries.

PubMed

Saupe, Jörn; Kunz, Oliver; Haustedt, Lars Ole; Jakupovic, Sven; Mang, Christian

2017-09-04

Macrocycles are a structural class bearing great promise for future challenges in medicinal chemistry. Nevertheless, there are few flexible approaches for the rapid generation of structurally diverse macrocyclic compound collections. Here, an efficient method for the generation of novel macrocyclic peptide-based scaffolds is reported. The process, named here as "MacroEvoLution", is based on a cyclization screening approach that gives reliable access to novel macrocyclic architectures. Classification of building blocks into specific pools ensures that scaffolds with orthogonally addressable functionalities are generated, which can easily be used for the generation of structurally diverse compound libraries. The method grants rapid access to novel scaffolds with scalable synthesis (multi gram scale) and the introduction of further diversity at a late stage. Despite being developed for peptidic systems, the approach can easily be extended for the synthesis of systems with a decreased peptidic character. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

How Proteins Bind Macrocycles

PubMed Central

Villar, Elizabeth A.; Beglov, Dmitri; Chennamadhavuni, Spandan; Porco, John A.; Kozakov, Dima; Vajda, Sandor; Whitty, Adrian

2014-01-01

The potential utility of synthetic macrocycles as drugs, particularly against low druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of macrocycles for good target protein-binding activity or bioavailability. To address this knowledge gap we analyze the binding modes of a representative set of macrocycle-protein complexes. The results, combined with consideration of the physicochemical properties of approved macrocyclic drugs, allow us to propose specific guidelines for the design of synthetic macrocycles libraries possessing structural and physicochemical features likely to favor strong binding to protein targets and also good bioavailability. We additionally provide evidence that large, natural product derived macrocycles can bind to targets that are not druggable by conventional, drug-like compounds, supporting the notion that natural product inspired synthetic macrocycles can expand the number of proteins that are druggable by synthetic small molecules. PMID:25038790

Macrocycles

DOEpatents

Raymond, Kenneth N.; Xu, Jide; Pham, Tiffany A.

2016-09-13

The invention provides macrocycles useful in chelating metal ions, particularly radionuclides, to provide metal ion complexes. The invention also provides methods of using the compounds and complexes of the invention, such as in therapeutic and diagnostic applications.

Polyether precursors of molecular recognition systems based on the 9,10-anthraquinone moiety

NASA Astrophysics Data System (ADS)

Wcisło, Anna; Cirocka, Anna; Zarzeczańska, Dorota; Niedziałkowski, Paweł; Nakonieczna, Sandra; Ossowski, Tadeusz

2015-02-01

A series of novel polyether derivatives of 9,10-anthraquinone (AQ) was synthesized and characterized by means of UV-Vis spectroscopy, acid-base titration and complexometric titration. The results were compared with 1-NEt2AQ and 1-NHEtAQ - model compounds of alkylaminoanthraquinones. Acetonitrile and methanol were used as solvents for determination of spectroscopic and acid-base properties. Complexometric titrations were carried out exclusively in acetonitrile. Spectral characteristic of these compounds strongly depends on pH. Addition of acid causes the decrease of absorption intensity and in some cases also a shift of the visible range band. The weakest base is the compound (2), and the strongest - compound (1), both in methanol and acetonitrile solution. The introduction of an additional substituent in the position 8 of the anthraquinone compound increases its basicity. The presence of metal ions causes changes in intensity of absorption (decrease for compounds (2) and (3) and increase with bathochromic shift for (1) and (4)). For the determination of the coordination properties aluminum (III) ions were chosen. The highest complex stability constant with Al (III) ions is observed for compound (1), and the weakest for compound (3). The elongation of the polyether chain decreases the stability of the complex formed.

Polyether precursors of molecular recognition systems based on the 9,10-anthraquinone moiety.

PubMed

Wcisło, Anna; Cirocka, Anna; Zarzeczańska, Dorota; Niedziałkowski, Paweł; Nakonieczna, Sandra; Ossowski, Tadeusz

2015-02-25

A series of novel polyether derivatives of 9,10-anthraquinone (AQ) was synthesized and characterized by means of UV-Vis spectroscopy, acid-base titration and complexometric titration. The results were compared with 1-NEt2AQ and 1-NHEtAQ--model compounds of alkylaminoanthraquinones. Acetonitrile and methanol were used as solvents for determination of spectroscopic and acid-base properties. Complexometric titrations were carried out exclusively in acetonitrile. Spectral characteristic of these compounds strongly depends on pH. Addition of acid causes the decrease of absorption intensity and in some cases also a shift of the visible range band. The weakest base is the compound (2), and the strongest--compound (1), both in methanol and acetonitrile solution. The introduction of an additional substituent in the position 8 of the anthraquinone compound increases its basicity. The presence of metal ions causes changes in intensity of absorption (decrease for compounds (2) and (3) and increase with bathochromic shift for (1) and (4)). For the determination of the coordination properties aluminum (III) ions were chosen. The highest complex stability constant with Al (III) ions is observed for compound (1), and the weakest for compound (3). The elongation of the polyether chain decreases the stability of the complex formed. Copyright © 2014 Elsevier B.V. All rights reserved.

A diversity-oriented synthesis strategy enabling the combinatorial-type variation of macrocyclic peptidomimetic scaffolds† †Electronic supplementary information (ESI) available: Experimental procedures, characterization data and details of the computational analyses. See DOI: 10.1039/c5ob00371g Click here for additional data file.

PubMed Central

Isidro-Llobet, Albert; Hadje Georgiou, Kathy; Galloway, Warren R. J. D.; Giacomini, Elisa; Hansen, Mette R.; Méndez-Abt, Gabriela; Tan, Yaw Sing; Carro, Laura; Sore, Hannah F.

2015-01-01

Macrocyclic peptidomimetics are associated with a broad range of biological activities. However, despite such potentially valuable properties, the macrocyclic peptidomimetic structural class is generally considered as being poorly explored within drug discovery. This has been attributed to the lack of general methods for producing collections of macrocyclic peptidomimetics with high levels of structural, and thus shape, diversity. In particular, there is a lack of scaffold diversity in current macrocyclic peptidomimetic libraries; indeed, the efficient construction of diverse molecular scaffolds presents a formidable general challenge to the synthetic chemist. Herein we describe a new, advanced strategy for the diversity-oriented synthesis (DOS) of macrocyclic peptidomimetics that enables the combinatorial variation of molecular scaffolds (core macrocyclic ring architectures). The generality and robustness of this DOS strategy is demonstrated by the step-efficient synthesis of a structurally diverse library of over 200 macrocyclic peptidomimetic compounds, each based around a distinct molecular scaffold and isolated in milligram quantities, from readily available building-blocks. To the best of our knowledge this represents an unprecedented level of scaffold diversity in a synthetically derived library of macrocyclic peptidomimetics. Cheminformatic analysis indicated that the library compounds access regions of chemical space that are distinct from those addressed by top-selling brand-name drugs and macrocyclic natural products, illustrating the value of our DOS approach to sample regions of chemical space underexploited in current drug discovery efforts. An analysis of three-dimensional molecular shapes illustrated that the DOS library has a relatively high level of shape diversity. PMID:25778821

Corona[5]arenes Accessed by a Macrocycle-to-Macrocycle Transformation Route and a One-Pot Three-Component Reaction.

PubMed

Wu, Zhi-Chen; Guo, Qing-Hui; Wang, Mei-Xiang

2017-06-12

Corona[5]arenes, a novel type of macrocyclic compound that is composed of alternating heteroatoms and para-arylenes, were synthesized efficiently by two distinct methods. In a macrocycle-to-macrocycle transformation approach, S 6 -corona[3]arene[3]tetrazine underwent sequential S N Ar reactions with HS-C 6 H 4 -X-C 6 H 4 -SH (X=S, CH 2 , CMe 2 , SO 2 , and O) to produce the corresponding corona[3]arene[2]tetrazines. Different corona[3]arene[2]tetrazine compounds were also constructed in a straightforward manner by a one-pot three-component reaction of HS-C 6 H 4 -X-C 6 H 4 -SH (X=S, CH 2 , CMe 2 , SO 2 , and O) with diethyl 2,5-dimercaptoterephthalate and 2 equiv of 3,6-dichlorotetrazine under very mild conditions. All corona[5]arenes adopted 1,2,4-alternate conformational structures in the crystalline state yielding similar nearly regular pentagonal cavities. Both the cavity size and the electronic property of the acquired macrocycles were fine-tuned by the nature of the bridging element X. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic Screening Strategy for Rapid Access to Polyether Ionophore Producers and Products in Actinomycetes ▿ †

PubMed Central

Wang, Hao; Liu, Ning; Xi, Lijun; Rong, Xiaoying; Ruan, Jisheng; Huang, Ying

2011-01-01

Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes. PMID:21421776

Genetic screening strategy for rapid access to polyether ionophore producers and products in actinomycetes.

PubMed

Wang, Hao; Liu, Ning; Xi, Lijun; Rong, Xiaoying; Ruan, Jisheng; Huang, Ying

2011-05-01

Polyether ionophores are a unique class of polyketides with broad-spectrum activity and outstanding potency for the control of drug-resistant bacteria and parasites, and they are produced exclusively by actinomycetes. A special epoxidase gene encoding a critical tailoring enzyme involved in the biosynthesis of these compounds has been found in all five of the complete gene clusters of polyether ionophores published so far. To detect potential producer strains of these antibiotics, a pair of degenerate primers was designed according to the conserved regions of the five known polyether epoxidases. A total of 44 putative polyether epoxidase gene-positive strains were obtained by the PCR-based screening of 1,068 actinomycetes isolated from eight different habitats and 236 reference strains encompassing eight major families of Actinomycetales. The isolates spanned a wide taxonomic diversity based on 16S rRNA gene analysis, and actinomycetes isolated from acidic soils seemed to be a promising source of polyether ionophores. Four genera were detected to contain putative polyether epoxidases, including Micromonospora, which has not previously been reported to produce polyether ionophores. The designed primers also detected putative epoxidase genes from diverse known producer strains that produce polyether ionophores unrelated to the five published gene clusters. Moreover, phylogenetic and chemical analyses showed a strong correlation between the sequence of polyether epoxidases and the structure of encoded polyethers. Thirteen positive isolates were proven to be polyether ionophore producers as expected, and two new analogues were found. These results demonstrate the feasibility of using this epoxidase gene screening strategy to aid the rapid identification of known products and the discovery of unknown polyethers in actinomycetes.

Polyether complexes of groups 13 and 14.

PubMed

Swidan, Ala'aeddeen; Macdonald, Charles L B

2016-07-21

Notable aspects of the chemistry of complexes of polyether ligands including crown ethers, cryptands, glycols, glymes, and related polyether ligands with heavier group 13 and 14 elements are reviewed with a focus on results from 2005 to the present. The majority of reported polyether complexes contain lead(ii) and thallium(i) but recent breakthroughs in regard to the preparation of low oxidation state reagents of the lighter congeners have allowed for the generation of complexes containing indium(i), gallium(i), germanium(ii), and even silicon(ii). The important roles of ligand size, donor types, and counter anions in regard to the chemical properties of the polyether complexes is highlighted. A particular focus on the structural aspects of the numerous coordination complexes provides a rationale for some of the spectacular contributions that such compounds have made to Modern Main Group Chemistry.

Anti-MRSA activity of isoplagiochin-type macrocyclic bis(bibenzyl)s is mediated through cell membrane damage.

PubMed

Onoda, Kenji; Sawada, Hiromi; Morita, Daichi; Fujii, Kana; Tokiwa, Hiroaki; Kuroda, Teruo; Miyachi, Hiroyuki

2015-07-01

We synthesized three geometrical isomers of a macrocyclic bis(bibenzyl) based on isoplagiochin, a natural product isolated from bryophytes, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The isomer containing a 1,4-linked ring (5) showed only weak activity, whereas the isomers containing a 1,3-linked (6) or 1,2-linked (7) C ring showed potent anti-MRSA activity. Molecular dynamics calculations indicated that these differences are probably due to differences in the conformational flexibility of the macrocyclic ring; the active compounds 6 and 7 were more rigid than 5. In order to understand the action mechanism of anti-MRSA activity, we investigated the cellular flux of a fluorescent DNA-binder, ethidium bromide (EtBr), in the presence and absence of these macrocycles. The active compound 6 increased the levels of EtBr inflow and outflow in S. aureus cells, as did our potent anti-MRSA riccardin derivative (4), indicating that these compounds increased the permeability of the cytoplasmic membrane. Inactive 5 had no effect on EtBr inflow or outflow. Furthermore, compound 6 abrogated the normal intracellular concentration gradients of Na(+) and K(+) in S. aureus cells, increasing the intracellular Na(+) concentration and decreasing the K(+) concentration, while 5 had no such effect. These results indicate that anti-MRSA-active macrocyclic bis(bibenzyl) derivatives directly damage the gram-positive bacterial membrane, resulting in increased permeability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Guanidinium/ammonium competition and proton transfer in the interaction of the amino acid arginine with the tetracarboxylic 18-crown-6 ionophore.

PubMed

Avilés-Moreno, Juan Ramón; Berden, Giel; Oomens, Jos; Martínez-Haya, Bruno

2018-02-07

The recognition of arginine plays a central role in modern proteomics and genomics. Arginine is unique among natural amino acids due to the high basicity of its guanidinium side chain, which sustains specific interactions and proton exchange biochemical processes. The search for suitable macrocyclic ionophores constitutes a promising route towards the development of arginine receptors. This study evaluates the conformational features involved in the binding of free arginine by the polyether macrocycle (18-crown-6)-tetracarboxylic acid. Infrared action vibrational spectroscopy and quantum-chemical computations are combined to characterize the complexes with net charges +1 and +2. The spectrum of the +1 complex can be explained in terms of a configuration predominantly stabilized by a robust bidentate coordination of guanidinium with a carboxylate group formed from the deprotonation of one side group of the crown ether. The released proton is transferred to the amino terminus of arginine, which then coordinates with the crown ether ring. In an alternative type of conformation, partly consistent with experiment, the amino terminus is neutral and the guanidinium group inserts into the crown ether cavity. In the +2 complexes, arginine is always doubly protonated and the most stable conformations are characterized by a tripodal coordination of the ammonium -NH 3 + group of arginine with the oxygen atoms of the macrocycle ring, while the interactions of the amino acid with the side carboxylic acid groups of the crown ether acquire a remarkable lesser role.

Synthetic approaches to aromatic belts: building up strain in macrocyclic polyarenes.

PubMed

Eisenberg, David; Shenhar, Roy; Rabinovitz, Mordecai

2010-08-01

This tutorial review discusses synthetic strategies towards aromatic belts, defined here as double-stranded conjugated macrocycles, such as [n]cyclacenes, [n]cyclophenacenes, Schlüter belt, and Vögtle belt. Their appeal stems, firstly, from the unique nature of their conjugation, having p orbitals oriented radially rather than perpendicular to the plane of the macrocycle. Secondly, as aromatic belts are model compounds of carbon nanotubes of different chiralities, a synthetic strategy towards the buildup of structural strain in these compounds could finally open a route towards rational chemical synthesis of carbon nanotubes. The elusiveness of these compounds has stimulated fascinating and ingenious synthetic strategies over the last decades. The various strategies are classified here by their approach to the buildup of structural strain, which is the main obstacle in the preparation of these curved polyarenes.

Final Technical Report: Targeting DOE-Relevant Ions with Supramolecular Strategies, DE-SC0010555

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowman-James, Kristin

The effectiveness of three popular supramolecular strategies to selectively target negatively charged ions (anions) was evaluated. Ions of interest included oxo anions, particularly sulfate, that hamper nuclear waste remediation. Three objectives were pursued using a simple building block strategies and by strategically placing anion-binding sites at appropriate positions on organic host molecules. The goal of the first objective was to assess the influence of secondary, tertiary and quaternized amines on binding tetrahedral anions using mixed amide/amine macrocyclic and urea/amine hosts containing aromatic or heteroaromatic spacers. Objective 2 focused on the design of ion pair hosts, using mixed macrocyclic anion hostsmore » joined through polyether linkages. Objective 3 was to explore the synthesis of new metal-linked extended macrocyclic frameworks to leverage anion binding. Key findings were that smaller 24-membered macrocycles provided the most complementary binding for sulfate ion and mixed urea/amine chelates showed enhanced binding over amide corollaries in addition to being highly selective for SO 4 2- in the presence of small quantities of water. In addition to obtaining prototype metal-linked macrocyclic anion hosts, a new dipincer ligand was designed that can be used to link macrocyclic or other supramolecular hosts in extended frameworks. When the tetraamide-based pincers are bound to two metal ions, an interesting phenomenon occurs. Upon deprotonation of the amides, two new protons appear between adjacent carbonyl pairs on the ligand, which may modify the chemistry, and metal-metal interactions in the complexes. Gel formation occurred for some of these extended hosts, and the physical properties are currently under investigation. The new tetracarboxamide-based pincers can also provide basic frameworks for double macrocycles capable of binding ion pairs as well as for binding metal ions and exploring intermetallic interactions through the pyrazine π system. Additionally appendages capable of influencing solvation effects can be introduced, and a number of other potential applications can be realized in areas such as soft materials chemistry, catalysis, sensing, and proton switches, the latter for binding and release of targeted guests. These findings provide a better foundation for understanding the selective binding of anions by targeted placement of hydrogen binding sites, and the strengths and weaknesses of various functional groups, that will allow for more the design of more effective anion sequestering agents. Our design strategy also used simple, cost-effective building blocks for host synthesis to allow for scale-up should real-world applications be forthcoming.« less

Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Arun K.; Sean Fyvie, W.; Brindisi, Margherita

Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki = 13.2 nM, IC50 = 22 nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki = 62 pM and 14 pM, respectively) and antiviral activity (IC50 = 5.3 nM and 2.0 nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.

Toxicity of pyrolysis gases from polyether sulfone

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Olcomendy, E. M.

1979-01-01

A sample of polyether sulfone was evaluated for toxicity of pyrolysis gases, using the toxicity screening test method developed at the University of San Francisco. Animal response times were relatively short at pyrolysis temperatures of 600 to 800 C, with death occurring within 6 min. The principal toxicant appeared to be a compound other than carbon monoxide.

High-Performance Synthetic Fibers for Composites

DTIC Science & Technology

1992-04-01

under evaluation today include polyether ether ketone , polyamide, 23 polyamideimide, polyimide, polysulfone, and polyphenylene sulfide. Epoxy resins...shrinkage under intense neutron radiation . This attribute, together with other properties of high-temperature strength, toughness, and low nuclear...and (2) liquid or solid resins cross-linked with other esters in chopped-fiber and mineral-filled molding compounds. Polyether ether ketone (PEEK) A

Methods and intermediates for the synthesis of dipyrrin-substituted porphyrinic macrocycles

DOEpatents

Yu, Lianhe; Muthukumaran, Kannan; Sreedharan, Prathapan; Lindsey, Jonathan S.

2010-05-25

The present invention provides dipyrrin substituted porphyrinic macrocycles, intermediates useful for making the same, and methods of making the same. Such compounds may be used for purposes including the making of molecular memory devices, solar cells and light harvesting arrays.

Synthesis of highly functionalized macrocycles by the peripheral functionalization of macrocyclic diimines.

PubMed

Sierra, Miguel A; Pellico, Daniel; Gómez-Gallego, Mar; Mancheño, María José; Torres, Rosario

2006-11-10

The easily available macrocyclic diimines 4-7 can be stereoselectively transformed to macrocyclic bis-beta-amino acids 13-17, macrocyclic bisazetidines 18-20, and macrocyclic bisamides 21 and 22 by means of the corresponding bis-beta-lactam scaffolds 8-12. These key intermediates are available through standard Staudinger reaction and obtained as the cis-cis diastereomers, exclusively. An interesting relation between the proximity of the reactive C=N bonds and the selectivity in the formation of the bis-beta-lactams 8-12 is observed. Thus, diimine 4 leads to low selectivities, producing a 1:1 mixture of cis-syn-cis and cis-anti-cis diastereomers, while diimines 5-7 having the diimine sites more separated lead almost exclusively to the cis-anti-cis diastereomers. The stereochemistry of all the products was unambiguously assigned by X-ray diffraction analysis of compounds cis-syn-cis 8 and cis-anti-cis 12-Co2CO6 complex.

Carbon nanohoops and methods of making

DOEpatents

Jasti, Ramesh; Bertozzi, Carolyn

2013-06-11

The present invention provides cycloparaphenylene compounds, their macrocyclic precursors, and methods for making the compounds. The cycloparaphenylene compounds can be used to prepare armchair carbon nanotubes.

Carbon nanohoops and methods of making

DOEpatents

Jasti, Ramesh; Bertozzi, Carolyn

2015-03-24

The present invention provides cycloparaphenylene compounds, their macrocyclic precursors, and methods for making the compounds. The cycloparaphenylene compounds can be used to prepare armchair carbon nanotubes.

Carbon nanohoops and methods of making

DOEpatents

Jasti, Ramesh; Bertozzi, Carolyn

2015-10-20

The present invention provides cycloparaphenylene compounds, their macrocyclic precursors, and methods for making the compounds. The cycloparaphenylene compounds can be used to prepare armchair carbon nanotubes.

Structural basis of nonribosomal peptide macrocyclization in fungi.

PubMed

Zhang, Jinru; Liu, Nicholas; Cacho, Ralph A; Gong, Zhou; Liu, Zhu; Qin, Wenming; Tang, Chun; Tang, Yi; Zhou, Jiahai

2016-12-01

Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (C T ) domain and the holo thiolation (T)-C T complex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.

A macrocyclic ellagitannin trimer, oenotherin T(1), from Oenothera species.

PubMed

Taniguchi, Shoko; Imayoshi, Yoko; Yabu-uchi, Ryoko; Ito, Hideyuki; Hatano, Tsutomu; Yoshida, Takashi

2002-01-01

Oenotherin T(1) was isolated from leaves of Oenothera tetraptera as a major ellagitannin. Its structure, that of a macrocyclic trimer with a new acyl group, an isodehydrovaloneoyl group, was established. This compound was also produced by callus tissues induced from O. laciniata leaves.

Advances in macrocyclic peptide-based antibiotics.

PubMed

Luther, Anatol; Bisang, Christian; Obrecht, Daniel

2018-06-01

Macrocyclic peptide-based natural products have provided powerful new antibiotic drugs, drug candidates, and scaffolds for medicinal chemists as a source of inspiration to design novel antibiotics. While most of those natural products are active mainly against Gram-positive pathogens, novel macrocyclic peptide-based compounds have recently been described, which exhibit potent and specific activity against some of the most problematic Gram-negative ESKAPE pathogens. This mini-review gives an up-date on recent developments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aureoverticillactam, a novel 22-atom macrocyclic lactam from the marine actinomycete Streptomyces aureoverticillatus.

PubMed

Mitchell, Scott S; Nicholson, Benjamin; Teisan, Sy; Lam, Kin S; Potts, Barbara C M

2004-08-01

During the course of our screening program designed to discover novel anticancer and anti-infective agents from marine microorganisms, a strain of Streptomyces aureoverticillatus (NPS001583) isolated from a marine sediment was found to produce a novel macrocyclic lactam with cytotoxicity against various tumor cell lines. Using extensive MS, UV, and NMR spectral analyses, the structure has been established as compound 1, aureoverticillactam, a 22-atom macrocyclic lactam incorporating both triene and tetraene conjugated olefins.

Comprehensive computational design of ordered peptide macrocycles

PubMed Central

Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fátima; Rettie, Stephen A.; Kim, David E.; Silva, Daniel-Adriano; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

2018-01-01

Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with L-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L- and D-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. PMID:29242347

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks.

PubMed

Maurya, Sushil K; Rana, Rohit

2017-01-01

An efficient, eco-compatible diversity-oriented synthesis (DOS) approach for the generation of library of sugar embedded macrocyclic compounds with various ring size containing 1,2,3-triazole has been developed. This concise strategy involves the iterative use of readily available sugar-derived alkyne/azide-alkene building blocks coupled through copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction followed by pairing of the linear cyclo-adduct using greener reaction conditions. The eco-compatibility, mild reaction conditions, greener solvents, easy purification and avoidance of hazards and toxic solvents are advantages of this protocol to access this important structural class. The diversity of the macrocycles synthesized (in total we have synthesized 13 macrocycles) using a set of standard reaction protocols demonstrate the potential of the new eco-compatible approach for the macrocyclic library generation.

Complexes of DOTA-bisphosphonate conjugates: probes for determination of adsorption capacity and affinity constants of hydroxyapatite.

PubMed

Vitha, Tomas; Kubícek, Vojtech; Hermann, Petr; Kolar, Zvonimir I; Wolterbeek, Hubert Th; Peters, Joop A; Lukes, Ivan

2008-03-04

The adsorption on hydroxyapatite of three conjugates of a bisphosphonate and a macrocycle having C1, C2, and C3 spacers and their terbium complexes was studied by the radiotracer method using 160Tb as the label. The radiotracer-containing complex of the conjugate with the C3 spacer was used as a probe for the determination of the adsorption parameters of other bisphosphonates that lack a DOTA unit. A physicochemical model describing the competitive adsorption was successfully applied in the fitting of the obtained data. The maximum adsorption capacity of bisphosphonates containing bulky substituents is determined mainly by their size. For bisphosphonates having no DOTA moiety, the maximum adsorption capacity is determined by the electrostatic repulsion between negatively charged bisphosphonate groups. Compounds with a hydroxy or amino group attached to the alpha-carbon atom show higher affinities. Macrocyclic compounds containing a short spacer between the different bisphosphonic acid groups and the macrocyclic unit exhibit high affinities, indicating a synergic effect of the bisphosphonic and the macrocyclic groups during adsorption. The competition method described uses a well-characterized complex and allows a simple evaluation of the adsorption behavior of bisphosphonates. The application of the macrocycle-bisphosphonate conjugates allows easy radiolabeling via complexation of a suitable metal isotope.

Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of Tripterygium regelii.

PubMed

Fan, Dongsheng; Zhu, Guo-Yuan; Li, Ting; Jiang, Zhi-Hong; Bai, Li-Ping

2016-08-29

Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3'-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.

Biodegradation of polyether algal toxins--isolation of potential marine bacteria.

PubMed

Shetty, Kateel G; Huntzicker, Jacqueline V; Rein, Kathleen S; Jayachandran, Krish

2010-12-01

Marine algal toxins such as brevetoxins, okadaic acid, yessotoxin, and ciguatoxin are polyether compounds. The fate of polyether toxins in the aqueous phase, particularly bacterial biotransformation of the toxins, is poorly understood. An inexpensive and easily available polyether structural analog salinomycin was used for enrichment and isolation of potential polyether toxin degrading aquatic marine bacteria from Florida bay area, and from red tide endemic sites in the South Florida Gulf coast. Bacterial growth on salinomycin was observed in most of the enrichment cultures from both regions with colony forming units ranging from 0 to 6×10(7) per mL. The salinomycin biodegradation efficiency of bacterial isolates determined using LC-MS ranged from 22% to 94%. Selected bacterial isolates were grown in media with brevetoxin as the sole carbon source to screen for brevetoxin biodegradation capability using ELISA. Out of the two efficient salinomycin biodegrading isolates MB-2 and MB-4, maximum brevetoxin biodegradation efficiency of 45% was observed with MB-4, while MB-2 was unable to biodegrade brevetoxin. Based on 16S rRNA sequence similarity MB-4 was found have a match with Chromohalobacter sp.

Structural basis for precursor protein-directed ribosomal peptide macrocyclization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Kunhua; Condurso, Heather L.; Li, Gengnan

Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved α-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight intomore » the unique protein–protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.« less

Kinetically E-selective macrocyclic ring-closing metathesis

NASA Astrophysics Data System (ADS)

Shen, Xiao; Nguyen, Thach T.; Koh, Ming Joo; Xu, Dongmin; Speed, Alexander W. H.; Schrock, Richard R.; Hoveyda, Amir H.

2017-01-01

Macrocyclic compounds are central to the development of new drugs, but preparing them can be challenging because of the energy barrier that must be surmounted in order to bring together and fuse the two ends of an acyclic precursor such as an alkene (also known as an olefin). To this end, the catalytic process known as ring-closing metathesis (RCM) has allowed access to countless biologically active macrocyclic organic molecules, even for large-scale production. Stereoselectivity is often critical in such cases: the potency of a macrocyclic compound can depend on the stereochemistry of its alkene; alternatively, one isomer of the compound can be subjected to stereoselective modification (such as dihydroxylation). Kinetically controlled Z-selective RCM reactions have been reported, but the only available metathesis approach for accessing macrocyclic E-olefins entails selective removal of the Z-component of a stereoisomeric mixture by ethenolysis, sacrificing substantial quantities of material if E/Z ratios are near unity. Use of ethylene can also cause adventitious olefin isomerization—a particularly serious problem when the E-alkene is energetically less favoured. Here, we show that dienes containing an E-alkenyl-B(pinacolato) group, widely used in catalytic cross-coupling, possess the requisite electronic and steric attributes to allow them to be converted stereoselectively to E-macrocyclic alkenes. The reaction is promoted by a molybdenum monoaryloxide pyrrolide complex and affords products at a yield of up to 73 per cent and an E/Z ratio greater than 98/2. We highlight the utility of the approach by preparing recifeiolide (a 12-membered-ring antibiotic) and pacritinib (an 18-membered-ring enzyme inhibitor), the Z-isomer of which is less potent than the E-isomer. Notably, the 18-membered-ring moiety of pacritinib—a potent anti-cancer agent that is in advanced clinical trials for treating lymphoma and myelofibrosis—was prepared by RCM carried out at a substrate concentration 20 times greater than when a ruthenium carbene was used.

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism.

PubMed

Vollmeyer, Joscha; Eberhagen, Friederike; Höger, Sigurd; Jester, Stefan-S

2014-01-01

Three shape-persistent naphthylene-phenylene-acetylene macrocycles of identical backbone structures and extraannular substitution patterns but different (empty, apolar, polar) nanopore fillings are self-assembled at the solid/liquid interface of highly oriented pyrolytic graphite and 1,2,4-trichlorobenzene. Submolecularly resolved images of the resulting two-dimensional (2D) crystalline monolayer patterns are obtained by in situ scanning tunneling microscopy. A concentration-dependent conformational polymorphism is found, and open and more dense packing motifs are observed. For all three compounds alike lattice parameters are found, therefore the intermolecular macrocycle distances are mainly determined by their size and symmetry. This is an excellent example that the graphite acts as a template for the macrocycle organization independent from their specific interior.

Host-guest capability of a three-dimensional heterometallic macrocycle.

PubMed

Fan, Qi-Jia; Lin, Yue-Jian; Hahn, F Ekkehardt; Jin, Guo-Xin

2018-02-13

A three-dimensional heterometallic coordination macrocycle is found to be capable of encapsulating planar pyrene (G1), coronene (G4) and non-planar corannulene (G2) guest molecules in high yields, giving rise to 1 : 1 host-guest complexes. The bowl-shaped guest corannulene is found to be significantly flattened upon inclusion within the cavity. However, macrocyclic compounds with larger cavity sizes, which form 1 : 1 stoichiometry assemblies with a naphthalene bisimide planar molecule (G3), are more inclined to form infinite sandwich structures. Furthermore, these heterometallic coordination macrocycles can be destroyed in the presence of a soft base to form hexanuclear triangular prism complexes. These structures are unambiguously revealed by single-crystal X-ray analysis.

Ferrocene- and Biferrocene-Containing Macrocycles towards Single-Molecule Electronics.

PubMed

Wilson, Lucy E; Hassenrück, Christopher; Winter, Rainer F; White, Andrew J P; Albrecht, Tim; Long, Nicholas J

2017-06-06

Cyclic multiredox centered systems are currently of great interest, with new compounds being reported and developments made in understanding their behavior. Efficient, elegant, and high-yielding (for macrocyclic species) synthetic routes to two novel alkynyl-conjugated multiple ferrocene- and biferrocene-containing cyclic compounds are presented. The electronic interactions between the individual ferrocene units have been investigated through electrochemistry, spectroelectrochemistry, density functional theory (DFT), and crystallography to understand the effect of cyclization on the electronic properties and structure. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

PubMed

Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

2017-02-22

Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

Ru(II) complexes of N 4 and N 2O 2 macrocyclic Schiff base ligands: Their antibacterial and antifungal studies

NASA Astrophysics Data System (ADS)

Shanker, Kanne; Rohini, Rondla; Ravinder, Vadde; Reddy, P. Muralidhar; Ho, Yen-Peng

2009-07-01

Reactions of [RuCl 2(DMSO) 4] with some of the biologically active macrocyclic Schiff base ligands containing N 4 and N 2O 2 donor group yielded a number of stable complexes, effecting complete displacement of DMSO groups from the complex. The interaction of tetradentate ligand with [RuCl 2(DMSO) 4] gave neutral complexes of the type [RuCl 2(L)] [where L = tetradentate macrocyclic ligand]. These complexes were characterized by elemental, IR, 1H, 13C NMR, mass, electronic, thermal, molar conductance and magnetic susceptibility measurements. An octahedral geometry has been proposed for all complexes. All the macrocycles and macrocyclic Ru(II) complexes along with existing antibacterial drugs were screened for antibacterial activity against Gram +ve ( Bacillus subtilis, Staphylococcus aureus) and Gram -ve ( Escherichia coli, Klebsiella pneumonia) bacteria. All these compounds were found to be more active when compared to streptomycin and ampicillin. The representative macrocyclic Schiff bases and their complexes were also tested in vitro to evaluate their activity against fungi, namely, Aspergillus flavus and Fusarium species.

Macrocyclic 2,7-Anthrylene Oligomers.

PubMed

Yamamoto, Yuta; Wakamatsu, Kan; Iwanaga, Tetsuo; Sato, Hiroyasu; Toyota, Shinji

2016-05-06

A macrocyclic compound consisting of six 2,7-anthrylene units was successfully synthesized by Ni-mediated coupling of the corresponding dibromo precursor as a novel π-conjugated compound. This compound was sufficiently stable and soluble in organic solvents due to the presence of mesityl groups. X-ray analysis showed that the molecule had a nonplanar and hexagonal wheel-shaped framework of approximately S6 symmetry. The dynamic process between two S6 structures was observed by using the dynamic NMR technique, the barrier being 58 kJ mol(-1) . The spectroscopic properties of the hexamer were compared with those of analogous linear oligomers. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cytotoxic Activity and Structure-Activity Relationship of Triazole-Containing Bis(Aryl Ether) Macrocycles.

PubMed

Hernández-Vázquez, Eduardo; Chávez-Riveros, Alejandra; Romo-Pérez, Adriana; Ramírez-Apán, María Teresa; Chávez-Blanco, Alma D; Morales-Bárcenas, Rocío; Dueñas-González, Alfonso; Miranda, Luis D

2018-05-17

Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20-, 21-, and 22-membered macrocycles containing triazole and bis(aryl ether) moieties. The compounds were prepared by a multicomponent approach from readily available commercial substrates. Notably, some of the compounds displayed interesting cytotoxicity against cancer (PC-3) and breast (MCF-7) cell lines, especially those bearing an aliphatic or a trifluoromethyl substituent on the N-phenyl moiety (IC 50 <13 μm). Additionally, some of the compounds were able to induce apoptosis relative to the solvent control; in particular, (Z)-N-cyclohexyl-7-oxo-6-[4-(trifluoromethyl)phenyl]-1 1 H-3,10-dioxa-6-aza-1(4,1)-triazola-4(1,3),9(1,4)-dibenzenacyclotridecaphane-5-carboxamide (12 f) was the most potent in this regard (22.7 % of apoptosis). © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities.

PubMed

Kitir, Betül; Maolanon, Alex R; Ohm, Ragnhild G; Colaço, Ana R; Fristrup, Peter; Madsen, Andreas S; Olsen, Christian A

2017-09-26

Histone deacetylases (HDACs) are validated targets for treatment of certain cancer types and play numerous regulatory roles in biology, ranging from epigenetics to metabolism. Small molecules are highly important as tool compounds for probing these mechanisms as well as for the development of new medicines. Therefore, detailed mechanistic information and precise characterization of the chemical probes used to investigate the effects of HDAC enzymes are vital. We interrogated Nature's arsenal of macrocyclic nonribosomal peptide HDAC inhibitors by chemical synthesis and evaluation of more than 30 natural products and analogues. This furnished surprising trends in binding affinities for the various macrocycles, which were then exploited for the design of highly potent class I and IIb HDAC inhibitors. Furthermore, thorough kinetic investigation revealed unexpected inhibitory mechanisms of important tool compounds as well as the approved drug Istodax (romidepsin). This work provides novel inhibitors with varying potencies, selectivity profiles, and mechanisms of inhibition and, importantly, affords insight into known tool compounds that will improve the interpretation of their effects in biology and medicine.

Three-dimensional aromatic networks.

PubMed

Toyota, Shinji; Iwanaga, Tetsuo

2014-01-01

Three-dimensional (3D) networks consisting of aromatic units and linkers are reviewed from various aspects. To understand principles for the construction of such compounds, we generalize the roles of building units, the synthetic approaches, and the classification of networks. As fundamental compounds, cyclophanes with large aromatic units and aromatic macrocycles with linear acetylene linkers are highlighted in terms of transannular interactions between aromatic units, conformational preference, and resolution of chiral derivatives. Polycyclic cage compounds are constructed from building units by linkages via covalent bonds, metal-coordination bonds, or hydrogen bonds. Large cage networks often include a wide range of guest species in their cavity to afford novel inclusion compounds. Topological isomers consisting of two or more macrocycles are formed by cyclization of preorganized species. Some complicated topological networks are constructed by self-assembly of simple building units.

Pyrrole-Based Macrocyclic Small-Molecule Inhibitors That Target Oocyte Maturation.

PubMed

Gunasekaran, Pethaiah; Lee, So-Rim; Jeong, Seung-Min; Kwon, Jeong-Woo; Takei, Toshiki; Asahina, Yuya; Bang, Geul; Kim, Seongnyeon; Ahn, Mija; Ryu, Eun Kyung; Kim, Hak Nam; Nam, Ki-Yub; Shin, Song Yub; Hojo, Hironobu; Namgoong, Suk; Kim, Nam-Hyung; Bang, Jeong Kyu

2017-04-20

Polo-like kinase 1 (PLK1) plays crucial roles in various stages of oocyte maturation. Recently, we reported that the peptidomimetic compound AB103-8, which targets the polo box domain (PBD) of PLK1, affects oocyte meiotic maturation and the resumption of meiosis. However, to overcome the drawbacks of peptidic compounds, we designed and synthesized a series of pyrrole-based small-molecule inhibitors and tested them for their effects on the rates of porcine oocyte maturation. Among them, the macrocyclic compound (E/Z)-3-(2,16-dioxo-19-(4-phenylbutyl)-3,19-diazabicyclo[15.2.1]icosa-1(20),6,17-trien-3-yl)propyl dihydrogen phosphate (4) showed the highest inhibitory activity with enhanced inhibition against embryonic blastocyst formation. Furthermore, the addition of this compound to culture media efficiently blocked the maturation of porcine and mouse oocytes, indicating its ability to penetrate the zona pellucida and cell membrane. We investigated mouse oocytes treated with compound 4, and the resulting impairment of spindle formation confirmed PLK1 inhibition. Finally, molecular modeling studies with PLK1 PBD also confirmed the presence of significant interactions between compound 4 and PLK1 PBD binding pocket residues, including those in the phosphate, tyrosine-rich, and pyrrolidine binding pockets. Collectively, these results suggest that the macrocyclic compound 4 may serve as a promising template for the development of novel contraceptive agents. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comprehensive computational design of ordered peptide macrocycles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple

Mixed chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to-date, but there is currently no way to systematically search through the structural space spanned by such compounds for new drug candidates. Natural proteins do not provide a useful guide: peptide macrocycles lack regular secondary structures and hydrophobic cores and have different backbone torsional constraints. Hence the development of new peptide macrocycles has been approached by modifying natural products or using library selection methods; the former is limited by the small number of known structures, and the latter by the limited size and diversity accessible throughmore » library-based methods. To overcome these limitations, here we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L and D amino acids. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. We synthesize and characterize by NMR twelve 7-10 residue macrocycles, 9 of which have structures very close to the design models in solution. NMR structures of three 11-14 residue bicyclic designs are also very close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide based macrocycles unparalleled for other molecular systems, and vastly increase the available starting scaffolds for both rational drug design and library selection methods.« less

Polyurethanes from fluoroalkyl propyleneglycol polyethers

NASA Technical Reports Server (NTRS)

Trischler, F. D. (Inventor)

1969-01-01

A description is given of highly stable polyurethane polymers prepared by reacting a polyether with a diisocyanate. Compounded stocks of these polymers may be shaped and cured in conventional equipment used in the rubber industry. The solutions are dispersed gels prepared from the polymers and may be used for forming supported or unsupported films for coating fabrics or solid surfaces, and for forming adhesive bonds between a wide variety of plastics, elastomers, fabrics, metals, wood, leather, ceramics and the like.

Biodegradation of polyether algal toxins–Isolation of potential marine bacteria

PubMed Central

SHETTY, KATEEL G.; HUNTZICKER, JACQUELINE V.; REIN, KATHLEEN S.; JAYACHANDRAN, KRISH

2012-01-01

Marine algal toxins such as brevetoxins, okadaic acid, yessotoxin, and ciguatoxin are polyether compounds. The fate of polyether toxins in the aqueous phase, particularly bacterial biotransformation of the toxins, is poorly understood. An inexpensive and easily available polyether structural analog salinomycin was used for enrichment and isolation of potential polyether toxin degrading aquatic marine bacteria from Florida bay area, and from red tide endemic sites in the South Florida Gulf coast. Bacterial growth on salinomycin was observed in most of the enrichment cultures from both regions with colony forming units ranging from 0 to 6 × 107 per mL. The salinomycin biodegradation efficiency of bacterial isolates determined using LC-MS ranged from 22% to 94%. Selected bacterial isolates were grown in media with brevetoxin as the sole carbon source to screen for brevetoxin biodegradation capability using ELISA. Out of the two efficient salinomycin biodegrading isolates MB-2 and MB-4, maximum brevetoxin biodegradation efficiency of 45% was observed with MB-4, while MB-2 was unable to biodegrade brevetoxin. Based on 16S rRNA sequence similarity MB-4 was found have a match with Chromohalobacter sp. PMID:20954040

Syntheses, solid state and solution structures of the palladium(II) complexes of malonamide-derived open-chain and macrocyclic ligands.

PubMed

Gavrish, Sergey P; Lampeka, Yaroslaw D; Pritzkow, Hans; Lightfoot, Philip

2010-09-07

The crystal structures of the palladium(II) complexes of the open-chain and macrocyclic ligands PdL(1).3H(2)O, PdL(2).6H(2)O and PdL(3).5H(2)O have been determined (H(2)L(1) = 1,4,8,11-tetraazaundecane-5,7-dione, H(2)L(2) = 1,4,8,11-tetraazacyclotetradecane-5,7-dione, H(2)L(3) = 1,4,8,11-tetraazacyclotridecane-5,7-dione). The coordination polyhedra of the palladium(II) ions in all complexes are formed by two deprotonated amide and two amine donors with Pd-N distances being similar in PdL(1) and PdL(2) and substantially shorter in PdL(3). A detailed analysis of the (1)H NMR spectra of the macrocyclic complexes supports the formation in aqueous solution of only N-meso isomers of both compounds in agreement with the X-ray data. The spectra of the palladium(II) macrocyclic complexes are shifted downfield as a whole as compared to those of the nickel(II) analogues with the shifts being essentially non-uniform. The latter feature can be related to the differences in magnetic anisotropy of the M-N bonds. The maxima of d-d absorption bands of the palladium(II) complexes demonstrate weaker dependence on the macrocycle size as compared to those of the nickel(II) analogues. Both macrocyclic compounds PdL(2).6H(2)O and PdL(3).5H(2)O are characterized by lamellar crystal structures consisting of interleaved layers formed by macrocyclic units and by water molecules with similar metal complex layers and different 2D water sheets. A columnar crystal structure is inherent for PdL(1).3H(2)O with the water molecules present as discrete (H(2)O)(3) clusters.

Electronic and vibrational exciton coupling in oxidized trianglimines.

PubMed

Szymkowiak, Joanna; Kwit, Marcin

2018-02-01

Readily available chiral trianglimine and their (poly)oxygenated congeners represent a unique class of macrocyclic rigid compounds optimal for testing electronic and vibrational circular dichroism exciton chirality methods. Electronic and vibrational circular dichroism spectra of such trianglimines are strongly affected by polar substituents in macrocycle skeletons. Double substitution by OH groups in each aromatic fragment of the macrocycle causes sign reversal of the exciton couplet in the region of the strongest UV absorption. On the other hand, electronic circular dichroism spectrum of the macrocycle having 2 methoxy groups shows 2 exciton couplets-the long-wavelength positive and the second of the negative sign, observed at the shorter wavelengths. VCD spectra of macrocyclic imines show vibrational exciton couplets in the region of strong C=N stretches. The signs of these couplets are positive and the opposite of the diamine chirality. For trianglimine macrocycles the interpretation of VCD spectra in terms of excitons is much more convincing than for electronic circular dichroism spectra. By contrast, trans-1,2-diaminocyclohexane-based vicinal diimines, being a one-third of the respective macrocycle, do not exhibit any vibrational exciton effect. Experimental data were confronted with DFT calculations. We observed good-to-excellent agreement between experimental and computed data. © 2017 Wiley Periodicals, Inc.

Tetraphenylethylene-Interweaving Conjugated Macrocycle Polymer Materials as Two-Photon Fluorescence Sensors for Metal Ions and Organic Molecules.

PubMed

Li, Xi; Li, Zheng; Yang, Ying-Wei

2018-05-01

A luminescent conjugated macrocycle polymer (CMP) with strong two-photon fluorescence property, namely, P[5]-TPE-CMP, is constructed from ditriflate-functionalized pillar[5]arene and a 1,1,2,2-tetrakis(4-ethynylphenyl)ethylene (TPE) linker through a Sonogashira-Hagihara cross-coupling reaction. Significantly, in sharp contrast with the corresponding conjugated microporous polymer without synthetic macrocycles, P[5]-TPE-CMP shows an outstanding stability against photobleaching and exhibits highly selective cation sensing capability toward Fe 3+ at different excitation wavelengths (both UV and red-near-infrared regions). Meanwhile, its fluorescence could also be sufficiently quenched by 4-amino azobenzene, a frequently used organic dye that is certified to be carcinogenic, as compared with a group of common organic compounds. This work paves a new way for enhancing the properties of porous organic polymers through the introduction of supramolecular macrocycles like macrocyclic arenes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel amide polar-embedded reversed-phase column for the fast liquid chromatography-tandem mass spectrometry method to determine polyether ionophores in environmental waters.

PubMed

Herrero, P; Borrull, F; Pocurull, E; Marcé, R M

2012-11-09

A fast chromatographic method has been developed that takes less than 5 min per run to determine five polyether ionophores with a novel amide polar-embedded reversed-phase column coupled to a triple quadrupole mass spectrometer. A comparison between Oasis HLB and Oasis MAX sorbents for the solid-phase extraction was done. Oasis HLB sorbent gave recoveries close to 90% and the repeatability (%RSD, 25-100 ng/L, n=3) of the method was less than 7% for all compounds in all matrices. The presence of polyether ionophores in environmental waters such as river water and sewage was investigated. Monensin and narasin were frequently determined in influent and effluent sewage at concentrations from 10 ng/L to 47 ng/L in influents and from 6 ng/L to 34 ng/L in effluents. In river waters, polyether ionophores were not detected in any sample. Copyright © 2012 Elsevier B.V. All rights reserved.

Macrocyclic fragrance materials--a screening-level environmental assessment using chemical categorization.

PubMed

Salvito, Daniel; Lapczynski, Aurelia; Sachse-Vasquez, Christen; McIntosh, Colin; Calow, Peter; Greim, Helmut; Escher, Beate

2011-09-01

A screening-level aquatic environmental risk assessment for macrocyclic fragrance materials using a "group approach" is presented using data for 30 macrocyclic fragrance ingredients. In this group approach, conservative estimates of environmental exposure and ecotoxicological effects thresholds for compounds within two subgroups (15 macrocyclic ketones and 15 macrocyclic lactones/lactides) were used to estimate the aquatic ecological risk potential for these subgroups. It is reasonable to separate these fragrance materials into the two subgroups based on the likely metabolic pathway required for biodegradation and on expected different ecotoxicological modes of action. The current volumes of use for the macrocyclic ketones in both Europe and North America ranges from <1 (low kg quantities) to no greater than 50 metric tonnes in either region and for macrocyclic lactones/lactides the volume of use range for both regions is <1 to no greater than 1000 metric tonnes in any one region. Based on these regional tonnages, biodegradability of these two subgroups of materials, and minimal in stream dilution (3:1), the conservatively predicted exposure concentrations for macrocyclic ketones would range from <0.01 to 0.05 μg/L in Europe and from <0.01 to 0.03 μg/L in North America. For macrocyclic lactones/lactides, the concentration within the mixing zone would range from <0.01 to 0.7 μg/L in Europe and from <0.01 to 1.0 μg/L in North America. The PNECs derived for the macrocyclic ketones is 0.22 μg/L and for macrocyclic lactones/lactides is 2.7 μg/L. The results of this screening-level aquatic ecological risk assessment indicate that at their current tonnage, often referred to as volumes of use, macrocyclic fragrance materials in Europe and North America, pose a negligible risk to aquatic biota; with no PEC/PNEC ratio exceeding 1 for any material in any subgroup. Copyright © 2011 Elsevier Inc. All rights reserved.

MODELING OF MULTICOMPONENT PERVAPORATION FOR REMOVAL OF VOLATILE ORGANIC COMPOUNDS FROM WATER

EPA Science Inventory

A resistance-in-series model was used to study the pervaporation of multiple volatile organic compounds (VOCs)-water mixtures. Permeation experiments were carried out for four membranes: poly(dimethylsiloxane) (PDMS), polyether-block-polyamides (PEBA), polyurethane (PUR) and sil...

Verbalactone, a new macrocyclic dimer lactone from the roots of Verbascum undulatum with antibacterial activity.

PubMed

Magiatis, P; Spanakis, D; Mitaku, S; Tsitsa, E; Mentis, A; Harvala, C

2001-08-01

A novel macrocyclic dimer lactone, named verbalactone, was isolated from the roots of Verbascum undulatum and exhibited interesting antibacterial activity. It is the first time that 1,7-dioxacyclododecane is reported as the ring system of a natural product. The structure and the absolute stereochemistry of the new compound were determined by spectral methods and chemical correlation.

New macrocyclic lactones with acaricidal and nematocidal activities from a genetically engineered strain Streptomyces bingchenggensis BCJ60.

PubMed

Li, Jian-Song; Zhang, Hui; Zhang, Shao-Yong; Wang, Hai-Yan; Zhang, Ji; Chen, An-Liang; Wang, Ji-Dong; Xiang, Wen-Sheng

2017-04-01

Two new macrocyclic lactones, 4,25-diethyl-4,25-demethyl-milbemycin β 3 (1) and 27-formaldehyde-milbemycin β 14 (2), were isolated from a genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as ESI-MS and comparison with data from the literature. The acaricidal and nematocidal capacities of compounds 1 and 2 were evaluated against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, respectively. The results showed that the two new macrocyclic lactones 1 and 2 possessed potent acaricidal and nematocidal activities.

Hydrolyzable tannins of tamaricaceous plants. V. Structures of monomeric-trimeric tannins and cytotoxicity of macrocyclic-type tannins isolated from Tamarix nilotica (1).

PubMed

Orabi, Mohamed A A; Taniguchi, Shoko; Sakagami, Hiroshi; Yoshimura, Morio; Yoshida, Takashi; Hatano, Tsutomu

2013-05-24

Three new ellagitannin monomers, nilotinins M5-M7 (1-3), a dimer, nilotinin D10 (4), and a trimer, nilotinin T1 (5), together with three known dimers, hirtellin D (7) and tamarixinins B (8) and C (9), and a trimer, hirtellin T2 (6), were isolated from Tamarix nilotica dried leaves. The structures of the tannins were elucidated by intensive spectroscopic methods and chemical conversions into known tannins. The new trimer (5) is a unique macrocyclic type whose monomeric units are linked together by an isodehydrodigalloyl and two dehydrodigalloyl moieties. Additionally, dimeric and trimeric macrocyclic-type tannins isolated from T. nilotica in this study were assessed for possible cytotoxic activity against four human tumor cell lines. Tumor-selective cytotoxicities of the tested compounds were higher than those of synthetic and natural potent cytotoxic compounds, including polyphenols, and comparable with those of 5-fluorouracil and melphalan.

"Crown Ether" Synthesis: An Organic Laboratory Experiment.

ERIC Educational Resources Information Center

Field, Kurt W.; And Others

1979-01-01

This experiment is designed to acquaint the student with a macromolecular synthesis of a crown ether type compound. The starting materials are readily available and the product, a cyclic polyether, belongs to a class of compounds that has aroused the interest of chemist and biologist alike. (Author/BB)

Process for separation and preconcentration of radium from water

DOEpatents

Dietz, Mark; Horwitz, E. Philip; Chiarizia, Renato; Bartsch, Richard A.

1999-01-01

A process for preconcentrating and separating radium from a contaminated solution containing at least water and radium includes the steps of adding a quantity of a water-soluble macrocyclic polyether to the contaminated solution to form a combined solution. An acid is added to the combined solution to form an acidic combined solution having an ›H.sup.+ ! concentration of about 0.5M. The acidic combined solution is contacted with a sulfonic acid-based strong acid cation exchange medium or a organophilic sulfonic acid medium having a plurality of binding sites thereon to bind the radium thereto and to form a radium-depleted solution. The radium-depleted solution is separated from the strong acid cation exchange medium or organophilic sulfonic acid medium. The radium remaining bound to the exchange medium or organophilic reagent is then stripped from the exchange medium or organophilic medium and the activity of the radium is measured.

Process for separation and preconcentration of radium from water

DOEpatents

Dietz, M.; Horwitz, E.P.; Chiarizia, R.; Bartsch, R.A.

1999-01-26

A process for preconcentrating and separating radium from a contaminated solution containing at least water and radium includes the steps of adding a quantity of a water-soluble macrocyclic polyether to the contaminated solution to form a combined solution. An acid is added to the combined solution to form an acidic combined solution having an [H{sup +}] concentration of about 0.5M. The acidic combined solution is contacted with a sulfonic acid-based strong acid cation exchange medium or a organophilic sulfonic acid medium having a plurality of binding sites thereon to bind the radium thereto and to form a radium-depleted solution. The radium-depleted solution is separated from the strong acid cation exchange medium or organophilic sulfonic acid medium. The radium remaining bound to the exchange medium or organophilic reagent is then stripped from the exchange medium or organophilic medium and the activity of the radium is measured. 24 figs.

Role of Modular Polyketide Synthases in the Production of Polyether Ladder Compounds in Ciguatoxin-Producing Gambierdiscus polynesiensis and G. excentricus (Dinophyceae).

PubMed

Kohli, Gurjeet S; Campbell, Katrina; John, Uwe; Smith, Kirsty F; Fraga, Santiago; Rhodes, Lesley L; Murray, Shauna A

2017-09-01

Gambierdiscus, a benthic dinoflagellate, produces ciguatoxins that cause the human illness Ciguatera. Ciguatoxins are polyether ladder compounds that have a polyketide origin, indicating that polyketide synthases (PKS) are involved in their production. We sequenced transcriptomes of Gambierdiscus excentricus and Gambierdiscus polynesiensis and found 264 contigs encoding single domain ketoacyl synthases (KS; G. excentricus: 106, G. polynesiensis: 143) and ketoreductases (KR; G. excentricus: 7, G. polynesiensis: 8) with sequence similarity to type I PKSs, as reported in other dinoflagellates. In addition, 24 contigs (G. excentricus: 3, G. polynesiensis: 21) encoding multiple PKS domains (forming typical type I PKSs modules) were found. The proposed structure produced by one of these megasynthases resembles a partial carbon backbone of a polyether ladder compound. Seventeen contigs encoding single domain KS, KR, s-malonyltransacylase, dehydratase and enoyl reductase with sequence similarity to type II fatty acid synthases (FAS) in plants were found. Type I PKS and type II FAS genes were distinguished based on the arrangement of domains on the contigs and their sequence similarity and phylogenetic clustering with known PKS/FAS genes in other organisms. This differentiation of PKS and FAS pathways in Gambierdiscus is important, as it will facilitate approaches to investigating toxin biosynthesis pathways in dinoflagellates. © 2017 The Author(s) Journal of Eukaryotic Microbiology © 2017 International Society of Protistologists.

Minimum structural requirements for cell membrane leakage-mediated anti-MRSA activity of macrocyclic bis(bibenzyl)s.

PubMed

Fujii, Kana; Morita, Daichi; Onoda, Kenji; Kuroda, Teruo; Miyachi, Hiroyuki

2016-05-01

Macrocyclic bis(bibenzyl)-type phenolic natural products, found exclusively in bryophytes, exhibit potent antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Here, in order to identify the minimum essential structure for cell membrane leakage-mediated anti-MRSA activity of these compounds, we synthesized acyclic fragment structures and evaluated their anti-MRSA activity. The activities of all of the acyclic fragments tested exhibited similar characteristics to those of the macrocycles, i.e., anti-MRSA bactericidal activity, an enhancing effect on influx and efflux of ethidium bromide (EtBr: fluorescent DNA-binder) in Staphylococcus aureus cells, and bactericidal activity towards a Staphylococcus aureus strain resistant to 2-phenoxyphenol (4). The latter result suggests that they have a different mechanism of action from 4, which is a FabI inhibitor previously proposed to be the minimum active fragment of riccardin-type macrocycles. Thus, cyclic structure is not a necessary condition for cell membrane leakage-mediated anti-MRSA activity of macrocyclic bis(bibenzyl)s. Copyright © 2016 Elsevier Ltd. All rights reserved.

Monensin, a polyether ionophore antibiotic, overcomes TRAIL resistance in glioma cells via endoplasmic reticulum stress, DR5 upregulation and c-FLIP downregulation.

PubMed

Yoon, Mi Jin; Kang, You Jung; Kim, In Young; Kim, Eun Hee; Lee, Ju Ahn; Lim, Jun Hee; Kwon, Taeg Kyu; Choi, Kyeong Sook

2013-08-01

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is preferentially cytotoxic to cancer cells over normal cells. However, many cancer cells, including malignant glioma cells, tend to be resistant to TRAIL. Monensin (a polyether ionophore antibiotic that is widely used in veterinary medicine) and salinomycin (a compound that is structurally related to monensin and shows cancer stem cell-inhibiting activity) are currently recognized as anticancer drug candidates. In this study, we show that monensin effectively sensitizes various glioma cells, but not normal astrocytes, to TRAIL-mediated apoptosis; this occurs at least partly via monensin-induced endoplasmic reticulum (ER) stress, CHOP-mediated DR5 upregulation and proteasome-mediated downregulation of c-FLIP. Interestingly, other polyether antibiotics, such as salinomycin, nigericin, narasin and lasalocid A, also stimulated TRAIL-mediated apoptosis in glioma cells via ER stress, CHOP-mediated DR5 upregulation and c-FLIP downregulation. Taken together, these results suggest that combined treatment of glioma cells with TRAIL and polyether ionophore antibiotics may offer an effective therapeutic strategy.

Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones

PubMed Central

Geyer, Joachim; Janko, Christina

2012-01-01

P-glycoprotein, encoded by the multidrug resistance gene MDR1, is an ATP-driven drug efflux pump which is highly expressed at the blood-brain barrier of vertebrates. Drug efflux of macrocyclic lactones by P-glycoprotein is highly relevant for the therapeutic safety of macrocyclic lactones, as thereby GABA-gated chloride channels, which are confined to the central nervous system in vertebrates, are protected from high drug concentrations that otherwise would induce neurological toxicity. A 4-bp deletion mutation exists in the MDR1 gene of many dog breeds such as the Collie and the Australian Shepherd, which results in the expression of a non-functional P-glycoprotein and is associated with multiple drug sensitivity. Accordingly, dogs with homozygous MDR1 mutation are in general prone to neurotoxicity by macrocyclic lactones due to their increased brain penetration. Nevertheless, treatment of these dogs with macrocyclic lactones does not inevitably result in neurological symptoms, since, the safety of treatment highly depends on the treatment indication, dosage, route of application, and the individual compound used as outlined in this review. Whereas all available macrocyclic lactones can safely be administered to MDR1 mutant dogs at doses usually used for heartworm prevention, these dogs will experience neurological toxicity following a high dose regimen which is common for mange treatment in dogs. Here, we review and discuss the neurotoxicological potential of different macrocyclic lactones as well as their treatment options in MDR1 mutant dogs. PMID:22039792

Aggregation of p-Sulfonatocalixarene-Based Amphiphiles and Supra-Amphiphiles

PubMed Central

Basilio, Nuno; Francisco, Vitor; Garcia-Rio, Luis

2013-01-01

p-Sulfonatocalixarenes are a special class of water soluble macrocyclic molecules made of 4-hydroxybenzenesulfonate units linked by methylene bridges. One of the main features of these compounds relies on their ability to form inclusion complexes with cationic and neutral species. This feature, together with their water solubility and apparent biological compatibility, had enabled them to emerge as one the most important host receptors in supramolecular chemistry. Attachment of hydrophobic alkyl chains to these compounds leads to the formation of macrocyclic host molecules with amphiphilic properties. Like other oligomeric surfactants, these compounds present improved performance with respect to their monomeric counterparts. In addition, they hold their recognition abilities and present several structural features that depend on the size of the macrocycle and on the length of the alkyl chain, such as preorganization, flexibility and adopted conformations, which make these molecules very interesting to study structure-aggregation relationships. Moreover, the recognition abilities of p-sulfonatocalixarenes enable them to be applied in the design of amphiphiles constructed from non-covalent, rather than covalent, bonds (supramolecular amphiphiles). In this review, we summarize the developments made on the design and synthesis of p-sulfonatocalixarenes-based surfactants, the characterization of their self-assembly properties and on how their structure affects these properties. PMID:23380960

Investigation of Coating Compounds and Adhesives for Self-Supporting Collapsible Fuel Storage Tanks.

DTIC Science & Technology

1977-06-01

guideline value of 25 lbs/ in. These low values were obtained because the prima ry mode of failure was between coats of the polyether coat- ing compound...method was developed for spray coating fabric substrates wi th one-shot pol yurethane materia ls yielding a coated fabric. Microscopic examination

The Discovery of Crown Ethers

NASA Astrophysics Data System (ADS)

Pedersen, Charles J.

1988-07-01

The discovery of the crown ethers stemmed from efforts to control the catalytic activity of vanadium and copper by complexation with multidentate ligands. The first crown ether, 2,3,11,12-dibenzo-1,4,7,10,13,16-hexaoxacyclo-octadeca-2,11-diene, was obtained in 0.4% yield during an attempt to prepare a phenolic ligand from catechol and bis(2-chloroethyl)ether. This compound, which complexed with the sodium cation, was the first compound known to display such activity and became known as dibenzo-18-crown-6, an 18-atom heterocycle containing 6 oxygen atoms. Some 60 related compounds were made involving heterocyclic rings containing 12 to 60 atoms including 4 and 10 oxygen atoms. There are optimum polyether ring sizes for the different alkali metal cations: 15 to 18 for sodium, 18 for potassium, and 18 to 21 for cesium. Complexes having polyether to cation ratios of 1:1, 3:2, and 2:1 were prepared. Solubilization of inorganic salts in aprotic solvents, especially by saturated crown ethers, was demonstrated.

Effect of the chemical modification of a macrocycle and the acidity of a medium on the spectral properties and basicity of tetraphenylporphyrin in HCl- N, N-dimethylformamide system at 298 K

NASA Astrophysics Data System (ADS)

Ivanova, Yu. B.; Razgonyaev, O. V.; Semeikin, A. S.; Mamardashvili, N. Zh.

2016-05-01

Spectrophotometric titration is used to study the basicity of tetraphenylporphine and its derivatives with electron-donor and electron-acceptor substituents in the 4-positions of meso-aryl fragments (5,10,15,20-tetra(4-R-phenyl)porphine, R:-OH,-NH2,-COOH,-Cl) in a system HCl- N, N-dimethylformamide at 298 K. An equation for calculating the dependence of the Hammett constant ( H 0) on the HCl concentration in a HCl- N, N-dimethylformamide system at 298 K is proposed. It is found that protonation of the intracycle nitrogen atoms of tetrapyrrole macrocycles of the indicated compounds occurs in two stages in this system. The corresponding ionization constants and concentration ranges of the existence of mono- and doubly-protonated dication forms of the indicated compounds are determined. It is found that both the introduction of strong substituents into the macrocycle of porphyrin and the properties of the medium facilitate the formation of mono- and doubly-protonated forms of porphyrins in solutions.

ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs

NASA Astrophysics Data System (ADS)

Cleves, Ann E.; Jain, Ajay N.

2017-05-01

We introduce the ForceGen method for 3D structure generation and conformer elaboration of drug-like small molecules. ForceGen is novel, avoiding use of distance geometry, molecular templates, or simulation-oriented stochastic sampling. The method is primarily driven by the molecular force field, implemented using an extension of MMFF94s and a partial charge estimator based on electronegativity-equalization. The force field is coupled to algorithms for direct sampling of realistic physical movements made by small molecules. Results are presented on a standard benchmark from the Cambridge Crystallographic Database of 480 drug-like small molecules, including full structure generation from SMILES strings. Reproduction of protein-bound crystallographic ligand poses is demonstrated on four carefully curated data sets: the ConfGen Set (667 ligands), the PINC cross-docking benchmark (1062 ligands), a large set of macrocyclic ligands (182 total with typical ring sizes of 12-23 atoms), and a commonly used benchmark for evaluating macrocycle conformer generation (30 ligands total). Results compare favorably to alternative methods, and performance on macrocyclic compounds approaches that observed on non-macrocycles while yielding a roughly 100-fold speed improvement over alternative MD-based methods with comparable performance.

A general strategy for synthesis of cyclophane-braced peptide macrocycles via palladium-catalysed intramolecular sp3 C-H arylation

NASA Astrophysics Data System (ADS)

Zhang, Xuekai; Lu, Gang; Sun, Meng; Mahankali, Madhu; Ma, Yanfei; Zhang, Mingming; Hua, Wangde; Hu, Yuting; Wang, Qingbing; Chen, Jinghuo; He, Gang; Qi, Xiangbing; Shen, Weijun; Liu, Peng; Chen, Gong

2018-05-01

New methods capable of effecting cyclization, and forming novel three-dimensional structures while maintaining favourable physicochemical properties are needed to facilitate the development of cyclic peptide-based drugs that can engage challenging biological targets, such as protein-protein interactions. Here, we report a highly efficient and generally applicable strategy for constructing new types of peptide macrocycles using palladium-catalysed intramolecular C(sp3)-H arylation reactions. Easily accessible linear peptide precursors of simple and versatile design can be selectively cyclized at the side chains of either aromatic or modified non-aromatic amino acid units to form various cyclophane-braced peptide cycles. This strategy provides a powerful tool to address the long-standing challenge of size- and composition-dependence in peptide macrocyclization, and generates novel peptide macrocycles with uniquely buttressed backbones and distinct loop-type three-dimensional structures. Preliminary cell proliferation screening of the pilot library revealed a potent lead compound with selective cytotoxicity toward proliferative Myc-dependent cancer cell lines.

Studies toward brevisulcenal F via convergent strategies for marine ladder polyether synthesis.

PubMed

Katcher, Matthew; Jamison, Timothy F

2018-03-15

Shortly after the initial isolation of marine ladder polyether natural products, biomimetic epoxide-opening cascade reactions were proposed as an efficient strategy for the synthesis of these compounds. However, difficulties in assembling the cascade precursors have limited the realization of these cascades. In this report, we describe strategies that provide convergent access to cascade precursors via regioselective allylation and efficient fragment coupling. We then investigate epoxide-opening cascades promoted by strong bases for the formation of fused tetrahydropyrans. These strategies are evaluated in the context of the synthesis of rings CDEFG of brevisulcenal F.

Synthesis and P1' SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ladziata, Vladimir; Glunz, Peter W.; Zou, Yan

Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1'-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1' group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1' substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity.

Extreme electronic modulation of the cofacial porphyrin structural motif.

PubMed

Fletcher, James T; Therien, Michael J

2002-04-24

The synthesis, electrochemistry, and optical spectroscopy of an extensive series of cofacial bis[(porphinato)zinc(II)] compounds are reported. These species were synthesized using sequential palladium-catalyzed cross-coupling and cobalt-mediated [2+2+2] cycloaddition reactions. This modular methodology enables facile control of the nature of macrocycle-to-macrocycle connectivity and allows unprecedented modulation of the redox properties of face-to-face porphyrin species. We report the synthesis of 5,6-bis[(5',5''-10',20'-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (1), 5,6-bis[(2'-5',10',15',20'-tetraphenylporphinato)zinc(II)]indane (2), 5-([2'-5',10',15',20'-tetraphenylporphinato]zinc(II))-6-[(5"-10'',20''-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (3), 5-([2'-5',10',15',20'-tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(5' '-10' ',20' '-bis[4-(3-methoxy-3-methylbutoxy)phenyl]porphinato)zinc(II)]indane (4), 5-(2'-5',10',15',20'-[tetrakis(trifluoromethyl)porphinato]zinc(II))-6-[(2''-5'',10'',15'',20''-tetraphenylporphinato)zinc(II)]indane (5), 5,6-bis([2'-5',15'-diphenyl-10',20'-(trifluoromethyl)porphinato]zinc(II))indane (6), and 5,6-bis([2'-5',10',15',20'-tetrakis(trifluoromethyl)porphinato]zinc(II))indane (7); 4-7 define the first examples of cofacial bis[(porphinato)metal] compounds in which sigma-electron-withdrawing perfluoroalkyl groups serve as macrocycle substituents, while 2, 6, and 7 constitute the first such structures that possess a beta-to-beta linkage topology. Cyclic voltammetric studies show that the electrochemically determined HOMO and LUMO energy levels of these cofacial bis(porphinato) complexes can be lowered by 780 and 945 mV, respectively, relative to the archetypal members of this class of compounds; importantly, these orbital energy levels can be modulated over well-defined increments throughout these wide potentiometric domains. Analyses of these cofacial bis[(porphinato)metal] potentiometric data, in terms of the absolute and relative frontier orbital energies of their constituent [porphinato]zinc(II) building blocks, as well as the nature of macrocycle-to-macrocycle connectivity, provide predictive electronic structural models that rationalize the redox behavior of these species.

Simple Syntheses of Two New Benzo-Fused Macrocycles Incorporating Chalcone Moiety

PubMed Central

Mondal, Rina; Samanta, Swati; Sarkar, Saheli; Mallik, Asok K.

2014-01-01

Simple syntheses of the benzo-fused 26-membered macrocyclic bischalcone (19E,43E)-2.11.27.36-tetroxaheptacyclo[44.4.0.04,9.012,17.021,26.029,34.037,42]pentaconta-1(46),4(9),5,7,12(17),13,15,19,21,23,25,29,31,33,37,39,41,43,47,49-icosaene-18,45-dione (3) and the benzo-fused 13-membered macrocyclic chalcone (19E)-2.11-dioxatetracyclo[19.4.0.04,9.012,17]pentacosa-1(25),4(9),5,7,12(17),13,15,19,21,23-decaen-18-one (5) using very common starting materials and reagents are described. The compounds are new and they have been characterized from their analytical and spectral data. PMID:27379283

Simple Syntheses of Two New Benzo-Fused Macrocycles Incorporating Chalcone Moiety.

PubMed

Mondal, Rina; Samanta, Swati; Sarkar, Saheli; Mallik, Asok K

2014-01-01

Simple syntheses of the benzo-fused 26-membered macrocyclic bischalcone (19E,43E)-2.11.27.36-tetroxaheptacyclo[44.4.0.0(4,9).0(12,17).0(21,26).0(29,34).0(37,42)]pentaconta-1(46),4(9),5,7,12(17),13,15,19,21,23,25,29,31,33,37,39,41,43,47,49-icosaene-18,45-dione (3) and the benzo-fused 13-membered macrocyclic chalcone (19E)-2.11-dioxatetracyclo[19.4.0.0(4,9).0(12,17)]pentacosa-1(25),4(9),5,7,12(17),13,15,19,21,23-decaen-18-one (5) using very common starting materials and reagents are described. The compounds are new and they have been characterized from their analytical and spectral data.

Turn on macrocyclic chemosensor for Al3+ ion with facile synthesis and application in live cell imaging

NASA Astrophysics Data System (ADS)

Ezhumalai, Dhineshkumar; Mathivanan, Iyappan; Chinnadurai, Anbuselvan

2018-06-01

An effort of a new Schiff base macrocyclic chemosensor, 14‑methyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecaphane‑2,5,8,11,14,17‑hexaene (me1) and 14,74‑dimethyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecadecaphane‑2,5,8,11,14,17‑hexaene (dm2), which enables selective sensing of Al3+ in aqueous DMF were synthesized by a simplistic one-step condensation reaction of macrocyclic compounds. The probe me1 and dm2 characterized by elemental analysis, FT-IR, 1H and 13C NMR, LC-MS spectral techniques. The compounds as mentioned above subjected to FE-SEM with EDS and elemental color mapping. On addition of Al3+, the fluorescent probe me1 and dm2 induces turn-on responses in both absorption and sensing spectra by a PET mechanism. The receptor me1 and dm2 serve highly selective, sensitive and turn-on detection of Al3+. Further, they did not interfere with other cations present in biological or environmental samples. The detection limit is found to be 3 μM and 5 μM. From the view of cytotoxic activity, the ability of these compounds me1 and dm2 to inhibit the growth of KB cell lines examined. The chelating functionality of compounds me1 and dm2 examined for their inhibitory properties of KB cell, live cell images. The compounds me1 and dm2 subjected to theoretical studies by DFT-B3LYP invoking the 6-31G level of theory. The energy of the HOMO and LUMO has been established.

Brevisulcatic acids, marine ladder-frame polyethers from the red tide dinoflagellate Karenia brevisulcata in New Zealand.

PubMed

Suzuki, Rina; Irie, Raku; Harntaweesup, Yanit; Tachibana, Kazuo; Holland, Patrick T; Harwood, D Tim; Shi, Feng; Beuzenberg, Veronica; Itoh, Yoshiyuki; Pascal, Steven; Edwards, Patrick J B; Satake, Masayuki

2014-11-21

The isolation and structural determination of new marine ladder-frame polyethers, brevisulcatic acids-1 (1) and -4 (2) are reported. Brevisulcatic acids were isolated from the dinoflagellate Karenia brevisulcata, which was identified as the causative species of a major red tide event in New Zealand in 1998. The ether ring composition and a β-hydroxy, γ-methylene valeric acid side chain of 1 and 2 are common, but 2 has a γ-lactone as the 5-membered A-ring while 1 is the seco acid analogue. Compound 2 has structural and bioactivity similarities to brevetoxin A.

Nonthmicin, a Polyether Polyketide Bearing a Halogen-Modified Tetronate with Neuroprotective and Antiinvasive Activity from Actinomadura sp.

PubMed

Igarashi, Yasuhiro; Matsuoka, Noriaki; In, Yasuko; Kataura, Tetsushi; Tashiro, Etsu; Saiki, Ikuo; Sudoh, Yuri; Duangmal, Kannika; Thamchaipenet, Arinthip

2017-03-17

Nonthmicin (1), a new polyether polyketide bearing a chlorinated tetronic acid, was isolated from the culture extract of a soil-derived Actinomadura strain. The structure of 1 was elucidated by interpretation of NMR and MS spectroscopic data, and the absolute configuration of 1 was proposed on the basis of the crystal structure of its dechloro congener ecteinamycin (2) also isolated from the same strain. Tetronic acids modified by halogenation have never been reported from natural products. Compounds 1 and 2 were found to have neuroprotective activity and antimetastatic properties at submicromolar concentrations in addition to antibacterial activity.

Fire-retardant epoxy polymers

NASA Technical Reports Server (NTRS)

Akawie, R. I.; Bilow, N.; Giants, T. W.

1978-01-01

Phosphorus atoms in molecular structure of epoxies make them fire-retardant without degrading their adhesive strength. Moreover, polymers are transparent, unlike compounds that contain arsenic or other inorganics. They have been used to bond polyvinylfluoride and polyether sulfone films onto polyimide glass laminates.

Macrocyclic polyaminocarboxylates for stable radiometal antibody conjugates for therapy, spect and pet imaging

DOEpatents

Mease, Ronnie C.; Mausner, Leonard F.; Srivastava, Suresh C.

1997-06-17

A simple method for the synthesis of 1,4,7, 10-tetraazacyclododecane N,N'N",N'"-tetraacetic acid and 1,4,8,11-tetraazacyclotetradecane N,N',N",N'"-tetraacetic acid involves cyanomethylating 1,4,7, 10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane to form a tetranitrile and hydrolyzing the tetranitrile. These macrocyclic compounds are functionalized through one of the carboxylates and then conjugated to various biological molecules including monoclonal antibodies. The resulting conjugated molecules are labeled with radiometals for SPECT and PET imaging and for radiotherapy.

Design and Synthesis of Novel Arylketo-containing P1-P3 Linked Macro-cyclic BACE-1 Inhibitors

PubMed Central

Sandgren, Veronica; Belda, Oscar; Kvarnström, Ingemar; Lindberg, Jimmy; Samuelsson, Bertil; Dahlgren, Anders

2015-01-01

A series of arylketo-containing P1-P3 linked macrocyclic BACE-1 inhibitors were designed, synthesized, and compared with compounds with a previously known and extensively studied corresponding P2 isophthalamide moiety with the aim to improve on permeability whilst retaining the enzyme- and cell-based activities. Several inhibitors displayed substantial increases in Caco-2 cell-based permeability compared to earlier synthesized inhibitors and notably also with retained activities, showing that this approach might yield BACE-1 inhibitors with improved properties. PMID:25937848

Complexation of β-cyclodextrin with dual molecular probes bearing fluorescent and paramagnetic moieties linked by short polyether chains.

PubMed

Mocanu, S; Matei, I; Ionescu, S; Tecuceanu, V; Marinescu, G; Ionita, P; Culita, D; Leonties, A; Ionita, Gabriela

2017-10-18

Electron paramagnetic resonance (EPR) and fluorescence spectroscopies provide molecular-level insights on the interaction of paramagnetic and fluorescent species with the microenvironment. A series of dual molecular probes bearing fluorescent and paramagnetic moieties linked by flexible short polyether chains have been synthesized. These new molecular probes open the possibility to investigate various multi-component systems such as host-guest systems, polymeric micelles, gels and protein solutions by using EPR and fluorescence spectroscopies concertedly. The EPR and fluorescence spectra of these compounds show that the dependence of the rotational correlation time and fluorescence quantum yield on the chain length of the linker is not linear, due to the flexibility of the polyether linker. The quenching effect of the nitroxide moiety on the fluorescence intensity of the pyrene group varies with the linker length and flexibility. The interaction of these dual molecular probes with β-cyclodextrin, in solution and in polymeric gels, was evaluated and demonstrated by analysis of EPR and fluorescence spectra.

Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)–Mixed Lineage Leukemia (MLL) Protein–Protein Interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karatas, Hacer; Li, Yangbing; Liu, Liu

We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) and block the WDR5–mixed lineage leukemia (MLL) protein–protein interaction. Compound 18 (MM-589) binds to WDR5 with an IC50 value of 0.90 nM (Ki value <1 nM) and inhibits the MLL H3K4 methyltransferase (HMT) activity with an IC50 value of 12.7 nM. Compound 18 potently and selectively inhibits cell growth in human leukemia cell lines harboring MLL translocations and is >40 times better than the previously reported compound MM-401. Cocrystal structures of 16 and 18 complexed with WDR5 provide structural basis formore » their high affinity binding to WDR5. Additionally, we have developed and optimized a new AlphaLISA-based MLL HMT functional assay to facilitate the functional evaluation of these designed compounds. Compound 18 represents the most potent inhibitor of the WDR5–MLL interaction reported to date, and further optimization of 18 may yield a new therapy for acute leukemia.« less

Second symposium on macrocyclic compounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izatt, R.M.; Christensen, J.J.

1978-01-01

Forty papers were presented at the sumposium under five session headings: inorganic reactions, industrial applications, biological and biochemistry, organic synthesis and reactions, and thermodynamics and kinetics. Abstracts of these papers are included in this document. (DLC)

Design, synthesis and characterization of macrocyclic ligand based transition metal complexes of Ni(II), Cu(II) and Co(II) with their antimicrobial and antioxidant evaluation

NASA Astrophysics Data System (ADS)

Gull, Parveez; Malik, Manzoor Ahmad; Dar, Ovas Ahmad; Hashmi, Athar Adil

2017-04-01

Three new complexes Ni(II), Cu(II) and Co(II) were synthesized of macrocyclic ligand derived from 1, 4-dicarbonyl-phenyl-dihydrazide and O-phthalaldehyde in the ratio of 2:2. The synthesized compounds were characterized by elemental analyses, molar conductance, magnetic susceptibility measurements, FTIR, UV-Vis., Mass and 1H NMR spectral studies. The electronic spectra of the metal complexes indicate a six coordinate octahedral geometry of the central metal ion. These metal complexes and the ligand were evaluated for antimicrobial activity against bacteria (E. coli, B. subtilis, S. aureus) and fungi (A. niger, A. flavus, C. albicans) and compared against standard drugs chloramphenicol and nystatin respectively. In addition, the antioxidant activity of the compounds was also investigated through scavenging effect on DPPH radicals.

Structure-based design of oxygen-linked macrocyclic kinase inhibitors: discovery of SB1518 and SB1578, potent inhibitors of Janus kinase 2 (JAK2) and Fms-like tyrosine kinase-3 (FLT3)

NASA Astrophysics Data System (ADS)

Poulsen, Anders; William, Anthony; Blanchard, Stéphanie; Lee, Angeline; Nagaraj, Harish; Wang, Haishan; Teo, Eeling; Tan, Evelyn; Goh, Kee Chuan; Dymock, Brian

2012-04-01

Macrocycles from our Aurora project were screened in a kinase panel and were found to be active on other kinase targets, mainly JAKs, FLT3 and CDKs. Subsequently these compounds became leads in our JAK2 project. Macrocycles with a basic nitrogen in the linker form a salt bridge with Asp86 in CDK2 and Asp698 in FLT3. This residue is conserved in most CDKs resulting in potent pan CDK inhibition. One of the main project objectives was to achieve JAK2 potency with 100-fold selectivity against CDKs. Macrocycles with an ether linker have potent JAK2 activity with the ether oxygen forming a hydrogen bond to Ser936. A hydrogen bond to the equivalent residues of JAK3 and most CDKs cannot be formed resulting in good selectivity for JAK2 over JAK3 and CDKs. Further optimization of the macrocyclic linker and side chain increased JAK2 and FLT3 activity as well as improving DMPK properties. The selective JAK2/FLT3 inhibitor 11 (Pacritinib, SB1518) has successfully finished phase 2 clinical trials for myelofibrosis and lymphoma. Another selective JAK2/FLT3 inhibitor, 33 (SB1578), has entered phase 1 clinical development for the non-oncology indication rheumatoid arthritis.

Syntheses and Functionalizations of Porphyrin Macrocycles

PubMed Central

Vicente, Maria da G.H.; Smith, Kevin M.

2014-01-01

Porphyrin macrocycles have been the subject of intense study in the last century because they are widely distributed in nature, usually as metal complexes of either iron or magnesium. As such, they serve as the prosthetic groups in a wide variety of primary metabolites, such as hemoglobins, myoglobins, cytochromes, catalases, peroxidases, chlorophylls, and bacteriochlorophylls; these compounds have multiple applications in materials science, biology and medicine. This article describes current methodology for preparation of simple, symmetrical model porphyrins, as well as more complex protocols for preparation of unsymmetrically substituted porphyrin macrocycles similar to those found in nature. The basic chemical reactivity of porphyrins and metalloporphyrin is also described, including electrophilic and nucleophilic reactions, oxidations, reductions, and metal-mediated cross-coupling reactions. Using the synthetic approaches and reactivity profiles presented, eventually almost any substituted porphyrin system can be prepared for applications in a variety of areas, including in catalysis, electron transport, model biological systems and therapeutics. PMID:25484638

A new spermidine macrocyclic alkaloid isolated from Gymnosporia arenicola leaf.

PubMed

da Silva, Gustavo; Martinho, Ana; Soengas, Raquel González; Duarte, Ana Paula; Serrano, Rita; Gomes, Elsa Teixeira; Silva, Olga

2015-10-01

The isolation and structural elucidation of a macrocyclic alkaloid, characterized by the presence of a 13-membered macrolactam ring containing a spermidine unit N-linked to a benzoyl group is hereby reported. The structure of this previously unknown spermidine alkaloid isolated from Gymnosporia arenicola (Celastraceae) leaves has been elucidated by (1)H and (13)C NMR spectroscopy (including bidimensional analysis) and further characterized by high-resolution mass spectrometry and polarimetry. A route for the biosynthesis of this new bioactive macrocycle is proposed and the cytotoxicity of the compound was evaluated against two ATCC cell lines - one normal-derived (MCF10A) and one cancer-derived cell line (MCF7) - using the MTT assay. The alkaloid revealed to be non-cytotoxic against both cell lines. The IC50 values from the cells were also determined. Copyright © 2015 Elsevier B.V. All rights reserved.

The interaction of amino acids with macrocyclic pH probes of pseudopeptidic nature.

PubMed

Izquierdo, M Angeles; Wadhavane, Prashant D; Vigara, Laura; Burguete, M Isabel; Galindo, Francisco; Luis, Santiago V

2017-08-09

The fluorescence quenching, by a series of amino acids, of pseudopeptidic compounds acting as probes for cellular acidity has been investigated. It has been found that amino acids containing electron-rich aromatic side chains like Trp or Tyr, as well as Met quench the emission of the probes mainly via a collisional mechanism, with Stern-Volmer constants in the 7-43 M -1 range, while other amino acids such as His, Val or Phe did not cause deactivation of the fluorescence. Only a minor contribution of a static quenching due to the formation of ground-state complexes has been found for Trp and Tyr, with association constants in the 9-24 M -1 range. For these ground-state complexes, a comparison between the macrocyclic probes and an open chain analogue reveals the existence of a moderate macrocyclic effect due to the preorganization of the probes in the more rigid structure.

Ladder Polyether Synthesis via Epoxide-Opening Cascades Directed by a Disappearing Trimethylsilyl Group

PubMed Central

Heffron, Timothy P.; Simpson, Graham L.; Merino, Estibaliz; Jamison, Timothy F.

2010-01-01

Epoxide-opening cascades offer the potential to construct complex polyether natural products expeditiously and in a manner that emulates the biogenesis proposed for these compounds. Herein we provide a full account of our development of a strategy that addresses several important challenges of such cascades. The centerpiece of the method is a trimethylsilyl (SiMe3) group that serves several purposes and leaves no trace of itself by the time the cascade has come to an end. The main function of the SiMe3 group is to dictate the regioselectivity of epoxide opening. This strategy is the only general method of effecting endo-selective cascades under basic conditions. PMID:20302314

One-pot synthesis and cytotoxicity studies of new Mannich base derivatives of polyether antibiotic--lasalocid acid.

PubMed

Huczyński, Adam; Rutkowski, Jacek; Borowicz, Izabela; Wietrzyk, Joanna; Maj, Ewa; Brzezinski, Bogumil

2013-09-15

Seven Mannich base derivatives of polyether antibiotic Lasalocid acid (2a-2g) were synthesized and screened for their antiproliferative activity against various human cancer cell lines. A novel chemoselective one-pot synthesis of these Mannich bases was developed. Compounds 2a-2c and 2g with sterically smaller dialkylamine substituent, displayed potent antiproliferative activity (IC50: 3.2-7.3 μM), and demonstrated higher than twofold selectivity for specific type of cancer. The nature of Mannich base substituent on C-2 atom at the aromatic ring may be critical in the search for selectivity towards a particular cancer cell. Copyright © 2013 Elsevier Ltd. All rights reserved.

QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity.

PubMed

Sousa, Inês J; Ferreira, Maria-José U; Molnár, Joseph; Fernandes, Miguel X

2013-02-14

Multidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatrophane-type diterpenes from Euphorbia species were found to be strong MDR reversing agents. In this study we applied quantitative structure-activity relationship (QSAR) methodology in order to identify the most relevant molecular features of macrocyclic diterpenes with P-gp inhibitory activity and to determine which structural modifications can be performed to improve their activity. Using experimental biological data at two concentrations (4 and 40 μg/ml), we developed a QSAR model for a set of 51 bioactive diterpenic compounds which includes lathyrane and jatrophane-type diterpenes and another model just for jatrophanes. The cross-validation correlation values for all diterpenes QSAR models developed for biological activities at compound concentrations of 4 and 40 μg/ml were 0.758 and 0.729, respectively. Regarding the prediction ability, we get R²(pred) values of 0.765 and 0.534 for biological activities at compound concentrations of 4 and 40 μg/ml, respectively. Applying the cross-validation test to jatrophanes QSAR models, we obtained 0.680 and 0.787 for biological activities at compound concentrations of 4 and 40 μg/ml concentrations, respectively. For the same concentrations, the obtained R²(pred) values for jatrophanes models were 0.541 and 0.534, respectively. The obtained models were statistically valid and showed high prediction ability. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis of macrocyclic polyaminocarboxylates and their use for preparing stable radiometal antibody immunoconjugates for therapy, spect and pet imaging

DOEpatents

Mease, Ronnie C.; Mausner, Leonard F.; Srivastava, Suresh C.

1995-06-27

A simple method for the synthesis of 1,4,7,10-tetraazacyclododecane N,N'N",N'"-tetraacetic acid and 1,4,8,11-tetraazacyclotetradecane N,N',N",N'"-tetraacetic acid involves cyanomethylating 1,4,7,10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane to form a tetranitrile and hydrolyzing the tetranitrile. These macrocyclic compounds are functionalized through one of the carboxylates and then conjugated to various biological molecules including monoclonal antibodies. The resulting conjugated molecules are labeled with radiometals for SPECT and PET imaging and for radiotherapy.

Synthesis and Characterization of Polyether Adducts of Barium and Strontium Carboxylates and Their Use in the Formation of MTiO(3) Films.

PubMed

Wojtczak, William A.; Atanassova, Paolina; Hampden-Smith, Mark J.; Duesler, Eileen

1996-11-20

The synthesis, characterization, and reactivity of new polyether adducts of strontium and barium carboxylates of general composition M(O(2)CCF(3))(n)()(L) (M = Ba, L = 15-crown-5, (1); M = Ba (2), Sr (3), respectively, with L = tetraglyme are reported. The compounds were synthesized by reaction of BaCO(3) or MH(2) (M = Sr or Ba) with organic acids in the presence of the polyether ligands. These compounds have been characterized by IR and (13)C and (1)H NMR spectroscopies, elemental analyses, and thermogravimetric analysis. The species Ba(2)(O(2)CCF(3))(4)(15-crown-5)(2) (1) and [Ba(2)(O(2)CCF(3))(4)(tetraglyme)](infinity) (2), were also characterized by single-crystal X-ray diffraction. Ba(2)(O(2)CCF(3))(4)(15-crown-5)(2) (1) crystallizes in the orthorhombic space group Cccm with cell dimensions of a = 13.949(1) Å, b = 19.376(2) Å, c = 16.029(1) Å, and Z = 8. [Ba(2)(O(2)CCF(3))(4)(tetraglyme)](infinity) (2) crystallizes in the monoclinic space group C2/c with cell dimensions of a = 12.8673(12) Å, b = 16.6981(13) Å, c = 15.1191(12) Å, beta = 99.049(8) degrees, and Z = 4. Compounds 1-3 thermally decompose at high temperatures in the solid state to give MF(2). However, solutions of compounds 1-3 dissolved in ethanol with Ti(O-i-Pr)(4) give crystalline perovskite phase MTiO(3) films, or in the case of mixtures of 2 and 3, Ba(1)(-)(x)()Sr(x)()TiO(3) films below 600 degrees C when spin coated onto silicon substrates and thermally treated. The crystallinity, purity, and elemental composition of the films was determined by glancing angle X-ray diffraction and Auger electron spectroscopy.

Highly Destructive Polymer-Contained Neutralizing Skin Protectants

DTIC Science & Technology

1997-06-01

compound derived by reaction with a polymer or monomer. Our Phase I experiments have identified and proved out the feasibility of at least 3 metal...neutralizing agents are incorporated into a base cream, containing a mixture of perfluorinated polyether oil and Teflon particulates as thickener, for...reaction. PURPOSE The ultimate purpose of this research effort was to develop neutralizing compounds , which when incorporated into a base cream, provide a

Spectroscopic, semiempirical studies and antibacterial activity of new urethane derivatives of natural polyether antibiotic - Monensin A

NASA Astrophysics Data System (ADS)

Huczyński, Adam; Stefańska, Joanna; Piśmienny, Mieszko; Brzezinski, Bogumil

2013-02-01

A series of new Monensin A dimers linked by diurethane moiety were synthesised and their molecular structures were studied using ESI-MS, FT-IR, 1H and 13C NMR and PM5 methods. The results showed that the compounds form a pseudo-cyclic structure stabilized by three intramolecular hydrogen bonds and the sodium cation was coordinated by five oxygen atoms of polyether skeleton of Monensin moiety. The NMR and FT-IR data of complexes of Monensin urethane sodium salts demonstrated that within the pseudo-cyclic structure the carbonyl oxygen atom of the urethane group did not coordinate the sodium cation. Monensin urethanes were tested in vitro for the activity against Gram-positive and Gram-negative bacteria and fungi as well as against a series of clinical isolates of Staphylococcus: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). The most active compound against MRSA and MSSA was 1,4-phenylene diurethane of Monensin with MIC 10.4-41.4 μmol/L).

Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin

PubMed Central

2011-01-01

Background The natural polyether ionophorous antibiotics are used for the treatment of coccidiosis in poultry and ruminants. They are effective agents against infections caused by Gram-positive microorganisms. On the other hand, it was found that some of these compounds selectively bind lead(II) ions in in vivo experiments, despite so far no Pb(II)-containing compounds of defined composition have been isolated and characterized. To assess the potential of polyether ionophores as possible antidotes in the agriculture, a detailed study on their in vitro complexation with toxic metal ions is required. In the present paper we report for the first time the preparation and the structure elucidation of salinomycin complexes with ions of cadmium(II) and lead(II). Results New metal(II) complexes of the polyether ionophorous antibiotic salinomycin with Cd(II) and Pb(II) ions were prepared and structurally characterized by IR, FAB-MS and NMR techniques. The spectroscopic information and elemental analysis data reveal that sodium salinomycin (SalNa) undergoes a reaction with heavy metal(II) ions to form [Cd(Sal)2(H2O)2] (1) and [Pb(Sal)(NO3)] (2), respectively. Abstraction of sodium ions from the cavity of the antibiotic is occurring during the complexation reaction. Salinomycin coordinates with cadmium(II) ions as a bidentate monoanionic ligand through the deprotonated carboxylic moiety and one of the hydroxyl groups to yield 1. Two salinomycin anions occupy the equatorial plane of the Cd(II) center, while two water molecules take the axial positions of the inner coordination sphere of the metal(II) cation. Complex 2 consists of monoanionic salinomycin acting in polydentate coordination mode in a molar ratio of 1: 1 to the metal ion with one nitrate ion for charge compensation. Conclusion The formation of the salinomycin heavy metal(II) complexes indicates a possible antidote activity of the ligand in case of chronic/acute intoxications likely to occur in the stock farming. PMID:21906282

Arg-Phe-Phe D-Amino Acid Stereochemistry Scan in the Macrocyclic Agouti-Related Protein Antagonist Scaffold c[Pro-Arg-Phe-Phe-Xaa-Ala-Phe-DPro] Results in Unanticipated Melanocortin-1 Receptor Agonist Profiles.

PubMed

Ericson, Mark D; Koerperich, Zoe M; Freeman, Katie T; Fleming, Katlyn A; Haskell-Luevano, Carrie

2018-06-20

The melanocortin-3 and melanocortin-4 receptors (MC3R and MC4R), endogenous agonists derived from the proopiomelanocortin gene transcript, and naturally-occurring antagonists agouti and agouti-related protein (AGRP) have been linked to biological pathways associated with energy homeostasis. The active tripeptide sequence of AGRP, Arg111-Phe112-Phe113, is located on a hypothesized β-hairpin loop. Herein, stereochemical modifications of the Arg-Phe-Phe sequence were examined in the octapeptide AGRP-derived macrocyclic scaffold c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was Asn or diaminopropionic acid (Dap). Macrocyclic peptides were synthesized with one, two, or three residues of the Arg-Phe-Phe sequence substituted with the corresponding D-isomer(s), generating a 14 compound library. While L-to-D inversions of the Arg-Phe-Phe sequence in a 20-residue AGRP-derived ligand previously resulted in agonist activity at the MC1R, MC3R, MC4R, and MC5R, only the MC1R was consistently stimulated by the macrocyclic ligands in the present study, with varying ligand potencies and efficacies observed at the MC1R. A general trend of increased MC4R antagonist potency was observed for Dap-containing compounds, while MC5R inverse agonist activity was observed for select ligands. It was observed that stereochemical modification of the Arg-Phe-Phe active tripeptide sequence was insufficient to convert melanocortin antagonist into agonists. Overall, these observations are important in the design of melanocortin ligands possessing potent and selective agonist and antagonist activities.

Turn on macrocyclic chemosensor for Al3+ ion with facile synthesis and application in live cell imaging.

PubMed

Ezhumalai, Dhineshkumar; Mathivanan, Iyappan; Chinnadurai, Anbuselvan

2018-06-15

An effort of a new Schiff base macrocyclic chemosensor, 1 4 ‑methyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecaphane‑2,5,8,11,14,17‑hexaene (me1) and 1 4 ,7 4 ‑dimethyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecadecaphane‑2,5,8,11,14,17‑hexaene (dm2), which enables selective sensing of Al 3+ in aqueous DMF were synthesized by a simplistic one-step condensation reaction of macrocyclic compounds. The probe me1 and dm2 characterized by elemental analysis, FT-IR, 1 H and 13 C NMR, LC-MS spectral techniques. The compounds as mentioned above subjected to FE-SEM with EDS and elemental color mapping. On addition of Al 3+ , the fluorescent probe me1 and dm2 induces turn-on responses in both absorption and sensing spectra by a PET mechanism. The receptor me1 and dm2 serve highly selective, sensitive and turn-on detection of Al 3+ . Further, they did not interfere with other cations present in biological or environmental samples. The detection limit is found to be 3μM and 5μM. From the view of cytotoxic activity, the ability of these compounds me1 and dm2 to inhibit the growth of KB cell lines examined. The chelating functionality of compounds me1 and dm2 examined for their inhibitory properties of KB cell, live cell images. The compounds me1 and dm2 subjected to theoretical studies by DFT-B3LYP invoking the 6-31G level of theory. The energy of the HOMO and LUMO has been established. Copyright © 2018 Elsevier B.V. All rights reserved.

A novel complexity-to-diversity strategy for the diversity-oriented synthesis of structurally diverse and complex macrocycles from quinine.

PubMed

Ciardiello, J J; Stewart, H L; Sore, H F; Galloway, W R J D; Spring, D R

2017-06-01

Recent years have witnessed a global decline in the productivity and advancement of the pharmaceutical industry. A major contributing factor to this is the downturn in drug discovery successes. This can be attributed to the lack of structural (particularly scaffold) diversity and structural complexity exhibited by current small molecule screening collections. Macrocycles have been shown to exhibit a diverse range of biological properties, with over 100 natural product-derived examples currently marketed as FDA-approved drugs. Despite this, synthetic macrocycles are widely considered to be a poorly explored structural class within drug discovery, which can be attributed to their synthetic intractability. Herein we describe a novel complexity-to-diversity strategy for the diversity-oriented synthesis of novel, structurally complex and diverse macrocyclic scaffolds from natural product starting materials. This approach exploits the inherent structural (including functional) and stereochemical complexity of natural products in order to rapidly generate diversity and complexity. Readily-accessible natural product-derived intermediates serve as structural templates which can be divergently functionalized with different building blocks to generate a diverse range of acyclic precursors. Subsequent macrocyclisation then furnishes compounds that are each based around a distinct molecular scaffold. Thus, high levels of library scaffold diversity can be rapidly achieved. In this proof-of-concept study, the natural product quinine was used as the foundation for library synthesis, and six novel structurally diverse, highly complex and functionalized macrocycles were generated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Macrocyclic polyaminocarboxylates for stable radiometal antibody conjugates for therapy, SPECT and PET imaging

DOEpatents

Mease, R.C.; Mausner, L.F.; Srivastava, S.C.

1997-06-17

A simple method for the synthesis of 1,4,7, 10-tetraazacyclododecane N,N{prime}N{double_prime},N{prime}{double_prime}-tetraacetic acid and 1,4,8,11-tetraazacyclotetradecane N,N{prime},N{double_prime},N{prime}{double_prime}-tetraacetic acid involves cyanomethylating 1,4,7,10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane to form a tetranitrile and hydrolyzing the tetranitrile. These macrocyclic compounds are functionalized through one of the carboxylates and then conjugated to various biological molecules including monoclonal antibodies. The resulting conjugated molecules are labeled with radiometals for SPECT and PET imaging and for radiotherapy. 4 figs.

The Screening Compound Collection: A Key Asset for Drug Discovery.

PubMed

Boss, Christoph; Hazemann, Julien; Kimmerlin, Thierry; von Korff, Modest; Lüthi, Urs; Peter, Oliver; Sander, Thomas; Siegrist, Romain

2017-10-25

In this case study on an essential instrument of modern drug discovery, we summarize our successful efforts in the last four years toward enhancing the Actelion screening compound collection. A key organizational step was the establishment of the Compound Library Committee (CLC) in September 2013. This cross-functional team consisting of computational scientists, medicinal chemists and a biologist was endowed with a significant annual budget for regular new compound purchases. Based on an initial library analysis performed in 2013, the CLC developed a New Library Strategy. The established continuous library turn-over mode, and the screening library size of 300'000 compounds were maintained, while the structural library quality was increased. This was achieved by shifting the selection criteria from 'druglike' to 'leadlike' structures, enriching for non-flat structures, aiming for compound novelty, and increasing the ratio of higher cost 'Premium Compounds'. Novel chemical space was gained by adding natural compounds, macrocycles, designed and focused libraries to the collection, and through mutual exchanges of proprietary compounds with agrochemical companies. A comparative analysis in 2016 provided evidence for the positive impact of these measures. Screening the improved library has provided several highly promising hits, including a macrocyclic compound, that are currently followed up in different Hit-to-Lead and Lead Optimization programs. It is important to state that the goal of the CLC was not to achieve higher HTS hit rates, but to increase the chances of identified hits to serve as the basis of successful early drug discovery programs. The experience gathered so far legitimates the New Library Strategy.

Safety and clinical efficacy of tenvermectin, a novel antiparasitic 16-membered macrocyclic lactone antibiotics.

PubMed

Fei, Chenzhong; She, Rufeng; Li, Guiyu; Zhang, Lifang; Fan, Wushun; Xia, Suhan; Xue, Feiqun

2018-05-30

Tenvermectin (TVM) is a novel 16-membered macrocyclic lactone antibiotics, which contains component TVM A and TVM B. However there is not any report on safety and clinical efficacy of TVM for developing as a potential drug. In order to understand the part of safety and clinical efficacy of TVM, we conducted the acute toxicity test, the standard bacterial reverse mutation (Ames) test and the clinical deworming test. In the acute toxicity studies, TVM, TVM A and ivermectin (IVM) were administrated once by oral gavage to mice and rats. Results showed that the oral LD 50 values of TVM, TVM A and IVM in mice were 74.41, 106.95 and 53.06 mg/kg respectively. The oral LD 50 values of TVM and TVM A in rats were determined to be 164.22 and 749.34 mg/kg respectively. TVM and IVM are moderately toxic substances, meanwhile the TVM A belongs to low toxic compounds, implying that the acute toxicity is highly related to the length of side chain of TVM at position C25. In the Ames test, results showed that TVM did not induce mutagenicity in Salmonella typhimurium TA97a, TA98, TA100, TA102 and TA1535 with and without metabolic activation system, speculating that the mutagenicity is probably not related to the side chain at position C25 of 16-membered macrocyclic lactone antibiotics. In the efficacy trail of TVM against swine nematodes, growing pigs natural infection of Ascaris suum and Trichuris suis were treated with a single subcutaneous injection 0.3 mg/kg b.w.. Results showed that TVM and IVM had excellent effect in expelling Ascaris suum, and TVM had potential efficacy against Trichuris suis, however IVM had no effect on Trichuris suis. This study suggests that the side chain of TVM at position C25 may have important biological functions, which is one of the key sites of the studies on structure-activity relationship of 16-membered macrocyclic lactone compounds. TVM is a new compound exhibited some advantages worthy of developing. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition.

PubMed

Pirali, Tracey; Faccio, Valeria; Mossetti, Riccardo; Grolla, Ambra A; Di Micco, Simone; Bifulco, Giuseppe; Genazzani, Armando A; Tron, Gian Cesare

2010-02-01

Novel macrocyclic peptide mimetics have been synthesized by exploiting a three-component reaction and an azide-alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed.

Synthesis, Structure, and Molecular Recognition of S6 - and (SO2 )6 -Corona[6](het)arenes: Control of Macrocyclic Conformation and Properties by the Oxidation State of the Bridging Heteroatoms.

PubMed

Guo, Qing-Hui; Zhao, Liang; Wang, Mei-Xiang

2016-05-10

We report herein the synthesis, structure, and molecular recognition of S6 - and (SO2 )6 -corona[6](het)arenes, and demonstrate a unique and efficient strategy of regulating macrocyclic conformation and properties by adjusting the oxidation state of the heteroatom linkages. The one-pot nucleophilic aromatic substitution reaction of 1,4-benzenedithiol derivatives, biphenyl-4,4'-dithiol and 9,9-dipropyl-9H-fluorene-2,7-dithiol with 3,6-dichlorotetrazine afforded S6 -corona[3]arene[3]tetrazines. These compounds underwent inverse-electron-demand Diels-Alder reaction with enamines and norbornadiene to produce S6 -corona[3]arene[3]pyridazines. Facile oxidation of sulfide linkages yielded (SO2 )6 -corona[3]arene[3]pyridazines. All corona[6](het)arenes adopted generally hexagonal macrocyclic ring structures; however, their electronic properties and conformation could be fine-tuned by altering the oxidation state of the sulfur linkages. Whereas (SO2 )6 -corona[3]arene[3]pyridazines were electron-deficient, S6 -corona[3]arene[3]pyridazines acted as electron-rich macrocyclic hosts that recognized various organic cations in both aqueous and organic solutions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Safe battery solvents

DOEpatents

Harrup, Mason K.; Delmastro, Joseph R.; Stewart, Frederick F.; Luther, Thomas A.

2007-10-23

An ion transporting solvent maintains very low vapor pressure, contains flame retarding elements, and is nontoxic. The solvent in combination with common battery electrolyte salts can be used to replace the current carbonate electrolyte solution, creating a safer battery. It can also be used in combination with polymer gels or solid polymer electrolytes to produce polymer batteries with enhanced conductivity characteristics. The solvents may comprise a class of cyclic and acyclic low molecular weight phosphazenes compounds, comprising repeating phosphorus and nitrogen units forming a core backbone and ion-carrying pendent groups bound to the phosphorus. In preferred embodiments, the cyclic phosphazene comprises at least 3 phosphorus and nitrogen units, and the pendent groups are polyethers, polythioethers, polyether/polythioethers or any combination thereof, and/or other groups preferably comprising other atoms from Group 6B of the periodic table of elements.

Dark and Photoinduced Cytotoxic Activity of the New Chlorophyll-a Derivatives with Oligoethylene Glycol Substituents on the Periphery of Their Macrocycles.

PubMed

Pylina, Yana I; Shadrin, Dmitry M; Shevchenko, Oksana G; Startseva, Olga M; Velegzhaninov, Igor O; Belykh, Dmitry V; Velegzhaninov, Ilya O

2017-01-05

In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series-pyropheophorbide-a 17-diethylene glycol ester (Compound 21 ) was performed. This new compound is characterized by lower dark cytotoxicity and higher photoinduced cytotoxicity than previously described in a similar compound (DH-I-180-3) and clinically used Photolon TM . Using fluorescent microscopy, it was shown that Compound 21 quickly penetrates the cells. Analysis of caspase-3 activity indicated an apoptosis induction 40 min after exposure to red light (λ = 660 nm). The induction of DNA damages and apoptosis was shown using Comet assay. The results of expression analysis of the stress-response genes indicate an activation of the genes which control the cell cycle and detoxification of the free radicals after an exposure of HeLa cells to Compound 21 and to red light. High photodynamic activity of this compound and the ability to oxidize biomolecules was demonstrated on nuclear-free mice erythrocytes. In addition, it was shown that Compound 21 is effectively activated with low energy 700 nm light, which can penetrate deep into the tissue. Thus, Compound 21 is a prospective substance for development of the new drugs for photodynamic therapy of cancer.

Supramolecular Organocatalysis in Water Mediated by Macrocyclic Compounds

NASA Astrophysics Data System (ADS)

De Rosa, Margherita; La Manna, Pellegrino; Talotta, Carmen; Soriente, Annunziata; Gaeta, Carmine; Neri, Placido

2018-04-01

In the last decades many efforts have been devoted to design supramolecular organocatalysts able to work in water as the reaction medium. The use of water as solvent provides promising benefits with respect to environmental impact. In this context, macrocyclic compounds played a role of primary importance thanks to their ease of synthesis and their molecular recognition abilities toward the reactants. The aim of this review is to give an overview of the recent advances in the field of supramolecular organocatalysis in water, focusing the attention on calixarene and cyclodextrins derivatives. Calixarenes and cyclodextrins, thanks to their hydrophobic cavities, are able to host selectively the substrates isolating they from the reaction environment. In addition, the synthetic versatilities of these macrocycles permits to introduce useful functional groups in close proximity of the hydrophobic binding sites. Regarding the cyclodextrins (CDs), we have here reviewed the their most recent uses as organocatalysts for the synthesis of heterocyclic compounds, in multi-component reactions and in carbon-carbon bond forming reactions. Examples have been reported in which CD catalysts are able to drive the regiochemistry of common organic reactions. In addition, cyclodextrins bearing catalytically active chiral groups, have shown excellent enantioselectivity in the catalysis of organic reactions. Recently reported results have shown that calixarene derivatives are able to accelerate organic reaction under "on-water" conditions with a significant selectivity toward the reactants. Under "on-water conditions" the hydrophobic effect, induced by insoluble calixarene derivatives, forces the reactants and the catalyst to aggregate and thus accelerating the reaction between them thanks to an amplification of weak secondary interactions. Regarding the use of water-soluble calixarene organocatalysts, we have here reviewed their role in the acceleration of common organic reactions.

Synthesis of macrocyclic polyaminocarboxylates and their use for preparing stable radiometal antibody immunoconjugates for therapy, SPECT and PET imaging

DOEpatents

Mease, R.C.; Mausner, L.F.; Srivastava, S.C.

1995-06-27

A simple method for the synthesis of 1,4,7,10-tetraazacyclododecane N,N{prime}N{double_prime},N{prime}{double_prime}-tetraacetic acid and 1,4,8,11-tetraazacyclotetradecane N,N{prime},N{double_prime},N{prime}{double_prime}-tetraacetic acid involves cyanomethylating 1,4,7,10-tetraazacyclododecane or 1,4,8,11-tetraazacyclotetradecane to form a tetranitrile and hydrolyzing the tetranitrile. These macrocyclic compounds are functionalized through one of the carboxylates and then conjugated to various biological molecules including monoclonal antibodies. The resulting conjugated molecules are labeled with radiometals for SPECT and PET imaging and for radiotherapy. 4 figs.

Solar cells incorporating light harvesting arrays

DOEpatents

Lindsey, Jonathan S.; Meyer, Gerald J.

2003-07-22

A solar cell incorporates a light harvesting array that comprises: (a) a first substrate comprising a first electrode; and (b) a layer of light harvesting rods electrically coupled to the first electrode, each of the light harvesting rods comprising a polymer of Formula I: ##EQU1## wherein m is at least 1, and may be from two, three or four to 20 or more; X.sup.1 is a charge separation group (and preferably a porphyrinic macrocycle, which may be one ligand of a double-decker sandwich compound) having an excited-state of energy equal to or lower than that of X.sup.2 ; and X.sup.2 through X.sup.m+1 are chromophores (and again are preferably porphyrinic macrocycles).

A Systematic Exploration of Macrocyclization in Apelin-13: Impact on Binding, Signaling, Stability, and Cardiovascular Effects.

PubMed

Trân, Kien; Murza, Alexandre; Sainsily, Xavier; Coquerel, David; Côté, Jérôme; Belleville, Karine; Haroune, Lounès; Longpré, Jean-Michel; Dumaine, Robert; Salvail, Dany; Lesur, Olivier; Auger-Messier, Mannix; Sarret, Philippe; Marsault, Éric

2018-03-22

The apelin receptor generates increasing interest as a potential target across several cardiovascular indications. However, the short half-life of its cognate ligands, the apelin peptides, is a limiting factor for pharmacological use. In this study, we systematically explored each position of apelin-13 to find the best position to cyclize the peptide, with the goal to improve its stability while optimizing its binding affinity and signaling profile. Macrocyclic analogues showed a remarkably higher stability in rat plasma (half-life >3 h versus 24 min for Pyr-apelin-13), accompanied by improved affinity (analogue 15, K i 0.15 nM and t 1/2 6.8 h). Several compounds displayed higher inotropic effects ex vivo in the Langendorff isolated heart model in rats (analogues 13 and 15, maximum response at 0.003 nM versus 0.03 nM of apelin-13). In conclusion, this study provides stable and active compounds to better characterize the pharmacology of the apelinergic system.

Antitumor activity of four macrocyclic ellagitannins from Cuphea hyssopifolia.

PubMed

Wang, C C; Chen, L G; Yang, L L

1999-06-01

We evaluated the antitumor activities of four macrocyclic hydrolyzable tannin dimers, cuphiin D1, cuphiin D2, oenothein B and woodfordin C isolated from Cuphea hyssopifolia (Lythraceae). All significantly inhibited the growth of the human carcinoma cell lines KB, HeLa, DU-145, Hep 3B, and the leukemia cell line HL-60, and showed less cytotoxicity than adriamycin against a normal cell line (WISH). All four compounds inhibited the viability of S-180 tumor cells in an in vitro assay and an in vivo S-180 tumor-bearing ICR mice model. Oenothein B demonstrated the greatest cytotoxicity (IC50 = 11.4 microg/ml) against S-180 tumor cells in culture, while cuphiin D1 resulted in the greatest increase in survival on S-180 tumor-bearing mice (%ILS = 84.1%). Our findings suggest that the antitumor effects of these compounds are not only related to their cytotoxicity on carcinoma cell lines, but also depended on a host-mediated mechanism; they may therefore have potential for antitumor applications.

Functionalized Derivatives of Benzo-Crown Ethers. Part 4. Antifungal Macrocyclic Supramolecular Complexes of Transition Metal Ions Acting as Lanosterol-14-α-Demethylase Ihibitors

PubMed Central

Barboiu, Mihai; Scozzafava, Andrea; Guran, Cornelia; Diaconescu, Paula; Bojin, Mihaela; Iluc, Vlad; Cot, Louis

1999-01-01

Poly- and mononuclear metal complexes of 2,3,11,12-bis[4-(10-aminodecylcarbonyl)]benzo-18- crown-6 (L) and Cu(II); Ni(II); Co(II) and Cr(III) have been synthesized and characterized by standard physico-chemical procedures. In the newly prepared complexes the crown moiety oxygen atoms of the macrocyclic host did not generally interact with metal ions, whereas the two amino groups of the ligand always did. Several of the newly synthesized compounds act as effective antifungal agents against Aspergillus and Candida spp., some of them showing activities comparable to ketoconazole, with minimum inhibitory concentrations in the range of 0.3−0.5 μg/mL. The mechanism of antifungal action of these coordination compounds is probably connected to an inhibition of lanosterol-14-α-demethylase, a metallo-enzyme playing a key role in sterol biosynthesis in fungi, bacteria and eukariotes. PMID:18475888

Structure-Activity Relationship Studies on a Macrocyclic Agouti-Related Protein (AGRP) Scaffold Reveal Agouti Signaling Protein (ASP) Residue Substitutions Maintain Melanocortin-4 Receptor Antagonist Potency and Result in Inverse Agonist Pharmacology at the Melanocortin-5 Receptor.

PubMed

Ericson, Mark D; Freeman, Katie T; Schnell, Sathya M; Fleming, Katlyn A; Haskell-Luevano, Carrie

2017-10-12

The melanocortin system consists of five reported receptors, agonists from the proopiomelanocortin gene transcript, and two antagonists, agouti-signaling protein (ASP) and agouti-related protein (AGRP). For both ASP and AGRP, the hypothesized Arg-Phe-Phe pharmacophores are on exposed β-hairpin loops. In this study, the Asn and Ala positions of a reported AGRP macrocyclic scaffold (c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro]) were explored with 14-compound and 8-compound libraries, respectively, to generate more potent, selective melanocortin receptor antagonists. Substituting diaminopropionic acid (Dap), DDap, and His at the Asn position yielded potent MC4R ligands, while replacing Ala with Ser maintained MC4R potency. Since these substitutions correlate to ASP loop residues, an additional Phe to Ala substitution was synthesized and observed to maintain MC4R potency. Seventeen compounds also possessed inverse agonist activity at the MC5R, the first report of this pharmacology. These findings are useful in developing molecular probes to study negative energy balance conditions and unidentified functions of the MC5R.

40 CFR 721.10410 - Polyether ester acid compound with a polyamine amide (generic) (P-05-714).

Code of Federal Regulations, 2014 CFR

2014-07-01

... polyamine amide (generic) (P-05-714). 721.10410 Section 721.10410 Protection of Environment ENVIRONMENTAL... polyamine amide (generic) (P-05-714). (a) Chemical substance and significant new uses subject to reporting... amide (PMN P-05-714) is subject to reporting under this section for the significant new uses described...

Spectroscopic and electrochemical investigation with coordination stabilities: Mononuclear manganese(II) complexes derived from different constituents macrocyclic ligands

NASA Astrophysics Data System (ADS)

Kumar, Rajiv; Chnadra, S.; Mishra, Parashuram

2007-12-01

Since the manganese(II) complexes are known as having a high degree of stability, some of them may be able to play a very important role in biosystems. We prepared manganese(II) complexes with different chromospheres containing macrocyclic ligands bearing N, S and O like functional donor atoms in order to obtain different models of compounds. So these new manganese(II) complexes were derived from macrocyclic ligands by chelating them with metal ions. Thus, two macrocyclic ligands, L 1: 2,4-diphenyl-1,5-diaza-8,12-dioxo-6,7:13,14-dibenzocyclo tetradeca-1,4-diene[N 2O 2]ane; L 2: 2,4,9,11-tetraphenyl-6,13-dimethyl-1,5,8,12-traazacyclotertr-adeca-1,4,8,11-tetraene[N 4]ane; and two more different form first one viz.—L 3: 1,7-diaza-4-monothia-10,14-dioxo-8,9:15,16-cyclohexadecane[N 2O 2S]ane and L 4: 4,13-diaoxa-1,7,10,16-hexazacyclooctadecane[N 4O 2]ane were prepared and their capacity to retain the manganese(II) ion in solid as well as aqueous solution was determined from various physiochemical techniques viz: characterized by elemental analyses, molar conductance measurements, magnetic susceptibility measurements, mass, IR, electronic, ESR spectral studies and cyclic voltammetric measurements.

Application of a macrocyclic compound, bambus[6]uril, in tailor-made liquid membranes for highly selective electromembrane extractions of inorganic anions.

PubMed

Šlampová, Andrea; Šindelář, Vladimír; Kubáň, Pavel

2017-01-15

A tailor-made liquid membrane consisting of a resistive organic solvent (nitrobenzene, NB) and a highly selective non-ionic macrocyclic compound (bambus[6]uril, BU6) was employed for electromembrane extraction (EME) of inorganic anions. BU6 facilitates strong host-guest interactions of its internal cavity with selected inorganic anions only and its presence in the liquid membrane ensured excellent selectivity of the EME process. EME transfers were directly related to association constants between BU6 and inorganic anions and nearly absolute selectivity was achieved for EMEs of iodide, bromide and perchlorate. Major inorganic anions (chloride, nitrate, sulphate and carbonate), which exhibit low interactions with BU6 cavity, were efficiently eliminated from the EME transfer. No interferences were observed for EMEs of target analytes from samples containing up to 100.000-fold higher concentrations of the major anions. Addition of species-specific macrocyclic modifiers to free and supported liquid membranes might thus open new directions in fine-tuning of EME selectivity. At optimized EME conditions (polypropylene hollow fiber impregnated with NB + 3% (w/w) BU6, extraction voltage 25 V, extraction time 15 min, deionized water as acceptor solution) perchlorate was selectively extracted from tap water at concentrations below the guideline value recommended by United States Environmental Protection Agency. Excellent selectivity of the tailor-made liquid membrane was further demonstrated by EME of bromide from sea water. Copyright © 2016 Elsevier B.V. All rights reserved.

Covalent lanthanide(III) macrocyclic complexes: the bonding nature and optical properties of a promising single antenna molecule.

PubMed

Rabanal-León, Walter A; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro

2014-12-21

The present work is focused on the elucidation of the electronic structure, bonding nature and optical properties of a series of low symmetry (C2) coordination compounds of type [Ln(III)HAM](3+), where "Ln(III)" are the trivalent lanthanide ions: La(3+), Ce(3+), Eu(3+) and Lu(3+), while "HAM" is the neutral six-nitrogen donor macrocyclic ligand [C22N6H26]. This systematic study has been performed in the framework of the Relativistic Density Functional Theory (R-DFT) and also using a multi-reference approach via the Complete Active Space (CAS) wavefunction treatment with the aim of analyzing their ground state and excited state electronic structures as well as electronic correlation. Furthermore, the use of the energy decomposition scheme proposed by Morokuma-Ziegler and the electron localization function (ELF) allows us to characterize the bonding between the lanthanide ions and the macrocyclic ligand, obtaining as a result a dative-covalent interaction. Due to a great deal of lanthanide optical properties and their technological applications, the absorption spectra of this set of coordination compounds were calculated using the time-dependent density functional theory (TD-DFT), where the presence of the intense Ligand to Metal Charge Transfer (LMCT) bands in the ultraviolet and visible region and the inherent f-f electronic transitions in the Near-Infra Red (NIR) region for some lanthanide ions allow us to propose these systems as "single antenna molecules" with potential applications in NIR technologies.

Macrocyclic drugs and synthetic methodologies toward macrocycles

PubMed Central

Yu, Xufen; Sun, Dianqing

2015-01-01

Macrocyclic scaffolds are commonly found in bioactive natural products and pharmaceutical molecules. So far, a large number of macrocyclic natural products have been isolated and synthesized. The construction of macrocycles is generally considered as a crucial and challenging step in the synthesis of macrocyclic natural products. Over the last several decades, numerous efforts have been undertaken toward the synthesis of complex naturally occurring macrocycles and great progresses have been made to advance the field of total synthesis. The commonly used synthetic methodologies toward macrocyclization include macrolactonization, macrolactamization, transition metal-catalyzed cross coupling, ring-closing metathesis, and click reaction, among others. Selected recent examples of macrocyclic synthesis of natural products and druglike macrocycles with significant biological relevance are highlighted in each class. The primary goal of this review is to summarize currently used macrocyclic drugs, highlight the therapeutic potential of this underexplored drug class and outline the general synthetic methodologies for the synthesis of macrocycles. PMID:23708234

Method for separating isotopes

DOEpatents

Jepson, B.E.

1975-10-21

Isotopes are separated by contacting a feed solution containing the isotopes with a cyclic polyether wherein a complex of one isotope is formed with the cyclic polyether, the cyclic polyether complex is extracted from the feed solution, and the isotope is thereafter separated from the cyclic polyether.

The macrocyclic peptide natural product CJ-15,208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior.

PubMed

Aldrich, Jane V; Senadheera, Sanjeewa N; Ross, Nicolette C; Ganno, Michelle L; Eans, Shainnel O; McLaughlin, Jay P

2013-03-22

The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-d-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.

40 CFR 721.10213 - Polyether polyester copolymer phosphate (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polyether polyester copolymer... Specific Chemical Substances § 721.10213 Polyether polyester copolymer phosphate (generic). (a) Chemical... as polyether polyester copolymer phosphate (PMN P-09-253) is subject to reporting under this section...

21 CFR 177.2430 - Polyether resins, chlorinated.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyether resins, chlorinated. 177.2430 Section 177... Components of Articles Intended for Repeated Use § 177.2430 Polyether resins, chlorinated. Chlorinated..., in accordance with the following prescribed conditions: (a) The chlorinated polyether resins are...

Extrusion-mixing compared with hand-mixing of polyether impression materials?

PubMed

McMahon, Caroline; Kinsella, Daniel; Fleming, Garry J P

2010-12-01

The hypotheses tested were two-fold (a) whether altering the base:catalyst ratio influences working time, elastic recovery and strain in compression properties of a hand-mixed polyether impression material and (b) whether an extrusion-mixed polyether impression material would have a significant advantage over a hand-mixed polyether impression material mixed to the optimum base:catalyst ratio. The polyether was hand-mixed at the optimum (manufacturers recommended) base:catalyst ratios (7:1) and further groups were made by increasing or decreasing the catalyst length by 25%. Additionally specimens were also made from an extrusion-mixed polyether impression material and compared with the optimum hand-mixed base:catalyst ratio. A penetrometer assembly was used to measure the working time (n=5). Five cylindrical specimens for each hand-mixed and extrusion mixed group investigated were employed for elastic recovery and strain in compression testing. Hand-mixing polyether impression materials with 25% more catalyst than that recommended significantly decreased the working time while hand-mixing with 25% less catalyst than that recommended significantly increased the strain in compression. The extrusion-mixed polyether impression material provided similar working time, elastic recovery and strain in compression to the hand-mixed polyether mixed at the optimum base:catalyst ratio.

40 CFR 721.10624 - Dicyclohexylmethane-4,4'-diisocyanate, polymer with ethoxylated, propoxylated polyethers (generic).

Code of Federal Regulations, 2014 CFR

2014-07-01

..., polymer with ethoxylated, propoxylated polyethers (generic). 721.10624 Section 721.10624 Protection of...,4'-diisocyanate, polymer with ethoxylated, propoxylated polyethers (generic). (a) Chemical substance... dicyclohexylmethane-4,4'-diisocyanate, polymer with ethoxylated, propoxylated polyethers (PMN P-12-326) is subject to...

40 CFR 721.10624 - Dicyclohexylmethane-4,4'-diisocyanate, polymer with ethoxylated, propoxylated polyethers (generic).

Code of Federal Regulations, 2013 CFR

2013-07-01

..., polymer with ethoxylated, propoxylated polyethers (generic). 721.10624 Section 721.10624 Protection of...,4'-diisocyanate, polymer with ethoxylated, propoxylated polyethers (generic). (a) Chemical substance... dicyclohexylmethane-4,4'-diisocyanate, polymer with ethoxylated, propoxylated polyethers (PMN P-12-326) is subject to...

21 CFR 177.2430 - Polyether resins, chlorinated.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Polyether resins, chlorinated. 177.2430 Section... as Components of Articles Intended for Repeated Use § 177.2430 Polyether resins, chlorinated. Chlorinated polyether resins may be safely used as articles or components of articles intended for repeated...

40 CFR 721.405 - Polyether acrylate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polyether acrylate. 721.405 Section... § 721.405 Polyether acrylate. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a polyether acrylate (PMN P-95-666) is subject to...

Salinomycin and other polyether ionophores are a new class of antiscarring agent.

PubMed

Woeller, Collynn F; O'Loughlin, Charles W; Roztocil, Elisa; Feldon, Steven E; Phipps, Richard P

2015-02-06

Although scarring is a component of wound healing, excessive scar formation is a debilitating condition that results in pain, loss of tissue function, and even death. Many tissues, including the lungs, heart, skin, and eyes, can develop excessive scar tissue as a result of tissue injury, chronic inflammation, or autoimmune disease. Unfortunately, there are few, if any, effective treatments to prevent excess scarring, and new treatment strategies are needed. Using HEK293FT cells stably transfected with a TGFβ-dependent luciferase reporter, we performed a small molecule screen to identify novel compounds with antiscarring activity. We discovered that the polyether ionophore salinomycin potently inhibited the formation of scar-forming myofibroblasts. Salinomycin (250 nm) blocked TGFβ-dependent expression of the cardinal myofibroblast products α smooth muscle actin, calponin, and collagen in primary human fibroblasts without causing cell death. Salinomycin blocked phosphorylation and activation of TAK1 and p38, two proteins fundamentally involved in signaling myofibroblast and scar formation. Expression of constitutively active mitogen activated kinase kinase 6, which activates p38 MAPK, attenuated the ability of salinomycin to block myofibroblast formation, demonstrating that salinomycin targets the p38 kinase pathway to disrupt TGFβ signaling. These data identify salinomycin and other polyether ionophores as novel potential antiscarring therapeutics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Salinomycin and Other Polyether Ionophores Are a New Class of Antiscarring Agent*

PubMed Central

Woeller, Collynn F.; O'Loughlin, Charles W.; Roztocil, Elisa; Feldon, Steven E.; Phipps, Richard P.

2015-01-01

Although scarring is a component of wound healing, excessive scar formation is a debilitating condition that results in pain, loss of tissue function, and even death. Many tissues, including the lungs, heart, skin, and eyes, can develop excessive scar tissue as a result of tissue injury, chronic inflammation, or autoimmune disease. Unfortunately, there are few, if any, effective treatments to prevent excess scarring, and new treatment strategies are needed. Using HEK293FT cells stably transfected with a TGFβ-dependent luciferase reporter, we performed a small molecule screen to identify novel compounds with antiscarring activity. We discovered that the polyether ionophore salinomycin potently inhibited the formation of scar-forming myofibroblasts. Salinomycin (250 nm) blocked TGFβ-dependent expression of the cardinal myofibroblast products α smooth muscle actin, calponin, and collagen in primary human fibroblasts without causing cell death. Salinomycin blocked phosphorylation and activation of TAK1 and p38, two proteins fundamentally involved in signaling myofibroblast and scar formation. Expression of constitutively active mitogen activated kinase kinase 6, which activates p38 MAPK, attenuated the ability of salinomycin to block myofibroblast formation, demonstrating that salinomycin targets the p38 kinase pathway to disrupt TGFβ signaling. These data identify salinomycin and other polyether ionophores as novel potential antiscarring therapeutics. PMID:25538236

Study of Nanocomposites of Amino Acids and Organic Polyethers by Means of Mass Spectrometry and Molecular Dynamics Simulation

NASA Astrophysics Data System (ADS)

Zobnina, V. G.; Kosevich, M. V.; Chagovets, V. V.; Boryak, O. A.

A problem of elucidation of structure of nanomaterials based on combination of proteins and polyether polymers is addressed on the monomeric level of single amino acids and oligomers of PEG-400 and OEG-5 polyethers. Efficiency of application of combined approach involving experimental electrospray mass spectrometry and computer modeling by molecular dynamics simulation is demonstrated. It is shown that oligomers of polyethers form stable complexes with amino acids valine, proline, histidine, glutamic, and aspartic acids. Molecular dynamics simulation has shown that stabilization of amino acid-polyether complexes is achieved due to winding of the polymeric chain around charged groups of amino acids. Structural motives revealed for complexes of single amino acids with polyethers can be realized in structures of protein-polyether nanoparticles currently designed for drug delivery.

40 CFR 721.3710 - Polyether modified fatty acids (generic).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polyether modified fatty acids... Specific Chemical Substances § 721.3710 Polyether modified fatty acids (generic). (a) Chemical substance... Polyether modified fatty acids (PMN P-99-0435) is subject to reporting under this section for the...

40 CFR 721.7500 - Nitrate polyether polyol (generic name).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Nitrate polyether polyol (generic name... Substances § 721.7500 Nitrate polyether polyol (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance nitrate polyether polyol (PMN P88-2540) is...

40 CFR 721.7500 - Nitrate polyether polyol (generic name).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Nitrate polyether polyol (generic name... Substances § 721.7500 Nitrate polyether polyol (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance nitrate polyether polyol (PMN P88-2540) is...

40 CFR 721.7500 - Nitrate polyether polyol (generic name).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Nitrate polyether polyol (generic name... Substances § 721.7500 Nitrate polyether polyol (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance nitrate polyether polyol (PMN P88-2540) is...

40 CFR 721.7500 - Nitrate polyether polyol (generic name).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Nitrate polyether polyol (generic name... Substances § 721.7500 Nitrate polyether polyol (generic name). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance nitrate polyether polyol (PMN P88-2540) is...

40 CFR 721.3710 - Polyether modified fatty acids (generic).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polyether modified fatty acids... Specific Chemical Substances § 721.3710 Polyether modified fatty acids (generic). (a) Chemical substance... Polyether modified fatty acids (PMN P-99-0435) is subject to reporting under this section for the...

The effect of polyether functional polydimethylsiloxane on surface and thermal properties of waterborne polyurethane

NASA Astrophysics Data System (ADS)

Zheng, Guikai; Lu, Ming; Rui, Xiaoping

2017-03-01

Waterborne polyurethanes (WPU) modified with polyether functional polydimethylsiloxane (PDMS) were synthesized by pre-polymerization method using isophorone diisocyanate (IPDI) and 1,4-butanediol (BDO) as hard segments and polybutylene adipate glycol (PBA) and polyether functional PDMS as soft segments. The effect of polyether functional PDMS on phase separation, thermal properties, surface properties including surface composition, morphology and wettability were investigated by FTIR, contact angle measurements, ARXPS, SEM-EDS, AFM, TG and DSC. The results showed that the compatibility between urethane hard segment and PDMS modified with polyether was good, and there was no distinct phase separation in both bulk and surface of WPU films. The degradation temperature and low temperature flexibility increased with increasing amounts of polyether functional PDMS. The enrichment of polyether functional PDMS with low surface energy on the surface imparted excellent hydrophobicity to WPU films.

Study of Wear-Preventive Properties of Macrocyclic Compounds for High Temperature Application

DTIC Science & Technology

1990-01-01

and hence its lubricating properties adversely affected. Another molybdenum based lubricant is molybdenum silicide . This has good resistance to...Porphyrins 21 Contract No. N62269-88-R-0234 Report No. NADC-91049-60 N N N N N\\ -/ N N .. 05 NICKEL PHTH-ALOCYANINE TETRASULFONIC ACID TETRA SODIUM SALT

Cyclic tetraureas with variable flexibility--synthesis, crystal structures and properties.

PubMed

Meshcheryakov, Denys; Arnaud-Neu, Françoise; Böhmer, Volker; Bolte, Michael; Cavaleri, Julien; Hubscher-Bruder, Véronique; Thondorf, Iris; Werner, Sabine

2008-09-21

Macrocyclic molecules containing several amide or urea functions may serve as anion receptors. We describe the synthesis of 32-membered macrocycles, in which four rigid xanthene units (X) and/or diphenyl ether units (D) as flexible analogues are linked via urea groups. All six possible combinations of these units (XXXX, XXXD, XXDD, XDXD, XDDD and DDDD) were synthesized and two examples were characterised by single-crystal X-ray analyses (DDDD and two structures for XXXD). Both macrocycles showed distinct differences in their overall conformation and consequently in their hydrogen-bonding pattern. Hydrogen-bonded solvent molecules are found for both compounds and intramolecular hydrogen bonds for the two structures of XXXD, but surprisingly no direct intermolecular hydrogen bonds between the macrocyclic tetraurea molecules. The interaction with various anions was studied by (1)H NMR spectroscopy. Stability constants for all tetramers were determined by UV spectroscopy for complexes with chloride, bromide, acetate and dihydrogenphosphate in acetonitrile-THF (3:1). The strongest binding was found for XXXD and acetate (log beta = 7.4 +/- 0.2), the weakest for XXXX and acetate (log beta = 5.1 +/- 0.5). MD simulations in chloroform and acetonitrile boxes show that all molecules except DDDD adopt very similar conformations characterized by an up-down-up-down arrangement of the spacer groups. Clustered solvation shells of acetonitrile molecules around XXXX and DDDD suggest their preorganization for spherical/planar and tetrahedral/bidentate anions, respectively, which in turn was corroborated by simulation of the corresponding complexes with chloride and dihydrogenphosphate.

Investigation of the Anti-Prostate Cancer Properties of Marine-Derived Compounds

PubMed Central

Fan, Meiqi; Nath, Amit Kumar; Tang, Yujiao; Choi, Young-Jin; Debnath, Trishna; Choi, Eun-Ju

2018-01-01

This review focuses on marine compounds with anti-prostate cancer properties. Marine species are unique and have great potential for the discovery of anticancer drugs. Marine sources are taxonomically diverse and include bacteria, cyanobacteria, fungi, algae, and mangroves. Marine-derived compounds, including nucleotides, amides, quinones, polyethers, and peptides are biologically active compounds isolated from marine organisms such as sponges, ascidians, gorgonians, soft corals, and bryozoans, including those mentioned above. Several compound classes such as macrolides and alkaloids include drugs with anti-cancer mechanisms, such as antioxidants, anti-angiogenics, antiproliferatives, and apoptosis-inducing drugs. Despite the diversity of marine species, most marine-derived bioactive compounds have not yet been evaluated. Our objective is to explore marine compounds to identify new treatment strategies for prostate cancer. This review discusses chemically and pharmacologically diverse marine natural compounds and their sources in the context of prostate cancer drug treatment. PMID:29757237

Synthesis, characterization, nano-sized binuclear nickel complexes, DFT calculations and antibacterial evaluation of new macrocyclic Schiff base compounds

NASA Astrophysics Data System (ADS)

Parsaee, Zohreh; Mohammadi, Khosro

2017-06-01

Some new macrocyclic bridged dianilines tetradentate with N4coordination sphere Schiff base ligands and their nickel(II)complexes with general formula [{Ni2LCl4} where L = (C20H14N2X)2, X = SO2, O, CH2] have been synthesized. The compounds have been characterized by FT-IR, 1H and 13C NMR, mass spectroscopy, TGA, elemental analysis, molar conductivity and magnetic moment techniques. Scanning electron microscopy (SEM) shows nano-sized structures under 100 nm for nickel (II) complexes. NiO nanoparticle was achieved via the thermal decomposition method and analyzed by FT-IR, SEM and X-ray powder diffraction which indicates closeaccordance to standard pattern of NiO nanoparticle. All the Schiff bases and their complexes have been detected in vitro both for antibacterial activity against two gram-negative and two gram-positive bacteria. The nickel(II) complexes were found to be more active than the free macrocycle Schiff bases. In addition, computational studies of three ligands have been carried out at the DFT-B3LYP/6-31G+(d,p) level of theory on the spectroscopic properties, including IR, 1HNMR and 13CNMR spectroscopy. The correlation between the theoretical and the experimental vibrational frequencies, 1H NMR and 13C NMR of the ligands were 0.999, 0.930-0.973 and 0.917-0.995, respectively. Also, the energy gap was determined and by using HOMO and LUMO energy values, chemical hardness-softness, electronegativity and electrophilic index were calculated.

40 CFR Table 4 to Subpart Ppp of... - Known Organic HAP From Polyether Polyol Products

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 11 2010-07-01 2010-07-01 true Known Organic HAP From Polyether Polyol... CATEGORIES National Emission Standards for Hazardous Air Pollutant Emissions for Polyether Polyols Production Pt. 63, Subpt. PPP, Table 4 Table 4 to Subpart PPP of Part 63—Known Organic HAP From Polyether Polyol...

The Macrocyclic Peptide Natural Product CJ-15,208 is Orally Active and Prevents Reinstatement of Extinguished Cocaine Seeking Behavior1

PubMed Central

Aldrich, Jane V.; Senadheera, Sanjeewa N.; Ross, Nicolette C.; Ganno, Michelle L.; Eans, Shainnel O.; McLaughlin, Jay P.

2013-01-01

The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug seeking behavior in abstinent subjects. PMID:23327691

Solar cells incorporating light harvesting arrays

DOEpatents

Lindsey, Jonathan S.; Meyer, Gerald J.

2002-01-01

A solar cell incorporates a light harvesting array that comprises: (a) a first substrate comprising a first electrode; and (b) a layer of light harvesting rods electrically coupled to the first electrode, each of the light harvesting rods comprising a polymer of Formula I: X.sup.1.paren open-st.X.sup.m+1).sub.m (I) wherein m is at least 1, and may be from two, three or four to 20 or more; X.sup.1 is a charge separation group (and preferably a porphyrinic macrocycle, which may be one ligand of a double-decker sandwich compound) having an excited-state of energy equal to or lower than that of X.sup.2 ; and X.sup.2 through X.sup.m+1 are chromophores (and again are preferably porphyrinic macrocycles).

Light harvesting arrays

DOEpatents

Lindsey, Jonathan S.

2002-01-01

A light harvesting array useful for the manufacture of devices such as solar cells comprises: (a) a first substrate comprising a first electrode; and (b) a layer of light harvesting rods electrically coupled to the first electrode, each of the light harvesting rods comprising a polymer of Formula I: X.sup.1.paren open-st.X.sup.m+1).sub.m (I) wherein m is at least 1, and may be from two, three or four to 20 or more; X.sup.1 is a charge separation group (and preferably a porphyrinic macrocycle, which may be one ligand of a double-decker sandwich compound) having an excited-state of energy equal to or lower than that of X.sup.2, and X.sup.2 through X.sup.m+1 are chromophores (and again are preferably porphyrinic macrocycles).

A Review on the Toxicity and Non-Target Effects of Macrocyclic Lactones in Terrestrial and Aquatic Environments

PubMed Central

Lumaret, Jean-Pierre; Errouissi, Faiek; Floate, Kevin; Römbke, Jörg; Wardhaugh, Keith

2012-01-01

The avermectins, milbemycins and spinosyns are collectively referred to as macrocyclic lactones (MLs) which comprise several classes of chemicals derived from cultures of soil micro-organisms. These compounds are extensively and increasingly used in veterinary medicine and agriculture. Due to their potential effects on non-target organisms, large amounts of information on their impact in the environment has been compiled in recent years, mainly caused by legal requirements related to their marketing authorization or registration. The main objective of this paper is to critically review the present knowledge about the acute and chronic ecotoxicological effects of MLs on organisms, mainly invertebrates, in the terrestrial and aquatic environment. Detailed information is presented on the mode-of-action as well as the ecotoxicity of the most important compounds representing the three groups of MLs. This information, based on more than 360 references, is mainly provided in nine tables, presenting the effects of abamectin, ivermectin, eprinomectin, doramectin, emamectin, moxidectin, and spinosad on individual species of terrestrial and aquatic invertebrates as well as plants and algae. Since dung dwelling organisms are particularly important non-targets, as they are exposed via dung from treated animals over their whole life-cycle, the information on the effects of MLs on dung communities is compiled in an additional table. The results of this review clearly demonstrate that regarding environmental impacts many macrocyclic lactones are substances of high concern particularly with larval instars of invertebrates. Recent studies have also shown that susceptibility varies with life cycle stage and impacts can be mitigated by using MLs when these stages are not present. However information on the environmental impact of the MLs is scattered across a wide range of specialised scientific journals with research focusing mainly on ivermectin and to a lesser extent on abamectin doramectin and moxidectin. By comparison, information on compounds such as eprinomectin, emamectin and selamectin is still relatively scarce. PMID:22039795

Influence of the redox active ligand on the reactivity and electronic structure of a series of Fe(TIM) complexes.

PubMed

Hess, Corinna R; Weyhermüller, Thomas; Bill, Eckhard; Wieghardt, Karl

2010-06-21

The redox properties of Fe and Zn complexes coordinated by an alpha-diimine based N(4)-macrocyclic ligand (TIM) have been examined using spectroscopic methods and density functional theory (DFT) computational analysis. DFT results on the redox series of [Zn(TIM*)](n) and [Fe(TIM*)](n) molecules indicate the preferential reduction of the alpha-diimine ligand moiety. In addition to the previously reported [Fe(TIM*)](2) dimer, we have now synthesized and characterized a further series of monomeric and dimeric complexes coordinated by the TIM ligand. This includes the five-coordinate monomeric [Fe(TIM*)I], the neutral and cationic forms of a monomeric phosphite adduct, [Fe(TIM*)(P(OPh)(3))] and [Fe(TIM*)(P(OPh)(3))](PF(6)), as well as a binuclear hydroxy-bridged complex, [{Fe(TIM*)}(2)(mu-OH)](PF(6)). Experimental and computational data for these synthetic compounds denote the presence of ferrous and ferric species, suggesting that the alpha-diimine based macrocycles do not readily support the formation of formally low-valent (M(0) or M(I)) metal complexes as previously speculated. Magnetochemical, Mossbauer, electron paramagnetic resonance (EPR), and electronic spectral data have been employed to experimentally determine the oxidation state of the central metal ion and of the macrocyclic ligand (TIM*) in each compound. The series of compounds is described as follows: [Fe(II)(TIM(0))(CH(3)CN(2))](2+), S(Fe) = S(T) = 0; [Fe(2.5)(TIM(2.5-))](2), S(T) = 1; [{Fe(III)(TIM(2-))}(2)(mu-OH)](+), S(Fe) = 3/2, S(T) = 0; [Fe(III)(TIM(2-))I], S(Fe) = 3/2, S(T) = 1/2; [Fe(II)(TIM(2-))(P(OPh(3)))], S(Fe) = S(T) = 0; and [Fe(II)(TIM(1-))(P(OPh(3)))](1+)/[Fe(I)(TIM(0))(P(OPh(3)))](1+), S(T) = 1/2. The results have been corroborated by DFT calculations.

Functional electrolyte for lithium-ion batteries

DOEpatents

Zhang, Lu; Zhang, Zhengcheng; Amine, Khalil

2015-04-14

Functional electrolyte solvents include compounds having at least one aromatic ring with 2, 3, 4 or 5 substituents, at least one of which is a substituted or unsubstituted methoxy group, at least one of which is a tert-butyl group and at least one of which is a substituted or unsubstituted polyether or poly(ethylene oxide) (PEO) group bonded through oxygen to the aromatic ring, are provided.

[A survey of occupational health among polyether-exposed workers].

PubMed

Fu, Xu-ying; Yu, Bin; Zhang, Chun-ping; Zheng, Guan-hua; Bai, Lan; Zhang, Pan-pan

2013-06-01

To investigate the occupational health of the workers simultaneously exposed to acrylonitrile, epoxyethane, epoxypropane, and styrene. A questionnaire survey was conducted in 70 front-line workers simultaneously exposed to acrylonitrile, epoxyethane, epoxypropane, and styrene (exposure group) and 50 managers (control group) in a polyether manufacturer; in addition, air monitoring at workplace and occupational health examination were also performed. The obtained data were analyzed. The female workers in exposure group and the spouses of male workers in exposure group had significantly higher spontaneous abortion rates than their counterparts in control group (P < 0.01). The exposure group had a significantly higher abnormal rate of blood urea nitrogen than the control group (P < 0.01). The workers with different polyether-exposed working years had significantly higher mean levels of DNA damage than the control group (P < 0.01); the workers with not less than 5 and less than 20 polyether-exposed working years and those with not less than 20 polyether-exposed working years had significantly higher mean micronucleus rates than the control group (P < 0.01); there were no significant differences in overall chromosome aberration rate and mean level of DNA damage between each two groups of workers with different polyether-exposed working years (P > 0.05); the workers with not less than 5 and less than 20 polyether-exposed working years and workers with not less than 20 polyether-exposed working years had significantly higher mean micronucleus rates than those with less than 5 polyether-exposed working years (P < 0.01). Simultaneous exposure to acrylonitrile, epoxyethane, epoxypropane, and styrene causes occupational hazards among the workers in polyether manufacturer.

Strategies for the control of Rhipicephalus microplus ticks in a world of conventional acaricide and macrocyclic lactone resistance.

PubMed

Rodriguez-Vivas, Roger I; Jonsson, Nicholas N; Bhushan, Chandra

2018-01-01

Infestations with the cattle tick, Rhipicephalus microplus, constitute the most important ectoparasite problem for cattle production in tropical and subtropical regions worldwide, resulting in major economic losses. The control of R. microplus is mostly based on the use of conventional acaricides and macrocyclic lactones. However, the intensive use of such compounds has resulted in tick populations that exhibit resistance to all major acaricide chemical classes. Consequently, there is a need for the development of alternative approaches, possibly including the use of animal husbandry practices, synergized pesticides, rotation of acaricides, pesticide mixture formulations, manual removal of ticks, selection for host resistance, nutritional management, release of sterile male hybrids, environmental management, plant species that are unfavourable to ticks, pasture management, plant extracts, essential oils and vaccination. Integrated tick management consists of the systematic combination of at least two control technologies aiming to reduce selection pressure in favour of acaricide-resistant individuals, while maintaining adequate levels of animal production. The purpose of this paper is to present a current review on conventional acaricide and macrocyclic lactone resistance for better understanding and control of resistant ticks with particular emphasis on R. microplus on cattle.

Two Macrocycles in One Shot: Synthesis, Spectroscopy, Photophysics, and Tautomerism of 23-Oxahemiporphycene and 21-Oxacorrole-5-carbaldehyde.

PubMed

Ostapko, Jakub; Kelm, Anna; Kijak, Michał; Leśniewska, Barbara; Waluk, Jacek

2018-04-19

The synthesis of 23-oxahemiporphycene, the first monooxa analogue of hemiporphycene, a structural isomer of porphyrin, is reported. Its generation under McMurry reaction conditions is surprisingly accompanied by the appearance of a formyl derivative of oxacorrole, 21-oxacorrole-5-carbaldehyde. A mechanism for the formation of the latter is proposed, relying on pinacol rearrangement of titanium pinacolate. The structures of the most stable tautomeric forms are established for both compounds based on IR and NMR spectra combined with DFT calculations. Spectral and photophysical characteristics are compared with those of structurally similar macrocycles. Replacement of one nitrogen by oxygen in hemiporphycene has only a minor impact. In contrast, for corrole it leads to the enhancement of stability and to strongly reduced rates of nonradiative deactivation of the lowest excited singlet state. This is explained by the planarity of oxacorroles, achieved by removing one of the inner hydrogen atoms from the inner cavity. Unusual crystal packing is observed for the protonated form of 23-oxahemiporphycene, which exhibits a π-π stacked columnar alignment of positively charged macrocycle units. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biosynthetic machinery of ionophore polyether lasalocid: enzymatic construction of polyether skeleton.

PubMed

Minami, Atsushi; Oguri, Hiroki; Watanabe, Kenji; Oikawa, Hideaki

2013-08-01

Diversity of natural polycyclic polyethers originated from very simple yet versatile strategy consisting of epoxidation of linear polyene followed by epoxide opening cascade. To understand two-step enzymatic transformations at molecular basis, a flavin containing monooxygenase (EPX) Lsd18 and an epoxide hydrolase (EH) Lsd19 were selected as model enzymes for extensive investigation on substrate specificity, catalytic mechanism, cofactor requirement and crystal structure. This pioneering study on prototypical lasalocid EPX and EH provides insight into detailed mechanism of ionophore polyether assembly machinery and clarified remaining issues for polyether biosynthesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gallium(III) complexes of methyl pyropheophorbide-a as synthetic models for investigation of diastereomerically controlled axial ligation towards chlorophylls.

PubMed

Sasaki, Shin-Ichi; Mizoguchi, Tadashi; Tamiaki, Hitoshi

2006-03-01

Gallium(III) chlorins possessing a series of axial ligands were synthesized as model compounds of natural chlorophylls. A pair of diastereomers arising from the fifth axial coordination onto the asymmetric chlorin pi-macrocycle could be discriminated in a solution by both (1)H- and (13)C NMR spectroscopies.

Biological activities of phthalocyanines--XVI. Tetrahydroxy- and tetraalkylhydroxy zinc phthalocyanines. Effect of alkyl chain length on in vitro and in vivo photodynamic activities.

PubMed Central

Boyle, R. W.; Leznoff, C. C.; van Lier, J. E.

1993-01-01

Zinc phthalocyanine substituted with four hydroxyl groups attached to the macrocycle, either directly or via spacer chains of three or six carbon atoms, were tested for their photodynamic ability to inactivate Chinese hamster lung fibroblasts (line V-79) in vitro, and to induce regression of EMT-6 tumours grown subcutaneously in Balb/c mice. Their potential to inflict direct cell killing during photodynamic therapy was investigated by examining vascular stasis immediately following photoirradiation using fluorescein as a marker, and also by an in vivo/in vitro EMT-6 cell survival assay. Both of the tetraalkylhydroxy substituted zinc phthalocyanines are effective photodynamic sensitisers in vivo with the tetrapropylhydroxy compound exhibiting about twice the activity of the tetrahexylhydroxy analogue. The differences in activities were accentuated in vitro, the tetrapropylhydroxy compound was two orders of magnitude more potent than the tetrahexylhydroxy analogue in photoinactivating V-79 cells. The tetrahydroxy compound lacking spacer chains failed to exhibit photodynamic activity in either system. Tumour response with the active compounds was preceded by vascular stasis immediate following irradiation which suggests, together with the absence of activity in the in vivo/in vitro assay, that tumour regression involves an indirect response to the photodynamic action rather than direct cell killing. These data demonstrate the importance of the spatial orientation of functional groups around the macrocycle of photosensitisers for their efficacy in the photodynamic therapy of cancer. PMID:8512803

Polyketide synthesis genes associated with toxin production in two species of Gambierdiscus (Dinophyceae).

PubMed

Kohli, Gurjeet S; John, Uwe; Figueroa, Rosa I; Rhodes, Lesley L; Harwood, D Tim; Groth, Marco; Bolch, Christopher J S; Murray, Shauna A

2015-05-28

Marine microbial protists, in particular, dinoflagellates, produce polyketide toxins with ecosystem-wide and human health impacts. Species of Gambierdiscus produce the polyether ladder compounds ciguatoxins and maitotoxins, which can lead to ciguatera fish poisoning, a serious human illness associated with reef fish consumption. Genes associated with the biosynthesis of polyether ladder compounds are yet to be elucidated, however, stable isotope feeding studies of such compounds consistently support their polyketide origin indicating that polyketide synthases are involved in their biosynthesis. Here, we report the toxicity, genome size, gene content and transcriptome of Gambierdiscus australes and G. belizeanus. G. australes produced maitotoxin-1 and maitotoxin-3, while G. belizeanus produced maitotoxin-3, for which cell extracts were toxic to mice by IP injection (LD50 = 3.8 mg kg(-1)). The gene catalogues comprised 83,353 and 84,870 unique contigs, with genome sizes of 32.5 ± 3.7 Gbp and 35 ± 0.88 Gbp, respectively, and are amongst the most comprehensive yet reported from a dinoflagellate. We found three hundred and six genes involved in polyketide biosynthesis, including one hundred and ninety-two ketoacyl synthase transcripts, which formed five unique phylogenetic clusters. Two clusters were unique to these maitotoxin-producing dinoflagellate species, suggesting that they may be associated with maitotoxin biosynthesis. This work represents a significant step forward in our understanding of the genetic basis of polyketide production in dinoflagellates, in particular, species responsible for ciguatera fish poisoning.

Tunable, antibacterial activity of silicone polyether surfactants.

PubMed

Khan, Madiha F; Zepeda-Velazquez, Laura; Brook, Michael A

2015-08-01

Silicone surfactants are used in a variety of applications, however, limited data is available on the relationship between surfactant structure and biological activity. A series of seven nonionic, silicone polyether surfactants with known structures was tested for in vitro antibacterial activity against Escherichia coli BL21. The compounds varied in their hydrophobic head, comprised of branched silicone structures with 3-10 siloxane linkages and, in two cases, phenyl substitution, and hydrophilic tail of 8-44 poly(ethylene glycol) units. The surfactants were tested at three concentrations: below, at, and above their Critical Micelle Concentrations (CMC) against 5 concentrations of E. coli BL21 in a three-step assay comprised of a 14-24h turbidometric screen, a live-dead stain and viable colony counts. The bacterial concentration had little effect on antibacterial activity. For most of the surfactants, antibacterial activity was higher at concentrations above the CMC. Surfactants with smaller silicone head groups had as much as 4 times the bioactivity of surfactants with larger groups, with the smallest hydrophobe exhibiting potency equivalent to sodium dodecyl sulfate (SDS). Smaller PEG chains were similarly associated with higher potency. These data link lower micelle stability and enhanced permeability of smaller silicone head groups to antibacterial activity. The results demonstrate that simple manipulation of nonionic silicone polyether structure leads to significant changes in antibacterial activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Electronic, Spectral, and Electrochemical Properties of (TPPBr(x)())Zn Where TPPBr(x)() Is the Dianion of beta-Brominated-Pyrrole Tetraphenylporphyrin and x Varies from 0 to 8.

PubMed

D'Souza, Francis; Zandler, Melvin E.; Tagliatesta, Pietro; Ou, Zhongping; Shao, Jianguo; Van Caemelbecke, Eric; Kadish, Karl M.

1998-09-07

The electronic, spectral, and electrochemical characterization of (meso-tetraphenylporphyrinato)zinc(II) complexes bearing between 0 and 8 bromo substituents at the beta-pyrrole positions is reported. The investigated compounds are represented as (TPPBr(x)())Zn where TPPBr(x)() is the dianion of brominated 5,10,15,20-tetraphenylporphyrin and x varies between 0 and 8. Each porphyrin undergoes four well-defined one-electron transfer reactions to yield porphyrin pi-cation radicals and dications upon oxidation and porphyrin pi-anion radicals and dianions upon reduction. Half-wave potentials for the first reduction of (TPPBr(x)())Zn can be described by a single linear free energy relationship, and plots of E(1/2) versus the number of Br groups on the complex show a linear correlation with a positive slope of 63 mV per Br group. This is not the case for the other three electron transfer processes of the compounds where plots of E(1/2) versus the number of Br groups show distinctly different linear correlations for derivatives with 0-4 Br groups and those with 4-8 Br groups. The effect of increasing number of Br groups on the spectral and electrochemical properties of the neutral complexes was examined over the whole series of compounds, and these experimental results are compared to results of theoretical calculations by semiempirical molecular orbital AM1 methods using configurational interactions (CI) over the four Gouterman frontier pi-orbitals. The dihedral angle containing the four porphyrin macrocycle ring nitrogens is proposed as a measure of porphyrin ring nonplanarity, and this value increases with increasing number of Br substituents on (TPPBr(x)())Zn. Results of the AM1-CI = 4 calculations indicate that the spectrally determined HOMO-LUMO gap, i.e., the energy corresponding to the low-energy absorption band, varies in a nonlinear fashion with increasing number of Br substituents on the macrocycle and this is due to both the electronic effect of the substituents and the macrocycle nonplanarity. The HOMO-LUMO gaps theoretically calculated by AM1-CI = 4 methods thus parallel values which are experimentally obtained by electrochemistry or spectroscopy. The lack of well-defined linear free energy relationships for all processes except for the first reduction can be explained on the basis of electronic effects caused by the halogen substituents and nonplanar macrocyclic distortions induced by steric interactions among the peripheral substituents. In the case of porphyrin dication formation, the redox potentials are virtually independent of the bromo substituents.

Antitumour polyether macrolides: four new halichondrins from the New Zealand deep-water marine sponge Lissodendoryx sp.

PubMed

Hickford, Sarah J H; Blunt, John W; Munro, Murray H G

2009-03-15

The isolation is reported of four new variants of the halichondrin B skeleton, very minor potently bioactive components from the Poecilosclerid sponge Lissodendoryx sp. These compounds were isolated in microgram quantities only from a collection of 1tonne of sponge. The structural elucidations relied heavily on the use of capillary NMR spectroscopy and the application of an HSQC-DEPT overlay technique.

Sequential enzymatic epoxidation involved in polyether lasalocid biosynthesis.

PubMed

Minami, Atsushi; Shimaya, Mayu; Suzuki, Gaku; Migita, Akira; Shinde, Sandip S; Sato, Kyohei; Watanabe, Kenji; Tamura, Tomohiro; Oguri, Hiroki; Oikawa, Hideaki

2012-05-02

Enantioselective epoxidation followed by regioselective epoxide opening reaction are the key processes in construction of the polyether skeleton. Recent genetic analysis of ionophore polyether biosynthetic gene clusters suggested that flavin-containing monooxygenases (FMOs) could be involved in the oxidation steps. In vivo and in vitro analyses of Lsd18, an FMO involved in the biosynthesis of polyether lasalocid, using simple olefin or truncated diene of a putative substrate as substrate mimics demonstrated that enantioselective epoxidation affords natural type mono- or bis-epoxide in a stepwise manner. These findings allow us to figure out enzymatic polyether construction in lasalocid biosynthesis. © 2012 American Chemical Society

Detection of airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins in the indoor environment.

PubMed

Brasel, T L; Martin, J M; Carriker, C G; Wilson, S C; Straus, D C

2005-11-01

The existence of airborne mycotoxins in mold-contaminated buildings has long been hypothesized to be a potential occupant health risk. However, little work has been done to demonstrate the presence of these compounds in such environments. The presence of airborne macrocyclic trichothecene mycotoxins in indoor environments with known Stachybotrys chartarum contamination was therefore investigated. In seven buildings, air was collected using a high-volume liquid impaction bioaerosol sampler (SpinCon PAS 450-10) under static or disturbed conditions. An additional building was sampled using an Andersen GPS-1 PUF sampler modified to separate and collect particulates smaller than conidia. Four control buildings (i.e., no detectable S. chartarum growth or history of water damage) and outdoor air were also tested. Samples were analyzed using a macrocyclic trichothecene-specific enzyme-linked immunosorbent assay (ELISA). ELISA specificity was tested using phosphate-buffered saline extracts of the fungal genera Aspergillus, Chaetomium, Cladosporium, Fusarium, Memnoniella, Penicillium, Rhizopus, and Trichoderma, five Stachybotrys strains, and the indoor air allergens Can f 1, Der p 1, and Fel d 1. For test buildings, the results showed that detectable toxin concentrations increased with the sampling time and short periods of air disturbance. Trichothecene values ranged from <10 to >1,300 pg/m3 of sampled air. The control environments demonstrated statistically significantly (P < 0.001) lower levels of airborne trichothecenes. ELISA specificity experiments demonstrated a high specificity for the trichothecene-producing strain of S. chartarum. Our data indicate that airborne macrocyclic trichothecenes can exist in Stachybotrys-contaminated buildings, and this should be taken into consideration in future indoor air quality investigations.

Epoxide hydrolase Lsd19 for polyether formation in the biosynthesis of lasalocid A: direct experimental evidence on polyene-polyepoxide hypothesis in polyether biosynthesis.

PubMed

Shichijo, Yoshihiro; Migita, Akira; Oguri, Hiroki; Watanabe, Mami; Tokiwano, Tetsuo; Watanabe, Kenji; Oikawa, Hideaki

2008-09-17

Polyether metabolites are an important class of natural products. Although their biosynthesis, especially construction of polyether skeletons, attracted organic chemists for many years, no experimental data on the enzymatic polyether formation has been obtained. In this study, a putative epoxide hydrolase gene lsd19 found on the biosynthetic gene cluster of an ionophore polyether lasalocid was cloned and successfully overexpressed in Escherichia coli. Using the purified Lsd19, a proposed substrate, bisepoxyprelasalocid, and its synthesized analogue were successfully converted into lasalocid A and its derivative via a 6-endo-tet cyclization mode. On the other hand, treatment of the bisepoxide with trichloroacetic acid gave isolasalocid A via a 5-exo-tet cyclization mode. Therefore, the enzymatic conversion observed in this study unambiguously showed that the bisepoxyprelasalocid is an intermediate of the lasalocid biosynthesis and that Lsd19 catalyzes the sequential cyclic ether formations involving an energetically disfavored 6-endo-tet cyclization. This is the first example of the enzymatic epoxide-opening reactions leading to a polyether natural product.

Antitumoral activity of 1,2-diaminocyclohexane derivatives in breast, colon and skin human cancer cells.

PubMed

Morales, Fátima; Ramírez, Alberto; Morata-Tarifa, Cynthia; Navarro, Saúl A; Marchal, Juan A; Campos, Joaquín M; Conejo-García, Ana

2017-03-01

Cancer is among the leading causes of death worldwide. Medical interest has focused on macrocyclic polyamines because of their properties as antitumor agents. Results/Methodology: We have designed and synthesized a series of 1,2-diaminocyclohexane derivatives with notable in vitro antiproliferative activities against the MCF-7, HCT-116 and A375 cancer cell lines. Cell cycle and apoptosis analyses were also carried out. Our results show that all the compounds are potent cytotoxic agents, especially against the A375 cell line. The selective activity of the macrocyclic derivative against A375, via apoptosis, supposes a great advantage for future therapeutic use. This exemplifies the potential of 1,2-diaminocyclohexane derivatives to qualify as lead structures for future anticancer drug development due to their easy syntheses and noteworthy bioactivity.

Screening of potential genes contributing to the macrocycle drug resistance of C. albicans via microarray analysis

PubMed Central

Yang, Jing; Zhang, Wei; Sun, Jian; Xi, Zhiqin; Qiao, Zusha; Zhang, Jinyu; Wang, Yan; Ji, Ying; Feng, Wenli

2017-01-01

The aim of the present study was to investigate the potential genes involved in drug resistance of Candida albicans (C. albicans) by performing microarray analysis. The gene expression profile of GSE65396 was downloaded from the Gene Expression Omnibus, including a control, 15-min and 45-min macrocyclic compound RF59-treated group with three repeats for each. Following preprocessing using RAM, the differentially expressed genes (DEGs) were screened using the Limma package. Subsequently, the Kyoto Encyclopedia of Genes and Genomes pathways of these genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery. Based on interactions estimated by the Search Tool for Retrieval of Interacting Gene, the protein-protein interaction (PPI) network was visualized using Cytoscape. Subnetwork analysis was performed using ReactomeFI. A total of 154 upregulated and 27 downregulated DEGs were identified in the 15-min treated group, compared with the control, and 235 upregulated and 233 downregulated DEGs were identified in the 45-min treated group, compared with the control. The upregulated DEGs were significantly enriched in the ribosome pathway. Based on the PPI network, PRP5, RCL1, NOP13, NOP4 and MRT4 were the top five nodes in the 15-min treated comparison. GIS2, URA3, NOP58, ELP3 and PLP7 were the top five nodes in the 45-min treated comparison, and its subnetwork was significantly enriched in the ribosome pathway. The macrocyclic compound RF59 had a notable effect on the ribosome and its associated pathways of C. albicans. RCL1, NOP4, MRT4, GIS2 and NOP58 may be important in RF59-resistance. PMID:28944888

Detection of airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins on particulates smaller than conidia.

PubMed

Brasel, T L; Douglas, D R; Wilson, S C; Straus, D C

2005-01-01

Highly respirable particles (diameter, <1 microm) constitute the majority of particulate matter found in indoor air. It is hypothesized that these particles serve as carriers for toxic compounds, specifically the compounds produced by molds in water-damaged buildings. The presence of airborne Stachybotrys chartarum trichothecene mycotoxins on particles smaller than conidia (e.g., fungal fragments) was therefore investigated. Cellulose ceiling tiles with confluent Stachybotrys growth were placed in gas-drying containers through which filtered air was passed. Exiting particulates were collected by using a series of polycarbonate membrane filters with decreasing pore sizes. Scanning electron microscopy was employed to determine the presence of conidia on the filters. A competitive enzyme-linked immunosorbent assay (ELISA) specific for macrocyclic trichothecenes was used to analyze filter extracts. Cross-reactivity to various mycotoxins was examined to confirm the specificity. Statistically significant (P < 0.05) ELISA binding was observed primarily for macrocyclic trichothecenes at concentrations of 50 and 5 ng/ml and 500 pg/ml (58.4 to 83.5% inhibition). Of the remaining toxins tested, only verrucarol and diacetylverrucarol (nonmacrocyclic trichothecenes) demonstrated significant binding (18.2 and 51.7% inhibition, respectively) and then only at high concentrations. The results showed that extracts from conidium-free filters demonstrated statistically significant (P < 0.05) antibody binding that increased with sampling time (38.4 to 71.9% inhibition, representing a range of 0.5 to 4.0 ng/ml). High-performance liquid chromatography analysis suggested the presence of satratoxin H in conidium-free filter extracts. These data show that S. chartarum trichothecene mycotoxins can become airborne in association with intact conidia or smaller particles. These findings may have important implications for indoor air quality assessment.

A rare allergy to a polyether dental impression material.

PubMed

Mittermüller, Pauline; Szeimies, Rolf-Markus; Landthaler, Michael; Schmalz, Gottfried

2012-08-01

Polyether impression materials have been used in dentistry for more than 40 years. Allergic reactions to these materials such as reported in the 1970s ceased after replacement of a catalyst. Very recently, however, patients have started to report symptoms that suggest a new allergic reaction from polyether impression materials. Here, we report on the results of allergy testing with polyether impression materials as well as with its components. Eight patients with clinical symptoms of a contact allergy (swelling, redness or blisters) after exposure to a polyether impression material were subjected to patch tests, two of them additionally to a prick test. A further patient with atypical symptoms of an allergy (nausea and vomiting after contact with a polyether impression material in the oral cavity) but with a history of other allergic reaction was also patch tested. The prick tests showed no immediate reactions in the two patients tested. In the patch tests, all eight patients with typical clinical symptoms showed positive reactions to the mixed polyether impression materials, to the base paste or to a base paste component. The patient with the atypical clinical symptoms did not show any positive patch test reactions. Polyether impression materials may evoke type IV allergic reactions. The causative agent was a component of the base paste. In consideration of the widespread use of this impression material (millions of applications per year) and in comparison to the number of adverse reactions from other dental materials, the number of such allergic reactions is very low. In very scarce cases, positive allergic reactions to polyether impression materials are possible.

Electrically conducting porphyrin and porphyrin-fullerene electropolymers

DOEpatents

Gust, Jr., John Devens; Liddell, Paul Anthony; Gervaldo, Miguel Andres; Bridgewater, James Ward; Brennan, Bradley James; Moore, Thomas Andrew; Moore, Ana Lorenzelli

2014-03-11

Compounds with aryl ring(s) at porphyrin meso position(s) bearing an amino group in position 4 relative to the porphyrin macrocycle, and at least one unsubstituted 5 (hydrogen-bearing) meso position with the 10-, 15-, and/or 20-relationship to the aryl ring bearing the amino group, and metal complexes thereof, feature broad spectral absorption throughout the visible region. These compounds are electropolymerized to form electrically conducting porphyrin and porphyrin-fullerene polymers that are useful in photovoltaic applications. The structure of one such electrically conducting porphyrin polymer is shown below. ##STR00001##

Enantioselective Fluorescent Recognition of Chiral Acids by Cyclohexane-1,2-diamine-Based Bisbinaphthyl Molecules

PubMed Central

Li, Zi-Bo; Lin, Jing; Sabat, Michal; Hyacinth, Marilise; Pu, Lin

2008-01-01

The cyclohexane-1,2-diamine-based bisbinaphthyl macrocycles (S)-/(R)-5 and their cyclic and acyclic analogs are synthesized. The interactions of these compounds with various chiral acids are studied. Compounds (S)-/(R)-5 exhibit highly enantioselective fluorescent responses and high fluorescent sensitivity toward α-hydroxycarboxylic acids and N-protected amino acids. Among these interactions, (S)-mandelic acid (10−3 M) led to over 20 fold fluorescence enhancement of (S)-5 (1.0 × 10−5 M in benzene/0.05% DME) at the monomer emission and (S)-hexahydromandelic acid (10−3 M) led to over 80 fold fluorescence enhancement. These results demonstrate that (S)-5 is useful as an enantioselective fluorescent sensor for the recognition of the chiral acids. On the basis of the study of the structures of (S)-5 and the previously reported 1,2-diphenylethylenediamine-based bisbinaphthyl macrocycle (S)-4, the large fluorescence enhancement of (S)-5 with achirality-matched α-hydroxycarboxylic acid is attributed to the formation of a structurally rigidified host-guest complex and the further interaction of this complex with the acid to suppress the photo-induced electron transfer fluorescent quenching caused by the nitrogens in (S)-5. PMID:17530897

Synthesis of novel macrocycles carrying pincer-type ligands as future candidates for potential applications in size-selective, stereochemical and recyclable catalysts

NASA Astrophysics Data System (ADS)

Khan, Burhan; Shah, Muhammad Raza; Rabnawaz, Muhammad

2018-03-01

Macrocycles with ultra dense functionalities are very useful but are difficult to synthesize. In this study, we report six novel macrocycles bearing a pincer ligand alone or a combination of pincer-calixarenes, and pincer-fluorene moieties. Click chemistry was utilized to synthesize the desired macrocycles in good yields. These macrocycles were fully characterized using mass spectrometry (EI-MS, ESI-MS, and MALDI-TOF MS), and NMR spectroscopy. These macrocycles are under investigations as size-selective and recyclable catalysts for various chemical transformations.

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids.

PubMed

Borgström, Björn; Huang, Xiaoli; Chygorin, Eduard; Oredsson, Stina; Strand, Daniel

2016-06-09

The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH(+) cells, a phenotype associated with cancer stem cells was not observed. Mechanistic implications are discussed.

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids

PubMed Central

2016-01-01

The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N- and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH+ cells, a phenotype associated with cancer stem cells was not observed. Mechanistic implications are discussed. PMID:27326340

Spectroscopic and computational study of a new isomer of salinomycin

NASA Astrophysics Data System (ADS)

Pankiewicz, Radosław

2013-09-01

A new derivative of polyether ionophore salinomycin was obtained as a result of a rearrangement catalysed by sulphuric acid in two-phase medium of water/methylene chloride solution. The new isomer was fully characterized by multinuclear 2D NMR, NOESY and MALDI-TOF. The properties of the new compound were additionally study by semiempirical (PM5) and DFT (B3LYP) methods. A potential mechanism of the rearrangement was also proposed.

Antiandrogen and Antimicrobial Aspects of Coordination Compounds of Palladium(II), Platinum(II) and Lead(II)

PubMed Central

Joshi, S. C.; Kulshrestha, Shalini; Nagpal, Pooja; Bansal, Anil

2001-01-01

Synthesis, characterization and antimicrobial activities of an interesting class of biologically potent macrocyclic complexes have been carried out. All the complexes have been evaluated for their antimicrobial effects on different species of pathogenic fungi and bacteria. The testicular sperm density, testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trails and biochemical parameters of reproductive organs have been examined and discussed. The resulting biologically active [M(MaLn)(R2)]Cl2 and [Pb(MaLn)(R2)X2] (where, M = PdII or PtII and X = Cl or NO3) type of complexes have been synthesized by the reactions of macrocyclic ligands (MaLn) with metal salts and different diamines in 1:1:1 molar ratio in methanol. Initially the complexes were characterized by elemental analyses, molecular weight determinations and conductivity measurements. The mode of bonding was established on the basis of IR, 1H NMR, 13C NMR, 195Pt NMR, 207Pb NMR, XRD and electronic spectral studies. The macrocyclic ligand coordinates through the four azomethine nitrogen atoms which are bridged by benzil moieties. IR spectra suggest that the pyridine nitrogen is not coordinating. The palladium and platinum complexes exhibit tetracoordinated square-planar geometry, whereas a hexacoordinated octahedral geometry is suggested for lead complexes. PMID:18475989

Protocols for the Design of Kinase-focused Compound Libraries.

PubMed

Jacoby, Edgar; Wroblowski, Berthold; Buyck, Christophe; Neefs, Jean-Marc; Meyer, Christophe; Cummings, Maxwell D; van Vlijmen, Herman

2018-05-01

Protocols for the design of kinase-focused compound libraries are presented. Kinase-focused compound libraries can be differentiated based on the design goal. Depending on whether the library should be a discovery library specific for one particular kinase, a general discovery library for multiple distinct kinase projects, or even phenotypic screening, there exists today a variety of in silico methods to design candidate compound libraries. We address the following scenarios: 1) Datamining of SAR databases and kinase focused vendor catalogues; 2) Predictions and virtual screening; 3) Structure-based design of combinatorial kinase inhibitors; 4) Design of covalent kinase inhibitors; 5) Design of macrocyclic kinase inhibitors; and 6) Design of allosteric kinase inhibitors and activators. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polyether-polyester graft copolymer

NASA Technical Reports Server (NTRS)

Bell, Vernon L. (Inventor)

1987-01-01

Described is a polyether graft polymer having improved solvent resistance and crystalline thermally reversible crosslinks. The copolymer is prepared by a novel process of anionic copolymerization. These polymers exhibit good solvent resistance and are well suited for aircraft parts. Previous aromatic polyethers, also known as polyphenylene oxides, have certain deficiencies which detract from their usefulness. These commercial polymers are often soluble in common solvents including the halocarbon and aromatic hydrocarbon types of paint thinners and removers. This limitation prevents the use of these polyethers in structural articles requiring frequent painting. In addition, the most popular commercially available polyether is a very high melting plastic. This makes it considerably more difficult to fabricate finished parts from this material. These problems are solved by providing an aromatic polyether graft copolymer with improved solvent resistance and crystalline thermally reversible crosslinks. The graft copolymer is formed by converting the carboxyl groups of a carboxylated polyphenylene oxide polymer to ionic carbonyl groups in a suitable solvent, reacting pivalolactone with the dissolved polymer, and adding acid to the solution to produce the graft copolymer.

Polyether ionophores-promising bioactive molecules for cancer therapy.

PubMed

Huczyński, Adam

2012-12-01

The natural polyether ionophore antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the polyether ionophores undergoing pre-clinical evaluation are reviewed. Most of polyether ionophores have shown potent activity against the proliferation of various cancer cells, including those that display multidrug resistance (MDR) and cancer stem cells (CSC). The mechanism underlying the anticancer activity of ionophore agents can be related to their ability to form complexes with metal cations and transport them across cellular and subcellular membranes. Increasing evidence shows that the anticancer activity of polyether ionophores may be a consequence of the induction of apoptosis leading to apoptotic cell death, arresting cell cycle progression, induction of the cell oxidative stress, loss of mitochondrial membrane potential, reversion of MDR, synergistic anticancer effect with other anticancer drugs, etc. Continued investigation of the mechanisms of action and development of new polyether ionophores and their derivatives may provide more effective therapeutic drugs for cancer treatments. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sustainable metal alkynyl chemistry: 3d metals and polyaza macrocyclic ligands.

PubMed

Ren, Tong

2016-02-25

We describe the chemistry of 3d metal alkynyls based on polyaza macrocyclic ligands, an emerging area of alkynyl chemistry that has previously been dominated by 4d and 5d metals with soft ligands. The abundance of 3d metals and low cost of tetraazacyclotetradecane ligands make these compounds more affordable, sustainable alternatives to metal alkynyls based on precious metals. Taking advantage of the rich variety of starting materials available in the literature, trans-[M(cyclam)(C2R)2]X (cyclam = 1,4,8,11-tetraazacyclotetradecane) compounds have been prepared from the reactions between [M(cyclam)X2]X (M = Cr, Fe and Co; X = Cl or OTf) and LiC2R. With [Co(cyclam)Cl2](+), both the {trans-[Co(cyclam)Cl]2(μ-(C≡C)n)}(2+) and trans-[Co(cyclam)(C2R)Cl](+) compounds have been prepared by a dehydrohalogenation reaction. The latter compounds undergo the second alkynylation reaction to afford dissymmetric trans-[Co(cyclam)(C2R)(C2R')](+) compounds. Similar alkynylation chemistry with complexes of the cyclam derivatives TMC (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and HMC (5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane) has been demonstrated in studies of [Ni(TMC)(C2R)](+) and trans-/cis-[Cr(HMC)(C2R)2](+). Me3TACN (1,4,7-N,N',N''-trimethyl-1,4,7-triazacyclononane) is also a supporting ligand that has been observed in transition metal alkynyls. The trans-[M(cyclam)(C2D)(C2A)](+) compounds (D = donor chromophore, A = acceptor chromophore) are excellent candidates for probing photoinduced electron transfer and related photophysical and photochemical processes. 3d Metal ions are often in high-spin ground states, which make these alkynyl compounds promising building blocks for magnetic materials.

Fixation of carbon dioxide by macrocyclic lanthanide(III) complexes under neutral conditions producing self-assembled trimeric carbonato-bridged compounds with μ3-η2:η2:η2 bonding.

PubMed

Bag, Pradip; Dutta, Supriya; Biswas, Papu; Maji, Swarup Kumar; Flörke, Ulrich; Nag, Kamalaksha

2012-03-28

A series of mononuclear lanthanide(III) complexes [Ln(LH(2))(H(2)O)(3)Cl](ClO(4))(2) (Ln = La, Nd, Sm, Eu, Gd, Tb, Lu) of the tetraiminodiphenolate macrocyclic ligand (LH(2)) in 95 : 5 (v/v) methanol-water solution fix atmospheric carbon dioxide to produce the carbonato-bridged trinuclear complexes [{Ln(LH(2))(H(2)O)Cl}(3)(μ(3)-CO(3))](ClO(4))(4)·nH(2)O. Under similar conditions, the mononuclear Y(III) complex forms the dimeric compound [{Y(LH(2))(H(2)O)Cl}(μ(2)-CO(3)){Y(LH(2))(H(2)O)(2)}](ClO(4))(3)·4H(2)O. These complexes have been characterized by their IR and NMR ((1)H, (13)C) spectra. The X-ray crystal structures have been determined for the trinuclear carbonato-bridged compounds of Nd(III), Gd(III) and Tb(III) and the dinuclear compound of Y(III). In all cases, each of the metal centers are 8-coordinate involving two imine nitrogens and two phenolate oxygens of the macrocyclic ligand (LH(2)) whose two other imines are protonated and intramolecularly hydrogen-bonded with the phenolate oxygens. The oxygen atoms of the carbonate anion in the trinuclear complexes are bonded to the metal ions in tris-bidentate μ(3)-η(2):η(2):η(2) fashion, while they are in bis-bidentate μ(2)-η(2):η(2) mode in the Y(III) complex. The magnetic properties of the Gd(III) complex have been studied over the temperature range 2 to 300 K and the magnetic susceptibility data indicate a very weak antiferromagnetic exchange interaction (J = -0.042 cm(-1)) between the Gd(III) centers (S = 7/2) in the metal triangle through the carbonate bridge. The luminescence spectral behaviors of the complexes of Sm(III), Eu(III), and Tb(III) have been studied. The ligand LH(2) acts as a sensitizer for the metal ions in an acetonitrile-toluene glassy matrix (at 77 K) and luminescence intensities of the complexes decrease in the order Eu(3+) > Sm(3+) > Tb(3+).

Control of the orientation and photoinduced phase transitions of macrocyclic azobenzene.

PubMed

Uchida, Emi; Sakaki, Kouji; Nakamura, Yumiko; Azumi, Reiko; Hirai, Yuki; Akiyama, Haruhisa; Yoshida, Masaru; Norikane, Yasuo

2013-12-16

Photoinduced phase transitions caused by photochromic reactions bring about a change in the state of matter at constant temperature. Herein, we report the photoinduced phase transitions of crystals of a photoresponsive macrocyclic compound bearing two azobenzene groups (1) at room temperature on irradiation with UV (365 nm) and visible (436 nm) light. The trans/trans isomer undergoes photoinduced phase transitions (crystal-isotropic phase-crystal) on UV light irradiation. The photochemically generated crystal exhibited reversible phase transitions between the crystal and the mesophase on UV and visible light irradiation. The molecular order of the randomly oriented crystals could be increased by irradiating with linearly polarized visible light, and the value of the order parameter was determined to be -0.84. Heating enhances the thermal cis-to-trans isomerization and subsequent cooling returned crystals of the trans/trans isomer. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Strained Cyclophane Macrocycles: Impact of Progressive Ring Size Reduction on Synthesis and Structure

PubMed Central

Bogdan, Andrew R.; Jerome, Steven V.; Houk, K. N.; James, Keith

2012-01-01

The synthesis, X-ray crystal structures, and calculated strain energies are reported for a homologous series of 11- to 14-membered drug-like cyclophane macrocycles, representing an unusual region of chemical space that can be difficult to access synthetically. The ratio of macrocycle to dimer, generated via a copper catalyzed azide-alkyne cycloaddition macrocyclization in flow at elevated temperature, could be rationalized in terms of the strain energy in the macrocyclic product. The progressive increase in strain resulting from reduction in macrocycle ring size, or the introduction of additional conformational constraints, results in marked deviations from typical geometries. These strained cyclophane macrocyclic systems provide access to spatial orientations of functionality that would not be readily available in unstrained or acyclic analogs. The most strained system prepared represents the first report of an 11-membered cyclophane containing a 1,4-disubstituted 1,2,3-triazole ring, and establishes a limit to the ring strain that can be generated using this macrocycle synthesis methodology. PMID:22133103

40 CFR 63.1425 - Process vent control requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Hazardous Air Pollutant Emissions for Polyether Polyols Production § 63.1425 Process vent... operators of all affected sources using epoxides in the production of polyether polyols are subject to the... (c) of this section only if epoxides are used in the production of polyether polyols and nonepoxide...

77 FR 20386 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-04

... Activities; Submission to OMB for Review and Approval; Comment Request; NESHAP for Polyether Polyols... electronic docket, go to www.regulations.gov . Title: NESHAP for Polyether Polyols Production (Renewal). ICR... Hazardous Air Pollutants (NESHAP) for Polyether Polyols Production (40 CFR part 63 subpart PPP) were...

Synthesis and Biological Evaluation of Neopeltolide and Analogs

PubMed Central

Cui, Yubo; Balachandran, Raghavan

2012-01-01

The synthesis of neopeltolide analogs that contain variations in the oxazole-containing side chain and in the macrolide core are reported along with the GI50 values for these compounds against MCF7, HCT-116, and p53 knockout HCT-116 cell lines. Although biological activity is sensitive to changes in the macrocycle and the side chain, several analogs displayed GI50 values of <25 nM. Neopeltolide and several of the more potent analogs were significantly less potent against p53 knockout cells, suggesting that p53 plays an auxiliary role in the activity of these compounds. PMID:22329423

Bambus[n]urils: a new family of macrocyclic anion receptors.

PubMed

Havel, Vaclav; Svec, Jan; Wimmerova, Michaela; Dusek, Michal; Pojarova, Michaela; Sindelar, Vladimir

2011-08-05

A recently discovered anion receptor is jointed by three related macrocycles differing in the number of glycoluril units and type of substitution. The synthesis is carried out in nonpolar solvents compared to aqueous media used in the case of the original macrocycle. The size of macrocycle is controlled by a template. A hexameric macrocycle with benzyl substitution binds halide anions with an affinity exceeding 10(9) M(-1) while a tetrameric analog does not bind any of the investigated anions. © 2011 American Chemical Society

Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 15. Effects of the pyridyl substituents and fused exocyclic rings on the UV-visible spectroscopic properties of Mg(II)-porphyrazines: a combined experimental and DFT/TDDFT study.

PubMed

Donzello, Maria Pia; De Mori, Giorgia; Viola, Elisa; Ercolani, Claudio; Ricciardi, Giampaolo; Rosa, Angela

2014-08-04

Two new Mg(II) porphyrazine macrocycles, the octakis(2-pyridyl)porphyrazinato-magnesium(II), [Py8PzMg(H2O)], and the tetrakis-[6,7-di(2-pyridyl)quinoxalino]porphyrazinato-magnesium(II), [Py8QxPzMg(H2O)], were prepared by Mg-template macrocyclization processes, and their general physicochemical properties were examined. The previously reported porphyrazine analog, the tetrakis-2,3-[5,6-di(2-pyridyl)-pyrazino]porphyrazinato-magnesium(II), [Py8PyzPzMg(H2O)], has been also considered in the present work. The UV-visible solution spectra in nonaqueous solvents of this triad of externally octapyridinated Mg(II) complexes exhibit the usual profile observed for phthalocyanine and porphyrazine macrocycles, with intense absorptions in the Soret (300-450 nm) and Q band (600-800 nm) regions. It is observed that the Q band maximum sensibly shifts toward the red with peak values at 635 → 658 → 759 nm along the series [Py8PzMg(H2O)], [Py8PyzPzMg(H2O)], and [Py8QxPzMg(H2O)], as the extension of the macrocycle π-system increases. TDDFT calculations of the electronic absorption spectra were performed for the related water-free model compounds [Py8PzMg], [Py8PyzPzMg], and [Py8QxPzMg] to provide an interpretation of the UV-visible spectral changes occurring upon introduction of the pyrazine and quinoxaline rings at the periphery of the Pz macrocycle. To discriminate the electronic effects of the fused exocyclic rings from those of the appended 2-pyridyl rings, the UV-visible spectra of [PzMg] and [PyzPzMg] were also theoretically investigated. The theoretical results prove to agree very well with the experimental data, providing an accurate description of the UV-visible spectra. The observed spectral changes are interpreted on the basis of the electronic structure changes occurring along the series.

Preparation of macrocycles with high carbon content: Toward the synthesis of endohedral metal fullerene complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, T.C.; Rubin, Y.

1995-12-31

This research is focused on the synthesis of macrocycles with high carbon content for the purpose of total synthesis of fullerenes or fullerene-like structures with the ultimate goal of obtaining endohedral metal complexes of fullerene C{sub 60}. Toward this goal, the authors have utilized organometallic chemistry to synthesize novel cyclophanes such as 1 which are constituted primarily of acetylenic units. The authors believe such macrocycles may be C{sub 60} precursors since studies have shown that acetylenic macrocycles form fullerenes in the gas phase. The authors have synthesized macrocycle 1 using a highly convergent route from commercially available starting materials. Themore » macrocycle 1 is produced from copper (I) catalyzed coupling of 2 which is obtained in turn by the coupling of the copper acetylide 3 with 4. The suitability of macrocycles such as 1 for fullerene precursors is currently under investigation.« less

Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis.

PubMed

Wong, Fong T; Hotta, Kinya; Chen, Xi; Fang, Minyi; Watanabe, Kenji; Kim, Chu-Young

2015-01-14

Biosynthesis of some polyether natural products involves a kinetically disfavored epoxide-opening cyclic ether formation, a reaction termed anti-Baldwin cyclization. One such example is the biosynthesis of lasalocid A, an ionophore antibiotic polyether. During lasalocid A biosynthesis, an epoxide hydrolase, Lsd19, converts the bisepoxy polyketide intermediate into the tetrahydrofuranyl-tetrahydropyran product. We report the crystal structure of Lsd19 in complex with lasalocid A. The structure unambiguously shows that the C-terminal domain of Lsd19 catalyzes the intriguing anti-Baldwin cyclization. We propose a general mechanism for epoxide selection by ionophore polyether epoxide hydrolases.

Accurate and Reliable Prediction of the Binding Affinities of Macrocycles to Their Protein Targets.

PubMed

Yu, Haoyu S; Deng, Yuqing; Wu, Yujie; Sindhikara, Dan; Rask, Amy R; Kimura, Takayuki; Abel, Robert; Wang, Lingle

2017-12-12

Macrocycles have been emerging as a very important drug class in the past few decades largely due to their expanded chemical diversity benefiting from advances in synthetic methods. Macrocyclization has been recognized as an effective way to restrict the conformational space of acyclic small molecule inhibitors with the hope of improving potency, selectivity, and metabolic stability. Because of their relatively larger size as compared to typical small molecule drugs and the complexity of the structures, efficient sampling of the accessible macrocycle conformational space and accurate prediction of their binding affinities to their target protein receptors poses a great challenge of central importance in computational macrocycle drug design. In this article, we present a novel method for relative binding free energy calculations between macrocycles with different ring sizes and between the macrocycles and their corresponding acyclic counterparts. We have applied the method to seven pharmaceutically interesting data sets taken from recent drug discovery projects including 33 macrocyclic ligands covering a diverse chemical space. The predicted binding free energies are in good agreement with experimental data with an overall root-mean-square error (RMSE) of 0.94 kcal/mol. This is to our knowledge the first time where the free energy of the macrocyclization of linear molecules has been directly calculated with rigorous physics-based free energy calculation methods, and we anticipate the outstanding accuracy demonstrated here across a broad range of target classes may have significant implications for macrocycle drug discovery.

Size-Selective Detection of Picric Acid by Fluorescent Palladium Macrocycles.

PubMed

Kumar, Sushil; Kishan, Ram; Kumar, Pramod; Pachisia, Sanya; Gupta, Rajeev

2018-02-19

This work presents the synthesis and characterization of two palladium-based fluorescent macrocycles offering hydrogen-bonding cavities of contrasting dimensions. Both palladium macrocycles function as chemosensors for the detection of nitroaromatics, whereas the larger macrocycle not only illustrates nanomolar detection of picric acid but also transports its significant amount from an aqueous to an organic phase.

Fragrance material review on 16-hydroxy-7-hexadecenoic acid lactone.

PubMed

McGinty, D; Letizia, C S; Api, A M

2011-12-01

A toxicologic and dermatologic review of 16-hydroxy-7-hexadecenoic acid lactone when used as a fragrance ingredient is presented. 16-Hydroxy-7-hexadecenoic acid lactone is a member of the fragrance structural group macrocyclic lactone and lactide derivatives. The fragrance ingredient described herein is one of 12 structurally diverse C14, C15 and C16 compounds that include (1) saturated mono-and (2) saturated di-ester lactones and (3) unsaturated lactones. For the latter, the double bond is not adjacent to (in conjugation with) the ester group. This review contains a detailed summary of all available toxicology and dermatology papers that are related to 16-hydroxy-7-hexadecenoic acid lactone and is not intended as a stand-alone document. Available data were evaluated, then summarized, and include physical properties data. A safety assessment of the entire macrocyclic lactone and lactide derivatives will be published simultaneously with this document. Please refer to Belsito et al., 2011 for an overall assessment of the safe use of this material and all macrocyclic lactone and lactide derivatives in fragrances. Belsito, D., Bickers, D., Bruze, M., Calow, P., Dagli, M., Fryer, A.D., Greim, H., Hanifin, J.H., Miyachi, Y., Saurat, J.H., Sipes, I.G., 2011. A toxicologic and dermatologic assessment of macrocylic lactones and lactide derivatives when used as fragrance ingredients. Copyright © 2011. Published by Elsevier Ltd.

40 CFR Table 4 to Subpart Ppp of... - Known Organic HAP From Polyether Polyol Products

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 11 2011-07-01 2011-07-01 false Known Organic HAP From Polyether Polyol Products 4 Table 4 to Subpart PPP of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION... Production Pt. 63, Subpt. PPP, Table 4 Table 4 to Subpart PPP of Part 63—Known Organic HAP From Polyether...

40 CFR Table 4 to Subpart Ppp of... - Known Organic HAP From Polyether Polyol Products

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 12 2014-07-01 2014-07-01 false Known Organic HAP From Polyether Polyol Products 4 Table 4 to Subpart PPP of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION... Polyether Polyols Production Pt. 63, Subpt. PPP, Table 4 Table 4 to Subpart PPP of Part 63—Known Organic HAP...

40 CFR Table 4 to Subpart Ppp of... - Known Organic HAP From Polyether Polyol Products

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 12 2013-07-01 2013-07-01 false Known Organic HAP From Polyether Polyol Products 4 Table 4 to Subpart PPP of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION... Polyether Polyols Production Pt. 63, Subpt. PPP, Table 4 Table 4 to Subpart PPP of Part 63—Known Organic HAP...

40 CFR Table 4 to Subpart Ppp of... - Known Organic HAP From Polyether Polyol Products

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 12 2012-07-01 2011-07-01 true Known Organic HAP From Polyether Polyol Products 4 Table 4 to Subpart PPP of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Pt. 63, Subpt. PPP, Table 4 Table 4 to Subpart PPP of Part 63—Known Organic HAP From Polyether Polyol...

Mycotoxins from mould infested building materials.

PubMed

Nielsen, K F

2000-03-01

Only limited documentation of non-allergenic, especially toxic reactions after inhalation of microfungal spores in water damaged buildings exists. Recently attention has been drawn to the mycotoxins as causal compounds, as some the dominating genera found in buildings are well known mycotoxin producers.Penicillium chrysogenum and A. ustus do not seem to produce any known mycotoxins when growing on building materials, whereasP. brevicompactum produces mycophenolic acid, someP. polonicum produces verrucosidin and verrucofortine,A. versicolor produces sterigmatocystins,A. niger produces nigragillin, orlandin, naphtho-γ-pyrones and tetracyclic compounds, someA. ochraceus produces ochratoxin A,Alternaria spp. produce alternariol and alternariol monomethyl ether,Chaetomium globosum produce chaetoglobosins, and finally 30-40% ofStachybotrys chartarum isolates from buildings produce macrocyclic trichothecenes and a number of other biologically active compounds.

Electron spectroscopic imaging of antigens by reaction with boronated antibodies.

PubMed

Qualmann, B; Kessels, M M; Klobasa, F; Jungblut, P W; Sierralta, W D

1996-07-01

Two small homogeneous markers for electron spectroscopic imaging (ESI) containing eight dodecaborane cages linked to a poly-alpha, epsilon-L-lysine dendrimer were synthesized; one of these was made water soluble by the attachment of a polyether. The markers were coupled to the sulfhydryl group of (monovalent) antibody fragments (Fab') by a homobifunctional cross-linker. While the coupling ratios of the poorly water-soluble compound did not exceed 20%, the polyether-containing variant reacted quantitatively. Its suitability for immunolabelling was tested in a study of the mechanism of the transcellular transport of an administered heterologous protein (bovine serum albumin, BSA) through ileal enterocytes of newborn piglets by endocytotic vesicles in comparison to conventional immunogold reagents. The post-embedding technique was employed. The boronated Fab' gave rise to considerably higher tagging frequencies than seen with immunogold, as could be expected from its form- and size-related physical advantages and the dense packing of BSA in the vesicles. The new probe, carrying the antigen-combining cleft at one end and the boron clusters at the opposite end of the oval-shaped conjugate, add to the potential of ESI-based immunocytochemistry.

Hindered Glymes for Graphite-Compatible Electrolytes.

PubMed

Shanmukaraj, Devaraj; Grugeon, Sylvie; Laruelle, Stephane; Armand, Michel

2015-08-24

Organic carbonate mixtures are used almost exclusively as lithium battery electrolyte solvents. The linear compounds (dimethyl carbonate, diethyl carbonate, ethyl methyl carbonate) act mainly as thinner for the more viscous and high-melting ethylene carbonate but are the least stable component and have low flash points; these are serious handicaps for lifetime and safety. Polyethers (glymes) are useful co-solvents, but all formerly known representatives solvate Li(+) strongly enough to co-intercalate in the graphite negative electrode and exfoliate it. We have put forward a new electrolyte composition comprising a polyether to which a bulky tert-butyl group is attached ("hindered glyme"), thus completely preventing co-intercalation while maintaining good conductivity. This alkyl-carbonate-free electrolyte shows remarkable cycle efficiency of the graphite electrode, not only at room temperature, but also at 50 and 70 °C in the presence of lithium bis(fluorosulfonimide). The two-ethylene-bridge hindered glyme has a high boiling point and a flash point of 80 °C, a considerable advantage for safety. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved photosensitizers for photodynamic therapy

NASA Astrophysics Data System (ADS)

Pandey, Ravindra K.; Shiau, Fuu-Yau; Meunier, Isabelle; Ramaprasad, Subbaraya; Sumlin, Adam B.; Dougherty, Thomas J.; Smith, Kevin M.

1992-06-01

In order to evaluate the effect of substituents in photosensitizing activity, a series of long wavelength absorbing photosensitizers related to pyropheophorbides, bacteriopheophorbides, and benzoporphyrin derivatives were synthesized. Pheophorbide dimers, covalently joining two molecules of pyropheophorbide-a and bacteriopheophorbide-a with lysine as a cross-link were also prepared. The syntheses and spectroscopic properties of these compounds are discussed. Some of these compounds were tested for in vivo photosensitizing activity vis-a-vis Photofrin IITM, using the standard screening system of DBA/2 mice bearing transplanted SMT/F tumors. The preliminary in vivo results suggest that replacement of substituents at peripheral positions of the macrocycles causes a significant difference in photosensitizing efficacy.

Boundary lubrication, thermal and oxidative stability of a fluorinated polyether and a perfluoropolyether triazine

NASA Technical Reports Server (NTRS)

Jones, W. R., Jr.; Snyder, C. E., Jr.

1979-01-01

Boundary lubricating characteristics, thermal stability and oxidation-corrosion stability were determined for a fluorinated polyether and a perfluoropolyether triazine. A ball-on-disk apparatus, a tensimeter and oxidation-corrosion apparatus were used. Results were compared to data for a polyphenyl ether and a C-ether. The polyether and triazine yielded better boundary lubricating characteristics than either the polyphenyl ether or C-ether. The polyphenyl ether had the greatest thermal stability (443 C) while the other fluids had stabilities in the range 389 to 397 C. Oxidation-corrosion results indicated the following order of stabilities: perfluoropolyether triazine greater than polyphenylether greater than C-ether greater than fluorinated polyether.

Boundary lubrication, thermal and oxidative stability of a fluorinated polyether and a perfluoropolyether triazine

NASA Technical Reports Server (NTRS)

Jones, W. R., Jr.; Snyder, C. E., Jr.

1979-01-01

Boundary lubricating characteristics, thermal stability, and oxidation-corrosion stability were determined for a fluorinated polyether and a perfluoropolyether triazine. A ball-on-disk apparatus, a tensimeter, and oxidation-corrosion apparatus were used. Results were compared to data for a polyphenyl ether and a C-ether. The polyether and triazine yielded better boundary lubricating characteristics than either the polyphenyl ether or C-ether. The polyphenyl ether had the greatest thermal stability (443 C) while the other fluids had stabilities in the range 389 to 397 C. Oxidation-corrosion results indicated the following order of stabilities: perfluoropolyether trizine greater than polyphenyl ether greater than C-ether greater than fluorinated polyether.

Handling of Polyvinylsiloxane Versus Polyether for Implant Impressions.

PubMed

Farhan, Daniel; Lauer, Wiebke; Heydecke, Guido; Aarabi, Ghazal; Reissmann, Daniel R

2016-01-01

This study compared polyvinylsiloxane with polyether in handling dental impressions. Each participant (N = 39) made four impressions, each a combination of pickup and reseating techniques with polyether or polyvinylsiloxane, of one implant cast representing a specific clinical situation (tooth gaps, limited residual dentition, or edentulous jaw). Handling of impressions was subsequently rated by using a 12-item questionnaire with 100-mm visual analog scales. While mean satisfaction scores were higher for polyvinylsiloxane than for polyether (69.5/63.0, P < .001), differences among subgroups were statistically significant only for pickup technique, limited residual dentition, and edentulous jaw. Implant impressions made with polyvinylsiloxane using a pickup technique seem to be the best option for most clinical situations.

Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.

PubMed

Giroud, Maude; Dietzel, Uwe; Anselm, Lilli; Banner, David; Kuglstatter, Andreas; Benz, Jörg; Blanc, Jean-Baptiste; Gaufreteau, Delphine; Liu, Haixia; Lin, Xianfeng; Stich, August; Kuhn, Bernd; Schuler, Franz; Kaiser, Marcel; Brun, Reto; Schirmeister, Tanja; Kisker, Caroline; Diederich, François; Haap, Wolfgang

2018-04-26

Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei ( T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors ( K i < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC 50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys-SOH) during crystallization. The P-glycoprotein efflux ratio was measured and the in vivo brain penetration in rats determined. When tested in vivo in acute HAT model, the compounds permitted up to 16.25 (vs 13.0 for untreated controls) mean days of survival.

Differential protein acetylation induced by novel histone deacetylase inhibitors.

PubMed

Glaser, K B; Li, J; Pease, L J; Staver, M J; Marcotte, P A; Guo, J; Frey, R R; Garland, R B; Heyman, H R; Wada, C K; Vasudevan, A; Michaelides, M R; Davidsen, S K; Curtin, M L

2004-12-17

Histone deacetylase (HDAC) inhibitors induce the hyperacetylation of nucleosomal histones in carcinoma cells resulting in the expression of repressed genes that cause growth arrest, terminal differentiation, and/or apoptosis. In vitro selectivity of several novel hydroxamate HDAC inhibitors including succinimide macrocyclic hydroxamates and the non-hydroxamate alpha-ketoamide inhibitors was investigated using isolated enzyme preparations and cellular assays. In vitro selectivity for the HDAC isozymes (HDAC1/2, 3, 4/3, and 6) was not observed for these HDAC inhibitors or the reference HDAC inhibitors, MS-275 and SAHA. In T24 and HCT116 cells these compounds caused the accumulation of acetylated histones H3 and H4; however, the succinimide macrocyclic hydroxamates and the alpha-ketoamides did not cause the accumulation of acetylated alpha-tubulin. These data suggest "selectivity" can be observed at the cellular level with HDAC inhibitors and that the nature of the zinc-chelating moiety is an important determinant of activity against tubulin deacetylase.

Self-assembly of a triangle-shaped, hexaplatinum-incorporated, supramolecular amphiphile in solution and at interfaces.

PubMed

Maran, Umamageswaran; Britt, David; Fox, Christopher B; Harris, Joel M; Orendt, Anita M; Conley, Hiram; Davis, Robert; Hlady, Vladamir; Stang, Peter J

2009-08-24

The self-assembly and characterization of a novel supramolecular amphiphile built from a new 60 degree amphiphilic precursor that incorporates hydrophilic platinum(II) metals and hydrophobic dioctadecyloxy chains is reported. The amphiphilic macrocycle and its precursor compound have been characterized by multinuclear NMR spectroscopy, ESI-MS, and other standard techniques. The coacervate morphology of the amphiphile at the liquid-liquid interface has been studied by using confocal optical microscopy and in situ Raman spectroscopy. The self-assembly of the amphiphilic macrocycle at the air-water interface has been investigated through Langmuir-trough techniques. The study indicates the possible formation of surface micelle-like aggregates. The disparity between the experimental molecular areas and those derived from molecular models support the idea of aggregation. AFM images of the surface aggregates show the formation of a flat topology with arbitrary ridgelike patterns. Reasonable molecular-packing arrangements are proposed to explain the molecular organization within the observed structures.

Electrochemically Triggered Co-Conformational Switching in a [2]catenane Comprising a Non-Symmetric Calix[6]arene Wheel and a Two-Station Oriented Macrocycle.

PubMed

Zanichelli, Valeria; Dallacasagrande, Luca; Arduini, Arturo; Secchi, Andrea; Ragazzon, Giulio; Silvi, Serena; Credi, Alberto

2018-05-11

Catenanes with desymmetrized ring components can undergo co-conformational rearrangements upon external stimulation and can form the basis for the development of molecular rotary motors. We describe the design, synthesis and properties of a [2]catenane consisting of a macrocycle-the 'track' ring-endowed with two distinct recognition sites (a bipyridinium and an ammonium) for a calix[6]arene-the 'shuttle' ring. By exploiting the ability of the calixarene to thread appropriate non-symmetric axles with directional selectivity, we assembled an oriented pseudorotaxane and converted it into the corresponding oriented catenane by intramolecular ring closing metathesis. Cyclic voltammetric experiments indicate that the calixarene wheel initially surrounds the bipyridinium site, moves away from it when it is reduced, and returns in the original position upon reoxidation. A comparison with appropriate model compounds shows that the presence of the ammonium station is necessary for the calixarene to leave the reduced bipyridinium site.

Zn and Fe complexes containing a redox active macrocyclic biquinazoline ligand.

PubMed

Banerjee, Priyabrata; Company, Anna; Weyhermüller, Thomas; Bill, Eckhard; Hess, Corinna R

2009-04-06

A series of iron and zinc complexes has been synthesized, coordinated by the macrocyclic biquinazoline ligand, 2-4:6-8-bis(3,3,4,4-tetramethyldihydropyrrolo)-10-15-(2,2'-biquinazolino)-[15]-1,3,5,8,10,14-hexaene-1,3,7,9,11,14-N(6) (Mabiq). The Mabiq ligand consists of a bipyrimidine moiety and two dihydropyrrole units. The electronic structures of the metal-Mabiq complexes have been characterized using spectroscopic and density-functional theory (DFT) computational methods. The parent zinc complex exhibits a ligand-centered reduction to generate the metal-coordinated Mabiq radical dianion, establishing the redox non-innocence of this ligand. Iron-Mabiq complexes have been isolated in three oxidation states. This redox series includes low-spin ferric and low-spin ferrous species, as well as an intermediate-spin Fe(II) compound. In the latter complex, the iron ion is antiferromagnetically coupled to a Mabiq-centered pi-radical. The results demonstrate the rich redox chemistry and electronic properties of metal complexes coordinated by the Mabiq ligand.

Glycerol etherification with TBA: high yield to poly-ethers using a membrane assisted batch reactor.

PubMed

Cannilla, Catia; Bonura, Giuseppe; Frusteri, Leone; Frusteri, Francesco

2014-05-20

In this work, a novel approach to obtain high yield to poly-tert-butylglycerolethers by glycerol etherification reaction with tert-butyl alcohol (TBA) is proposed. The limit of this reaction is the production of poly-ethers, which inhibits the formation of poly-ethers potentially usable in the blend with conventional diesel for transportation. The results herein reported demonstrate that the use of a water permselective membrane offers the possibility to shift the equilibrium toward the formation of poly-ethers since the water formed during reaction is continuously and selectively removed from the reaction medium by the recirculation of the gas phase. Using a proper catalyst and optimizing the reaction conditions, in a single experiment, a total glycerol conversion can be reached with a yield to poly-ethers close to 70%, which represents data never before reached using TBA as reactant. The approach here proposed could open up new opportunities for all catalytic reactions affected by water formation.

Ultraviolet-induced surface grafting of octafluoropentyl methacrylate on polyether ether ketone for inducing antibiofilm properties.

PubMed

Amdjadi, Parisa; Nojehdehian, Hanieh; Najafi, Farhood; Ghasemi, Amir; Seifi, Massoud; Dashtimoghadam, Erfan; Fahimipour, Farahnaz; Tayebi, Lobat

2017-07-01

Since octafluoropentyl methacrylate is an antifouling polymer, surface modification of polyether ether ketone with octafluoropentyl methacrylate is a practical approach to obtaining anti-biofilm biocompatible devices. In the current study, the surface treatment of polyether ether ketone by the use of ultraviolet irradiation, so as to graft (octafluoropentyl methacrylate) polymer chains, was initially implemented and then investigated. The Fourier-transform infrared and nuclear magnetic resonance spectra corroborated the appearance of new signals associated with the fluoroacrylate group. Thermogravimetric curves indicated enhanced asymmetry in the polymer structure due to the introduction of the said new groups. Measuring the peak area in differential scanning calorimetry experiments also showed additional bond formation. Static water contact angle measurements indicated a change in wettability to the more hydrophobic surface. The polyether ether ketone-octafluoropentyl methacrylate surface greatly reduced the protein adsorption. This efficient method can modulate and tune the surface properties of polyether ether ketone according to specific applications.

Computational screening of oxetane monomers for novel hydroxy terminated polyethers.

PubMed

Sarangapani, Radhakrishnan; Ghule, Vikas D; Sikder, Arun K

2014-06-01

Energetic hydroxy terminated polyether prepolymers find paramount importance in search of energetic binders for propellant applications. In the present study, density functional theory (DFT) has been employed to screen the various novel energetic oxetane derivatives, which usually construct the backbone for these energetic polymers. Molecular structures were investigated at the B3LYP/6-31G* level, and isodesmic reactions were designed for calculating the gas phase heats of formation. The condensed phase heats of formation for designed compounds were calculated by the Politzer approach using heats of sublimation. Among the designed oxetane derivatives, T4 and T5 possess condensed phase heat of formation above 210 kJ mol(-1). The crystal packing density of the designed oxetane derivatives varied from 1.2 to 1.6 g/cm(3). The detonation velocities and pressures were evaluated using the Kamlet-Jacobs equations, utilizing the predicted densities and HOFCond. It was found that most of the designed oxetane derivatives have detonation performance comparable to the monomers of benchmark energetic polymers viz., NIMMO, AMMO, and BAMO. The strain energy (SE) for the oxetane derivatives were calculated using homodesmotic reactions, while intramolecular group interactions were predicted through the disproportionation energies. The concept of chemical hardness is used to analyze the susceptibility of designed compounds to reactivity and chemical transformations. The heats of formation, density, and predicted performance imply that the designed molecules are expected to be candidates for polymer synthesis and potential molecules for energetic binders.

Characterization of the P. Brevis Polyether Neurotoxin Binding Component in Excitable Membranes

DTIC Science & Technology

1991-09-14

International Conference on Ciguatera . (T. R. Tosteson and D. Ballantyne, Eds.) in press. Baden, D.G. (1991) The Polyether Brevetoxins and Site Five of the...Confomrations and Potency Correlations. Third Intl. Conf. Ciguatera , Puerto Rico 1990. Tosteson, T.R., and Baden, D.G. Polyether Dinoflagellate Toxins...and Caribbean Ciguatera : Correlation of Fish Toxins with Standard Toxins Third International Conference on Ciguatera , Peurto Rico 1990. Baden, D.G

Influence of Layer Thickness and Raster Angle on the Mechanical Properties of 3D-Printed PEEK and a Comparative Mechanical Study between PEEK and ABS.

PubMed

Wu, Wenzheng; Geng, Peng; Li, Guiwei; Zhao, Di; Zhang, Haibo; Zhao, Ji

2015-09-01

Fused deposition modeling (FDM) is a rapidly growing 3D printing technology. However, printing materials are restricted to acrylonitrile butadiene styrene (ABS) or poly (lactic acid) (PLA) in most Fused deposition modeling (FDM) equipment. Here, we report on a new high-performance printing material, polyether-ether-ketone (PEEK), which could surmount these shortcomings. This paper is devoted to studying the influence of layer thickness and raster angle on the mechanical properties of 3D-printed PEEK. Samples with three different layer thicknesses (200, 300 and 400 μm) and raster angles (0°, 30° and 45°) were built using a polyether-ether-ketone (PEEK) 3D printing system and their tensile, compressive and bending strengths were tested. The optimal mechanical properties of polyether-ether-ketone (PEEK) samples were found at a layer thickness of 300 μm and a raster angle of 0°. To evaluate the printing performance of polyether-ether-ketone (PEEK) samples, a comparison was made between the mechanical properties of 3D-printed polyether-ether-ketone (PEEK) and acrylonitrile butadiene styrene (ABS) parts. The results suggest that the average tensile strengths of polyether-ether-ketone (PEEK) parts were 108% higher than those for acrylonitrile butadiene styrene (ABS), and compressive strengths were 114% and bending strengths were 115%. However, the modulus of elasticity for both materials was similar. These results indicate that the mechanical properties of 3D-printed polyether-ether-ketone (PEEK) are superior to 3D-printed ABS.

Influence of Layer Thickness and Raster Angle on the Mechanical Properties of 3D-Printed PEEK and a Comparative Mechanical Study between PEEK and ABS

PubMed Central

Wu, Wenzheng; Geng, Peng; Li, Guiwei; Zhao, Di; Zhang, Haibo; Zhao, Ji

2015-01-01

Fused deposition modeling (FDM) is a rapidly growing 3D printing technology. However, printing materials are restricted to acrylonitrile butadiene styrene (ABS) or poly (lactic acid) (PLA) in most Fused deposition modeling (FDM) equipment. Here, we report on a new high-performance printing material, polyether-ether-ketone (PEEK), which could surmount these shortcomings. This paper is devoted to studying the influence of layer thickness and raster angle on the mechanical properties of 3D-printed PEEK. Samples with three different layer thicknesses (200, 300 and 400 μm) and raster angles (0°, 30° and 45°) were built using a polyether-ether-ketone (PEEK) 3D printing system and their tensile, compressive and bending strengths were tested. The optimal mechanical properties of polyether-ether-ketone (PEEK) samples were found at a layer thickness of 300 μm and a raster angle of 0°. To evaluate the printing performance of polyether-ether-ketone (PEEK) samples, a comparison was made between the mechanical properties of 3D-printed polyether-ether-ketone (PEEK) and acrylonitrile butadiene styrene (ABS) parts. The results suggest that the average tensile strengths of polyether-ether-ketone (PEEK) parts were 108% higher than those for acrylonitrile butadiene styrene (ABS), and compressive strengths were 114% and bending strengths were 115%. However, the modulus of elasticity for both materials was similar. These results indicate that the mechanical properties of 3D-printed polyether-ether-ketone (PEEK) are superior to 3D-printed ABS. PMID:28793537

A Multidimensional Diversity‐Oriented Synthesis Strategy for Structurally Diverse and Complex Macrocycles

PubMed Central

Nie, Feilin; Kunciw, Dominique L.; Wilcke, David; Stokes, Jamie E.; Galloway, Warren R. J. D.; Bartlett, Sean; Sore, Hannah F.

2016-01-01

Abstract Synthetic macrocycles are an attractive area in drug discovery. However, their use has been hindered by a lack of versatile platforms for the generation of structurally (and thus shape) diverse macrocycle libraries. Herein, we describe a new concept in library synthesis, termed multidimensional diversity‐oriented synthesis, and its application towards macrocycles. This enabled the step‐efficient generation of a library of 45 novel, structurally diverse, and highly‐functionalized macrocycles based around a broad range of scaffolds and incorporating a wide variety of biologically relevant structural motifs. The synthesis strategy exploited the diverse reactivity of aza‐ylides and imines, and featured eight different macrocyclization methods, two of which were novel. Computational analyses reveal a broad coverage of molecular shape space by the library and provides insight into how the various diversity‐generating steps of the synthesis strategy impact on molecular shape. PMID:27484830

Structural and conformational determinants of macrocycle cell permeability.

PubMed

Over, Björn; Matsson, Pär; Tyrchan, Christian; Artursson, Per; Doak, Bradley C; Foley, Michael A; Hilgendorf, Constanze; Johnston, Stephen E; Lee, Maurice D; Lewis, Richard J; McCarren, Patrick; Muncipinto, Giovanni; Norinder, Ulf; Perry, Matthew W D; Duvall, Jeremy R; Kihlberg, Jan

2016-12-01

Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 non-peptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.

Synthesis and properties of amphiphilic hyperbranched polyethers as pigment dispersant

NASA Astrophysics Data System (ADS)

Xu, Q.; Zhou, Y. J.; Long, S. J.; Liu, Y. G.; Li, J. H.

2018-01-01

Hyperbranched polymers possess prominent properties such as low viscosity, good solubility, high rheological property, environmental non-toxic, and so on, which have potential applications in coatings. In this study, the amphiphilic hyperbranched polyethers (AHPs) consisting of hydrophobic hyperbranched polyethers core and hydrophilic poly (ethylene glycol) arms with different degree of branching (DB) under various reaction temperatures was prepared by the cation ring-opening polymerization. Their structures were characterized by IR, 13CNMR and GPC. Their dispersion properties for pigment particles were investigated. The AHP47 with 0.47 DB was found to have good dispersion properties for Yellow HGR. This work would provide experimental data and theoretical foundation for the application of hyperbranched polyethers in environmental protection coating.

Synthesis of 5-iodo-1,2,3-triazole-containing macrocycles using copper flow reactor technology.

PubMed

Bogdan, Andrew R; James, Keith

2011-08-05

A new macrocyclization strategy to synthesize 12- to 31-membered 5-iodo-1,2,3-triazole-containing macrocycles is described. The macrocycles have been generated using a simple and efficient copper-catalyzed cycloaddition in flow under environmentally friendly conditions. This methodology also permits the facile, regioselective synthesis of 1,4,5-trisubstituted-1,2,3-triazole-containing macrocyles using palladium-catalyzed cross-coupling reactions. © 2011 American Chemical Society

Comparison of classic and microwave-assisted synthesis of benzo-thio crown ethers, and investigation of their ion pair extractions

NASA Astrophysics Data System (ADS)

Calisir, Umit; Çiçek, Baki

2017-11-01

Macrocyclic benzo-thio crown ethers and benzo-oxo crown ethers were prepared using an esterification-ring closing method. These compounds were synthesised using 2,2‧-dithiodibenzoyl chloride, and various glycols and dithiols, in the presence of pyridine base under a nitrogen atmosphere in chloroform. All reactions were performed under reflux condition with conventional heating and microwave (MW) irradiation. The synthesised macrocycles were characterised by FT-IR, 1H NMR, 13C NMR, LC-MS, and elemental analysis methods. Extraction studies have been performed on these original macrocycles using liquid-liquid ion-pair extraction with Li+, Na+, K+, Ni2+, Ca2+, Mg2+, Zn2+, Fe2+,Fe3+, Co3+, Pb2+, Cr3+, Ag+, and Cd2+.The KD, ext.%, ΔG and log KExt values were also calculated. While (U1-U7) ligands exhibits selectivity for Zn2+, Ag+, Ca2+, Pb2+, Fe3+, Cr3+, Co2+, Mg2+, Cd2+, and Ni2+ metal salts, they showed no selectivity for Li+, K+ and Na+ metal salts. Furthermore, Fe3+is the most selective cation for all ligands for competitive extraction. We also observed that microwave heating can have certain benefits over conventional ovens: reaction rate acceleration, milder reaction conditions, higher chemical yield, and lower energy usage. These ligands could be used as metal sensors, enzyme inhibitors, antimicrobial/antifungal agents, and in biological applications.

Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

PubMed

Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

2017-08-03

The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

Macrocyclic bifunctional chelating agents

DOEpatents

Meares, Claude F.; DeNardo, Sally J.; Cole, William C.; Mol, Min K.

1987-01-01

A copper chelate conjugate which is stable in human serum. The conjugate includes the copper chelate of a cyclic tetraaza di-, tri-, or tetra-acetic acid, a linker attached at one linker end to a ring carbon of the chelate, and a biomolecule joined at the other end of the linker. The conjugate, or the linker-copper chelate compound used in forming the conjugate, are designed for use in diagnostic and therapeutic applications which involve Cu(II) localization via the systemic route.

Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms.

PubMed

David, S; Ordway, D; Arroz, M J; Costa, J; Delgado, R

2001-01-01

The novel tetraaza-macrocyclic compound 3,7,11-tris(carboxymethyl)-3,7,11,17-tetraaza-bicyclo[11.3.1]heptadeca-1(17),13,15-triene, abbreviated as ac3py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac3py14 and its Fe3+ 1:1 complex, [Fe(ac3py14)], inhibited radiometric growth of several strains of M. tuberculosis. Inhibition with 25 microg/mL varied from 99% for H37Rv to 80% and above for multiple drug-resistant clinical isolates. The capacity of ac3py14 to elicit a beneficial immune response without cellular apoptosis was assessed and compared to the effects of virulent M. tuberculosis. The present study produces evidence that after stimulation with ac3py14 there was significant production of interferon gamma (IFN-gamma), whereas the production of interleukin-5 (IL-5) remained low, and there was development of a memory population (CD45RO). The level of binding of Annexin V, a marker of apoptosis, was not sufficient to result in toxic effects toward alphabeta and gammadelta T cells and CD14+ macrophages. This preliminary study is the first report of a compound that simultaneously exerts an inhibitory effect against M. tuberculosis and induces factors associated with protective immune responses.

Correlation between oxygen adsorption energy and electronic structure of transition metal macrocyclic complexes.

PubMed

Liu, Kexi; Lei, Yinkai; Wang, Guofeng

2013-11-28

Oxygen adsorption energy is directly relevant to the catalytic activity of electrocatalysts for oxygen reduction reaction (ORR). In this study, we established the correlation between the O2 adsorption energy and the electronic structure of transition metal macrocyclic complexes which exhibit activity for ORR. To this end, we have predicted the molecular and electronic structures of a series of transition metal macrocyclic complexes with planar N4 chelation, as well as the molecular and electronic structures for the O2 adsorption on these macrocyclic molecules, using the density functional theory calculation method. We found that the calculated adsorption energy of O2 on the transition metal macrocyclic complexes was linearly related to the average position (relative to the lowest unoccupied molecular orbital of the macrocyclic complexes) of the non-bonding d orbitals (d(z(2)), d(xy), d(xz), and d(yz)) which belong to the central transition metal atom. Importantly, our results suggest that varying the energy level of the non-bonding d orbitals through changing the central transition metal atom and/or peripheral ligand groups could be an effective way to tuning their O2 adsorption energy for enhancing the ORR activity of transition metal macrocyclic complex catalysts.

NEW FRONTIERS IN DRUGGABILITY

PubMed Central

Kozakov, Dima; Hall, David R.; Napoleon, Raeanne L.; Yueh, Christine; Whitty, Adrian; Vajda, Sandor

2016-01-01

A powerful early approach to evaluating the druggability of proteins involved determining the hit rate in NMR-based screening of a library of small compounds. Here we show that a computational analog of this method, based on mapping proteins using small molecules as probes, can reliably reproduce druggability results from NMR-based screening, and can provide a more meaningful assessment in cases where the two approaches disagree. We apply the method to a large set of proteins. The results show that, because the method is based on the biophysics of binding rather than on empirical parameterization, meaningful information can be gained about classes of proteins and classes of compounds beyond those resembling validated targets and conventionally druglike ligands. In particular, the method identifies targets that, while not druggable by druglike compounds, may become druggable using compound classes such as macrocycles or other large molecules beyond the rule-of-five limit. PMID:26230724

Systematic Experimental and Computational Investigation of Ion Transport in Novel Polyether Electrolytes

NASA Astrophysics Data System (ADS)

Pesko, Danielle; Webb, Michael; Jung, Yukyung; Zheng, Qi; Miller, Thomas, III; Coates, Geoffrey; Balsara, Nitash

Polyethers, such as poly(ethylene oxide) (PEO), are considered to be the most promising polymer electrolyte materials due to their high ionic conductivity and electrochemical stability, both essential for battery applications. To gain a fundamental understanding of the transport properties of polyether systems, we design a systematic set of linear PEO-like polymers to explore the effect of adding carbon spacers to the backbone of the chain. Ac impedance spectroscopy is employed to measure the ionic conductivity of polyether/lithium salt electrolytes; the results elucidate tradeoffs between lowering the glass transition temperature and diluting the polar groups on the polymer chain. Molecular-level insight is provided by molecular dynamics simulations of the polyether electrolytes. We define the useful and intuitive metric of ``connectivity'', a parameter calculated from simulations which describes the physical arrangements of solvation sites in a polymer melt. Direct comparison of experiment and theory allows us to determine the relationship between connectivity and conductivity. The comparison provides insight regarding the factors that control conductivity, and highlights considerations that must be taken when designing new ion-conducting polymers.

Taggants, method for forming a taggant, and a method for detecting an object

DOEpatents

Harrup, Mason K [Idaho Falls, ID; Stewart, Frederick F [Idaho Falls, ID; Stone, Mark L [Idaho Falls, ID

2012-02-28

A taggant comprising at least one perfluorocarbon compound surrounded by a polyphosphazene compound. The polyphosphazene compound has the chemical structure: ##STR00001## wherein G.sub.1 and G.sub.2 are pendant groups having different polarities, m is an integer greater than or equal to 100, and each of A and B is independently selected from hydrogen, an alkyl, an alkene, an alkoxide, a polyether, a polythioether, a siloxane, and --X(CH.sub.2).sub.nY.sup.1(CH.sub.2)p.sub.1Y.sup.2(CH.sub.2)p.sub.2 . . . Y.sup.i(CH.sub.2)p.sub.iCH.sub.3, where n ranges from 1 to 6, X and Y are independently selected from oxygen, sulfur, selenium, tellurium, and polonium, and p.sub.1 through p.sub.i range from 1 to 6. Cyclic polyphosphazene compounds lacking the A and B groups are also disclosed, as are methods of forming the taggant and of detecting an object.

Material with high dielectric constant, low dielectric loss, and good mechanical and thermal properties produced using multi-wall carbon nanotubes wrapped with poly(ether sulphone) in a poly(ether ether ketone) matrix

NASA Astrophysics Data System (ADS)

Zhang, Shuling; Wang, Hongsong; Wang, Guibin; Jiang, Zhenhua

2012-07-01

A material with high dielectric constant, low dielectric loss, and good mechanical and thermal properties was produced using multi-wall carbon nanotubes (MWCNTs) wrapped with poly(ether sulphone) (PES) dispersed in a poly(ether ether ketone) (PEEK) matrix. The material was fabricated using melt-blending, and MWCNT/PEEK composites show different degrees of improvement in the measured dielectric, mechanical, and thermal properties as compared to pure PEEK. This is attributed to the high conductivity of MWCNTs, the effect of wrapping MWCNTs with PES, the good dispersion of the wrapped MWCNTs in PEEK, and the strong interfacial adhesion between the wrapped MWCNTs and the PEEK.

Complexation of triptycene-derived macrotricyclic polyether with paraquat derivatives, diquat, and a 2,7-diazapyrenium salt: guest-induced conformational changes of the host.

PubMed

Han, Ying; Cao, Jing; Li, Peng-Fei; Zong, Qian-Shou; Zhao, Jian-Min; Guo, Jia-Bin; Xiang, Jun-Feng; Chen, Chuan-Feng

2013-04-05

Complexation between a triptycene-derived macrotricyclic polyether containing two dibenzo-[30]-crown-10 cavities and different functionalized paraquat derivatives, diquat, and a 2,7-diazapyrenium salt in both solution and solid state was investigated in detail. It was found that depending on the guests with different terminal functional groups and structures, the macrotricyclic polyether could form 1:1 or 1:2 complexes with the guests in different complexation modes in solution and also in the solid state. Especially, the conformation of the macrotricyclic polyether was efficiently adjusted by the encapsulated guests, which was to some extent similar to substrate-induced fit of enzymes. Moreover, the binding and releasing of the guests in the complexes could be controlled by potassium ions.

(5-n-Butyl-10,20-diiso­butyl­porphyrin­ato)nickel(II)

PubMed Central

Senge, Mathias O.; Dahms, Katja

2014-01-01

The asymmetric unit of the title compound, [Ni(C32H36N4)], contains two independent mol­ecules exhibiting an overall ruffled conformation of the porphyrin macrocycle and differing mainly in the positions of the methyl groups. The average Ni—N bond lengths are 1.912 (2) and 1.910 (2) Å in the two mol­ecules. The mol­ecules form a closely spaced lattice structure in which neighbouring porphyrins are oriented in a nearly perpendicular fashion to each other. The compound was prepared via nucleophilic substitution of (5,15-diiso­butyl­porphyrinato)nickel(II) with n-butyl­lithium. PMID:25161518

Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

PubMed Central

Daigle, Maxime; Cantin, Katy

2014-01-01

Summary The synthesis and self-assembly of two new phenylacetylene macrocycle (PAM) organogelators were performed. Polar 2-hydroxyethoxy side chains were incorporated in the inner part of the macrocycles to modify the assembly mode in the gel state. With this modification, it was possible to increase the reactivity of the macrocycles in the xerogel state to form polydiacetylenes (PDAs), leading to a significant enhancement of the polymerization yields. The organogels and the PDAs were characterized using Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). PMID:25161718

The addition of a second lanthanide ion to increase the luminescence of europium(III) macrocyclic complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bromm, A.J. Jr.; Vallarino, L.M.; Leif, R.C.

At present, the microscopic visualization of luminescent labels containing lanthanide(III) ions, primarily europium(III), as light-emitting centers is best performed with time-gated instrumentation, which by virtually eliminating the background fluorescence results in an improved signal to noise ratio. However, the use of the europium(III) macrocycle, Quantum Dye{trademark}, in conjunction with the strong luminescence enhancing effect (cofluorescence) of yttrium(III) or gadolinium(III), can eliminate the need for such specialized instrumentation. In the presence of Gd(III), the luminescence of the Eu(III)-macrocycles can be conveniently observed with conventional fluorescence instrumentation at previously unattainable low levels. The Eu(III) {sup 5}D{sub 0} {r_arrow} {sup 7}F{sub 2} emissionmore » of the Eu(III)-macrocycles was observed as an extremely sharp band with a maximum at 619 nm and a clearly resolved characteristic pattern. At very low Eu(III)-macrocycle concentrations, another sharp emission was detected at 614 nm, arising from traces of Eu(III) present in even the purest commercially available gadolinium products. Discrimination of the resolved emissions of the Eu(III)-macrocycle and Eu(III) contaminant should provide a means to further lower the limit of detection of the Eu(III)-macrocycle.« less

Fifty years of oxacalix[3]arenes: A review

PubMed Central

Cottet, Kevin; Marcos, Paula M

2012-01-01

Summary Hexahomotrioxacalix[3]arenes, commonly called oxacalix[3]arenes, were first reported in 1962. Since then, their chemistry has been expanded to include numerous derivatives and complexes. This review describes the syntheses of the parent compounds, their derivatives, and their complexation behaviour towards cations. Extraction data are presented, as are crystal structures of the macrocycles and their complexes with guest species. Applications in fields as diverse as ion selective electrode modifiers, fluorescence sensors, fullerene separations and biomimetic chemistry are described. PMID:22423288

Ionic complexation of N 2O 4 by 18-crown-6

NASA Astrophysics Data System (ADS)

Ricard, S.; Audet, P.; Savoie, R.

1988-08-01

An ionic complex has been obtained from N 2O 4 in the presence of the macrocyclic ether 18-crown-6. This crystalline compound has been shown from its Raman spectrum to have the formula NO +·crown·H(NO 3) 2-, with the nitrosonium ion closely associated with the crown ether rather than with the hydrogen dinitrate accompanying ion. This adduct decomposes readily in moist air to give the known complex (HNO 3·H 2O) 2·crown.

Effects of organic silicon compounds as additives on charge-discharge cycling efficiencies of lithium in nonaqueous electrolytes for rechargeable lithium cells

NASA Astrophysics Data System (ADS)

Yanagisawa, Ryota; Endo, Hisayuki; Unno, Masafumi; Morimoto, Hideyuki; Tobishima, Shin-ichi

2014-11-01

Influence of mixing organic silicon compounds into 1 M (M: mol L-1) LiPF6-ethylene carbonate (EC)/ethylmethyl carbonate (EMC) (mixing volume ratio = 3:7) mixed solvent electrolytes on charge-discharge cycling efficiencies of lithium metal negative electrodes is examined. As organic silicon compounds, polyether-modified siloxanes with polyethylene oxide chains, chlorotrimethylsilane, tetraethoxysilane, cis-tetra [isobutyl (dimethylsiloxy)] cyclotetrasiloxane and cage-type silsesquioxane are investigated. Charge-discharge cycling tests of lithium are galvanostatically carried out using stainless steel working electrodes. Charge-discharge cycling efficiencies of lithium tend to improve by mixing organic silicon compounds. A cage-type silsesquioxane, octaphenyloctasilsesquioxane (Ph8T8) exhibits the highest cycling efficiency of approximately 80% with small mixing amount of 0.02 M Ph8T8. Mechanism of enhancement of lithium cycling efficiencies by mixing organic silicon compounds is considered to be due to the suppression of excess reduction of LiPF6-EC/EMC by lithium and the growth of surface film on lithium.

Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as gene transfection agents.

PubMed

Bromberg, Lev; Raduyk, Svetlana; Hatton, T Alan; Concheiro, Angel; Rodriguez-Valencia, Cosme; Silva, Maite; Alvarez-Lorenzo, Carmen

2009-05-20

Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through polyether activation by cyanuric chloride followed by attachment to PEI and guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently complexed plasmid DNA, and their polyplexes possessed enhanced colloidal stability in the presence of serum proteins. In vitro studies with mammalian CHO-1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced the conjugates' interaction with genetic material and reduced the cytotoxicity of the polyplexes in experiments with the L929 cell line.

Parasites modulate within-colony activity and accelerate the temporal polyethism schedule of a social insect, the honey bee.

PubMed

Natsopoulou, Myrsini E; McMahon, Dino P; Paxton, Robert J

Task allocation in social insect colonies is generally organised into an age-related division of labour, termed the temporal polyethism schedule, which may in part have evolved to reduce infection of the colony's brood by pests and pathogens. The temporal polyethism schedule is sensitive to colony perturbations that may lead to adaptive changes in task allocation, maintaining colony homeostasis. Though social insects can be infected by a range of parasites, little is known of how these parasites impact within-colony behaviour and the temporal polyethism schedule. We use honey bees ( Apis mellifera ) experimentally infected by two of their emerging pathogens, Deformed wing virus (DWV), which is relatively understudied concerning its behavioural impact on its host, and the exotic microsporidian Nosema ceranae . We examined parasite effects on host temporal polyethism and patterns of activity within the colony. We found that pathogens accelerated the temporal polyethism schedule, but without reducing host behavioural repertoire. Infected hosts exhibited increased hyperactivity, allocating more time to self-grooming and foraging-related tasks. The strength of behavioural alterations we observed was found to be pathogen specific; behavioural modifications were more pronounced in virus-treated hosts versus N. ceranae -treated hosts, with potential benefits for the colony in terms of reducing within-colony transmission. Investigating the effects of multiple pathogens on behavioural patterns of social insects could play a crucial role in understanding pathogen spread within a colony and their effects on colony social organisation.

Influence of disinfection with peracetic acid and hypochlorite in dimensional alterations of casts obtained from addition silicone and polyether impressions.

PubMed

Queiroz, Daher Antonio; Peçanha, Marcelo Massaroni; Neves, Ana Christina Claro; Frizzera, Fausto; Tonetto, Mateus Rodrigues; Silva-Concílio, Laís Regiane

2013-11-01

Dental impressions disinfection is important to reduce the risk of cross contamination but this process may produce dimensional distortions. Peracetic acid is a disinfectant agent with several favorable characteristics yet underutilized in Dentistry. The aim of this paper is to compare the dimensional stability of casts obtained from addition silicone and polyether impressions that were immersed for 10 minutes in a solution of 0.2% peracetic acid or 1% sodium hypochlorite. Sixty samples in type IV gypsum were produced after a master cast that simulated a full crown preparation of a maxillary premolar. Samples were divided in 6 groups (n = 10) according to the impression material and disinfection agent: Group AC--addition silicone control (without disinfectant); Group APA--addition silicone + 0.2% peracetic acid; Group AH--addition silicone + 1% sodium hypochlorite; Group PC--polyether control (without disinfectant); Group PPA--polyether + 0.2% peracetic acid; Group PH--polyether + 1% sodium hypochlorite. Cast height, base and top diameter were measured and a mean value was obtained for each sample and group all data was statistically analyzed (ANOVA, p < 0.05). There was not a significant statistical difference between addition silicone and polyether impressions regardless of the disinfectant materials. It can be concluded that disinfection with the proposed agents did not produce significant alterations of the impressions and the peracetic acid could be considered a reliable material to disinfect dental molds.

Distinguishing Two Ammonium and Triazolium Sites of Interaction in a Three-Station [2]Rotaxane Molecular Shuttle.

PubMed

Waelès, Philip; Fournel-Marotte, Karine; Coutrot, Frédéric

2017-08-25

This paper reports on the synthesis of a tri-stable [2]rotaxane molecular shuttle, in which the motion of the macrocycle is triggered by either selective protonation/deprotonation or specific carbamoylation/decarbamoylation of an alkylbenzylamine. The threaded axle is surrounded by a dibenzo[24]crown[8] (DB24C8) macrocycle and contains three sites of different binding affinities towards the macrocycle. An N-methyltriazolium moiety acts as a molecular station that has weak affinity for the DB24C8 macrocycle and is located in the centre of the molecular axle. Two other molecular stations, arylammonium and alkylbenzylammonium moieties, sit on either side of the triazolium moiety along the molecular axle and have stronger affinities for the DB24C8 macrocycle. These two ammonium moieties are covalently linked to two different stopper groups at each extremity of the thread: a tert-butylphenyl group and a substituted DB24C8 unit. Owing to steric hindrance, the former does not allow any π-π stacking interactions with the encircling DB24C8 macrocycle, whereas the latter residue does; therefore, this allows the discrimination of the two ammonium stations by the surrounding DB24C8 macrocycle in the fully protonated state. In the deprotonated state, the contrasting reactivity of the amine functional groups, as either a base or a nucleophile, allows for selective reactions that trigger the controlled shuttling of the macrocycle around the three molecular stations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapid fixation of methylene chloride by a macrocyclic amine.

PubMed

Lee, Jung-Jae; Stanger, Keith J; Noll, Bruce C; Gonzalez, Carlos; Marquez, Manuel; Smith, Bradley D

2005-03-30

A simple macrocyclic amine is alkylated by methylene chloride to give a quaternary ammonium chloride salt. When methylene chloride is the solvent, the reaction exhibits pseudo-first-order kinetics, and the reaction half-life at 25.0 degrees C is 2.0 min. The reaction half-life for a structurally related, acyclic amine is approximately 50 000 times longer. Detailed calculations favor a mechanism where the methylene chloride associates with the macrocycle to form an activated prereaction complex. The macrocyclic nitrogen subsequently attacks the methylene chloride with a classic SN2 trajectory, and although the carbon-chlorine bond breaks, the chloride leaving group does not separate from the newly formed cationic macrocycle, such that the product is a tightly associated ion-pair. X-ray crystal structures of the starting amine and the product salt, as well as kinetic data, support this mechanism.

Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria.

PubMed

Gunasekera, Sarath P; Li, Yang; Ratnayake, Ranjala; Luo, Danmeng; Lo, Jeannette; Reibenspies, Joseph H; Xu, Zhengshuang; Clare-Salzler, Michael J; Ye, Tao; Paul, Valerie J; Luesch, Hendrik

2016-06-06

A new dimeric macrolide xylopyranoside, cocosolide (1), was isolated from the marine cyanobacterium preliminarily identified as Symploca sp. from Guam. The structure was determined by a combination of NMR spectroscopy, HRMS, X-ray diffraction studies and Mosher's analysis of the base hydrolysis product. Its carbon skeleton closely resembles that of clavosolides A-D isolated from the sponge Myriastra clavosa, for which no bioactivity is known. We performed the first total synthesis of cocosolide (1) along with its [α,α]-anomer (26) and macrocyclic core (28), thus leading to the confirmation of the structure of natural 1. The convergent synthesis featured Wadsworth-Emmons cyclopropanation, Sakurai annulation, Yamaguchi macrocyclization/dimerization reaction, α-selective glycosidation and β-selective glycosidation. Compounds 1 and 26 potently inhibited IL-2 production in both T-cell receptor dependent and independent manners. Full activity requires the presence of the sugar moiety as well as the intact dimeric structure. Cocosolide also suppressed the proliferation of anti-CD3-stimulated T-cells in a dose-dependent manner. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unusual nanosized associates of carboxy-calix[4]resorcinarene and cetylpyridinium chloride: the macrocycle as a glue for surfactant micelles.

PubMed

Morozova, Ju E; Syakaev, V V; Shalaeva, Ya V; Ermakova, A M; Nizameev, I R; Kadirov, M K; Voloshina, A D; Zobov, V V; Antipin, I S; Konovalov, A I

2017-03-08

The association of cetylpyridinium chloride (CPC) micelles in the presence of octaacetated tetraphenyleneoxymethylcalix[4]resorcinarene (CR) leads to the formation of unusual spherical supramolecular nanoparticles (SNPs). Within the range of CR/CPC molar ratios from 10/1 to 1/10 (except for 1/8), CR, acting as a counterion, decreases the critical micelle concentration of CPC by one order of magnitude and leads to the formation of SNPs with an average hydrodynamic radius of 164 nm and an average zeta potential of -60 mV. The formation of SNPs was studied by NMR FT-PGSE and 2D NOESY, DLS, TEM, fluorimetry, and UV-Vis methods. The stability of SNPs at different temperatures and pH values and in the presence of electrolytes was investigated. The specificity of the interactions of the SNPs with substrates that were preferentially bound by a macrocycle or CPC micelle was studied. The enhancement of cation dye binding in the presence of SNPs is shown. The presented supramolecular system may serve as a nanocapsule for water-soluble and water-insoluble compounds.

Nano-Assemblies of Modified Cyclodextrins and Their Complexes with Guest Molecules: Incorporation in Nanostructured Membranes and Amphiphile Nanoarchitectonics Design

PubMed Central

Zerkoune, Leïla; Angelova, Angelina; Lesieur, Sylviane

2014-01-01

A variety of cyclodextrin-based molecular structures, with substitutions of either primary or secondary faces of the natural oligosaccharide macrocycles of α-, β-, or γ-cyclodextrins, have been designed towards innovative applications of self-assembled cyclodextrin nanomaterials. Amphiphilic cyclodextrins have been obtained by chemical or enzymatic modifications of their macrocycles using phospholipidyl, peptidolipidyl, cholesteryl, and oligo(ethylene oxide) anchors as well as variable numbers of grafted hydrophobic hydrocarbon or fluorinated chains. These novel compounds may self-assemble in an aqueous medium into different types of supramolecular nanoassemblies (vesicles, micelles, nanorods, nanospheres, and other kinds of nanoparticles and liquid crystalline structures). This review discusses the supramolecular nanoarchitectures, which can be formed by amphiphilic cyclodextrin derivatives in mixtures with other molecules (phospholipids, surfactants, and olygonucleotides). Biomedical applications are foreseen for nanoencapsulation of drug molecules in the hydrophobic interchain volumes and nanocavities of the amphiphilic cyclodextrins (serving as drug carriers or pharmaceutical excipients), anticancer phototherapy, gene delivery, as well as for protection of instable active ingredients through inclusion complexation in nanostructured media. PMID:28344245

Catalytic efficiency of macrocyclic-capped gold nanoparticles: cucurbit[n]urils versus cyclodextrins

NASA Astrophysics Data System (ADS)

del Pozo, María; Blanco, Elías; Hernández, Pedro; Casas, José A.; Quintana, Carmen

2018-05-01

In this work, different macrocyclic systems, belonging to cucurbit[n]urils and cyclodextrins families, were employed as stabilizers of gold nanoparticles and their performance as catalysts in the reduction reaction of the toxic 4-nitrophenol to produce the valuable 4-aminophenol, was evaluated. To this goal, six nanosystems were prepared and compared under identical experimental conditions. The influence that (i) differences in shape, (ii) nature of chemical groups constituting the receptor entrances and (iii) differences in the portal sizes of those stabilizing agents have in the activity of these nanoparticles as catalysts in a nitro compound reduction reaction is evaluated and discussed. The TEM characterization of the nanocatalysts prepared is included. From these data, nanoparticles ranging from 3.7-10.7 nm in diameter, depending on the stabilizer employed, were obtained. The evaluation of kinetic rate constants normalized respect to gold concentration and catalyst surface for each system is included and discussed. In addition, the stability of the different nanocatalyst depending on the capping agent employed is also evaluated. [Figure not available: see fulltext.

Mössbauer and electronic spectral characterization of homo-bimetallic Fe(III) complexes of unsymmetrical [N10] and [N12] macrocyclic ligands.

PubMed

Siddiqi, Zafar Ahmad; Arif, Razia; Kumar, Sarvendra; Khalid, Mohd

2008-10-01

The homo-bimetallic complexes of stoichiometry Fe2(L)ClO4(ClO4)2 where L are novel unsymmetrical [N10] (L1.2HClO4) and [N12] (L2.2HClO4) macrocyclic ligands, have been prepared. The ligands were obtained from an in situ capping reaction of the reactive substrate, N,N'-bis(N-ethylaniline)hydrazine-1,2-diimine with a mixture of aniline or 1,3-diaminopropane and HCHO in presence of HClO4. The compounds have been characterized by elemental analyses, conductometric, IR, FAB-mass and electronic spectral studies. IR data of complexes suggest coordination from unsymmetrical aza sites as a tridentate (N,N,N) or tetradentate (N,N,N,N) ligand. mu(eff) values of the complexes suggest presence of antiferromagnetically coupled (Fe3+-Fe3+=S5/2-S5/2) spin exchange. Mössbauer parameters of the complexes support (+/-3/2)-->(+/-1/2) nuclear transition in high-spin configurations of Fe(III) nuclei of the homo-bimetallic complexes with the presence of Kramer's double degeneracy.

Templated synthesis of cyclic [4]rotaxanes consisting of two stiff rods threaded through two bis-macrocycles with a large and rigid central plate as spacer.

PubMed

Collin, Jean-Paul; Durola, Fabien; Frey, Julien; Heitz, Valérie; Reviriego, Felipe; Sauvage, Jean-Pierre; Trolez, Yann; Rissanen, Kari

2010-05-19

Two related cyclic [4]rotaxanes consisting of double macrocycles and rigid rods incorporating two bidentate chelates have each been prepared in high yield. The first step is a multigathering and threading reaction driven by coordination of two different bidentate chelates (part of either the rings or the rods) to each copper(I) center so as to afford the desired precursor. In both cases, the assembly step is done under very mild conditions, and it is quantitative. The second key reaction is the stopper-attaching reaction, based on click chemistry. Even if the quadruple stoppering reaction is not quantitative, it is relatively high-yielding (60% and 95%), and the copper-driven assembly process is carried out at room temperature without any aggressive reagent. The final copper-complexed [4]rotaxanes obtained contain two aromatic plates roughly parallel to one another located at the center of each bis-macrocycle. In the most promising case in terms of host-guest properties, the plates are zinc(II) porphyrins of the tetra-aryl series. The compounds have been fully characterized by various spectroscopic techniques ((1)H NMR, mass spectrometry, and electronic absorption spectroscopy). Unexpectedly, the copper-complexed porphyrinic [4]rotaxane could be crystallized as its 4PF(6)(-) salt to afford X-ray quality crystals. The structure obtained is in perfect agreement with the postulated chemical structure of the compound. It is particularly attractive in terms of symmetry and molecular aesthetics. The distance between the zinc atoms of the two porphyrins is 8.673 A, which is sufficient to allow insertion between the two porphyrinic plates of small ditopic basic substrates able to interact with the central porphyrinic Zn atoms. This prediction has been confirmed by absorption spectroscopy measurements in the presence of various organic substrates. However, large substrates cannot be introduced in the corresponding recognition site and are thus complexed mostly in an exo fashion, being located outside the receptor cavity. Noteworthy, the stability constants of the 1:1 host-guest complexes are high (10(7) M(-1)).

An investigation of the preparation of high molecular weight perfluorocarbon polyethers

NASA Technical Reports Server (NTRS)

Watts, R. O.; Tarrant, P.

1972-01-01

High molecular weight perfluorocarbon polyether gums were obtained by photolysis of perfluorodienes and discyl fluorides containing a perfluorocarbon polyether backbond. The materials obtained are represented by chemical formulas. A method was developed whereby reactive acyl fluoride and trifluorovinyl end groups are converted into inert structures. In order to investigate the possible preparation of difunctional molecules which may be useful in polymer synthesis, the reactions of hexafluoropropene oxide (HFPO) with Grignard and organolithium reagents have been studied. Reactions of various nucleophilic reagents with HFPO were also investigated.

Squaraine rotaxanes with boat conformation macrocycles.

PubMed

Fu, Na; Baumes, Jeffrey M; Arunkumar, Easwaran; Noll, Bruce C; Smith, Bradley D

2009-09-04

Mechanical encapsulation of fluorescent, deep-red bis(anilino)squaraine dyes inside Leigh-type tetralactam macrocycles produces interlocked squaraine rotaxanes. The surrounding macrocycles are flexible and undergo rapid exchange of chair and boat conformations in solution. A series of X-ray crystal structures show how the rotaxane co-conformational exchange process involves simultaneous lateral oscillation of the macrocycle about the center of the encapsulated squaraine thread. Rotaxane macrocycles with 1,4-phenylene sidewalls and 2,6-pyridine dicarboxamide bridging units are more likely to adopt boat conformations in the solid state than analogous squaraine rotaxane systems with isophthalamide-containing macrocycles. A truncated squaraine dye, with a secondary amine attached directly to the central C(4)O(2) core, is less electrophilic than the extended bis(anilino)squaraine analogue, but it is still susceptible to chemical and photochemical bleaching. Its stability is greatly enhanced when it is encapsulated as an interlocked squaraine rotaxane. An X-ray crystal structure of this truncated squaraine rotaxane shows the macrocycle in a boat conformation, and NMR studies indicate that the boat is maintained in solution. Encapsulation as a rotaxane increases the dye's brightness by a factor of 6. The encapsulation process appears to constrain the dye and reduce deformation of the chromophore from planarity. This study shows how mechanical encapsulation as a rotaxane can be used as a rational design parameter to fine-tune the chemical and photochemical properties of squaraine dyes.

Squaraine Rotaxanes with Boat Conformation Macrocycles

PubMed Central

Fu, Na; Baumes, Jeffrey M.; Arunkumar, Easwaran; Noll, Bruce C.; Smith, Bradley D.

2010-01-01

Mechanical encapsulation of fluorescent, deep-red bis(anilino)squaraine dyes inside Leigh-type tetralactam macrocycles produces interlocked squaraine rotaxanes. The surrounding macrocycles are flexible and undergo rapid exchange of chair and boat conformations in solution. A series of X-ray crystal structures show how the rotaxane co-conformational exchange process involves simultaneous lateral oscillation of the macrocycle about the center of the encapsulated squaraine thread. Rotaxane macrocycles with 1,4-phenylene-sidewalls and 2,6-pyridine dicarboxamide bridging units are more likely to adopt boat conformations in the solid-state than analogous squaraine rotaxane systems with isophthalamide-containing macrocycles. A truncated squaraine dye, with a secondary amine attached directly to the central C4O2 core, is less electrophilic than the extended bis(anilino)squaraine analogue, but it is still susceptible to chemical and photochemical bleaching. Its stability is greatly enhanced when it is encapsulated as an interlocked squaraine rotaxane. An X-ray crystal structure of this truncated squaraine rotaxane shows the macrocycle in a boat conformation, and NMR studies indicate that the boat is maintained in solution. Encapsulation as a rotaxane increases the dye’s brightness by a factor of six. The encapsulation process appears to constrain the dye and reduce deformation of the chromophore from planarity. This study shows how mechanical encapsulation as a rotaxane can be used as a rational design parameter to fine-tune the chemical and photochemical properties of squaraine dyes. PMID:19639940

Aggregation behaviors of PEO-PPO-ph-PPO-PEO and PPO-PEO-ph-PEO-PPO at an air/water interface: experimental study and molecular dynamics simulation.

PubMed

Gong, Houjian; Xu, Guiying; Liu, Teng; Xu, Long; Zhai, Xueru; Zhang, Jian; Lv, Xin

2012-09-25

The block polyethers PEO-PPO-ph-PPO-PEO (BPE) and PPO-PEO-ph-PEO-PPO (BEP) are synthesized by anionic polymerization using bisphenol A as initiator. Compared with Pluronic P123, the aggregation behaviors of BPE and BEP at an air/water interface are investigated by the surface tension and dilational viscoelasticity. The molecular construction can influence the efficiency and effectiveness of block polyethers in decreasing surface tension. BPE has the most efficient ability to decrease surface tension of water among the three block polyethers. The maximum surface excess concentration (Γ(max)) of BPE is larger than that of BEP or P123. Moreover, the dilational modulus of BPE is almost the same as that of P123, but much larger than that of BEP. The molecular dynamics simulation provides the conformational variations of block polyethers at the air/water interface.

Mechanism of Thioesterase-Catalyzed Chain Release in the Biosynthesis of the Polyether Antibiotic Nanchangmycin

PubMed Central

Liu, Tiangang; Lin, Xin; Zhou, Xiufen; Deng, Zixin; Cane, David E.

2008-01-01

Summary The polyketide backbone of the polyether ionophore antibiotic nanchangmycin (1) is assembled by a modular polyketide synthase in Streptomyces nanchangensis NS3226. The ACP-bound polyketide is thought to undergo a cascade of oxidative cyclizations to generate the characteristic polyether. Deletion of the glycosyl transferase gene nanG5 resulted in accumulation of the corresponding nanchangmycin aglycone (6). The discrete thioesterase NanE exhibited a nearly 17-fold preference for hydrolysis of 4, the N-acetylcysteamine (SNAC) thioester of nanchangmycin, over 7, the corresponding SNAC derivative of the aglycone, consistent with NanE-catalyzed hydrolysis of ACP-bound nanchangmycin being the final step in the biosynthetic pathway. Site directed mutagenesis established that Ser96, His261, and Asp120, the proposed components of the NanE catalytic triad, were all essential for thioesterase activity, while Trp97 was shown to influence the preference for polyether over polyketide substrates. PMID:18482697

Acetone-Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling.

PubMed

Assem, Naila; Ferreira, David J; Wolan, Dennis W; Dawson, Philip E

2015-07-20

Macrocyclization is a broadly applied approach for overcoming the intrinsically disordered nature of linear peptides. Herein, it is shown that dichloroacetone (DCA) enhances helical secondary structures when introduced between peptide nucleophiles, such as thiols, to yield an acetone-linked bridge (ACE). Aside from stabilizing helical structures, the ketone moiety embedded in the linker can be modified with diverse molecular tags by oxime ligation. Insights into the structure of the tether were obtained through co-crystallization of a constrained S-peptide in complex with RNAse S. The scope of the acetone-linked peptides was further explored through the generation of N-terminus to side chain macrocycles and a new approach for generating fused macrocycles (bicycles). Together, these studies suggest that acetone linking is generally applicable to peptide macrocycles with a specific utility in the synthesis of stabilized helices that incorporate functional tags. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interference of interchromophoric energy-transfer pathways in π-conjugated macrocycles

DOE PAGES

Alfonso Hernandez, Laura; Nelson, Tammie Renee; Gelin, Maxim F.; ...

2016-11-10

The interchromophoric energy-transfer pathways between weakly coupled units in a π-conjugated phenylene–ethynylene macrocycle and its half-ring analogue have been investigated using the nonadiabatic excited-state molecular dynamics approach. To track the flow of electronic transition density between macrocycle units, we formulate a transition density flux analysis adapted from the statistical minimum flow method previously developed to investigate vibrational energy flow. Following photoexcitation, transition density is primarily delocalized on two chromophore units and the system undergoes ultrafast energy transfer, creating a localized excited state on a single unit. In the macrocycle, distinct chromophore units donate transition density to a single acceptor unitmore » but do not interchange transition density among each other. We find that energy transfer in the macrocycle is slower than in the corresponding half ring because of the presence of multiple interfering energy-transfer pathways. Finally, simulation results are validated by modeling the fluorescence anisotropy decay.« less

Characterization of various analytes using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 2-[(2E)-3-(4-tert-butylphenyl)-2-methylprop-2-enylidene]malononitrile matrix.

PubMed

Wyatt, Mark F; Stein, Bridget K; Brenton, A Gareth

2006-01-01

2-[(2E)-3-(4-tert-Butylphenyl)-2-methylprop-2-enylidene]malononitrile (DCTB) is a nonpolar, aprotic matrix and was used in the analysis of a variety of compounds by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The classes of compounds include coordination compounds, organometallics, conjugated organic compounds (including porphyrins and phthalocyanines), carbohydrates, calixarenes, and macrocycles. For some samples, comparisons are made with spectra acquired with the use of 1,8,9-trihydroxyanthracene (dithranol), 2,5-dihydroxybenzoic acid, and 2,4,6-trihydroxyacetophenone matrixes. Traditionally, the majority of these compounds would have been analyzed by fast-atom bombardment (FAB), liquid secondary ion mass spectrometry (LSIMS), or electrospray techniques, but this work shows that MALDI-TOFMS using DCTB has advantages over these techniques, particularly FAB and LSIMS. Certain limitations of DCTB are noted, for example, in the analysis of water-soluble compounds such as peptides, proteins, and oligonucleotides, and good working practices for the use of the matrix are also outlined.

Driving mechanisms of ionic polymer actuators having electric double layer capacitor structures.

PubMed

Imaizumi, Satoru; Kato, Yuichi; Kokubo, Hisashi; Watanabe, Masayoshi

2012-04-26

Two solid polymer electrolytes, composed of a polyether-segmented polyurethaneurea (PEUU) and either a lithium salt (lithium bis(trifluoromethanesulfonyl)amide: Li[NTf2]) or a nonvolatile ionic liquid (1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide: [C2mim][NTf2]), were prepared in order to utilize them as ionic polymer actuators. These salts were preferentially dissolved in the polyether phases. The ionic transport mechanism of the polyethers was discussed in terms of the diffusion coefficients and ionic transference numbers of the incorporated ions, which were estimated by means of pulsed-field gradient spin-echo (PGSE) NMR. There was a distinct difference in the ionic transport properties of each polymer electrolyte owing to the difference in the magnitude of interactions between the cations and the polyether. The anionic diffusion coefficient was much faster than that of the cation in the polyether/Li[NTf2] electrolyte, whereas the cation diffused faster than the anion in the polyether/[C2mim][NTf2] electrolyte. Ionic polymer actuators, which have a solid-state electric-double-layer-capacitor (EDLC) structure, were prepared using these polymer electrolyte membranes and ubiquitous carbon materials such as activated carbon and acetylene black. On the basis of the difference in the motional direction of each actuator against applied voltages, a simple model of the actuation mechanisms was proposed by taking the difference in ionic transport properties into consideration. This model discriminated the behavior of the actuators in terms of the products of transference numbers and ionic volumes. The experimentally observed behavior of the actuators was successfully explained by this model.

Molecular Mechanism by Which a Potent Hepatitis C Virus NS3-NS4A Protease Inhibitor Overcomes Emergence of Resistance

PubMed Central

O'Meara, Jeff A.; Lemke, Christopher T.; Godbout, Cédrickx; Kukolj, George; Lagacé, Lisette; Moreau, Benoît; Thibeault, Diane; White, Peter W.; Llinàs-Brunet, Montse

2013-01-01

Although optimizing the resistance profile of an inhibitor can be challenging, it is potentially important for improving the long term effectiveness of antiviral therapy. This work describes our rational approach toward the identification of a macrocyclic acylsulfonamide that is a potent inhibitor of the NS3-NS4A proteases of all hepatitis C virus genotypes and of a panel of genotype 1-resistant variants. The enhanced potency of this compound versus variants D168V and R155K facilitated x-ray determination of the inhibitor-variant complexes. In turn, these structural studies revealed a complex molecular basis of resistance and rationalized how such compounds are able to circumvent these mechanisms. PMID:23271737

Fused tetracycles with a benzene or cyclohexadiene core: [2 + 2 + 2] cycloadditions on macrocyclic systems.

PubMed

Brun, Sandra; Garcia, Lídia; González, Iván; Torrent, Anna; Dachs, Anna; Pla-Quintana, Anna; Parella, Teodor; Roglans, Anna

2008-09-28

A series of fused tetracycles with a benzene or cyclohexadiene core (2a-h) is satisfactorily prepared by intramolecular [2 + 2 + 2] cycloadditions of triynic and enediynic macrocycles (1a-h) under RhCl(PPh3)3 catalysis; the enantioselective cycloaddition of macrocycles 1b and 1e and gives chiral tetracycles with moderate enantiomeric excess.

Polyether ether ketone encased monolith frits made of polyether ether ketone tubing with a 0.25 mm opening resulting in an improved separation performance in liquid chromatography.

PubMed

Park, Sin Young; Cheong, Won Jo

2016-05-01

Tiny polyether ether ketone encased monolith frits have been prepared by modified catalytic sulfonation of the inner surface of polyether ether tubing (1.6 mm od, 0.25 mm id) followed by modified formation of organic monolith and cutting of the tubing into slices. The frit was placed below the central hole of the column outlet union and supported by a combination of a silica capillary (0.365 mm od, 0.05 mm id) and a polyether ether ketone sleeve (1.6 mm od, 0.38 mm id) tightened with a nut and a ferrule when the column was packed to prevent sinking of the frit element into the union hole (0.25 mm opening) otherwise. The column packed this way with the frits investigated in this study has shown better separation performance owing to the reduced frit volume in comparison to the column packed with a commercial stainless-steel screen frit. This study establishes the strategy of disposable microcolumns in which cheap disposable frits are used whenever the column is re-packed to yield columns of even better chromatographic performance than the columns with commercial frits. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro studies on the effect of physical cross-linking on the biological performance of aliphatic poly(urethane urea) for blood contact applications.

PubMed

Thomas, V; Kumari, T V; Jayabalan, M

2001-01-01

The effect of physical cross-linking in candidate cycloaliphatic and hydrophobic poly(urethane urea) (4,4'-methylenebis(cyclohexylisocyanate), H(12)MDI/hydroxy-terminated polybutadiene, HTPBD/hexamethylenediamine, HDA) and poly(ether urethane urea)s (H(12)MDI/HTPBD-PTMG/HDA) on the in vitro calcification and blood-material interaction was studied. All the candidate poly(urethane urea)s and poly(ether urethane urea)s elicit acceptable hemolytic activity, cytocompatibility, calcification, and blood compatibility in vitro. The studies on blood-material interaction reveal that the present poly(urethane urea)s are superior to polystyrene microtiter plates which were used for the studies on blood-material interaction. The present investigation reveals the influence of physical cross-link density on biological interaction differently with poly(urethane urea) and poly(ether urethane urea)s. The higher the physical cross-link density in the poly(urethane urea)s, the higher the calcification and consumption of WBC in whole blood. On the other hand, the higher the physical cross-link density in the poly(ether urethane urea)s, the lesser the calcification and consumption of WBC in whole blood. However a reverse of the above trend has been observed with the platelet consumption in the poly(urethane urea)s and poly(ether urethane urea)s.

High Affinity Macrocycle Threading by a Near-Infrared Croconaine Dye with Flanking Polymer Chains

PubMed Central

Liu, Wenqi; Peck, Evan M.; Smith, Bradley D.

2016-01-01

Croconaine dyes have narrow and intense absorption bands at ~800 nm, very weak fluorescence, and high photostabilities, which combine to make them very attractive chromophores for absorption-based imaging or laser heating technologies. The physical supramolecular properties of croconaine dyes have rarely been investigated, especially in water. This study focuses on a molecular threading process that encapsulates a croconaine dye inside a tetralactam macrocycle in organic or aqueous solvent. Macrocycle association and rate constant data are reported for a series of croconaine structures with different substituents attached to the ends of the dye. The association constants were highest in water (Ka ~109 M−1), and the threading rate constants (kon) increased in the solvent order H2O > MeOH > CHCl3. Systematic variation of croconaine substituents located just outside the croconaine/macrocycle complexation interface hardly changed Ka but had a strong influence on kon. A croconaine dye with N-propyl groups at each end of the structure exhibited a desirable mixture of macrocycle threading properties; that is, there was rapid and quantitative croconaine/macrocycle complexation at relatively high concentrations in water, and no dissociation of the pre-assembled complex when it was diluted into a solution of fetal bovine serum, even after laser induced photothermal heating of the solution. The combination of favorable near-infrared absorption properties and tunable mechanical stability makes threaded croconaine/macrocycle complexes very attractive as molecular probes or as supramolecular composites for various applications in absorption-based imaging or photothermal therapy. PMID:26807599

Selective CO2 gas adsorption in the narrow crystalline cavities of flexible peptide metallo-macrocycles.

PubMed

Miyake, Ryosuke; Kuwata, Chika; Masumoto, Yui

2015-02-21

Crystalline peptide Ni(ii)-macrocycles (BF4(-) salt) exhibited moderate CO2 gas adsorption (ca. 6-7 CO2 molecules per macrocycle) into very narrow cavities (narrowest part <2 Å), accompanied by the expansion of the cavities. The BF4(-) salt demonstrated selective uptake of CO2 gas in preference to CH4 and N2 gases.

Highly selective Ba2+ separations with acyclic, lipophilic di-[N-(X)sulfonyl carbamoyl] polyethers.

PubMed

Elshani, Sadik; Chun, Sangki; Amiri-Eliasi, Bijan; Bartsch, Richard A

2005-01-14

New lipophilic acyclic polyethers with two N-(X)sulfonyl carbamoyl groups of "tunable" acidity exhibit remarkable selectivity for Ba2+ over other alkaline earth metal ions in competitive solvent extraction and transport across polymer inclusion membranes.

New milbemycin metabolites from the genetically engineered strain Streptomyces bingchenggensis BCJ60.

PubMed

Li, Jian-Song; Du, Min-Na; Zhang, Hui; Zhang, Ji; Zhang, Shao-Yong; Wang, Hai-Yan; Chen, An-Liang; Wang, Ji-Dong; Xiang, Wen-Sheng

2017-04-01

Two new milbemycin derivatives, 27-methoxylmilbemycin α 31 (1) and 27-oxomilbemycin α 31 (2), were isolated from the genetically engineered strain Streptomyces bingchenggensis BCJ60. Their structures were determined by 1D NMR, 2D NMR and HR-ESI-MS spectral analysis, and comparison with previous reports. The acaricidal and nematocidal capacities of compounds 1 and 2 were evaluated against Tetranychus cinnabarinus and Bursaphelenchus xylophilus, respectively. The results showed that the two new macrocyclic lactones 1 and 2 possessed potent acaricidal and nematocidal activities.

Comparative study to evaluate the accuracy of polyether occlusal bite registration material and occlusal registration wax as a guide for occlusal reduction during tooth preparation.

PubMed

Joshi, Niranjan; Shetty, Sridhar N; Prasad, Krishna D

2013-01-01

The use of different materials and techniques has been studied to decide the safest quantum of reduction of the occlusal surfaces. However, these methods provide limited information as to the actual amount of reduction with limitations in accuracy, accessibility and complexity. The objective of this study was to compare and evaluate the reliability of the most commonly used occlusal registration wax that with polyether bite registration material as a guide for occlusal reduction required during tooth preparations. For the purpose of this study, 25 abutment teeth requiring tooth preparation for fixed prosthesis were selected and tooth preparations carried out. Modeling wax strips of specific dimensions were placed onto the cast of prepared tooth, which was mounted on maximum intercuspation on the articulator and the articulator was closed. The thickness of the wax registration was measured at three zones namely two functional cusps and central fossa. Similar measurements were made using the polyether bite registration material and prosthesis at the same zones. The data was tabulated and was subjected to statistical analysis using anova test and Tukey honestly significant difference test. The differences in thickness between wax record and prosthesis by 0.1346 mm, whereas the difference between polyether and prosthesis was 0.02 mm with a P value of 0.042, which is statistically significant. This means that the wax record was 8.25% larger than the prosthesis while polyether was just 1.27% larger than the prosthesis. The clinical significance of the above analysis is that Ramitec polyether bite registration material is most suitable material when compared with commonly used modeling wax during the tooth preparation.

On-Surface Synthesis and Characterization of Honeycombene Oligophenylene Macrocycles.

PubMed

Chen, Min; Shang, Jian; Wang, Yongfeng; Wu, Kai; Kuttner, Julian; Hilt, Gerhard; Hieringer, Wolfgang; Gottfried, J Michael

2017-01-24

We report the on-surface formation and characterization of [30]-honeycombene, a cyclotriacontaphenylene, which consists of 30 phenyl rings (C 180 H 120 ) and has a diameter of 4.0 nm. This shape-persistent, conjugated, and unsubstituted hexagonal hydrocarbon macrocycle was obtained by solvent-free synthesis on a silver (111) single-crystal surface, making solubility-enhancing alkyl side groups unnecessary. Side products include strained macrocycles with square, pentagonal, and heptagonal shape. The molecules were characterized by scanning tunneling microscopy and density functional theory (DFT) calculations. On the Ag(111) surface, the macrocycles act as molecular quantum corrals and lead to the confinement of surface-state electrons inside the central cavity. The energy of the confined surface state correlates with the size of the macrocycle and is well described by a particle-in-the-box model. Tunneling spectroscopy suggests conjugation within the planar rings and reveals influences of self-assembly on the electronic structure. While the adsorbed molecules appear to be approximately planar, the free molecules have nonplanar conformation, according to DFT.

Supramolecular recognition control of polyethylene glycol modified N-doped graphene quantum dots: tunable selectivity for alkali and alkaline-earth metal ions.

PubMed

Yang, Siwei; Sun, Jing; Zhu, Chong; He, Peng; Peng, Zheng; Ding, Guqiao

2016-02-07

The graphene quantum dot based fluorescent probe community needs unambiguous evidence about the control on the ion selectivity. In this paper, polyethylene glycol modified N-doped graphene quantum dots (PN-GQDs) were synthesized by alkylation reaction between graphene quantum dots and organic halides. We demonstrate the tunable selectivity and sensitivity by controlling the supramolecular recognition through the length and the end group size of the polyether chain on PN-GQDs. The relationship formulae between the selectivity/detection limit and polyether chains are experimentally deduced. The polyether chain length determines the interaction between the PN-GQDs and ions with different ratios of charge to radius, which in turn leads to a good selectivity control. Meanwhile the detection limit shows an exponential growth with the size of end groups of the polyether chain. The PN-GQDs can be used as ultrasensitive and selective fluorescent probes for Li(+), Na(+), K(+), Mg(2+), Ca(2+) and Sr(2+), respectively.

Two-piece impression procedure for implant-retained orbital prostheses.

PubMed

Ozcelik, Tuncer Burak; Yilmaz, Burak

2012-01-01

Obtaining an accurate impression of facial tissues with undercuts and extraoral implants has always been a challenge for both clinicians and patients. This report describes a three-step, two-piece technique that enables an accurate and comfortable impression of undercut tissues and extraoral implants in an orbital defect. An impression of the basal tissue surface of the defect area was made using a medium-body polyether impression material followed by an impression of the entire face of the patient made with a polyvinyl siloxane (PVS) impression material. First, the PVS impression material was removed; second, the impression posts were removed from the magnets; and third, the polyether impression was removed from the defect. The impression posts were attached to the implant analogs and placed in the negative spaces in the polyether impression. The polyether impression, which carries the implant analogs and impression posts, was placed in the PVS impression through the negative spaces. This technique minimizes trauma to the soft tissues and implants during impression making and also does not require additional materials.

Epoxide-Opening Cascades in the Synthesis of Polycyclic Polyether Natural Products

PubMed Central

2009-01-01

The group of polycyclic polyether natural products is of special interest due to the fascinating structure and biological effects displayed by its members. The latter includes potentially therapeutic antibiotic, antifungal, and anticancer properties, as well as extreme lethality. The polycyclic structural features of this family can, in some cases, be traced to their biosynthetic origin, but in others that are less well understood, only to proposed biosynthetic pathways that feature dramatic, yet speculative, epoxide–opening cascades. In this review we summarize how such epoxide–opening cascade reactions have been used in the synthesis of polycyclic polyethers and related natural products. PMID:19572302

Safety Assessment of Polyether Lanolins as Used in Cosmetics.

PubMed

Becker, Lillian C; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan; Heldreth, Bart

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 39 polyether lanolin ingredients as used in cosmetics. These ingredients function mostly as hair conditioning agents, skin conditioning agent-emollients, and surfactant-emulsifying agents. The Panel reviewed available animal and clinical data, from previous CIR safety assessments of related ingredients and components. The similar structure, properties, functions, and uses of these ingredients enabled grouping them and using the available toxicological data to assess the safety of the entire group. The Panel concluded that these polyether lanolin ingredients are safe in the practices of use and concentration as given in this safety assessment.

A thin film degradation study of a fluorinated polyether liquid lubricant using an HPLC method

NASA Technical Reports Server (NTRS)

Morales, W.

1986-01-01

A High Pressure Liquid Chromatography (HPLC) separation method was developed to study and analyze a fluorinated polyether fluid which is promising liquid lubricant for future applications. This HPLC separation method was used in a preliminary study investigating the catalytic effect of various metal, metal alloy, and ceramic engineering materials on the degradation of this fluid in a dry air atmosphere at 345 C. Using a 440 C stainless steel as a reference catalytic material it was found that a titanium alloy and a chromium plated material degraded the fluorinated polyether fluid substantially more than the reference material.

SEPARATION OF OCTYLPHENOL POLYETHER ALCOHOLS SURFACTANTS BY CAPILLARY COLUMN AND HPLC

EPA Science Inventory

Separation of nonionic octylphenol polyether alcohols (OPA) by supercritical fluid chromatography (SFC) and HPLC is described. sing a density programming and a 50-pm i.d. capillary column, a total of 18 group oligomers was separated. he effects of the operating parameters, such a...

Poly(ether ester) Ionomers as Water-Soluble Polymers for Material Extrusion Additive Manufacturing Processes.

PubMed

Pekkanen, Allison M; Zawaski, Callie; Stevenson, André T; Dickerman, Ross; Whittington, Abby R; Williams, Christopher B; Long, Timothy E

2017-04-12

Water-soluble polymers as sacrificial supports for additive manufacturing (AM) facilitate complex features in printed objects. Few water-soluble polymers beyond poly(vinyl alcohol) enable material extrusion AM. In this work, charged poly(ether ester)s with tailored rheological and mechanical properties serve as novel materials for extrusion-based AM at low temperatures. Melt transesterification of poly(ethylene glycol) (PEG, 8k) and dimethyl 5-sulfoisophthalate afforded poly(ether ester)s of sufficient molecular weight to impart mechanical integrity. Quantitative ion exchange provided a library of poly(ether ester)s with varying counterions, including both monovalent and divalent cations. Dynamic mechanical and tensile analysis revealed an insignificant difference in mechanical properties for these polymers below the melting temperature, suggesting an insignificant change in final part properties. Rheological analysis, however, revealed the advantageous effect of divalent countercations (Ca 2+ , Mg 2+ , and Zn 2+ ) in the melt state and exhibited an increase in viscosity of two orders of magnitude. Furthermore, time-temperature superposition identified an elevation in modulus, melt viscosity, and flow activation energy, suggesting intramolecular interactions between polymer chains and a higher apparent molecular weight. In particular, extrusion of poly(PEG 8k -co-CaSIP) revealed vast opportunities for extrusion AM of well-defined parts. The unique melt rheological properties highlighted these poly(ether ester) ionomers as ideal candidates for low-temperature material extrusion additive manufacturing of water-soluble parts.

Macrocyclic BACE inhibitors: Optimization of a micromolar hit to nanomolar leads.

PubMed

Huang, Yifang; Strobel, Eric D; Ho, Chih Y; Reynolds, Charles H; Conway, Kelly A; Piesvaux, Jennifer A; Brenneman, Douglas E; Yohrling, George J; Moore Arnold, H; Rosenthal, Daniel; Alexander, Richard S; Tounge, Brett A; Mercken, Marc; Vandermeeren, Marc; Parker, Michael H; Reitz, Allen B; Baxter, Ellen W

2010-05-15

We have identified macrocyclic inhibitors of the aspartic protease BACE, implicated in the etiology of Alzheimer's disease. An X-ray structure of screening hit 1 in the BACE active site revealed a hairpin conformation suggesting that constrained macrocyclic derivatives may also bind there. Several of the analogs we prepared were >100x more potent than 1, such as 7 (5 nM K(i)). Copyright 2010 Elsevier Ltd. All rights reserved.

American Chemical Society--238th National Meeting & Exposition. Developments in medicinal chemistry: part 1. 16-20 August 2009, Washington DC, USA.

PubMed

Gater, Deborah; Macauley, Donald

2009-10-01

The 238th National Meeting and Exposition of the American Chemical Society, held in Washington DC, included topics covering new compounds and developments in the field of medicinal chemistry. This conference report highlights selected presentations on a novel KV1.5 blocker, a state-dependent CaV2.2 antagonist, therapeutic uses of macrocycles, a novel P2X7 antagonist, developments using the StaR technology platform, the optimization of a neuropeptide S receptor antagonist, and type 1 glycine transport modulators. Investigational drugs discussed include WYE-160020 (Wyeth), Trox-1 (Neuromed Pharmaceuticals Inc), ulimorelin (Tranzyme Pharma Inc), E-32224 (Ensemble Discovery Corp) and PF-03463275 (Pfizer Inc); the discontinued compound AZD-9056 is also highlighted.

Novel crosslinked membranes based on sulfonated poly(ether ether ketone) for direct methanol fuel cells.

PubMed

Zhu, Yuanqin; Zieren, Shelley; Manthiram, Arumugam

2011-07-14

Novel covalently crosslinked membranes based on sulfonated poly(ether ether ketone) and carboxylated polysulfone exhibit much lower methanol crossover and better performance in direct methanol fuel cells at 65 °C in 1 and 2 M methanol solutions compared to Nafion 115 membranes.

40 CFR 63.1428 - Process vent requirements for group determination of PMPUs using a nonepoxide organic HAP to make...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Hazardous Air Pollutant Emissions for Polyether Polyols Production § 63.1428 Process vent requirements for... make or modify a polyether polyol for a PMPU are less than 11,800 kg/yr, the owner or operator of that...

SEPARATION OF OCTYLPHENOL POLYETHER ALCOHOLS SURFACTANTS BY CAPILLARY COLUMN SFC AND HPLC

EPA Science Inventory

Separation of nonionic octylphenol polyether alcohols (OPA) by supercritical fluid chromatography (SFC) and HPLC is described. Using a density programming and a 50-μm i.d. capillary column, a total of 18 group oligomers was separated. The effects of the operating parameters, such...

A New Class of Macrocyclic Chiral Selectors for Stereochemical Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1999-03-11

This report summarizes the work accomplished in the authors laboratories over the previous three years. During the funding period they have had 23 monographs published or in press, 1 book chapter, 1 patent issued and have delivered 28 invited seminars or plenary lectures on DOE sponsored research. This report covers the work that has been published (or accepted). The most notable aspect of this work involves the successful development and understanding of a new class of fused macrocyclic compounds as pseudophases and selectors in high performance separations (including high performance liquid chromatography, HPLC; capillary electrophoresis, CE; and thin layer chromatography,more » TLC). They have considerably extended their chiral biomarker work from amber to crude oil and coal. In the process of doing this we've developed several novel separation approaches. They finished their work on the new GSC-PLOT column which is now being used by researchers world-wide for the analysis of gases, light hydrocarbons and halocarbons. Finally, we completed basic studies on immobilizing a cyclodextrin/oligosiloxane hybrid on the wall of fused silica, as well as a basic study on the separation behavior of buckminster fullerene and higher fullerenes.« less

Macrocyclic cavitands cucurbit[n]urils: prospects for application in biochemistry, medicine and nanotechnology

NASA Astrophysics Data System (ADS)

Gerasko, O. A.; Kovalenko, E. A.; Fedin, V. P.

2016-08-01

The prospects of using the organic macrocyclic cavitands cucurbit[n]urils (CB[n]) and their derivatives in biochemistry, medicine and nanotechnology are considered. A combination of CB[n] characteristics, such as a rigid highly symmetrical structure, polarized hydrophilic portals, a rather large intramolecular hydrophobic cavity, as well as high resistance to thermolysis and corrosive media and low toxicity, account for a wide range of unique opportunities for the deliberate design of new functional materials, which may find application in various areas of modern chemistry and new technologies. Inclusion compounds of CB[n] with biologically active molecules demonstrate a high potential for the design of a new generation of prolonged action pharmaceuticals. The review presents the prospects for the application of CB[n] to manufacture unique materials, such as CB[n]-containing vesicles, films and surfaces, suitable for immobilization of various molecules and nanoparticles on their surface and for the separation of complex mixtures. Potential applications of CB[n]-modified electrodes and hydrogels are analyzed, and the use of CB[n] in proton-conducting materials and materials for the gas sorption and separation are discussed. The bibliography includes 164 references.

Virtual screening using combinatorial cyclic peptide libraries reveals protein interfaces readily targetable by cyclic peptides.

PubMed

Duffy, Fergal J; O'Donovan, Darragh; Devocelle, Marc; Moran, Niamh; O'Connell, David J; Shields, Denis C

2015-03-23

Protein-protein and protein-peptide interactions are responsible for the vast majority of biological functions in vivo, but targeting these interactions with small molecules has historically been difficult. What is required are efficient combined computational and experimental screening methods to choose among a number of potential protein interfaces worthy of targeting lead macrocyclic compounds for further investigation. To achieve this, we have generated combinatorial 3D virtual libraries of short disulfide-bonded peptides and compared them to pharmacophore models of important protein-protein and protein-peptide structures, including short linear motifs (SLiMs), protein-binding peptides, and turn structures at protein-protein interfaces, built from 3D models available in the Protein Data Bank. We prepared a total of 372 reference pharmacophores, which were matched against 108,659 multiconformer cyclic peptides. After normalization to exclude nonspecific cyclic peptides, the top hits notably are enriched for mimetics of turn structures, including a turn at the interaction surface of human α thrombin, and also feature several protein-binding peptides. The top cyclic peptide hits also cover the critical "hot spot" interaction sites predicted from the interaction crystal structure. We have validated our method by testing cyclic peptides predicted to inhibit thrombin, a key protein in the blood coagulation pathway of important therapeutic interest, identifying a cyclic peptide inhibitor with lead-like activity. We conclude that protein interfaces most readily targetable by cyclic peptides and related macrocyclic drugs may be identified computationally among a set of candidate interfaces, accelerating the choice of interfaces against which lead compounds may be screened.

TRPV1 as a key determinant in ciguatera and neurotoxic shellfish poisoning

PubMed Central

Cuypers, Eva; Yanagihara, Angel; Rainier, Jon D.; Tytgat, Jan

2007-01-01

Ciguatera fish poisoning and neurotoxic shellfish poisoning are distinct clinical entities characterized by gastrointestinal and neurological disturbances, following the consumption of certain reef fish and shellfish containing toxic polyether compounds sporadically present in certain toxic marine dinoflagellates. The biotransformation and bioaccumulation of gambierol and brevetoxin, and their congeners, are believed to be involved in the pathogenesis of these “food-chain diseases”, for which no effective treatments are available. Here, we describe for the first time the potent effect of gambierol and brevetoxin on TRPV1 channels, a key player in thermal and pain sensation. Our findings may lead to promising new therapeutic interventions. PMID:17659256

Propenyl ether monomers for photopolymerization

DOEpatents

Crivello, J.V.

1996-10-22

Propenyl ether monomers of formula A(OCH{double_bond}CHCH{sub 3}){sub n} wherein n is an integer from one to six and A is selected from cyclic ethers, polyether and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of the above formula together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Propenyl ether monomers for photopolymerization

DOEpatents

Crivello, James V.

1996-01-01

Propenyl ether monomers of formula V A(OCH.dbd.CHCH.sub.3).sub.n wherein n is an integer from one to six and A is selected from cyclic ethers, polyether and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of formula V together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Process for making propenyl ethers and photopolymerizable compositions containing them

DOEpatents

Crivello, James V.

1996-01-01

Propenyl ether monomers of formula V A(OCH.dbd.CHCH.sub.3).sub.n wherein n is an integer from one to six and A is selected from cyclic ethers, polyether and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of formula V together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Catalytic "active-metal" template synthesis of [2]rotaxanes, [3]rotaxanes, and molecular shuttles, and some observations on the mechanism of the cu(i)-catalyzed azide-alkyne 1,3-cycloaddition.

PubMed

Aucagne, Vincent; Berna, José; Crowley, James D; Goldup, Stephen M; Hänni, Kevin D; Leigh, David A; Lusby, Paul J; Ronaldson, Vicki E; Slawin, Alexandra M Z; Viterisi, Aurélien; Walker, D Barney

2007-10-03

A synthetic approach to rotaxane architectures is described in which metal atoms catalyze covalent bond formation while simultaneously acting as the template for the assembly of the mechanically interlocked structure. This "active-metal" template strategy is exemplified using the Huisgen-Meldal-Fokin Cu(I)-catalyzed 1,3-cycloaddition of azides with terminal alkynes (the CuAAC "click" reaction). Coordination of Cu(I) to an endotopic pyridine-containing macrocycle allows the alkyne and azide to bind to metal atoms in such a way that the metal-mediated bond-forming reaction takes place through the cavity of the macrocycle--or macrocycles--forming a rotaxane. A variety of mono- and bidentate macrocyclic ligands are demonstrated to form [2]rotaxanes in this way, and by adding pyridine, the metal can turn over during the reaction, giving a catalytic active-metal template assembly process. Both the stoichiometric and catalytic versions of the reaction were also used to synthesize more complex two-station molecular shuttles. The dynamics of the translocation of the macrocycle by ligand exchange in these two-station shuttles could be controlled by coordination to different metal ions (rapid shuttling is observed with Cu(I), slow shuttling with Pd(II)). Under active-metal template reaction conditions that feature a high macrocycle:copper ratio, [3]rotaxanes (two macrocycles on a thread containing a single triazole ring) are also produced during the reaction. The latter observation shows that under these conditions the mechanism of the Cu(I)-catalyzed terminal alkyne-azide cycloaddition involves a reactive intermediate that features at least two metal ions.

Mechanically Resilient Polymeric Films Doped with a Lithium Compound

NASA Technical Reports Server (NTRS)

Meador, Mary Ann B. (Inventor); Kinder, James D. (Inventor)

2005-01-01

This invention is a series of mechanically resilient polymeric films, comprising rod-coil block polyimide copolymers, which are doped with a lithium compound providing lithium ion conductivity, that are easy to fabricate into mechanically resilient films with acceptable ionic or protonic conductivity at a variety of temperatures. The copolymers consists of short-rigid polyimide rod segments alternating with polyether coil segments. The rods and coil segments can be linear, branched or mixtures of linear and branched segments. The highly incompatible rods and coil segments phase separate, providing nanoscale channels for ion conduction. The polyimide segments provide dimensional and mechanical stability and can be functionalized in a number of ways to provide specialized functions for a given application. These rod-coil black polyimide copolymers are particularly useful in the preparation of ion conductive membranes for use in the manufacture of fuel cells and lithium based polymer batteries.

Adaptive self-assembly and induced-fit transformations of anion-binding metal-organic macrocycles

NASA Astrophysics Data System (ADS)

Zhang, Ting; Zhou, Li-Peng; Guo, Xiao-Qing; Cai, Li-Xuan; Sun, Qing-Fu

2017-06-01

Container-molecules are attractive to chemists due to their unique structural characteristics comparable to enzymes and receptors in nature. We report here a family of artificial self-assembled macrocyclic containers that feature induced-fit transformations in response to different anionic guests. Five metal-organic macrocycles with empirical formula of MnL2n (M=Metal L=Ligand n=3, 4, 5, 6, 7) are selectively obtained starting from one simple benzimidazole-based ligand and square-planar palladium(II) ions, either by direct anion-adaptive self-assembly or induced-fit transformations. Hydrogen-bonding interactions between the inner surface of the macrocycles and the anionic guests dictate the shape and size of the product. A comprehensive induced-fit transformation map across all the MnL2n species is drawn, with a representative reconstitution process from Pd7L14 to Pd3L6 traced in detail, revealing a gradual ring-shrinking mechanism. We envisage that these macrocyclic molecules with adjustable well-defined hydrogen-bonding pockets will find wide applications in molecular sensing or catalysis.

A 26-Membered Macrocycle Obtained by a Double Diels-Alder Cycloaddition Between Two 2H-Pyran-2-one Rings and Two 1,1'-(Hexane-1,6-diyl)bis (1H-pyrrole-2,5-dione)s.

PubMed

Turek, Bor Lucijan; Kočevar, Marijan; Kranjc, Krištof; Perdih, Franc

2017-12-01

With the application of a double dienophile 1,1'-(hexane-1,6-diyl)bis(1H-pyrrole-2,5-dione) for a [4+2] cycloaddition with a substituted 2H-pyran-2-one a novel 26-membered tetraaza heteromacrocyclic system 3 was prepared via a direct method under solvent-free conditions with microwave irradiation. The macrocycle prepared is composed of two units of the dienophile and two of the diene. The structure of the macrocycle was characterized on the basis of IR, 1H and 13C NMR and mass spectroscopy, as well as by the elemental analysis and melting point determination. With X-ray diffraction of a single crystal of the macrocycle we have determined that the two acetyl groups (attached to the bridging double bond of the bicyclo[2.2.2]octene fragments) are oriented towards each other (and also towards the inside of the cavity of the macrocycle), therefore, mostly filling it completely.

Kinetic Analysis for Macrocyclizations Involving Anionic Template at the Transition State

PubMed Central

Martí-Centelles, Vicente; Burguete, M. Isabel; Luis, Santiago V.

2012-01-01

Several kinetic models for the macrocyclization of a C2 pseudopeptide with a dihalide through a SN2 reaction have been developed. These models not only focus on the kinetic analysis of the main macrocyclization reaction, but also consider the competitive oligomerization/polymerization processes yielding undesired oligomeric/polymeric byproducts. The effect of anions has also been included in the kinetic models, as they can act as catalytic templates in the transition state reducing and stabilizing the transition state. The corresponding differential equation systems for each kinetic model can be solved numerically. Through a comprehensive analysis of these results, it is possible to obtain a better understanding of the different parameters that are involved in the macrocyclization reaction mechanism and to develop strategies for the optimization of the desired processes. PMID:22666148

Biodegradative Activities of Selected Environmental Fungi on a Polyester Polyurethane Varnish and Polyether Polyurethane Foams

PubMed Central

Álvarez-Barragán, Joyce; Domínguez-Malfavón, Lilianha; Vargas-Suárez, Martín; González-Hernández, Ricardo; Aguilar-Osorio, Guillermo

2016-01-01

ABSTRACT Polyurethane (PU) is widely used in many aspects of modern life because of its versatility and resistance. However, PU waste disposal generates large problems, since it is slowly degraded, there are limited recycling processes, and its destruction may generate toxic compounds. In this work, we isolated fungal strains able to grow in mineral medium with a polyester PU (PS-PU; Impranil DLN) or a polyether PU (PE-PU; Poly Lack) varnish as the only carbon source. Of the eight best Impranil-degrading strains, the six best degraders belonged to the Cladosporium cladosporioides complex, including the species C. pseudocladosporioides, C. tenuissimum, C. asperulatum, and C. montecillanum, and the two others were identified as Aspergillus fumigatus and Penicillium chrysogenum. The best Impranil degrader, C. pseudocladosporioides strain T1.PL.1, degraded up to 87% after 14 days of incubation. Fourier transform infrared (FTIR) spectroscopy analysis of Impranil degradation by this strain showed a loss of carbonyl groups (1,729 cm−1) and N—H bonds (1,540 and 1,261 cm−1), and gas chromatography-mass spectrometry (GC-MS) analysis showed a decrease in ester compounds and increase in alcohols and hexane diisocyanate, indicating the hydrolysis of ester and urethane bonds. Extracellular esterase and low urease, but not protease activities were detected at 7 and 14 days of culture in Impranil. The best eight Impranil-degrading fungi were also able to degrade solid foams of the highly recalcitrant PE-PU type to different extents, with the highest levels generating up to 65% of dry-weight losses not previously reported. Scanning electron microscopy (SEM) analysis of fungus-treated foams showed melted and thinner cell wall structures than the non-fungus-treated ones, demonstrating fungal biodegradative action on PE-PU. IMPORTANCE Polyurethane waste disposal has become a serious problem. In this work, fungal strains able to efficiently degrade different types of polyurethanes are reported, and their biodegradative activity was studied by different experimental approaches. Varnish biodegradation analyses showed that fungi were able to break down the polymer in some of their precursors, offering the possibility that they may be recovered and used for new polyurethane synthesis. Also, the levels of degradation of solid polyether polyurethane foams reported in this work have never been observed previously. Isolation of efficient polyurethane-degrading microorganisms and delving into the mechanisms they used to degrade the polymer provide the basis for the development of biotechnological processes for polyurethane biodegradation and recycling. PMID:27316963

Biodegradative Activities of Selected Environmental Fungi on a Polyester Polyurethane Varnish and Polyether Polyurethane Foams.

PubMed

Álvarez-Barragán, Joyce; Domínguez-Malfavón, Lilianha; Vargas-Suárez, Martín; González-Hernández, Ricardo; Aguilar-Osorio, Guillermo; Loza-Tavera, Herminia

2016-09-01

Polyurethane (PU) is widely used in many aspects of modern life because of its versatility and resistance. However, PU waste disposal generates large problems, since it is slowly degraded, there are limited recycling processes, and its destruction may generate toxic compounds. In this work, we isolated fungal strains able to grow in mineral medium with a polyester PU (PS-PU; Impranil DLN) or a polyether PU (PE-PU; Poly Lack) varnish as the only carbon source. Of the eight best Impranil-degrading strains, the six best degraders belonged to the Cladosporium cladosporioides complex, including the species C. pseudocladosporioides, C. tenuissimum, C. asperulatum, and C. montecillanum, and the two others were identified as Aspergillus fumigatus and Penicillium chrysogenum The best Impranil degrader, C. pseudocladosporioides strain T1.PL.1, degraded up to 87% after 14 days of incubation. Fourier transform infrared (FTIR) spectroscopy analysis of Impranil degradation by this strain showed a loss of carbonyl groups (1,729 cm(-1)) and N-H bonds (1,540 and 1,261 cm(-1)), and gas chromatography-mass spectrometry (GC-MS) analysis showed a decrease in ester compounds and increase in alcohols and hexane diisocyanate, indicating the hydrolysis of ester and urethane bonds. Extracellular esterase and low urease, but not protease activities were detected at 7 and 14 days of culture in Impranil. The best eight Impranil-degrading fungi were also able to degrade solid foams of the highly recalcitrant PE-PU type to different extents, with the highest levels generating up to 65% of dry-weight losses not previously reported. Scanning electron microscopy (SEM) analysis of fungus-treated foams showed melted and thinner cell wall structures than the non-fungus-treated ones, demonstrating fungal biodegradative action on PE-PU. Polyurethane waste disposal has become a serious problem. In this work, fungal strains able to efficiently degrade different types of polyurethanes are reported, and their biodegradative activity was studied by different experimental approaches. Varnish biodegradation analyses showed that fungi were able to break down the polymer in some of their precursors, offering the possibility that they may be recovered and used for new polyurethane synthesis. Also, the levels of degradation of solid polyether polyurethane foams reported in this work have never been observed previously. Isolation of efficient polyurethane-degrading microorganisms and delving into the mechanisms they used to degrade the polymer provide the basis for the development of biotechnological processes for polyurethane biodegradation and recycling. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Precursor Ion Scan Mode-Based Strategy for Fast Screening of Polyether Ionophores by Copper-Induced Gas-Phase Radical Fragmentation Reactions.

PubMed

Crevelin, Eduardo J; Possato, Bruna; Lopes, João L C; Lopes, Norberto P; Crotti, Antônio E M

2017-04-04

The potential of copper(II) to induce gas-phase fragmentation reactions in macrotetrolides, a class of polyether ionophores produced by Streptomyces species, was investigated by accurate-mass electrospray tandem mass spectrometry (ESI-MS/MS). Copper(II)/copper(I) transition directly induced production of diagnostic acylium ions with m/z 199, 185, 181, and 167 from α-cleavages of [macrotetrolides + Cu] 2+ . A UPLC-ESI-MS/MS methodology based on the precursor ion scan of these acylium ions was developed and successfully used to identify isodinactin (1), trinactin (2), and tetranactin (3) in a crude extract of Streptomyces sp. AMC 23 in the precursor ion scan mode. In addition, copper(II) was also used to induce radical fragmentation reactions in the carboxylic acid polyether ionophore nigericin. The resulting product ions with m/z 755 and 585 helped to identify nigericin in a crude extract of Streptomyces sp. Eucal-26 by means of precursor ion scan experiments, demonstrating that copper-induced fragmentation reactions can potentially identify different classes of polyether ionophores rapidly and selectively.

A Macrocyclic Chelator That Selectively Binds Ln 4+ over Ln 3+ by a Factor of 10 29

DOE PAGES

Pham, Tiffany A.; Altman, Alison B.; Stieber, S. Chantal E.; ...

2016-06-24

A tetravalent cerium macrocyclic complex (CeLK 4) was prepared with an octadentate terephthalamide ligand comprised of hard catecholate donors and characterized in the solution state by spectrophotometric titrations and electrochemistry and in the crystal by X-ray diffraction. The solution-state studies showed that L exhibits a remarkably high affinity toward Ce 4+, with log β 110 = 61(2) and ΔG = -348 kJ/mol, compared with log β 110 = 32.02(2) for the analogous Pr 3+ complex. In addition, L exhibits an unusual preference for forming CeL 4- relative to formation of the analogous actinide complex, ThL 4- , which has βmore » 110 = 53.7(5). The extreme stabilization of tetravalent cerium relative to its trivalent state is also evidenced by the shift of 1.91 V in the redox potential of the Ce 3+/Ce 4+ couple of the complex (measured at -0.454 V vs SHE). The unprecedented behavior prompted an electronic structure analysis using L 3 - and M 5,4-edge X-ray absorption near-edge structure (XANES) spectroscopies and configuration interaction calculations, which showed that 4f-orbital bonding in CeLK 4 has partial covalent character due to ligand-to-metal charge transfer (LMCT) in the ground state. The experimental results are presented in the context of earlier measurements on tetravalent cerium compounds, indicating that the amount of LMCT for CeLK 4 is similar to that observed for [Et 4N] 2[CeCl 6] and CeO 2 and significantly less than that for the organometallic sandwich compound cerocene, (C 8H 8) 2Ce. A simple model to rationalize changes in 4f orbital bonding for tri- and tetravalent lanthanide and actinide compounds is also provided.« less

The Setting Time of Polyether Impression Materials after Contact with Conventional and Experimental Gingival Margin Displacement Agents.

PubMed

Nowakowska, Danuta; Raszewski, Zbigniew; Ziętek, Marek; Saczko, Jolanta; Kulbacka, Julita; Więckiewicz, Włodzimierz

2018-02-01

The compatibility of chemical gingival margin displacement agents with polyether impression materials has not been determined. The aim of this study was to evaluate the setting time of polyether impression elastomers after contact with conventional and experimental gingival displacement agents. The study compared the setting time of two polyether impression materials: medium body (Impregum Penta Soft) and light body (Impregum Garant L DuoSoft) after contact with 10 gingival displacement agents, including 5 conventional astringents (10%, 20%, and 25% aluminum chloride, 25% aluminum sulfate, and 15.5% ferric sulfate) and 5 experimental adrenergics (0.1% and 0.01% HCl-epinephrine, 0.05% HCl-tetrahydrozoline, 0.05% HCl-oxymetazoline, and 10% HCl-phenylephrine). As many as 120 specimens (60 light body and 60 medium body) were mixed with 20 μl of each of 10 gingival displacement agents, and the time to achieve maximum viscosity was measured with a viscometer. The setting times of these specimens were compared with the control group of 12 specimens, which were polymerized without contact with the displacement agents. The experiments were performed in two environments: 23°C and 37°C (± 0.1°C). Individual and average polymerization time compatibility indices (PTCI) were calculated. Data were analyzed by 2-way ANOVA (α = 0.05). The evaluated chemical displacement agents from both groups changed the setting time of light- and medium-body PE. The negative individual PTCI values achieved astringent (20% aluminum chloride) with two PE in both temperature environments. The average PTCI values of the experimental displacement agents at laboratory and intraoral temperatures were significantly higher than the conventional agents. The present findings suggest that experimental retraction agents can be recommended clinically as gingival margin displacement agents with minimal effects on the setting time of medium- and light-body polyether impression materials; however, direct contact of chemical displacement agents and polyether impression materials can be avoided. © 2016 by the American College of Prosthodontists.

Cyclic peptide unguisin A is an anion receptor with high affinity for phosphate and pyrophosphate.

PubMed

Daryl Ariawan, A; Webb, James E A; Howe, Ethan N W; Gale, Philip A; Thordarson, Pall; Hunter, Luke

2017-04-05

Unguisin A (1) is a marine-derived, GABA-containing cyclic heptapeptide. The biological function of this flexible macrocycle is obscure. Here we show that compound 1 lacks any detectable activity in antimicrobial growth inhibition assays, a result that runs contrary to a previous report. However, we find that 1 functions as a promiscuous host molecule in a variety of anion-binding interactions, with high affinity particularly for phosphate and pyrophosphate. We also show that a series of rigidified, backbone-fluorinated analogues of 1 displays altered affinity for chloride ions.

Bone targeting compounds for radiotherapy and imaging: *Me(III)-DOTA conjugates of bisphosphonic acid, pamidronic acid and zoledronic acid.

PubMed

Meckel, M; Bergmann, R; Miederer, M; Roesch, F

2017-01-01

Bisphosphonates have a high adsorption on calcified tissues and are commonly used in the treatment of bone disorder diseases. Conjugates of bisphosphonates with macrocyclic chelators open new possibilities in bone targeted radionuclide imaging and therapy. Subsequent to positron emission tomography (PET) examinations utilizing 68 Ga-labelled analogues, endoradiotheraphy with 177 Lu-labelled macrocyclic bisphosphonates may have a great potential in the treatment of painful skeletal metastases. Based on the established pharmaceuticals pamidronate and zoledronate two new DOTA-α-OH-bisphosphonates, DOTA PAM and DOTA ZOL (MM1.MZ) were successfully synthesized. The ligands were labelled with the positron emitting nuclide 68 Ga and the β - emitting nuclide 177 Lu and compared in in vitro studies and in ex vivo biodistribution studies together with small animal PET and single photon emission computed tomography (SPECT) studies against [ 18 F]NaF and a known DOTA-α-H-bisphosphonate conjugate (BPAPD) in healthy Wistar rats. The new DOTA-bisphosphonates can be labelled in high yield of 80 to 95 % in 15 min with post-processed 68 Ga and >98 % with 177 Lu. The tracers showed very low uptake in soft tissue, a fast renal clearance and a high accumulation on bone. The best compound was [ 68 Ga]DOTA ZOL (SUV Femur  = 5.4 ± 0.6) followed by [ 18 F]NaF (SUV Femur  = 4.8 ± 0.2), [ 68 Ga]DOTA PAM (SUV Femur  = 4.5 ± 0.2) and [ 68 Ga]BPAPD (SUV Femur  = 3.2 ± 0.3). [ 177 Lu]DOTA ZOL showed a similar distribution as the diagnostic 68 Ga complex. The 68 Ga labelled compounds showed a promising pharmacokinetics, with similar uptake profile and distribution kinetics. Bone accumulation was highest for [ 68 Ga]DOTA ZOL , which makes this compound probably an interesting bone targeting agent for a therapeutic approach with 177 Lu. The therapeutic compound [ 177 Lu]DOTA ZOL showed a high target-to-background ratio. SPECT experiments showed concordance to the PET scans in healthy rats. [ 68 Ga/ 177 Lu]DOTA ZOL appears to be a potential theranostic combination in the management of disseminated bone metastases.

Cycloaddition Reactions of Cobalt-Complexed Macrocyclic Alkynes: The Transannular Pauson-Khand Reaction.

PubMed

Karabiyikoglu, Sedef; Boon, Byron A; Merlic, Craig A

2017-08-04

The Pauson-Khand reaction is a powerful tool for the synthesis of cyclopentenones through the efficient [2 + 2 + 1] cycloaddition of dicobalt alkyne complexes with alkenes. While intermolecular and intramolecular variants are widely known, transannular versions of this reaction are unknown and the basis of this study. Macrocyclic enyne and dienyne complexes were readily synthesized by palladium(II)-catalyzed oxidative macrocyclizations of bis(vinyl boronate esters) or ring-closing metathesis reactions followed by complexation with dicobalt octacarbonyl. Several reaction modalities of these macrocyclic complexes were uncovered. In addition to the first successful transannular Pauson-Khand reactions, other intermolecular and transannular cycloaddition reactions included intermolecular Pauson-Khand reactions, transannular [4 + 2] cycloaddition reactions, intermolecular [2 + 2 + 2] cycloaddition reactions, and intermolecular [2 + 2 + 1 + 1] cycloaddition reactions. The structural and reaction requirements for each process are presented.

Structural characterization of synthetic and protein-bound porphyrins in terms of the lowest-frequency normal coordinates of the macrocycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jentzen, W.; Song, X.Z.; Shelnutt, J.A.

1997-02-27

The X-ray crystal structures of synthetic and protein-bound metalloporphyrins are analyzed using a new normal structural decomposition method for classifying and quantifying their out-of-plane and in-plane distortions. These distortions are characterized in terms of equivalent displacements along the normal coordinates of the D{sub 4h}-symmetric porphyrin macrocycle (normal deformations). It is shown that the macrocyclic structure is, even in highly distorted porphyrins, accurately represented by displacements along only the lowest-frequency normal coordinates. Accordingly, the macrocyclic structure obtained from just the out-of-plane normal deformations of the saddling (sad, B{sub 2u})-, ruffling (ruf, B{sub 1u})-, doming (dom, A{sub 2u})-, waving [wav(x), wav(y); E{submore » g}]-, and propellering (pro, A{sub 1u})-type essentially simulates the out-of-plane distortion of the X-ray crystal structure. Similarly, the observed in-plane distortions are decomposed into in-plane normal deformations corresponding to the lowest-frequency vibrational modes including macrocycle stretching in the direction of the meso-carbon atoms (meso-str, B{sub 2g}), stretching in the direction of the nitrogen atoms (N-str, B{sub 1g}), x and y pyrrole translations [trn(x), trn(y); E{sub u}], macrocycle breathing (bre, A{sub 1g}), and pyrrole rotation (rot, A{sub 2g}). 71 refs., 9 figs., 4 tabs.« less

Self-Assembling Organic Nanopores as Synthetic Transmembrane Channels with Tunable Functions

NASA Astrophysics Data System (ADS)

Wei, Xiaoxi

A long-standing goal in the area of supramolecular self-assembly involves the development of synthetic ion/water channels capable of mimicking the mass-transport characteristics of biological channels and pores. Few examples of artificial transmembrane channels with large lumen, high conductivity and selectivity are known. A review of pronounced biological transmembrane protein channels and some representative synthetic models have been provided in Chapter 1, followed by our discovery and initial investigation of shape-persistent oligoamide and phenylene ethynylene macrocycles as synthetic ion/water channels. In Chapter 2, the systematic structural modification of oligoamide macrocycles 1, the so-called first-generation of these shape-persistent macrocycles, has led to third-generation macrocycles 3. The third generation was found to exhibit unprecedented, strong intermolecular association in both the solid state and solution via multiple techniques including X-ray diffraction (XRD), SEM, and 1H NMR. Fluorescence spectroscopy paired with dynamic light scattering (DLS) revealed that macrocycles 3 can assemble into a singly dispersed nanotubular structure in solution. The resultant self-assembling pores consisting of 3 were examined by HPTS-LUVs assays and BLM studies (Chapter 3) and found to form cation-selective (PK+/PCl- = 69:1) transmembrane ion channels with large conductance (200 ˜ 2000 pS for alkali cations) and high stability with open times reaching to 103 seconds. Tuning the aggregation state of macrocycles by choosing an appropriate polar solvent mixture (i.e., 3:1, THF:DMF, v/v) and concentration led to the formation of ion channels with well-defined square top behavior. A parallel study using DLS to examine the size of aggregates was used in conjunction with channel activity assays (LUVs/BLM) to reveal the effects of the aggregation state on channel activity. Empirical evidence now clearly indicates that a preassembled state, perhaps that of a nanotubular assembly, rather than the individual molecules of 3, is required to partition into the lipid bilayer in order for these macrocycles to act as channels. Further structural modification has led to fourth-generation macrocycles 4 having readily-tunable cavities (Chapter 4). Macrocycles 4 , with a hybrid backbone composed half of the oligoamide and half of the phenylene ethynylene moieties, exhibits similar self-assembling behavior by forming nanotubular stacks. The results of a preliminary study based on LUVs-assays and BLM single channel recording experiments are summarized and clearly indicate that ion channels formed by this fourth-generation exhibit high stability and differing ion selectivity largely consistent with the corresponding structural modification of the interior cavity. Especially, the increased anion conductance observed for 4d indicates that our strategy of tuning supramolecular function based on synthetic modification of the backbone and pore is effective. In Chapter 5, our four-residue tetraurea macrocycles 5 have shown significant potency to selectively interact with the G-quadruplex, leading to a strong stabilization effect for G-quadruplex without binding to duplex DNA as observed by UV-melt assays. The ready synthetic availability of these macrocycles makes them amenable to future chemical modification, which allows systematic improvement of binding affinity and specificity. Moreover, it has been discovered that these macrocycles can partition into lipid bilayers and form very stable transmembrane ion channels with a pore size of ˜5 A. Preliminary data shows that this smaller ion channel may lead to exceptional ion conducting selectivity, which is rarely seen in the field of synthetic ion pores. These molecules may serve as a unique platform for the rational development of potent and versatile therapeutic agents. The exceptional ion conducting properties of these channels place aromatic oligoamide macrocycles 3 and 4 at a unique position with both high conductance and long channel-opening duration. These results demonstrate that oligoamide macrocycles provide us a reliable platform based on which further development of highly conducting and selective synthetic mass-transporting channels, with functions that are comparable to or even rival those of natural channels and pores, may be developed. Further improvement of these synthetic channels could lead to numerous applications, such as those for complementing ion channel deficiency in clinical medicine, designing biosensors, and the development of new materials, as well as their use in separation and purifications.

Synthesis, crystal structure and antioxidant evaluation of C-4-acetamidophenylcalix[4]pyrogallolarene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abosadiya, Hamza M.; Hasbullah, Siti Aishah; Yamin, Bohari M.

2015-09-25

C-4-acetamidophenylcalix[4]pyrogallolarene was synthesized by an acid catalyzed condensation reaction of pyrogallol with 4-acetamidobenzaldehyde. The compound was characterized by IR, {sup 1}H and {sup 13}C NMR spectroscopy. Single crystal X-ray analysis revealed that the molecule crystallized in a triclinic system with space group Pī and the unit cell dimensions a= 12.2948(16) Å, b= 13.4423(17) Å, c= 13.5906(18) Å, α =107.549(4)°, β =102.034(4)°, γ =90.535(4)°, Z= 1 and V= 2088.2(5) Å{sup 3}. The macrocyclic calix adopts a chair (C{sub 2h}) conformation and the molecule is associated with eight DMSO molecules of crystallization. Antioxidant test by DPPH method showed that the compound exhibitsmore » good antioxidant activity of about 72%.« less

Enhanced liquid-liquid anion exchange using macrocyclic anion receptors: effect of receptor structure on sulphate-nitrate exchange selectivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moyer, Bruce A; Sloop Jr, Frederick; Fowler, Christopher J

2010-01-01

When certain macrocyclic anion receptors are added to a chloroform solution of the nitrate form of a lipophilic quaternary ammonium salt (methyltri-C8,10-ammonium nitrate, Aliquat 336N), the extraction of sulphate from an aqueous sodium nitrate solution via exchange with the organic-phase nitrate is significantly enhanced. Eight macrocycles were surveyed, including two derivatives of a tetraamide macrocycle, five derivatives of calix[4]pyrrole and -decafluorocalix[5]pyrrole. Under the hypothesis that the enhancement originates from sulphate binding by the anion receptors in the chloroform phase, it was possible to obtain reasonable fits to the sulphate distribution survey data based on the formation of 1:1 and 2:1more » receptor:sulphate complexes in the chloroform phase. Apparent 1:1 sulphate-binding constants obtained from the model in this system fell in the range . Comparison of the results for the various anion receptors included in this study reveals that sulphate binding is sensitive to the nature of the substituents on the parent macrocycle scaffolds in a way that does not follow straightforwardly from simple chemical expectations, such as electron-withdrawing effects on hydrogen-bond donor strength.« less

Reactions of copper macrocycles with antioxidants and HOCl: potential for biological redox sensing.

PubMed

Sowden, Rebecca J; Trotter, Katherine D; Dunbar, Lynsey; Craig, Gemma; Erdemli, Omer; Spickett, Corinne M; Reglinski, John

2013-02-01

A series of simple copper N(2)S(2) macrocycles were examined for their potential as biological redox sensors, following previous characterization of their redox potentials and crystal structures. The divalent species were reduced by glutathione or ascorbate at a biologically relevant pH in aqueous buffer. A less efficient reduction was also achieved by vitamin E in DMSO. Oxidation of the corresponding univalent copper species by sodium hypochlorite resulted in only partial (~65 %) recovery of the divalent form. This was concluded to be due to competition between metal oxidation and ligand oxidation, which is believed to contribute to macrocycle demetallation. Electrospray mass spectrometry confirmed that ligand oxidation had occurred. Moreover, the macrocyclic complexes could be demetallated by incubation with EDTA and bovine serum albumin, demonstrating that they would be inappropriate for use in biological systems. The susceptibility to oxidation and demetallation was hypothesized to be due to oxidation of the secondary amines. Consequently these were modified to incorporate additional oxygen donor atoms. This modification led to greater resistance to demetallation and ligand oxidation, providing a better platform for further development of copper macrocycles as redox sensors for use in biological systems.

Design, synthesis, and anaplastic lymphoma kinase (ALK) inhibitory activity for a novel series of 2,4,8,22-tetraazatetracyclo[14.3.1.1³,⁷.1⁹,¹³]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene macrocycles.

PubMed

Breslin, Henry J; Lane, Brandon M; Ott, Gregory R; Ghose, Arup K; Angeles, Thelma S; Albom, Mark S; Cheng, Mangeng; Wan, Weihua; Haltiwanger, R Curtis; Wells-Knecht, Kevin J; Dorsey, Bruce D

2012-01-12

A novel set of 2,4,8,22-tetraazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene macrocycles were prepared as potential anaplastic lymphoma kinase (ALK) inhibitors, designed to rigidly lock an energy-minimized bioactive conformation of the diaminopyrimidine (DAP) scaffold, a well-documented kinase platform. From 13 analogues prepared, macrocycle 2m showed the most promising in vitro ALK enzymatic (IC(50) = 0.5 nM) and cellular (IC(50) = 10 nM) activities. In addition, macrocycle 2m exhibited a favorable kinase selectivity preference for inhibition of ALK relative to the highly homologous insulin receptor (IR) kinase (IR/ALK ratio of 173). The inclusive in vitro biological results for this set of macrocycles validate this scaffold as a viable kinase template and further corroborate recent DAP/ALK solid state studies indicating that the inverted "U" shaped conformation of the acyclic DAPs is a preferred bioactive conformation.

Morphological studies on block copolymer modified PA 6 blends

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poindl, M., E-mail: marcus.poindl@ikt.uni-stuttgart.de, E-mail: christian.bonten@ikt.uni-stuttgart.de; Bonten, C., E-mail: marcus.poindl@ikt.uni-stuttgart.de, E-mail: christian.bonten@ikt.uni-stuttgart.de

Recent studies show that compounding polyamide 6 (PA 6) with a PA 6 polyether block copolymers made by reaction injection molding (RIM) or continuous anionic polymerization in a reactive extrusion process (REX) result in blends with high impact strength and high stiffness compared to conventional rubber blends. In this paper, different high impact PA 6 blends were prepared using a twin screw extruder. The different impact modifiers were an ethylene propylene copolymer, a PA PA 6 polyether block copolymer made by reaction injection molding and one made by reactive extrusion. To ensure good particle matrix bonding, the ethylene propylene copolymermore » was grafted with maleic anhydride (EPR-g-MA). Due to the molecular structure of the two block copolymers, a coupling agent was not necessary. The block copolymers are semi-crystalline and partially cross-linked in contrast to commonly used amorphous rubbers which are usually uncured. The combination of different analysis methods like atomic force microscopy (AFM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) gave a detailed view in the structure of the blends. Due to the partial cross-linking, the particles of the block copolymers in the blends are not spherical like the ones of ethylene propylene copolymer. The differences in molecular structure, miscibility and grafting of the impact modifiers result in different mechanical properties and different blend morphologies.« less

A New Microextraction Technique for the Assay of Alkaloids in Chinese Compound Formula-Based Polyether Sulfone Membrane Fiber Decorated by TiO2 Nanoparticles.

PubMed

Sun, Xinjie; Wei, Yingqin; Hou, Baojuan; Zhou, Guowei

2017-03-01

A new nanocomposite membrane was used to clean up impurities from complex samples and the obvious synergy was obtained in this paper. The nanocomposite membrane was prepared by dispersing TiO2 nanoparticles in chloroform and filled in the pores and lumen of polyether sulfone membrane fiber. The novel microextraction method showed the ideal selective extraction effect for alkaloids in the formulae composed of Rhizoma coptidis and the excellent clean-up efficiency compared with the single membrane method. The optimum extraction conditions were as follows: chloroform as accepted phase; the number of nanocomposite membrane fiber bars, 7; extraction time, 30 min; pH of the sample solution, 10.55; desorption solvent, methanol. The limit of detection for the described alkaloids was estimated at 0.122 μg mL-1. The recovery of the four alkaloids in complex samples ranged from 93.24% to 97.94% with relative standard deviation of <4.99 (n = 5). The validated method had been successfully applied to study the transfer rate of alkaloids in the producing process of Qihuang capsule and the ideal transfer rate of alkaloids was obtained in this paper. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Proof of Principle: Immobilisation of Robust CuII3 TbIII -Macrocycles on Small, Suitably Pre-functionalised Gold Nanoparticles.

PubMed

Feltham, Humphrey L C; Dumas, Christophe; Mannini, Matteo; Otero, Edwige; Sainctavit, Philippe; Sessoli, Roberta; Meledandri, Carla J; Brooker, Sally

2017-02-21

In a proof-of-principle study, a soluble macrocyclic single-molecule magnet (SMM) containing a Cu II 3 Tb III magnetic core was covalently grafted onto small gold nanoparticles pre-functionalised with carboxylate-terminated tethers. A modified microemulsion method allowed production of the small and monodisperse nanoparticles (approximately 3.5 nm in diameter) for the chemisorption of a large amount of intact macrocyclic complexes in the hybrid system. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo Study of the Accuracy of Dual-arch Impressions.

PubMed

de Lima, Luciana Martinelli Santayana; Borges, Gilberto Antonio; Junior, Luiz Henrique Burnett; Spohr, Ana Maria

2014-06-01

This study evaluated in vivo the accuracy of metal (Smart®) and plastic (Triple Tray®) dual-arch trays used with vinyl polysiloxane (Flexitime®), in the putty/wash viscosity, as well as polyether (Impregum Soft®) in the regular viscosity. In one patient, an implant-level transfer was screwed on an implant in the mandibular right first molar, serving as a pattern. Ten impressions were made with each tray and impression material. The impressions were poured with Type IV gypsum. The width and height of the pattern and casts were measured in a profile projector (Nikon). The results were submitted to Student's t-test for one sample (α = 0.05). For the width distance, the plastic dual-arch trays with vinyl polysiloxane (4.513 mm) and with polyether (4.531 mm) were statistically wider than the pattern (4.489 mm). The metal dual-arch tray with vinyl polysiloxane (4.504 mm) and with polyether (4.500 mm) did not differ statistically from the pattern. For the height distance, only the metal dual-arch tray with polyether (2.253 mm) differed statistically from the pattern (2.310 mm). The metal dual-arch tray with vinyl polysiloxane, in the putty/wash viscosities, reproduced casts with less distortion in comparison with the same technique with the plastic dual-arch tray. The plastic or metal dual-arch trays with polyether reproduced cast with greater distortion. How to cite the article: Santayana de Lima LM, Borges GA, Burnett LH Jr, Spohr AM. In vivo study of the accuracy of dual-arch impressions. J Int Oral Health 2014;6(3):50-5.

Zn2+ -Ion Sensing by Fluorescent Schiff Base Calix[4]arene Macrocycles.

PubMed

Ullmann, Steve; Schnorr, René; Handke, Marcel; Laube, Christian; Abel, Bernd; Matysik, Jörg; Findeisen, Matthias; Rüger, Robert; Heine, Thomas; Kersting, Berthold

2017-03-17

A macrocyclic ligand (H 2 L) containing two o,o'-bis(iminomethyl)phenol and two calix[4]arene head units has been synthesized and its coordination chemistry towards divalent Ni and Zn investigated. The new macrocycle forms complexes of composition [ML] (M=Zn, M=Ni) and [ZnL(py) 2 ], which were characterized by elemental analysis; IR, UV/Vis, and NMR spectroscopy; electrospray ionization mass spectrometry (ESI-MS); and X-ray crystallography (for [ZnL(py) 2 ] and [NiL]). H 2 L allows the sensitive optical detection of Zn 2+ among a series of biologically relevant metal ions by a dual fluorescence enhancement/quenching effect in solution. The fluorescence intensity of the macrocycle increases by a factor of ten in the presence of Zn 2+ with a detection limit in the lower nanomolar region. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recent Advances in Macrocyclic Fluorescent Probes for Ion Sensing.

PubMed

Wong, Joseph K-H; Todd, Matthew H; Rutledge, Peter J

2017-01-25

Small-molecule fluorescent probes play a myriad of important roles in chemical sensing. Many such systems incorporating a receptor component designed to recognise and bind a specific analyte, and a reporter or transducer component which signals the binding event with a change in fluorescence output have been developed. Fluorescent probes use a variety of mechanisms to transmit the binding event to the reporter unit, including photoinduced electron transfer (PET), charge transfer (CT), Förster resonance energy transfer (FRET), excimer formation, and aggregation induced emission (AIE) or aggregation caused quenching (ACQ). These systems respond to a wide array of potential analytes including protons, metal cations, anions, carbohydrates, and other biomolecules. This review surveys important new fluorescence-based probes for these and other analytes that have been reported over the past five years, focusing on the most widely exploited macrocyclic recognition components, those based on cyclam, calixarenes, cyclodextrins and crown ethers; other macrocyclic and non-macrocyclic receptors are also discussed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alfonso Hernandez, Laura; Nelson, Tammie Renee; Gelin, Maxim F.

The interchromophoric energy-transfer pathways between weakly coupled units in a π-conjugated phenylene–ethynylene macrocycle and its half-ring analogue have been investigated using the nonadiabatic excited-state molecular dynamics approach. To track the flow of electronic transition density between macrocycle units, we formulate a transition density flux analysis adapted from the statistical minimum flow method previously developed to investigate vibrational energy flow. Following photoexcitation, transition density is primarily delocalized on two chromophore units and the system undergoes ultrafast energy transfer, creating a localized excited state on a single unit. In the macrocycle, distinct chromophore units donate transition density to a single acceptor unitmore » but do not interchange transition density among each other. We find that energy transfer in the macrocycle is slower than in the corresponding half ring because of the presence of multiple interfering energy-transfer pathways. Finally, simulation results are validated by modeling the fluorescence anisotropy decay.« less

Response of a benzoxainone derivative linked to monoaza-15-crown-5 with divalent heavy metals.

PubMed

Addleman, R S; Bennett, J; Tweedy, S H; Elshani, S; Wai, C M

1998-08-01

The response of a monoaza-15-crown-5 with an optically active aminobenzoxazinone moiety to divalent cations was investigated. The crown ether was found to undergo a strong emission shift to the blue when complexed with specific divalent metals that have ionic diameters between 1.9-2.4 A. Consequently the photoactive macrocycle is responsive to Mg(2+), Ca(2+), Ba(2+), Sr(2+), Cd(2+), and particularly responsive to Hg(2+)and Pb(2+). Macrocycle emission spectra are shown to be a function of cation concentration. Alkaline metal cations and smaller transition metals ions such as Ni(2+), Co(2+)and Zn(2+)do not cause significant changes in the macrocycle emission spectra. Emission, absorption, and complex stability constants are determined. Mechanisms of cation selectivity and spectral emission shifts are discussed. Challenges involving immobilization of the macrocycle while preserving its spectral response to cations are explored.

Implant Failure After Motec Wrist Joint Prosthesis Due to Failure of Ball and Socket-Type Articulation-Two Patients With Adverse Reaction to Metal Debris and Polyether Ether Ketone.

PubMed

Karjalainen, Teemu; Pamilo, Konsta; Reito, Aleksi

2018-04-21

We describe 2 cases of articulation-related failures resulting in revision surgery after a Motec total wrist arthroplasty: one with an adverse reaction to metal debris and the other with an adverse reaction to polyether ether ketone. In the first patient, blood cobalt and chrome levels were elevated and magnetic resonance imaging showed clear signs of a pseudotumor. The other patient had an extensive release of polyether ether ketone particles into the surrounding synovia due to adverse wear conditions in the cup, leading to the formation of a fluid-filled cyst sac with a black lining and diffuse lymphocyte-dominated inflammation in the synovia. We recommend regular follow-up including x-rays, monitoring of cobalt and chrome ion levels, and a low threshold for cross-sectional imaging in patients who have undergone total wrist arthroplasty with a Motec joint prosthesis. Wear-related problems can also develop in implants in which polyether ether ketone is the bulk material. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Alanine analogues of [D-Trp]CJ-15,208: novel opioid activity profiles and prevention of drug- and stress-induced reinstatement of cocaine-seeking behaviour.

PubMed

Aldrich, J V; Senadheera, S N; Ross, N C; Reilley, K A; Ganno, M L; Eans, S E; Murray, T F; McLaughlin, J P

2014-07-01

The novel macrocyclic peptide cyclo[Phe-D-Pro-Phe-D-Trp] ([D-Trp]CJ-15,208) exhibits κ opioid (KOP) receptor antagonist activity in both in vitro and in vivo assays. The four alanine analogues of this peptide were synthesized and characterized both in vitro and in vivo to assess the contribution of different amino acid residues to the activity of [D-Trp]CJ-15,208. The peptides were synthesized by a combination of solid phase peptide synthesis and cyclization in solution. The analogues were evaluated in vitro in receptor binding and functional assays, and in vivo with mice using a tail-withdrawal assay for antinociceptive and opioid antagonist activity. Mice demonstrating extinction of cocaine conditioned-place preference (CPP) were pretreated with selected analogues to evaluate prevention of stress or cocaine-induced reinstatement of CPP. The alanine analogues displayed pharmacological profiles in vivo distinctly different from [D-Trp]CJ-15,208. While the analogues exhibited varying opioid receptor affinities and κ and μ opioid receptor antagonist activity in vitro, they produced potent opioid receptor-mediated antinociception (ED50 = 0.28-4.19 nmol, i.c.v.) in vivo. Three of the analogues also displayed KOP receptor antagonist activity in vivo. Pretreatment with an analogue exhibiting both KOP receptor agonist and antagonist activity in vivo prevented both cocaine- and stress-induced reinstatement of cocaine-seeking behaviour in the CPP assay in a time-dependent manner. These unusual macrocyclic peptides exhibit in vivo opioid activity profiles different from the parent compound and represent novel compounds for potential development as therapeutics for drug abuse and possibly as analgesics. © 2014 The British Pharmacological Society.

Alanine analogues of [D-Trp]CJ-15,208: novel opioid activity profiles and prevention of drug- and stress-induced reinstatement of cocaine-seeking behaviour

PubMed Central

Aldrich, J V; Senadheera, S N; Ross, N C; Reilley, K A; Ganno, M L; Eans, S E; Murray, T F; McLaughlin, J P

2014-01-01

BACKGROUND AND PURPOSE The novel macrocyclic peptide cyclo[Phe-D-Pro-Phe-D-Trp] ([D-Trp]CJ-15,208) exhibits κ opioid (KOP) receptor antagonist activity in both in vitro and in vivo assays. The four alanine analogues of this peptide were synthesized and characterized both in vitro and in vivo to assess the contribution of different amino acid residues to the activity of [D-Trp]CJ-15,208. EXPERIMENTAL APPROACH The peptides were synthesized by a combination of solid phase peptide synthesis and cyclization in solution. The analogues were evaluated in vitro in receptor binding and functional assays, and in vivo with mice using a tail-withdrawal assay for antinociceptive and opioid antagonist activity. Mice demonstrating extinction of cocaine conditioned-place preference (CPP) were pretreated with selected analogues to evaluate prevention of stress or cocaine-induced reinstatement of CPP. KEY RESULTS The alanine analogues displayed pharmacological profiles in vivo distinctly different from [D-Trp]CJ-15,208. While the analogues exhibited varying opioid receptor affinities and κ and μ opioid receptor antagonist activity in vitro, they produced potent opioid receptor-mediated antinociception (ED50 = 0.28–4.19 nmol, i.c.v.) in vivo. Three of the analogues also displayed KOP receptor antagonist activity in vivo. Pretreatment with an analogue exhibiting both KOP receptor agonist and antagonist activity in vivo prevented both cocaine- and stress-induced reinstatement of cocaine-seeking behaviour in the CPP assay in a time-dependent manner. CONCLUSIONS AND IMPLICATIONS These unusual macrocyclic peptides exhibit in vivo opioid activity profiles different from the parent compound and represent novel compounds for potential development as therapeutics for drug abuse and possibly as analgesics. PMID:24588614

Synthesis, spectroscopic, physicochemical and structural characterization of tetrandrine-based macrocycles functionalized with acridine and anthracene groups: DNA binding and anti-proliferative activity.

PubMed

Calvillo-Páez, Viviana; Sotelo-Mundo, Rogerio R; Leyva-Peralta, Mario; Gálvez-Ruiz, Juan Carlos; Corona-Martínez, David; Moreno-Corral, Ramón; Escobar-Picos, Raymundo; Höpfl, Herbert; Juárez-Sánchez, Octavio; Lara, Karen Ochoa

2018-04-25

In this work, we report on the synthesis of two new mono-alkylated tetrandrine derivatives with acridine and anthracene units, MAcT and MAnT. The compounds were fully characterized by physicochemical techniques and single-crystal X-ray diffraction analysis. In addition, both derivatives were studied as nucleotide receptors and double-stranded DNA binders in aqueous phosphate buffer at pH = 7.2 using UV-vis and fluorescence spectroscopy. According to the molecular recognition studies, MAcT and MAnT exhibit high affinity (K ∼ 10 5  M -1 ) and selectivity for ds-DNA, presumably in an intercalation mode. Finally, the anti-proliferative effects of the tetrandrine derivatives on different cancer cell lines were explored, revealing promising activities. Particularly, the mono-anthracene tetrandrine derivative MAnT showed an IC 50 of 2.74 μg/mL on the HeLa cervical cancer cell line, representing a value 3.3 times smaller than that obtained for unsubstituted tetrandrine. Examination of the cytotoxic effects on the HeLa cell line by inverted microscopy suggests that the cell death mechanism consists basically in apoptosis. The molecular modelling of three ds-DNA-MAcT complexes, suggested that the macrocycles may use an intercalation binding mode towards DNA. MAcT is predicted to bind into the major groove of the ds-DNA providing non-covalent interactions such as electrostatic, van der Waals and hydrophobic interactions that lead to selectivity. Overall experimental data supports the mode of action of MAnT and MAcT as cytotoxic compounds against cancer cell lines via a DNA interaction mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

Lanthanide paramagnetic probes for NMR spectroscopic studies of fast molecular conformational dynamics and temperature control. Effective six-site proton exchange in 18-crown-6 by exchange spectroscopy.

PubMed

Babailov, Sergey P

2012-02-06

(1)H and (13)C NMR measurements are reported for the CDCl(3) and CD(2)Cl(2) solutions of [La(18-crown-6)(NO(3))(3)] (I), [Pr(18-crown-6) (NO(3))(3)] (II), [Ce(18-crown-6)(NO(3))(3)] (III), and [Nd(18-crown-6)(NO(3))(3)] (IV) complexes. Temperature dependencies of the (1)H NMR spectra of paramagnetic II-IV have been analyzed using the dynamic NMR (DNMR) methods for six-site exchange. Two types of conformational dynamic processes were identified (the first one is conditioned by interconversion of complex enantiomeric forms and pseudorotation of a macrocycle molecule upon the C(2) symmetry axis; the second one is conditioned by macrocycle molecule inversion). Application of exchange spectroscopy (2D-EXSY) of DNMR for investigation of this dynamic system (II-IV) simplifies the assignment of the NMR signals and represents the first experimental study of multisite exchange. In the present work, the methodology of paramagnetic 4f (Ce, Pr, and Nd) probe applications for the study of free-energy, enthalpy, and entropy changes in chemical exchange processes, as well as the advantages of this method in a comparison with DNMR studies of diamagnetic substances, is discussed. In particular, as a result of paramagnetic chemical shifts in 4f complexes, the range of measurable rate constants expands considerably compared to the analogous range in diamagnetic compounds. Coordination compounds investigated in the paper represent new types of thermometric NMR sensors and lanthanide paramagnetic probes for in situ temperature control in solution.

Ciguatera poisoning.

PubMed

Achaibar, Kira C; Moore, Simon; Bain, Peter G

2007-10-01

Ciguatera is a form of poisoning that occurs after eating tropical and subtropical ciguatoxic fish. The ciguatoxins are a family of heat stable, lipid soluble cyclic polyether compounds that bind to and open voltage-sensitive Na(+) channels at resting membrane potential, resulting in neural hyperexcitability, as well as swelling of the nodes of Ranvier. The authors describe a 45-year-old man who developed acute gastrointestinal symptoms in Antigua soon after eating red snapper and grouper, potentially "ciguatoxic fish". This was followed by neurological symptoms 24-48 hours later, including temperature reversal (paradoxical dysaesthesia), intense pruritus and increased nociception as a result of a small fibre peripheral neuropathy. The patient's symptoms and small fibre neuropathy improved over a period of 10 months.

Process for making propenyl ethers and photopolymerizable compositions containing them

DOEpatents

Crivello, J.V.

1996-01-23

Propenyl ether monomers of formula A(OCH{double_bond}CHCH{sub 3}){sub n} (V) wherein n is an integer from one to six and A is selected from cyclic ethers, polyether, and alkanes are disclosed. The monomers are readily polymerized in the presence of cationic photoinitiators, when exposed to actinic radiation, to form poly(propenyl ethers) that are useful for coatings, sealants, varnishes and adhesives. Compositions for preparing polymeric coatings comprising the compounds of formula V together with particular cationic photoinitiators are also disclosed, as are processes for making the monomers from allyl halides and readily available alcohols. The process involves rearranging the resulting allyl ethers to propenyl ethers.

Synthesis and Detonation Properties of 5-Amino-2,4,6-trinitro-1,3-dihydroxy-benzene.

PubMed

Zhang, Xingcheng; Xiong, Hualin; Yang, Hongwei; Cheng, Guangbin

2017-06-01

5-Amino-4,6-dinitro-1,3-dihydroxy-benzene ( 6 ) was synthesized through the ring-opening reaction of macrocyclic compound  4 with the aid of VNS (vicarious nucleophilic substitution of hydrogen) reaction conditions. The mechanism of ring opening of macrocyclic compound  4 was studied. 5-Amino-2,4,6-trinitro-1,3-dihydroxy-benzene ( 8 ) was obtained after the nitration of 6 in KNO 3 and concentrated sulfuric acid. The thermal stability, sensitivity, and other detonation performances of 6 or 8 were compared to commercially used 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) or 1,3,5-trinitrotriazacyclohexane (RDX), respectively. All target compounds were characterized by using single-crystal X-ray diffraction, NMR spectroscopy, elemental analysis, and differential scanning calorimetry. The sensitivities were determined by using BAM methods (drop-hammer and friction tests). Performance parameters, including heats of formation and detonation properties, were calculated by using Gaussian 03 and EXPLO5 v6.01 programs, respectively. It is worth pointing out that compound  8 has a remarkable measured density of 2.078 g cm -3 at 298 K. In addition, compound  8 is more insensitive than RDX (compound  8 : IS =11 J; RDX: IS =7 J; IS is the impact sensitivity).

A macrocyclic polyamine as an anion receptor in the capillary electrochromatographic separation of carbohydrates.

PubMed

Liu, Chuen-Ying; Chen, Tse-Hsien; Misra, Tarun Kumar

2007-06-22

An analytical approach of the 32-membered macrocyclic polyamine, 1,5,9,13,17,21,25,29-octaazacyclodotriacontane ([32]ane-N8) was described for the capillary electrochromatographic (CEC) separation of derivatized mono- and disaccharides. The column displayed reversal electroosmotic flow (EOF) at pH below 7.0, while a cathodic EOF was shown at pH above 7.0. The reductive amination of saccharides was carried out with p-aminobenzoic acid. Some parameters that affect the CEC separations were investigated. Several competitive ligands, such as Tris, EDTA and phosphate were also examined for the effect on the performance. We achieved a complete separation of all compounds as well as the excess derivatizing agent by using borate buffer (pH 9.0) in a mode of concentration gradient (60 mM inlet side and 70 mM outlet side). The relative standard deviation of the retention time measured for each sample was less than 4% in six continuous runs, suggesting that the bonded phase along with the gradient formed inside the column was quite stable. With the mixing modes of anion coordination, anion exchange, and shape discrimination, the interaction adequately accomplishes the separation of carbohydrates which are epimers or have different glycosidic linkage, although the electrophoretic migration is also involved in the separation mechanism.

A Reliable Hybrid Adsorbent for Efficient Radioactive Cesium Accumulation from Contaminated Wastewater

PubMed Central

Awual, Md. Rabiul; Yaita, Tsuyoshi; Miyazaki, Yuji; Matsumura, Daiju; Shiwaku, Hideaki; Taguchi, Tomitsugu

2016-01-01

Cesium (Cs) removal from nuclear liquid wastewater has become an emerging issue for safeguarding public health after the accident at the Fukushima Daiichi Nuclear Power Plant. A novel macrocyclic ligand of o-benzo-p-xylyl-22-crown-6-ether (OBPX22C6) was developed and successfully immobilized onto mesoporous silica for the preparation of hybrid adsorbent. The benzene ring π electron is the part of crown ether of OBPX22C6 for easy orientation of the macrocyclic compound for making the π electron donation with Cs complexation. The potential and feasibility of the hybrid adsorbent as being Cs selective was evaluated in terms of sensitivity, selectivity and reusability. The results clarified that the Cs removal process was rapid and reached saturation within a short time. Considering the effect of competitive ions, sodium (Na) did not markedly affect the Cs adsorption whereas potassium (K) was slightly affected due to the similar ionic radii. However, the oxygen in long ethylene glycol chain in OBPX22C6 was expected to show strong coordination, including Cs-π interaction with Cs even in the presence of the high amount of K and Na. Due to its high selectivity and reusability, significant volume reduction is expected as this promising hybrid adsorbent is used for Cs removal in Fukushima wastewater. PMID:26818070

A Reliable Hybrid Adsorbent for Efficient Radioactive Cesium Accumulation from Contaminated Wastewater.

PubMed

Awual, Md Rabiul; Yaita, Tsuyoshi; Miyazaki, Yuji; Matsumura, Daiju; Shiwaku, Hideaki; Taguchi, Tomitsugu

2016-01-28

Cesium (Cs) removal from nuclear liquid wastewater has become an emerging issue for safeguarding public health after the accident at the Fukushima Daiichi Nuclear Power Plant. A novel macrocyclic ligand of o-benzo-p-xylyl-22-crown-6-ether (OBPX22C6) was developed and successfully immobilized onto mesoporous silica for the preparation of hybrid adsorbent. The benzene ring π electron is the part of crown ether of OBPX22C6 for easy orientation of the macrocyclic compound for making the π electron donation with Cs complexation. The potential and feasibility of the hybrid adsorbent as being Cs selective was evaluated in terms of sensitivity, selectivity and reusability. The results clarified that the Cs removal process was rapid and reached saturation within a short time. Considering the effect of competitive ions, sodium (Na) did not markedly affect the Cs adsorption whereas potassium (K) was slightly affected due to the similar ionic radii. However, the oxygen in long ethylene glycol chain in OBPX22C6 was expected to show strong coordination, including Cs-π interaction with Cs even in the presence of the high amount of K and Na. Due to its high selectivity and reusability, significant volume reduction is expected as this promising hybrid adsorbent is used for Cs removal in Fukushima wastewater.

Synthesis, spectroscopic studies and electrochemistry of palladium (II) macrocyclic complexes derived from a new tetraazahalogen substituted ligands by template method and their antimicrobial and pesticidal activities

NASA Astrophysics Data System (ADS)

Masih, Iffat; Fahmi, Nighat

2011-09-01

A new series of Pd(II) macrocyclic complexes have been synthesized by template condensation of bis(benzil)4-chloro 1,2-phenylenediamine (ML 1) and bis(benzil)4-fluro 1,2-phenylenediamine (ML 2) respectively, with appropriate diamine i.e. 1,2-phenylenediamine, 4-chloro 1,2-phenylenediamine and 4-fluro 1,2-phenylenediamine in the presence of PdCl 2 to form complexes of the type [Pd(C 40H 26N 4ClF)]Cl 2, [Pd(C 40H 27N 4X)]Cl 2 and [Pd(C 40H 26N 4X 2)]Cl 2, where X = Cl, F. The complexes have been characterized with the help of elemental analysis, IR, 1H NMR, electronic spectra, conductance measurement, magnetic susceptibility, cyclic voltammetry and X-ray powder diffraction studies. On the basis of these studies a square planar geometry has been proposed around the metal ion. The newly synthesized ligands and their complexes have been screened for antimicrobial and pesticidal activities. The results obtained from bioassays indicate that this class of compounds can be utilized for the design of new substance with pesticidal activity and promising antimicrobial activity.

How to synthesize macrocycles efficiently by using virtual combinatorial libraries.

PubMed

Storm, Ole; Lüning, Ulrich

2002-02-15

The selection of different diimines 4 a-c by alkaline earth ions from a virtual combinatorial library (VCL) is described. The products were stabilized by reduction to the diamines 6 a-c; this allowed easy analysis. The library can be directed toward different target molecules 6 a-c upon addition of alkaline earth ions with different radii. Competition experiments show the possibility of synthesizing the macrocycles 6 a, 6 b, and 6 c simultaneously when using Mg(2+), Ca(2+), and Ba(2+) as template ions. The scope of this thermodynamically controlled, reversible approach for macrocycle syntheses is illustrated.

Self-assembled photosynthesis-inspired light harvesting material and solar cells containing the same

DOEpatents

Lindsey, Jonathan S [Raleigh, NC; Chinnasamy, Muthiah [Raleigh, NC; Fan, Dazhong [Raleigh, NC

2009-12-15

A solar cell is described that comprises: (a) a semiconductor charge separation material; (b) at least one electrode connected to the charge separation material; and (c) a light-harvesting film on the charge separation material, the light-harvesting film comprising non-covalently coupled, self-assembled units of porphyrinic macrocycles. The porphyrinic macrocycles preferably comprise: (i) an intramolecularly coordinated metal; (ii) a first coordinating substituent; and (iii) a second coordinating substituent opposite the first coordinating substituent. The porphyrinic macrocycles can be assembled by repeating intermolecular coordination complexes of the metal, the first coordinating substituent and the second coordinating substituent.

Interlocked Photo-degradable Macrocycles Allow One-Off Photo-triggerable Gelation of Organo- and Hydrogelators.

PubMed

Tung, Shun-Te; Cheng, Hung-Te; Inthasot, Alex; Hsueh, Fang-Che; Gu, Ting-Jia; Yan, Pei-Cong; Lai, Chien-Chen; Chiu, Sheng-Hsien

2018-02-01

[2]Rotaxanes displaying one-off photo-triggerable gelation properties have been synthesized through the "clipping" of photo-degradable macrocycles around the amide or urea functionalities of organo- and hydrogelators. Irradiation with UV-light cleaved the photo-labile macrocyclic components from the [2]rotaxanes, resulting in the free gelators being released into solution and, thereafter, forming gels. When the rate of gelation was sufficiently rapid, selective gelation of specific regions of the solution-and, indeed, photo-patterning of the solution-was possible. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gas Sorption and Storage Properties of Calixarenes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patil, Rahul S.; Banerjee, Debasis; Atwood, Jerry L.

2016-12-01

Calixarenes, a class of organic macrocyclic molecules have shown interesting gas sorption properties towards industrially important gases such as carbon di-oxide, hydrogen, methane and acetylene. These macrocycles are involved in weak van der Waals interaction to form multidimensional supramolecular frameworks. The gas-diffusion and subsequent sorption occurs due to a cooperative behavior between neighboring macrocycles. Furthermore, the flexibility at the upper rim functional group also plays a key role in the overall gas uptake of calixarene. In this book chapter, we give a brief account of interaction and diffusion of gases in calixarene and selected derivatives.

Development of inexpensive metal macrocyclic complexes for use in fuel cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doddapaneni, N.; Ingersoll, D.; Kosek, J.A.

Several metal macrocyclic complexes were synthesized for use as catalysts in fuel cells. An initial evaluation of their ability to catalyze the fuel cell reactions were completed. Based on this initial evaluation, one metal macrocyclic catalyst was selected and long-term stability testing in a fuel cell was initiated. The fuel cell employing this catalyst was operated continuously for one year with little signs of catalyst degradation. The effect of synthetic reformates on the performance of the catalyst in the fuel cell environment also demonstrated high tolerance of this catalyst for common contaminants and poisons.

Martinomycin, a new polyether antibiotic produced by Streptomyces salvialis. I. Taxonomy, fermentation and biological activity.

PubMed

Bernan, V S; Montenegro, D A; Goodman, J J; Alluri, M R; Carter, G T; Abbanat, D R; Pearce, C J; Maiese, W M; Greenstein, M

1994-12-01

Actinomycete culture LL-D37187 has been found to produce the new polyether antibiotic martinomycin. Taxonomic studies, including morphological, physiological, and cell wall chemistry analyses, revealed that culture LL-D37187 is a novel streptomycete species, and the proposed name is Streptomyces salvialis. Martinomycin exhibits activity against the Southern Army Worm (Spodoptera eridania) and Gram-positive bacteria.

Total synthesis of complestatin: development of a Pd(0)-mediated indole annulation for macrocyclization.

PubMed

Shimamura, Hiroyuki; Breazzano, Steven P; Garfunkle, Joie; Kimball, F Scott; Trzupek, John D; Boger, Dale L

2010-06-09

Full details of the initial development and continued examination of a powerful intramolecular palladium(0)-mediated indole annulation for macrocyclization closure of the strained 16-membered biaryl ring system found in complestatin (1, chloropeptin II) and the definition of factors impacting its intrinsic atropodiastereoselectivity are described. Its examination and use in an alternative, second-generation total synthesis of complestatin are detailed in which the order of the macrocyclization reactions was reversed from our first-generation total synthesis. In this approach and with the ABCD biaryl ether ring system in place, the key Larock cyclization was conducted with substrate 36 (containing four phenols, five secondary amides, one carbamate, and four labile aryl chlorides) and provided the product 37 (56%) exclusively as a single atropisomer (>20:1, detection limits) possessing the natural (R)-configuration. In this instance, the complexity of the substrate and the reverse macrocyclization order did not diminish the atropodiastereoselectivity; rather, it provided an improvement over the 4:1 selectivity that was observed with the analogous substrate used to provide the isolated DEF ring system in our first-generation approach. Just as significant, the atroposelectivity represents a complete reversal of the diasteroselectivity observed with analogous macrocyclizations conducted using a Suzuki biaryl coupling.

Fabrication of reduced graphene oxide/macrocyclic cobalt complex nanocomposites as counter electrodes for Pt-free dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Tsai, Chih-Hung; Shih, Chun-Jyun; Wang, Wun-Shiuan; Chi, Wen-Feng; Huang, Wei-Chih; Hu, Yu-Chung; Yu, Yuan-Hsiang

2018-03-01

In this study, macrocyclic Co complexes were successfully grafted onto graphene oxide (GO) to produce GO/Co nanocomposites with a large surface area, high electrical conductivity, and excellent catalytic properties. The novel GO/Co nanocomposites were applied as counter electrodes for Pt-free dye-sensitized solar cells (DSSCs). Various ratios of macrocyclic Co complexes were used as the reductant to react with the GO, with which the surface functional groups of the GO were reduced and the macrocyclic ligand of the Co complexes underwent oxidative dehydrogenation, after which the conjugated macrocyclic Co systems were grafted onto the surface of the reduced GO to form GO/Co nanocomposites. The surface morphology, material structure, and composition of the GO/Co composites and their influences on the power-conversion efficiency of DSSC devices were comprehensively investigated. The results showed that the GO/Co (1:10) counter electrode (CE) exhibited an optimal power conversion efficiency of 7.48%, which was higher than that of the Pt CE. The GO/Co (1:10) CE exhibited superior electric conductivity, catalytic capacity, and redox capacity. Because GO/Co (1:10) CEs are more efficient and cheaper than Pt CEs, they could potentially be used as a replacement for Pt electrodes.

Concurrent treatment with a macrocyclic lactone and benzimidazole provides season long performance advantages in grazing cattle harboring macrocyclic lactone resistant nematodes.

PubMed

Edmonds, M D; Vatta, A F; Marchiondo, A A; Vanimisetti, H B; Edmonds, J D

2018-03-15

In 2013, a 118-day study was initiated to investigate the efficacy of concurrent treatment at pasture turnout with an injectable macrocyclic lactone with activity up to 28 days and an oral benzimidazole, referred to as "conventional" anthelmintics, when compared to treatment with conventional macrocyclic lactone alone or an injectable macrocyclic lactone with extended activity of 100 days or longer. A group of 210 steers were obtained from a ranch in California and transported to Idaho, USA. A total of 176 steers with the highest fecal egg counts were blocked by pre-treatment body weights and pasture location. A total of 44 pasture paddocks were assigned with 4 steers per paddock with 12 paddocks per therapeutic treatment group and 8 paddocks per controls. The four treatments were injectable doramectin (Dectomax ® , Zoetis Inc., 0.2 mg kg -1 BW, SC), injectable doramectin concurrently with oral albendazole (Valbazen ® , Zoetis Inc., 10 mg kg -1 BW, PO), extended release injectable eprinomectin (LongRange™, Merial Limited, 1 mg kg -1 BW, SC) or saline. Cattle were individually weighed and sampled for fecal egg count on Days 0, 31/32, 61, 88, and 117/118 with an additional fecal sample on Day 14. At conclusion, one steer per paddock was euthanized for nematode recovery. The results from the first 32 days found evidence of macrocyclic lactone resistance against injectable doramectin and extended release eprinomectin. During this period the concurrent therapy provided nearly 100% efficacy based on fecal egg count reduction and a 19.98% improvement in total weight gain compared to controls (P = 0.039). At the conclusion of the 118-day study and past the approved efficacy for the conventional anthelmintics, the concurrent therapy with conventional anthelmintics provided a 22.98% improvement in total weight gain compared to controls (P = 0.004). The 118-day improvement in weight gain for the extended release eprinomectin group (29.06% compared to control) was not statistically different from the concurrent therapy with conventional anthelmintics. The results indicate that concurrent treatment with a conventional macrocyclic lactone and benzimidazole may provide production benefits early in the grazing period that continue throughout the entire period for cattle harboring macrocyclic lactone resistant nematodes. By using two different anthelmintic classes together, macrocyclic lactone resistant parasites were effectively controlled early in the period. Furthermore, the use of an effective conventional anthelmintic treatment regimen without an extended period of drug release may help to promote refugia and decrease the further selection for anthelmintic resistant parasites. Copyright © 2018 Elsevier B.V. All rights reserved.

Oxidation reaction of polyether-based material and its suppression in lithium rechargeable battery using 4 V class cathode, LiNi1/3Mn1/3Co1/3O2.

PubMed

Kobayashi, Takeshi; Kobayashi, Yo; Tabuchi, Masato; Shono, Kumi; Ohno, Yasutaka; Mita, Yuichi; Miyashiro, Hajime

2013-12-11

The all solid-state lithium battery with polyether-based solid polymer electrolyte (SPE) is regarded as one of next-generation lithium batteries, and has potential for sufficient safety because of the flammable-electrolyte-free system. It has been believed that polyether-based SPE is oxidized at the polymer/electrode interface with 4 V class cathodes. Therefore, it has been used for electric devices such as organic transistor, and lithium battery under 3 V. We estimated decomposition reaction of polyether used as SPE of all solid-state lithium battery. We first identified the decomposed parts of polyether-based SPE and the conservation of most main chain framework, considering the results of SPE analysis after long cycle operations. The oxidation reaction was found to occur slightly at the ether bond in the main chain with the branched side chain. Moreover, we resolved the issue by introducing a self-sacrificing buffer layer at the interface. The introduction of sodium carboxymethyl cellulose (CMC) to the 4 V class cathode surface led to the suppression of SPE decomposition at the interface as a result of the preformation of a buffer layer from CMC, which was confirmed by the irreversible exothermic reaction during the first charge, using electrochemical calorimetry. The attained 1500 cycle operation is 1 order of magnitude longer than those of previously reported polymer systems, and compatible with those of reported commercial liquid systems. The above results indicate to proceed to an intensive research toward the realization of 4 V class "safe" lithium polymer batteries without flammable liquid electrolyte.

Photochemical electron transfer in chlorophyll-porphyrin-quinone triads. The role of the porphyrin-bridging molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, D.G.; Niemczyk, M.P.; Minsek, D.W.

1993-06-30

The photochemistry of four chlorophyll-porphyrin-naphthoquinone molecules possessing both fixed distances and orientations between the three components is described. These molecules consist of a methyl pyropheophorbide a or pyrochlorophyllide a that is directly bonded at its 3-position to the 5-position of a 2,8,12,18-tetraethyl-3,7,13,-17-tetramethylporphyrin, which is in turn bonded at its 15-position to a 2-triptycenenaphthoquinone. In addition, porphyrin-quinone compounds in which the chlorins are replaced by a p-tolyl group were also prepared as reference compounds. Selective metalation of the macrocycles with zinc gives the series ZCHPNQ, ZCZPNQ, HCZPNQ, HCHPNQ, HPNQ, and ZPNQ, where H, Z, C, P, and NQ denote free base,more » Zn derivative, chlorophyll, porphyrin, and naphthoquinone, respectively. Selective excitation of ZC in ZCZPNQ and ZCHPNQ, and HC in HCHPNQ dissolved in butyronitrile yields ZC[sup +]ZPNQ[sup [minus

Photochemical and Photophysical Properties of Phthalocyanines Modified with Optically Active Alcohols.

PubMed

Ramos, Aline A; Nascimento, Francisco B; de Souza, Thaiza F M; Omori, Alvaro T; Manieri, Tânia M; Cerchiaro, Giselle; Ribeiro, Anderson O

2015-07-24

Three phthalocyanine derivatives were synthesized and characterized: one modified with a racemic mixture of 1-(4-bromophenyl)ethanol and two other macrocycles modified with each one of the enantioenriched isomers (R)-1-(4-bromophenyl)ethanol and (S)-1-(4-bromophenyl)ethanol. The compounds were characterized by 1H-NMR spectroscopy, mass spectrometry, UV-Vis absorption, and excitation and emission spectra. Additionally, partition coefficient values and the quantum yield of the generation of oxygen reactive species were determined. Interestingly, the phthalocyanine containing a (R)-1-(4-bromophenyl)ethoxy moiety showed higher quantum yield of reactive oxygen species generation than other compounds under the same conditions. In addition, the obtained fluorescence microscopy and cell viability results have shown that these phthalocyanines have different interactions with mammary MCF-7 cells. Therefore, our results indicate that the photochemical and biological properties of phthalocyanines with chiral ligands should be evaluated separately for each enantiomeric species.

Functionalization of Carbon Spheres with a Porphyrin-Ferrocene Dyad.

PubMed

Possanza, Fabio; Limosani, Francesca; Tagliatesta, Pietro; Zanoni, Robertino; Scarselli, Manuela; Ciotta, Erica; Pizzoferrato, Roberto

2018-05-21

Meso-tetraphenylporphyrin connected with a ferrocene molecule in the beta-position of the macrocycle through a triple carbon-carbon bond has been bound to carbon spheres using the Prato-Maggini reaction. The ethynyl or/and phenylene ethynylene subunits were chosen as a linking bridge to give a high conjugation degree between the donor (i. e., ferrocene), the photoactive compound (i. e., porphyrin), and the acceptor (i. e., carbon spheres). The molecular bridges have been directly linked to the beta-pyrrole positions of the porphyrin ring, generating a new example of a long-range donor-acceptor system. Steady-state fluorescence studies together with Raman and XPS measurements helped understanding the chemical and physical properties of the porphyrin ring in the new adduct. The spectroscopic characteristics were also compared with those obtained from a similar compound bearing fullerene instead of carbon spheres. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and characterization of Ni(II) complex with 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium bromide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yusoff, Latifah M.; Yusoff, Siti Fairus M.; Ismail, Wafiuddin

Nickel(II) complex have been synthesized by treating a 14-membered ring tetraaza macrocyclic compound, 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-dienium, bromide (Me{sub 6}N{sub 4}H{sub 4})Br{sub 2} with nickel acetate in metanol. The complex was characterized using elemental analysis, Fourier Transform Infrared (FTIR), Ultraviolet-Visible (UV-Vis), and single crystal diffraction (X-ray). The nickel atom coordinates through four nitrogen atoms in the ligand. Square planar geometry has been proposed for this complex.

Porphyrinoids as a platform of stable radicals

PubMed Central

Shimizu, Daiki

2018-01-01

The non-innocent ligand nature of porphyrins was observed for compound I in enzymatic cycles of cytochrome P450. Such porphyrin radicals were first regarded as reactive intermediates in catabolism, but recent studies have revealed that porphyrinoids, including porphyrins, ring-contracted porphyrins, and ring-expanded porphyrins, display excellent radical-stabilizing abilities to the extent that radicals can be handled like usual closed-shell organic molecules. This review surveys four types of stable porphyrinoid radical and covers their synthetic methods and properties such as excellent redox properties, NIR absorption, and magnetic properties. The radical-stabilizing abilities of porphyrinoids stem from their unique macrocyclic conjugated systems with high electronic and structural flexibilities. PMID:29675188

Optimisation of dynamic nuclear polarisation of [1-13C] pyruvate by addition of gadolinium-based contrast agents

NASA Astrophysics Data System (ADS)

Friesen-Waldner, Lanette; Chen, Albert; Mander, Will; Scholl, Timothy J.; McKenzie, Charles A.

2012-10-01

Dynamic nuclear polarisation (DNP) of carbon-13 (13C) enriched endogenous compounds provides a novel means for magnetic resonance imaging and spectroscopy of biological processes. Adding small amounts of gadolinium-based contrast agents (GBCAs) to the 13C-enriched substrate matrix increases the amount of hyperpolarisation that can be achieved, but also may decrease the longitudinal relaxation time (T1) of the 13C nucleus in solution. This study examined the effects of five different GBCA at concentrations of 0.5, 1, 2, and 3 mM on [1-13C]-enriched pyruvic acid. It was found that contrast agents with an open chain structure (Gadobenate dimeglumine, Gadopentetate dimeglumine, Gadodiamide) caused the largest enhancement (up to 82%) in solid state polarisation relative to solutions without GBCA. In the liquid state, T1 of pyruvate decreased by as much as 62% and polarisation was much lower (70%) relative to solutions without GBCA added. Conversely, for GBCA with macrocyclic structures (Gadoterate meglumine, Gadoteridol), the solid state polarisation enhancement was only slightly less than the open chain GBCA, but enhanced polarisation was retained much better in the liquid state with minimal decrease in T1 (25% at the highest GBCA concentrations). Near maximum polarisation in the solid state was obtained at a GBCA concentration of 2 mM, with a higher concentration of 3 mM producing minimal improvement. These results indicate that the macrocyclic contrast agents provide the best combination of high solid state and liquid state polarisations with minimal loss of T1 in experiments with hyperpolarised 13C-enriched pyruvate. This suggests that macrocyclic contrast agents should be the GBCA of choice for maximising signal in experiments with hyperpolarised 13C-enriched pyruvate, particularly for in vivo measurements where shortened substrate T1 is especially problematic.

Preparation and Characterization of Various Poly(ether ether ketone) Containing Imidazolium Moiety for Anion Exchange Membrane Fuel Cell Application.

PubMed

Lee, Byeol-Nim; Son, Tae Yang; Park, Chi Hoon; Kim, Tae Hyun; Nam, Sang Yong

2018-09-01

In this study, various poly(ether ether ketone) were synthesized using three different monomers and the imidazolium group was introduced into synthesized poly(ether ether ketone)s by using substitution reaction. Synthesized polymers were used to prepare anion exchange membranes and to evaluate its properties. Thermal, chemical and structural properties were carried out using thermogravimetric analysis, nuclear magnetic resonance. The anion exchange membranes with different imidazolium moieties were characterized by several different analytical techniques such as water up take, ion exchange capacity, hydroxide conductivity for checking the possibility to apply the anion exchange membrane fuel cell. Consequently, results of characterization were studied to understand the correlation between stabilities of the membrane and functional group and polymer backbone structures. And we confirm membrane performance was improved by increasing imidazolium cation groups.

Applicable research in practice: understanding the hydrophilic and flow property measurements of impression materials.

PubMed

Perry, Ronald D; Goldberg, Jeffrey A; Benchimol, Jacques; Orfanidis, John

2006-10-01

The flow properties and hydrophilicity of an impression material are key factors that affect its performance. This article details in vitro studies comparing these properties in 1 polyether and several vinyl polysiloxane light-body impression materials. The first series of studies examined the materials' flow properties used in a "shark fin" measurement procedure to determine which exhibited superior flow characteristics. The second series of studies reviewed the hydrophilic properties of the materials. Video analysis was used to record contact angle measurements at the early- and late-stage working times. Results showed 1 polyether material to be more hydrophilic. Applying this knowledge to practice, the authors present a clinical case in which a polyether's superior flow and quality of detail were used to make impressions for a patient receiving 8 single-unit zirconia crowns.

m-Diethynylbenzene macrocycles: syntheses and self-association behavior in solution.

PubMed

Tobe, Yoshito; Utsumi, Naoto; Kawabata, Kazuya; Nagano, Atsushi; Adachi, Kiyomi; Araki, Shunji; Sonoda, Motohiro; Hirose, Keiji; Naemura, Koichiro

2002-05-15

m-Diethynylbenzene macrocycles (DBMs), buta-1,3-diyne-bridged [4(n)]metacyclophanes, have been synthesized and their self-association behaviors in solution were investigated. Cyclic tetramers, hexamers, and octamers of DBMs having exo-annular octyl, hexadecyl, and 3,6,9-trioxadecyl ester groups were prepared by intermolecular oxidative coupling of dimer units or intramolecular cyclization of the corresponding open-chain oligomers. The aggregation properties were investigated by two methods, the (1)H NMR spectra and the vapor pressure osmometry (VPO). Although some discrepancies were observed between the association constants obtained from the two methods, the qualitative view was consistent with each other. The analysis of self-aggregation by VPO revealed unique aggregation behavior of DBMs in acetone and toluene, which was not elucidated by the NMR method. Namely, the association constants for infinite association are several times larger than the dimerization constant, suggesting that the aggregation is enhanced by the formation of dimers (a nucleation mechanism). In polar solvents, DBMs aggregate more strongly than in chloroform due to the solvophobic interactions between the macrocyclic framework and the solvents. Moreover, DBMs self-associate in aromatic solvents such as toluene and o-xylene more readily than in chloroform. In particular, the hexameric DBM having a large macrocyclic cavity exhibits extremely large association constants in aromatic solvents. By comparing the aggregation properties of DBMs with the corresponding acyclic oligomers, the effect of the macrocyclic structure on the aggregation propensity was clarified. Finally, it turned out that DBMs tend to aggregate more readily than the corresponding phenylacetylene macrocycles, acetylene-bridged [2(n)]metacyclophanes, owing to the withdrawal of the electron density from the aromatic rings by the butadiyne linkages which facilitates pi-pi stacking interactions.

Solubility of polyethers in hydrocarbons at low temperatures. A model for potential genetic backbones on warm titans.

PubMed

McLendon, Christopher; Opalko, F Jeffrey; Illangkoon, Heshan I; Benner, Steven A

2015-03-01

Ethers are proposed here as the repeating backbone linking units in linear genetic biopolymers that might support Darwinian evolution in hydrocarbon oceans. Hydrocarbon oceans are found in our own solar system as methane mixtures on Titan. They may be found as mixtures of higher alkanes (propane, for example) on warmer hydrocarbon-rich planets in exosolar systems ("warm Titans"). We report studies on the solubility of several short polyethers in propane over its liquid range (from 85 to 231 K, or -188 °C to -42 °C). These show that polyethers are reasonably soluble in propane at temperatures down to ca. 200 K. However, their solubilities drop dramatically at still lower temperatures and become immeasurably low below 170 K, still well above the ∼ 95 K in Titan's oceans. Assuming that a liquid phase is essential for any living system, and genetic biopolymers must dissolve in that biosolvent to support Darwinism, these data suggest that we must look elsewhere to identify linear biopolymers that might support genetics in Titan's surface oceans. However, genetic molecules with polyether backbones may be suitable to support life in hydrocarbon oceans on warm Titans, where abundant organics and environments lacking corrosive water might make it easier for life to originate.

Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis.

PubMed

Hotta, Kinya; Chen, Xi; Paton, Robert S; Minami, Atsushi; Li, Hao; Swaminathan, Kunchithapadam; Mathews, Irimpan I; Watanabe, Kenji; Oikawa, Hideaki; Houk, Kendall N; Kim, Chu-Young

2012-03-04

Polycyclic polyether natural products have fascinated chemists and biologists alike owing to their useful biological activity, highly complex structure and intriguing biosynthetic mechanisms. Following the original proposal for the polyepoxide origin of lasalocid and isolasalocid and the experimental determination of the origins of the oxygen and carbon atoms of both lasalocid and monensin, a unified stereochemical model for the biosynthesis of polyether ionophore antibiotics was proposed. The model was based on a cascade of nucleophilic ring closures of postulated polyepoxide substrates generated by stereospecific oxidation of all-trans polyene polyketide intermediates. Shortly thereafter, a related model was proposed for the biogenesis of marine ladder toxins, involving a series of nominally disfavoured anti-Baldwin, endo-tet epoxide-ring-opening reactions. Recently, we identified Lsd19 from the Streptomyces lasaliensis gene cluster as the epoxide hydrolase responsible for the epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A. Here we report the X-ray crystal structure of Lsd19 in complex with its substrate and product analogue to provide the first atomic structure-to our knowledge-of a natural enzyme capable of catalysing the disfavoured epoxide-opening cyclic ether formation. On the basis of our structural and computational studies, we propose a general mechanism for the enzymatic catalysis of polyether natural product biosynthesis. © 2012 Macmillan Publishers Limited. All rights reserved

Interpreting medium ring canonical conformers by a triangular plane tessellation of the macrocycle

NASA Astrophysics Data System (ADS)

Khalili, Pegah; Barnett, Christopher B.; Naidoo, Kevin J.

2013-05-01

Cyclic conformational coordinates are essential for the distinction of molecular ring conformers as the use of Cremer-Pople coordinates have illustrated for five- and six-membered rings. Here, by tessellating medium rings into triangular planes and using the relative angles made between triangular planes we are able to assign macrocyclic pucker conformations into canonical pucker conformers such as chairs, boats, etc. We show that the definition is straightforward compared with other methods popularly used for small rings and that it is computationally simple to implement for complex macrocyclic rings. These cyclic conformational coordinates directly couple to the motion of individual nodes of a ring. Therefore, they are useful for correlating the physical properties of macrocycles with their ring pucker and measuring the dynamic ring conformational behavior. We illustrate the triangular tessellation, assignment, and pucker analysis on 7- and 8-membered rings. Sets of canonical states are given for cycloheptane and cyclooctane that have been previously experimentally analysed.

Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization

PubMed Central

2018-01-01

Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that bypasses current limitations in conformational sampling and extensively profiles the free energy landscape of peptidic macrocycles in solution. We perform accelerated molecular dynamics simulations to capture a diverse conformational ensemble. By applying an energetic cutoff, followed by geometric clustering, we demonstrate the striking robustness and efficiency of the approach in identifying highly populated conformational states of cyclic peptides. The resulting structural and thermodynamic information is benchmarked against interproton distances from NMR experiments and conformational states identified by X-ray crystallography. Using three different model systems of varying size and flexibility, we show that the method reliably reproduces experimentally determined structural ensembles and is capable of identifying key conformational states that include the bioactive conformation. Thus, the described approach is a robust method to generate conformations of peptidic macrocycles and holds promise for structure-based drug design. PMID:29652495

Templated bilayer self-assembly of fully conjugated π-expanded macrocyclic oligothiophenes complexed with fullerenes

PubMed Central

Cojal González, José D.; Iyoda, Masahiko; Rabe, Jürgen P.

2017-01-01

Fully conjugated macrocyclic oligothiophenes exhibit a combination of highly attractive structural, optical and electronic properties, and multifunctional molecular thin film architectures thereof are envisioned. However, control over the self-assembly of such systems becomes increasingly challenging, the more complex the target structures are. Here we show a robust self-assembly based on hierarchical non-covalent interactions. A self-assembled monolayer of hydrogen-bonded trimesic acid at the interface between an organic solution and graphite provides host-sites for the epitaxial ordering of Saturn-like complexes of fullerenes with oligothiophene macrocycles in mono- and bilayers. STM tomography verifies the formation of the templated layers. Molecular dynamics simulations corroborate the conformational stability and assign the adsorption sites of the adlayers. Scanning tunnelling spectroscopy determines their rectification characteristics. Current–voltage characteristics reveal the modification of the rectifying properties of the macrocycles by the formation of donor–acceptor complexes in a densely packed all-self-assembled supramolecular nanostructure. PMID:28281557

Lysine-Tryptophan-Crosslinked Peptides Produced by Radical SAM Enzymes in Pathogenic Streptococci.

PubMed

Schramma, Kelsey R; Seyedsayamdost, Mohammad R

2017-04-21

Macrocycles represent a common structural framework in many naturally occurring peptides. Several strategies exist for macrocyclization, and the enzymes that incorporate them are of great interest, as they enhance our repertoire for creating complex molecules. We recently discovered a new peptide cyclization reaction involving a crosslink between the side chains of lysine and tryptophan that is installed by a radical SAM enzyme. Herein, we characterize relatives of this metalloenzyme from the pathogens Streptococcus agalactiae and Streptococcus suis. Our results show that the corresponding enzymes, which we call AgaB and SuiB, contain multiple [4Fe-4S] clusters and catalyze Lys-Trp crosslink formation in their respective substrates. Subsequent high-resolution-MS and 2D-NMR analyses located the site of macrocyclization. Moreover, we report that AgaB can accept modified substrates containing natural or unnatural amino acids. Aside from providing insights into the mechanism of this unusual modification, the substrate promiscuity of AgaB may be exploited to create diverse macrocyclic peptides.

Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization.

PubMed

Kamenik, Anna S; Lessel, Uta; Fuchs, Julian E; Fox, Thomas; Liedl, Klaus R

2018-05-29

Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that bypasses current limitations in conformational sampling and extensively profiles the free energy landscape of peptidic macrocycles in solution. We perform accelerated molecular dynamics simulations to capture a diverse conformational ensemble. By applying an energetic cutoff, followed by geometric clustering, we demonstrate the striking robustness and efficiency of the approach in identifying highly populated conformational states of cyclic peptides. The resulting structural and thermodynamic information is benchmarked against interproton distances from NMR experiments and conformational states identified by X-ray crystallography. Using three different model systems of varying size and flexibility, we show that the method reliably reproduces experimentally determined structural ensembles and is capable of identifying key conformational states that include the bioactive conformation. Thus, the described approach is a robust method to generate conformations of peptidic macrocycles and holds promise for structure-based drug design.

Templated bilayer self-assembly of fully conjugated π-expanded macrocyclic oligothiophenes complexed with fullerenes

NASA Astrophysics Data System (ADS)

Cojal González, José D.; Iyoda, Masahiko; Rabe, Jürgen P.

2017-03-01

Fully conjugated macrocyclic oligothiophenes exhibit a combination of highly attractive structural, optical and electronic properties, and multifunctional molecular thin film architectures thereof are envisioned. However, control over the self-assembly of such systems becomes increasingly challenging, the more complex the target structures are. Here we show a robust self-assembly based on hierarchical non-covalent interactions. A self-assembled monolayer of hydrogen-bonded trimesic acid at the interface between an organic solution and graphite provides host-sites for the epitaxial ordering of Saturn-like complexes of fullerenes with oligothiophene macrocycles in mono- and bilayers. STM tomography verifies the formation of the templated layers. Molecular dynamics simulations corroborate the conformational stability and assign the adsorption sites of the adlayers. Scanning tunnelling spectroscopy determines their rectification characteristics. Current-voltage characteristics reveal the modification of the rectifying properties of the macrocycles by the formation of donor-acceptor complexes in a densely packed all-self-assembled supramolecular nanostructure.

Chiral Recognition with Macrocyclic Glycopeptides: Mechanisms and Applications

NASA Astrophysics Data System (ADS)

Berthod, Alain; Qiu, Hai Xiao; Staroverov, Sergey M.; Kuznestov, Mikhail A.; Armstrong, Daniel W.

The macrocyclic glycopeptide chiral selectors are natural molecules produced by bacterial fermentation. Purified and bonded to silica particles, they make very useful chiral stationary phases (CSP) with a broad spectrum of applicability in enantiomeric separation. The macrocyclic glycopeptide CSPs are multimodal, the same column being able to work in normal phase mode with apolar mobile phase, in reversed-phase mode, or in polar ionic mode with 100% alcoholic mobile phase of adjusted pH. The role of the carbohydrate units is described as well as the critical charge-charge docking interaction responsible for the amino acid enantiomer recognition. The complimentary phenomenon is also exposed.

A Macrocyclic β-Iodoallenolate Intermediate is Key: Synthesis of the ABD Core of Phomactin A

PubMed Central

Ciesielski, Jennifer; Cariou, Kevin

2012-01-01

An enantioselective strategy for the synthesis of phomactin natural products is described. The Lewis acid-triggered cyclization of a β-iodoallenolate embedded in a 12-membered macrocycle was used to obtain a highly functionalized bicyclo[9.3.1]pentadecane in good yield and high diastereoselectivity. This iodoenone contains the substituents of the AD ring system of the phomactin family of natural products, appropriate for further functionalization. Synthesis of the oxadecalin core of phomactin A from the AD iodoenone intermediate was achieved. In this unusual strategy, rings A and B are both fashioned within a macrocyclic precursor. PMID:22853449

Development of a matrix-assisted laser desorption ionization mass spectrometric method for rapid process-monitoring of phthalocyanine compounds.

PubMed

Chen, Yi-Ting; Wang, Fu-Shing; Li, Zhendong; Li, Liang; Ling, Yong-Chien

2012-07-29

Phthalocyanines (PCs), an important class of chemicals widely used in many industrial sectors, are macrocyclic compounds possessing a heteroaromatic π-electron system with optical properties influenced by chemical structures and impurities or by-products introduced during the synthesis process. Analytical tools allowing for rapid monitoring of the synthesis processes are of significance for the development of new PCs with improved performance in many application areas. In this work, we report a matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOFMS) method for rapid and convenient monitoring of PC synthesis reactions. For this class of compounds, intact molecular ions could be detected by MALDI using retinoic acid as matrix. It was shown that relative quantification results of two PC compounds could be generated by MALDI MS. This method was applied to monitor the bromination reactions of nickel- and copper-containing PCs. It was demonstrated that, compared to the traditional UV-visible method, the MALDI MS method offers the advantage of higher sensitivity while providing chemical species and relative quantification information on the reactants and products, which are crucial to process monitoring. Copyright © 2012 Elsevier B.V. All rights reserved.

Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

PubMed

Radbruch, Alexander; Weberling, Lukas D; Kieslich, Pascal J; Hepp, Johanna; Kickingereder, Philipp; Wick, Wolfgang; Schlemmer, Heinz-Peter; Bendszus, Martin

2016-11-01

Recent studies reported an increase in the dentate nucleus (DN)-to-pons signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images in patients who received consecutive serial injections of linear gadolinium-based contrast agents (GBCAs). In contrast, most studies found no increase in the DN-pons SI ratio when patients were treated with consecutive serial injections of macrocyclic GBCAs. However, the potential difference between macrocyclic and linear GBCAs has never been assessed in individuals who received subsequent applications of both contrast agents. In this retrospective study, we assessed the evolution of the DN-pons SI ratio change in patients that were treated with a comparable number of serial consecutive injections of the linear GBCA gadopentetate dimeglumine and subsequent serial injections of the macrocyclic GBCAs gadobutrol and gadoterate meglumine. Data of 36 patients was analyzed. All patients underwent at least 5 consecutive administrations of the linear GBCA gadopentetate dimeglumine followed by an equal number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12 of the 36 patients, 5 or more final consecutive injections of the macrocyclic GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons SI ratios on unenhanced T1-weighted images was calculated by subtracting the ratio at the first examination from the ratio at the last examination in each of the 3 periods. The mean DN-pons SI ratio difference in the gadopentetate dimeglumine period was significantly greater than 0 (mean ± SD, 0.0448 ± 0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the subsequent gadobutrol and gadoterate meglumine period was significantly smaller than 0 (gadobutrol: -0.0178 ± 0.0459, P = 0.026; gadoterate meglumine: -0.0250 ± 0.0284, P = 0.011). In this observational study, the application of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI ratio increase, whereas subsequent applications of the macrocyclic GBCAs gadobutrol or gadoterate meglumine in the same patients were not. Rather, the current data tentatively suggest a decrease in preexisting hyperintensities over time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a washout effect or precipitation of gadolinium. Future patient studies need to include control groups to replicate the present results, and additional animal studies should be conducted to clarify the underlying mechanism of the proposed SI decrease.

Photoswitchable Dihydroazulene Macrocycles for Solar Energy Storage: The Effects of Ring Strain.

PubMed

Vlasceanu, Alexandru; Frandsen, Benjamin N; Skov, Anders B; Hansen, Anne Schou; Rasmussen, Mads Georg; Kjaergaard, Henrik G; Mikkelsen, Kurt V; Nielsen, Mogens Brøndsted

2017-10-06

Efficient energy storage and release are two major challenges of solar energy harvesting technologies. The development of molecular solar thermal systems presents one approach to address these issues by tuning the isomerization reactions of photo/thermoswitches. Here we show that the incorporation of photoswitches into macrocyclic structures is a particularly attractive solution for increasing the storage time. We present the synthesis and properties of a series of macrocycles incorporating two dihydroazulene (DHA) photoswitching subunits, bridged by linkers of varying chain length. Independent of ring size, all macrocycles exhibit stepwise, light-induced, ring-opening reactions (DHA-DHA to DHA-VHF to VHF-VHF; VHF = vinylheptafulvene) with the first DHA undergoing isomerization with a similar efficiency as the uncyclized parent system while the second (DHA-VHF to VHF-VHF) is significantly slower. The energy-releasing, VHF-to-DHA, ring closures also occur in a stepwise manner and are systematically found to proceed slower in the more strained (smaller) cycles, but in all cases with a remarkably slow conversion of the second VHF to DHA. We managed to increase the half-life of the second VHF-to-DHA conversion from 65 to 202 h at room temperature by simply decreasing the ring size. A computational study reveals the smallest macrocycle to have the most energetic VHF-VHF state and hence highest energy density.

NIR dual luminescence from an extended porphyrin. Spectroscopy, photophysics and theory.

PubMed

Gourlaouen, Christophe; Daniel, Chantal; Durola, Fabien; Frey, Julien; Heitz, Valérie; Sauvage, Jean-Pierre; Ventura, Barbara; Flamigni, Lucia

2014-05-22

Spectroscopic and photophysical properties of an extended Zn porphyrin with fused bis(tetraazaanthracene) arms including a 2,9-diphenyl-1,10-phenanthroline incorporated in a polyether macrocycle are investigated in solvents of different polarity pointing to the presence of two emitting singlet excited states. The absorption and emission features are identified and ascribed, on the basis of solvent polarity dependence, to a π-π* and to a charge transfer (CT) state, respectively. Whereas the intraligand π-π* transition is assigned to the intense absorption observed at 442-455 nm, the CT states contribute to the bands at 521-525 nm and 472-481 nm. The theoretical analysis of the absorption spectrum confirms the presence of two strong bands centered at 536 and 437 nm corresponding to CT and π-π* states, respectively. Weak CT transitions are calculated at 657 and 486 nm. Two emission maxima are observed in toluene at 724 nm from a (1)π-π* state and at 800 nm from a (1)CT state, respectively. (1)CT bands shift bathochromically by increasing the solvent polarity whereas the energy of the (1)π-π band is less affected. Likewise, the emission yield and lifetime associated with the low energy (1)CT band are strongly affected by solvent polarity. This is rationalized by a (1)π-π* → (1)CT internal conversion driven by solvent polarity, this process being competitive with the (1)π-π* to ground state deactivation channel. Time resolved absorption spectra indicate the presence of two triplet states, a short-lived one (nanoseconds range) and a longer lived one (hundreds of microsecond range) ascribed to a (3)π-π* and a (3)CT, respectively. For them, a conversion mechanism similar to that of the singlet excited states is suggested.

Intermolecular electron-transfer mechanisms via quantitative structures and ion-pair equilibria for self-exchange of anionic (dinitrobenzenide) donors.

PubMed

Rosokha, Sergiy V; Lü, Jian-Ming; Newton, Marshall D; Kochi, Jay K

2005-05-25

Definitive X-ray structures of "separated" versus "contact" ion pairs, together with their spectral (UV-NIR, ESR) characterizations, provide the quantitative basis for evaluating the complex equilibria and intrinsic (self-exchange) electron-transfer rates for the potassium salts of p-dinitrobenzene radical anion (DNB(-)). Three principal types of ion pairs, K(L)(+)DNB(-), are designated as Classes S, M, and C via the specific ligation of K(+) with different macrocyclic polyether ligands (L). For Class S, the self-exchange rate constant for the separated ion pair (SIP) is essentially the same as that of the "free" anion, and we conclude that dinitrobenzenide reactivity is unaffected when the interionic distance in the separated ion pair is r(SIP) > or =6 Angstroms. For Class M, the dynamic equilibrium between the contact ion pair (with r(CIP) = 2.7 Angstroms) and its separated ion pair is quantitatively evaluated, and the rather minor fraction of SIP is nonetheless the principal contributor to the overall electron-transfer kinetics. For Class C, the SIP rate is limited by the slow rate of CIP right arrow over left arrow SIP interconversion, and the self-exchange proceeds via the contact ion pair by default. Theoretically, the electron-transfer rate constant for the separated ion pair is well-accommodated by the Marcus/Sutin two-state formulation when the precursor in Scheme 2 is identified as the "separated" inner-sphere complex (IS(SIP)) of cofacial DNB(-)/DNB dyads. By contrast, the significantly slower rate of self-exchange via the contact ion pair requires an associative mechanism (Scheme 3) in which the electron-transfer rate is strongly governed by cationic mobility of K(L)(+) within the "contact" precursor complex (IS(CIP)) according to the kinetics in Scheme 4.

The ability of different materials to reproduce accurate records of interocclusal relationships in the vertical dimension.

PubMed

Ghazal, M; Albashaireh, Z S; Kern, M

2008-11-01

Restorations made on incorrectly mounted casts might require considerable intra-oral adjustments to correct the occlusion or might even necessitate a remake of the restoration. The aim of this study was to evaluate interocclusal recording materials for their ability to reproduce accurate vertical interocclusal relationships after a storage time of 1 and 48 h, respectively. A custom-made apparatus was used to simulate the maxilla and mandible. Eight interocclusal records were made in each of the following groups: G1: Aluwax (aluminium wax), G2: Beauty Pink wax (hydrocarbon wax compound), G3: Futar D, G4: Futar D Fast, G5: Futar Scan (G3-G5: vinyl polysiloxane), G6: Ramitec (polyether). The vertical discrepancies were measured by an inductive displacement transducer connected to a carrier frequency amplifier after storage of the records for two periods of 1 and 48 h. Two-way anova was used for statistical analysis. The mean vertical discrepancies in mum (1/48 h) for G1 (31/35) and G2 (35/38) were statistically significantly higher than for the other groups G3 (8/10), G4 (11/12), G5 (6/8) and G6 (5/8) (P < or = 0.05). There were no statistically significant differences between the elastomers tested. The effect of storage on the vertical discrepancies was statistically significant (P < 0.001). Vinyl polysiloxane and polyether interocclusal records can be used to relate working casts during mounting procedures without significant vertical displacement of the casts.

Abrasive slurry composition for machining boron carbide

DOEpatents

Duran, Edward L.

1985-01-01

An abrasive slurry particularly suited for use in drilling or machining boron carbide consists essentially of a suspension of boron carbide and/or silicon carbide grit in a carrier solution consisting essentially of a dilute solution of alkylaryl polyether alcohol in octyl alcohol. The alkylaryl polyether alcohol functions as a wetting agent which improves the capacity of the octyl alcohol for carrying the grit in suspension, yet without substantially increasing the viscosity of the carrier solution.

Abrasive slurry composition for machining boron carbide

DOEpatents

Duran, E.L.

1984-11-29

An abrasive slurry particularly suited for use in drilling or machining boron carbide consists essentially of a suspension of boron carbide and/or silicon carbide grit in a carrier solution consisting essentially of a dilute solution of alkylaryl polyether alcohol in octyl alcohol. The alkylaryl polyether alcohol functions as a wetting agent which improves the capacity of the octyl alcohol for carrying the grit in suspension, yet without substantially increasing the viscosity of the carrier solution.

Morphology and properties of amine terminated poly(arylene ether ketone) and poly(arylene ether sulfone) modified epoxy resin systems

NASA Technical Reports Server (NTRS)

Cecere, J. A.; Mcgrath, J. E.; Hedrick, J. L.

1986-01-01

Epoxy resin networks cured with DDS were modified by incorporating tough ductile thermoplastics such as the amine terminated polyether sulfones and amine terminated polyether ketones. Both linear copolymers were able to significantly improve the fracture toughness values at the 15 and 30 weight percent concentrations examined. These improvements in fracture toughness were achieved without any significant change in the flexural modulus.

Fluorescent aliphatic hyperbranched polyether: chromophore-free and without any N and P atoms.

PubMed

Miao, Xuepei; Liu, Tuan; Zhang, Chen; Geng, Xinxin; Meng, Yan; Li, Xiaoyu

2016-02-14

The strong fluorescence, in both the solution and the bulk state, of a chromophore-free aliphatic hyperbranched polyether which does not contain N and P atoms was reported for the first time. Effects of concentration and solvent solubility were measured. Its ethanol solution shows a strong blue-green fluorescence (Yu = 0.11-0.39), and its fluorescence shows a strong selective quenching with respect to Fe(3+).

Roll-on perfume compositions containing polyoxybutylene-polyoxyethylene copolymers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmolka, I.R.

1987-05-26

This patent describes a liquid roll-on composition containing, in weight percent based upon the total composition weight, from 5 percent to 15 percent of a perfume oil, from 25 percent to 40 percent of a volatile alcohol, from 10 percent to 60 percent water, and from 10 percent to 30 percent of a nonionic polyether surfactant. The improvement comprises employing as the nonionic polyether surfactant a cogeneric polyoxybutylene-polyoxyethylene block copolymer.

Ureasil-polyether hybrid film-forming materials.

PubMed

Souza, L K; Bruno, C H; Lopes, L; Pulcinelli, S H; Santilli, C V; Chiavacci, L A

2013-01-01

The objectives of this work were to study the suitability and highlight the advantages of the use of cross-linked ureasil-polyether hybrid matrices as film-forming systems. The results revealed that ureasil-polyethers are excellent film-forming systems due to specific properties, such as their biocompatibility, their cosmetic attractiveness for being able to form thin and transparent films, their short drying time to form films and their excellent bioadhesion compared to the commercial products known as strong adhesives. Rheological measurements have demonstrated the ability of these hybrid matrices to form a film in only a few seconds and Water Vapor Transmitting Rate (WVTR) showed adequate semi-occlusive properties suggesting that these films could be used as skin and wound protectors. Both the high skin bioadhesion and non-cytotoxic character seems to be improved by the presence of multiple amine groups in the hybrid molecules. Copyright © 2012 Elsevier B.V. All rights reserved.

Conductivity and properties of polysiloxane-polyether cluster-LiTFSI networks as hybrid polymer electrolytes

NASA Astrophysics Data System (ADS)

Boaretto, Nicola; Joost, Christine; Seyfried, Mona; Vezzù, Keti; Di Noto, Vito

2016-09-01

This report describes the synthesis and the properties of a series of polymer electrolytes, composed of a hybrid inorganic-organic matrix doped with LiTFSI. The matrix is based on ring-like oligo-siloxane clusters, bearing pendant, partially cross-linked, polyether chains. The dependency of the thermo-mechanic and of the transport properties on several structural parameters, such as polyether chains' length, cross-linkers' concentration, and salt concentration is studied. Altogether, the materials show good thermo-mechanical and electrochemical stabilities, with conductivities reaching, at best, 8·10-5 S cm-1 at 30 °C. In conclusion, the cell performances of one representative sample are shown. The scope of this report is to analyze the correlations between structure and properties in networked and hybrid polymer electrolytes. This could help the design of optimized polymer electrolytes for application in lithium metal batteries.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Custelcean, Radu; Bartsch, Richard A.

Two series of novel mono-ionizable calix[4]arene-benzocrown-6 ligands in 1,3-alternate conformations are synthesized. In one series, the proton-ionizable group (PIG) is attached to the para position of one aromatic ring in the calixarene framework, thereby positioning it over the polyether ring cavity. In the other series, the PIG is a substituent on the benzo group in the polyether ring. This orients the PIG away from the crown ether cavity. In addition to carboxylic acid functions, the PIGs include N-(X)sulfonyl carboxamide groups. With X group variation from methyl to phenyl to 4-nitrophenyl to trifluoromethyl, the acidity of the PIG is 'tuned'. Solventmore » extraction of Ag{sup +} from aqueous solutions into chloroform is used to probe the influence of structural variation within the mono-ionizable calixcrown ligand on metal ion extraction efficiency, including the identity and acidity of the PIG and its orientation with respect to the polyether ring.« less

Dynamically analyte-responsive macrocyclic host-fluorophore systems.

PubMed

Ghale, Garima; Nau, Werner M

2014-07-15

CONSPECTUS: Host-guest chemistry commenced to a large degree with the work of Pedersen, who in 1967 first reported the synthesis of crown ethers. The past 45 years have witnessed a substantial progress in the field, from the design of highly selective host molecules as receptors to their application in drug delivery and, particularly, analyte sensing. Much effort has been expended on designing receptors and signaling mechanism for detecting compounds of biological and environmental relevance. Traditionally, the design of a chemosensor comprises one component for molecular recognition, frequently macrocycles of the cyclodextrin, cucurbituril, cyclophane, or calixarene type. The second component, used for signaling, is typically an indicator dye which changes its photophysical properties, preferably its fluorescence, upon analyte binding. A variety of signal transduction mechanisms are available, of which displacement of the dye from the macrocyclic binding site is one of the simplest and most popular ones. This constitutes the working principle of indicator displacement assays. However, indicator displacement assays have been predominantly exploited in a static fashion, namely, to determine absolute analyte concentrations, or, by using combinations of several reporter pairs, to achieve a differential sensing and, thus, identification of specific food products or brands. In contrast, their use in biological systems, for example, with membranes, cells, or with enzymes has been comparably less explored, which led us to the design of the so-called tandem assays, that is, dynamically analyte-responsive host-dye systems, in which the change in analyte concentrations is induced by a biological reaction or process. This methodological variation has practical application potential, because the ability to monitor these biochemical pathways or to follow specific molecules in real time is of paramount interest for both biochemical laboratories and the pharmaceutical industry. We will begin by describing the underlying principles that govern the use of macrocycle-fluorescent dye complexes to monitor time-dependent changes in analyte concentrations. Suitable chemosensing ensembles are introduced, along with their fluorescence responses (switch-on or switch-off). This includes supramolecular tandem assays in their product- and substrate-selective variants, and in their domino and enzyme-coupled modifications, with assays for amino acid decarboxylases, diamine, and choline oxidase, proteases, methyl transferases, acetylcholineesterase (including an unpublished direct tandem assay), choline oxidase, and potato apyrase as examples. It also includes the very recently introduced tandem membrane assays in their published influx and unpublished efflux variants, with the outer membrane protein F as channel protein and protamine as bidirectionally translocated analyte. As proof-of-principle for environmental monitoring applications, we describe sensing ensembles for volatile hydrocarbons.

LANTHANIDE ENHANCE LUMINESCENCE (LEL) WITH ONE AND TWO PHOTON EXCITATION OF QUANTUM DYES LANTHANIDE (III) - MACROCYCLES

EPA Science Inventory

Title: Lanthanide Enhance Luminescence (LEL) with one and two photon excitation of Quantum Dyes? Lanthanide(III)-Macrocycles
Principal Author:
Robert C. Leif, Newport Instruments
Secondary Authors:
Margie C. Becker, Phoenix Flow Systems
Al Bromm, Virginia Commonw...

Metacridamides A and B, bioactive macrocycles from conidia of the entomopathogenic fungus Metarhizium acridum

USDA-ARS?s Scientific Manuscript database

Metarhizium acridum, an entomopathogenic fungus, has been commercialized and used successfully for biocontrol of grasshopper pests in Africa and Australia. Its conidia produce two novel 17-membered macrocycles, metacridamides A (1) and B (2), which consist of a Phe unit condensed with a nonaketide....

Synthesis, characterization, MCD spectroscopy, and TD-DFT calculations of copper-metalated nonperipherally substituted octaoctyl derivatives of tetrabenzotriazaporphyrin, cis- and trans-tetrabenzodiazaporphyrin, tetrabenzomonoazaporphyrin, and tetrabenzoporphyrin.

PubMed

Mack, John; Sosa-Vargas, Lydia; Coles, Simon J; Tizzard, Graham J; Chambrier, Isabelle; Cammidge, Andrew N; Cook, Michael J; Kobayashi, Nagao

2012-12-03

Synthesis of the title compounds has been achieved through refinement of a recently reported synthetic protocol whereby varying equivalents of MeMgBr are reacted with 1,4-dioctylphthalonitrile to produce mixtures favoring specific hybrid structures. The initially formed magnesium-metalated compounds are obtained as pure materials and include, for the first time, both isomers (cis and trans) of tetrabenzodiazaporphyrin. The compounds were demetalated to the metal-free analogues, which were then converted into the copper-metalated derivatives. The X-ray structure of the copper tetrabenzotriazaporphyrin derivative is reported. The metal-free and copper-metalated macrocycles exhibit columnar mesophase behavior, and it is found that the mesophase stability is unexpectedly reduced in the diazaporphyrin derivatives compared to the rest of the series. The results of time-dependent density functional theory calculations for the copper complexes are compared to the observed optical properties. Michl's perimeter model was used as a conceptual framework for analyzing the magnetic circular dichroism spectral data, which predicted and accounted for trends in the observed experimental spectra.

The Synthesis of Carborane-Oxetane Monomers and their Polymerization

DTIC Science & Technology

1988-07-11

polyether glycol was liter demonstrated.’ During this time, " modified cationic polymerization technique was developef’, which allowed the synthesis of...Migration of these chemicals in the propellant grain is a continuous and serious problem. We proposed that a urethane curable polyether glycol with a...Br CH3 g 3 Cl CH3 This scheme has the advantage that the leaving group is not on the oxetane. Oxetane is a neopentyl type system which is typically

Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis

PubMed Central

Hotta, Kinya; Chen, Xi; Paton, Robert S.; Minami, Atsushi; Li, Hao; Swaminathan, Kunchithapadam; Mathews, Irimpan I.; Watanabe, Kenji; Oikawa, Hideaki; Houk, Kendall N.; Kim, Chu-Young

2012-01-01

Polycyclic polyether natural products have fascinated chemists and biologists alike owing to their useful biological activity, highly complex structure and intriguing biosynthetic mechanisms. Following the original proposal for the polyepoxide origin of lasalocid and isolasalocid1 and the experimental determination of the origins of the oxygen and carbon atoms of both lasalocid and monensin, a unified stereochemical model for the biosynthesis of polyether ionophore antibiotics was proposed2. The model was based on a cascade of nucleophilic ring closures of postulated polyepoxide substrates generated by stereospecific oxidation of all-trans polyene polyketide intermediates2. Shortly thereafter, a related model was proposed for the biogenesis of marine ladder toxins, involving a series of nominally disfavoured anti-Baldwin, endo-tet epoxide-ring-opening reactions3–5. Recently, we identified Lsd19 from the Streptomyces lasaliensis gene cluster as the epoxide hydrolase responsible for the epoxide-opening cyclization of bisepoxyprelasalocid A6 to form lasalocid A7,8. Here we report the X-ray crystal structure of Lsd19 in complex with its substrate and product analogue9 to provide the first atomic structure—to our knowledge—of a natural enzyme capable of catalysing the disfavoured epoxide-opening cyclic ether formation. On the basis of our structural and computational studies, we propose a general mechanism for the enzymatic catalysis of polyether natural product biosynthesis. PMID:22388816

Effect of mixing techniques on bacterial attachment and disinfection time of polyether impression material

PubMed Central

Guler, Umut; Budak, Yasemin; Ruh, Emrah; Ocal, Yesim; Canay, Senay; Akyon, Yakut

2013-01-01

Objective: The aim of this study was 2-fold. The first aim was to evaluate the effects of mixing technique (hand-mixing or auto-mixing) on bacterial attachment to polyether impression materials. The second aim was to determine whether bacterial attachment to these materials was affected by length of exposure to disinfection solutions. Materials and Methods: Polyether impression material samples (n = 144) were prepared by hand-mixing or auto-mixing. Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were used in testing. After incubation, the bacterial colonies were counted and then disinfectant solution was applied. The effect of disinfection solution was evaluated just after the polymerization of impression material and 30 min after polymerization. Differences in adherence of bacteria to the samples prepared by hand-mixing and to those prepared by auto-mixing were assessed by Kruskal-Wallis and Mann-Whitney U-tests. For evaluating the efficiency of the disinfectant, Kruskal-Wallis multiple comparisons test was used. Results: E. coli counts were higher in hand-mixed materials (P < 0.05); no other statistically significant differences were found between hand- and auto-mixed materials. According to the Kruskal-Wallis test, significant differences were found between the disinfection procedures (Z > 2.394). Conclusion: The methods used for mixing polyether impression material did not affect bacterial attachment to impression surfaces. In contrast, the disinfection procedure greatly affects decontamination of the impression surface. PMID:24966729

Electrospray ionization tandem mass spectrometry of ammonium cationized polyethers.

PubMed

Nasioudis, Andreas; Heeren, Ron M A; van Doormalen, Irene; de Wijs-Rot, Nicolette; van den Brink, Oscar F

2011-05-01

Quaternary ammonium salts (Quats) and amines are known to facilitate the MS analysis of high molar mass polyethers by forming low charge state adduct ions. The formation, stability, and behavior upon collision-induced dissociation (CID) of adduct ions of polyethers with a variety of Quats and amines were studied by electrospray ionization quadrupole time-of-flight, quadrupole ion trap, and linear ion trap tandem mass spectrometry (MS/MS). The linear ion trap instrument was part of an Orbitrap hybrid mass spectrometer that allowed accurate mass MS/MS measurements. The Quats and amines studied were of different degree of substitution, structure, and size. The stability of the adduct ions was related to the structure of the cation, especially the amine's degree of substitution. CID of singly/doubly charged primary and tertiary ammonium cationized polymers resulted in the neutral loss of the amine followed by fragmentation of the protonated product ions. The latter reveals information about the monomer unit, polymer sequence, and endgroup structure. In addition, the detection of product ions retaining the ammonium ion was observed. The predominant process in the CID of singly charged quaternary ammonium cationized polymers was cation detachment, whereas their doubly charged adduct ions provided the same information as the primary and tertiary ammonium cationized adduct ions. This study shows the potential of specific amines as tools for the structural elucidation of high molar mass polyethers. © American Society for Mass Spectrometry, 2011

Accuracy of impressions with different impression materials in angulated implants.

PubMed

Reddy, S; Prasad, K; Vakil, H; Jain, A; Chowdhary, R

2013-01-01

To evaluate the dimensional accuracy of the resultant (duplicative) casts made from two different impression materials (polyvinyl siloxane and polyether) in parallel and angulated implants. Three definitive master casts (control groups) were fabricated in dental stone with three implants, placed at equi-distance. In first group (control), all three implants were placed parallel to each other and perpendicular to the plane of the cast. In the second and third group (control), all three implants were placed at 10° and 15 o angulation respectively to the long axis of the cast, tilting towards the centre. Impressions were made with polyvinyl siloxane and polyether impression materials in a special tray, using a open tray impression technique from the master casts. These impressions were poured to obtain test casts. Three reference distances were evaluated on each test cast by using a profile projector and compared with control groups to determine the effect of combined interaction of implant angulation and impression materials on the accuracy of implant resultant cast. Statistical analysis revealed no significant difference in dimensional accuracy of the resultant casts made from two different impression materials (polyvinyl siloxane and polyether) by closed tray impression technique in parallel and angulated implants. On the basis of the results of this study, the use of both the impression materials i.e., polyether and polyvinyl siloxane impression is recommended for impression making in parallel as well as angulated implants.

Effect of mixing techniques on bacterial attachment and disinfection time of polyether impression material.

PubMed

Guler, Umut; Budak, Yasemin; Ruh, Emrah; Ocal, Yesim; Canay, Senay; Akyon, Yakut

2013-09-01

The aim of this study was 2-fold. The first aim was to evaluate the effects of mixing technique (hand-mixing or auto-mixing) on bacterial attachment to polyether impression materials. The second aim was to determine whether bacterial attachment to these materials was affected by length of exposure to disinfection solutions. Polyether impression material samples (n = 144) were prepared by hand-mixing or auto-mixing. Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were used in testing. After incubation, the bacterial colonies were counted and then disinfectant solution was applied. The effect of disinfection solution was evaluated just after the polymerization of impression material and 30 min after polymerization. Differences in adherence of bacteria to the samples prepared by hand-mixing and to those prepared by auto-mixing were assessed by Kruskal-Wallis and Mann-Whitney U-tests. For evaluating the efficiency of the disinfectant, Kruskal-Wallis multiple comparisons test was used. E. coli counts were higher in hand-mixed materials (P < 0.05); no other statistically significant differences were found between hand- and auto-mixed materials. According to the Kruskal-Wallis test, significant differences were found between the disinfection procedures (Z > 2.394). The methods used for mixing polyether impression material did not affect bacterial attachment to impression surfaces. In contrast, the disinfection procedure greatly affects decontamination of the impression surface.

Biodegradation of polyether-polyol-based polyurethane elastomeric films: influence of partial replacement of polyether polyol by biopolymers of renewable origin.

PubMed

Obruca, Stanislav; Marova, Ivana; Vojtova, Lucy

2011-07-01

In this work we investigated the degradation process ofpolyether-polyol-based polyurethane (PUR) elastomeric films in the presence of a mixed thermophilic culture as a model of a natural bacterial consortium. The presence of PUR material in cultivation medium resulted in delayed but intensive growth of the bacterial culture. The unusually long lag phase was caused by the release of unreacted polyether polyol and tin catalyst from the material. The lag phase was significantly shortened and the biodegradability of PUR materials was enhanced by partial replacement (10%) of polyether polyol with biopolymers (carboxymethyl cellulose, hydroxyethyl cellulose, acetyl cellulose and actylated starch). The process of material degradation consisted of two steps. First, the materials were mechanically disrupted and, second, the bacterial culture was able to utilize abiotic degradation products, which resulted in supported bacterial growth. Direct utilization of PUR by the bacterial culture was observed as well, but the bacterial culture contributed only slightly to the total mass losses. The only exception was PUR material modified by acetyl cellulose. In this case, direct biodegradation represented the major mechanism of material decomposition. Moreover, PUR material modified by acetyl cellulose did not tend to undergo abiotic degradation. In conclusion, the modification of PUR by proper biopolymers is a promising strategy for reducing potential negative effects of waste PUR materials on the environment and enhancing their biodegradability.

UV-Surface Treatment of Fungal Resistant Polyether Polyurethane Film-Induced Growth of Entomopathogenic Fungi.

PubMed

Lando, Gabriela Albara; Marconatto, Letícia; Kessler, Felipe; Lopes, William; Schrank, Augusto; Vainstein, Marilene Henning; Weibel, Daniel Eduardo

2017-07-18

Synthetic polymers are the cause of some major environmental impacts due to their low degradation rates. Polyurethanes (PU) are widely used synthetic polymers, and their growing use in industry has produced an increase in plastic waste. A commercial polyether-based thermoplastic PU with hydrolytic stability and fungus resistance was only attacked by an entomopathogenic fungus, Metarhiziumanisopliae , when the films were pre-treated with Ultraviolet (UV) irradiation in the presence of reactive atmospheres. Water contact angle, Fourier transform infrared spectroscopy in attenuated total reflection mode (FTIR-ATR), scanning electron microscopy (SEM), and profilometer measurements were mainly used for analysis. Permanent hydrophilic PU films were produced by the UV-assisted treatments. Pristine polyether PU films incubated for 10, 30, and 60 days did not show any indication of fungal growth. On the contrary, when using oxygen in the UV pre-treatment a layer of fungi spores covered the sample, indicating a great adherence of the microorganisms to the polymer. However, if acrylic acid vapors were used during the UV pre-treatment, a visible attack by the entomopathogenic fungi was observed. SEM and FTIR-ATR data showed clear evidence of fungal development: growth and ramifications of hyphae on the polymer surface with the increase in UV pre-treatment time and fungus incubation time. The results indicated that the simple UV surface activation process has proven to be a promising alternative for polyether PU waste management.

Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Hao; Dranchak, Patricia; Li, Zhiru

Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanismmore » placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.« less

Synthesis of N₄ donor macrocyclic Schiff base ligands and their Ru (II), Pd (II), Pt (II) metal complexes for biological studies and catalytic oxidation of didanosine in pharmaceuticals.

PubMed

Ravi Krishna, E; Muralidhar Reddy, P; Sarangapani, M; Hanmanthu, G; Geeta, B; Shoba Rani, K; Ravinder, V

2012-11-01

A series of tetraaza (N(4) donor) macrocyclic ligands (L(1)-L(4)) were derived from the condensation of o-phthalaldehyde (OPA) with some substituted aromatic amines/azide, and subsequently used to synthesize the metal complexes of Ru(II), Pd(II) and Pt(II). The structures of macrocyclic ligands and their metal complexes were characterized by elemental analyses, IR, (1)H &(13)C NMR, mass and electronic spectroscopy, thermal, magnetic and conductance measurements. Both the ligands and their complexes were screened for their antibacterial activities against Gram positive and Gram negative bacteria by MIC method. Besides, these macrocyclic complexes were investigated as catalysts in the oxidation of pharmaceutical drug didanosine. The oxidized products were further treated with sulphanilic acid to develop the colored products to determine by spectrophotometrically. The current oxidation method is an environmentally friendly, simple to set-up, requires short reaction time, produces high yields and does not require co-oxidant. Copyright © 2012 Elsevier B.V. All rights reserved.

Toxicity, Spectroscopic Characterization and Electrochemical Behaviour of New Macrocclic Complexes of Lead(II) and Palladium(II) Metals

PubMed Central

Bansal, Anil; Singh, Randhir

2000-01-01

Tetraazamacrocyclie complexes of lead and palladium have been synthesized by the template process using the bis(benzil)ethylenediamine precursor. The tetradentate macrocycle (maL) reacts with PbCl2, PdCl2 and different diamines in a 1:1:1 molar ratio in methanol to give several solid complexes of the types [Pb(maL)(R)Cl2] and [Pd(maL)(R)]Cl2 (where R = 2,6-diaminopyridine or 1,2-phenylenediamine). The macrocycle and its metal complexes have been characterized by elemental analysis, molecular weight determinations, molar conductivity, IR, 1H NMR, 13C NMR, electronic, mass and electrochemical studies. The macrocyclic ligand coordinates through the four azomethine nitrogen atoms which are bridged by benzil moieties. IR spectra suggest that the pyridine nitrogen is not coordinating. The palladium complexes exhibit tetracoordinated square-planar geometry, whereas a hexacoordinated octahedral geometry is suggested for lead complexes. The macrocycle along with its complexes have been screened in vitro against a number of pathogenic fungi and bacteria to assess their growth inhibiting potential. PMID:18475947

Trimodal Control of Ion-Transport Activity on Cyclo-oligo-(1→6)-β-D-glucosamine-Based Artificial Ion-Transport Systems.

PubMed

Roy, Arundhati; Saha, Tanmoy; Gening, Marina L; Titov, Denis V; Gerbst, Alexey G; Tsvetkov, Yury E; Nifantiev, Nikolay E; Talukdar, Pinaki

2015-11-23

Cyclo-oligo-(1→6)-β-D-glucosamines functionalized with hydrophobic tails are reported as a new class of transmembrane ion-transport system. These macrocycles with hydrophilic cavities were introduced as an alternative to cyclodextrins, which are supramolecular systems with hydrophobic cavities. The transport activities of these glycoconjugates were manipulated by altering the oligomericity of the macrocycles, as well as the length and number of attached tails. Hydrophobic tails of 3 different sizes were synthesized and coupled with each glucosamine scaffold through the amide linkage to obtain 18 derivatives. The ion-transport activity increased from di- to tetrameric glucosamine macrocycles, but decreased further when flexible pentameric glucosamine was introduced. The ion-transport activity also increased with increasing length of attached linkers. For a fixed length of linkers, the transport activity decreased when the number of such tails was reduced. All glycoconjugates displayed a uniform anion-selectivity sequence: Cl(-) >Br(-) >I(-) . From theoretical studies, hydrogen bonding between the macrocycle backbone and the anion bridged through water molecules was observed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of covalently linked dimeric derivatives of chlorophyll a, pyrochlorophyll a, chlorophyll b, and bacteriochlorophyll a

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wasielewski, M.R.; Svec, W.A.

1980-05-09

Bis(chlorophyllide) ethylene glycol diesters were prepared for each of the title compounds. Pheophytins a and b isolated from alfalfa and bacteriochlorophyll a isolated from R. sphaeroides were treated with 80% aqueous trifluoroacetic acid to yield the corresponding pheophorbides. Pyropheophorbide was prepared by a literature procedure. Carbonic anhydride and benzotriazole-1-methanesulfonate activation methods were used in the esterification of the pheophorbides with ethylene glycol at ambient temperature. Each method yielded 75%+ of the pheophorbide ethylene glycol monoester. These monoesters were treated with equimolar amounts of the corresponding pheophorbide by using benzotriazol-1-methanesulfonate/4-(dimethylamino)pyridine in CH/sub 2/Cl/sub 2/ or dicyclohexylcarbodiimide/4-(dimethylamino)pyridine in CH/sub 2/Cl/sub 2/ atmore » ambient temperature. Yields of bis(phenophorbide) ethylene glycol diesters averaged about 50% for the former method and 70% for the latter method. Insertion of the magnesium atoms into the a series macrocycles was accomplished with iodomagnesium 2,6-di-tert-butyl-4-methylphenolate, IMgBHT, in CH/sub 2/Cl/sub 2/, while the metalation of the b and bacterial series macrocycles was carried out with a mixture of IMgBHT and lithium 2,2,6,6-tetramethylpiperidide in thiophen, all at ambient temperature. Both mono- and dimetalated derivatives were isolated and characterized in each case.« less

Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors.

PubMed

Molgó, Jordi; Marchot, Pascale; Aráoz, Rómulo; Benoit, Evelyne; Iorga, Bogdan I; Zakarian, Armen; Taylor, Palmer; Bourne, Yves; Servent, Denis

2017-08-01

We present an overview of the toxicological profile of the fast-acting, lipophilic macrocyclic imine toxins, an emerging family of organic compounds associated with algal blooms, shellfish contamination and neurotoxicity. Worldwide, shellfish contamination incidents are expanding; therefore, the significance of these toxins for the shellfish food industry deserves further study. Emphasis is directed to the dinoflagellate species involved in their production, their chemical structures, and their specific mode of interaction with their principal natural molecular targets, the nicotinic acetylcholine receptors, or with the soluble acetylcholine-binding protein, used as a surrogate receptor model. The dinoflagellates Karenia selliformis and Alexandrium ostenfeldii / A. peruvianum have been implicated in the biosynthesis of gymnodimines and spirolides, while Vulcanodinium rugosum is the producer of pinnatoxins and portimine. The cyclic imine toxins are characterized by a macrocyclic skeleton comprising 14-27 carbon atoms, flanked by two conserved moieties, the cyclic imine and the spiroketal ring system. These phycotoxins generally display high affinity and broad specificity for the muscle type and neuronal nicotinic acetylcholine receptors, a feature consistent with their binding site at the receptor subunit interfaces, composed of residues highly conserved among all nAChRs, and explaining the diverse toxicity among animal species. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

Synthesis and Detonation Properties of 5‐Amino‐2,4,6‐trinitro‐1,3‐dihydroxy‐benzene

PubMed Central

Zhang, Xingcheng; Xiong, Hualin; Yang, Hongwei

2017-01-01

Abstract 5‐Amino‐4,6‐dinitro‐1,3‐dihydroxy‐benzene (6) was synthesized through the ring‐opening reaction of macrocyclic compound 4 with the aid of VNS (vicarious nucleophilic substitution of hydrogen) reaction conditions. The mechanism of ring opening of macrocyclic compound 4 was studied. 5‐Amino‐2,4,6‐trinitro‐1,3‐dihydroxy‐benzene (8) was obtained after the nitration of 6 in KNO3 and concentrated sulfuric acid. The thermal stability, sensitivity, and other detonation performances of 6 or 8 were compared to commercially used 1,3,5‐triamino‐2,4,6‐trinitrobenzene (TATB) or 1,3,5‐trinitrotriazacyclohexane (RDX), respectively. All target compounds were characterized by using single‐crystal X‐ray diffraction, NMR spectroscopy, elemental analysis, and differential scanning calorimetry. The sensitivities were determined by using BAM methods (drop‐hammer and friction tests). Performance parameters, including heats of formation and detonation properties, were calculated by using Gaussian 03 and EXPLO5 v6.01 programs, respectively. It is worth pointing out that compound 8 has a remarkable measured density of 2.078 g cm−3 at 298 K. In addition, compound 8 is more insensitive than RDX (compound 8: IS=11 J; RDX: IS=7 J; IS is the impact sensitivity). PMID:28638778

Reversible adaptation to photoinduced shape switching by oligomer-macrocycle interconversion with component selection in a three-state constitutional dynamic system.

PubMed

Vantomme, Ghislaine; Lehn, Jean-Marie

2014-12-01

Light irradiation of the molecular photoswitch 1-E causes isomerization into the 1-Z configuration stabilized by an internal hydrogen bond. 1-E bears aldehyde groups allowing for dynamic covalent reaction with linear diamines. On photoinduced E/Z shape switching of 1 in presence of diamines, the system undergoes interconversion between two states, a non-cyclic oligomeric one and a macrocyclic one, corresponding respectively to the E and Z configurations of 1. With a mixture of linear α,ω-diamines, 1-E yields non-selective dynamic oligomers by random incorporation of diamine components. Photoswitching to the 1-Z form leads to constitutional adaptation with preferential formation of the macrocycle incorporating the best suited diamine, H2 N(CH2 )7 NH2 . In presence of metal cations, the E form switches from its unbound W shape to its coordinated U shape and yields the macrocycle resulting from the selective incorporation of the diamine H2 NCH2 CH2 OCH2 CH2 NH2 that contains an additional O coordination site. Taken together, the results obtained describe constitutional adaptation in a triple state system: an oligomeric one and two different macrocyclic ones generated in response to two orthogonal agents, a physical stimulus, light, or a chemical effector, metal cations. These three states present, towards the incorporation of diamine components, respectively no selection, photoselection and metalloselection. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrochemical studies of DNA interaction and antimicrobial activities of MnII, FeIII, CoII and NiII Schiff base tetraazamacrocyclic complexes

NASA Astrophysics Data System (ADS)

Kumar, Anuj; Vashistha, Vinod Kumar; Tevatia, Prashant; Singh, Randhir

2017-04-01

Tetraazamacrocyclic complexes of MnII, FeIII, CoII and NiII have been synthesized by template method. These tetraazamacrocycles have been analyzed with various techniques like molar conductance, IR, UV-vis, mass spectral and cyclic voltammetric studies. On the basis of all these studies, octahedral geometry has been assigned to these tetraazamacrocyclic complexes. The DNA binding properties of these macrocyclic complexes have been investigated by electronic absorption spectra, fluorescence spectra, cyclic voltammetric and differential pulse voltammetric studies. The cyclic voltammetric data showed that ipc and ipa were effectively decreased in the presence of calf thymus DNA, which is a strong evidence for the interaction of these macrocyclic complexes with the calf thymus DNA (ct-DNA). The heterogeneous electron transfer rate constant found in the order: KCoII > KNiII > KMnII which indicates that CoII macrocyclic complex has formed a strong intercalated intermediate. The Stern-Volmer quenching constant (KSV) and voltammetric binding constant were found in the order KSV(CoII) > KSV(NiII) > KSV(MnII) and K+(CoII) > K+(NiII) > K+(MnII) which shows that CoII macrocyclic complex exhibits the high interaction affinity towards ct-DNA by the intercalation binding. Biological studies of the macrocyclic complexes compared with the standard drug like Gentamycin, have shown antibacterial activities against E. coli, P. aeruginosa, B. cereus, S. aureus and antifungal activity against C. albicans.

Additives for high-temperature liquid lubricants

NASA Technical Reports Server (NTRS)

Lawton, Emil A.; Yavrouian, Andre H.; Repar, John

1988-01-01

A preliminary research program was conducted to demonstrate a new concept for additives to liquid lubricants. It was demonstrated that suspensions of o-phthalonitrile and a substituted 1,2-maleonitrile in mineral oil and dilute solutions of o-phthalonitrile and tetrafluoro-o-phthalonitrile extended the lifetime of bearings under boundary lubricating conditions. The solutions exhibited coefficients of friction under high loads of 0.02-0.03. These results were consistent with the hypothesis that these compounds react with the hot metal surface to form a planar lubricating film by means of a metal or metal oxide template reaction. Also, the adherence was very strong due to the chelating action of the planar macrocycles postulated to form under the experimental conditions.

Production of Avaroferrin and Putrebactin by Heterologous Expression of a Deep-Sea Metagenomic DNA

PubMed Central

Fujita, Masaki J.; Sakai, Ryuichi

2014-01-01

The siderophore avaroferrin (1), an inhibitor of Vibrio swarming that was recently identified in Shewanella algae B516, was produced by heterologous expression of the biosynthetic gene cluster cloned from a deep-sea sediment metagenomic DNA, together with two analogues, bisucaberin (2) and putrebactin (3). Avaroferrin (1) is a macrocyclic heterodimer of N-hydroxy-N-succinyl cadaverine (4) and N-hydroxy-N-succinyl-putrescine (5), whereas analogues 2 and 3 are homodimers of 4 and 5, respectively. Heterologous expression of two other related genes from culturable marine bacteria resulted in production of compounds 1–3, but in quite different proportions compared with production through expression of the metagenomic DNA. PMID:25222668

Nanoparticles functionalized with supramolecular host-guest systems for nanomedicine and healthcare.

PubMed

Wu, Zilong; Song, Nan; Menz, Ryan; Pingali, Bharadwaj; Yang, Ying-Wei; Zheng, Yuebing

2015-05-01

Synthetic macrocyclic host compounds can interact with suitable guest molecules via noncovalent interactions to form functional supramolecular systems. With the synergistic integration of the response of molecules and the unique properties at the nanoscale, nanoparticles functionalized with the host-guest supramolecular systems have shown great potentials for a broad range of applications in the fields of nanoscience and nanotechnology. In this review article, we focus on the applications of the nanoparticles functionalized with supramolecular host-guest systems in nanomedicine and healthcare, including therapeutic delivery, imaging, sensing and removal of harmful substances. A large number of examples are included to elucidate the working mechanisms, advantages, limitations and future developments of the nanoparticle-supramolecule systems in these applications.

Synthesis of β-C-Glycopyranosyl Aldehydes and 2,6-Anhydro-heptitols.

PubMed

Khatri, Vinod; Kumar, Amit; Singh, Balram; Malhotra, Shashwat; Prasad, Ashok K

2015-11-06

A convenient route has been developed for the diastereoselective synthesis of β-C-glycopyranosyl aldehydes from D-glucose, D-mannose, and D-galactose. The key step in the synthesis of C-glycosyl aldehydes is the aryl driven reductive dehydration on 1-phenyl-2-(2',3',4',6'-tetra-O-acetyl-β-D-glycopyranosyl)ethanone to afford alkenes, which on oxidation afford the desired compounds in good yield. β-C-Glycopyranosyl aldehydes have been converted to 2,6-anhydro-heptitols in quantitative yields. The 2,6-anhydro-heptitols derived from D-mannose and D-galactose are enantiomeric and are useful linkers for the synthesis of macrocycles/amphiphiles of complementary chirality.

Binding Assays for the Quantitative Detection of P. brevis Polyether Neurotoxins in Biological Samples and Antibodies as Therapeutic Aids for Polyether Marine Intoxication

DTIC Science & Technology

1987-12-01

editions are obsolete. -I Block 19 continued structure. Preliminary experiments involving conversion of the radio- immunoassay to a urease enzyme linked...the radioimmunoassay to a urease I enzyme linked form have been successful. DTIC GTAB Di tributioul AV~i~b~±~YCoded Avsi abi11i ntY___ tat Special...necessary prior to thin- layer chromatography. A preparative thin- layer chromatography step using silica gel plates (1000 u thickness) utilizes acetone

Tribological reactions of perfluoroalkyl polyether oils with stainless steel under ultrahigh vacuum conditions at room temperature

NASA Technical Reports Server (NTRS)

Mori, Shigeyuki; Morales, Wilfredo

1989-01-01

The reaction between three types of commercial perfluoroalkyl polyether (PFPE) oils and stainless steel 440C was investigated experimentally during sliding under ultrahigh vacuum conditions at room temperature. It is found that the tribological reaction of PFPE is mainly affected by the activity of the mechanically formed fresh surfaces of metals rather than the heat generated at the sliding contacts. The fluorides formed on the wear track act as a boundary layer, reducing the friction coefficient.

Novel octanuclear copper(I) metallomacrocycles and their transformation into hexanuclear 2-dimensional grids of copper(i) coordination polymers containing cyclodiphosphazanes, [(micro-NtBuP)2(NC4H8X)2] (X = NMe, O).

PubMed

Suresh, D; Balakrishna, Maravanji S; Mague, Joel T

2008-07-07

Novel octanuclear copper(I) macrocyclic complexes and hexanuclear 2-dimensional grid-like polymers containing [P(micro-NR)](2) scaffold in which the anionic moieties are trapped inside the cationic macrocyclic cavities are reported.

Organic Materials as Electrodes for Li-ion Batteries

DTIC Science & Technology

2015-09-04

Various macrocycles, their synthesis, characterization and subsequent use in lithium - ion batteries were attempted. Ellagic acid, alizarin and...Various macrocycles, their synthesis, characterization and subsequent use in lithium - ion batteries were attempted. Ellagic acid, alizarin and...characterization and subsequent use in lithium - ion batteries have been attempted to. Lithium -based batteries are at the forefront of battery

Polymers containing nickel(II) complexes of Goedken's macrocycle: optimized synthesis and electrochemical characterization.

PubMed

Paquette, Joseph A; Sauvé, Ethan R; Gilroy, Joe B

2015-04-01

The synthesis and characterization of a new class of nickel-containing polymers is described. The optimized copolymerization of alkyne-bearing nickel(II) complexes of Goedken's macrocycle (4,11-dihydro-5,7,12,14-tetramethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine) and brominated 9,9-dihexylfluorene produced polymers with potential application as functional redox-active materials. The title polymers exhibit electrochemically reversible, ligand-centered oxidation events at 0.24 and 0.73 V versus the ferrocene/ferrocenium redox couple. They also display exceptional thermal stability and interesting absorption properties due to the presence of the macrocyclic nickel(II) complexes and π-conjugated units incorporated in their backbones. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isopropyl Myristate-Modified Polyether-Urethane Coatings as Protective Barriers for Implantable Medical Devices

PubMed Central

Roohpour, Nima; Wasikiewicz, Jaroslaw M.; Moshaverinia, Alireza; Paul, Deepen; Rehman, Ihtesham U.; Vadgama, Pankaj

2009-01-01

Polyurethane films have potential applications in medicine, especially for packaging implantable medical devices. Although polyether-urethanes have superior mechanical properties and are biocompatible, achieving water resistance is still a challenge. Polyether based polyurethanes with two different molecular weights (PTMO1000, PTMO2000) were prepared from 4,4’-diphenylmethane diisocyanate and poly(tetra-methylene oxide). Polymer films were introduced using different concentrations (0.5-10 wt %) of isopropyl myristate lipid (IPM) as a non-toxic modifying agent. The physical and mechanical properties of these polymers were characterised using physical and spectroscopy techniques (FTIR, Raman, DSC, DMA, tensile testing). Water contact angle and water uptake of the membranes as a function of IPM concentration was also determined accordingly. The FTIR and Raman data indicate that IPM is dispersed in polyurethane at ≤ 2wt% and thermal analysis confirmed this miscibility to be dependent on soft segment length. Modified polymers showed increased tensile strength and failure strain as well as reduced water uptake by up to 24% at 1-2 wt% IPM.

Parasite infection accelerates age polyethism in young honey bees

PubMed Central

Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C.

2016-01-01

Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens. PMID:26912310

Parasite infection accelerates age polyethism in young honey bees.

PubMed

Lecocq, Antoine; Jensen, Annette Bruun; Kryger, Per; Nieh, James C

2016-02-25

Honey bees (Apis mellifera) are important pollinators and their health is threatened worldwide by persistent exposure to a wide range of factors including pesticides, poor nutrition, and pathogens. Nosema ceranae is a ubiquitous microsporidian associated with high colony mortality. We used lab micro-colonies of honey bees and video analyses to track the effects of N. ceranae infection and exposure on a range of individual and social behaviours in young adult bees. We provide detailed data showing that N. ceranae infection significantly accelerated the age polyethism of young bees, causing them to exhibit behaviours typical of older bees. Bees with high N. ceranae spore counts had significantly increased walking rates and decreased attraction to queen mandibular pheromone. Infected bees also exhibited higher rates of trophallaxis (food exchange), potentially reflecting parasite manipulation to increase colony infection. However, reduction in queen contacts could help bees limit the spread of infection. Such accelerated age polyethism may provide a form of behavioural immunity, particularly if it is elicited by a wide variety of pathogens.

Sulfonated poly(ether sulfone)s containing pyridine moiety for PEMFC.

PubMed

Jang, Hohyoun; Islam, Md Monirul; Lim, Youngdon; Hossain, Md Awlad; Cho, Younggil; Joo, Hyunho; Kim, Whangi; Jeon, Heung-Seok

2014-10-01

Sulfonated poly(ether sulfone)s with varied degree of sulfonation (DS) were prepared via post-sulfonation of synthesized pyridine based poly(ether sulfone) (PPES) using concentrated sulfuric acid as sulfonating agent. The DS was varied with different mole ratio of 4,4'-(2,2-diphenylethenylidene)diphenol, DHTPE in the polymer unit. PPES copolymers were synthesized by direct polycondensation of pyridine unit with bis-(4-fluorophenyl)-sulfone, 4, 4'-sulfonyldiphenol and DHTPE. The structure of the resulting PPES copolymer membranes with different sulfonated units were studied by 1H NMR spectroscopy and thermogravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymer with water. The ion exchange capacity (IEC) and proton conductivity were evaluated according to the increase of DS. The water uptake (WU) of the resulting membranes was in the range of 17-58%, compared to that of Nafion 211 28%. The membranes provided proton conductivities of 65-95 mS/cm in contrast to 103 mS/cm of Nafion 211.

Crosslinked wholly aromatic polyether membranes based on quinoline derivatives and their application in high temperature polymer electrolyte membrane fuel cells

NASA Astrophysics Data System (ADS)

Kallitsis, K. J.; Nannou, R.; Andreopoulou, A. K.; Daletou, M. K.; Papaioannou, D.; Neophytides, S. G.; Kallitsis, J. K.

2018-03-01

An AB type difunctional quinoline based monomer bearing a pentafluorophenyl unit combined with a phenol functionality is being synthesized and homopolymerized to create linear aromatic polyethers as polymer electrolytes for HT-PEM FCs applications. Several conditions are tested for the optimized synthesis of the monomer and homopolymer. Additionally, covalent crosslinking through aromatic polyether bond formation enables the creation of wholly aromatic crosslinked polymeric electrolyte membranes. More specifically, the perfluorophenyl units are crosslinked with other hydroxyl end functionalized moieties, providing membranes with enhanced chemical and mechanical properties that are moreover easily doped with phosphoric acid even at ambient temperatures. All membranes are evaluated for their structural and thermal characteristics and their doping ability with phosphoric acid. Selected crosslinked membranes are further tested in terms of their single cell performance at the temperature range 160 °C-200 °C showing promising performance and high conductivity values even up to 0.2 S cm-1 in some cases.

Controlled synthesis of multi-arm star polyether-polycarbonate polyols based on propylene oxide and CO2.

PubMed

Hilf, Jeannette; Schulze, Patricia; Seiwert, Jan; Frey, Holger

2014-01-01

Multi-arm star copolymers based on a hyperbranched poly(propylene oxide) polyether-polyol (hbPPO) as a core and poly(propylene carbonate) (PPC) arms are synthesized in two steps from propylene oxide (PO), a small amount of glycidol and CO2 . The PPC arms are prepared via carbon dioxide (CO2 )/PO copolymerization, using hbPPO as a multifunctional macroinitiator and the (R,R)-(salcy)CoOBzF5 catalyst. Star copolymers with 14 and 28 PPC arms, respectively, and controlled molecular weights in the range of 2700-8800 g mol(-1) are prepared (Mw /Mn = 1.23-1.61). Thermal analysis reveals lowered glass transition temperatures in the range of -8 to 10 °C for the PPC star polymers compared with linear PPC, which is due to the influence of the flexible polyether core. Successful conversion of the terminal hydroxyl groups with phenylisocyanate demonstrates the potential of the polycarbonate polyols for polyurethane synthesis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organotin Polyethers as Biomaterials

PubMed Central

Carraher, Charles E.; Roner, Michael R.

2009-01-01

Organotin polyethers are easily synthesized employing interfacial polymerization systems involving the reaction of hydroxyl-containing Lewis bases and organotin halides. A wide variety of organotin-containing polymeric products have been synthesized including those derived from natural and synthetic polymers such as lignin, xylan, cellulose, dextran, and poly(vinyl alcohol). Others have been synthesized employing known drug diols such as dicumarol, DES, and dienestrol and a wide variety of synthetic diols. Included in these materials are the first water soluble organotin polymers. The organotin polyethers exhibit a wide range of biological activities. Some selectively inhibit a number of unwanted bacteria, including Staph. MRSA, and unwanted yeasts such as Candida albicans. Some also inhibit a variety of viruses including those responsible for herpes infections and smallpox. Others show good inhibition of a wide variety of cancer cell lines including cell lines associated with ovarian, colon, lung, prostrate, pancreatic and breast cancer. The synthesis, structural characterization, and biological characterization of these materials is described in this review.

Safety Assessment of Methyl Glucose Polyethers and Esters as Used in Cosmetics.

PubMed

Johnson, Wilbur; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

2016-11-01

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of methyl glucose polyethers and esters which function in cosmetics as skin/hair-conditioning agents, surfactants, or viscosity increasing agents. The esters included in this assessment are mono-, di-, or tricarboxyester substituted methyl glucosides, and the polyethers are mixtures of various chain lengths. The Panel reviewed available animal and clinical data, including the molecular weights, log K ow s, and other properties in making its determination of safety on these ingredients. Where there were data gaps, similarities between molecular structures, physicochemical and biological characteristics, and functions and concentrations in cosmetics allowed for extrapolation of the available toxicological data to assess the safety of the entire group. The Panel concluded that there likely would be no significant systemic exposure from cosmetic use of these ingredients, and that these ingredients are safe in cosmetic formulations in the present practices of use and concentration. © The Author(s) 2016.

Bis-Acridines as Lead Antiparasitic Agents: Structure-Activity Analysis of a Discrete Compound Library In Vitro▿

PubMed Central

Caffrey, Conor R.; Steverding, Dietmar; Swenerton, Ryan K.; Kelly, Ben; Walshe, Deirdre; Debnath, Anjan; Zhou, Yuan-Min; Doyle, Patricia S.; Fafarman, Aaron T.; Zorn, Julie A.; Land, Kirkwood M.; Beauchene, Jessica; Schreiber, Kimberly; Moll, Heidrun; Ponte-Sucre, Alicia; Schirmeister, Tanja; Saravanamuthu, Ahilan; Fairlamb, Alan H.; Cohen, Fred E.; McKerrow, James H.; Weisman, Jennifer L.; May, Barnaby C. H.

2007-01-01

Parasitic diseases are of enormous public health significance in developing countries—a situation compounded by the toxicity of and resistance to many current chemotherapeutics. We investigated a focused library of 18 structurally diverse bis-acridine compounds for in vitro bioactivity against seven protozoan and one helminth parasite species and compared the bioactivities and the cytotoxicities of these compounds toward various mammalian cell lines. Structure-activity relationships demonstrated the influence of both the bis-acridine linker structure and the terminal acridine heterocycle on potency and cytotoxicity. The bioactivity of polyamine-linked acridines required a minimum linker length of approximately 10 Å. Increasing linker length resulted in bioactivity against most parasites but also cytotoxicity toward mammalian cells. N alkylation, but less so N acylation, of the polyamine linker ameliorated cytotoxicity while retaining bioactivity with 50% effective concentration (EC50) values similar to or better than those measured for standard drugs. Substitution of the polyamine for either an alkyl or a polyether linker maintained bioactivity and further alleviated cytotoxicity. Polyamine-linked compounds in which the terminal acridine heterocycle had been replaced with an aza-acridine also maintained acceptable therapeutic indices. The most potent compounds recorded low- to mid-nanomolar EC50 values against Plasmodium falciparum and Trypanosoma brucei; otherwise, low-micromolar potencies were measured. Importantly, the bioactivity of the library was independent of P. falciparum resistance to chloroquine. Compound bioactivity was a function of neither the potential to bis-intercalate DNA nor the inhibition of trypanothione reductase, an important drug target in trypanosomatid parasites. Our approach illustrates the usefulness of screening focused compound libraries against multiple parasite targets. Some of the bis-acridines identified here may represent useful starting points for further lead optimization. PMID:17371810

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ying

My graduate research has focused on separation science and bioanalytical analysis, which emphasized in method development. It includes three major areas: enantiomeric separations using high performance liquid chromatography (HPLC), Super/subcritical fluid chromatography (SFC), and capillary electrophoresis (CE); drug-protein binding behavior studies using CE; and carbohydrate analysis using liquid chromatograph-electrospray ionization mass spectrometry (LC-ESI-MS). Enantiomeric separations continue to be extremely important in the pharmaceutical industry. An in-depth evaluation of the enantiomeric separation capabilities of macrocyclic glycopeptides CSPs with SFC mobile phases was investigated using a set of over 100 chiral compounds. It was found that the macrocyclic based CSPs were ablemore » to separate enantiomers of various compounds with different polarities and functionalities. Seventy percent of all separations were achieved in less than 4 min due to the high flow rate (4.0 ml/min) that can be used in SFC. Drug-protein binding is an important process in determining the activity and fate of a drug once it enters the body. Two drug/protein systems have been studied using frontal analysis CE method. More sensitive fluorescence detection was introduced in this assay, which overcame the problem of low sensitivity that is common when using UV detection for drug-protein studies. In addition, the first usage of an argon ion laser with 257 nm beam coupled with CCD camera as a frontal analysis detection method enabled the simultaneous observation of drug fluorescence as well as the protein fluorescence. LC-ESI-MS was used for the separation and characterization of underivatized oligosaccharide mixtures. With the limits of detection as low as 50 picograms, all individual components of oligosaccharide mixtures (up to 11 glucose-units long) were baseline resolved on a Cyclobond I 2000 column and detected using ESI-MS. This system is characterized by high chromatographic resolution, high column stability, and high sensitivity. In addition, this method showed potential usefulness for the sensitive and quick analysis of hydrolysis products of polysaccharides, and for trace level analysis of individual oligosaccharides or oligosaccharide isomers from biological systems.« less

Crystal structures of complexes of the cys-syn-cys isomer of dicyclohexano-18-crown-6 with oxonium hexafluorotantalate and oxonium hexafluoroniobate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fonari, M. S.; Alekseeva, O. A.; Furmanova, N. G.

2007-03-15

The crystal structures of [(cys-syn-cys-dicyclohexano-18-crown-6 . H{sub 3}O)][TaF{sub 6}] and [(cys-syn-cys-dicyclohexano-18-crown-6 . H{sub 3}O)][NbF{sub 6}] complex compounds are determined using X-ray diffraction analysis. The tantalum complex has two polymorphic modifications, namely, the monoclinic (I) and triclinic (II) modifications. The unit cell parameters of these compounds are as follows: a = 8.507(4) A, b = 11.947(5) A, c = 27.392(12) A, {beta} = 93.11(1) deg., Z = 4, and space group P2{sub 1}/n for modification I; and a = 10.828(1) A, b = 11.204(1) A, c = 12.378(1) A, {alpha} = 72.12(1) deg., {beta} = 79.40(1) deg., {gamma} = 73.70(1) deg.,more » Z = 2, and space group P-1 for modification II. The triclinic niobium complex [(cys-syn-cys-dicyclohexano-18-crown-6 . H{sub 3}O)][NbF{sub 6}] (III) with the unit cell parameters a = 10.796(3) A, b = 11.183(3) A, c = 12.352(3) A, {alpha} = 72.364(5) deg., {beta} = 79.577(5) deg., {gamma} = 73.773(4) deg., Z = 2, and space group P-1 is isostructural with tantalum complex II. The structures of all three complexes are ionic in character. The oxonium cation in complexes I-III is encapsulated by the crown ether and thus forms one ordinary and two bifurcated hydrogen bonds with the oxygen atoms of the crown ether. This macrocyclic cation is bound to the anions through the C-H...F contacts (H...F, 2.48-2.58 A). The conformation of the macrocycle in complex I differs substantially from that in complex II (III)« less

Synthesis, characterization and in vitro antimicrobial studies of Co(II), Ni(II) and Cu(II) complexes derived from macrocyclic compartmental ligand

NASA Astrophysics Data System (ADS)

El-Gammal, O. A.; Bekheit, M. M.; El-Brashy, S. A.

2015-02-01

New Co(II), Ni(II) and Cu(II) complexes derived from tetradentate macrocyclic nitrogen ligand, (1E,4E,8E,12E)-5,8,13,16-tetramethyl-1,4,9,12-tetrazacyclohexadeca-4,8,12,16-tetraene (EDHDH) have been synthesized. The complexes have been characterized by elemental analysis, spectral (IR, UV-Vis, 1H NMR and ESR (for Cu(II) complex)) mass, and magnetic as well as thermal analysis measurements. The complexes afforded the formulae: [Cu(EDHDH)Cl2]·2EtOH and [M(EDHDH)X2]·nH2O where M = Co(II) and Ni(II), X = Cl- or OH-, n = 1,0, respectively. The data revealed an octahedral arrangement with N4 tetradentate donor sites in addition to two Cl atoms occupying the other two sites. ESR spectrum of Cu2+ complex confirmed the suggested geometry with values of a α2and β2 indicating that the in-plane σ-bonding and in-plane π-bonding are appreciably covalent, and are consistent with very strong σ-in-plane bonding in the complexes. The molecular modeling is drawn and showed the bond length, bond angle, chemical reactivity, energy components (kcal/mol) and binding energy (kcal/mol) for all the title compounds using DFT method. Also, the thermal behavior and the kinetic parameters of degradation were determined using Coats-Redfern and Horowitz-Metzger methods. Moreover, the in vitro antibacterial studies of all compounds screened against pathogenic bacteria (two Gram +ve and two Gram -ve) to assess their inhibiting potential. The assay indicated that the inhibition potential is metal ion dependent. The ligand, EDHDH, Co(II) and Cu(II) complexes exhibited a remarkable antibacterial activity against Streptococcus Pyogenes as Gram +ve and Proteus vulgaris as Gram -ve bacterial strains. On the other hand, Ni(II) complex revealed a moderate antibacterial activity against both Gram +ve organisms and no activity against Gram -ve bacterial strain.

Magnetic solid-phase extraction based on carbon nanotubes for the determination of polyether antibiotic and s-triazine drug residues in animal food with LC-MS/MS.

PubMed

Liu, Xiaoxing; Xie, Shuyu; Ni, Tengteng; Chen, Dongmei; Wang, Xu; Pan, Yuanhu; Wang, Yulian; Huang, Lingli; Cheng, Guyue; Qu, Wei; Liu, Zhenli; Tao, Yanfei; Yuan, Zonghui

2017-06-01

Carbon nanotubes-magnetic nanoparticles, comprising ferroferric oxide nanoparticles and carbon nanotubes, were prepared through a simple one-step synthesis method and subsequently applied to magnetic solid-phase extraction for the determination of polyether antibiotic and s-triazine drug residues in animal food coupled with liquid chromatography with tandem mass spectrometry. The nanocomposites were characterized by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry. The components within the nanocomposites endowed the material with high extraction performance and manipulative convenience. Compared with carbon nanotubes, the as-prepared carbon nanotubes-magnetic nanoparticles showed better extraction and separation efficiencies for polyether antibiotics and s-triazine drugs thanks to the contribution of the iron-containing magnetic nanoparticles. Various experimental parameters affecting the extraction efficiency had been investigated in detail. Under the optimal conditions, the good linearity ranging from 1 to 200 μg/kg for diclazuril, toltrazuril, toltrazuril sulfone, lasalocid, monensin, salinomycin, narasin, nanchangmycin, and maduramicin, low limits of detection ranging from 1 to 5 μg/kg, and satisfactory spiked recoveries (77.1-91.2%, with the inter relative standard deviation values from 4.0 to 12.2%) were shown. It was confirmed that this novel method was an efficient pretreatment and enrichment procedure and could be successfully applied for extraction and determination of polyether and s-triazine drug residues in complex matrices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

UV-Surface Treatment of Fungal Resistant Polyether Polyurethane Film-Induced Growth of Entomopathogenic Fungi

PubMed Central

Lando, Gabriela Albara; Marconatto, Letícia; Schrank, Augusto; Vainstein, Marilene Henning

2017-01-01

Synthetic polymers are the cause of some major environmental impacts due to their low degradation rates. Polyurethanes (PU) are widely used synthetic polymers, and their growing use in industry has produced an increase in plastic waste. A commercial polyether-based thermoplastic PU with hydrolytic stability and fungus resistance was only attacked by an entomopathogenic fungus, Metarhiziumanisopliae, when the films were pre-treated with Ultraviolet (UV) irradiation in the presence of reactive atmospheres. Water contact angle, Fourier transform infrared spectroscopy in attenuated total reflection mode (FTIR-ATR), scanning electron microscopy (SEM), and profilometer measurements were mainly used for analysis. Permanent hydrophilic PU films were produced by the UV-assisted treatments. Pristine polyether PU films incubated for 10, 30, and 60 days did not show any indication of fungal growth. On the contrary, when using oxygen in the UV pre-treatment a layer of fungi spores covered the sample, indicating a great adherence of the microorganisms to the polymer. However, if acrylic acid vapors were used during the UV pre-treatment, a visible attack by the entomopathogenic fungi was observed. SEM and FTIR-ATR data showed clear evidence of fungal development: growth and ramifications of hyphae on the polymer surface with the increase in UV pre-treatment time and fungus incubation time. The results indicated that the simple UV surface activation process has proven to be a promising alternative for polyether PU waste management. PMID:28718785

Langmuir and Langmuir-Blodgett films of multifunctional, amphiphilic polyethers with cholesterol moieties.

PubMed

Reuter, Sascha; Hofmann, Anna M; Busse, Karsten; Frey, Holger; Kressler, Jörg

2011-03-01

Langmuir films of multifunctional, hydrophilic polyethers containing a hydrophobic cholesterol group (Ch) were studied by surface pressure-mean molecular area (π-mmA) measurements and Brewster angle microscopy (BAM). The polyethers were either homopolymers or diblock copolymers of linear poly(glycerol) (lPG), linear poly(glyceryl glycidyl ether) (lPGG), linear poly(ethylene glycol) (lPEG), or hyperbranched poly(glycerol) (hbPG). Surface pressure measurements revealed that the homopolymers lPG and hbPG did not stay at the water surface after spreading and solvent evaporation, in contrast to lPEG. Because of the incorporation of the Ch group in the polymer structure, stable Langmuir films were formed by Ch-lPG(n), Ch-lPGG(n), and Ch-hbPG(n). The Ch-hbPG(n), Ch-lPEG(n), Ch-lPEG(n)-b-lPG(m), Ch-lPEG(n)-b-lPGG(m), and Ch-lPEG(n)-b-hbPG(m) systems showed an extended plateau region assigned to a phase transition involving the Ch groups. Typical hierarchically ordered morphologies of the LB films on hydrophilic substrates were observed for all Ch-initiated polymers. All LB films showed that Ch of the Ch-initiated homopolymers is able to crystallize. This strong tendency of self-aggregation then triggers further dewetting effects of the respective polyether entities. Fingerlike morphologies are observed for Ch-lPEG(69), since the lPEG(69) entity is able to undergo crystallization after transfer onto the silicon substrate.

Evaluation of the Efficacy of Different Mixing Techniques and Disinfection on Microbial Colonization of Polyether Impression Materials: A Comparative Study.

PubMed

Singla, Youginder; Pachar, Renu B; Poriya, Sangeeta; Mishra, Aalok; Sharma, Rajni; Garg, Anshu

2018-03-01

This study aims to determine the role of mixing techniques of polyether impression materials and efficacy of disinfection on microbial colonization of these impression materials. Polyether impression material was mixed using two methods: First by hand mixing (group I) and second using an automixer (group II) with a total of 100 samples. Four microbial strains were studied, which included Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. After incubation, the bacterial colonies were counted, and then, disinfectant solution was applied. The effect of disinfection solution was evaluated for each specimen. The surface of polyether impression materials mixed with an automixer has less number of voids and overall a smoother surface as compared with the hand-mixed ones. On comparing the disinfection procedures, i.e., specimens without any disinfection and specimens after disinfection, statistically highly significant difference was seen between all the groups. We can conclude that impression mixing procedures are important in determining the surface characteristics of the impression and ultimately the colonization of bacteria and also determine the importance of disinfection on microbial colonization. This study emphasises the deleterious role of nosocomial infections and specific measures that should be taken regarding the prevention of such diseases. Dental impressions are proved to be a source of such infections and may lead to transmission of such diseases. Thus, proper measures should be taken right from the first step of impression taking to minimizing and preventing such kind of contaminations in clinical practice.

Red Soils Harbor Diverse Culturable Actinomycetes That Are Promising Sources of Novel Secondary Metabolites

PubMed Central

Guo, Xiaoxuan; Liu, Ning; Li, Xiaomin; Ding, Yun; Shang, Fei; Gao, Yongsheng; Ruan, Jisheng

2015-01-01

Red soils, which are widely distributed in tropical and subtropical regions of southern China, are characterized by low organic carbon, high content of iron oxides, and acidity and, hence, are likely to be ideal habitats for acidophilic actinomycetes. However, the diversity and biosynthetic potential of actinomycetes in such habitats are underexplored. Here, a total of 600 actinomycete strains were isolated from red soils collected in Jiangxi Province in southeast China. 16S rRNA gene sequence analysis revealed a high diversity of the isolates, which were distributed into 26 genera, 10 families, and 7 orders within the class Actinobacteria; these taxa contained at least 49 phylotypes that are likely to represent new species within 15 genera. The isolates showed good physiological potentials for biosynthesis and biocontrol. Chemical screening of 107 semirandomly selected isolates spanning 20 genera revealed the presence of at least 193 secondary metabolites from 52 isolates, of which 125 compounds from 39 isolates of 12 genera were putatively novel. Macrolides, polyethers, diketopiperazines, and siderophores accounted for most of the known compounds. The structures of six novel compounds were elucidated, two of which had a unique skeleton and represented characteristic secondary metabolites of a putative novel Streptomyces phylotype. These results demonstrate that red soils are rich reservoirs for diverse culturable actinomycetes, notably members of the families Streptomycetaceae, Pseudonocardiaceae, and Streptosporangiaceae, with the capacity to synthesize novel bioactive compounds. PMID:25724963

Dependence of the basic properties of meso-nitro-substituted derivatives of β-octaethylporphyrin on the nature of substituents

NASA Astrophysics Data System (ADS)

Pukhovskaya, S. G.; Ivanova, Yu. B.; Nam, Dao The; Vashurin, A. S.

2014-10-01

Spectrophotometric titration is used to study the basic properties of a series of porphyrins with a continuously increasing degree of macrocycle deformation resulting from the introduction of strong electron-withdrawing substituents: 2,3,7,8,12,13,17,18-octaethylporphyrin ( I), 5-nitro-2,3,7,8,12,13,17,18-octaethylporphyrin ( II), 5,15-dinitro-2,3,7,8,12,13,17,18-octaethylporphyrin ( III), 5,10,15-trinitro-2,3,7,8,12,13,17,18-octaethylporphyrin ( IV), and 5,10,15,20-tetranitro-2,3,7,8,12,13,17,18-octaethylporphyrin ( V). It is found that the values of log K b (total basicity constants) obtained for the investigated compounds consistently diminish with an increase in the number of meso-substituents: 11.85 ( I) > 10.45 ( II) > 10.31 ( III) > 10.23 ( IV) > 9.56 ( V). It is shown that two opposing factors, the steric and electronic effects of the substituents, change the basic properties of the above series of compounds.

Polyacylated oligosaccharides from medicinal Mexican morning glory species as antibacterials and inhibitors of multidrug resistance in Staphylococcus aureus.

PubMed

Pereda-Miranda, Rogelio; Kaatz, Glenn W; Gibbons, Simon

2006-03-01

Twenty-two convolvulaceous oligosaccharides selected from the tricolorin (1-7), scammonin (8, 9), and orizabin (10-22) series were evaluated for activity against a panel of Staphylococcus aureus strains possessing or lacking specific efflux pumps. The minimum inhibitory concentrations (MIC values) for most of the amphipatic compounds ranged from 4 to 32 microg/mL against XU-212 (possessing the TetK multidrug efflux pump) and SA-1199B (overexpressing the NorA multidrug efflux pump), compared with 64 and 0.25 microg/mL, respectively, for tetracycline. This activity was shown to be bactericidal. Two microbiologically inactive members of the orizabin series (10, 20) increased norfloxacin susceptibility of strain SA-1199B. At low concentrations, compound 10 was a more potent inhibitor of multidrug pump-mediated EtBr efflux than reserpine. The wide range of antimicrobial activity displayed by these compounds is an example of synergy between related components occurring in the same medicinal crude drug extract, i.e., microbiologically inactive components disabling a resistance mechanism, potentiating the antibiotic properties of the active substances. These results provide an insight into the antimicrobial potential of these complex macrocyclic lactones and open the possibility of using these compounds as starting points for the development of potent inhibitors of S. aureus multidrug efflux pumps.

Magnetism in (Semi)Conducting Macrocycles of pi conjugated Polymers

DTIC Science & Technology

2016-12-09

wise and avoiding a break in the continuity of the macrocycle. As a first criterion we tested the continuity of the electron orbitals over the...magnesium chloride) and post polymerization functionalization by a Sonogashira coupling reaction is required (scheme 2). Scheme 2: Synthetic...Sonogashira post - polymerization chain end functionalization and B isotopic model of the different population present in the final batch

Neighbor-Directed Histidine N (s)–Alkylation: A Route to Imidazolium-Containing Phosphopeptide Macrocycles-Biopolymers | Center for Cancer Research

Cancer.gov

Our recently discovered, selective, on-resin route to N(s)-alkylated imidazolium-containing histidine residues affords new strategies for peptide mimetic design. In this, we demonstrate the use of this chemistry to prepare a series of macrocyclic phosphopeptides, in which imidazolium groups serve as ring-forming junctions. Interestingly, these cationic moieties subsequently

Multicomponent Macrocyclization Reactions (MCMRs) Employing Highly Reactive Acyl Ketene and Nitrile Oxide Intermediates

PubMed Central

Knapp, John M.; Fettinger, James C.; Kurth, Mark J.

2011-01-01

An efficient synthesis of spiro-fused macrolactams by a multicomponent macrocyclization reaction (MCMR) is reported. The use of highly reactive, transient intermediates in this MCMR permits short reaction times, even at high dilution. The methods employed for this MCMR were first developed as a four component strategy for the synthesis of β-ketoamide isoxazolines. PMID:21827181

Hydrolyzable tannins of tamaricaceous plants. III. Hellinoyl- and macrocyclic-type ellagitannins from Tamarix nilotica.

PubMed

Orabi, Mohamed A A; Taniguchi, Shoko; Yoshimura, Morio; Yoshida, Takashi; Kishino, Kaori; Sakagami, Hiroshi; Hatano, Tsutomu

2010-05-28

Three new hellinoyl-type ellagitannins, nilotinins M4 (7), D7 (8), and D8 (9), and a new macrocyclic-type, nilotinin D9 (10), together with eight known tannins, hirtellins B (2), C (11), and F (12), isohirtellin C (13), tamarixinin A (3), tellimagrandins I and II, and 1,2,6-tri-O-galloyl-beta-d-glucose (14), were isolated from an aqueous acetone extract of Tamarix nilotica dried leaves. Nilotinin M4 (7) is a monomeric tannin possessing a hellinoyl moiety. The structure of 8 demonstrated replacement of one of the HHDP groups at the glucose core O-4/O-6 in ordinary dimeric tannins with a galloyl moiety at O-6. This is a new structural feature among the tamaricaceous ellagitannins. On the basis of the results, reported spectroscopic assignments for 2, 3, and the macrocyclic tannins 11-13 were revised. Unusual shifts in the NMR spectra of these macrocyclic tannins are also discussed in relation to their conformations. Several tannins isolated from T. nilotica were assessed for possible cytotoxic activity against four human tumor cell lines, and nilotinin D8 (9) and hirtellin A (1) showed high cytotoxic effects.

Characterization of the macrocyclase involved in the biosynthesis of RiPP cyclic peptides in plants.

PubMed

Chekan, Jonathan R; Estrada, Paola; Covello, Patrick S; Nair, Satish K

2017-06-20

Enzymes that can catalyze the macrocyclization of linear peptide substrates have long been sought for the production of libraries of structurally diverse scaffolds via combinatorial gene assembly as well as to afford rapid in vivo screening methods. Orbitides are plant ribosomally synthesized and posttranslationally modified peptides (RiPPs) of various sizes and topologies, several of which are shown to be biologically active. The diversity in size and sequence of orbitides suggests that the corresponding macrocyclases may be ideal catalysts for production of cyclic peptides. Here we present the biochemical characterization and crystal structures of the plant enzyme PCY1 involved in orbitide macrocyclization. These studies demonstrate how the PCY1 S9A protease fold has been adapted for transamidation, rather than hydrolysis, of acyl-enzyme intermediates to yield cyclic products. Notably, PCY1 uses an unusual strategy in which the cleaved C-terminal follower peptide from the substrate stabilizes the enzyme in a productive conformation to facilitate macrocyclization of the N-terminal fragment. The broad substrate tolerance of PCY1 can be exploited as a biotechnological tool to generate structurally diverse arrays of macrocycles, including those with nonproteinogenic elements.

Dielectric Properties of Polyether Sulfone/Bismaleimide Resin Composite Based on Nanolumina Modified by Super-Critical Ethanol

NASA Astrophysics Data System (ADS)

Chen, Yufei; Li, Zhichao; Teng, Chengjun; Li, Fangliang; Han, Yang

2016-11-01

Nano-alumina was chemically modified with super-critical ethanol enabling a surface active coating. Modified nano-alumina was incorporated in polymer blends based on thermoplastic polyether sulfone and thermosetting bismaleimide resin to produce novel nanocomposites designated as SCE-Al2O3/PES-MBAE. In the SCE-Al2O3/PES-MBAE nano-composites, the matrix was originally formed from 4,4'-diamino diphenyl methane bismaleimide (MBMI) using the diluents of 3,3'-diallyl bisphenol A (BBA) and bisphenol-A diallyl ether (BBE), while polyether sulfone (PES) was used as toughening agent along with super-critically modified nano-alumina (SCE-Al2O3) as filler material. The content of SCE-Al2O3 was varied from 0 wt.% to 6 wt.%. The nano-composites were characterized for their morphological, spectroscopic and dielectric properties. Fourier transform infrared spectroscopy (FT-IR) indicated that ethanol molecules had adhered to the surface of the nano-Al2O3 in super-critical state. A reaction between MBMI and allyl compound occurred and SCE-Al2O3 was doped into the polymer matrix. Volume resistivity of the composite initially increased and then decreased. The modification due to SCE-Al2O3 could overcome the undesirable impact of PES by using a bare minimum level of SCE-Al2O3. The dielectric constant ( ɛ) and dielectric loss (tan δ) as in the case of volume resistivity were initially increased and then decreased with the content of SCE-Al2O3 in the composite. The dielectric constant, dielectric loss and dielectric strength of SCE-Al2O3 (4 wt.%)/PES (5 wt.%)-MBAE nano-composite were 3.53 (100 Hz), 1.52 × 10-3 (100 Hz) and 15.66 kV/mm, respectively, which indicated that the dielectric properties of the composite fulfilled the basic requirements of electrical and insulating material. It was evident from the morphological analysis that the SCE-Al2O3 was evenly dispersed at the nanoscale; for example, the size of SCE-Al2O3 in SCE-Al2O3 (4 wt.%)/PES (5 wt.%)-MBAE measured less than 50 nm.

Metal-templated synthesis of macrocyclic (triphosphine)molybdenum complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diel, B.N.; Brandt, P.F.; Haltiwanger, R.C.

1989-07-12

Reaction of CH{sub 2}=CHCH{sub 2}PH{sub 2}, CH{sub 2}=CHCH{sub 2}CH{sub 2}PH{sub 2}, and CH{equivalent to}CCH{sub 2}PPH{sub 2} with (mesitylene)Mo(CO){sub 3} or (cycloheptatriene)Mo(CO){sub 3} yields the complexes (CH{sub 2}=CHCH{sub 2}PH{sub 2}){sub 3} (1), (CH{sub 2}=CHCH{sub 2}CH{sub 2}PH{sub 2}){sub 3}Mo(CO){sub 3} (2), and (CH{equivalent to}CCH{sub 2}PH{sub 2}){sub 3}Mo(CO){sub 3}, (3), respectively. Reaction of CH{sub 2}=CHCH{sub 2}PH{sub 2} and CH{equivalent to}CCH{sub 2}PH{sub 2} with cis-(piperidine){sub 2}Mo(CO){sub 4} yields cis-(CH{sub 2}=CHCH{sub 2}PH{sub 2}){sub 2}Mo(CO){sub 4} (4) and cis-(CH{equivalent to}CCH{sub 2}PH{sub 2}){sub 2}Mo(CO){sub 4} (5). Free-radical-initiated cyclooligomerization of 1 and 2 yields the triligated macrocyclic secondary-phosphine complexes fac-(HP(CH{sub 2}){sub 3}){sub 3}Mo(CO){sub 3} (6) and fac-(HP-(CH{sub 2}){submore » 4}){sub 3}Mo(CO){sub 3} (7). Under similar conditions, reaction of 4 yields an acyclic diphosphine complex characterized tentatively as cis-(H{sub 2}P(CH{sub 2}){sub 3}PH(CH{sub 2}CH=CH{sub 2}))Mo(CO){sub 4} (8). Compounds 1-7 and 10 have been characterized by spectral ({sup 31}P, {sup 13}C, and {sup 1}H, NMR and IR and mass) data. 6 has been characterized in the solid state by single-crystal x-ray analysis, and the results are reported. {sup 31}P NMR spectra studies of the cyclooligomerization of 1 show the partially cyclized intermediates formed prior to 6. The macrocyclic complexes 6 and 7 are kinetically stable, showing no sign of ligand displacement in reactions with pH{sub 3}P, PF{sub 3}, KCN, or P(OMe){sub 3}. 44 refs., 4 figs., 4 tabs.« less

Alkali metal cation complexation by 1,3-alternate, mono-ionisable calix[4]arene-benzocrown-6 compounds

DOE PAGES

Surowiec, Malgorzata A.; Custelcean, Radu; Surowiec, Kazimierz; ...

2014-04-23

Alkali metal cation extraction behavior for two series of 1,3-alternate, mono-ionizable calix[4]arene-benzocrown-6 compounds is examined. In Series 1, the proton-ionizable group is a substituent on the benzo group of the polyether ring that directs it away from the crown ether cavity. In Series 2, the proton-ionizable group is attached to one para position in the calixarene framework, thus positioning it over the crown ether ring. Competitive solvent extraction of alkali metal cations from aqueous solutions into chloroform shows high Cs+ efficiency and selectivity. Single-species extraction pH profiles of Cs+ for Series 1 and 2 ligands with the same proton-ionizable groupmore » are very similar. Thus, association of Cs+ with the calixcrown ring is more important than the the proton-ionizable group’s position in relation to the crown ether cavity. Solid-state structures are presented for two unionized ligands from Series 2, as is a crystal containing two different ionized ligand–Cs+ complexes.« less

Binding Assays for the Quantitative Detection of P. brevis Polyether Neurotoxins in Biological Samples and Antibodies as Therapeutic Aids for Polyether Marine Intoxication

DTIC Science & Technology

1990-05-15

was also linked to urease and toxin-enzyme conjugates were evaluated. 4. Toxin Enzyme Conjugates. Brevetoxins linked to either Jack Bean urease or...described in materials and methods. For urease conjugates, 1:2, 1:4 and 1:6 molar ratios were investigated. The following protocol yielded the most...fold excess urease in 1 volume equivalent of water, in three equal aliquots. Total volume after addition is 2-fold the volume in step [2], final

Isolation and purification of macrocyclic components from Penicillium fermentation broth by high-speed counter-current chromatography.

PubMed

Gao, Xiang; Zhuang, Rongqiang; Guo, Jiannan; Bao, Jian; Fang, Meijuan; Liu, Yan; Xu, Pengxiang; Zhao, Yufen

2010-02-01

In this paper, high-speed counter-current chromatography (HSCCC), assisted with ESI-MS, was first successfully applied to the preparative separation of three macrolide antibiotics, brefeldin A (12.6 mg, 99.0%), 7'-O-formylbrefeldin A (6.5 mg, 95.0%) and 7'-O-acetylbrefeldin A (5.0 mg, 92.3%) from the crude extract of the microbe Penicillium SHZK-15. Considering the chemical nature and partition coefficient (K) values of the three target compounds, a two-step HSCCC isolation protocol was developed in order to obtain products with high purity. In the two-step method, the crude ethyl acetate extract was first fractionated and resulted in two peak fractions by HSCCC using solvent system n-hexane/ethyl acetate/methanol/water (HEMWat) (3:7:5:5 v/v/v/v), then purified using solvent systems HEMWat (3:5:3:5 v/v/v/v) and HEMWat (7:3:5:5 v/v/v/v) for each fraction. The purities and structures of the isolated compounds were determined by HPLC, X-ray crystallography, ESI-MS and NMR. The results demonstrated that HSCCC is a fast and efficient technique for systematic isolation of bioactive compounds from the microbes.

Phototoxic Activity and DNA Interactions of Water-Soluble Porphyrins and Their Rhenium(I) Conjugates.

PubMed

Mion, Giuliana; Gianferrara, Teresa; Bergamo, Alberta; Gasser, Gilles; Pierroz, Vanessa; Rubbiani, Riccardo; Vilar, Ramon; Leczkowska, Anna; Alessio, Enzo

2015-11-01

In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one [1,4,7]-triazacyclononane (TACN) units are connected to the porphyrin macrocycle through a hydrophilic linker; we also report their corresponding tetracationic Re(I) conjugates. The in vitro (photo)toxic effects of the compounds toward the human cell lines HeLa (cervical cancer), H460M2 (non-small-cell lung carcinoma), and HBL-100 (non-tumorigenic epithelial cells) are reported. Three of the compounds are not cytotoxic in the dark up to 100 μm, and the fourfold-symmetric couple revealed very good phototoxic indexes (PIs). The intracellular localization of all derivatives was studied in HeLa cells by confocal fluorescence microscopy. Although low nuclear localization was observed for some of them, it still prompted us to investigate their capacity to bind both quadruplex and duplex DNA; we observed significant selectivity in the tris-methylpyridinium derivatives for G-quadruplex interactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microscale Synthesis, Reactions, and (Super 1)H NMR Spectroscopic Investigations of Square Planar Macrocyclic, Tetramido-N Co(III) Complexes Relevant to Green Chemistry

ERIC Educational Resources Information Center

Watson, Tanya T.; Uffelman, Erich S.; Lee, Daniel W., III; Doherty, Jonathan R.; Schulze, Carl; Burke, Amy L.; Bonnema, Kristen, R.

2004-01-01

The microscale preparation, characterization, and reactivity of a square planar Co(III) complex that has grown out of a program to introduce experiments of relevance to green chemistry into the undergraduate curriculum is presented. The given experiments illustrate the remarkable redox and aqueous acid-base stability that make the macrocycles very…

Conformational analysis of a condensed macrocyclic β-lactam by NMR and molecular dynamics calculations

NASA Astrophysics Data System (ADS)

Keserű, György M.; Vásárhelyi, Helga; Makara, Gergely

1994-09-01

The conformation of the new macrocyclic β-lactam ( 1) was investigated by NMR and molecular dynamics (MD) calculations. Restraints obtained from NOESY and ROESY experiments were introduced into MD simulations which led to well-defined conformations. The preference for the calculated minimum energy conformation was confirmed by the analysis of vicinal coupling constants. Experimental coupling constants agreed with computed values.

Organic Materials as Electrodes for Li-ion Batteries

DTIC Science & Technology

2015-09-04

given for each class of materials. Various macrocycles, their synthesis, characterization and subsequent use in lithium - ion batteries were attempted...macrocycles, their synthesis, characterization and subsequent use in lithium - ion batteries have been attempted to. Lithium -based batteries are at the...organic dye can be used for storing reversibly, both lithium and sodium ions for rechargeable battery applications. In the present study, we have

Bistable or oscillating state depending on station and temperature in three-station glycorotaxane molecular machines.

PubMed

Busseron, Eric; Romuald, Camille; Coutrot, Frédéric

2010-09-03

High-yield, straightforward synthesis of two- and three-station [2]rotaxane molecular machines based on an anilinium, a triazolium, and a mono- or disubstituted pyridinium amide station is reported. In the case of the pH-sensitive two-station molecular machines, large-amplitude movement of the macrocycle occurred. However, the presence of an intermediate third station led, after deprotonation of the anilinium station, and depending on the substitution of the pyridinium amide, either to exclusive localization of the macrocycle around the triazolium station or to oscillatory shuttling of the macrocycle between the triazolium and monosubstituted pyridinium amide station. Variable-temperature (1)H NMR investigation of the oscillating system was performed in CD(2)Cl(2). The exchange between the two stations proved to be fast on the NMR timescale for all considered temperatures (298-193 K). Interestingly, decreasing the temperature displaced the equilibrium between the two translational isomers until a unique location of the macrocycle around the monosubstituted pyridinium amide station was reached. Thermodynamic constants K were evaluated at each temperature: the thermodynamic parameters DeltaH and DeltaS were extracted from a Van't Hoff plot, and provided the Gibbs energy DeltaG. Arrhenius and Eyring plots afforded kinetic parameters, namely, energies of activation E(a), enthalpies of activation DeltaH( not equal), and entropies of activation DeltaS( not equal). The DeltaG values deduced from kinetic parameters match very well with the DeltaG values determined from thermodynamic parameters. In addition, whereas signal coalescence of pyridinium hydrogen atoms located next to the amide bond was observed at 205 K in the oscillating rotaxane and at 203 K in the two-station rotaxane with a unique location of the macrocycle around the pyridinium amide, no separation of (1)H NMR signals of the considered hydrogen atoms was seen in the corresponding nonencapsulated thread. It is suggested that the macrocycle acts as a molecular brake for the rotation of the pyridinium-amide bond when it interacts by hydrogen bonding with both the amide NH and the pyridinium hydrogen atoms at the same time.

Synthesis of spiro quasi[1]catenanes and quasi[1]rotaxanes via a templated backfolding strategy

PubMed Central

Steemers, Luuk; Wanner, Martin J.; Lutz, Martin; Hiemstra, Henk; van Maarseveen, Jan H.

2017-01-01

Due to their well-defined three-dimensional geometry, spiro compounds are widely utilized in drug research. From the central tetrahedral carbon atom, besides the regular structure, an inverted spiro connectivity may be envisioned. Here we disclose the synthesis of this molecule class that we have coined quasi[1]catenanes. Next to their fascinating and aesthetic shape, the higher compactness as compared to regular spiro bicycles is noteworthy. To enable synthetic access to compact entangled multimacrocyclic molecules, we have developed a new strategy. The key element is a template, which is covalently connected to the linear precursors, and spatially directs the sterically congested backfolding macrocyclizations that are required to give quasi[1]catenanes. Similarly, quasi[1]rotaxanes are made. PMID:28541349

The metallic thread in a patchwork thesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hull, Emily A.

This thesis contains research that is being prepared for publication. Chapter 2 presents research on water and THF solvated macrocyclic Rh and Co compounds and the effects of different axial ligands (NO 2, NO, Cl, CH 3) on their optical activity. Chapter 3 involves the study of gas-phase Nb mono and dications with CO and CO 2. Chapter 4 is a study of reactions of CO and CO 2 with Ta mono and dications. Chapter 5 is a study on virtual orbitals, their usefulness, the use of basis sets in modeling them, and the inclusion of transition metals into themore » QUasi Atomic Minimal Basis (QUAMBO) method.68-72 Chapter 6 presents the conclusions drawn from the work presented in this dissertation.« less

Reactions of rhenium(V) and molybdenum(V) oxypentahalides with 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashurova, N.Kh.; Yakubov, K.G.

1993-11-01

The author studied complexation reactions of rhenium(V) and molybdenum(V) with a macrocyclic ligand 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane (Tet a). The authors found that in hydrohalic acid medium, the onium complexes [H{sub 2}(Tet a)][EOX{sub 5}] are formed, with E = Re, Mo; X = Cl, Br. Reactions of [EOX{sub 5}]{sup 2{minus}} with (Tet a) in nitrometane yield complexes of molecular and cation types [EO(Tet a)Cl{sub 3}] and [EO(Tet a)Br]Br{sub 2}. Composition and structure of the obtained compounds are established by elemental analysis, conductometry, and mid- and far-IR spectroscopy.

Convergent synthesis of multiporphyrin light-harvesting rods

DOEpatents

Lindsey, Jonathan S.; Loewe, Robert S.

2003-08-05

The present invention provides a convergent method for the synthesis of light harvesting rods. The rods are oligomers of the formula A.sup.1 (A.sup.b+1).sub.b, wherein b is at least 1, A.sup.1 through A.sup.b+1 are covalently coupled rod segments, and each rod segment A.sup.1 through A.sup.1+b comprises a compound of the formula X.sup.1 (X.sup.m+1).sub.m wherein m is at least 1 and X.sup.1 through X.sup.m+1 are covalently coupled porphyrinic macrocycles. Light harvesting arrays and solar cells containing such light harvesting rods are also described, along with intermediates useful in such methods and rods produced by such methods.

[Transformation of natural products into more potent compounds: chemical modification of monensin].

PubMed

Nagatsu, A; Sakakibara, J

1997-09-01

Monensin (1) is a representative compound of polyether ionophore antibiotics, which selectively transport Na+ ions. In order to obtain potent Na+ ionophores, the modification of the carboxyl group of monensin was carried out to yield monensylamino acids (2) and monensylamino acid-1,29-lactones (3). The Na+ permeability of ion through the erythrocyte membrane of 2 and 3 was evaluated by the 23Na-NMR method. Compound 2 showed less Na+ ion transport activity than monensin, probably due to the lower lipophilicity caused by the conformational change of the chain moiety of the molecules. Although 3 showed higher lipophilisity than 1, 3 had no Na+ ion permeability, probably due to loss of the carboxyl group. As more lipophilic compounds possessing a carboxyl group was supposed to have more ion transport activity, 7-O-acylmonensins (8) and 7-O-alkylmonensins (11) were synthesized. Among these compounds, the value of Na+ ion permeability of 7-O-benzylmonensin (11c) was 1.4 time that of 1. Further investigation was carried out by preparing various 7-O-(substituted benzyl)monensins (13), and 7-O-(p-ethylbenzyl)monensin (13b) exhibited the largest Na+ ion permeability, about twice the value of 1. In order to convert monensin (1) to Ca2+ ionophore, 7-carboxylmethylmonensin (18) via protected 7-oxomonensin (15), and 25-carboxylmonensin (26) were prepared. In the course of the synthesis, 15 was clarified as a useful intermediate to give 7-amino and 7-alkyl derivatives. Ca2+ ion transport activities of 18 and 26 were determined by a CHCl3 liquid membrane system. 25-carboxylmonensin (26) showed 70% of the activity of Ca2+ ionophore, lasalocid A, and compound 26 could be the lead compound for the preparation of a new Ca2+ ionophore.

Improved selectivity for Pb(II) by sulfur, selenium and tellurium analogues of 1,8-anthraquinone-18-crown-5: synthesis, spectroscopy, X-ray crystallography and computational studies.

PubMed

Mariappan, Kadarkaraisamy; Alaparthi, Madhubabu; Hoffman, Mariah; Rama, Myriam Alcantar; Balasubramanian, Vinothini; John, Danielle M; Sykes, Andrew G

2015-07-14

We report here a series of heteroatom-substituted macrocycles containing an anthraquinone moiety as a fluorescent signaling unit and a cyclic polyheteroether chain as the receptor. Sulfur, selenium, and tellurium derivatives of 1,8-anthraquinone-18-crown-5 (1) were synthesized by reacting sodium sulfide (Na2S), sodium selenide (Na2Se) and sodium telluride (Na2Te) with 1,8-bis(2-bromoethylethyleneoxy)anthracene-9,10-dione in a 1 : 1 ratio. The optical properties of the new compounds are examined and the sulfur and selenium analogues produce an intense green emission enhancement upon association with Pb(II) in acetonitrile. Selectivity for Pb(II) is markedly improved as compared to the oxygen analogue 1 which was also competitive for Ca(II) ion. UV-Visible and luminescence titrations reveal that 2 and 3 form 1 : 1 complexes with Pb(II), confirmed by single-crystal X-ray studies where Pb(II) is complexed within the macrocycle through coordinate covalent bonds to neighboring carbonyl, ether and heteroether donor atoms. Cyclic voltammetry of 2-8 showed classical, irreversible oxidation potentials for sulfur, selenium and tellurium heteroethers in addition to two one-electron reductions for the anthraquinone carbonyl groups. DFT calculations were also conducted on 1, 2, 3, 6, 6 + Pb(II) and 6 + Mg(II) to determine the trend in energies of the HOMO and the LUMO levels along the series.

In vitro photodynamic activity of lipid vesicles with zinc phthalocyanine derivative against Enterococcus faecalis.

PubMed

Sobotta, Lukasz; Dlugaszewska, Jolanta; Kasprzycki, Piotr; Lijewski, Sebastian; Teubert, Anna; Mielcarek, Jadwiga; Gdaniec, Maria; Goslinski, Tomasz; Fita, Piotr; Tykarska, Ewa

2018-06-01

Zinc(II) phthalocyanine bearing eight non-peripheral 2-propoxy substituents was subjected to physicochemical study and, after incorporation in lipid vesicles, assessed as a potential photosensitizer for antibacterial photodynamic therapy. The phthalocyanine derivative obtained in the macrocyclization reaction was characterized by MS and NMR techniques. Moreover, its chemical purity was confirmed by HPLC analysis. X-ray structural analysis revealed that overcrowding of the phthalocyanine derivative leads to a strong out-of-plane distortion of the π-system of the macrocycle core. In the UV-Vis absorption spectra of zinc(II) phthalocyanine two characteristic bands were found: the Soret (300-450 nm) and the Q band (600-800 nm). Photophysical properties of mono- and diprotonated forms of phthalocyanine derivative were studied with time-resolved fluorescence spectroscopy. Its tri- and tetraprotonated forms could not be obtained, because compound decomposes in higher acid concentrations. The presented zinc(II) phthalocyanine showed values of singlet oxygen generation Φ Δ  = 0.18 and 0.16, the quantum yield of the photodecomposition Φ P  = 3.06∙10 -4 and 1.23∙10 -5 and the quantum yield of fluorescence Φ FL  = 0.005 and 0.004, designated in DMF and DMSO, respectively. For biological studies, phthalocyanine has been incorporated into modified liposome vesicles containing ethanol. In vitro bacteria photoinactivation study revealed no activity against Escherichia coli and 5.7 log reduction of the Enterococcus faecalis growth. Copyright © 2018 Elsevier B.V. All rights reserved.

Short communication: Macrocyclic lactone residues in butter from Brazilian markets.

PubMed

Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Almeida Furtado, Leonardo; Brasil, Taila Figueredo; Pereira Netto, Annibal Duarte

2015-06-01

Macrocyclic lactones (ML) are commonly used in drug formulations for the treatment of parasites in cattle. In Brazil, except for drugs (or formulations) with long-term (half-life) effects, ML are registered for use in bovines. Indiscriminate use of ML may result in the presence of residues in milk and dairy products due to their lipophilic properties and thermal stability. This study applied a method of liquid chromatography with fluorimetric detection, recently developed and validated for the determination of residues of abamectin, doramectin, ivermectin, and moxidectin in butter. The method was applied to 38 samples of commercial butter purchased in the metropolitan area of Rio de Janeiro, Brazil, between June and September 2013, analyzed in triplicate. Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3 and 119.4 µg/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 µg/kg) and 55.2% contained abamectin (0.7 to 4.5 µg/kg). Most butter samples (76.3%) contained residues of more than 1 ML; however, no residues of moxidectin were detected. The results showed a high incidence of the presence of avermectins in butter samples. Butter is not included in the Brazilian National Plan for Control of Residues and Contaminants in Animal Products. As ML residues concentrate in lipophilic compounds, butter and other fatty dairy products should be screened for the presence of ML residues. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

In vivo three-dimensional molecular imaging with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) at high spatiotemporal resolution.

PubMed

Coman, Daniel; de Graaf, Robin A; Rothman, Douglas L; Hyder, Fahmeed

2013-11-01

Spectroscopic signals which emanate from complexes between paramagnetic lanthanide (III) ions (e.g. Tm(3+)) and macrocyclic chelates (e.g. 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate, or DOTMA(4-)) are sensitive to physiology (e.g. temperature). Because nonexchanging protons from these lanthanide-based macrocyclic agents have relaxation times on the order of a few milliseconds, rapid data acquisition is possible with chemical shift imaging (CSI). Thus, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) which originate from nonexchanging protons of these paramagnetic agents, but exclude water proton detection, can allow molecular imaging. Previous two-dimensional CSI experiments with such lanthanide-based macrocyclics allowed acquisition from ~12-μL voxels in rat brain within 5 min using rectangular encoding of k space. Because cubical encoding of k space in three dimensions for whole-brain coverage increases the CSI acquisition time to several tens of minutes or more, a faster CSI technique is required for BIRDS to be of practical use. Here, we demonstrate a CSI acquisition method to improve three-dimensional molecular imaging capabilities with lanthanide-based macrocyclics. Using TmDOTMA(-), we show datasets from a 20 × 20 × 20-mm(3) field of view with voxels of ~1 μL effective volume acquired within 5 min (at 11.7 T) for temperature mapping. By employing reduced spherical encoding with Gaussian weighting (RESEGAW) instead of cubical encoding of k space, a significant increase in CSI signal is obtained. In vitro and in vivo three-dimensional CSI data with TmDOTMA(-), and presumably similar lanthanide-based macrocyclics, suggest that acquisition using RESEGAW can be used for high spatiotemporal resolution molecular mapping with BIRDS. Copyright © 2013 John Wiley & Sons, Ltd.

Synthesis, characterization and anti-microbial activity of a novel macrocyclic ligand derived from the reaction of 2,6-pyridinedicarboxylic acid with homopiperazine and its Co(II), Ni(II), Cu(II), and Zn(II) complexes

NASA Astrophysics Data System (ADS)

Soleimani, Esmaiel

2011-05-01

The preparation of a novel macrocyclic ligand ( 1), N,N'-diethylhomopiperazinyl,2,6-pyridinedicarboxylate and its Co(II), Ni(II), Cu(II), and Zn(II) complexes are described. The ligand was prepared in EtOH from the reaction of dipotassium salt of 2,6-pyridinedicarboxylic acid with 1,2-dibromoethane in the presence of homopiperazine. Reaction of macrocyclic ligand ( 1) in EtOH with CoCl 2.6H 2O, NiCl 2.6H 2O, CuCl 2.2H 2O, and ZnCl 2·2H 2O yielded the complexes with the general formula [M(L)Cl 2] {where M = Co(II) ( 2), Ni(II) ( 3), Cu(II) ( 4), Zn ( 5), respectively}. The analysis of IR, 1H and 13C NMR spectral data of macrocyclic ligand ( 1) and its Zn(II) complex ( 5) together with their molar conductivity values, and the magnetic moments of the complexes suggest that the macrocyclic ligand ( 1) is bonded to metal(II) ions through two oxygen atoms of ester moiety and the two nitrogen atoms of homopiperazine ring. The electronic spectral data of these complexes in DMSO are in good agreement with the octahedral coordination of M(II) ions. The ligand field parameters for these complexes, i.e. splitting energy and Racah parameter were calculated to be 14,945 and 673 cm -1 for the Co(II) ( 2), 16,260 and 774 cm -1 for the Ni(II) ( 3) complexes respectively. The spliting energy of 17,262 cm -1 was obtained for the Cu(II) complex ( 4).

Comparison of Linear and Hyperbranched Polyether Lipids for Liposome Shielding by 18F-Radiolabeling and Positron Emission Tomography.

PubMed

Wagener, Karolin; Worm, Matthias; Pektor, Stefanie; Schinnerer, Meike; Thiermann, Raphael; Miederer, Matthias; Frey, Holger; Rösch, Frank

2018-04-27

Multifunctional and highly biocompatible polyether structures play a key role in shielding liposomes from degradation in the bloodstream, providing also multiple functional groups for further attachment of targeting moieties. In this work hyperbranched polyglycerol ( hbPG) bearing lipids with long alkyl chain anchor are evaluated with respect to steric stabilization of liposomes. The branched polyether lipids possess a hydrophobic bis(hexadecyl)glycerol membrane anchor for the liposomal membrane. hbPG was chosen as a multifunctional alternative to PEG, enabling the eventual linkage of multiple targeting vectors. Different hbPG lipids ( M n = 2900 and 5200 g mol -1 ) were examined. A linear bis(hexadecyl)glycerol-PEG lipid ( M n = 3000 g mol -1 ) was investigated as well, comparing hbPG and PEG with respect to shielding properties. Radiolabeling of the polymers was carried out using 1-azido-2-(2-(2-[ 18 F]fluoroethoxy)ethoxy)ethane ([ 18 F]F-TEG-N) 3 via copper-catalyzed alkyne-azide cycloaddition with excellent radiochemical yields exceeding 95%. Liposomes were prepared by the thin-film hydration method followed by repeated extrusion. Use of a custom automatic extrusion device gave access to reproducible sizes of the liposomes (hydrodynamic radius of 60-94 nm). The in vivo fate of the bis(hexadecyl)glycerol polyethers and their corresponding assembled liposome structures were evaluated via noninvasive small animal positron emission tomography (PET) imaging and biodistribution studies (1 h after injection and 4 h after injection) in mice. Whereas the main uptake of the nonliposomal polyether lipids was observed in the kidneys and in the bladder after 1 h due to rapid renal clearance, in contrast, the corresponding liposomes showed uptake in the blood pool as well as in organs with good blood supply, that is, heart and lung over the whole observation period of 4 h. The in vivo behavior of all three liposomal formulations was comparable, albeit with remarkable differences in splenic uptake. Overall, liposomes shielded by the branched polyglycerol lipids show a favorable biodistribution with greatly prolonged blood circulation times, rendering them promising novel nanovesicles for drug transport and targeting.

Laser desorption vs. electrospray of polyyne-threaded rotaxanes: Preventing covalent cross-linking and promoting noncovalent aggregation

NASA Astrophysics Data System (ADS)

Neugebauer, Thomas S.; Franz, Michael; Frankenberger, Stephanie; Tykwinski, Rik R.; Drewello, Thomas

2018-02-01

Laser-induced cross-linking of polyynes is successfully hindered when the polyyne is encapsulated as part of a rotaxane and therefore protected by a surrounding macrocycle. When the rotaxane is electrosprayed, however, noncovalent aggregate ions are efficiently formed. Aggregates of considerable size (including more than 50 rotaxane molecules with masses beyond 100k Da) and charge states (up to 13 charges and beyond) have been observed. Either protons or sodium cations act as the charge carriers. These aggregates are not formed when the individual components of the rotaxane, i.e., the macrocycle or the polyyne, are separately electrosprayed. This underlines the structural importance of the rotaxane for the aggregate formation. Straightforward force field calculations indicate that the polyyne thread hinders the folding of the macrocycles, which facilitates the bonding interaction between the two components.

Bambus[6]uril as a novel macrocyclic receptor for the nitrate anion.

PubMed

Toman, Petr; Makrlík, Emanuel; Vanura, Petr

2013-01-01

By using quantum mechanical DFT calculations, the most probable structure of the bambus[6]uril x NO3(-) anionic complex species was derived. In this complex having C3 symmetry, the nitrate anion NO3(-), included in the macrocyclic cavity, is bound by twelve weak hydrogen bonds between methine hydrogen atoms on the convex face of glycoluril units and the considered NO3(-) ion.

Oxidative Carbocation Formation in Macrocycles: Synthesis of the Neopeltolide Macrocycle**

PubMed Central

Tu, Wangyang

2009-01-01

Processes for the functionalization of carbon–hydrogen bonds are the focus of significant attention in organic synthesis[1] in response to the need to streamline molecular assembly. As a continuation of our efforts to generate carbocations through single-electron oxidation reactions,[2] we recently reported[3] DDQ-mediated cyclization reactions of benzylic and allylic ethers (Scheme 1; DDQ =2,3-dichloro-4,5-dicyanoquinone). PMID:19455526

Two-Dimensional Nanoporous Networks Formed by Liquid-to-Solid Transfer of Hydrogen-Bonded Macrocycles Built from DNA Bases.

PubMed

Bilbao, Nerea; Destoop, Iris; De Feyter, Steven; González-Rodríguez, David

2016-01-11

We present an approach that makes use of DNA base pairing to produce hydrogen-bonded macrocycles whose supramolecular structure can be transferred from solution to a solid substrate. A hierarchical assembly process ultimately leads to two-dimensional nanostructured porous networks that are able to host size-complementary guests. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis, Characterization and Antifertility Activity of New Unsymmetrical Macrocyclic Complexes of Tin(II)

PubMed Central

Sharma, Kripa; Joshi, S. C.

2000-01-01

A new series of unsymmetrical macrocyclic complexes of tin(ll) has been prepared by the template process using bis(3-oxo-2-butylidene)propane-1,3-diamine as precursor. This affords a method to synthesize these complexes with various ring sizes. The tetradentate macrocyclic precursor [N4mL] reacts with SnCl2 and different diamines in a 1:1:1 molar ratio in refluxing methanol to give complexes of the type [Sn(N4mL)Cl2]. The ring expansion has been achieved by varying the diamine between the two diacetyl amino nitrogen atoms. The macrocyclic precursor and its metal complexes have been characterized on the basis of elemental analysis, molar conductance, molecular weight determinations, IR, 1H NMR,13C NMR, 119Sn NMR and electronic spectral studies. An octahedral geometry around the metal ion is suggested for these complexes. On the basis of molecular weights and conductivity measurements, their monomeric and non-electrolytic nature has been confirmed. The precursor and complexes have been screened in vitro against a number of pathogenic fungi and bacteria to assess their growth inhibiting potential. The testicular sperm density and testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trails and biochemicals parameters of reproductive organs have been examined and discussed. PMID:18475951

Sensitized terbium(III) macrocyclic-phthalimide complexes as luminescent pH switches.

PubMed

Chen, Gaoyun; Wardle, Nicholas J; Sarris, Jason; Chatterton, Nicholas P; Bligh, S W Annie

2013-10-21

Four new macrocyclic-phthalimide ligands were synthesised via the coupling of N-(3-bromopropyl)phthalimide either to cyclen (1,4,7,10-tetraazacyclododecane) itself or its carboxylate-functionalized analogues, and photophysical studies were carried out on their corresponding Tb(III) complexes in aqueous media as a function of pH. Luminescence intensities of Tb·L1a–Tb·L3a were in ‘switched off’ mode under acidic conditions (pH < 4), and were activated on progression to basic conditions as the phthalimido functions therein were hydrolysed to their corresponding phthalamates Tb·L1b–Tb·L3b. Emission of phthalamate-based macrocyclic Tb(III) complexes Tb·L1b–Tb·L3b was in ‘switched on’ mode between pH 4 and 11, exhibiting high quantum yields (Φ) and long lifetimes (τ) of the order of milliseconds at pH ~ 6. Tb(III) emissions were found to decline with increasing number of chromophores. The values of Φ and τ were 46% and 2.4 ms respectively for Tb·L1b at pH ~ 6 when activated. This is the best pH-dependent sensor based on a Tb(III) complex reported to date, benefiting from the macrocyclic architecture of the ligand.

Spectroscopic, cyclic voltammetric and biological studies of transition metal complexes with mixed nitrogen-sulphur (NS) donor macrocyclic ligand derived from thiosemicarbazide

NASA Astrophysics Data System (ADS)

Chandra, Sulekh; Gupta, Lokesh Kumar; Sangeetika

2005-11-01

The complexation of new mixed thia-aza-oxa macrocycle viz., 2,12-dithio-5,9,14,18-tetraoxo-7,16-dithia-1,3,4,10,11,13-hexaazacyclooctadecane containing thiosemicarba-zone unit with a series of transition metals Co(II), Ni(II) and Cu(II) has been investigated, by different spectroscopic techniques. The structural features of the ligand have been studied by EI-mass, 1H NMR and IR spectral techniques. Elemental analyses, magnetic moment susceptibility, molar conductance, IR, electronic, and EPR spectral studies characterized the complexes. Electronic absorption and IR spectra of the complexes indicate octahedral geometry for chloro, nitrato, thiocyanato or acetato complexes. The dimeric and neutral nature of the sulphato complexes are confirmed from magnetic susceptibility and low conductance values. Electronic spectra suggests square-planar geometry for all sulphato complexes. The redox behaviour was studied by cyclic voltammetry, show metal-centered reduction processes for all complexes. The complexes of copper show both oxidation and reduction process. The redox potentials depend on the conformation of central atom in the macrocyclic complexes. Newly synthesized macrocyclic ligand and its transition metal complexes show markedly growth inhibitory activity against pathogenic bacterias and plant pathogenic fungi under study. Most of the complexes have higher activity than that of the metal free ligand.

Discovery of (10 R )-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro- 2H -8,4-(metheno)pyrazolo[4,3- h ][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Ted W.; Richardson, Paul F.; Bailey, Simon

2014-06-12

Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinoma patients, progression during treatment eventually develops. Resistant patient samples revealed a variety of point mutations in the kinase domain of ALK, including the L1196M gatekeeper mutation. In addition, some patients progress due to cancer metastasis in the brain. Using structure-based drug design, lipophilic efficiency, and physical-property-based optimization, highly potent macrocyclic ALK inhibitors were prepared with good absorption, distribution, metabolism, and excretion (ADME), low propensity for p-glycoprotein 1-mediated efflux, and good passive permeability. These structurally unusual macrocyclic inhibitors were potent against wild-type ALK and clinically reported ALK kinasemore » domain mutations. Significant synthetic challenges were overcome, utilizing novel transformations to enable the use of these macrocycles in drug discovery paradigms. This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity.« less

A Saturn-Like Complex Composed of Macrocyclic Oligothiophene and C60 Fullerene: Structure, Stability, and Photophysical Properties in Solution and the Solid State.

PubMed

Shimizu, Hideyuki; Park, Kyu Hyung; Otani, Hiroyuki; Aoyagi, Shinobu; Nishinaga, Tohru; Aso, Yoshio; Kim, Dongho; Iyoda, Masahiko

2018-03-12

A Saturn-like 1:1 complex composed of macrocyclic oligothiophene E-8T7A and C 60 fullerene (C 60 ) was synthesized to investigate the interaction between macrocyclic oligothiophenes and C 60 in solution and the solid state. Because the Saturn-like 1:1 complex E-8T7A⋅C 60 is mainly stabilized by van der Waals interactions between C 60 and the sulfur atoms of the E-8T7A macrocycle, C 60 is rather weakly incorporated inside the macro-ring in solution. However, in the solid state the Saturn-like 1:1 complex preferentially formed single crystals or nanostructured polymorphs. Interestingly, X-ray analysis and theoretical calculations exhibited hindered rotation of C 60 in the Saturn-like complex due to interactions between C 60 and the sulfur atoms. Furthermore, the photoinduced charge transfer (CT) interaction between E-8T7A and C 60 in solution was investigated by using femtosecond transient absorption (TA) spectroscopy. The ultrafast TA spectral changes in the photoinduced absorption bands were attributed to the CT process in the Saturn-like structure. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

One-Pot Approach to Organo-Phosphorus-Chalcogen Macrocycles Incorporating Double OP(S)SCn or OP(Se)SeCn Scaffolds: A Synthetic and Structural Study.

PubMed

Hua, Guoxiong; Du, Junyi; Slawin, Alexandra M Z; Woollins, J Derek

2016-06-01

The development of new methodology for the preparation of functional macrocycles with practical applications is an important research area in macromolecular science. In this study, we report a new one-pot route for the synthesis of a series of macro-heterocycles by incorporating two phosphorus atoms and two chalcogen atoms and two oxygen atoms (double OP(S)SCn or OP(Se)SeCn scaffolds). The three-component condensation reactions of 2,4-diferrocenyl-1,3,2,4-diathiadiphosphetane 2,4-disulfide (FcLR, a ferrocene analogue of Lawesson's reagent) or 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide (LR, Lawesson's reagent), or 2,4-diphenyl-1,3,2,4-diselenadiphosphetane 2,4-diselenide (WR, Woollins' reagent), disodium alkenyl-diols, and dihalogenated alkanes are performed, giving rise to soluble and air or moisture-stable macrocycles in good-to-excellent yields (up to 92 %). This is the first systemically preparative and readily scalable example of one-pot ring opening/ring extending reaction of three-components to prepare phosphorus-chalcogen containing macrocycles. We also provide a systematic crystallographic study. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differences in cooperative behavior among Damaraland mole rats are consequences of an age-related polyethism

PubMed Central

Zöttl, Markus; Vullioud, Philippe; Mendonça, Rute; Torrents Ticó, Miquel; Gaynor, David; Mitchell, Adam; Clutton-Brock, Tim

2016-01-01

In many cooperative breeders, the contributions of helpers to cooperative activities change with age, resulting in age-related polyethisms. In contrast, some studies of social mole rats (including naked mole rats, Heterocephalus glaber, and Damaraland mole rats, Fukomys damarensis) suggest that individual differences in cooperative behavior are the result of divergent developmental pathways, leading to discrete and permanent functional categories of helpers that resemble the caste systems found in eusocial insects. Here we show that, in Damaraland mole rats, individual contributions to cooperative behavior increase with age and are higher in fast-growing individuals. Individual contributions to different cooperative tasks are intercorrelated and repeatability of cooperative behavior is similar to that found in other cooperatively breeding vertebrates. Our data provide no evidence that nonreproductive individuals show divergent developmental pathways or specialize in particular tasks. Instead of representing a caste system, variation in the behavior of nonreproductive individuals in Damaraland mole rats closely resembles that found in other cooperatively breeding mammals and appears to be a consequence of age-related polyethism. PMID:27588902

Validation of a liquid chromatography-electrospray ionization tandem mass spectrometric method to determine six polyether ionophores in raw, UHT, pasteurized and powdered milk.

PubMed

Pereira, Mararlene Ulberg; Spisso, Bernardete Ferraz; Jacob, Silvana do Couto; Monteiro, Mychelle Alves; Ferreira, Rosana Gomes; Carlos, Betânia de Souza; da Nóbrega, Armi Wanderley

2016-04-01

This study aimed to validate a method developed for the determination of six antibiotics from the polyether ionophore class (lasalocid, maduramicin, monensin, narasin, salinomycin and semduramicin) at residue levels in raw, UHT, pasteurized and powdered milk using QuEChERS extraction and high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). The validation was conducted under an in-house laboratory protocol that is primarily based on 2002/657/EC Decision, but takes in account the variability of matrix sources. Overall recoveries between 93% and 113% with relative standard deviations up to 16% were obtained under intermediate precision conditions. CCα calculated values did not exceed 20% the Maximum Residue Limit for monensin and 25% the Maximum Levels for all other substances. The method showed to be simple, fast and suitable for verifying the compliance of raw and processed milk samples regarding the limits recommended by Codex Alimentarius and those adopted in European Community for polyether ionophores. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Impact of Polyether Chain Length on the Iron Clearing Efficiency and Physiochemical Properties of Desferrithiocin Analogues

PubMed Central

Bergeron, Raymond J.; Bharti, Neelam; Wiegand, Jan; McManis, James S.; Singh, Shailendra; Abboud, Khalil A.

2010-01-01

(S)-2-(2,4-Dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic acid (2) was abandoned in clinical trials as an iron chelator for the treatment of iron overload disease because of its nephrotoxicity. However, subsequent investigations revealed that replacing the 4′-(HO) of 2 with a 3,6,9-trioxadecyloxy group, ligand 4, increased iron clearing efficiency (ICEa) and ameliorated the renal toxicity of 2. This compelled a closer look at additional polyether analogues, the subject of this work. The 3,6,9,12-tetraoxatridecyloxy analogue of 4, chelator 5, an oil, had twice the ICE in rodents of 4, although its ICE in primates was reduced relative to 4. The corresponding 3,6-dioxaheptyloxy analogue of 2, 6 (a crystalline solid), had high ICEs in both the rodent and primate models. It significantly decorporated hepatic, renal, and cardiac iron, with no obvious histopathologies. These findings suggest that polyether chain length has a profound effect on ICE, tissue iron decorporation, and ligand physiochemical properties. PMID:20232803

Development of many-body polarizable force fields for Li-battery components: 1. Ether, alkane, and carbonate-based solvents.

PubMed

Borodin, Oleg; Smith, Grant D

2006-03-30

Classical many-body polarizable force fields were developed for n-alkanes, perflouroalkanes, polyethers, ketones, and linear and cyclic carbonates on the basis of quantum chemistry dimer energies of model compounds and empirical thermodynamic liquid-state properties. The dependence of the electron correlation contribution to the dimer binding energy on basis-set size and level of theory was investigated as a function of molecular separation for a number of alkane, ether, and ketone dimers. Molecular dynamics (MD) simulations of the force fields accurately predicted structural, dynamic, and transport properties of liquids and unentangled polymer melts. On average, gas-phase dimer binding energies predicted with the force field were between those from MP2/aug-cc-pvDz and MP2/aug-cc-pvTz quantum chemistry calculations.

Accelerated simulations of aromatic polymers: application to polyether ether ketone (PEEK)

NASA Astrophysics Data System (ADS)

Broadbent, Richard J.; Spencer, James S.; Mostofi, Arash A.; Sutton, Adrian P.

2014-10-01

For aromatic polymers, the out-of-plane oscillations of aromatic groups limit the maximum accessible time step in a molecular dynamics simulation. We present a systematic approach to removing such high-frequency oscillations from planar groups along aromatic polymer backbones, while preserving the dynamical properties of the system. We consider, as an example, the industrially important polymer, polyether ether ketone (PEEK), and show that this coarse graining technique maintains excellent agreement with the fully flexible all-atom and all-atom rigid bond models whilst allowing the time step to increase fivefold to 5 fs.

Gd-complexes of macrocyclic DTPA conjugates of 1,1'-bis(amino)ferrocenes as high relaxivity MRI blood-pool contrast agents (BPCAs).

PubMed

Kim, Hee-Kyung; Park, Ji-Ae; Kim, Kyeong Min; Nasiruzzaman, Sk Md; Kang, Duk-Sik; Lee, Jongmin; Chang, Yongmin; Kim, Tae-Jeong

2010-11-28

We report the synthesis of macrocyclic DTPA conjugates of 1,1'-bis(amino)ferrocenes (1a-b) and their Gd-complexes [Gd(L)(H(2)O)] (2a-b, L = 1a-b) for use as new MRI blood-pool contrast agents. High R(1) relaxivity in HSA as well as high thermodynamic and kinetic stabilities is observed for 2a.

Lead Diversification through a Prins-Driven Macrocyclization Strategy: Application to C13-Diversified Bryostatin Analogues.

PubMed

Wender, Paul A; Billingsley, Kelvin L

2013-01-01

The design, synthesis, and biological evaluation of a novel class of C13-diversified bryostatin analogues are described. An innovative and general strategy based on a Prins macrocyclization-nucleophilic trapping cascade was used to achieve late-stage diversification. In vitro analysis of selected library members revealed that modification at the C13 position of the bryostatin scaffold can be used as a diversification handle to regulate biological activity.

Macrocyclic lactones: A versatile source for omega radiohalogenated fatty acid analogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dougan, A.H.; Lyster, D.M.; Robertson, K.A.

For each omega halogenated fatty acid there exists a potential omega hydroxy fatty acid and the corresponding macrocyclic lactone. The authors have utilized such lactones as starting materials for omega /sup 123/I fatty acid analogs intended for myocardial imaging. Macrocyclic musk lactones are industrially available; 120 analogs are described in the literature. The preparation requires saponification, tosylation, and radio-iodide substitution. Iodo-fatty acids are readily separated from tosylate fatty acids on TLC. While providing a secure source of 16-iodo-hexadecanoic acid and 17-iodo-heptadecanoic acid, the scheme allows ready access to a large number of untried fatty acid analogs. Examples presented are 16-iodo-hexadecanoicmore » acid, 16-iodo-7-hexadecanoic acid, 16-iodo-12-oxa-hexadecanoic acid, 15-iodo-pentadecanoic acid, and 15-iodo-12-keto-pentadecanoic acid. Metabolic studies are in progress in mice and dogs to assess the utility of these analogs for myocardial imaging.« less

Biodegradable polyester-based eco-composites containing hemp fibers modified with macrocyclic oligomers

NASA Astrophysics Data System (ADS)

Conzatti, Lucia; Utzeri, Roberto; Hodge, Philip; Stagnaro, Paola

2016-05-01

An original compatibilizing pathway for hemp fibers/poly(1,4-butylene adipate-co-terephtalate) (PBAT) eco-composites was explored exploiting the capability of macrocyclic oligomers (MCOs), obtained by cyclodepolymerization (CDP) of PBAT at high dilution, of being re-converted into linear chains by entropically-driven ring-opening polymerization (ED-ROP) that occurs simply heating the MCOS in the bulk. CDP reaction of PBAT was carried out varying solvent, catalyst and reaction time. Selected MCOs were used to adjust the conditions of the ED-ROP reaction. The best experimental conditions were then adopted to modify hemp fibers. Eco-composites based on PBAT and hemp fibers as obtained or modified with PBAT macrocyclics or oligomers were prepared by different process strategies. The best fiber-PBAT compatibility was observed when the fibers were modified with PBAT oligomers before incorporation in the polyester matrix.

Diels-Alder active-template synthesis of rotaxanes and metal-ion-switchable molecular shuttles.

PubMed

Crowley, James D; Hänni, Kevin D; Leigh, David A; Slawin, Alexandra M Z

2010-04-14

A synthesis of [2]rotaxanes in which Zn(II) or Cu(II) Lewis acids catalyze a Diels-Alder cycloaddition to form the axle while simultaneously acting as the template for the assembly of the interlocked molecules is described. Coordination of the Lewis acid to a multidentate endotopic 2,6-di(methyleneoxymethyl)pyridyl- or bipyridine-containing macrocycle orients a chelated dienophile through the macrocycle cavity. Lewis acid activation of the double bond causes it to react with an incoming "stoppered" diene, affording the [2]rotaxane in up to 91% yield. Unusually for an active-template synthesis, the metal binding site "lives on" in these rotaxanes. This was exploited in the synthesis of a molecular shuttle containing two different ligating sites in which the position of the macrocycle could be switched by complexation with metal ions [Zn(II) and Pd(II)] with different preferred coordination geometries.

Solar Thermal Energy Storage in a Photochromic Macrocycle.

PubMed

Vlasceanu, Alexandru; Broman, Søren L; Hansen, Anne S; Skov, Anders B; Cacciarini, Martina; Kadziola, Anders; Kjaergaard, Henrik G; Mikkelsen, Kurt V; Nielsen, Mogens Brøndsted

2016-07-25

The conversion and efficient storage of solar energy is recognized to hold significant potential with regard to future energy solutions. Molecular solar thermal batteries based on photochromic systems exemplify one possible technology able to harness and apply this potential. Herein is described the synthesis of a macrocycle based on a dimer of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo/thermal couple. By taking advantage of conformational strain, this DHA-DHA macrocycle presents an improved ability to absorb and store incident light energy in chemical bonds (VHF-VHF). A stepwise energy release over two sequential ring-closing reactions (VHF→DHA) combines the advantages of an initially fast discharge, hypothetically addressing immediate energy consumption needs, followed by a slow process for consistent, long-term use. This exemplifies another step forward in the molecular engineering and design of functional organic materials towards solar thermal energy storage and release. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Divergent unprotected peptide macrocyclisation by palladium-mediated cysteine arylation.

PubMed

Rojas, Anthony J; Zhang, Chi; Vinogradova, Ekaterina V; Buchwald, Nathan H; Reilly, John; Pentelute, Bradley L; Buchwald, Stephen L

2017-06-01

Macrocyclic peptides are important therapeutic candidates due to their improved physicochemical properties in comparison to their linear counterparts. Here we detail a method for a divergent macrocyclisation of unprotected peptides by crosslinking two cysteine residues with bis-palladium organometallic reagents. These synthetic intermediates are prepared in a single step from commercially available aryl bis-halides. Two bioactive linear peptides with cysteine residues at i , i + 4 and i , i + 7 positions, respectively, were cyclised to introduce a diverse array of aryl and bi-aryl linkers. These two series of macrocyclic peptides displayed similar linker-dependent lipophilicity, phospholipid affinity, and unique volume of distributions. Additionally, one of the bioactive peptides showed target binding affinity that was predominantly affected by the length of the linker. Collectively, this divergent strategy allowed rapid and convenient access to various aryl linkers, enabling the systematic evaluation of the effect of appending unit on the medicinal properties of macrocyclic peptides.

Cascade Cyclizations of Acyclic and Macrocyclic Alkynones: Studies toward the Synthesis of Phomactin A

PubMed Central

Ciesielski, Jennifer; Gandon, Vincent; Frontier, Alison J.

2013-01-01

A study of the reactivity and diastereoselectivity of the Lewis acid-promoted cascade cyclizations of both acyclic and macrocyclic alkynones is described. In these reactions, a β-iodoallenolate intermediate is generated via conjugate addition of iodide to an alkynone, followed by an intramolecular aldol reaction with a tethered aldehyde to afford a cyclohexenyl alcohol. The Lewis acid magnesium iodide (MgI2) was found to promote irreversible ring closure, while cyclizations using BF3·OEt2 as promoter occurred reversibly. For both acyclic and macrocyclic ynones, high diastereoselectivity was observed in the intramolecular aldol reaction. The MgI2 protocol for cyclization was applied to the synthesis of advanced intermediates relevant to the synthesis of phomactin natural products, during which a novel transannular cation-olefin cyclization was observed. DFT calculations were conducted to analyze the mechanism of this unusual MgI2-promoted process. PMID:23724905

Oocydin A, a chlorinated macrocyclic lactone with potent anti-oomycete activity from Serratia marcescens.

PubMed

Srobel, G; Li, J Y; Sugawara, F; Koshino, H; Harper, J; Hess, W M

1999-12-01

A unique chlorinated macrocyclic lactone, termed oocydin A, was isolated from a strain of Serratia marcescens growing as an epiphyte on Rhyncholacis pedicillata, an aquatic plant native to the Carrao river of the Venezuelan-Guyanan region of South America. The lactone has a molecular mass of 470 Da, and contains one atom of chlorine, a carboxyl group and a tetrahydrofuran ring internal to a larger macrocyclic ring. MICs of approximately 0.03 microg ml(-1) were noted for oocydin A against such phytopathogenic oomycetes as Pythium ultimum, Phytophthora parasitica, Phytophthora cinnamomi and Phytophthora citrophora. With regard to the true fungi, oocydin A had either minimal or no effect against certain Fungi Imperfecti (including several pathogens of humans), two ascomycetes and a basidiomycete. Oocydin A may have potential as an antimycotic in agricultural applications and especially for crop protection.

Macrocyclic metal complexes for metalloenzyme mimicry and sensor development.

PubMed

Joshi, Tanmaya; Graham, Bim; Spiccia, Leone

2015-08-18

Examples of proteins that incorporate one or more metal ions within their structure are found within a broad range of classes, including oxidases, oxidoreductases, reductases, proteases, proton transport proteins, electron transfer/transport proteins, storage proteins, lyases, rusticyanins, metallochaperones, sporulation proteins, hydrolases, endopeptidases, luminescent proteins, iron transport proteins, oxygen storage/transport proteins, calcium binding proteins, and monooxygenases. The metal coordination environment therein is often generated from residues inherent to the protein, small exogenous molecules (e.g., aqua ligands) and/or macrocyclic porphyrin units found, for example, in hemoglobin, myoglobin, cytochrome C, cytochrome C oxidase, and vitamin B12. Thus, there continues to be considerable interest in employing macrocyclic metal complexes to construct low-molecular weight models for metallobiosites that mirror essential features of the coordination environment of a bound metal ion without inclusion of the surrounding protein framework. Herein, we review and appraise our research exploring the application of the metal complexes formed by two macrocyclic ligands, 1,4,7-triazacyclononane (tacn) and 1,4,7,10-tetraazacyclododecane (cyclen), and their derivatives in biological inorganic chemistry. Taking advantage of the kinetic inertness and thermodynamic stability of their metal complexes, these macrocyclic scaffolds have been employed in the development of models that aid the understanding of metal ion-binding natural systems, and complexes with potential applications in biomolecule sensing, diagnosis, and therapy. In particular, the focus has been on "coordinatively unsaturated" metal complexes that incorporate a kinetically inert and stable metal-ligand moiety, but which also contain one or more weakly bound ligands, allowing for the reversible binding of guest molecules via the formation and dissociation of coordinate bonds. With regards to mimicking metallobiosites, examples are presented from our work on tacn-based complexes developed as simplified structural models for multimetallic enzyme sites. In particular, structural comparisons are made between multinuclear copper(II) complexes formed by such ligands and multicopper enzymes featuring type-2 and type-3 copper centers, such as ascorbate oxidase (AO) and laccase (Lc). Likewise, with the aid of relevant examples, we highlight the importance of cooperativity between either multiple metal centers or a metal center and a proximal auxiliary unit appended to the macrocyclic ligand in achieving efficient phosphate ester cleavage. Finally, the critical importance of the Zn(II)-imido and Zn(II)-phosphate interactions in Zn-cyclen-based systems for delivering highly sensitive electrochemical and fluorescent chemosensors is also showcased. The Account additionally highlights some of the factors that limit the performance of these synthetic nucleases and the practical application of the biosensors, and then identifies some avenues for the development of more effective macrocyclic constructs in the future.

Wettability changes in polyether impression materials subjected to immersion disinfection.

PubMed

Shetty, Shweta; Kamat, Giridhar; Shetty, Rajesh

2013-07-01

Disinfection of impression materials prevents cross-contamination; however, the disinfectants may alter the wettability property. The purpose of this investigation was to evaluate the wettability changes of polyether impression material after immersing in four different chemical disinfectant solutions for a period of 10 min and 30 min, respectively. A total of 45 samples of polyether dental impression material (Impregum soft, 3MESPE, St. Paul, MN, USA) were randomly divided into nine groups with five specimens each. Each specimen was disc shaped, flat of 32 mm diameter and 3 mm thickness. The samples were immersed in four disinfectant solutions: 2% Glutaraldehyde, 5% sodium hypochlorite, 0.05% iodophor, and 5.25% phenol for 10 min and 30 min, respectively. The control was without disinfection. Wettability of the samples was assessed by measuring the contact angle by using the Telescopic Goniometer. Data were subjected to analysis of variance (Fisher's test) and Tukey's post hoc test for multiple comparisons at 5% level of significance. The contact angle of 20.21° ± 0.22° were recorded in the control samples. After 10 min, the samples that were immersed in 5% sodium hypochlorite and 5.25% phenol showed significant statistical increase in the contact angle as compared to the control (P < 0.001). After 30 min of disinfection, only the samples immersed in 0.05% iodophor showed there were no significant changes in the contact angle, whereas the other disinfectants significantly increased the contact angle and decreased the wettability of the polyether material. Within the limitations of the study, 2% glutaraldehyde proved safe for 10 min of immersion disinfection while 0.05% iodophor holds promise as an effective disinfectant without affecting the wettability of the material.

Wettability changes in polyether impression materials subjected to immersion disinfection

PubMed Central

Shetty, Shweta; Kamat, Giridhar; Shetty, Rajesh

2013-01-01

Background: Disinfection of impression materials prevents cross-contamination; however, the disinfectants may alter the wettability property. The purpose of this investigation was to evaluate the wettability changes of polyether impression material after immersing in four different chemical disinfectant solutions for a period of 10 min and 30 min, respectively. Materials and Methods: A total of 45 samples of polyether dental impression material (Impregum soft, 3MESPE, St. Paul, MN, USA) were randomly divided into nine groups with five specimens each. Each specimen was disc shaped, flat of 32 mm diameter and 3 mm thickness. The samples were immersed in four disinfectant solutions: 2% Glutaraldehyde, 5% sodium hypochlorite, 0.05% iodophor, and 5.25% phenol for 10 min and 30 min, respectively. The control was without disinfection. Wettability of the samples was assessed by measuring the contact angle by using the Telescopic Goniometer. Data were subjected to analysis of variance (Fisher's test) and Tukey's post hoc test for multiple comparisons at 5% level of significance. Results: The contact angle of 20.21° ± 0.22° were recorded in the control samples. After 10 min, the samples that were immersed in 5% sodium hypochlorite and 5.25% phenol showed significant statistical increase in the contact angle as compared to the control (P < 0.001). After 30 min of disinfection, only the samples immersed in 0.05% iodophor showed there were no significant changes in the contact angle, whereas the other disinfectants significantly increased the contact angle and decreased the wettability of the polyether material. Conclusion: Within the limitations of the study, 2% glutaraldehyde proved safe for 10 min of immersion disinfection while 0.05% iodophor holds promise as an effective disinfectant without affecting the wettability of the material. PMID:24130593

Stereoisomers Separation

NASA Astrophysics Data System (ADS)

Wieczorek, Piotr

The use of capillary electrophoresis for enantiomer separation and optical purity determination is presented. The contents start with basic information about the nature of stereoizomers and the mechanism of enantioseparation using capillary electrophoresis techniques. The molecules to be separated show identical chemical structure and electrochemical behavior. Therefore, the chiral recognition of enantiomers is possible only by bonding to chiral selector and the separation based on very small differences in complexation energies of diastereomer complexes formed. This method is useful for this purpose due to the fact that different compounds can be used as chiral selectors. The mostly used chiral selectors like cyclodextrins, crown ethers, chiral surfactants, macrocyclic antibiotics, transition metal complexes, natural, and synthetic polymers and their application for this purpose is also discussed. Finally, examples of practical applications of electromigration techniques for enantiomers separation and determination are presented.

Total synthesis and structural revision of the marine macrolide neopeltolide.

PubMed

Custar, Daniel W; Zabawa, Thomas P; Scheidt, Karl A

2008-01-23

The total synthesis and structural revision of the marine natural product neopeltolide is reported. The key bond-forming step involves a Lewis acid-catalyzed intramolecular cyclization to install the tetrahydropyran ring and the macrocycle simultaneously. This type of cyclization is the first of its kind and assembles the carbon backbone of the natural product efficiently. The synthesis of the reported structure revealed differences in the data between the natural and synthetic material. After significant investigation, the diastereomeric molecule with the C11 and C13 configurations inverted was synthesized using the initial route. This compound matches the data reported for neopeltolide (1H, 13C, HRMS, IR, NOESY, [alpha]), thereby establishing the correct overall structure for this potent macrolide natural product, including the relative and absolute stereochemistry.

Around the macrolide - Impact of 3D structure of macrocycles on lipophilicity and cellular accumulation.

PubMed

Koštrun, Sanja; Munic Kos, Vesna; Matanović Škugor, Maja; Palej Jakopović, Ivana; Malnar, Ivica; Dragojević, Snježana; Ralić, Jovica; Alihodžić, Sulejman

2017-06-16

The aim of this study was to investigate lipophilicity and cellular accumulation of rationally designed azithromycin and clarithromycin derivatives at the molecular level. The effect of substitution site and substituent properties on a global physico-chemical profile and cellular accumulation of investigated compounds was studied using calculated structural parameters as well as experimentally determined lipophilicity. In silico models based on the 3D structure of molecules were generated to investigate conformational effect on studied properties and to enable prediction of lipophilicity and cellular accumulation for this class of molecules based on non-empirical parameters. The applicability of developed models was explored on a validation and test sets and compared with previously developed empirical models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Neurotoxic, inflammatory, and mucosecretory responses in the nasal airways of mice repeatedly exposed to the macrocyclic trichothecene mycotoxin roridin A: dose-response and persistence of injury.

PubMed

Corps, Kara N; Islam, Zahidul; Pestka, James J; Harkema, Jack R

2010-04-01

Macrocyclic trichothecene mycotoxins encountered in water-damaged buildings have been suggested to contribute to illnesses of the upper respiratory tract. Here, the authors characterized the adverse effects of repeated exposures to roridin A (RA), a representative macrocyclic trichothecene, on the nasal airways of mice and assessed the persistence of these effects. Young, adult, female C57BL/6 mice were exposed to single daily, intranasal, instillations of RA (0.4, 2, 10, or 50 microg/kg body weight [bw]) in saline (50 microl) or saline alone (controls) over 3 weeks or 250 microg/kg RA over 2 weeks. Histopathologic, immunohistochemical, and morphometric analyses of nasal airways conducted 24 hr after the last instillation revealed that the lowest-effect level was 10 microg/kg bw. RA exposure induced a dose-dependent, neutrophilic rhinitis with mucus hypersecretion, atrophy and exfoliation of nasal transitional and respiratory epithelium, olfactory epithelial atrophy and loss of olfactory sensory neurons (OSNs). In a second study, the persistence of lesions in mice instilled with 250 microg/kg bw RA was assessed. Nasal inflammation and excess luminal mucus were resolved after 3 weeks, but OSN loss was still evident in olfactory epithelium (OE). These results suggest that nasal inflammation, mucus hypersecretion, and olfactory neurotoxicity could be important adverse health effects associated with short-term, repeated, airborne exposures to macrocyclic trichothecenes.

On-Surface Pseudo-High-Dilution Synthesis of Macrocycles: Principle and Mechanism.

PubMed

Fan, Qitang; Wang, Tao; Dai, Jingya; Kuttner, Julian; Hilt, Gerhard; Gottfried, J Michael; Zhu, Junfa

2017-05-23

Macrocycles have attracted much attention due to their specific "endless" topology, which results in extraordinary properties compared to related linear (open-chain) molecules. However, challenges still remain in their controlled synthesis with well-defined constitution and geometry. Here, we report the successful application of the (pseudo-)high-dilution method to the conditions of on-surface synthesis in ultrahigh vacuum. This approach leads to high yields (up to 84%) of cyclic hyperbenzene ([18]-honeycombene) via an Ullmann-type reaction from 4,4″-dibromo-meta-terphenyl (DMTP) as precursor on a Ag(111) surface. The mechanism of macrocycle formation was explored in detail using scanning tunneling microscopy and X-ray photoemission spectroscopy. We propose that the dominant pathway for hyperbenzene (MTP) 6 formation is the stepwise desilverization of an organometallic (MTP-Ag) 6 macrocycle, which forms via cyclization of (MTP-Ag) 6 chains under pseudo-high-dilution conditions. The high probability of cyclization on the stage of the organometallic phase results from the reversibility of the C-Ag bond. The case is different from that in solution, in which cyclization typically occurs on the stage of a covalently bonded open-chain precursor. This difference in the cyclization mechanism on a surface compared to that in solution stems mainly from the 2D confinement exerted by the surface template, which hinders the flipping of chain segments necessary for cyclization.

Experimental Observation of Redox-Induced Fe-N Switching Behavior as a Determinant Role for Oxygen Reduction Activity.

PubMed

Jia, Qingying; Ramaswamy, Nagappan; Hafiz, Hasnain; Tylus, Urszula; Strickland, Kara; Wu, Gang; Barbiellini, Bernardo; Bansil, Arun; Holby, Edward F; Zelenay, Piotr; Mukerjee, Sanjeev

2015-12-22

The commercialization of electrochemical energy conversion and storage devices relies largely upon the development of highly active catalysts based on abundant and inexpensive materials. Despite recent achievements in this respect, further progress is hindered by the poor understanding of the nature of active sites and reaction mechanisms. Herein, by characterizing representative iron-based catalysts under reactive conditions, we identify three Fe-N4-like catalytic centers with distinctly different Fe-N switching behaviors (Fe moving toward or away from the N4-plane) during the oxygen reduction reaction (ORR), and show that their ORR activities are essentially governed by the dynamic structure associated with the Fe(2+/3+) redox transition, rather than the static structure of the bare sites. Our findings reveal the structural origin of the enhanced catalytic activity of pyrolyzed Fe-based catalysts compared to nonpyrolyzed Fe-macrocycle compounds. More generally, the fundamental insights into the dynamic nature of transition-metal compounds during electron-transfer reactions will potentially guide rational design of these materials for broad applications.

Synthetic and structural studies on syringolin A and B reveal critical determinants of selectivity and potency of proteasome inhibition

PubMed Central

Clerc, Jérôme; Groll, Michael; Illich, Damir J.; Bachmann, André S.; Huber, Robert; Schellenberg, Barbara; Dudler, Robert; Kaiser, Markus

2009-01-01

Syrbactins, a family of natural products belonging either to the syringolin or glidobactin class, are highly potent proteasome inhibitors. Although sharing similar structural features, they differ in their macrocyclic lactam core structure and exocyclic side chain. These structural variations critically influence inhibitory potency and proteasome subsite selectivity. Here, we describe the total synthesis of syringolin A and B, which together with enzyme kinetic and structural studies, allowed us to elucidate the structural determinants underlying the proteasomal subsite selectivity and binding affinity of syrbactins. These findings were used successfully in the rational design and synthesis of a syringolin A-based lipophilic derivative, which proved to be the most potent syrbactin-based proteasome inhibitor described so far. With a Ki′ of 8.65 ± 1.13 nM for the chymotryptic activity, this syringolin A derivative displays a 100-fold higher potency than the parent compound syringolin A. In light of the medicinal relevance of proteasome inhibitors as anticancer compounds, the present findings may assist in the rational design and development of syrbactin-based chemotherapeutics. PMID:19359491

Synthesis and Photophysical Properties of Sulfonamidophenyl Porphyrins as Models for Activatable Photosensitizers

PubMed Central

Bhaumik, Jayeeta; Weissleder, Ralph; McCarthy, Jason R.

2009-01-01

The ability to localize agents to specific anatomic sites remains an important aspect in designing more efficient therapeutics. Light-activated therapies, in particular, allow for the focal ablation of target tissues and cells. In order to increase the specificity of these agents, stimuli-activated systems have been developed, which are non-phototoxic in the absence of activation. To this end, we propose a novel paradigm for excited state quenching and activation based upon the direct conjugation of quenching moieties to the porphyrinic macrocycle. Model compounds, based upon meso-(p-aminophenyl)porphyrins were synthesized bearing 1 to 4 sulfonamide-linked 2,4-dinitrobenzene. The singlet oxygen and fluorescence quantum yields of these compounds were obtained and compared, as well as the kinetics of activation with relevant activating agents. In addition, methods were developed to further modify the porphyrin in order to modulate the polarity and effect conjugation to biomolecules or nanoparticulate scaffolds. These systems may prove useful in the treatment of a number of disease states, such as cancer and bacterial infection. PMID:19610602

Ex(2)Box: interdependent modes of binding in a two-nanometer-long synthetic receptor.

PubMed

Juríček, Michal; Barnes, Jonathan C; Dale, Edward J; Liu, Wei-Guang; Strutt, Nathan L; Bruns, Carson J; Vermeulen, Nicolaas A; Ghooray, Kala C; Sarjeant, Amy A; Stern, Charlotte L; Botros, Youssry Y; Goddard, William A; Stoddart, J Fraser

2013-08-28

Incorporation of two biphenylene-bridged 4,4'-bipyridinium extended viologen units into a para-phenylene-based cyclophane results in a synthetic receptor that is ~2 nm long and adopts a box-like geometry. This cyclophane, Ex(2)Box(4+), possesses the ability to form binary and ternary complexes with a myriad of guest molecules ranging from long π-electron-rich polycyclic aromatic hydrocarbons, such as tetracene, tetraphene, and chrysene, to π-electron-poor 2,6-dinitrotoluene, 1,2,4-trichlorobenzene, and both the 9,10- and 1,4-anthraquinone molecules. Moreover, Ex(2)Box(4+) is capable of forming one-to-one complexes with polyether macrocycles that consist of two π-electron-rich dioxynaphthalene units, namely, 1,5-dinaphtho[38]crown-10. This type of broad molecular recognition is possible because the electronic constitution of Ex(2)Box(4+) is such that the pyridinium rings located at the "ends" of the cyclophane are electron-poor and prefer to enter into donor-acceptor interactions with π-electron-rich guests, while the "middle" of the cyclophane, consisting of the biphenylene spacer, is more electron-rich and can interact with π-electron-poor guests. In some cases, these different modes of binding can act in concert to generate one-to-one complexes which possess high stability constants in organic media. The binding affinity of Ex(2)Box(4+) was investigated in the solid state by way of single-crystal X-ray diffraction and in solution by using UV-vis and NMR spectroscopy for 12 inclusion complexes consisting of the tetracationic cyclophane and the corresponding guests of different sizes, shapes, and electronic compositions. Additionally, density functional theory was carried out to elucidate the relative energetic differences between the different modes of binding of Ex(2)Box(4+) with anthracene, 9,10-anthraquinone, and 1,4-anthraquinone in order to understand the degree with which each mode of binding contributes to the overall encapsulation of each guest.