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A methylation-mediator complex in hormone signaling  

Microsoft Academic Search

The recruitment of coactivators by nuclear hormone receptors (NRs) promotes transcription by subverting chromatin-mediated repression.Although the histone methylation enzym e CARM1 and an ATP-remodeling complex have been individually implicated in nuclear receptor-dependent transcription, neither a functional nor mechanistic linkage between these systems has been identified.In the process of purifying endogenous CARM1-interacting proteins, we identified an associated complex, nucleosomal methylation activator

Wei Xu; Helen Cho; Shilpa Kadam; Ester M. Banayo; Scott Anderson; John R. Yates; Beverly M. Emerson; Ronald M. Evans



Reactions of guanine with methyl chloride and methyl bromide: O6-methylation versus charge transfer complex formation  

NASA Astrophysics Data System (ADS)

Density functional theory (DFT) at the B3LYP/6-31+G* and B3LYP/AUG-cc-pVDZ levels was employed to study O6-methylation of guanine due to its reactions with methyl chloride and methyl bromide and to obtain explanation as to why the methyl halides cause genotoxicity and possess mutagenic and carcinogenic properties. Geometries of the various isolated species involved in the reactions, reactant complexes (RCs), and product complexes (PCs) were optimized in gas phase. Transition states connecting the reactant complexes with the product complexes were also optimized in gas phase at the same levels of theory. The reactant complexes, product complexes, and transition states were solvated in aqueous media using the polarizable continuum model (PCM) of the self-consistent reaction field theory. Zero-point energy (ZPE) correction to total energy and the corresponding thermal energy correction to enthalpy were made in each case. The reactant complexes of the keto form of guanine with methyl chloride and methyl bromide in water are appreciably more stable than the corresponding complexes involving the enol form of guanine. The nature of binding in the product complexes was found to be of the charge transfer type (O6mG+ · X-, X dbond Cl, Br). Binding of HCl, HBr, and H2O molecules to the PCs obtained with the keto form of guanine did not alter the positions of the halide anions in the PCs, and the charge transfer character of the PCs was also not modified due to this binding. Further, the complexes obtained due to the binding of HCl, HBr, and H2O molecules to the PCs had greater stability than the isolated PCs. The reaction barriers involved in the formation of PCs were found to be quite high (?50 kcal/mol). Mechanisms of genotoxicity, mutagenesis and carcinogenesis caused by the methyl halides appear to involve charge transfer-type complex formation. Thus the mechanisms of these processes involving the methyl halides appear to be quite different from those that involve the other strongly carcinogenic methylating agents.

Shukla, P. K.; Mishra, P. C.; Suhai, S.


Copper(II) complexes of imino-bis(methyl phosphonic acid) with some bio-relevant ligands. Equilibrium studies and hydrolysis of glycine methyl ester through complex formation  

Microsoft Academic Search

Binary and ternary complexes of Cu(II) involving imino-bis(methyl phosphonic acid) (IdP) abbreviated as H4A and some selected bio-ligands, amino acids, peptides and DNA constituents (L), were examined. Cu(II) forms CuA and CuAH complexes with IdP. Ternary complexes are formed in a stepwise mechanism whereby iminodiphosphonic acid binds to Cu(II), followed by coordination of amino acid, peptide or DNA. The concentration

Ahmed A. El-Sherif; Mohamed M. Shoukry



DNA methylation in complex disease: applications in nursing research, practice, and policy.  


DNA methylation is an epigenomic modification that is essential to normal human development and biological processes. DNA methylation patterns are heritable and dynamic throughout the life span. Environmental exposures can alter DNA methylation patterns, contributing to the development of complex disease. Identification and modulation of environmental factors influencing disease susceptibility through alterations in DNA methylation are amenable to nursing intervention and form the basis for individualized patient care. Here we describe the evidence supporting the translation of DNA methylation analyses as a tool for screening, diagnosis, and treatment of complex disease in nursing research and practice. The ethical, legal, social, and economic considerations of advances in genomics are considered as a model for epigenomic policy. We conclude that contemporary and informed nurse scientists and clinicians are uniquely poised to apply innovations in epigenomic research to clinical populations and develop appropriate policies that guide equitable and ethical use of new strategies to improve patient care. PMID:23849553

Wright, Michelle L; Ralph, Jody L; Ohm, Joyce E; Anderson, Cindy M


A Powerful Statistical Method for Identifying Differentially Methylated Markers in Complex Diseases  

PubMed Central

DNA methylation is an important epigenetic modification that regulates transcriptional expression and plays an important role in complex diseases, such as cancer. Genome-wide methylation patterns have unique features and hence require the development of new analytic approaches. One important feature is that methylation levels in disease tissues often differ from those in normal tissues with respect to both average and variability. In this paper, we propose a new score test to identify methylation markers of disease. This approach simultaneously utilizes information from the first and second moments of methylation distribution to improve statistical efficiency. Because the proposed score test is derived from a generalized regression model, it can be used for analyzing both categorical and continuous disease phenotypes, and for adjusting for covariates. We evaluate the performance of the proposed method and compare it to other tests including the most commonly-used t-test through simulations. The simulation results show that the validity of the proposed method is robust to departures from the normal assumption of methylation levels and can be substantially more powerful than the t-test in the presence of heterogeneity of methylation variability between disease and normal tissues. We demonstrate our approach by analyzing the methylation dataset of an ovarian cancer study and identify novel methylation loci not identified by the t-test.

Ahn, Surin; Wang, Tao



CpG Methylation of DNA Restricts Prereplication Complex Assembly in Xenopus Egg Extracts  

Microsoft Academic Search

In a Xenopus egg replication system, the origin recognition complex (ORC) does not bind to CpG methylated DNA and DNA replication is inhibited. Insertion of low density CpG DNA of at least 1.2 kb into methylated plasmids rescues both replication and ORC binding. Using this pseudo-origin, we find that ORC binding is restricted to low-CpG-density DNA; however, MCM is loaded

Kevin J. Harvey; John Newport



Complexation of Inorganic Mercury by Cysteine Promotes Bacterial Methylation of Mercury  

NASA Astrophysics Data System (ADS)

One critical factor controlling methylmercury (MeHg) accumulation in the environment is the chemical form of Hg(II) available for methylation by bacteria. Current models suggest that passive diffusion of neutral sulfide complexes may determine the bioavailability and methylation of mercury; however, these hypotheses have never been thoroughly tested. We have investigated how the chemical speciation of Hg(II) affects mercury methylation in washed cell suspensions of the Hg(II)-methylating bacterium, Geobacter sulfurreducens. In assays where the dominant Hg-binding ligand is either chloride or sulfide, MeHg is produced at a rate of about 10-21 mol MeHg/h/cell, with 1-5% of the total Hg(II) (HgT = 5 nM) being eventually methylated. The binding of Hg to cysteine greatly accelerates MeHg formation with near complete methylation of the added Hg(II). MeHg formation is directly proportional to the concentration of Hg-cysteine complex and can be reduced by increasing the proportion of Hg- chloride or Hg-sulfide species. The addition of Cu(II) results in a large reduction in the methylation of Hg(II) presumably as the result of the chemical oxidation of cysteine. Exudates released by G. sulfurreducens during growth appear to enhance mercury methylation in washed cell suspensions relative to control assays. This response is likely due to the release of cysteine or other thiols into the bulk medium during growth. The results of this study suggest a need to reevaluate our models for mercury uptake and methylation in anaerobic bacteria to include the importance of small molecular weight thiols in controlling methylmercury formation.

Schaefer, J. K.; Walsh, M. J.; Ahner, B. A.; Morel, F. M.



New iron(III) complexes with thiosemicarbazones derived from 5-methyl-3-formylpyrazole  

Microsoft Academic Search

New iron(III) complexes of 5-methyl-3-formylpyrazole thiosemicarbazone (HMPzTS) and 5-methyl-3-formylpyrazole-4-phenylthiosemicarbazone (HMPzPTS), namely [Fe(MPzTS)2]X and [Fe(MPzPTS)2]X respectively, where X=Cl, NO3, SCN and ClO4, have been synthesised and physico-chemically characterised by magnetic measurements (polycrystalline state), electronic, i.r., e.s.r. and Mössbauer spectra. All are cationic complexes containing two monoprotonic tridentate ligands with NNS donor sites and an anionic counterpart; they behave as 1:1 electrolytes

Pulakesh Bera; Nityananda Saha; Sanjay Kumar; D. Banerjee; R. Bhattacharya



Antifungal activity of ?-methyl trans cinnamaldehyde, its ligand and metal complexes: promising growth and ergosterol inhibitors  

Microsoft Academic Search

Antifungal effectivity and utility of cinnamaldehyde is limited because of its high MIC and skin sensitivity. In this study,\\u000a ?-methyl trans cinnamaldehyde, a less irritating derivative, have been self coupled and complexed with Co(II) and Ni(II) to\\u000a generate N, N?–Bis (?-methyl trans cinnamadehyde) ethylenediimine [C22H24N2], [Co(C44H48N4)Cl2] and [Ni(C44H48N4)Cl2]. Ligand and complexes were characterized on the basis of FTIR, ESI–MS, IR

Sheikh Shreaz; Rayees A. Sheikh; Rimple Bhatia; Khan Neelofar; Sheikh Imran; Athar A. Hashmi; Nikhat Manzoor; Seemi F. Basir; Luqman A. Khan


Histone H3 Lysine 36 Methylation Targets the Isw1b Remodeling Complex to Chromatin  

PubMed Central

Histone H3 lysine 36 methylation is a ubiquitous hallmark of productive transcription elongation. Despite the prevalence of this histone posttranslational modification, however, the downstream functions triggered by this mark are not well understood. In this study, we showed that H3K36 methylation promoted the chromatin interaction of the Isw1b chromatin-remodeling complex in Saccharomyces cerevisiae. Similar to H3K36 methylation, Isw1b was found at the mid- and 3? regions of transcribed genes genome wide, and its presence at active genes was dependent on H3K36 methylation and the PWWP domain of the Isw1b subunit, Ioc4. Moreover, purified Isw1b preferentially interacted with recombinant nucleosomes that were methylated at lysine 36, and this interaction also required the Ioc4 PWWP domain. While H3K36 methylation has been shown to regulate the binding of numerous factors, this is the first time that it has been shown to facilitate targeting of a chromatin-remodeling complex.

Maltby, Vicki E.; Martin, Benjamin J. E.; Schulze, Julia M.; Johnson, Ian; Hentrich, Thomas; Sharma, Aishwariya; Kobor, Michael S.



INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis  

SciTech Connect

At least three pathways control maintenance of DNA cytosine methylation in Arabidopsis thaliana. However, the RNA-directed DNA methylation (RdDM) pathway is solely responsible for establishment of this silencing mark. We previously described INVOLVED IN DE NOVO 2 (IDN2) as being an RNA-binding RdDM component that is required for DNA methylation establishment. In this study, we describe the discovery of two partially redundant proteins that are paralogous to IDN2 and that form a stable complex with IDN2 in vivo. Null mutations in both genes, termed IDN2-LIKE 1 and IDN2-LIKE 2 (IDNL1 and IDNL2), result in a phenotype that mirrors, but does not further enhance, the idn2 mutant phenotype. Genetic analysis suggests that this complex acts in a step in the downstream portion of the RdDM pathway. We also have performed structural analysis showing that the IDN2 XS domain adopts an RNA recognition motif (RRM) fold. Finally, genome-wide DNA methylation and expression analysis confirms the placement of the IDN proteins in an RdDM pathway that affects DNA methylation and transcriptional control at many sites in the genome. Results from this study identify and describe two unique components of the RdDM machinery, adding to our understanding of DNA methylation control in the Arabidopsis genome.

Ausin, Israel; Greenberg, Maxim V.C.; Simanshu, Dhirendra K.; Hale, Christopher J.; Vashisht, Ajay A.; Simon, Stacey A.; Lee, Tzuu-fen; Feng, Suhua; Española, Sophia D.; Meyers, Blake C.; Wohlschlegel, James A.; Patel, Dinshaw J.; Jacobsen, Steven E. (UCLA); (MSKCC); (Delaware)



Synthesis and antimicrobial studies of silver N-heterocyclic carbene complexes bearing a methyl benzoate substituent  

Microsoft Academic Search

Due to the properties of silver as an antimicrobial, our research group has synthesized many different silver carbene complexes. Two new silver N-heterocyclic carbene complexes derived from 4,5-dichloroimidazole and theobromine bearing methyl benzoate substituents were synthesized by in situ carbene formation using silver acetate as the base in the reaction. The new compounds were fully characterized by several methods including

Amanda R. Knapp; Matthew J. Panzner; Doug A. Medvetz; Brian D. Wright; Claire A. Tessier; Wiley J. Youngs



Signaling within a coactivator complex: methylation of SRC-3/AIB1 is a molecular switch for complex disassembly.  


Recent studies indicate that steroid receptor-mediated transcriptional initiation is a cyclical process involving multiple rounds of coactivator assembly and disassembly. Steroid receptor coactivator 3 (SRC-3) coactivator phosphorylation has been shown to regulate coactivator complex assembly, but the mechanisms by which coactivator disassembly is triggered are not well understood. In this study, we provide in vitro and in vivo evidence that members of the SRC coactivator family serve as substrates for the enzymatic coactivator coactivator-associated arginine methyltransferase 1 (CARM1). Methylation of SRC-3 was localized to an arginine in its CARM1 binding region and correlated with decreased estrogen receptor alpha-mediated transcription, as seen with both cell-based and in vitro transcription assays. Consistent with this finding, we demonstrated that methylation promotes dissociation of the SRC-3/CARM1 coactivator complex. Methylation of SRC-3 is regulated by estrogen signaling in MCF7 cells and serves as a molecular switch for disassembly of the SRC-3 transcriptional coactivator complex. We propose that CARM1 is a dual-function coactivator, as it not only activates transcription by modifying core histone tails but also terminates hormone signaling by disassembly of the coactivator complex. PMID:16923966

Feng, Qin; Yi, Ping; Wong, Jiemin; O'Malley, Bert W



Using epigenome-wide association scans of DNA methylation in age-related complex human traits.  


With rapid technological advancements emerging epigenetic studies of complex traits have shifted from candidate gene analyses towards epigenome-wide association studies (EWAS). EWAS aim to systematically identify epigenetic variants across the genome that associate with complex phenotypes. Recent EWAS using case-control and disease-discordant identical twin designs have identified phenotype-associated differentially methylated regions for several traits. However, EWAS still face many challenges related to methodology, design and interpretation, owing to the dynamic nature of epigenetic variants over time. This article reviews analytical considerations in conducting EWAS and recent applications of this approach to human aging and age-related complex traits. PMID:23130833

Tsai, Pei-Chien; Spector, Tim D; Bell, Jordana T



CCR4/NOT complex associates with the proteasome and regulates histone methylation  

PubMed Central

The proteasome regulates histone lysine methylation and gene transcription, but how it does so is poorly understood. To better understand this process, we used the epistatic miniarray profile (E-MAP) approach to identify factors that genetically interact with proteasomal subunits. In addition to members of the Set1 complex that mediate histone H3 lysine 4 methylation (H3K4me), we found that deleting members of the CCR4/NOT mRNA processing complex exhibit synthetic phenotypes when combined with proteasome mutants. Further biochemical analyses revealed physical associations between CCR4/NOT and the proteasome in vivo. Consistent with the genetic and biochemical interactions linking CCR4/NOT with proteasome and Set1-mediated methylation, we find that loss of Not4 decreases global and gene-specific H3K4 trimethylation (H3K4me3) and decreases 19S proteasome recruitment to the PMA1 gene. Similar to proteasome regulation of histone methylation, loss of CCR4/NOT members does not affect ubiquitinated H2B. Mapping of Not4 identified the RING finger domain as essential for H3K4me3, suggesting a role for ubiquitin in this process. Consistent with this idea, loss of the Not4-interacting protein Ubc4, a known ubiquitin-conjugating enzyme, decreases H3K4me3. These studies implicate CCR4/NOT in the regulation of H3K4me3 through a ubiquitin-dependent pathway that likely involves the proteasome.

Laribee, R. Nicholas; Shibata, Yoichiro; Mersman, Douglas P.; Collins, Sean R.; Kemmeren, Patrick; Roguev, Assen; Weissman, Jonathan S.; Briggs, Scott D.; Krogan, Nevan J.; Strahl, Brian D.



On the complexation of quercetin with methyl-?-cyclodextrin: photostability and antioxidant studies  

Microsoft Academic Search

Quercetin, a plant-derived flavonoid, has been extensively investigated for a wide range of potential health benefits linked\\u000a to its antioxidant properties. Unfortunately the topical administration of this molecule is restricted by its fast photodegradation.\\u000a In the attempt to overcome this limitation the inclusion complex between quercetin (Q) and methyl-?-cyclodextrin (Me-?-CD)\\u000a was prepared and previously investigated by a molecular modelling study,

M. E. Carlotti; S. Sapino; E. Ugazio; G. Caron



Methylated Trivalent Arsenic-Glutathione Complexes are More Stable than their Arsenite Analog  

PubMed Central

The trivalent arsenic glutathione complexes arsenic triglutathione, methylarsonous diglutathione, and dimethylarsinous glutathione are key intermediates in the mammalian metabolism of arsenite and possibly represent the arsenic species that are transported from the liver to the kidney for urinary excretion. Despite this, the comparative stability of the arsenic-sulfur bonds in these complexes has not been investigated under physiological conditions resembling hepatocyte cytosol. Using size-exclusion chromatography and a glutathione-containing phosphate buffered saline mobile phase (5 or 10 mM glutathione, pH 7.4) in conjunction with an arsenic-specific detector, we chromatographed arsenite, monomethylarsonous acid, and dimethylarsinous acid. The on-column formation of the corresponding arsenic-glutathione complexes between 4 and 37°C revealed that methylated arsenic-glutathione complexes are more stable than arsenic triglutathione. The relevance of these results with regard to the metabolic fate of arsenite in mammals is discussed.

Percy, Andrew J.; Gailer, Jurgen



Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.  


ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation. PMID:10444591

Zhang, Y; Ng, H H; Erdjument-Bromage, H; Tempst, P; Bird, A; Reinberg, D



Decoding of Methylated Histone H3 Tail by the Pygo-BCL9 Wnt Signaling Complex  

PubMed Central

Summary Pygo and BCL9/Legless transduce the Wnt signal by promoting the transcriptional activity of ?-catenin/Armadillo in normal and malignant cells. We show that human and Drosophila Pygo PHD fingers associate with their cognate HD1 domains from BCL9/Legless to bind specifically to the histone H3 tail methylated at lysine 4 (H3K4me). The crystal structures of ternary complexes between PHD, HD1, and two different H3K4me peptides reveal a unique mode of histone tail recognition: efficient histone binding requires HD1 association, and the PHD-HD1 complex binds preferentially to H3K4me2 while displaying insensitivity to methylation of H3R2. Therefore, this is a prime example of histone tail binding by a PHD finger (of Pygo) being modulated by a cofactor (BCL9/Legless). Rescue experiments in Drosophila indicate that Wnt signaling outputs depend on histone decoding. The specificity of this process provided by the Pygo-BCL9/Legless complex suggests that this complex facilitates an early step in the transition from gene silence to Wnt-induced transcription.

Fiedler, Marc; Sanchez-Barrena, Maria Jose; Nekrasov, Maxim; Mieszczanek, Juliusz; Rybin, Vladimir; Muller, Jurg; Evans, Phil; Bienz, Mariann



Intermediate-Valence Tautomerism in Decamethylytterbocene Complexes of Methyl-Substituted Bipyridines  

SciTech Connect

Multiconfigurational, intermediate valent ground states are established in several methyl-substituted bipyridine complexes of bispentamethylcyclopentadienylytterbium, Cp*{sub 2} Yb(Me{sub x}-bipy). In contrast to Cp*{sub 2} Yb(bipy) and other substituted-bipy complexes, the nature of both the ground state and the first excited state are altered by changing the position of the methyl or dimethyl substitutions on the bipyridine rings. In particular, certain substitutions result in multiconfigurational, intermediate valent open-shell singlet states in both the ground state and the first excited state. These conclusions are reached after consideration of single-crystal x-ray diffraction (XRD), the temperature dependence of x-ray absorption near-edge structure (XANES), extended x-ray absorption fine-structure (EXAFS), and magnetic susceptibility data, and are supported by CASSCF-MP2 calculations. These results place the various Cp*{sub 2}Yb(bipy) complexes in a new tautomeric class, that is, intermediate-valence tautomers.

Booth, Corwin H.; Kazhdan, Daniel; Werkema, Evan L.; Walter, Marc D.; Lukens, Wayne W.; Bauer, Eric D.; Hu, Yung-Jin; Maron, Laurent; Eisenstein, Odile; Head-Gordon, Martin; Andersen, Richard A.



IDN2 and Its Paralogs Form a Complex Required for RNA-Directed DNA Methylation  

PubMed Central

IDN2/RDM12 has been previously identified as a component of the RNA–directed DNA methylation (RdDM) machinery in Arabidopsis thaliana, but how it functions in RdDM remains unknown. By affinity purification of IDN2, we co-purified two IDN2 paralogs IDP1 and IDP2 (IDN2 PARALOG 1 and 2). The coiled-coil domain between the XS and XH domains of IDN2 is essential for IDN2 homodimerization, whereas the IDN2 C-terminal XH domain but not the coiled-coil domain is required for IDN2 interaction with IDP1 and IDP2. By introducing the wild-type IDN2 sequence and its mutated derivatives into the idn2 mutant for complementation testing, we demonstrated that the previously uncharacterized IDN2 XH domain is required for the IDN2-IDP1/IDP2 complex formation as well as for IDN2 function. IDP1 is required for de novo DNA methylation, siRNA accumulation, and transcriptional gene silencing, whereas IDP2 has partially overlapping roles with IDP1. Unlike IDN2, IDP1 and IDP2 are incapable of binding double-stranded RNA, suggesting that the roles of IDP1 and IDP2 are different from those of IDN2 in the IDN2-IDP1/IDP2 complex and that IDP1 and IDP2 are essential for the functioning of the complex in RdDM.

Zhang, Cui-Jun; Ning, Yong-Qiang; Zhang, Su-Wei; Chen, Qing; Shao, Chang-Rong; Guo, Yan-Wu; Zhou, Jin-Xing; Li, Lin; Chen, She; He, Xin-Jian



G9a/GLP complexes independently mediate H3K9 and DNA methylation to silence transcription  

PubMed Central

Methylation of DNA and lysine 9 of histone H3 (H3K9) are well-conserved epigenetic marks for transcriptional silencing. Although H3K9 methylation directs DNA methylation in filamentous fungi and plants, this pathway has not been corroborated in mammals. G9a and GLP/Eu-HMTase1 are two-related mammalian lysine methyltransferases and a G9a/GLP heteromeric complex regulates H3K9 methylation of euchromatin. To elucidate the function of G9a/GLP-mediated H3K9 methylation in the regulation of DNA methylation and transcriptional silencing, we characterized ES cells expressing catalytically inactive mutants of G9a and/or GLP. Interestingly, in ES cells expressing a G9a-mutant/GLP complex that does not rescue global H3K9 methylation, G9a/GLP-target genes remain silent. The CpG sites of the promoter regions of these genes were hypermethylated in such mutant ES cells, but hypomethylated in G9a- or GLP-KO ES cells. Treatment with a DNA methyltransferase inhibitor reactivates these G9a/GLP-target genes in ES cells expressing catalytically inactive G9a/GLP proteins, but not the wild-type proteins. This is the first clear evidence that G9a/GLP suppresses transcription by independently inducing both H3K9 and DNA methylation.

Tachibana, Makoto; Matsumura, Yasuko; Fukuda, Mikiko; Kimura, Hiroshi; Shinkai, Yoichi



Temperature dependent luminescence of a europium complex incorporated in poly(methyl methacrylate).  


An europium ?-diketonate complex with a dipyrazolyltriazine derivative ligand, Eu(TTA)3DPBT, has been incorporated into poly(methyl methacryate) (PMMA). The influence of temperature on its luminescence properties has been investigated. The fluorescence emission spectra and luminescence lifetimes showed temperature sensitivity. The analysis of the relative intensity ratio (R) of (5)D0?(7)F2 to (5)D0?(7)F1 transition and Judd-Ofelt experimental intensity parameters ?2 indicated that the local structure and asymmetry in the vicinity of europium ions show no obvious change when the temperature is increased. PMID:23973573

Liang, Hao; Xie, Fang; Ren, Xiaojun; Chen, Yifa; Chen, Biao; Guo, Fuquan



Isomerization of methyl linoleate on ruthenium(III) alkoxide complex; Mathematical modeling  

SciTech Connect

The isomerization of methyl linoleate using ruthenium alkoxide complexes is described. With alcohols, such as isopropyl alcohol (IPA), 1-butanol, 1-hexanol, and 1-octanol, isomerization of double bonds to produce a conjugated system is the main reaction, with hydrogenation being the side reaction. The latter is formed via the conjugated product. Based on kinetic and infrared spectroscopic data, it is concluded that the active catalytic species is a ruthenium hydride complex formed by the decomposition of the unstable alkoxide. The reaction is mathematically modeled, and the rate parameters are obtained by fitting the simulation to experimental data. These values are compared with data obtained from reactions carried out with supported ruthenium-nickel heterogeneous catalyst.

Mukesh, D.; Narasimhan, C.S.; Ramnarayan, K.; Deshpande, V.M



Abstraction of methyl from neutral Fischer-type carbene complexes: A new site for nucleophilic attack  

SciTech Connect

Reactions of Fischer-type carbene complexes, M(CO){sub 5}(C(OMe)pH) (M = Cr, W), with metal carbonyl anions (M`{sup -} = CpFe(CO){sub 2}{sup -@}, Re(CO){sub 5}{sup -}, Mn(CO){sub 4}PPh{sub 3}{sup -}, Co(CO){sub 3}PPh{sub 3}{sup -}, Cp{sup *}Cr(CO){sub 3}{sup -}, CpMo(CO){sub 3}{sup -}) result in demethylation of the carbene complexes. The products are M(CO){sub 5}C(O)Ph{sup -} and M`-Me, characterized by infrared and NMR spectroscopy. A slower rate for reaction with W(CO){sub 5}(C(OEt)Ph) in comparison to the methyl analogue is consistent with nucleophilic attack of the metal carbonyl anion on the methyl of the methoxy group of the carbene. This is a new type of nucleophilic attack of a Fischer-type carbene. 22 refs., 1 fig., 1 tab.

Toomey, L.M.; Atwood, J.D. [State Univ. of New York, Buffalo, NY (United States)



Multiple Histone Methyl and Acetyltransferase Complex Components Bind the HLA-DRA Gene  

PubMed Central

Major histocompatibility complex class II (MHC-II) genes are fundamental components that contribute to adaptive immune responses. While characterization of the chromatin features at the core promoter region of these genes has been studied, the scope of histone modifications and the modifying factors responsible for activation of these genes are less well defined. Using the MHC-II gene HLA-DRA as a model, the extent and distribution of major histone modifications associated with active expression were defined in interferon-? induced epithelial cells, B cells, and B-cell mutants for MHC-II expression. With active transcription, nucleosome density around the proximal regulatory region was diminished and histone acetylation and methylation modifications were distributed throughout the gene in distinct patterns that were dependent on the modification examined. Irrespective of the location, the majority of these modifications were dependent on the binding of either the X-box binding factor RFX or the class II transactivator (CIITA) to the proximal regulatory region. Importantly, once established, the modifications were stable through multiple cell divisions after the activating stimulus was removed, suggesting that activation of this system resulted in an epigenetic state. A dual crosslinking chromatin immunoprecipitation method was used to detect histone modifying protein components that interacted across the gene. Components of the MLL methyltransferase and GCN5 acetyltransferase complexes were identified. Some MLL complex components were found to be CIITA independent, including MLL1, ASH2L and RbBP5. Likewise, GCN5 containing acetyltransferase complex components belonging to the ATAC and STAGA complexes were also identified. These results suggest that multiple complexes are either used or are assembled as the gene is activated for expression. Together the results define and illustrate a complex network of histone modifying proteins and multisubunit complexes participating in MHC-II transcription.

Choi, Nancy M.; Boss, Jeremy M.



Reaction time dependent formation of Pd(II) and Pt(II) complexes of bis(methyl)thiasalen podand.  


Thiasalen podand 9 having S2N2 donor set has been synthesized by the condensation of 2-methylthiobenzaldehyde with ethylenediamine. The reaction of the thiasalen podand ligand with Pd(II) afforded two complexes depending on the reaction time. Shorter reaction time (5 min) afforded thioether complex 10; whereas with increase in reaction time (4 h) thioether-thiolate complex 11 was obtained via cleavage of one of the two S-C(Me) bonds of bis(methyl)thiasalen podand upon complexation. The reaction of 9 with Pt(II) afforded only thiolate-thioether complex 12 independent of the reaction time. The cleavage of both the S-C(Me) bonds of bis(methyl)thiasalen to afford bisthiolate complexes has never been observed. The structures of thiasalen podands and all three complexes have been determined by single crystal X-ray diffraction analysis. All three complexes possess a square planar geometry around the metal centres. Weak van der Waals interactions through C-H···F interactions are present in all three complexes leading to the formation of supramolecular synthons and the supramolecular structures are stabilized by aromatic ?···? interactions, which leads to the formation of 3D pseudo-double helical network packing. Under similar conditions bis(methyl)salen did not form any complexes with Pd(II) and Pt(II). PMID:23073301

Dutta, Pradip Kr; Panda, Snigdha; Krishna, G Rama; Reddy, C Malla; Zade, Sanjio S



Intramolecular reductive elimination of methane from a dinuclear palladium complex containing methyl and hydride on adjacent palladium centers  

SciTech Connect

The preparation, isolation, and determination of structure of a dinuclear palladium complex containing methyl and hydride on adjacent palladium atoms its facile 1,1-dinuclear intramolecular elimination of methane are reported. The complex was isolated as its tetraphenylborate salt and was fully characterized including its x-ray structure. Reductive elimination from the deuterated complex containing deutride on one palladium and trideuteriomethyl on the other gave a quantitative yield of methane. 16 references, 3 figures.

Kellenberger, B.; Young, S.J.; Stille, J.K.



MBD2 is a critical component of a methyl cytosine-binding protein complex isolated from primary erythroid cells.  


The chicken embryonic beta-type globin gene, rho, is a member of a small group of vertebrate genes whose developmentally regulated expression is mediated by DNA methylation. Previously, we have shown that a methyl cytosine-binding complex binds to the methylated rho-globin gene in vitro. We have now chromatographically purified and characterized this complex from adult chicken primary erythroid cells. Four components of the MeCP1 transcriptional repression complex were identified: MBD2, RBAP48, HDAC2, and MTA1. These 4 proteins, as well as the zinc-finger protein p66 and the chromatin remodeling factor Mi2, were found to coelute by gel-filtration analysis and pull-down assays. We conclude that these 6 proteins are components of the MeCPC. In adult erythrocytes, significant enrichment for MBD2 is seen at the inactive rho-globin gene by chromatin immunoprecipitation assay, whereas no enrichment is observed at the active beta(A)-globin gene, demonstrating MBD2 binds to the methylated and transcriptionally silent rho-globin gene in vivo. Knock-down of MBD2 resulted in up-regulation of a methylated rho-gene construct in mouse erythroleukemic (MEL)-rho cells. These results represent the first purification of a MeCP1-like complex from a primary cell source and provide support for a role for MBD2 in developmental gene regulation. PMID:16778143

Kransdorf, Evan P; Wang, Shou Zhen; Zhu, Sheng Zu; Langston, Timothy B; Rupon, Jeremy W; Ginder, Gordon D



RNA Methylation by the MIS Complex Regulates a Cell Fate Decision in Yeast  

PubMed Central

For the yeast Saccharomyces cerevisiae, nutrient limitation is a key developmental signal causing diploid cells to switch from yeast-form budding to either foraging pseudohyphal (PH) growth or meiosis and sporulation. Prolonged starvation leads to lineage restriction, such that cells exiting meiotic prophase are committed to complete sporulation even if nutrients are restored. Here, we have identified an earlier commitment point in the starvation program. After this point, cells, returned to nutrient-rich medium, entered a form of synchronous PH development that was morphologically and genetically indistinguishable from starvation-induced PH growth. We show that lineage restriction during this time was, in part, dependent on the mRNA methyltransferase activity of Ime4, which played separable roles in meiotic induction and suppression of the PH program. Normal levels of meiotic mRNA methylation required the catalytic domain of Ime4, as well as two meiotic proteins, Mum2 and Slz1, which interacted and co-immunoprecipitated with Ime4. This MIS complex (Mum2, Ime4, and Slz1) functioned in both starvation pathways. Together, our results support the notion that the yeast starvation response is an extended process that progressively restricts cell fate and reveal a broad role of post-transcriptional RNA methylation in these decisions.

Agarwala, Sudeep D.; Blitzblau, Hannah G.; Hochwagen, Andreas; Fink, Gerald R.



Magnetic and Spectroscopic Studies of Metallic Halide Complexes with N-Methyl-1,2,4-Triazoles  

Microsoft Academic Search

Complexes of metal (II) halides with N-methyl-1,2,4-triazoles have been prepared, characterized, and studied by magnetism, and electronic and vibrational spectroscopies. The complex with 1:4 stoichiometry is monomeric; those of 1:1 or 1:2 stoichiometries are polymeric. It is seen from electronic studies that metal ions are trans-octahedrally coordinated and chromophores are MX4N2 or MX2N4. These structural results are in accordance with

S. Zaydoun; F. Guedira; M. Saidi Idrissi; A. Zrineh; C. Garrigou-Lagrange; A. Rubbens-Lorriaux



Group-4 eta(1)-pyrrolyl complexes incorporating N,N-di(pyrrolyl-alpha-methyl)-N-methylamine.  


Syntheses and properties of group-4 complexes incorporating the tridentate, dianionic ligand N,N-(dipyrrolyl-alpha-methyl)-N-methylamine, dpma, have been investigated. Addition of 1 equiv of H(2)dpma to Ti(NMe(2))(4) and Zr(NMe(2))(4) results in transamination with 2 dimethylamides providing Ti(NMe(2))(2)(dpma) and Zr(NMe(2))(2)(NHMe(2))(dpma), respectively. Addition of 2 equiv of H(2)dpma to Zr(NMe(2))(4) and Hf(NMe(2))(4) results in production of the homoleptic complexes Zr(dpma)(2) and Hf(dpma)(2). Conversely, treatment of Ti(NMe(2))(4) with 2 equiv of H(2)dpma does not provide Ti(dpma)(2), which was available by addition of 2 Li(2)dpma to TiCl(4). The properties of the isostructural series M(dpma)(2) were investigated by single crystal X-ray diffraction, cyclic voltammetry, (14)N NMR, and other techniques. By (14)N NMR, it was found that the pyrrolyl resonance chemical shift changes approximately linearly with the electronegativity of the metal center, which was attributed to pi-interaction between the pyrrolyl nitrogen lone pair and the metal. Other complexes produced during this study include Ti(CH(2)SiMe(3))(NMe(2))(dpma), TiCl(2)(THF)(dpma), and Ti(OCH(2)CF(3))(2)(THF)(dpma). Two isomers for Ti(CH(2)SiMe(3))(NMe(2))(dpma) were isolated and characterized. PMID:12444773

Li, Yahong; Turnas, Angie; Ciszewski, James T; Odom, Aaron L



Synthesis and Crystal Structures of Copper(II) Complexes Derived from 5Methoxy2-[(pyridin-2-ylmethylimino)methyl]phenol  

Microsoft Academic Search

The synthesis and crystal structures of two new mononuclear copper(II) complexes, [CuL(H2O)][CuL(H2O)2]·2ClO4 (1) and [CuL(dca)] (2) (HL = 5-methoxy-2-[(pyridin-2-ylmethylimino)methyl]phenol, dca = dicyanamide anion), are described. The infrared spectra of the complexes have also been discussed. Complex 1 contains a [CuL(H2O)] cation, in which the Cu atom adopts a square planar coordination, a [CuL(H2O)2] cation, in which the Cu atom adopts

Zeng-Xin Liu



Spectroscopic and Electrochemical Studies of Some Molybdenum and Ruthenium Complexes of N -[(2-pyridyl)methyl]-2,2?-dipyridylamine  

Microsoft Academic Search

Interaction of the tripodal ligand N-[(2-pyridyl)methyl]-2,2?-dipyridylamine (pmdpa) with [Mo(CO)6] under reduced pressure gave two complexes [Mo(CO)4(pmdpa)] and [Mo(CO)2(pmdpa)2], depending on the mole ratio and reaction time. The i.r. spectra of the two complexes gave patterns in the metal carbonyl\\u000a region confirming the proposed structures. Reaction of [Ru3(CO)12] with pmdpa in benzene gave the mononuclear complex [Ru(CO)3(pmdpa)]. The electronic absorption spectra

Ramadan M. Ramadan; Mohamed S. A. Hamza; Hassan A. Mohamed; Samir M. El-Medani



Platinum complexes with 5-methyl-5(4-pyridyl)hydantoin and its 3-methyl derivatives: synthesis and cytotoxic activity - quantitative structure-activity relationships.  


3,5-Dimethyl-5-(4-pyridyl)hydantoin (L) and its platinum(II) and platinum(IV) complexes with the general formula cis-[PtL(2) X(2) ]?·?n H(2) O and [PtL(2) Cl(4) ], where X?Cl, I and n?=?2-4 were synthesized. A new Pt(IV) complex with 5-methyl-5-(4-pyridyl)hydantoin (L') with the formula cis-[Pt(L')(2) Cl(2) (OH)(2) ]?·?5 H(2) O was also synthesized. The novel compounds were characterized by elemental analysis, IR, (1) H-, (13) C-, (195) Pt-NMR spectra and molar conductivity. The cytotoxic effects of these complexes were examined on three human tumor cell lines by MTT-dye reduction assay. These four new Pt(II) and Pt(IV) complexes and a set of another twelve Pt(II), Pt(IV), and Pd(II) complexes previously synthesized and tested were compiled and a QSAR model was derived in order to direct the further rational synthesis. PMID:21469169

Bakalova, Adriana; Varbanov, Hristo; Buyukliev, Rossen; Momekov, Georgi; Ivanov, Darvin; Doytchinova, Irini



Enantioselective DNA binding of iron(II) complexes of methyl-substituted phenanthroline.  


The enantioselective binding of [Fe(4,7-dmp)(3)](2+) (dmp: 4,7-dimethyl-1,10-phenantroline) and [Fe(3,4,7,8-tmp)(3)](2+) (tmp: 3,4,7,8-tetramethyl-1,10-phenanthroline) to calf-thymus DNA (ct-DNA) has been systematically studied by monitoring the circular dichroism (CD) spectral profile of the iron(II) complexes in the absence and presence of ct-DNA. The effect of salt concentration and temperature on the degree of enantioselectivity of the ct-DNA binding of the iron(II) complexes, i.e. the molar ratio of Delta- to Lambda-enantiomer in the solution or vice versa has been rigorously evaluated. It is noticeable that Delta-[Fe(4,7-dmp)(3)](2+) and Lambda-[Fe(3,4,7,8-tmp)(3)](2+) are preferentially bound to ct-DNA as reflected in their opposite CD spectral profiles. The preferential binding of the Lambda-enantiomer of [Fe(3,4,7,8-tmp)(3)](2+) to ct-DNA compared to that of the Delta-enantiomer is associated with the bulkiness of the ancillary ligands due to substitution of four hydrogen atoms in 1,10-phenanthroline for four methyl groups. The determination of enantiomeric inversion constant (K(inv)) at various salt concentrations has revealed that the degree of enantioselectivity is salt concentration dependent, indicating that electrostatic interaction is involved in the enantioselective binding of the iron(II) complexes to ct-DNA. Although [Fe(4,7-dmp)(3)](2+) and [Fe(3,4,7,8-tmp)(3)](2+) exhibit an opposite pattern in the CD spectra, the degree of their enantioselectivity (K(inv)) is not different from each other significantly. A thermodynamic study on the enantioselective binding of [Fe(4,7-dmp)(3)](2+) to ct-DNA using the van't Hoff plot of In K(inv) versus 1/T has demonstrated that the enthalpy change (Delta H degrees ) in the inversion process from the Lambda- to Delta-enantiomer of [Fe(4,7-dmp)(3)](2+) ct-DNA is positive, indicating that the process is endothermic and thus entropically driven. PMID:18457882

Mudasir; Yoshioka, Naoki; Inoue, Hidenari




Microsoft Academic Search

1-(1H-Benzotriazol-1-acetyl)-5-hydroxy-3-methyl-5-phenyl-2-pyrazoline (H2L) and 1-(2H-benzotriazol-2-acetyl)-5-hydroxy-3-methyl-5-phenyl-2-pyrazoline (H2L) have been synthesized by condensing 1H-benzotriazol-1-acetic acid hydrazide or 2H-benzotriazol-2-acetic acid hydrazide with 1-phenyl-1,3-butanedione. Complexes of the type [ML]2 and [M(HL)(AcO)] [M=Zn(II), Cu(II), Ni(II)] have been prepared by refluxing the pyrazolines with the metal acetate hydrates in ethanol. The ligands and their complexes have been characterized by elemental analyses, IR, H NMR and MS spectra.

Zenglu Liu; Yongqiang Tu



Thermal properties of poly(ethylene oxide)-poly(methyl methacrylate) blends and copolymers complexed with sodium thiocyanate  

Microsoft Academic Search

The phase behaviour of poly(ethylene oxide) (PEO) and poly(methyl methacrylate) (PMMA) blends, a partially miscible system, and of PEO\\/PMMA block copolymers, all cast from acetonitrile, were determined in the presence of added NaSCN. The phase behaviour is dominated by the added salt, which forms an insoluble P(EO3.NaSCN) complex and induces separation of PEO and PMMA in homopolymer blends. In block

P. Sakellariou



Initial rate of alternating copolymerization of anethole with maleic anhydride in methyl ethyl ketone analysis by a complex model  

Microsoft Academic Search

Dilatometrically determined initial rate of alternating copolymerization of anethole (M1) and maleic anhydride (M2) in methyl ethyl ketone (MEK) is reported for the total monomer concentrations of 1M, 2M and 3M polymerized at 50°C with AIBN. The rate is larger than the first order with respect to the monomer concentration. The simplified complex model adopted by Shirota et al is

Kiyohisa Fujimori; Wayne S. Schiller; Ian E. Craven



Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange  

Microsoft Academic Search

A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of benzydamine HCl (BENZ), levamisole HCl (LEV) and mebeverine HCl (MBV) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH 3.6. The formed yellow ion-pair complexes were extracted with dichloromethane and

Akram M. El-Didamony



DNA binding, DNA cleavage, antioxidant and cytotoxicity studies on ruthenium(II) complexes of benzaldehyde 4-methyl-3-thiosemicarbazones  

NASA Astrophysics Data System (ADS)

Four new ruthenium(II) complexes with N(4)-methyl thiosemicarbazone ligands, (E)-2-(2-chlorobenzylidene)-N-methylhydrazinecarbothioamide (HL1) and (E)-N-methyl-2-(2-nitrobenzylidene)hydrazinecarbothioamide (HL2), were prepared and fully characterized by various spectro-analytical techniques. The Schiff bases act as bidentate, monobasic chelating ligands with S and N as the donor sites and are preferably found in the thiol form in all the complexes studied. The molecular structure of HL1 and HL2 were determined by single crystal X-ray diffraction method. DNA binding of the compounds was investigated by absorption spectroscopy which indicated that the complexes bind to DNA via intercalation. The oxidative cleavage of the complexes with CT-DNA inferred that the effects of cleavage are dose dependent. Antioxidant studies of the ligands and complexes showed the significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of the ligands and complexes against MCF-7 cell line was assayed which showed higher cytotoxic activity with the lower IC50 values indicating their efficiency in killing the cancer cells even at low concentrations.

Sampath, Krishnan; Sathiyaraj, Subbaiyan; Jayabalakrishnan, Chinnasamy



New square-planar cationic Pt(II) complexes containing a methyl and an olefin in cis position  

Microsoft Academic Search

An effective method for the synthesis of square-planar cationic Pt(II) complexes containing a methyl and an olefin in cis position is described. The addition of Me3OBF4 to [Pt(phen)(?3-E-MeO2CCH?CHCO2Me)] affords the cationic olefin complex [PtMe(phen)(?2-E-MeO2CCH?CHCO2Me)]+(BF4?). Dimethylfumarate is easily displaced by electron-rich olefins RCH?CH2 (R ? H, Ph, Me) and the products [PtMe(phen)(?2-RCH?CH2)]+(BF4?) can be isolated in good yield.

Ida Orabona; Achille Panunzi; Francesco Ruffo



Application of high vacuum fractional distillation to complex mixtures of methyl esters of polyunsaturated fatty acids  

Microsoft Academic Search

A technique for the high vacuum fractional distillation, with a spinning band column, of methyl esters of polyunsaturated\\u000a fatty acids employing a carrier of long chain acetates is described. The carrier is used to facilitate the fractionation of\\u000a minor components and minimize artifact formation in mixtures of methyl esters containing up to six double bonds. The technique\\u000a is demonstrated on

O. S. Privett; J. D. Nadenicek; F. J. Pusch; E. C. Nickell



Stable Uranium(VI) Methyl and Acetylide Complexes and the Elucidation of an Inverse Trans Influence Ligand Series.  


Thermally stable uranium(VI)-methyl and -acetylide complexes: U(VI)OR[N(SiMe3)2]3 R = -CH3, -C?CPh were prepared in which coordination of the hydrocarbyl group is directed trans to the uranium-oxo multiple bond. The stability of the uranium-carbon bond is attributed to an inverse trans influence. The hydrocarbyl complexes show greater ITI stabilization than that of structurally related U(VI)OX[N(SiMe3)2]3 (X = F(-), Cl(-), Br(-)) complexes, demonstrated both experimentally and computationally. An inverse trans influence ligand series is presented, developed from a union of theoretical and experimental results and based on correlations between the extent of cis-destabilization, the complexes stabilities toward electrochemical reduction, the thermodynamic driving forces for U?O bond formation, and the calculated destabilization of axial ?* and ?* antibonding interactions. PMID:23924364

Lewis, Andrew J; Carroll, Patrick J; Schelter, Eric J



Purification of fat-containing wastewater with a complex based on poly- N,N,N,N -trimethyl[methacryloyloxyethyl]ammonium methyl sulfate and sodium dodecyl sulfate  

Microsoft Academic Search

Possibility of using complexes based on poly-N,N,N,N-trimethyl[methacryloyloxyethyl]ammonium methyl sulfate and sodium dodecyl sulfate for purification of fat-containing wastewater\\u000a was examined.

Yu. V. Shulevich; T. Kh. Nguen; A. V. Navrotskii; I. A. Novakov



Synthesis and antimicrobial studies of 1-methyl-2-dimethylaminoethyl-substituted benzimidazolium salts and N-heterocyclic carbene–silver complexes  

Microsoft Academic Search

The synthesis and antimicrobial studies of 1-methyl-2-dimethylaminoethyl-substituted carbene precursors and silver complexes are reported. The carbene precursors (1a–d) have been prepared from 1-methyl-2-dimethylaminoethyl-substituted benzimidazole and various alkyl halides. The silver–NHC complexes (2a–d) were synthesized from the benzimidazolium salts and Ag2O in dichloromethane at room temperature. The new compounds were characterized by H NMR, C NMR, FT-IR, and elemental analyses. The

Beyhan Y???t; Yetk?n Gök; ?lknur Özdem?r; Selam? Günal



Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation  

SciTech Connect

Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse and human DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2), and methyltransferase domains bound to DNA-containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, in which unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.

Song, Jikui; Rechkoblit, Olga; Bestor, Timothy H.; Patel, Dinshaw J. (MSKCC); (Columbia)



Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation  

SciTech Connect

Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse and human DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2), and methyltransferase domains bound to DNA-containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, in which unmethylated CpG dinucleotides are occluded from the active site to ensure that only hemimethylated CpG dinucleotides undergo methylation.

J Song; O Rechkoblit; T Bestor; D Patel



Thermal history effects and methyl tunneling dynamics in a supramolecular complex of calixarene and para-xylene.  


The low-temperature structure and dynamics of guest molecules of p-xylene incorporated in the isopropyl-calix[4] arene(2:1) p-xylene complex have been investigated by solid state nuclear magnetic resonance (NMR). Using one-dimensional 1H-decoupled 13C cross-polarization magic-angle-spinning (MAS) NMR and two-dimensional 1H-13C correlation spectroscopy, a full assignment of the 13C and 1H chemical shifts has been made. Using 1H NMR relaxometry, the effects of thermal history on the structure of the system have been investigated. Rapidly cooled samples have 1H spin-lattice relaxation times T1, which at low temperature (T<60 K) are typically two orders of magnitude faster than those observed in annealed samples which have been cooled slowly over many hours. In both forms, the low-temperature relaxation is driven by the dynamics of the weakly hindered methyl rotors of the p-xylene guest. The substantial difference in T1 is attributed in the rapidly cooled sample to disorder in the structure of the complex leading to a wide distribution of correlation times and methyl barrier heights. A comparison of the linewidths and splittings in the high resolution 13C MAS spectra of the two forms provides structural insight into the nature of the disorder. Using 1H field-cycling NMR relaxometry, the methyl dynamics of the p-xylene guest in the annealed sample have been fully characterized. The B-field dependence of the 1H T1 maps out the spectral density from which the correlation times are directly measured. The methyl barrier heights are determined from an analysis of the temperature dependence. PMID:18412464

Panesar, K S; Horsewill, A J; Cuda, F; Carravetta, M; Mamone, S; Danquigny, A; Grossel, M C; Levitt, M H



Model studies of methyl CoM reductase: methane formation via CH3-S bond cleavage of Ni(I) tetraazacyclic complexes having intramolecular methyl sulfide pendants.  


The Ni(I) tetraazacycles [Ni(dmmtc)](+) and [Ni(mtc)](+), which have methylthioethyl pendants, were synthesized as models of the reduced state of the active site of methyl coenzyme M reductase (MCR), and their structures and redox properties were elucidated (dmmtc, 1,8-dimethyl-4,11-bis{(2-methylthio)ethyl}-1,4,8,11-tetraaza-1,4,8,11-cyclotetradecane; mtc, 1,8-{bis(2-methylthio)ethyl}-1,4,8,11-tetraaza-1,4,8,11-cyclotetradecane). The intramolecular CH(3)-S bond of the thioether pendant of [Ni(I)(dmmtc)](OTf) was cleaved in THF at 75 °C in the presence of the bulky thiol DmpSH, which acts as a proton source, and methane was formed in 31% yield and a Ni(II) thiolate complex was concomitantly obtained (Dmp = 2,6-dimesityphenyl). The CH(3)-S bond cleavage of [Ni(I)(mtc)](+) also proceeded similarly, but under milder conditions probably due to the lower potential of the [Ni(I)(mtc)](+) complex. These results indicate that the robust CH(3)-S bond can be homolytically cleaved by the Ni(I) center when they are properly arranged, which highlights the significance of the F430 Ni environment in the active site of the MCR protein. PMID:22439643

Nishigaki, Jun-ichi; Matsumoto, Tsuyoshi; Tatsumi, Kazuyuki



MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex.  


Methyl-CpG-binding domain proteins 2 and 3 (MBD2 and MBD3) are transcriptional repressors that contain methyl-CpG binding domains and are components of a CpG-methylated DNA binding complex named MeCP1. Methyl-CpG-binding protein 3-like 1 (MBD3L1) is a protein with substantial homology to MBD2 and MBD3, but it lacks the methyl-CpG binding domain. MBD3L1 interacts with MBD2 and MBD3 in vitro and in yeast two-hybrid assays. Gel shift experiments with a CpG-methylated DNA probe indicate that recombinant MBD3L1 can supershift an MBD2-methylated DNA complex. In vivo, MBD3L1 associates with and colocalizes with MBD2 but not with MBD3 and is recruited to 5-methylcytosine-rich pericentromeric heterochromatin in mouse cells. In glutathione S-transferase pull-down assays MBD3L1 is found associated with several known components of the MeCP1.NuRD complex, including HDAC1, HDAC2, MTA2, MBD2, RbAp46, and RbAp48, but MBD3 is not found in the MBD3L1-bound fraction. MBD3L1 enhances transcriptional repression of methylated DNA by MBD2. The data are consistent with a role of MBD3L1 as a methylation-dependent transcriptional repressor that may interchange with MBD3 as an MBD2-interacting component of the NuRD complex. MBD3L1 knockout mice were created and were found to be viable and fertile, indicating that MBD3L1 may not be essential or there is functional redundancy (through MBD3) in this pathway. Overall, this study reveals additional complexities in the mechanisms of transcriptional repression by the MBD family proteins. PMID:15456747

Jiang, Chun-Ling; Jin, Seung-Gi; Pfeifer, Gerd P



Spectroscopic studies of inclusion complexes of methyl-p-dimethylaminobenzoate and its ortho derivative with ?- and ?-cyclodextrins.  


The effects of ?- and ?-cyclodextrins (CDs) on the both emission modes (LE -locally excited and TICT -twisted intramolecular charge transfer) of the fluorescence spectrum of methyl-p-dimethylaminobenzoate (I) and its o-methoxy (II) derivative in aqueous solution have been investigated using steady-state and time-resolved fluorescence techniques. It is found that the intensity of both fluorescence bands increases with increasing concentration of ?- and ?-CD. The stoichiometries and equilibrium constants of the fluorophore-cyclodextrin inclusion complexes have been determined by steady-state fluorescence measurements. Performed spectroscopic studies demonstrate that in the case of I in ?-CD and ?-CD, both 1:1 and 1:2 inclusion complexes are formed, whereas only 1:1 inclusion complex is formed between II and ?-CD. PMID:22112580

Lazarowska, Agata; Józefowicz, Marek; Heldt, Janina R; Heldt, Józef



Mononuclear and Dinuclear Manganese(II) Complexes from the Use of Methyl(2-pyridyl)ketone Oxime  

PubMed Central

The reactions of methyl(2-pyridyl)ketone oxime, (py)C(Me)NOH, with manganese(II) sulfate monohydrate have been investigated. The reaction between equimolar quantities of MnSO4 · H2O and (py)C(Me)NOH in H2O lead to the dinuclear complex [Mn2(SO4)2{(py)C(Me)NOH}4] · (py)C(Me)NOH, 1 · (py)C(Me)NOH, while employment of NaOMe as base affords the compound [Mn(HCO2)2{(py)C(Me)NOH}2] (2). The structures of both compounds have been determined by single crystal X-ray diffraction. In both complexes, the organic ligand chelates through its nitrogen atoms. The IR data are discussed in terms of the nature of bonding and the structures of the two complexes.

Efthymiou, Constantinos G.; Nastopoulos, Vassilios; Raptopoulou, Catherine; Tasiopoulos, Anastasios; Perlepes, Spyros P.; Papatriantafyllopoulou, Constantina



Extraction and complex formation of niobium(V) with 3-hydroxy-2-methyl-1-(4-tolyl)-4-pyridone.  


The extraction of niobium(V) from aqueous hydrochloric and sulphuric acid solutions with 3-hydroxy-2-methyl-1-(4-tolyl)-4-pyridone (HY) dissolved in chloroform is described. Niobium(V) can be quantitatively extracted with HY in the form of two different complexes depending on the chloride ion concentration in the aqueous phase. At a low chloride concentration or without chloride in the aqueous phase niobium(V) is extracted with HY in the form of Nb(OH)(3)Y(2) and at a high chloride concentration as a mixed Nb(OH)(3)ClY complex. Niobium extraction with HY enables the separation of niobium(V) from zirconium(IV) and hafnium(IV). The formation of a mixed chloro-4-pyridone complex is also applicable for the spectrophotometric determination of niobium in the organic phase at the maximum absorption at 350 nm. PMID:18965316

Ivsi?, A G; Tamhina, B




EPA Science Inventory

Methyl tert-butyl ether (MTBE) is a well-known environmental contaminant owing to its high solubility in water. Since the early 1990s, MTBE has been added to gasoline to improve air quality in some metropolitan areas of the United States. Improved air quality was, however, achiev...


Microwave spectrum, dipole moment, and internal dynamics of the methyl fluoride-carbonyl sulfide weakly bound complex.  


Rotational spectra for the normal and four isotopically substituted species of the 1:1 complex between methyl fluoride (H3CF) and carbonyl sulfide (OCS) have been measured using Fourier-transform microwave spectroscopy in the 5-16 GHz frequency region. The observed spectra fit well to a semirigid Watson Hamiltonian, and an analysis of the rotational constants has allowed a structure to be determined for this complex. The dipole moment vectors of the H3CF and OCS monomers are aligned approximately antiparallel with a C...C separation of 3.75(3) A and with an ab plane of symmetry. The values of the Pcc planar moments were found to be considerably different from the expected rigid values for all isotopologues. An estimate of approximately 14.5(50) cm-1 for the internal rotation barrier of the CH3 group with respect to the framework of the complex has been made using the Pcc values for the H3CF-OCS and D3CF-OCS isotopic species. Two structures, very close in energy and approximately related by a 60 degrees rotation about the C3 axis of the methyl fluoride, were identified by ab initio calculations at the MP2/6-311++G(2d,2p) level and provide reasonable agreement with the experimental rotational constants and dipole moment components. PMID:18217737

Serafin, Michal M; Peebles, Sean A



Iron(III) complexes of some thiosemicarbazones derived from 2-acetylpyridine, its 6-methyl derivative and its N -oxide  

Microsoft Academic Search

A series of iron(III) complexes of thiosemicarbazones derived from 2-acetylpyridine, 6-methyl-2-acetylpyridine and 2-acetylpyridineN-oxide have been prepared from Fe(ClO4)3 and FeCl3. All of the isolated solids have cations involving two monobasic tridentate ligands, and either perchlorate or tetrachloroferrate(III) anions and are 1:1 electrolytes. Coordinationvia the pyridine nitrogen (or theN-oxide oxygen), the imine nitrogen and the sulphur atom are confirmed by infrared

Douglas X. West; Patricia M. Ahrweiler; Gözen Ertem; John P. Scovill; Daniel L. Klayman; Judith L. Flippen-Anderson; Richard Gilardi; Clifford George; Lewis K. Pannell



ADP-ribose polymers localized on Ctcf-Parp1-Dnmt1 complex prevent methylation of Ctcf target sites  

PubMed Central

PARylation [poly(ADP-ribosyl)ation] is involved in the maintenance of genomic methylation patterns through its control of Dnmt1 [DNA (cytosine-5)-methyltransferase 1] activity. Our previous findings indicated that Ctcf (CCCTC-binding factor) may be an important player in key events whereby PARylation controls the unmethylated status of some CpG-rich regions. Ctcf is able to activate Parp1 [poly(ADP-ribose) polymerase 1], which ADP-ribosylates itself and, in turn, inhibits DNA methylation via non-covalent interaction between its ADP-ribose polymers and Dnmt1. By such a mechanism, Ctcf may preserve the epigenetic pattern at promoters of important housekeeping genes. The results of the present study showed Dnmt1 as a new protein partner of Ctcf. Moreover, we show that Ctcf forms a complex with Dnmt1 and PARylated Parp1 at specific Ctcf target sequences and that PARylation is responsible for the maintenance of the unmethylated status of some Ctcf-bound CpGs. We suggest a mechanism by which Parp1, tethered and activated at specific DNA target sites by Ctcf, preserves their methylation-free status.

Zampieri, Michele; Guastafierro, Tiziana; Calabrese, Roberta; Ciccarone, Fabio; Bacalini, Maria G.; Reale, Anna; Perilli, Mariagrazia; Passananti, Claudio; Caiafa, Paola




Microsoft Academic Search

Mossbauer absorption spectra were investigated on compound I which is an ; addition product of DTOHâ and FeClâ (II), on compound II which can be ; represented by a formula Fe(DTOH) (removal of two hydrogen atoms), and on ; compound III or Fe(DTOMe)² which is a methyl ether derivative. Co⁵⁷ ; plated on chromium and fixed by thermodiffusion at 800

A. V. Ablov; G. N. Belozerskii; V. I. Goldanskii; E. F. Makarov; V. A. Trukhtanov; V. V. Khrapov



Platinum(IV) Complexes with Some Derivatives of 5-Methyl-5-(4-pyridyl)Hydantoin. Synthesis, Study and Comparative Pharmacological Investigation.  


3 Pt(IV) complexes with 3-ethyl-5-methyl-5-(4-pyridyl)hydantoin (4), 3-propyl-5-methyl-5-(4-pyridyl)hydantoin (5) and 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin (6) with general formulae cis-[Pt(L)2Cl4] were synthesized. The novel compounds were characterized by elemental analysis, IR, 1H, 13C, NMR spectra in solid state and in solution. The studies showed that the ligands coordinate to the platinum ions in a monodentate manner through the nitrogen atom from the pyridine ring. The cytotoxic activity in vitro of newly synthesized complexes as well as their previously prepared analogous of Pt(IV) with other derivatives like 3-amino-5-methyl-5-(4-pyridyl)hydantoin (1), 5-methyl-5-(4-pyridyl)hydantoin (2), 3,5-dimethyl-5-(4-pyridyl)hydantoin (3) was screened against a panel of human tumor cell lines. The tested compounds displayed cytotoxic activity which was invariably superior with the Pt(IV) complex with 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin (6) causing 50% inhibition of cellular viability at micromolar concentration, though the activity of the other studied Pt(IV) complexes proved to greatly decrease in the order 5-4-3-2-1. PMID:23677699

Bakalova, A; Buyukliev, R; Ivanova, Z; Momekov, G; Ivanov, D



Electrochemical study of some cobalt schiff base complexes and their methyl derivatives. Relation to the behaviour of the cobalt-carbon bond  

Microsoft Academic Search

Two series of methyl and nonmethyl cobalt complexes involving closely related quadridentate Schiff bases have been investigated. The use of nonsymmetrical or substituted ligands allows the reduction potential of the cobalt centre to be gradually modified. The data thus obtained are considered in connection with the ability of the cobalt complexes to alkylate tin (IV).

Jean-Pierre Costes; Gérard Cros; Marie-Hélène Darbieu; Jean-Pierre Laurent



Nonradiative Decay Dynamics of METHYL-4-HYDROXYCINNAMATE and its Monohydrated Complex Revealed by Picosecond Pump-Probe Spectroscopy  

NASA Astrophysics Data System (ADS)

The lifetimes of methyl 4-hydroxycinnamate (OMpCA) and its mono-hydrated complex (OMpCA-H_2O) in the S_1 state have been measured by picosecond pump-probe spectroscopy in a supersonic beam. For OMpCA, the lifetime of the S_1 - S_0 origin is 8 - 9 ps. On the other hand, the lifetime of OMpCA-H_2O complex at the origin is 930 ps, which is 100 times longer than that. Furthermore, in the complex the S_1 lifetime shows rapid decrease at an energy of 200 cm-1 above the origin and becomes as short as 9 ps at 500 cm-1. Theoretical calculations with symmetry-adapted cluster-configuration interaction (SAC-CI) method suggest that in OMpCA, the trans - cis isomerization occurs smoothly without a barrier on the S_1surface, while in OMpCA-H_2O complex, there exists a barrier along the isomerization coordinate. The calculated barrier height of OMpCA-H_2O is in good agreement with that estimated from the lifetime measurements.

Ebata, T.; Shimada, D.; Kusaka, R.; Inokuchi, Y.; Ehara, M.



Vinyl Polymerization Initiated by Metal Chelates. II. Polymerization of Methyl Methacrylate Initiated by Acetylacetonato Complexes of Manganese(III), Cobalt(III), and Iron(III)  

Microsoft Academic Search

The polymerization of methyl methacrylate was studied using Mn(acac)3, Co(acac)3, and Fe(acac)3 complexes. The rate of polymerization at various complex and monomer concentrations were investigated and it was observed that the plots of Rp versus [M] and Rp versus 1\\/[complex] were linear. The reactions were studied at different temperatures and the overall activation energies were computed to be 4.70, 5.50,

Subasini Lenka; Padma L. Nayak



Lanthanide complexes of 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one  

SciTech Connect

The title ligand (H(Dh), dehydroacetic acid) reacts with lanthanide(III) acetates in anhydrous methanol to form complexes of formula (M(Dh){sub 3}(MeOH)). When hydrated lanthanide acetates are used, hydrated compounds such as (Ce(Dh){sub 3}(H{sub 2}O)) or (Eu(Dh){sub 3}(H{sub 2}O)).H{sub 2}O are obtained. The reaction of lanthanum triacetate with H(Dh) yields the mixed complex (La(Dh){sub 2}(O{sub 2}CMe)), formation of the 1:3 complex also being unfavored in the presence of a large ligand excess. The complexes have been characterized by infrared and NMR ({sup 1}H and {sup 13}C) spectroscopy and by thermogravimetric measurements.

Sitran, S; Fregona, D. (Istituto di Chimica e Tecnologia dei Radioelementi del C.N.R., Padova (Italy)); Faraglia, G. (Dipartimento di Chimica Inorganica, Metallorganica ed Analitica dell'Universita, Padova (Italy))



Spectroscopic Studies of Zinc Benzenethiolate Complexes: Electron Transfer to Methyl Viologen. (Reannouncement with New Availability Information).  

National Technical Information Service (NTIS)

Mononuclear and tetranuclear zinc benzenethiolate complexes are studied by both spectroscopic and electrochemical methods. Zn(SPh)4 2- and Zn4(SPh)102- represent tetrahedral fragments of the cubic zinc sulfide lattice. The structured absorption spectra of...

T. Turk U. Resch M. A. Fox A. Vogler



MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing.  


MBD2 and MBD3 are two proteins that contain methyl-CpG binding domains and have a transcriptional repression function. Both proteins are components of a large CpG-methylated DNA binding complex named MeCP1, which consists of the nucleosome remodeling and histone deacetylase complex Mi2-NuRD and MBD2. MBD3L2 (methyl-CpG-binding protein 3-like 2) is a protein with substantial homology to MBD2 and MBD3, but it lacks the methyl-CpG-binding domain. Unlike MBD3L1, which is specifically expressed in haploid male germ cells, MBD3L2 expression is more widespread. MBD3L2 interacts with MBD3 in vitro and in vivo, co-localizes with MBD3 but not MBD2, and does not localize to methyl-CpG-rich regions in the nucleus. In glutathione S-transferase pull-down assays, MBD3L2 is found associated with several known components of the Mi2-NuRD complex, including HDAC1, HDAC2, MTA1, MBD3, p66, RbAp46, and RbAp48. Gel shift experiments with nuclear extracts and a CpG-methylated DNA probe indicate that recombinant MBD3L2 can displace a form of the MeCP1 complex from methylated DNA. MBD3L2 acts as a transcriptional repressor when tethered to a GAL4-DNA binding domain. Repression by GAL4-MBD3L2 is relieved by MBD2 and vice versa, and repression by MBD2 from a methylated promoter is relieved by MBD3L2. The data are consistent with a role of MBD3L2 as a transcriptional modulator that can interchange with MBD2 as an MBD3-interacting component of the NuRD complex. Thus, MBD3L2 has the potential to recruit the MeCP1 complex away from methylated DNA and reactivate transcription. PMID:15701600

Jin, Seung-Gi; Jiang, Chun-Ling; Rauch, Tibor; Li, Hongwei; Pfeifer, Gerd P



Syntheses and Crystal Structures of Two Isostructural Zinc(II) Complexes With Schiff-bases 2-Bromo-4-chloro-6-[(3-methylaminopropylimino)methyl]phenol and 2,4-Dichloro-6-[(3-methylaminopropylimino)methyl]phenol  

Microsoft Academic Search

Two new isostructural mononuclear zinc(II) complexes, [Zn(C11H14Cl2N2O)(NCS)(CH3COO)] and [Zn(C11H14BrClN2O) (NCS)(CH3COO)], have been synthesized from the Schiff-bases 2-bromo-4-chloro-6-[(3-methylaminopropylimino)methyl]phenol and 2,4-dichloro-6-[(3-methylaminopropylimino)methyl]phenol, respectively. Both complexes were characterized by elemental analysis, IR spectra and single-crystal X-ray diffraction. The Zn atom in each of the complexes is coordinated by one phenolic oxygen atom and one imine nitrogen atom of a Schiff-base ligand, one nitrogen atom

De-Suo Yang; Hai-Yun Zhu



Rinse and evaporation coating of poly(methyl methacrylate) microchip for separation of sodium dodecyl sulfate-protein complex.  


We developed a novel channel wall coating on a poly(methyl methacrylate) (PMMA) microchip using methylcellulose (MC) as a coating reagent to suppress electroosmotic flow (EOF) following the strong analytes adsorption via hydrophobic interaction with channel walls of PMMA. Our coating was obtained by first rinsing channel walls with MC-containing aqueous solution followed by evaporation. The coating made the hydrophilic channel wall lowering EOF by two orders of magnitude (1.2 x 10(-5)cm(2)V(-1)s(-1)) as well as reducing the hydrophobic adsorption. On the coated channel walls, we successfully separated sodium dodecyl sulfate-protein complexes with high reproducibility and efficiency using dextran as a lower viscosity protein separation medium. PMID:18430430

Okada, Hiroki; Kaji, Noritada; Tokeshi, Manabu; Baba, Yoshinobu



Synthesis and photophysics of a new deep red soluble phosphorescent iridium(III) complex based on chlorine-methyl-substituted 2,4 diphenyl quinoline  

NASA Astrophysics Data System (ADS)

A new iridium complex with a chlorine-methyl-substituted 2,4 diphenyl quinoline, (Cl-MDPQ) ligand has been synthesized. The synthesized iridium metal complex, Ir(Cl-MDPQ)2(acac) where Cl-MDPQ=chlorine-methyl substituted, 2,4 diphenyl quinoline, acac=acetyl acetone is characterized by employing different techniques such as mass spectrometry, 1H NMR, DTA/TGA, XRD, and FTIR. The molecular structures of Cl-MDPQ and Ir(Cl-MDPQ)2(acac) complexes are confirmed by the FTIR spectra. Strong singlet metal-to-ligand charge-transfer (1MLCT) and triplet metal-to-ligand charge-transfer (3MLCT) absorption peaks at 353 and 437 nm in tetrahydrofuran (THF) are reported in the synthesized complex, respectively. A deep red emitting Ir(Cl-MDPQ)2(acac) complex at 662 nm is promising for flexible organic devices.

Dahule, H. K.; Dhoble, S. J.; Ahn, J.-S.; Pode, Ramchandra



Major impact of N-methylation on cytotoxicity and hydrolysis of salan Ti(IV) complexes: sterics and electronics are intertwined.  


A series of Ti(IV) complexes containing diamino bis(phenolato) "salan" type ligands with NH coordination were prepared, and their hydrolysis and cytotoxicity were analyzed and compared to the N-methylated analogues. Substituting methyl groups on the coordinative nitrogen donor of highly active and stable Ti(IV) salan complexes with H atoms has two main consequences: the hydrolysis rate increases and the cytotoxic activity diminishes. In addition, the small modification of a single replacement of Me with H leads to a different major hydrolysis product, where a dinuclear Ti(IV) complex with two bridging oxo ligands is obtained, as characterized by X-ray crystallography, rather than a trinuclear cluster. A partial hydrolysis product containing a single oxo bridge was also crystallographically analyzed. Investigation of a series of complexes with NH donors of different steric and electronic effects revealed that cytotoxicity may be restored by fine tuning these parameters even for complexes of low stability. PMID:21874187

Meker, Sigalit; Manna, Cesar M; Peri, Dani; Tshuva, Edit Y



Photochromic metal complexes of N-methyl-4,4'-bipyridinium: mechanism and influence of halogen atoms.  


Photochromism of N-methyl-4,4'-bipyridinium (MQ(+)) salts and their metal complexes has never been reported. A series of MQ(+) coordinated halozinc complexes [(MQ)ZnX(3)] (X = Cl (1), Br (2), I (3)) and [(MQ)ZnCl(1.53)I(1.47)](2)(MQ)ZnCl(1.68)I(1.32) (4), with better physicochemical stability than halide salts of the MQ(+) cation, have been found to exhibit different photochromic behaviors. Compounds 1-3 are isostructural, but only 1 and 2 show photochromism. Introduction of partial Cl atoms to nonphotochromic compound 3 yields compound 4, which also displays photochromism. The photochromic response of 1, 2, and 4 indicates the presence of their long-lived charge separation states, which originate from X ? MQ(+) electron transfer according to ESR and XPS measurements. Studies on the influence of different coordinated halogen atoms demonstrate that the Cl atom may be a more suitable electron donor than Br and I atoms to design redox photochromic metal complexes. PMID:22409439

Lv, Xiang-Ying; Wang, Ming-Sheng; Yang, Chen; Wang, Guan-E; Wang, Shuai-Hua; Lin, Rong-Guang; Guo, Guo-Cong



Catalysis of acetyl-CoA cleavage and tetrahydrosarcinapterin methylation by a carbon monoxide dehydrogenase-corrinoid enzyme complex.  


An enzyme complex containing carbon monoxide dehydrogenase and a corrinoid protein has been isolated from Methanosarcina barkeri. Sodium dodecyl sulfate-gel electrophoresis revealed five polypeptides of molecular masses alpha = 19,700, beta = 84,500, gamma = 63,200, delta = 53,000, and epsilon = 51,400 Da in equimolar amounts. One mol of cobamide cofactor was found per minimal alpha beta gamma delta epsilon unit. The molecular mass of the native complex was 1,600,000 Da by high pressure liquid chromatography (HPLC) gel filtration, which suggested an alpha 6 beta 6 gamma 6 delta 6 epsilon 6 oligomeric structure. Catalysis of a reaction involving cleavage of acetyl-CoA and methylation of tetrahydrosarcinapterin was indicated by spectrophotometric analyses; a time-dependent absorption decrease in the 300-320 nm region was observed in the complete reaction mixture which contained acetyl-CoA, tetrahydrosarcinapterin, and the enzyme complex. In control samples lacking any one of the these components the absorption spectrum remained virtually unaltered. Reversed-phase HPLC analysis confirmed that tetrahydrosarcinapterin was converted to a product that co-eluted with authentic methyltetrahydrosarcinapterin. The product also exhibited the UV-visible absorption spectrum expected for methyltetrahydrosarcinapterin. Free CoA was identified as an additional product of the reaction. The carbonyl group of acetyl-CoA was oxidized to carbon dioxide. Spectral changes indicated concomitant Fe/S center reduction. Production of CoA was essentially stoichiometric with methyltetrahydrosarcinapterin formation and tetrahydrosarcinapterin consumption. Analyses during purification showed that catalytic activity was restricted exclusively to the fractions that contained the carbon monoxide dehydrogenase-corrinoid enzyme complex. PMID:1939246

Grahame, D A



Photoluminescence and raman studies of curium and americium complexes of 6-methyl 2-(2-pyridyl)-benzimidazole: evidence for an efficient intramolecular energy transfer.  


The 6-methyl-2-(2-pyridyl)-benzimidazole (biz) ligand coordinates with the actinide species in solution, and the complexes display efficient intramolecular energy-transfer processes. The energy transfer in the Cm(III)-biz system proceeds in a nonradiative mode, whereas a radiative mode is the principal mechanism in the Am(III)-biz system. PMID:14606830

Assefa, Zerihun; Yaita, T; Haire, R G; Tachimori, S



Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange.  


A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of benzydamine HCl (BENZ), levamisole HCl (LEV) and mebeverine HCl (MBV) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH 3.6. The formed yellow ion-pair complexes were extracted with dichloromethane and measured quantitatively with maximum absorption at 422 nm. The analytical parameters and their effects on the reported systems are investigated. The extracts are intensely colored and very stable at room temperature. The calibration graphs were linear over the concentration range of 2-10 microg ml(-1) for BENZ, 6-24 microg ml(-1) for LEV and 4-14 microg ml(-1) for MBV. The stoichiometry of the reaction was found to be 1:1 in all cases and the conditional stability constant (K(f)) of the complexes have been calculated. The proposed method was successfully extended to pharmaceutical preparations-tablets. Excipients used as additive in commercial formulations did not interfere in the analysis. The proposed method can be recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance. PMID:17625955

El-Didamony, Akram M



Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange  

NASA Astrophysics Data System (ADS)

A simple, rapid and sensitive spectrophotometric method has been proposed for the assay of benzydamine HCl (BENZ), levamisole HCl (LEV) and mebeverine HCl (MBV) in bulk and pharmaceutical formulations. The method based on the reaction of the selected drugs with methyl orange (MO) in buffered aqueous solution at pH 3.6. The formed yellow ion-pair complexes were extracted with dichloromethane and measured quantitatively with maximum absorption at 422 nm. The analytical parameters and their effects on the reported systems are investigated. The extracts are intensely colored and very stable at room temperature. The calibration graphs were linear over the concentration range of 2-10 ?g ml -1 for BENZ, 6-24 ?g ml -1 for LEV and 4-14 ?g ml -1 for MBV. The stoichiometry of the reaction was found to be 1:1 in all cases and the conditional stability constant ( Kf) of the complexes have been calculated. The proposed method was successfully extended to pharmaceutical preparations-tablets. Excipients used as additive in commercial formulations did not interfere in the analysis. The proposed method can be recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical technique are of great importance.

El-Didamony, Akram M.



Anion binding to a ferric porphyrin complexed with per-O-methylated beta-cyclodextrin in aqueous solution.  


5,10,15,20-Tetrakis(4-sulfonatophenyl)porphinato iron(III) (Fe(III)TPPS) forms a very stable 1:2 complex with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD), whose iron(III) center is located at a hydrophobic cleft formed by two face-to-face TMe-beta-CD molecules. Various inorganic anions (X(-)) such as F(-), Cl(-), Br(-), I(-), N(3)(-), and SCN(-) coordinate to Fe(III)TPPS(TMe-beta-CD)(2) to form five-coordinate high-spin Fe(III)TPPS(X)(TMe-beta-CD)(2), while no coordination occurs with ClO(4)(-), H(2)PO(4)(-), NO(3)(-), and HSO(4)(-). Except for F(-), none of the anions investigated coordinate to Fe(III)TPPS in the absence of TMe-beta-CD due to extensive hydration to the anions as well as to Fe(III)TPPS. The present system shows a high selectivity toward the N(3)(-) anion. The thermodynamics suggests that Lewis basicity, hydrophilicity, and shape of an X(-) anion are the main factors to determine the stability of the Fe(III)TPPS(X)(TMe-beta-CD)(2) complex. PMID:15548017

Kano, Koji; Kitagishi, Hiroaki; Tamura, Shigeto; Yamada, Akihisa



A cocrystal of two Mo(VI) complexes bearing different diastereomers of the 2,4-di-tert-butyl-6-{[(1-oxido-1-phenylpropan-2-yl)(methyl)amino]methyl}phenolate ligand derived from (+)-ephedrine.  


The title cocrystal contains two chiral conformational diastereomers, viz. (1S,2R,RN)- and (1S,2R,SN)-, of [2,4-di-tert-butyl-6-{[(1-oxido-1-phenylpropan-2-yl)(methyl)amino]methyl}phenolato](methanol)-cis-dioxidomolybdenum(VI), [Mo(C25H35NO2)O2(CH3OH)], representing the first example of a structurally characterized molybdenum complex with enantiomerically pure ephedrine derivative ligands. The Mo(VI) cations exhibit differently distorted octahedral coordination environments, with two oxide ligands positioned cis to each other. The remainder of the coordination comprises phenoxide, alkoxide and methanol O atoms, with an amine N atom completing the octahedron. The distinct complexes are linked by strong intermolecular O-H···O hydrogen bonds, resulting in one-dimensional molecular chains. Furthermore, the phenyl rings are involved in weak T-shaped/edge-to-face ?-? interactions with each other. PMID:23629903

Sillanpää, Reijo; Hänninen, Mikko M



Transition metal(II) complexes of 1-(?-hydroxynaphthyl)-2-(3?-methyl-5?-mercapto-1?,2?,4?-triazole)-2-aza-ethane  

Microsoft Academic Search

Summary Binuclear metal complexes of the type [M(HMTE)-(H2O)2]2, where HMTE=1-(a-hydroxynaphthyl)-2-(3'-methyl-5'-mercapto-1',2',4'-triazolc)2-aza-ethane and M-CuII, CoII, NiII and MnII have been prepared and characterized. An octahedral geometry around the metals is proposed. The complexes have been screened as possible fungicides.

Krushna C. Satpathy; Ashok K. Panda; Rushabha Mishra; Aditya P. Chopdar; Sarada K. Pradhan



Effect of N?Methyl Imidazole and Dimethyl Pyrazole Ligands on Polymerization of di(2,4,6?Trichlorophenolato)Cu(II)\\/Co(II) Complexes in Solid State  

Microsoft Academic Search

Polymerization of 2,4,6?trichlorophenol (TCPH) was achieved through the thermal decomposition of the copper and cobalt complexes of TCPH with N?containing ligands [N?methyl imidazole (NMIz) and 3,5?dimethyl pyrazole (DMPz)]. The structural analysis of the complexes was performed by using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), mass (MS), UV?VIS, diffuse reflectance (DRS) and electron spin resonance (ESR) spectroscopies, magnetic susceptibility

Meray Ba?türkmen; Duygu K?sakürek



Light-induced absorption spectra of the D1–D2–cytochrome b 559 complex of Photosystem II: Effect of methyl viologen concentration  

Microsoft Academic Search

The light-induced difference absorption spectra associated to the photo-accumulation of reduced pheophytin a were studied in the isolated D1–D2–Cyt b559 complex in the presence of variable methyl viologen concentrations and different illumination conditions under anaerobiosis.\\u000a Depending on the methyl viologen\\/reaction centre ratio, the relative intensities of the spectral bands at 681.5±0.5, 667.0±0.5\\u000a and 542.5±0.5 nm were modified. The reduced pheophytin

Inmaculada Yruela; Elena Torrado; Mercedes Roncel; Rafael Picorel



Synthesis, spectroscopic characterization and biological evaluation studies of Schiff's base derived from naphthofuran-2-carbohydrazide with 8-formyl-7-hydroxy-4-methyl coumarin and its metal complexes  

NASA Astrophysics Data System (ADS)

Metal complexes of the type ML2, where M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and L = Schiff's base derived from the condensation of naphthofuran-2-carbohydrazide with 8-formyl-7-hydroxy-4-methyl coumarin have been synthesized. The chelation of the complexes have been elucidated in the light of analytical, IR, UV-vis, 1H NMR, mass, ESR spectral data, thermal and magnetic studies. The measured molar conductance values indicate that, the complexes are non-electrolytic in nature. The redox behavior of one of the synthesized metal complexes was investigated by cyclic voltammetry. The Schiff's base and its metal complexes have been screened for their in vitro antibacterial and antifungal activities by MIC method. The DNA cleavage activities of all the complexes were studied by agarose gel electrophoresis method. In addition, the free ligand along with its complexes has been studied for their antioxidant activity.

Halli, M. B.; Sumathi, R. B.; Kinni, Mallikarjun



Synthesis, spectroscopic characterization and biological evaluation studies of Schiff's base derived from naphthofuran-2-carbohydrazide with 8-formyl-7-hydroxy-4-methyl coumarin and its metal complexes.  


Metal complexes of the type ML(2), where M=Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Hg(II) and L=Schiff's base derived from the condensation of naphthofuran-2-carbohydrazide with 8-formyl-7-hydroxy-4-methyl coumarin have been synthesized. The chelation of the complexes have been elucidated in the light of analytical, IR, UV-vis, (1)H NMR, mass, ESR spectral data, thermal and magnetic studies. The measured molar conductance values indicate that, the complexes are non-electrolytic in nature. The redox behavior of one of the synthesized metal complexes was investigated by cyclic voltammetry. The Schiff's base and its metal complexes have been screened for their in vitro antibacterial and antifungal activities by MIC method. The DNA cleavage activities of all the complexes were studied by agarose gel electrophoresis method. In addition, the free ligand along with its complexes has been studied for their antioxidant activity. PMID:23041921

Halli, M B; Sumathi, R B; Kinni, Mallikarjun



Crystal structures of copper(II) and nickel(II) nitrate and chloride complexes with 4-bromo-2-[(2-hydroxyethylimino)-methyl]phenol  

SciTech Connect

The crystal structures of {l_brace}4-bromo-2-[(2-hydroxyethylimino)-methyl]phenolo{r_brace}aquacopper(II) nitrate hemihydrate (I), chloro-{l_brace}4-bromo-2-[(2-hydroxyethylimino)-methyl]phenolo{r_brace}copper hemihydrate (II), and chloro-{l_brace}4-bromo-2-[(2-hydroxyethylimino)-methyl]phenolo{r_brace}aquanickel (III) are determined using X-ray diffraction. Crystals of compound I are formed by cationic complexes, nitrate ions, and solvate water molecules. In the cation, the copper atom coordinates the singly deprotonated molecule of tridentate azomethine and the water molecule. The copper complexes are joined into centrosymmetric dimers by the O{sub w}-H...O hydrogen bonds. The crystal structure of compound II is composed of binuclear copper complexes and solvate water molecules. The copper atom coordinates the O,N,O ligand molecule and the chlorine ion, which fulfills a bridging function. The coordination polyhedron of the metal atom is a distorted tetragonal bipyramid in which the vertex is occupied by the chlorine atom of the neighboring complex in the dimer. Compound III is a centrosymmetric dimer complex. The coordination polyhedra of two nickel atoms related via the inversion center are distorted octahedra shared by the edge.

Chumakov, Yu. M. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Tsapkov, V. I. [State University of Moldova (Moldova, Republic of); Filippova, I. G., E-mail: [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Bocelli, G. [National Research Council (IMEM-CNR), Institute of Materials for Electronics and Magnetism (Italy); Gulea, A. P. [State University of Moldova (Moldova, Republic of)



The spider toxin, argiotoxin636, binds to a Mg2+ site on the N-methyl-D-aspartate receptor complex.  

PubMed Central

1. The mechanism of action of the arylalkylamine spider toxin, argiotoxin636, on the N-methyl-D-aspartate (NMDA) receptor was investigated by use of [3H]-dizocilpine binding to well-washed membranes obtained from rat brain. 2. Argiotoxin636 decreased [3H]-dizocilpine binding with an apparent potency of about 3 microM. The inhibition of [3H]-dizocilpine by argiotoxin636 was insensitive to the concentration of glutamate, glycine and spermidine in the assay. 3. Argiotoxin636 alone had no effect on the dissociation of [3H]-dizocilpine. However, argiotoxin636 reversed the actions of Mg2+ on the dissociation of [3H]-dizocilpine by decreasing the apparent potency of Mg2+. Argiotoxin636 also reversed the action of Ca2+ on the dissociation of [3H]-dizocilpine. 4. These results suggest that argiotoxin636 exerts a novel inhibitory effect on the NMDA receptor complex by binding to one of the Mg2+ sites located within the NMDA-operated ion channel.

Reynolds, I. J.



Crystal structure and catecholase-like activity of a mononuclear complex [Cu(EDTB)] 2+ (EDTB= N, N, N ?, N ?-tetrakis(2 ?-benzimidazolyl methyl)-1,2-ethanediamine)  

Microsoft Academic Search

The crystal structure and catecholase-like activity of a mononuclear complex, Cu(EDTB)(NO3)2·C2H5OH (here EDTB stands N,N,N?,N?-tetrakis(2?-benzimidazolyl methyl)-1,2-ethanediamine) has been studied in comparison with a binuclear complex Cu2(EDTB)(NO3)4·3H2O. The results show that the reactive rate constants increase with increases of reaction temperature and pH value of intermediate. Electrospray ionization mass spectrum (ESI-MS) shows that tautomerism isomers of catechol with the title complex

Zhan-Fen Chen; Zhan-Ru Liao; Dong-Feng Li; Wu-Ke Li; Xiang-Gao Meng



A High Molar Extinction Coefficient Bisterpyridyl Homoleptic Ru(II) Complex with trans-2-Methyl-2-butenoic Acid Functionality: Potential Dye for Dye-Sensitized Solar Cells  

PubMed Central

In our continued efforts in the synthesis of ruthenium(II) polypyridine complexes as potential dyes for use in varied applications, such as the dye-sensitized solar cells (DSSCs), this work particularly describes the synthesis, absorption spectrum, redox behavior and luminescence properties of a new homoleptic ruthenium(II) complex bearing a simple trans-2-methyl-2-butenoic acid functionality as the anchoring ligand on terpyridine moiety. The functionalized terpyridine ligand: 4?-(trans-2-methyl-2-butenoic acid)-terpyridyl (L1) was synthesized by aryl bromide substitution on terpyridine in a basic reaction condition under palladium carbide catalysis. In particular, the photophysical and redox properties of the complex formulated as: bis-4?-(trans-2-methyl-2-butenoic acid)-terpyridyl ruthenium(II) bis-hexafluorophosphate [Ru(L1)2(PF6)2] are significantly better compared to those of [Ru(tpy)2]2+ and compare well with those of the best emitters of Ru(II) polypyridine family containing tridentate ligands. Reasons for the improved photophysical and redox properties of the complex may be attributed partly to the presence of a substituted ?,?-unsaturated carboxylic acid moiety leading to increase in the length of ?-conjugation bond thereby enhancing the MLCT-MC (Metal-to-ligand-charge transfer-metal centred) energy gap, and to the reduced difference between the minima of the excited and ground states potential energy surfaces.

Adeloye, Adewale O.; Olomola, Temitope O.; Adebayo, Akinbulu I.; Ajibade, Peter A.



Synthesis and characterization of methylated poly(L-histidine) to control the stability of its siRNA polyion complexes for RNAi.  


Poly(L-histidine) (PLH) with dimethylimidazole groups has been synthesized as a pH-sensitive polypeptide to control the stability of its small interfering RNA (siRNA) polyion complexes for RNA interference (RNAi). The resulting methylated PLH (PLH-Me) was water-soluble despite deprotonation of the imidazole groups at physiological pH, as determined by acid-base titration and solution turbidity measurement. Agarose gel retardation assay proved that the quaternary dimethylimidazole groups worked as cationic groups to retain siRNA. The stability of the PLH-Me/siRNA complexes has depended on the content of hydrophobic groups, that is, ?/?-methylimidazole groups as well as deprotonated imidazole groups. PLH-Me exhibited no significant cytotoxicity despite the existence of cationic dimethylimidazole groups. By use of PLH-Me as a pH-sensitive siRNA carrier, the PLH-Me/siRNA complexes mediated efficient siRNA delivery attributed to the dimethylimidazole groups, and the gene silencing depended on the content balance among dimethyl, ?/?-methyl, and unmodified imidazole groups. These results suggest that PLH-Me controls the stability of siRNA polyion complexes by enhancing noncytotoxic siRNA delivery by optimizing the content balance of dimethyl, ?/?-methyl, and unmodified imidazole groups. PMID:22681572

Asayama, Shoichiro; Kumagai, Takao; Kawakami, Hiroyoshi



Crystal structures of copper(II) nitrate complexes containing 4,4'-bipyridyl and halogen-substituted 2-[(2-hydroxyethylimino)methyl]phenols  

SciTech Connect

The crystal structures of ({mu}-4,4'-bipyridyl)-di{l_brace}nitrato-2,4-dibromo-6-[(2-hydroxyethylimino)methyl] phenolo (1-)copper{r_brace} (I), ({mu}-4,4'-bipyridyl)-di{l_brace}nitrato-2,4-dichloro-6-[(2-hydroxyethylimino)methyl] phenolo(1-)copper{r_brace} (II), and ({mu}-4,4'-bipyridyl)-{l_brace}4-chloro-2-[(2-hydroxyethylimino)methyl]phenolo(2-) copper-nitrato-4-chloro-2-[(2-hydroxyethylimino)methyl]phenolo(1-)copper{r_brace} tetrahydrate (III) are determined. The crystal structures of compounds I and II contain binuclear complexes, in which each copper atom is coordinated by the singly deprotonated tridentate molecule of the corresponding azomethine, the monodentate nitrate ion, and bipyridyl that plays the role of a bridge between the central atoms. In the structures of compounds I and II, the coordination polyhedra of the copper atoms are slightly distorted tetragonal pyramids. The pyramid base is formed by the imine and bipyridyl nitrogen atoms and the phenol and alcohol oxygen atoms. The axial vertices of the pyramids are occupied by the oxygen atoms of the monodentate nitrato groups. The crystal structure of compound III involves tetranuclear complexes in which the coordination polyhedra of the central copper atoms are (4 + 1 + 1) bipyramids. The base of these bipyramids is formed by the imine and bipyridyl nitrogen atoms and the phenol and alcohol oxygen atoms. One apical vertex is occupied by the bridging phenol oxygen atom of the nearest complex. The sixth coordination site of the first copper atom is occupied by the chlorine atom of the salicylidene fragment of the neighboring complex related to the initial complex through the center of symmetry. In turn, the sixth coordination site of the second copper atom is occupied by the oxygen atom of the monodentate nitrato group.

Chumakov, Yu. M., E-mail: [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Tsapkov, V. I. [State University of Moldova (Moldova, Republic of); Petrenko, P. A. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Popovski, L. G. [State University of Moldova (Moldova, Republic of); Simonov, Yu. A. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of); Bocelli, G. [National Research Council (IMEM-CNR), Institute of Materials for Electronics and Magnetism (Italy); Gulea, A. P. [State University of Moldova (Moldova, Republic of)



Polystyrene bound oxidovanadium(IV) and dioxidovanadium(V) complexes of histamine derived ligand for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin.  


Ligand Hsal-his (I) derived from salicylaldehyde and histamine has been covalently bound to chloromethylated polystyrene cross-linked with 5% divinylbenzene. Upon treatment with [VO(acac)(2)] in DMF, the polystyrene-bound ligand (abbreviated as PS-Hsal-his, II) gave the stable polystyrene-bound oxidovanadium(iv) complex PS-[V(IV)O(sal-his)(acac)] , which upon oxidation yielded the dioxidovanadium(v) PS-[V(V)O(2)(sal-his)] complex. The corresponding non polymer-bound complexes [V(IV)O(sal-his)(acac)] and [V(V)O(2)(sal-his)] have also been obtained. These complexes have been characterised by IR, electronic, (51)V NMR and EPR spectral studies, and thermal as well as scanning electron micrograph studies. Complexes and have been used as a catalyst for the oxidation of methyl phenyl sulfide, diphenyl sulfide and benzoin with 30% H(2)O(2) as oxidant. Under the optimised reaction conditions, a maximum of 93.8% conversion of methyl phenyl sulfide with 63.7% selectivity towards methyl phenyl sulfoxide and 36.3% towards methyl phenyl sulfone has been achieved in 2 h with 2 . Under similar conditions, diphenyl sulfide gave 83.4% conversion where selectivity of reaction products varied in the order: diphenyl sulfoxide (71.8%) > diphenyl sulfone (28.2%). A maximum of 91.2% conversion of benzoin has been achieved within 6 h, and the selectivities of reaction products are: methylbenzoate (37.0%) > benzil (30.5%) > benzaldehyde-dimethylacetal (22.5%) > benzoic acid (8.1%). The PS-bound complex, 1 exhibits very comparable catalytic potential. These polymer-anchored heterogeneous catalysts do not leach during catalytic action, are recyclable and show higher catalytic activity and turnover frequency than the corresponding non polymer-bound complexes. EPR and (51)V NMR spectroscopy was used to characterise methanolic solutions of 3 and 4 and to identify species formed upon addition of H(2)O(2) and/or acid and/or methyl phenyl sulfide. PMID:19274297

Maurya, Mannar R; Arya, Aarti; Kumar, Amit; Pessoa, João Costa



16- 18-electron ruthenium(II) complexes of the neutral, potentially tridentate triamine logand 2,6-[bis(dimethylamino)methyl]pyridine (NN'N)  

Microsoft Academic Search

The potentially tridentate coordinating ligands NN'N (2,6-bis[(dimethylamino)methyl]pyridine) and PNP (2,6-bis[(diphenylphosphino)methyl]pyridine) react with [RuCl2(PPh3)3] to give [mer,trans-RuCl2(NN'N)(PPh3)] (1) and [mer,trans-RuCl2(PNP)(PPh3)] (2), respectively. Complex 1 functions as a starting material for a variety of Ru[NN'N] complexes. It reacts with either 1 or 2 equiv of AgOTf (OTf- = SO3CF3-) to yield monocationic [RuCl(NN'N)(PPh3)]OTf (3) and [RuOTf(NN'N)(PPh3)]OTf (4), respectively. The molecular structure of

G. van Koten; R. A. T. M. Abbenhuis; I. del Rio; M. M. Bergshoef; N. Veldman; A. L. Spek



Inclusion complex of charge transfer probe 4-amino-3-methyl benzoic acid methyl ester (AMBME) with ?-CD in aqueous and non-aqueous medium: medium dependent stoichiometry of the complex and orientation of probe molecule inside ?-CD nanocavity  

Microsoft Academic Search

The absorption and emission characteristics of donor?acceptor charge transfer system 4-amino-3-methyl benzoic acid methyl\\u000a ester (AMBME), capable of dual emission, i.e., local emission (LE) and charge transfer (CT) emission, have been investigated\\u000a inside the ?-cyclodextrin (?-CD) nanocavity in the aqueous and non-aqueous dimethylsulphoxide (DMSO) medium. Large enhancement\\u000a of both LE and CT band in aqueous ?-CD medium is due to

Amrita Chakraborty; Nikhil Guchhait



Specifics of polymerization of trimethyl(methacryloyloxyethyl)ammonium methyl sulfate in a sodium dodecyl sulfate solution and the properties of resultant complexes  

Microsoft Academic Search

The specifics of polymerization of trimethyl(methacryloyloxyethyl)ammonium methyl sulfate in the presence of sodium dodecyl\\u000a sulfate and the properties of complexes that appear as polymerization products or are formed from these products were studied.\\u000a It was found that the addition of the surfactant to the polymerization medium in sufficiently large amounts changes the polymerization\\u000a rate and has a substantial effect on

Yu. V. Shulevich; O. Yu. Kovaleva; A. V. Navrotskii; Yu. A. Zakharova; A. B. Zezin; I. A. Novakov



Chronic treatment with 1-aminocyclopropanecarboxylic acid desensitizes behavioral responses to compounds acting at the N-methyl- d -aspartate receptor complex  

Microsoft Academic Search

Functional antagonists at the N-methyl-d-aspartate (NMDA) receptor complex produce anti-depressant-like actions in preclinical models. Thus, an injection of a glycine partial agonist (1-aminocyclopropanecarboxylic acid; ACPC), a competitive NMDA antagonist (2-amino-7-phosphonoheptanoic acid; AP-7) or a use-dependent cation channel blocker (MK-801) reduced immobility in the forced swim test (FST) with efficacies comparable to imipramine (Trullas and Skolnick 1990). Seven daily injections of

Phil Skolnick; Rachel Miller; Andrew Young; Kathleen Boje; Ramon Trullas



Structure and isomerization comparison of Zn(ii), Cd(ii) and Hg(ii) perchlorate complexes of 2,6-bis([(2-pyridyl-methyl)amino]methyl)pyridine.  


The divalent zinc triad perchlorate coordination chemistry of 2,6-bis([(2-pyridyl-methyl)amino]methyl)pyridine () was investigated by X-ray crystallography and solution state (1)H NMR. New complexes [Hg(ClO4)2] () and [Cd(ClO4)2] () were isolated as bicapped distorted square pyramidal racemates, contrasting with the approximate trigonal bipyramidal structure of [Zn](ClO4)2 (). Although rapid inter- and intramolecular exchange is common for simple complexes of zinc triad metal ions, conditions for slow intramolecular isomerization on both the ? and JHH time scales were established for , and . Trends in geminal (1)H coupling suggested that an asymmetric structure was favored for all three metal ions at or below 40 °C. Contributions of a symmetric structure to solution equilibria were both temperature- and metal ion-dependent. Spectral trends were consistent with interconversion of a pair of enantiomeric square pyramidal ligand conformers through a symmetric trigonal bipyramidal ligand conformer by M-N bond cleavage and nitrogen inversion. Racemization was slower than the coupling constant time scale up to 40 °C for all complexes. Differential stabilization of specific small ligand conformations in solution has potential toxicological significance. PMID:23963250

Carra, Bradley J; Berry, Steven M; Pike, Robert D; Bebout, Deborah C



Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence.  


Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ?20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome. PMID:22800725

Gordon, Lavinia; Joo, Jihoon E; Powell, Joseph E; Ollikainen, Miina; Novakovic, Boris; Li, Xin; Andronikos, Roberta; Cruickshank, Mark N; Conneely, Karen N; Smith, Alicia K; Alisch, Reid S; Morley, Ruth; Visscher, Peter M; Craig, Jeffrey M; Saffery, Richard



4-Amino-3-methyl-5-mercapto-1,2,4-triazole as a gravimetric reagent for determination of silver in silver compounds, alloys and complexes.  


A simple, convenient and accurate gravimetric method for the determination of silver is presented. 4-Amino-3-methyl-5-mercapto-1,2,4-triazole precipitates silver quantitatively from ammoniacal tartrate medium. The complex is weighed as AgC(3)H(5)N(4)S after drying at 120-30 degrees . Separation of silver from a large number of cations is described. Application of the method for quantitative analysis of alloys and complexes of silver is reported. The average relative error for the range 20-70 mg of silver is +/- 0.25% and the relative standard deviation at the 40-mg level is 0.2%. PMID:18962291

Gadag, R V; Gajendragad, M R



Spectroscopic, structural and antibacterial properties of copper(II) complexes with bio-relevant 5-methyl-3-formylpyrazole N(4)benzylN(4)-methylthiosemicarbazone  

Microsoft Academic Search

The coordination behaviour of the title ligand, 5-methyl-3-formylpyrazole N(4)-benzyl-N(4)-methylthiosemicarbazone(HMPz4BM), is reported with solid state isolation of copper(II) complexes, [Cu(HMPz4BM)X2] (X = Cl, Br, NO3, ClO4 and BF4) which have been spectroscopically and structurally characterised. I.r. data for the free ligand and its Cu(II) complexes indicate that HMPz4BM exhibits a neutral NNS tridentate function via the pyrazolyl nitrogen(tertiary), azomethine nitrogen and

Dhiman Kumar Sau; Ray J. Butcher; Siddhartha Chaudhuri; Nityananda Saha



Syntheses, structures and thermal stabilities of eight 1-((benzotriazol-yl)methyl)-1H-1,3-imidazole complexes based on different anions  

Microsoft Academic Search

The main aim of the work herein presented is to investigate the influence of different anions on the structures of a series of complexes. Through the self-assembly of a new unsymmetrical ligand 1-((benzotriazol-yl)methyl)-1H-1,3-imidazole (bmi) with M(NO3)2 or MSO4 [M=Zn(II), Co(II), Cd(II), Cu(II)], a series of new complexes, [M(bmi)2(NO3)2]n [M=Zn (1), Co (2), Cd (3), Cu (4)] and [M(bmi)(H2O)4(SO4)]·2H2O [M=Zn (5),

Xiangru Meng; Xiaoqing Zhu; Yongfang Qi; Hongwei Hou; Yaoting Fan



Crystal structures of bis-ligand complexes of copper(II) with 2-[(2-hydroxyethylamino)-methyl]-4,6-dinitrophenol, 2,4-dichloro-6-[(2-hydroxyethylamino)-methyl]phenol, and 2,4-dibromo-6-[(2-hydroxyethylamino)-methyl]phenol  

SciTech Connect

The crystal structures of bis{l_brace}2,4-dibromo-6-[(2-hydroxyethylamino)-methyl]phenolato{r_brace}copper (I), bis{l_brace}2,4-dichloro-6-[(2-hydroxyethylamino)-methyl]phenolato{r_brace}copper (II), and bis{l_brace}2-[(2-hydroxyethylamino)-methyl]-4,6-dinitrophenolato{r_brace}copper (III) in which the metal atom is located at the center of symmetry are determined using X-ray diffraction. Crystals of compounds I and II are isostructural. The copper atom in the structures of compounds I and I coordinates two singly deprotonated bidentate molecules of the ligand through the phenol oxygen atoms and the azomethine nitrogen atoms with the formation of a distorted planar square. In the crystals, complexes I and II form one-dimensional infinite chains along the b axis. In the structure of compound III, the coordination polyhedron of the central atom is an elongated tetragonal bipyramid with the base formed by the azomethine nitrogen atoms and the phenol oxygen atoms. Both vertices of the bipyramid are occupied by the oxygen atoms of the amino alcohol groups of the neighboring complexes, which are related to the initial complex through the center of symmetry. In turn, the oxygen atoms of the alcohol groups of the initial complex are located at the vertices of the coordination bipyramids of the metal atoms of the neighboring centrosymmetric complexes, thus forming infinite polymer chains along the a axis.

Chumakov, Yu. M. [Academy of Sciences of Moldova, Institute of Applied Physics (Moldova, Republic of)], E-mail:; Tsapkov, V. I. [State University of Moldova (Moldova, Republic of); Bocelli, G. [National Research Council (IMEM-CNR), Institute of Materials for Electronics and Magnetism (Italy); Palomares-Sanchez, S. A.; Ortiz, R. S. [Universidad Autonoma de San Luis Potosi, Facultad de Ciencias (Mexico); Gulea, A. P. [State University of Moldova (Moldova, Republic of)



Hydrogen-bonded complexes of phenylacetylene with water, methanol, ammonia, and methylamine. The origin of methyl group-induced hydrogen bond switching.  


The infrared spectra in the acetylenic C-H stretching region for the complexes of phenylacetylene with water, methanol, ammonia, and methylamine are indicative of change in the intermolecular structure upon substitution with a methyl group. High-level ab initio calculations at CCSD(T)/aug-cc-pVDZ level indicate that the observed complexes of water and ammonia are energetically the most favored structures, and electrostatics play a dominant role in stabilizing these structures. The ability of the pi electron density of the benzene ring to offer a larger cross-section for the interaction and the increased polarizability of the O-H and N-H groups in methanol and methylamine favor the formation of pi hydrogen-bonded complexes, in which dispersion is the dominant force. Further, the observed phenylacetylene-methylamine complex can be tentatively assigned to a kinetically trapped higher energy structure. The observed methyl group-induced hydrogen bond switching in the phenylacetylene complexes can be attributed to the switching of the dominant interaction from electrostatic to dispersion. PMID:19514784

Sedlak, Robert; Hobza, Pavel; Patwari, G Naresh



Stereospecific ligands and their complexes. Part XIX. Synthesis, characterization, circular dichroism and antimicrobial activity of oxalato and malonato-(S,S)-ethylenediamine-N,N?-di-2-(3-methyl)butanoato-chromate(III) complexes  

NASA Astrophysics Data System (ADS)

The s-cis-[Cr(S,S-eddv)L]-complexes (1,2) (S,S-eddv = (S,S)-ethylenediamine-N,N?-di-2-(3-methyl)butanoato ion; L = oxalate or malonate ion) were prepared. The complexes were purified by ion-exchange chromatography. The geometry of the complexes has been supposed on the basis of the infrared and electronic absorption spectra, and the absolute configurations of the isolated s-cis-[Cr(S,S-eddv)L]-complexes have been predicted on the basis of their circular dichroism (CD) spectra. Also, the results of thermal decomposition have been discussed. Antimicrobial activity of the prepared complexes (1-4) was investigated against 28 species of microorganisms. Testing was performed by microdilution method and minimum inhibitory concentrations (MIC) and minimum microbicidal concentration (MMC) have been determined. Complexes demonstrated in generally low antibacterial and antifungal activity.

Ili?, Dragoslav; Jevti?, Verica V.; Radojevi?, Ivana D.; Vasi?, Sava M.; Stefanovi?, Olgica D.; ?omi?, Ljiljana R.; Vasojevi?, Miorad M.; Jeli?, Miodrag Ž.; Koval'chuk, Tatyana V.; Loginova, Natalia V.; Trifunovi?, Sre?ko R.



SODs, DNA binding and cleavage studies of new Mn(III) complexes with 2-((3-(benzyloxy)pyridin-2-ylimino)methyl)phenol.  


Newly synthesized ligand [2-((3-(benzyloxy)pyridin-2-ylimino)methyl)phenol] (Bpmp) react with manganese(II) to form mononuclear complexes [Mn(phen)(Bpmp)(CH3COO)(H2O)]·4H2O (1), (phen=1,10-phenanthroline) and [Mn(Bpmp)2(CH3COO)(H2O)]·5H2O (2). These complexes were characterized by elemental analysis, IR, (1)H NMR, Mass, UV-vis spectral studies. Molar conductance and thermogravimetric analysis of these complexes were also recorded. The in vitro SOD mimic activity of Mn(III) complexes were carried out and obtained with good result. The DNA-binding properties of the complexes 1 and 2 were investigated by UV-spectroscopy, fluorescence spectroscopy and viscosity measurements. The spectral results suggest that the complexes 1 and 2 can bind to Calf thymus DNA by intercalation mode. The cleavage properties of these complexes with super coiled pUC19 have been studied using the gel electrophoresis method, wherein both complexes 1 and 2 displayed chemical nuclease activity in the absence and presence of H2O2 via an oxidative mechanism. All the complexes inhibit the growth of both Gram positive and Gram negative bacteria to competent level. The MIC was determined by microtiter method. PMID:23429055

Shivakumar, L; Shivaprasad, K; Revanasiddappa, Hosakere D



Synthesis, spectroscopic characterization, electrochemical behaviour and antibacterial activity of Ru(III) complexes of 2-[(4-N,N'-dimethylaminophenylimino)-methyl]-4-halophenol.  


The reaction of the chelating Schiff base ligands 2-[(4-N,N'-dimethylaminophenylimino)-methyl]-4-X-phenol with [Ru(Cl)(3)(EPh(3))(3)]; (E=P or As); (X=Cl, Br or I) in the benzene afforded new stable ruthenium complexes of the general formula [Ru(Cl)(2)(EPh(3))(2)(L)] (L=anion of bidentate Schiff bases). The newly synthesized complexes were characterized using molar conductivity, spectral (UV-vis, FT-IR and EPR) and electrochemical studies. The molar conductance measurements proved that all these complexes are non-electrolytes. All complexes show strong d-d transition in the visible region. The coordination of imine nitrogen and phenolic oxygen of ligands to ruthenium metal was confirmed with the change in the IR stretching frequency values. The EPR spectral data showed that the complexes are paramagnetic with one unpaired electrons. The redox behaviour of the complexes have been investigated by the cyclic voltammetric technique. All the complexes display an irreversible reduction (Ru(III)/Ru(II)) in the range of -0.826 to -0.971V. In view of the biological activity, the ligands and the complexes were observed that all the complexes showed moderate activity. Also the antibacterial activity of the ligand increased on chelation with metal ion. PMID:19112044

Puthilibai, G; Vasudhevan, S; Kutti Rani, S; Rajagopal, G



Synthesis and characterization of 3-methyl-5-oxo-N,1-diphenyl-4,5-dihydro-1-H-pyrazole-4-carbothioamide and its metal complexes  

NASA Astrophysics Data System (ADS)

The molecular parameters have been calculated to confirm the geometry of 3-methyl-5-oxo-N,1-diphenyl-4,5-dihydro-1-H-pyrazole-4-carbothioamide, HL. The compound is introduced as a new chelating agent for complexation with Cr(III), Fe(III), Co(II), Ni(II) and Cu(II) ions. The isolated chelates were characterized by partial elemental analyses, magnetic moments, spectra (IR, UV-vis, ESR; 1H NMR) and thermal studies. The protonation constant of HL (5.04) and the stepwise stability constants of its Co(II), Cu(II), Cr(III) and Fe(III) complexes were calculated. The ligand coordinates as a monobasic bidentate through hydroxo and thiol groups in all complexes except Cr(III) which acts as a monobasic monodentate through the enolized carbonyl oxygen. Cr(III) and Fe(III) complexes measured normal magnetic moments; Cu(II) and Co(II) measured subnormal while Ni(II) complex is diamagnetic. The data confirm a high spin and low spin octahedral structures for the Fe(III) and Co(II) complexes. The ESR spectrum of the Cu(II) complex support the binuclear structure. The molecular parameters have also been calculated for the Cu(II) and Fe(III) complexes. The thermal decomposition stages of the complexes confirm the MS to be the residual part. Also, the thermodynamic and kinetic parameters were calculated for some decomposition steps.

El-Shazly, R. M.



SODs, DNA binding and cleavage studies of new Mn(III) complexes with 2-((3-(benzyloxy)pyridin-2-ylimino)methyl)phenol  

NASA Astrophysics Data System (ADS)

Newly synthesized ligand [2-((3-(benzyloxy)pyridin-2-ylimino)methyl)phenol] (Bpmp) react with manganese(II) to form mononuclear complexes [Mn(phen)(Bpmp)(CH3COO)(H2O)]·4H2O (1), (phen = 1,10-phenanthroline) and [Mn(Bpmp)2(CH3COO)(H2O)]·5H2O (2). These complexes were characterized by elemental analysis, IR, 1H NMR, Mass, UV-vis spectral studies. Molar conductance and thermogravimetric analysis of these complexes were also recorded. The in vitro SOD mimic activity of Mn(III) complexes were carried out and obtained with good result. The DNA-binding properties of the complexes 1 and 2 were investigated by UV-spectroscopy, fluorescence spectroscopy and viscosity measurements. The spectral results suggest that the complexes 1 and 2 can bind to Calf thymus DNA by intercalation mode. The cleavage properties of these complexes with super coiled pUC19 have been studied using the gel electrophoresis method, wherein both complexes 1 and 2 displayed chemical nuclease activity in the absence and presence of H2O2via an oxidative mechanism. All the complexes inhibit the growth of both Gram positive and Gram negative bacteria to competent level. The MIC was determined by microtiter method.

Shivakumar, L.; Shivaprasad, K.; Revanasiddappa, Hosakere D.



Convergent evolution of chromatin modification by structurally distinct enzymes: comparative enzymology of histone H3 Lys²? methylation by human polycomb repressive complex 2 and vSET.  


H3K27 (histone H3 Lys27) methylation is an important epigenetic modification that regulates gene transcription. In humans, EZH (enhancer of zeste homologue) 1 and EZH2 are the only enzymes capable of catalysing methylation of H3K27. There is great interest in understanding structure-function relationships for EZH2, as genetic alterations in this enzyme are thought to play a causal role in a number of human cancers. EZH2 is challenging to study because it is only active in the context of the multi-subunit PRC2 (polycomb repressive complex 2). vSET is a viral lysine methyltransferase that represents the smallest protein unit capable of catalysing H3K27 methylation. The crystal structure of this minimal catalytic protein has been solved and researchers have suggested that vSET might prove useful as an EZH2 surrogate for the development of active site-directed inhibitors. To test this proposition, we conducted comparative enzymatic analysis of human EZH2 and vSET and report that, although both enzymes share similar preferences for methylation of H3K27, they diverge in terms of their permissiveness for catalysing methylation of alternative histone lysine sites, their relative preferences for utilization of multimeric macromolecular substrates, their active site primary sequences and, most importantly, their sensitivity to inhibition by drug-like small molecules. The cumulative data led us to suggest that EZH2 and vSET have very distinct active site structures, despite the commonality of the reaction catalysed by the two enzymes. Hence, the EZH2 and vSET pair of enzymes represent an example of convergent evolution in which distinct structural solutions have developed to solve a common catalytic need. PMID:23679895

Swalm, Brooke M; Hallenbeck, Kenneth K; Majer, Christina R; Jin, Lei; Scott, Margaret Porter; Moyer, Mikel P; Copeland, Robert A; Wigle, Tim J



Exposing the Molecular Complexity of Sgr B2(N): The Interstellar Detection of Methyl Isocyanate (CH3NCO) from the GBT PRIMOS Survey  

NASA Astrophysics Data System (ADS)

CH3NCO is one of just a few interstellar molecules that contain H, C, N, and O, all of which are constituents of the simple amino acid, glycine, a species that has yet to be detected in the interstellar medium. Methyl isocyanate is thus an important molecule in bridging the gap to more complex, organic biomolecules. Using data from the publicly available Green Bank Telescope Prebiotic Interstellar Molecular Survey (PRIMOS) towards Sgr B2(N), we have observed, for the first time, 20 rotational transitions of methyl isocyanate. The spectral regions are free of molecular line confusion and the features observed are consistent with the source structure of this source with an LSR velocity of +64 and +73 km/s. It is likely that CH3NCO is produced in a neutral-radical reaction with the neutral reactant HNCO, which is ubiquitous in SgrB2(N), and the radicals CH2 or CH3.

Pulliam, Robin; Remijan, A. J.; Loomis, R. A.



Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP.  

PubMed Central

After the start of transcription, the 5' ends of eukaryotic mRNA molecules are modified by the addition of a guanylyl residue to form a cap structure, G(5')ppp(5')N. The guanylyltransferase (GTP:mRNA guanylyltransferase, EC reaction responsible for cap formation usually proceeds via a covalent enzyme-GMP intermediate. We have studied the alphavirus-specific guanylyltransferase by incubating lysates from Semliki Forest and Sindbis virus-infected cells with [alpha-32P]GTP, using vaccinia virus and mock-infected cells as controls. One additional 32P-labeled protein was detected in alphavirus-infected cells but only in the presence of S-adenosylmethionine. This protein was identified as the nonstructural protein nsP1. The properties of the covalent enzyme-guanylate complex were studied with Semliki Forest virus nsP1 expressed in recombinant baculovirus-infected cells. S-Adenosylmethionine and divalent cations were required for the complex formation. The reaction was specific for guanylate nucleotides (GTP, dGTP) and was inhibited by pyrophosphate. nsP1 could be labeled with S-adenosyl[methyl-3H]methionine but only under conditions in which the nsP1-guanylate complex was formed. 7-Methyl-GMP was released from the nsP1-guanylate complex by treatment with acid or acidic hydroxylamine. Similar treatment of vaccinia virus capping enzyme released GMP. These findings suggest that in the capping of alphavirus mRNAs the guanine is methylated before linkage to the mRNA molecule. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5

Ahola, T; Kaariainen, L




Microsoft Academic Search

A new series of oxorhenium(V) complexes were prepared by the reaction of 2-amino-5-methyl-1,3,4-thiadiazole (L), alone or with addition of NaSCN, with H2[ReOCl5]. Mononuclear complexes of various types, [ReOLCl3- (OH2)], [ReOL2Cl2(OH2)]Cl, [ReOLCl(SCN)2(OH2)], [ReOL2Cl3] and [ReOLCl2(SCN) (OH2)], along with binuclear complexes, Re2O2(µ-L)Cl6(OH2)2·2H2O and [Re2O3(µ-L)Cl4]·2H2O, were obtained depending on the metal:ligand molar ratio and the concentration of hydrochloric acid containing the dissolved parent

Mahmoud M. Mashaly



Grafting of methyl methacrylate to cellulose and polypropylene with UV and ionising radiation in the presence of additives including CT complexes  

NASA Astrophysics Data System (ADS)

Detailed studies of the grafting of polar methyl methacrylate (MMA) to two representative backbone polymers, cellulose and polypropylene (PPE) in the presence of additives, using ionising radiation and UV as initiating sources, are reported. The results are compared with analogous grafting work with non polar styrene previously studied. The additives chosen for examination were predominantly components used in radiation curing formulations since grafting and curing are known to be mechanistically related. The additives were mineral acid, photoinitiators, vinyl ethers, oligomers, polyfunctional monomers including multifunctional acrylates (MFAs) and methacrylates (MFMAs). For the first time charge transfer (CT) monomer complexes have been used as additives in the current work. The CT complexes themselves, being monomers, have also been directly radiation grafted to cellulose. Mechanisms for the above grafting processes are proposed. The significance of this grafting work in analogous radiation curing is discussed. The grafting of the CT complexes, themselves, is shown to lead to new copolymers with potential industrial applications.

Garnett, J. L.; Ng, L.-T.; Viengkhou, V.



Fluorimetric properties of a 2-hydroxypropyl-beta-cyclodextrin: 9-methyl-benzo[a]phenothiazine inclusion complex in aqueous media. Analytical usefulness.  


The formation of an inclusion complex between 9-methyl-12H-benzo[a]phenothiazine (MeBPHT) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated in aqueous medium. A 12-fold fluorescence emission intensity enhancement was found for the complexed relative to the free analyte. MeBPHT forms a 1:1 stoichiometry complex with HP-beta-CD. A formation constant of 460 (+/-100) M(-1) was calculated using the Benesi-Hildebrand method and fluorimetric data. The limit of detection was 7 ng ml(-1) for MeBPHT in the presence of HP-beta-CD instead of 60 ng ml(-1) in the absence of HP-beta-CD. PMID:18966968

Maafi, M; Mahedero, M C; Aaron, J J



Synthesis, structure and magnetic properties of Mn(II) and Cu(II) complexes with the dicyano-acetic acid methyl ester anion  

Microsoft Academic Search

The preparation of the sodium salt of dicyano-acetic acid methyl ester (NaCH3OC(O)C(CN)2) (NaL) is reported. The structure of this anion is related to the structure of the dicyanamide, whose chelating capability has been used to develop 2D networks. Two new complexes of formula [M(L)2(H2O)2] (M=Mn2+ (1) and Cu2+ (2)) have been synthesized and their crystal structures determined by single-crystal X-ray

Carlos Kremer; Cecilia Melián; Julia Torres; Mar??a P Juanicó; Claudia Lamas; Horacio Pezaroglo; Eduardo Manta; Herbert Schumann; Joachim Pickardt; Frank Girgsdies; Oscar N Ventura; Francesc Lloret



Transition metal complexes of the novel hexadentate ligand 1,4-bis(di(N-methylimidazol-2-yl)methyl)phthalazine.  


The novel polydentate ligand 1,4-bis(di(N-methylimidazol-2-yl)methyl)phthalazine, bimptz, has been synthesized and its coordination chemistry was investigated. Bimptz is neutral and contains a central phthalazine unit, to which two di-(N-methylimidazol-2-yl)methyl groups are attached in the 1,4-positions. This ligand therefore provides up to 6 donor sites for coordination to metal ions. A series of metal complexes of bimptz was prepared and their molecular structures were determined by X-ray diffraction. Upon reaction of bimptz with two equivalents of MnCl(2)·4H(2)O, CoCl(2)·6H(2)O and [Ru(dmso)(4)Cl(2)], the dinuclear complexes [Mn(2)(bimptz)(µ-Cl)(2)Cl(2)] (1), [Co(2)(bimptz)(CH(3)OH)(2)(µ-Cl)(2)](PF(6))(2) (3) and [Ru(2)(bimptz)(dmso)(2)(µ-Cl)(2)](PF(6))(2) (4), respectively, were isolated. The latter were found to have similar solid state structures with octahedrally coordinated metal centers bridged by the phthalazine unit and two chloro ligands. The cobalt and ruthenium complexes 3 and 4 were isolated as PF(6)(-) salts and contain neutral methanol and dmso ligands, respectively, at the terminal coordination sites of the metal centres. The mononuclear ruthenium complex [Ru(Hbimptz)(2)](PF(6))(4) (6) was obtained from the reaction of two equivalents bimptz with [Ru(dmso)(4)Cl(2)]. In complex 6, three donor sites per ligand molecule are used for coordination of the Ru(ii) center. In each bimptz ligand, one of the remaining, dangling N-methylimidazole rings is protonated and forms a hydrogen bond with the unprotonated N-methylimidazole ring of the other bimptz ligand. PMID:21409278

Roggan, Stefan; Limberg, Christian; Knispel, Christina; Tilley, T Don



Charge-Transfer Complexation Mechanism of Poly (4-Vinyl Pyridine)/[6,6] - Phenyl-C61-Butyric Acid Methyl Ester in DMF Solution  

NASA Astrophysics Data System (ADS)

The mechanism of charge-transfer complexation in electron-donor(D)/electron-acceptor(A) active layer was studied for a pseudo-binary blend model system, poly(4-vinyl pyridine) /[6,6]-phenyl-C61-butyric acid methyl ester in DMF. The time evolution of the system can be characterized by four distinct stages, i.e., induction, complexation, aggregation and precipitation, respectively. In the induction stage, the conformation of P4VP remained unchanged, while the UV-vis showed that the charge-transfer complexation had almost accomplished. In the complexation stage, each P4VP chains complexed with about 3 PCBM molecules at [4VP]/[PCBM]=57:1, and shrinked in size with almost no change in UV-vis spectrum. In the subsequent aggregation stage, P4VP/PCBM complexes aggregated with each other to form spherical aggregates with again unchanged UV-vis signals. FA model can be used to explain this mechanism. In the final precipitation stage, huge P4VP/PCBM agglomerate began to phase out. The almost unchanged UV-vis spectrum after the induction stage indicated that the electronic transition from ground to excited state is not necessarily to be influenced by any inter- or intra-polymer structural transition.

Cheng, He; Wei, Guangmin; Han, Charles



Laser mass-resolved spectroscopy and theoretical study of methyl-p-aminobenzoate(H2O)n (n=2,3,4) complexes  

NASA Astrophysics Data System (ADS)

A combined computational and experimental study of the methyl-p-aminobenzoate(H2O)n, (n=2,3,4) complexes [MAB(H2O)n] is reported. Complexes potential energy surfaces were explored by ab initio density functional theory (DFT) methods, at the B3LYP/6-31G level, and the stable isomer structures and vibrational modes further computed at the B3LYP/6-31+G* level. A set of self-contained experimental techniques, including laser induced fluorescence (LIF), resonance enhanced multiphoton ionization mass-resolved spectroscopy (REMPI), two-color resonance enhanced multiphoton ionization mass-resolved spectroscopy (R2PI), ``hole burning'' spectroscopy (HB), and two-color ionization thresholds were used to study the spectra and other physical features of the complexes. Of the three title complexes only MAB(H2O)4 has been observed with our experimental methods, while the MAB(H2O)3 was formed by evaporation and MAB(H2O)2 was not detected at all. It has been shown that the observed MAB(H2O)4 complex has only one isomer with a hydrogen bonded water ring structure attached to the amino hydrogens and its low vibrational modes (up to 165 cm-1) have been assigned. A discussion of the results, including structures of stable isomers, isomer energies, ionization thresholds, and the difficulties in observing some solvated complexes is presented.

Fernández, José A.; Longarte, Asier; Unamuno, Iñigo; Castaño, Fernando



Reactions of methyl(phenyl)silylene with CO and PH 3—the formation of acid–base complexes  

Microsoft Academic Search

The thermal reaction of methyl(phenyl)silylene 1a with CO and PH3, respectively, was investigated using matrix isolation spectroscopy in combination with DFT calculations. The silylene 1a was produced by UV irradiation (?>400 nm followed by ?>350 nm) of (phenyl)silyldiazomethane 2 in high yields. The thermal reaction of 2 with CO in CO-doped argon matrices produces the acid–base adduct 3 which was

Holger Bornemann; Wolfram Sander



Synthesis, Characterization, and Photochemical Studies of Some Copper Complexes of Schiff Bases Derived from 3?Hydrazino?6?methyl[1,2,4]triazin?5(4H)one  

Microsoft Academic Search

Cu(II) complexes of new bidentate and tridentate Schiff bases derived from the condensation of 3?hydrazino?6?methyl[1,2,4]triazin?5(4H)one and aromatic aldehyde derivatives were synthesized and characterized. The structure of the complexes proposed according to elemental analyses, molar conductance, IR UV?Visible absorption spectra is square?planar. The thermodecomposition kinetics of the complexes were investigated under non?isothermal condition. TG and DTG curves indicated that the complexes

Ahmed H. Osman; Magda S. Saleh; Sanaa M. Mahmoud



Catalytic asymmetric aza-Morita-Baylis-Hillman reaction of methyl acrylate: role of a bifunctional La(O-iPr)3/linked-BINOL complex.  


The catalytic asymmetric aza-Morita-Baylis-Hillman reaction using unactivated methyl acrylate is described. A simple Lewis acidic metal catalyst, such as La(OTf)(3), was not suitable for the reaction, but rare earth metal alkoxide/linked-BINOL complexes possessing bifunctional Lewis acid and Brønsted base properties efficiently promoted the reaction in combination with an achiral nucleophilic organocatalyst. The combined use of a La(O-iPr)(3)/(S,S)-TMS-linked-BINOL complex with a catalytic amount of DABCO promoted the aza-Morita-Baylis-Hillman reaction of a broad range of N-diphenylphosphinoyl imines. Products from aryl, heteroaryl, and alkenyl imines were obtained in 67-99% yield and 81-95% ee. It is noteworthy that isomerizable alkyl imines could be employed as well, giving products in 78-89% yield and 94-98% ee. Initial rate kinetic studies as well as kinetic isotope effect experiments using alpha-deuterio-methyl acrylate support the importance of both the nucleophilicity of La-enolate and the Brønsted basicity of a La-catalyst for promoting the reaction. PMID:20690698

Yukawa, Takafumi; Seelig, Bianca; Xu, Yingjie; Morimoto, Hiroyuki; Matsunaga, Shigeki; Berkessel, Albrecht; Shibasaki, Masakatsu



The role of thiol and nitrosothiol compounds in the nitric oxide-forming reactions of the iron-N-methyl-d-glucamine dithiocarbamate complex.  


The object of the present study is to investigate whether the physiologically dominant thiol compounds such as GSH and cysteine or their nitrosothiol compounds affect the formation of the iron- N -methyl-D-glucamine dithiocarbamate [(MGD)(2)Fe(2+)]-nitric oxide complex. The present study provided experimental evidence that physiological concentrations of GSH (approx. 5 mM) and L-cysteine (approx. 0.5 mM) accelerated the formation of the (MGD)(2)Fe(2+)-NO complex from nitrite by two and three times respectively. The rate constants for the reduction of (MGD)(3)Fe(3+) to (MGD)(2)Fe(2+) by GSH and cysteine were calculated as 1.3 and 2.0x10(2) M(-1).s(-1) respectively. Furthermore, depletion of GSH was demonstrated in PC12 cells, and thiol compounds enhanced the formation of reactive oxygen species by the (MGD)(2)Fe(2+) complex by accelerating its redox turnover. The main effect of the physiological concentration of thiols was the reduction of (MGD)(3)Fe(3+). S -nitrosoglutathione spontaneously reacted with (MGD)(2)Fe(2+) to produce the (MGD)(2)Fe(2+)-NO complex with a 1:2 stoichiometry. In fact, (MGD)(2)Fe(2+) was as good an indicator of nitrosothiols as it was of NO itself. The present study elucidates the difficulties of utilizing the (MGD)(2)Fe(2+) complex for the quantification of NO in biological samples, especially in vivo. PMID:12141947

Tsuchiya, Koichiro; Kirima, Kazuyoshi; Yoshizumi, Masanori; Houchi, Hitoshi; Tamaki, Toshiaki; Mason, Ronald P



Synthesis and room temperature single crystal EPR studies of a dinickel complex having an Ni2(?-phenoxide)2 2+ unit supported by a macrocyclic ligand environment [Ni2(L)2(OClO3)2] [L = 2-[(4-methyl-pyridin-2-ylimino)-methyl]-phenol  

Microsoft Academic Search

A bimetallic nickel(II) complex with the ligand Hsalamp (2 -((4-methyl- pyridin-2-ylimino)-methyl)-phenol), having the molecular formula, Ni2C26H22 N4O10Cl2, is synthesized and characterized by elemental, UV -Vis, IR and EPR studies. The IR spectrum confirms the presence of coordinated perchlorate ion and the UV-Vis. spectrum substantiates that the geometry around the metal ion is distorted square pyramidal. In the solvent methanol, the

R. Srinivasan; I. Sougandi; R. Venkatesan; P. Sambasiva Rao



Formation mechanism of 2-methyl-2-buten-1,4-diol and 2-methyl-3-buten-1,2-diol from 2-methyl-1,3-butadiene on a head-to-head pivalamidato-bridged cis-diammineplatinum(III) binuclear complex.  


Reactions of a pivalamidato-bridged head-to-head (HH) platinum(III) binuclear complex with 2-methyl-1,3-butadiene (isoprene) and p-styrenesulfonate and of an ?-pyrrolidonato-bridged HH platinum(III) binuclear complex with p-styrenesulfonate were studied kinetically using UV-vis spectrophotometry and (1)H NMR spectroscopy, and detailed reaction mechanisms are proposed. Pt(III) binuclear complexes react with p-styrenesulfonate in four successive steps with mechanisms similar to that for an HH ?-pyridonato-bridged Pt(III) binuclear complex with p-styrenesulfonate. In the case of isoprene, four steps were observed on the basis of UV-vis spectrophotometry. However, the reaction kinetics for steps 1 and 2 correspond to those for the previous reaction system, and those for steps 3 and 4 do not correspond to those for the previous system or to those observed by using (1)H NMR spectroscopy for the present isoprene system. By using UV-vis spectrophotometry, it was shown that isoprene preferentially ?-coordinates to the Pt(N(2)O(2)) atom via the double bond adjacent to the methyl group in step 1. In step 2, a second isoprene molecule ?-coordinates to the Pt(N(4)) atom, which is the rate-determining step, followed by nucleophilic attack of a water molecule on the ?-coordinated isoprene on the Pt(N(2)O(2)) atom to form two isomeric ?-complexes. In the same step, ?-coordinated isoprene on the Pt(N(4)) atom of the ?-complexes is released. This is different from the reaction of the Pt(III) binuclear complexes with other olefins. In step 3, reductive elimination of the ?-complexes occurs to form two diols and the HH pivalamidato-bridged Pt(II) binuclear complex. Finally, acid decomposition of the Pt(II) binuclear complex occurs to form monomers in step 4. From (1)H NMR spectroscopic observations, fast isomerization between ?-complexes and reductive elimination of the ?-complexes occurs in step 3, and isomerization from a 1,4-diol to a 1,2-diol occurs in step 4. PMID:21643602

Nagashima, Jun; Shimazaki, Kazuhiro; Sekiya, Hideo; Iwatsuki, Satoshi; Ishihara, Koji; Matsumoto, Kazuko



Zinc complexes supported by methyl salicylato ligands: synthesis, structure, and application in ring-opening polymerization of l-lactide.  


Two novel zinc alkoxides supported by chelating methyl salicylato (MesalO; MesalOH = methyl salicylate) ligands were successfully synthesized and characterized. Reaction of MesalOH with ZnEt2 (2?:?1) gives a tetranuclear cluster [Zn(MesalO)2]4 (1), which by addition of pyridine is transformed to the mononuclear compound [Zn(MesalO)2(py)2] (2). Compounds 1 and 2 were characterized by elemental analysis, NMR, IR, and single crystal X-ray diffraction. The catalytic activity of both compounds was tested for the ring-opening polymerization (ROP) of l-lactide (l-LA). It was found that compounds 1 and 2 are efficient initiators of the ROP of l-LA, yielding cyclic PLLA with weight average molecular weights up to 100 kDa for 2. The treatment of 2 with 1 equiv. of BnOH in toluene afforded a dimeric compound [Zn(OBn)(MesalO)(py)]2 (3). The addition of l-LA to a combination of 1 and 4 equiv. of BnOH in THF or 2 and 1 equiv. of BnOH in toluene led to the rapid and efficient generation of PLLA with end-capped BnO groups. PMID:23811782

Petrus, Rafa?; Sobota, Piotr



Metal-catalysed oxidation processes in thiosemicarbazones: new complexes with the ligand N-{2-([4-N-ethylthiosemicarbazone]methyl)phenyl}-p-toluenesulfonamide.  


The coordination behaviour of a new thiosemicarbazone Schiff-base building block, N-{2-([4-N-ethylthiosemicarbazone]methyl)phenyl}-p-toluenesulfonamide, H2L1 (1), incorporating a bulky tosyl group, towards Mn II, Fe II, Co II, Ni II, Cu II, Zn II, Cd II, Ag I, Sn II, and Pb II has been investigated by means of an electrochemical preparative procedure. Most metal complexes of L1 have the general formula [M(L1)]2.nX (M=Mn, Fe, Co, Ni, Cu, Cd, Pb; n=0-4, X=H2O or CH3CN), as confirmed by the structure of [Pb(L1)]2 (15), in which the lone pair on lead is stereochemically active. This lead(II) complex shows an intense fluorescence emission with a quantum yield of 0.13. In the case of silver, the complex formed was found to possess a stoichiometry of [Ag2(L1)]2.3H2O. During reactions with manganese and copper metals, interesting catalysed processes have been found to take place, with remarkable consequences regarding the ligand skeleton structure. In synthesising the manganese complex, we obtained an unexpected dithiolate thiosemicarbazone tosyl ligand, H2L2, as a side-product, which has been fully characterised, including by X-ray diffraction analysis. In the case of copper, the solid complex has the formula [CuL1]2, but the crystallised product shows the copper atoms coordinated to a new cyclised thiosemicarbazone ligand, H2L3, as in the structures of the complexes [Cu(L3)]2.CH3CN (8) and [Cu(L3)(H2O)]2.CH3CN.H2O (9). The zinc complex [Zn(L1)]4 (12) displays a particular tetranuclear zeolite-type structure capable of hosting small molecules or ions, presumably through hydrogen bonding. PMID:17918755

Pedrido, Rosa; Romero, María J; Bermejo, Manuel R; González-Noya, Ana M; García-Lema, Iria; Zaragoza, Guillermo



Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2?-O-Methylation by nsp16/nsp10 Protein Complex  

PubMed Central

The 5?-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5?-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2?-O positions, catalyzed by nsp14 N7-MTase and nsp16 2?-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2?-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1?1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.

Ke, Min; Jin, Xu; Xu, Lirong; Zhang, Zhou; Wu, Andong; Sun, Ying; Yang, Zhouning; Tien, Po; Ahola, Tero; Liang, Yi; Liu, Xinqi; Guo, Deyin



Mononuclear Manganese-Peroxo and Bis(?-oxo)dimanganese Complexes Bearing a Common N-Methylated Macrocyclic Ligand.  


Mononuclear Mn(III) -peroxo and dinuclear bis(?-oxo)Mn(III) 2 complexes that bear a common macrocyclic ligand were synthesized by controlling the concentration of the starting Mn(II) complex in the reaction of H2 O2 (i.e., a Mn(III) -peroxo complex at a low concentration (?1?mM) and a bis(?-oxo)Mn(III) 2 complex at a high concentration (?30?mM)). These intermediates were successfully characterized by various physicochemical methods such as UV-visible spectroscopy, ESI-MS, resonance Raman, and X-ray analysis. The structural and spectroscopic characterization combined with density functional theory (DFT) calculations demonstrated unambiguously that the peroxo ligand is bound in a side-on fashion in the Mn(III) -peroxo complex and the Mn2 O2 diamond core is in the bis(?-oxo)Mn(III) 2 complex. The reactivity of these intermediates was investigated in electrophilic and nucleophilic reactions, in which only the Mn(III) -peroxo complex showed a nucleophilic reactivity in the deformylation of aldehydes. PMID:24027090

Kang, Hyeona; Cho, Jaeheung; Cho, Kyung-Bin; Nomura, Takashi; Ogura, Takashi; Nam, Wonwoo



Effects of methyl substituent on the charge-transfer complexations of dicarbazolylalkanes with p-chloranil, tetracyanoethylene and tetracyanoquinodimethane.  


Series of 1,n-dicarbazolylalkanes and 1,n-di(3-methylcarbazolyl)alkanes (where n=1-5) were synthesized and the molar extinction coefficients, equilibrium constants, enthalpies, and entropies of their charge-transfer (CT) complexes with the ?-acceptors p-chloranil, tetracyanoethylene, and tetracyanoquinodimethane were investigated. 1,n-Di(3-methylcarbazolyl)alkanes formed CT complexes with higher equilibrium constants, more negative enthalpies and entropies than 1,n-dicarbazolylalkanes. Vibrational spectra of CT complexes of one of the donor molecules (1,4-dicarbazolylbutane) with all three acceptors were compared. PMID:21700488

Asker, Erol; Uzkara, Ece; Zeybek, Orhan



Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes.  


Meiotic chromosomes are organized into arrays of loops that are anchored to the chromosome axis structure. Programmed DNA double-strand breaks (DSBs) that initiate meiotic recombination, catalyzed by Spo11 and accessory DSB proteins, form in loop sequences in promoters, whereas the DSB proteins are located on chromosome axes. Mechanisms bridging these two chromosomal regions for DSB formation have remained elusive. Here we show that Spp1, a conserved member of the histone H3K4 methyltransferase Set1 complex, is required for normal levels of DSB formation and is associated with chromosome axes during meiosis, where it physically interacts with the Mer2 DSB protein. The PHD finger module of Spp1, which reads H3K4 methylation close to promoters, promotes DSB formation by tethering these regions to chromosome axes and activating cleavage by the DSB proteins. This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination. PMID:23246437

Sommermeyer, Vérane; Béneut, Claire; Chaplais, Emmanuel; Serrentino, Maria Elisabetta; Borde, Valérie



Thermal and spectral studies of 3- N-methyl-morpholino-4-amino-5-mercapto-1,2,4-triazole and 3- N-methyl-piperidino-4-amino-5-mercapto-1,2,4-triazole complexes of cobalt(II), nickel(II) and copper(II)  

Microsoft Academic Search

Novel complexes obtained by 3-N-methyl-morpholino-4-amino-5-mercapto-1,2,4-triazole and 3-N-methyl-piperidino-4-amino-5-mercapto-1,2,4-triazole with Co(II), Ni(II) and Cu(II) have been synthesized and characterized by elemental analysis, electronic, IR, ESR and TG studies. TG studies of these complexes showed that thermal degradation proceeds in two steps. Kinetic and thermodynamic parameters were computed from the thermal decomposition data. The activation energy of both the thermal degradation steps is

P. B Maravalli; T. R Goudar



Synthesis and room temperature single crystal EPR studies of a dinickel complex having an Ni 2 (?-phenoxide) 2 2+ unit supported by a macrocyclic ligand environment [Ni 2 (L) 2 (OClO 3 ) 2 ] [L = 2-[(4-methyl-pyridin-2-ylimino)-methyl]-phenol  

Microsoft Academic Search

A bimetallic nickel(II) complex with the ligand Hsalamp (2-[(4-methyl-pyridin-2-ylimino)-methyl]-phenol), having the molecular\\u000a formula, Ni2C26H22 N4O10Cl2, is synthesized and characterized by elemental, UV-Vis, IR and EPR studies. The IR spectrum confirms the presence of coordinated\\u000a perchlorate ion and the UV-Vis. spectrum substantiates that the geometry around the metal ion is distorted square pyramidal.\\u000a In the solvent methanol, the complex undergoes dissociation

R. Srinivasan; I. Sougandi; R. Venkatesan; P. Sambasiva Rao



Spectral and thermal characterization of 3-acetyl-5-azophenyl-4-hydroxy-6-methyl-pyran-2-one and its metal complexes  

NASA Astrophysics Data System (ADS)

Five chelates of 3-acetyl-5-azophenyl-4-hydroxy-6-methyl-pyran-2-one (phenylazo dehydroacetic acid) with Cr(III), Fe(III), Ni(II), Cu(II) and Zn(II) have been synthesized and characterized by elemental analysis, magnetic susceptibility measurements, electronic, 1H NMR, FAB mass, IR-spectral and thermal (TG/DTG) analytical techniques. In the present work it has been found that oxygen of the deprotonated sbnd OH group and one of the azo-nitrogens of the ligand take part in coordination. The Cr(III), Fe(III) and Ni(II) complexes were found to be having octahedral geometry and the Cu(II) and Zn(II) tetrahedral.

Seth, Susannah; Aravindakshan, K. K.



An octa-nuclear zinc(II) complex with 6,6'-dihydr-oxy-2,2'-[1,2-phenyl-enebis(nitrilo-methyl-idyne)]diphenol.  


The asymmetric unit of the title compound, tetra-aqua-tetrakis-{?(3)-6,6'-di-oxido-2,2'-[1,2-phenyl-enebis(nitrilo-methyl-idyne)]diphenolato}octa-zinc(II) dimethyl sulfoxide tetra-solvate dihydrate, [Zn(8)(C(20)H(12)N(2)O(4))(4)(H(2)O)(4)]·4C(2)H(6)OS·2H(2)O, contains one quarter of a Zn(II) octa-nuclear complex with symmetry, one dimethyl sulfoxide mol-ecule and one half of a water mol-ecule which lies on a twofold rotation axis. The Zn(II) atoms of the octa-nuclear complex have two different five-coordinate environments, viz. ZnN(2)O(3) and ZnO(5). All eight Zn(II) centers adopt a distorted square-pyramidal coordination; four Zn(II) ions have the N(2)O(2) tetra-dentate Schiff base ligand bound in a basal plane and the coordinated water mol-ecule occupying the apical site, while the remaing four Zn(II) ions are bound by five O atoms from three Schiff base ligands. In the crystal structure, Zn(II) complex mol-ecules, coordinated and uncoord-inated water mol-ecules and dimethyl sulfoxide mol-ecules are linked via O-H?O and C-H?O hydrogen bonds and C-H?? inter-actions, forming a three-dimensional framework. PMID:21202773

Eltayeb, Naser Eltaher; Teoh, Siang Guan; Chantrapromma, Suchada; Fun, Hoong-Kun; Adnan, Rohana



Improving the photosensitizing properties of ruthenium polypyridyl complexes using 4-methyl-2,2'-bipyridine-4'-carbonitrile as an auxiliary ligand.  


We report in this work the synthesis and spectroscopic, electrochemical, spectroelectrochemical, and photophysical characterization of a novel series of ruthenium polypyridyl complexes with 4-methyl-2,2'-bipyridine-4'-carbonitrile (Mebpy-CN) as an auxiliary ligand of general formula [Ru(bpy)3-x(Mebpy-CN)x](PF6)2 (x = 1-3) (with bpy = 2,2'-bipyridine). A significant increase in the lifetime and quantum yield of emission of the lowest (3)MLCT excited state is disclosed when going from x = 1 to x = 3, evidencing an improvement of the photosensitizing properties with respect to [Ru(bpy)3](PF6)2. Furthermore, quenching by molecular oxygen of (3)MLCT excited states of the three complexes produced singlet molecular oxygen ((1)O2) with quantum yield values higher than that of [Ru(bpy)3](2+) in CH3CN. The structure of the complex with x = 1 has been determined by X-ray diffraction. The photoconductivity of ZnO nanowires covered with this same complex is increased by an order of magnitude, pointing to its feasibility as a component of a DSSC. A new dinuclear complex with Mebpy-CN as a bridging ligand has also been prepared and characterized by physicochemical techniques. The derived mixed-valent species of formula [(bpy)2Ru(II)(Mebpy-CN)Ru(III)(NH3)5](5+) displays a considerable metal-metal electronic coupling due to the delocalization effect of a nitrile group in the 4' position of the bpy ring. PMID:23574015

Ortiz, Juan H Mecchia; Vega, Nadia; Comedi, David; Tirado, Mónica; Romero, Isabel; Fontrodona, Xavier; Parella, Teodor; Vieyra, F Eduardo Morán; Borsarelli, Claudio D; Katz, Néstor E



Methylation matters  

PubMed Central

DNA methylation is not just for basic scientists any more. There is a growing awareness in the medical field that having the correct pattern of genomic methylation is essential for healthy cells and organs. If methylation patterns are not properly established or maintained, disorders as diverse as mental retardation, immune deficiency, and sporadic or inherited cancers may follow. Through inappropriate silencing of growth regulating genes and simultaneous destabilisation of whole chromosomes, methylation defects help create a chaotic state from which cancer cells evolve. Methylation defects are present in cells before the onset of obvious malignancy and therefore cannot be explained simply as a consequence of a deregulated cancer cell. Researchers are now able to detect with exquisite sensitivity the cells harbouring methylation defects, sometimes months or years before the time when cancer is clinically detectable. Furthermore, aberrant methylation of specific genes has been directly linked with the tumour response to chemotherapy and patient survival. Advances in our ability to observe the methylation status of the entire cancer cell genome have led us to the unmistakable conclusion that methylation abnormalities are far more prevalent than expected. This methylomics approach permits the integration of an ever growing repertoire of methylation defects with the genetic alterations catalogued from tumours over the past two decades. Here we discuss the current knowledge of DNA methylation in normal cells and disease states, and how this relates directly to our current understanding of the mechanisms by which tumours arise.???Keywords: methylation; cancer

Costello, J.; Plass, C.



Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP) pathway enzyme expression in Catharanthus roseus.  


In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation. PMID:23650515

Han, Mei; Heppel, Simon C; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas



A Novel Non-SET Domain Multi-subunit Methyltransferase Required for Sequential Nucleosomal Histone H3 Methylation by the Mixed Lineage Leukemia Protein-1 (MLL1) Core Complex*  

PubMed Central

Gene expression within the context of eukaryotic chromatin is regulated by enzymes that catalyze histone lysine methylation. Histone lysine methyltransferases that have been identified to date possess the evolutionarily conserved SET or Dot1-like domains. We previously reported the identification of a new multi-subunit histone H3 lysine 4 methyltransferase lacking homology to the SET or Dot1 family of histone lysine methyltransferases. This enzymatic activity requires a complex that includes WRAD (WDR5, RbBP5, Ash2L, and DPY-30), a complex that is part of the MLL1 (mixed lineage leukemia protein-1) core complex but that also exists independently of MLL1 in the cell. Here, we report that the minimal complex required for WRAD enzymatic activity includes WDR5, RbBP5, and Ash2L and that DPY-30, although not required for enzymatic activity, increases the histone substrate specificity of the WRAD complex. We also show that WRAD requires zinc for catalytic activity, displays Michaelis-Menten kinetics, and is inhibited by S-adenosyl-homocysteine. In addition, we demonstrate that WRAD preferentially methylates lysine 4 of histone H3 within the context of the H3/H4 tetramer but does not methylate nucleosomal histone H3 on its own. In contrast, we find that MLL1 and WRAD are required for nucleosomal histone H3 methylation, and we provide evidence suggesting that each plays distinct structural and catalytic roles in the recognition and methylation of a nucleosome substrate. Our results indicate that WRAD is a new H3K4 methyltransferase with functions that include regulating the substrate and product specificities of the MLL1 core complex.

Patel, Anamika; Vought, Valarie E.; Dharmarajan, Venkatasubramanian; Cosgrove, Michael S.



Role of B(C 6F 5) 3 in activating the nickel-methyl complex (? 5-C 5H 5)Ni(CH 3)(PPh 3) to initiate the vinyl polymerization of norbornene  

Microsoft Academic Search

The Ni-methyl complex (?5-C5H5)Ni(CH3)(PPh3) (1) reacted with B(C6F5)3 to give an unstable contact ion-pair complex with a ?-methyl bridge between the Ni and B atoms. Formation of the B-CH3 bond was confirmed by the reaction of this complex with PPh3 to give [(?5-C5H5)Ni(PPh3)2][B(CH3)(C6F5)3] which was structurally characterized. Spontaneous decomposition of the contact ion-pair complex yielded (?5-C5H5)Ni(C6F5)(PPh3) which is very stable

Takeo Yamamoto; Chie Shikada; Shojiro Kaita; Tardif Olivier; Yooichiroh Maruyama; Yasuo Wakatsuki



Improving the inhibitory activity of arylidenaminoguanidine compounds at the N-methyl-D-aspartate receptor complex from a recursive computational-experimental structure-activity relationship study.  


Using a combination of both the partial least squares (PLS) and back-propagation artificial neural network (ANN) pattern recognition methods, several models have been developed to predict the activity of a series of arylidenaminoguanidine analogs as inhibitory modulators of the N-methyl-D-aspartate receptor complex. This was done by correlating structural and physicochemical descriptors obtained from computation software with the experimentally observed [(3)H]MK-801 displacement ability of a small library of synthesized and in vitro screened arylidenaminoguanidines. Results for the generated PLS model were r(2)=0.814, rmsd=0.208, rCV(2)=0.714, loormsd=0.261. The ANN model was created utilizing the eleven descriptors from the PLS model for comparison. The quality of the ANN model (r(2)=0.828, rmsd=0.200, rCV(2)=0.721, loormsd=0.257) is similar to the PLS model, and indicates that the feature between the inputs and the output is majorly linear. These computational models were able to predict inhibition of the NMDA receptor complex by this series of compounds in silico, affording a predictive structure-based 'pre-screening' paradigm for the arylideneaminoguanidine analogs. PMID:23465801

Ring, Joshua R; Zheng, Fang; Haubner, Aaron J; Littleton, John M; Crooks, Peter A



Complexes with metal-carbon bonds, part IV( 1 ). Binuclear diarylplatinum(III) complexes. Long-range trans -effect in platinum-platinum bonded compounds containing methyl and aryl groups  

Microsoft Academic Search

Summary The platinum-platinum bonded [PtR2(OAc)L1]2 complexes (R = Ph, L1 = Et2S, n-Pr2S; R =p-tolyl, L1 = Et2S), have been prepared by oxidising [PrR2L1 ]2 with AgOAc or Tl(OAc)3. The sulphide ligand is replaced by weak ligands to give [PtR2(OAc)L2]2 (L2 = PhNH2, 4-picoline, CI-) whereas PEt3 or P(OMe)3 react to give Pt2R4(OAc)2(PR'3)(R' = Et, OMe). The methyl platinum analogues

Barry R. Steele; Kees Vrieze



The Effect of Methylated Vitamin B Complex on Depressive and Anxiety Symptoms and Quality of Life in Adults with Depression  

PubMed Central

Depression, the most common type of mental illness, is the second leading cause of disability and is increasing among Americans. The effect of improved nutrition, particularly with dietary supplements, on depression may provide an alternative to standard medical treatment. Some studies have shown that certain nutrients (e.g., inositol and S-adenosyl methionine) are effective at improving depressed mood, although the results are not unequivocal. The current study was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a vitamin B complex nutritional supplement (Max Stress B) for improving depressive and anxiety symptoms according to the Beck Depression and Anxiety Inventories (BDI and BAI) in 60 adults diagnosed with major depression or other forms of depressive disorders. Secondary outcomes included quality of life according to the SF-36. Participants were assessed at baseline and 30- and 60-day followups. Max Stress B showed significant and more continuous improvements in depressive and anxiety symptoms, compared to placebo. Additionally, Max Stress B showed significant improvement on the mental health scale of the SF-36 compared to placebo. Thus, we showed modest utility of Max Stress B to improve mood symptoms and mental health quality of life in adults with depression.

Lewis, John E.; Tiozzo, Eduard; Melillo, Angelica B.; Leonard, Susanna; Chen, Lawrence; Mendez, Armando; Woolger, Judi M.; Konefal, Janet



The proto-oncoprotein FBI-1 interacts with MBD3 to recruit the Mi-2/NuRD-HDAC complex and BCoR and to silence p21WAF/CDKN1A by DNA methylation.  


The tumour-suppressor gene CDKN1A (encoding p21Waf/Cip1) is thought to be epigenetically repressed in cancer cells. FBI-1 (ZBTB7A) is a proto-oncogenic transcription factor repressing the alternative reading frame and p21WAF/CDKN1A genes of the p53 pathway. FBI-1 interacts directly with MBD3 (methyl-CpG-binding domain protein 3) in the nucleus. We demonstrated that FBI-1 binds both non-methylated and methylated DNA and that MBD3 is recruited to the CDKN1A promoter through its interaction with FBI-1, where it enhances transcriptional repression by FBI-1. FBI-1 also interacts with the co-repressors nuclear receptor corepressor (NCoR), silencing mediator for retinoid and thyroid receptors (SMRT) and BCL-6 corepressor (BCoR) to repress transcription. MBD3 regulates a molecular interaction between the co-repressor and FBI-1. MBD3 decreases the interaction between FBI-1 and NCoR/SMRT but increases the interaction between FBI-1 and BCoR. Because MBD3 is a subunit of the Mi-2 autoantigen (Mi-2)/nucleosome remodelling and histone deacetylase (NuRD)-HDAC complex, FBI-1 recruits the Mi-2/NuRD-HDAC complex via MBD3. BCoR interacts with the Mi-2/NuRD-HDAC complex, DNMTs and HP1. MBD3 and BCoR play a significant role in the recruitment of the Mi-2/NuRD-HDAC complex- and the NuRD complex-associated proteins, DNMTs and HP. By recruiting DNMTs and HP1, Mi-2/NuRD-HDAC complex appears to play key roles in epigenetic repression of CDKN1A by DNA methylation. PMID:23658227

Choi, Won-Il; Jeon, Bu-Nam; Yoon, Jae-Hyeon; Koh, Dong-In; Kim, Myung-Hwa; Yu, Mi-Young; Lee, Kyung-Mi; Kim, Youngsoo; Kim, Kyunggon; Hur, Sujin Susanne; Lee, Choong-Eun; Kim, Kyung-Sup; Hur, Man-Wook



Reporter molecules as probes of DNA conformation: structure of a crystalline complex containing 2-methyl-4-nitro-aniline ethylene dimethylammonium hydrobromide - 5-iodocytidylyl(3'-5')guanosine  

SciTech Connect

2-Methyl-4-nitroaniline ethylene dimethylammonium hydrobromide forms a crystalline complex with the self-complementary dinucleoside monophosphate, 5-iodocytidylyl(3'-5')guanosine. The crystals are tetragonal, with a = b = 32.192 A and c = 23.964 A, space group P4/sub 3/2/sub 1/2. The structure has been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares. 5-Iodocytidylyl(3'-5')guanosine molecules are held together in pairs through Watson-Crick base-pairing, forming an antiparallel duplex structure. Nitroaniline molecules stack above and below guanine-cytosine pairs in this duplex structure. In addition, a third nitroaniline molecule stacks on one of the other two nitroaniline molecules. The asymmetric unit contains two 5-iodocytidylyl(3'-5')guanosine molecules, three nitroaniline molecules, one bromide ion and thirty-one water molecules, at total of 160 atoms. Details of the structure are described. 15 references, 4 figures, 2 tables.

Vyas, N.K.; Nyas, M.N.; Jain, S.C.; Sobell, H.M.



Multivalent di-nucleosome recognition enables the Rpd3S histone deacetylase complex to tolerate decreased H3K36 methylation levels  

PubMed Central

The Rpd3S histone deacetylase complex represses cryptic transcription initiation within coding regions by maintaining the hypo-acetylated state of transcribed chromatin. Rpd3S recognizes methylation of histone H3 at lysine 36 (H3K36me), which is required for its deacetylation activity. Rpd3S is able to function over a wide range of H3K36me levels, making this a unique system to examine how chromatin regulators tolerate the reduction of their recognition signal. Here, we demonstrated that Rpd3S makes histone modification-independent contacts with nucleosomes, and that Rpd3S prefers di-nucleosome templates since two binding surfaces can be readily accessed simultaneously. Importantly, this multivalent mode of interaction across two linked nucleosomes allows Rpd3S to tolerate a two-fold intramolecular reduction of H3K36me. Our data suggest that chromatin regulators utilize an intrinsic di-nucleosome-recognition mechanism to prevent compromised function when their primary recognition modifications are diluted.

Huh, Jae-Wan; Wu, Jun; Lee, Chul-Hwan; Yun, Miyong; Gilada, Daniel; Brautigam, Chad A; Li, Bing



Binding of the Mn(III) complex of meso-tetrakis (4-N-methyl-pyridiniumyl) porphyrin to DNA. Effect of ionic strength.  


Interactions of the water-soluble Mn(III) complex of meso-tetrakis (4-N-methyl-pyridiniumyl) porphyrin (Mn(III)TMPyP) with DNA in aqueous solutions at low (0.01 M) and high (0.2 M) ionic strengths have been studied by optical absorption, resonance light scattering (RLS) and 1H NMR spectroscopies. Optical absorption and RLS measurements have demonstrated that in DNA solutions at low ionic strength the Mn(III)TMPyP form aggregates, which are decomposed at DNA excess. At high ionic strength the aggregation was not observed. We explain this effect by assuming that upon increase in ionic strength, Mn(III) TMPyP dislocates from the DNA sites, which produces better conditions for the porphyrin aggregation, to sites where the aggregation is hindered. The 1H NMR data demonstrated that the aggregation observed at low ionic strength reduces the paramagnetism of Mn(III)TMPyP. This phenomenon was not observed at the high ionic strength in the absence of aggregation. PMID:10212993

Gandini, S C; Yushmanov, V E; Perussi, J R; Tabak, M; Borissevitch, I E


The Influence of Linker Geometry on Uranyl Complexation by Rigidly-Linked Bis(3-hydroxy-N-methyl-pyridin-2-one)  

SciTech Connect

A series of bis(3-hydroxy-N-methyl-pyridin-2-one) ligands was synthesized, and their respective uranyl complexes were characterized by single crystal X-ray diffraction analyses. These structures were inspected for high-energy conformations and evaluated using a series of metrics to measure co-planarity of chelating moieties with each other and the uranyl coordination plane, as well as to measure coordinative crowding about the uranyl dication. Both very short (ethyl, 3,4-thiophene and o-phenylene) and very long ({alpha},{alpha}{prime}-m-xylene and 1,8-fluorene) linkers provide optimal ligand geometries about the uranyl cation, resulting in planar, unstrained molecular arrangements. The planarity of the rigid linkers also suggests there is a degree of pre-organization for a planar coordination mode that is ideal for uranyl-selective ligand design. Comparison of intramolecular N{sub amide}-O{sub phenolate} distances and {sup 1}H NMR chemical shifts of amide protons supports earlier results that short linkers provide the optimal geometry for intramolecular hydrogen bonding.

Szigethy, Geza; Raymond, Kenneth



Deciphering arginine methylation: Tudor tells the tale  

Microsoft Academic Search

Proteins can be modified by post-translational modifications such as phosphorylation, methylation, acetylation and ubiquitylation, creating binding sites for specific protein domains. Methylation has pivotal roles in the formation of complexes that are involved in cellular regulation, including in the generation of small RNAs. Arginine methylation was discovered half a century ago, but the ability of methylarginine sites to serve as

Timothy J. Nott; Jing Jin; Chen Chen; Tony Pawson



Infrared spectra of the CH3-MX, CH2=MHX, and CH[triple bond]MH2X- complexes formed by reaction of methyl halides with laser-ablated group 5 metal atoms.  


Reactions of group 5 metal atoms and methyl halides give carbon-metal single, double, and triple bonded complexes that are identified from matrix IR spectra and vibrational frequencies computed by DFT. Two different pairs of complexes are prepared in reactions of methyl fluoride with laser-ablated vanadium and tantalum atoms. The two vanadium complexes (CH(3)-VF and CH(2)=VHF) are persistently photoreversible and show a kinetic isotope effect on the yield of CD(2)=VDF. Identification of CH(2)=TaHF and CH[triple bond]TaH(2)F(-), along with the similar anionic Nb complex, suggests that the anionic methylidyne complex is a general property of the heavy group 5 metals. Reactions of Nb and Ta with CH(3)Cl and CH(3)Br have also been carried out to understand the ligand effects on the calculated structures and the vibrational characteristics. The methylidene complexes become more distorted with increasing halogen size, while the calculated C=M bond lengths and stretching frequencies decrease and increase, respectively. The anionic methylidyne complexes are less favored with increasing halogen size. Infrared spectra show a dramatic increase of the Ta methylidenes upon annealing, suggesting that the formation of CH(3)-TaX and its conversion to CH(2)=TaHX require essentially no activation energy. PMID:16913680

Cho, Han-Gook; Andrews, Lester



Evaluating the Identity and Diiron Core Transformations of a (?-Oxo)diiron(III) Complex Supported by Electron-Rich Tris(pyridyl-2-methyl)amine Ligands  

PubMed Central

The composition of a (?-oxo)diiron(III) complex coordinated by tris((3,5-dimethy-4-methoxy)pyridyl-2-methyl)amine (R3TPA) ligands was investigated. Characterization using a variety of spectroscopic methods and X-ray crystallography indicated that the reaction of iron(III) perchlorate, sodium hydroxide, and R3TPA affords [Fe2(?-O)(?-OH)(R3TPA)2](ClO4)3 (2), rather than the previously reported species, [Fe2(?-O)(OH)(H2O)(R3TPA)2](ClO4)3 (1). Facile conversion of the (?-oxo)(?-hydroxo)diiron(III) core of 2 to the (?-oxo)(hydroxo)(aqua)diiron(III) core of 1 occurs in the presence of water and at low temperature. When 2 is exposed to wet acetonitrile at room temperature, the CH3CN adduct is hydrolyzed to CH3COO?, which forms the compound [Fe2(?-O)(?-CH3COO)(R3TPA)2](ClO4)3 (10). The identity of 10 was confirmed by comparison of its spectroscopic properties with those of an independently prepared sample. To evaluate whether or not 1 and 2 are capable of generating the diiron(IV) species [Fe2(?-O)(OH)(O)(R3TPA)2]3+ (4), which has previously been generated as a synthetic model for high-valent diiron protein oxygenated intermediates, studies were performed to investigate their reactivity with hydrogen peroxide. Because 2 reacts rapidly with hydrogen peroxide in CH3CN but not in CH3CN/H2O, conditions that favor conversion to 1, complex 1 is not a likely precursor to 4. Compound 4 also forms in the reaction of 2 with H2O2 in solvents lacking a nitrile, suggesting that hydrolysis of CH3CN is not involved in the H2O2 activation reaction. These findings shed light on the formation of several diiron complexes of electron-rich R3TPA ligands and elaborate on conditions required to generate synthetic models of diiron(IV) protein intermediates with this ligand framework.

Do, Loi H.; Xue, Genqiang



Mössbauer and magnetic studies on the spin states of mono- and binuclear iron(III) complexes with quinquedentate ligand methyl-substituted pyridine and bridged by pyrazine or bis(pyridine) compounds  

NASA Astrophysics Data System (ADS)

Mono- and binuclear iron(III) complexes with the general formula [FeXL] and [LFe-Y-FeL](BPh4)2 have been prepared and their spin states of the iron atom in the complexes has been investigated by means of the temperature-dependent Mössbauer spectroscopy and magnetic measurements, where X is a methyl-substituted pyridine, L denotes a quinquedentate Schiff-base derived from salicylaldehyde with N-(2-aminoethyl)-1,3-propanediamine and Y denotes bridged ligands such as pyrazine(pyr), 4,4'-pyridine(bpy), 4,4'-vinylenepyridine(vipy). On the basis of the Mössbauer and magnetic data, it was concluded that the spintransition characteristics depends on the methyl substituent of pyridine and the bridged ligand.

Wei, H. H.; Sheu, J. F.



Spectrophotometric studies of proton transfer complexes between 2-amino-4-methoxy-6-methyl-pyrimidine and 2-amino-4,6-dimethyl-pyrimidine with 2,6-dichloro-4-nitrophenol in acetonitrile  

Microsoft Academic Search

2-Amino-4-methoxy-6-methyl-pyrimidine (AMMP) and 2-amino-4,6-dimethyl-pyrimidine (ADMP) react with 2,6-dichloro-4-nitrophenol (DCNP) to form yellow proton transfer (PT) complexes in acetonitrile at absorption maxima around 420nm. These PT reactions have been applied to the simultaneous spectrophotometric determination of (AMMP) and (ADMP) in acetonitrile. Factors controlling the PT process were studied and optimized. Job's method of continuous variations was applied to identify the composition

Moustafa M. Habeeb; Amirah S. AL-Attas; Maram T. Basha



Phototaxis of Halobacterium salinarium requires a signalling complex of sensory rhodopsin I and its methyl-accepting transducer HtrI.  

PubMed Central

Sensory rhodopsin I (SRI) is a photoreceptor that mediates phototaxis in the archaeon Halobacterium salinarium. Receptor excitation is relayed to the motility system of the cell by the methyl-accepting transducer protein HtrI. In membranes prepared from cells that lack HtrI the absorbance difference maximum of SRI was shifted from 587 to 565 nm. The thermal decay of the metastable photocycle intermediate SRI373 was measured as time-dependent recovery of the absorbance at 590 nm. In the absence of HtrI the decay was slowed down by two orders of magnitude. When SRI was overproduced in cells that contained normal levels of HtrI, the decay of SRI373 was biexponential indicating two kinetically distinct species. Spectroscopic measurements on intact cells revealed the same effect of HtrI on SRI photocycling as found in isolated membranes. By transient exposure of membranes from wild-type cells to low ionic strength, the decay of SR373 was slowed to the same value found for untreated membranes in the absence of HtrI. In parallel, the absorbance difference maximum was shifted to 565 nm indicating that a physical interaction of HtrI and SRI had been irreversibly destroyed. Overproduction of SRI in the presence of wild-type amounts of HtrI did not increase the light sensitivity of the cells to orange light step down stimulation. It is concluded that SRI and HtrI form a stable complex in the cell membrane that signals to the flagellar motor and defines absorbance maximum, photocycling rate and photochemical efficiency of SRI.

Krah, M; Marwan, W; Vermeglio, A; Oesterhelt, D



Synthesis and Characterization of Cobalt(II) and Nickel(II) Complexes of Some Schiff Bases Derived from 3-hydrazino-6-methyl[1,2,4] triazin-5(4H)one  

Microsoft Academic Search

Cobalt(II) and nickel(II) complexes of bidentate and tridentate Schiff bases derived from the condensation of 3-hydrazino-6-methyl[1,2,4]triazin-5(4H)one\\u000a and aromatic aldehyde derivatives were synthesized and characterized. Elemental and thermal analyses as well as i.r., electronic\\u000a spectra, molar conductance and magnetic moment measurements were utilized for the investigation of the complexes. From these\\u000a investigation data, the structural formulae, the mode of bonding, and

Ahmed H. Osman



Synthesis, spectroscopic studies and structures of square-planar nickel(II) and copper(II) complexes derived from 2-{(Z)-[furan-2-ylmethyl]imino]methyl}-6-methoxyphenol  

Microsoft Academic Search

Two new nickel(II) [Ni(L)2] and copper(II) [Cu(L)2] complexes have been synthesized with bidentate NO donor Schiff base ligand (2-{(Z)-[furan-2-ylmethyl]imino]methyl}-6-methoxyphenol) (HL) and both complexes Ni(L)2 and Cu(L)2 have been characterized by elemental analyses, IR, UV–vis, 1H, 13C NMR, mass spectroscopy and room temperature magnetic susceptibility measurement. The tautomeric equilibria (phenol-imine, O–H?N and keto-amine, O?H–N forms) have been systemetically studied by using

Hüseyin Ünver; Zeliha Hayvali



Structural Characterization and Antimicrobial Activity of 2-(5-H\\/methyl-1 H -benzimidazol-2-yl)-4-bromo\\/nitrophenol Ligands and their Fe(NO 3 ) 3 Complexes  

Microsoft Academic Search

2-(5-H\\/methyl-1H-benzimidazol-2-yl)-4-bromo\\/nitro-phenol (HLx:X=1–4) ligands and their iron(III) nitrate complexes have been synthesized and characterized. In all of the complexes, the\\u000a ligands are bidentate, via one imine nitrogen atom and a phenolate oxygen atom. The coordination is completed with a bidentate nitrate anion, and a\\u000a water molecule. Elemental analysis, molar conductivity, magnetic susceptibility, FT-Raman, FT-IR (mid i.r., far i.r.), UV–visible\\u000a and as

Aydin Tavman; Naz M. Agh-Atabay; Abdollah Neshat; Fahrettin Gucin; Basaran Dulger; Durata Haciu



Metal nitrosyl complexes of bioinorganic, catalytic, and environmental relevance: A novel single-step synthesis of dinitrosylmolybdenum(0) complexes of {Mo(NO)2}6 electron configuration involving Schiff bases derived from 4-acyl-3-methyl-1-phenyl-2-pyrazolin-5-one and 4-aminoantipyrine, directly from molybdate(VI) and their characterization  

NASA Astrophysics Data System (ADS)

This paper reports the synthesis of five new hexa-coordinated mixed-ligand dinitrosyl complexes of molybdenum(0) of the composition [Mo(NO)2(L)(OH)], where LH = N-(3?-methyl-1?-phenyl-4?-valerylidene-2?-pyrazolin-5?-one)-4-aminoantipyrine (mphvp-aapH), N-(4?-benzoylidene-3?-methyl-1?-phenyl-2 ?-pyrazolin-5?-one)-4-aminoantipyrine (bmphp-aapH), N-(3?-methyl-1?-phenyl-4?-propionylidene-2?-pyrazolin-5?-one)-4-aminoantipyrine (mphpp-aapH), N-(4?-acetylidene-3?-methyl-1?-phenyl-2?-pyrazolin-5 ?-one)-4-aminoantipyrine (amphp-aapH) or N-(-4?-iso-butyrylidene-3?-methyl-1?-phenyl-2?-pyrazolin-5?-one)-4-aminoantipyrine (iso-bumphp-aapH) directly from molybdate (VI) in a single step and in a single pot. The compounds so obtained have been characterized by elemental analyses, molar conductance, decomposition temperature and magnetic measurements, thermogravimetric analyses, infrared and electronic spectral studies. They were found to contain low-spin [Mo(NO)2]6 electron configuration. A cis-octahedral structure has been proposed for these complexes. The 3D molecular modeling and analysis for bond lengths and bond angles have also been carried out for one of the representative compounds, [Mo(NO)2(bmphp-aap)(OH)] (2).

Maurya, R. C.; Pandey, A.; Chaurasia, J.; Martin, H.



Synthesis and X-ray crystal structures of two transition metal complexes based on functionalised 1,5-anhydro-2-deoxy-D-galactitol and methyl 2-deoxy-alpha-D-galactopyranoside.  


Two new ligands of transition metal cations based on galactose-derived scaffolds were synthesised: 1,5-anhydro-2-deoxy-3,4,6-tri-O-(2-picolyl)-D-galactitol and methyl 2-deoxy-3,4,6-tri-O-(2-picolyl)-alpha-D-galactopyranoside. These ligands permitted the isolation as single crystals of a Co(II) and a Ni(II) complex, respectively. The structures of both complexes were determined by X-ray crystallography showing a coordination sphere including sugar-bound oxygen atoms. The sugar-derived ligands were found to be in both cases in high energy conformations in the crystal structures of the complexes. These conformations contain an arrangement of sugar-bound oxygen atoms similar to those observed in polyol-metal and carbohydrate-metal complexes. PMID:18179787

Cisnetti, Federico; Guillot, Régis; Ibrahim, Nada; Lambert, François; Thérisod, Michel; Policar, Clotilde



Synthesis, spectral characterization and antioxidant activity studies of a bidentate Schiff base, 5-methyl thiophene-2-carboxaldehyde-carbohydrazone and its Cd(II), Cu(II), Ni(II) and Zn(II) complexes  

NASA Astrophysics Data System (ADS)

A new Schiff base bidentate ligand (L), 5-methyl thiophene-2-carboxaldehyde-carbohydrazone and its metal (Cu(II), Cd(II), Ni(II) and Zn(II)) complexes with general stoichiometry [M(L)2X2] (where X = Cl) were synthesized. The ligand and its metal complexes were characterized by elemental analyses, IR, 1H NMR, ESR spectral analyses, and molar conductance studies. The molar conductance data revealed that all the metal chelates are non-electrolytes. IR spectra showed that ligand (L) is coordinated to the metal ions in a bidentate manner with N and O donor sites of the azomethine-N, and carbonyl-O. ESR and UV-Vis spectral data showed that the geometrical structure of the complexes are Orthorhombic. Furthermore, the antioxidant activity of the ligand and its complexes was determined by hydroxyl radical scavenging, DPPH, NO, reducing power methods in vitro. The obtained IC50 value of the DPPH activity for the copper complex (IC50 = 66.4 ?m) was higher than other compounds. Microbial assay of the above complexes against Staphylococcus aureus, Escherichia coli, Rhizocotonia bataticola and Alternaria alternata showed that copper complex exhibited higher activity than the other complexes.

Harinath, Y.; Harikishore Kumar Reddy, D.; Naresh Kumar, B.; Apparao, Ch.; Seshaiah, K.



Crystal structure and catecholase-like activity of a mononuclear complex [Cu(EDTB)]2+ (EDTB=N,N,N',N'-tetrakis(2'-benzimidazolyl methyl)-1,2-ethanediamine).  


The crystal structure and catecholase-like activity of a mononuclear complex, Cu(EDTB)(NO3)2.C2H5OH (here EDTB stands N,N,N',N'-tetrakis(2'-benzimidazolyl methyl)-1,2-ethanediamine) has been studied in comparison with a binuclear complex Cu2(EDTB)(NO3)4.3H2O. The results show that the reactive rate constants increase with increases of reaction temperature and pH value of intermediate. Electrospray ionization mass spectrum (ESI-MS) shows that tautomerism isomers of catechol with the title complex exist in reaction solution, and catechol is oxidized to quinone, then it is further oxidized resulting in muconic acid and its derivatives via an intradiol mechanism, just like that catalyzed by a mononuclear non-heme iron-containing dioxygenase. PMID:15271507

Chen, Zhan-Fen; Liao, Zhan-Ru; Li, Dong-Feng; Li, Wu-Ke; Meng, Xiang-Gao



Reactivity of cationic methyl rhodium(III) complexes cis-[Rh(?-diket)(PPh 3) 2(CH 3)(CH 3CN)][BPh 4] toward ligands of different character: pyridine, carbon monoxide, and triphenylphosphine  

Microsoft Academic Search

Cationic methyl complex of rhodium(III), cis-[Rh(Acac)(PPh3)2(CH3)(Py)][BPh4] (1) as a single isomer with Py in the trans to PPh3 position, is formed upon the reaction of cis-[Rh(Acac)(PPh3)2(CH3)(CH3CN)][BPh4] with pyridine in methylene chloride solution.Complex 1 was characterized by elemental analysis and by 31P{1H} and 1H NMR spectra.Cationic pentacoordinate acetyl complexes, trans-[Rh(Acac)(PPh3)2(COCH3)][BPh4] (2) and trans-[Rh(BA)(PPh3)2(COCH3)][BPh4] (3), are prepared by action of carbon monoxide

Elizaveta P. Shestakova; Yuri S. Varshavsky; Aleksei B. Nikolskii



Arginine/lysine-methyl/methyl switches: biochemical role of histone arginine methylation in transcriptional regulation.  


Post-translational modifications (PTMs) are commonly used to modify protein function. Modifications such as phosphorylation, acetylation and methylation can influence the conformation of the modified protein and its interaction with other proteins or DNA. In the case of histones, PTMs on specific residues can influence chromatin structure and function by modifying the biochemical properties of key amino acids. Histone methylation events, especially on arginine- and lysine-residues, are among the best-characterized PTMs, and many of these modifications have been linked to downstream effects. The addition of a methyl group to either residue results in a slight increase in hydrophobicity, in the loss of a potential hydrogen-bond donor site and, in the alteration of the protein interaction surface. Thus far, a number of protein domains have been demonstrated to directly bind to methylated lysine residues. However, the biochemical mechanisms linking histone arginine methylation to downstream biological outputs remain poorly characterized. This review will focus on the role of histone arginine methylation in transcriptional regulation and on the crosstalk between arginine methylation and other PTMs. We will discuss the mechanisms by which differentially methylated arginines on histones modulate transcriptional outcomes and contribute to the complexity of the 'histone code'. PMID:22122749

Migliori, Valentina; Phalke, Sameer; Bezzi, Marco; Guccione, Ernesto



Methyl eucomate  

PubMed Central

The crystal structure of the title compound [systematic name: methyl 3-carboxy-3-hydr­oxy-3-(4-hydroxy­benz­yl)propanoate], C12H14O6, is stabilized by inter­molecular O—H?O and C—H?O hydrogen bonds. The mol­ecules are arranged in layers, parallel to (001), which are inter­connected by the O—H?O hydrogen bonds.

Li, Linglin; Zhou, Guang-Xiong; Jiang, Ren-Wang



Synthesis, properties, and catecholase-like activity of the [1,4-di(6?-methyl-2?-pyridyl)aminophthalazine]dimanganese(II) complex, Mn 2 (6?Me 2 PAP) 2 Cl 4  

Microsoft Academic Search

The preparation, spectroscopic properties, and catecholase-like activity of the dimanganese(II) complex [Mn2(6?Me2PAP)2Cl4] [6?Me2PAP: 1,4-di(6?-methyl-2?-pyridyl)aminophthalazine] are reported. The title compound was suitable catalyst for the oxidation\\u000a of 3,5-di-t-butylcatechol (3,5-DTBCH2) to 3,5-di-t-butyl-1,2-benzoquinone (3,5-DTBQ) with dioxygen under ambient conditions in good yields. The catalytic oxidation was found\\u000a to obey Michaelis–Menten type kinetics.

József Kaizer; Róbert Csonka; Gábor Baráth; Gábor Speier



Synthesis and biodistribution of new oxo and nitrido 99mTc complexes with asymmetrical potentially dianionic or trianionic tetradentate SNNO ligands derived from methyl-2-aminocyclopentene-1-dithiocarboxylic acid.  


In this work, 10 new asymmetrical tetradentate SNNO ligands were prepared by reaction of the amine function of methyl 2-[(beta-aminoethyl)amino]cyclopentene-1-dithiocarboxylate with various bifunctional substituents bearing hydroxyl/ketone and hydroxyl/aldehyde functional groups and with diethyl oxalate. 99mTc labeling efficiency was optimized by adjusting temperature and pH conditions. Seven nitrido and two oxo 99mTc complexes were isolated. Six of them proved to be stable near physiological conditions. Biodistribution studies in the rat showed a significant heart uptake for four of them and strong kidney and liver uptake for the other two. PMID:9466364

Belhadj-Tahar, H; Ouhayoun, E; Cros, G; Darbieu, M H; Tafani, J A; Fabre, J; Esquerre, J P; Coulais, Y



Methyl gallate  

PubMed Central

The crystal structure of the title compound (systematic name: methyl 3,4,5-trihydroxy­benzoate), C8H8O5, is composed of essentially planar mol­ecules [maximum departures from the mean carbon and oxygen skeleton plane of 0.0348?(10)?Å]. The H atoms of the three hydroxyl groups, which function as hydrogen-bond donors and acceptors simultaneously, are oriented in the same direction around the aromatic ring. In addition to two intra­molecular hydrogen bonds, each mol­ecule is hydrogen bonded to six others, creating a three-dimensional hydrogen-bonded network.

Bebout, Deborah; Pagola, Silvina



Synthesis and oxidation of chiral rhenium phosphine methyl complexes of the formula (? 5-C 5Me 5)Re(NO)(PR 3)(CH 3): in search of radical cations with enhanced kinetic stabilities  

Microsoft Academic Search

Reactions of racemic [(?5-C5Me5)Re(NO)(NCCH3)(CO)]+ BF4? and phosphines PR3 (R=C6H5a; 4-C6H4CH3b; 4-C6H4-t-C4H9c; 4-C6H4C6H5d; 4-C6H4OCH3e; c-C6H11f) give the phosphine carbonyl complexes [(?5-C5Me5)Re(NO)(PR3)(CO)]+ BF4? (5a–5f+ BF4?; 55–95%). These are treated with LiEt3BH and then BH3·THF to give the phosphine methyl complexes (?5-C5Me5)Re(NO)(PR3)(CH3) (2a–2f, 50–86%). Cyclic voltammetry shows that the new compounds 2b–2f undergo chemically reversible one-electron oxidations that are thermodynamically more favorable than

Wayne E Meyer; Angelo J Amoroso; Monika Jaeger; Jean Le Bras; Wing-Tak Wong; J. A Gladysz



Synthesis, spectroscopic, crystal structure and DNA binding of Ru(II) complexes with 2-hydroxy-benzoic acid [1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-ethylidene]-hydrazide  

NASA Astrophysics Data System (ADS)

Reactions of 2-hydroxy-benzoic acid [1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-ethylidene]-hydrazide (H 2L) with [RuHCl(CO)(EPh 3) 3] (E = P or As) were carried out and the new complexes obtained were characterized by elemental analysis, electronic, IR, 1H NMR and 13C NMR spectroscopic techniques and single crystal X-ray diffraction studies. Complex ( 1) crystallizes in the monoclinic space group P2(1)/ c with unit cell dimensions a = 18.6236(17) Å, b = 12.8627(12) Å, c = 21.683(2) Å, ? = 90.00, ? = 114.626(2), ? = 90.00 V = 4721.8(8) Å, Z = 4. The crystal structure of the complex shows Ru(II) atom is six-coordinated, forming a slightly distorted octahedral geometry with two P atoms in axial positions, and three chelating donor atoms of the tridentate Schiff base ligand and one carbonyl group located in the equatorial plane. The molecular structure is stabilized by intramolecular O—H···N interactions. No intermolecular hydrogen bond was observed. The intramolecular hydrogen bond exists between the oxygen atom from salicylic acid moiety and nitrogen from the same moiety. A variety of solution studies were carried out for the determination of DNA binding mode of the complexes. The results suggest that both complexes bind to Herring sperm DNA via non intercalative mode.

Chitrapriya, Nataraj; Sathiya Kamatchi, Thangavel; Zeller, Matthias; Lee, Hyosun; Natarajan, Karuppannan



The influence of counter ion and ligand methyl substitution on the solid-state structures and photophysical properties of mercury(II) complexes with (E)-N-(pyridin-2-ylmethylidene)arylamines.  


Ten neutral monomeric, dimeric and polymeric mercury(II) complexes of compositions HgX(2)L (3, 8), [HgX(2)L](2) (1, 2, 4-6 and 7), [Hg(NO(3))(2)L](n) (9) and {[Hg(N(3))(2)L](2)}(n) (10) where X = chloride, bromide, iodide, nitrate and azide, and L = (E)-N-(pyridin-2-ylmethylidene)arylamine, are described. Compounds 1-10 were characterized by elemental analyses, and IR and (1)H NMR spectroscopic studies. The solution-state photophysical properties of the complexes are highly dependent on the anions as seen in the fluorescence emission features. Single-crystal X-ray crystallography showed that the molecular complexes can aggregate into larger entities depending upon the anion coordinated to the metal centre. Iodide gives discrete monomeric complexes, chloride and bromide generate binuclear complexes formed through Hg-X-Hg bridges, while nitrate and azide lead to 1D coordination polymers. The significant differences in the observed aggregation patterns of the compounds indicate that the anions exert a substantial influence on the formation of the compounds. A further influence upon supramolecular aggregation is the presence of methyl substituents in L(3) and L(4), which generally enhances the probability of forming supramolecular ?? interactions involving the five-membered C(2)N(2)Hg chelate rings in their crystal structures. PMID:23172550

Basu Baul, Tushar S; Kundu, Sajal; Mitra, Sivaprasad; Höpfl, Herbert; Tiekink, Edward R T; Linden, Anthony



Synthesis, characterization, and tyrosinase biomimetic catalytic activity of copper(II) complexes with schiff base ligands derived from ?-diketones with 2-methyl-3-amino-(3H)-quinazolin-4-one  

NASA Astrophysics Data System (ADS)

A template condensation of ?-diketones (biacetyl, benzile and 2,3-pentanedione) with 2-methyl-3-amino-(3H)-quinazolin-4-one (AMQ) in the presence of CuX2 (X = Cl-, Br-, NO3- or ClO4-) resulted in the formation of tetradentate Schiff base copper(II) complexes of the type [CuLX]X and [CuL]X2. Structural characterization of the complex species was achieved by several physicochemical methods, namely elemental analysis, electronic spectra, IR, ESR, molar conductivity, thermal analysis (TAG & DTG), and magnetic moment measurements. The stereochemistry, the nature of the metal chelates, and the catalytic reactivity are markedly dependent upon the type of counter anions and the ligand substituent within the carbonyl moiety. A square planar monomeric structure is proposed for the perchlorate, nitrate, and bromide complexes, in which the counter anions are loosely bonded to copper(II) ion. For the chloride complexes, the molar conductivities and the spectral data indicated that they have square-pyramidal environments around copper(II) center. The reported copper(II) complexes exhibit promising tyrosinase catalytic activity towards the hydroxylation of phenol followed by the aerobic oxidation of the resulting catechol. A linear correlation almost exists between the catalytic reactivity and the Lewis-acidity of the central copper(II) ion created by the donating properties of the parent ligand. The steric considerations could be accounted to clarify the difference in the catalytic activity of these functional models.

Ramadan, Abd El-Motaleb M.; Ibrahim, Mohamed M.; Shaban, Shaban Y.



Analytical Methodologies for Detection of Gamma-valerolactone, Delta-valerolactone, Acephate, and Azinphos Methyl and their Associated Metabolites in Complex Biological Matrices  

SciTech Connect

Non-invasive biomonitoring for chemicals of interest in law enforcement and similar monitoring of pesticides together with their metabolites can not only save money but can lead to faster medical attention for individuals exposed to these chemicals. This study describes methods developed for the analysis of gamma-valerolactone (GVL), delta-valerolactone (DVL), acephate, and azinphos methyl in saliva and serum. Liquid chromatography/mass spectrometry (LC/MS) operated in the negative ion mode and in the positive ion mode and gas chromatography/mass spectrometry (GC/MS) were used to analyze GVL and DVL. Although both analytical techniques worked well, lower detection limits were obtained with GC/MS. The lactones and their corresponding sodium salts were spiked into both saliva and serum. The lactones were isolated from saliva or serum using newly developed extraction techniques and then subsequently analyzed using GC/MS. The sodium salts of the lactones are nonvolatile and require derivatization prior to analysis by this method. N-methyl-N-(t-butyldimethylsilyl)-trifluoroacetamide (MTBSTFA) was ultimately selected as the reagent for derivatization because the acidic conditions required for reactions with diazomethane caused the salts to undergo intramolecular cyclization to the corresponding lactones. In vitro studies were conducted using rat liver microsomes to determine other metabolites associated with these compounds. Azinphos methyl and acephate are classified as organophosphate pesticides, and are known to be cholinesterase inhibitors in humans and insects, causing neurotoxicity. For this reason they have both exposure and environmental impact implications. These compounds were spiked into serum and saliva and prepared for analysis by GC/MS. Continuation of this research would include analysis by GC/MS under positive ion mode to determine the parent ions of the unknown metabolites. Further research is planned through an in vivo analysis of the lactones and pesticides. These methodologies could be extended for further analysis of other similar compounds as well as chemical and biological warfare agents.

Zink, Erika M.; Clark, Ryan J.; Grant, Karen E.; Campbell, James A.; Hoppe, Eric W.



Preparation Complex Photocatalyst of Modified TiO2\\/K2Ti6O13 by Tungstosilicic Acid and Study its Degradation of Methyl Orange  

Microsoft Academic Search

With potassium titanate (VI) whisker as carrier, and silicotungstic acid (H4SiW12O40) as modified reagent, the compound photocatalyst H4SiW12O40\\/TiO2\\/K2Ti6O13 was prepared by sol-gel-dipping method. UV-vis spectra showed that the compound photocatalyst had strongly responded to UV light and had some absorbency of visible light. The photocatalytic activity was evaluated by degradation of methyl orange under UV light. The photocatalytic influences of

Songtian Li; Weichun Yang; Changhao Li



Oxidation of methyl formylstearate with molecular oxygen  

Microsoft Academic Search

Methyl formylstearate, containing soluble rhodium complex from rhodium-catalyzed hydroformylation of methyl oleate, is oxidized\\u000a in an emulsion to methyl carboxystearate. The reaction is carried out in a closed system at 20–25 C in the presence of either\\u000a air or oxygen (1–3 atm). Conversion to methyl carboxystearate is 87–89% in 2–3 hr; when catalytic amounts of calcium acetate\\u000a are present, 93–95%

J. P. Friedrich



Cigarette smoking and DNA methylation  

PubMed Central

DNA methylation is the most studied epigenetic modification, capable of controlling gene expression in the contexts of normal traits or diseases. It is highly dynamic during early embryogenesis and remains relatively stable throughout life, and such patterns are intricately related to human development. DNA methylation is a quantitative trait determined by a complex interplay of genetic and environmental factors. Genetic variants at a specific locus can influence both regional and distant DNA methylation. The environment can have varying effects on DNA methylation depending on when the exposure occurs, such as during prenatal life or during adulthood. In particular, cigarette smoking in the context of both current smoking and prenatal exposure is a strong modifier of DNA methylation. Epigenome-wide association studies have uncovered candidate genes associated with cigarette smoking that have biologically relevant functions in the etiology of smoking-related diseases. As such, DNA methylation is a potential mechanistic link between current smoking and cancer, as well as prenatal cigarette-smoke exposure and the development of adult chronic diseases.

Lee, Ken W. K.; Pausova, Zdenka



Synthesis, Characterization, and Biological Activity of N1-Methyl-2-(1H-1,2,3-Benzotriazol-1-y1)-3-Oxobutan- ethioamide Complexes with Some Divalent Metal (II) Ions  

PubMed Central

A new series of Zn2+, Cu2+, Ni2+, and Co2+ complexes of N1-methyl-2-(1H-1,2,3-benzotriazol-1-yl)-3-oxobutanethioamide (MBOBT), HL, has been synthesized and characterized by different spectral and magnetic measurements and elemental analysis. IR spectral data indicates that (MBOBT) exists only in the thione form in the solid state while 13C NMR spectrum indicates its existence in thione and thiole tautomeric forms. The IR spectra of all complexes indicate that (MBOBT) acts as a monobasic bidentate ligand coordinating to the metal(II) ions via the keto-oxygen and thiolato-sulphur atoms. The electronic spectral studies showed that (MBOBT) bonded to all metal ions through sulphur and nitrogen atoms based on the positions and intensity of their charge transfer bands. Furthermore, the spectra reflect four coordinate tetrahedral zinc(II), tetragonally distorted copper(II), square planar nickel(II), and cobalt(II) complexes. Thermal decomposition study of the complexes was monitored by TG and DTG analyses under N2 atmosphere. The decomposition course and steps were analyzed and the activation parameters of the nonisothermal decomposition are determined. The isolated metal chelates have been screened for their antimicrobial activities and the findings have been reported and discussed in relation to their structures.

Al-Awadi, Nouria A.; Shuaib, Nadia M.; Abbas, Alaa; El-Sherif, Ahmed A.; El-Dissouky, Ali; Al-Saleh, Esmaeil



Synthesis, characterization, and theoretical studies of Co(II) and Cu(II) complexes of 1-[(5-mercapto-[1,3,4]thiadiazol-2-ylimino)-methyl]-naphthalen-2-ol and its interaction with Cu nanoparticles  

NASA Astrophysics Data System (ADS)

The electronic absorption spectra of Schiff base namely 1-[(5-mercapto-[1,3,4]thiadiazol-2-ylimino)-methyl]-naphthalen-2-ol (H2L) was studied in organic solvents of different polarity as well as in universal buffer solutions of varying pH values at room temperature; the pKa values were calculated. The effect of Co(II) and Cu(II) ions on the electronic absorption spectra of H2L was also assigned and the stability constants of the complexes were calculated. The stoichiometry of the metal complexes was determined spectrophotometrically. Solid Co(II) and Cu(II) complexes with H2L have been synthesized and characterized on the basis of elemental analyses, molar conductance, magnetic susceptibility measurements, IR, electronic as well as ESR spectral studies. The thermal decomposition of the metal complexes was studied by TGA and DTA techniques. The thermo-kinetic parameters; activation energy, pre-exponential factor and entropy of activation were estimated. The interaction between the Schiff base under investigation and the copper nanoparticles in the ground and excited state was considered. The fluorescence quenching rate constant of Schiff base by Cu nanoparticles has a large value.

El-Wakiel, Nadia; El-Sayed, Yusif; Gaber, Mohamed



Synthesis, characterization, and biological activity of metal complexes of 4-ethyl vanillideneamino-3-methyl-5-mercapto-1,2,4-triazole  

Microsoft Academic Search

A series of transition metal–triazole derivatives have been synthesized and characterized by microanalytical, thermal, magneto-chemical, and spectral studies. The synthesized complexes were screened for biological activities. The complexes of Co(II) and Ni(II) emerged as a good antibacterial agent against Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Bacillus subtilis, and Shigella flexneri.

A. S. Ramasubramanian; B. Ramachandra Bhat; R. Dileep



Ni(II)/H(2)O(2) reactivity in bis[(pyridin-2-yl)methyl]amine tridentate ligand system. aromatic hydroxylation reaction by bis(mu-oxo)dinickel(III) complex.  


The nickel(II) complexes 1(X) supported by bis[(pyridin-2-yl)methyl]benzylamine tridentate ligands carrying m-substituted phenyl groups (X = OMe, Me, H, Cl, NO(2)) at the 6-position of pyridine donor groups (L(X), N,N-bis[(6-m-substituted-phenylpyridin-2-yl)methyl]benzylamine) have been synthesized and characterized. The X-ray crystallographic analyses have revealed that [Ni(II)(L(H))(CH(3)CN)(H(2)O)](ClO(4))(2) (1(H)), [Ni(II)(L(OMe))(CH(3)CN)(MeOH)](ClO(4))(2) (1(OMe)), [Ni(II)(L(Me))(CH(3)CN)(H(2)O)](ClO(4))(2) (1(Me)), and [Ni(II)(L(Cl))(CH(3)CN)(H(2)O)](ClO(4))(2) (1(Cl)) have a five-coordinate square pyramidal geometry, whereas [Ni(II)(L(NO(2)))(CH(3)CN)(2)(H(2)O)](ClO(4))(2) (1(NO(2))) exhibits a six-coordinate octahedral geometry having an additional CH(3)CN co-ligand. (1)H NMR spectra of the nickel(II) complexes 1(X) in CD(3)CN have indicated that all the complexes have a high spin ground state. The nickel(II) complexes 1(X) react with hydrogen peroxide (H(2)O(2)) in acetone to give bis(mu-oxo)dinickel(III) complexes 2(X) exhibiting a characteristic UV-vis absorption band at approximately 420 nm. In the case of 2(H), a resonance Raman band ascribable to a Ni(2)O(2) core vibration was observed at 611 cm(-1) that shifted to 586 cm(-1) upon H(2)(18)O(2). The bis(mu-oxo)dinickel(III) intermediates 2(X) undergo an efficient aromatic ligand hydroxylation reaction, producing a mononuclear nickel(II)-phenolate complexes 4(X) via a putative intermediate (mu-phenoxo)(mu-hydroxo)dinickel(II) (3(X)). The kinetic studies on the aromatic ligand hydroxylation process including m-substituent effects (Hammett analysis) and kinetic deuterium isotope effects (KIE) have indicated that the reaction of 2(X) to 3(X) involves an electrophilic aromatic substitution mechanism, where C-O bond formation and C-H bond cleavage occur in a concerted manner. Intermediate 3(H) was detected by ESI-MS during the course of the reaction, and the final product 4(H) was characterized by elemental analysis, ESI-MS, and X-ray crystallographic analysis. PMID:19374371

Kunishita, Atsushi; Doi, Yoshitaka; Kubo, Minoru; Ogura, Takashi; Sugimoto, Hideki; Itoh, Shinobu



Coordination chemistry and bioactivity of Ni 2+, Cu 2+, Cd 2+ and Zn 2+ complexes containing bidentate Schiff bases derived from S-benzyldithiocarbazate and the X-ray crystal structure of bis[ S-benzyl-?- N-(5-methyl-2-furylmethylene)dithiocarbazato]cadmium(II)  

Microsoft Academic Search

New bidentate isomeric NS and NS? Schiff bases were derived from the condensation of S-benzyldithiocarbazate (SBDTC) with 5-methyl-2-furyldehyde and 2-furyl-methylketone. Reaction of NS ligand with Ni(II), Cu(II), Cd(II) and Zn(II) salts gave solid complexes. Only the Ni(II) complex of the NS? ligand was isolated. All complexes were characterized by a variety of physico-chemical techniques, viz. elemental analyses, molar conductivity, i.r.

M. T. H Tarafder; Khoo Teng Jin; Karen A Crouse; A. M Ali; B. M Yamin; H.-K Fun



Protein Methylation in Full Length Chlamydomonas Flagella  

PubMed Central

Post-translational protein modification occurs extensively in eukaryotic flagella. Here we examine protein methylation, a protein modification that has only recently been reported to occur in flagella (Schneider et al. 2008). The cobalamin (vitamin B12) independent form of the enzyme methionine synthase (MetE), which catalyzes the final step in methionine production, is localized to flagella. Here we demonstrate, using immunogold scanning electron microscopy, that MetE is bound to the outer doublets of the flagellum. Methionine can be converted to S-adenosyl methionine, which then serves as the methyl donor for protein methylation reactions. Using antibodies that recognize symmetrically or asymmetrically methylated arginine residues, we identify three highly methylated proteins in intact flagella: two symmetrically methylated proteins of about 30 and 40 kDa, and one asymmetrically methylated protein of about 75 kDa. Several other relatively less methylated proteins could also be detected. Fractionation and immunoblot analysis shows that these proteins are components of the flagellar axoneme. Immunogold thin section electron microscopy indicates that the symmetrically methylated proteins are located in the central region of the axoneme, perhaps as components of the central pair complex and the radial spokes, while the asymmetrically methylated proteins are associated with the outer doublets.

Sloboda, Roger D.; Howard, Louisa



Pd(II)– N-heterocyclic carbene complexes of 2,6- bis{ N-methyl-(imidazolium\\/benzimidazolium)}pyrazinechloride: Synthesis, structure, catalysis and theoretical studies  

Microsoft Academic Search

The multitopic pyrazine functionalized pro-ligand 2,6-bis(N-methylimidazolium)pyrazinedichloride, L-1; 2,6-bis(N-methylbenzimidazolium)pyrazinedichloride, L-2 and their respective Pd(II)–NHC complexes 1 and 2 have been synthesised and characterized by different spectroscopic methods and have been analyzed within a conceptual DFT framework. Single crystal X-ray structures of (L-1)PF6 and complex 1 have been determined. X-ray structure revels that 1 form a 12 member palladacycle. Both complex 1

Gourisankar Roymahapatra; Santanab Giri; Anders A. Danopoulos; Pratim Kumar Chattaraj; Ambikesh Mahapatra; Valerio Bertolasi; Joydev Dinda


Pyridine Complexes of Chlorine Atoms,  

National Technical Information Service (NTIS)

Chlorine atom complexes with pyridine, with methyl nicotinate, and with methyl isonicotinate have been studied by three techniques. The effect of the pyridine derivatives on the selectivity of free radical chlorination of 2,3-dimethylbutane was examined a...

R. Breslow M. Brandl J. Hunger N. Turro K. Cassidy



Establishment of Histone H3 Methylation on the Inactive X Chromosome Requires Transient Recruitment of Eed-Enx1 Polycomb Group Complexes  

Microsoft Academic Search

Previous studies have implicated the Eed-Enx1 Polycomb group complex in the maintenance of imprinted X inactivation in the trophectoderm lineage in mouse. Here we show that recruitment of Eed-Enx1 to the inactive X chromosome (Xi) also occurs in random X inactivation in the embryo proper. Localization of Eed-Enx1 complexes to Xi occurs very early, at the onset of Xist expression,

Jose Silva; Winifred Mak; Ilona Zvetkova; Ruth Appanah; Tatyana B Nesterova; Zoe Webster; Antoine H. F. M Peters; Thomas Jenuwein; Arie P Otte; Neil Brockdorff



Catalysis of methyl acetate formation from methanol alone by ({mu}{sup 5}-C{sub 5}H{sub 5})(PPh{sub 3}){sub 2}RuX (X=Cl, SnCl{sub 3}, SnF{sub 3}): High activity for the SnF{sub 3} complex  

SciTech Connect

The authors have recently shown that the Ru(II)-Sn(II) bimetallic complex can catalyze the unprecedented one-step formation of acetic acid (or methyl acetate) with methanol used as the sole source. It was suggested that the reaction consists of sequential processes of methanol {r_arrow} formaldehyde (methyl){r_arrow}methyl formate {r_arrow} acetic acid (methyl acetate). While the Ru(II) complexes capable of catalyzing the dehydrogenation of methanol into methyl formate are known, this catalyst system is unique because of its extra ability to isomerize methyl formate to acetic acid without a CO atmosphere (usually high pressure) or an iodide promoter (often corrosive to reaction apparatus). In this communication, the authors examine the cyclopentadienyl bis(triphenylphosphine) ruthenium(II) auxilliary in view of its well defined geometry and configurational stability, and demonstrate that combination with the SnF{sub 3} ligand gives quite high catalytic ability compared to the conventional SnCl{sub 3} ligand. 12 refs., 1 fig.

Einaga, Hisahiro; Yamakawa, Tetsu; Shinoda, Sumio [Univ. of Tokyo (Japan)



Novel light-conversion hybrids of SBA-16 functionalized with rare earth (Eu3+, Nd3+, Yb3+) complexes of modified 2-methyl-9-hydroxyphenalenone and 1,10-phenanthroline  

NASA Astrophysics Data System (ADS)

Novel rare earth complex-functionalized mesoporous SBA-16-type hybrid materials are synthesized by the co-condensation of modified 2-methyl-9-hydroxyphenalenone (MHPOSi), from modified 3-(triethoxysilyl)-propyl isocyanate (TEPIC), and tetraethoxysilane (TEOS) in the presence of Pluronic F127 as a template. These inorganic-organic mesoporous hybrids are characterized by FT-IR spectra, small-angle X-ray diffraction (SAXRD), N2 adsorption-desorption measurements, thermal analysis and spectroscopy. Their photophysical properties, which show novel light conversion properties, are discussed in detail. The Eu3+ hybrid system shows ultraviolet excitation and visible emission, and the Nd+ and Yb3+ hybrids exhibit visible excitation and NIR emission.

Gu, Yan-Jing; Yan, Bing; Qiao, Xiao-Fei



A DFT/TD DFT study of the structure and spectroscopic properties of 5-methyl-2-(8-quinolinyl)benzoxazole and its complexes with Zn(II) ion  

NASA Astrophysics Data System (ADS)

The structure and spectroscopic properties of 5-methyl-2-(8-quinolinyl)benzoxazole and its complexes with Zn(II) ion were studied using a DFT and TD DFT methods with def2-TZVP basis set. It was shown that the type of functional used (B3-LYP or pbe0) implemented in TURBOMOLE package does not have essential influence on the geometry (small differences in bond length, valence and dihedral angles) of studied compounds in both ground and excited states. However, significant differences were obtained for the position of vertical absorption and emission transition but not for the oscillator strength of transition. Application of pbe0 functional seems to reproduce better the experimental spectrum.

Guzow, Katarzyna; Milewska, Magda; Czaplewski, Cezary; Wiczk, Wies?aw



Structural and magnetic properties of three novel complexes with the versatile ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one.  


Conventional reactions of the versatile multidentate ligand 5-methyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one (HmtpO) with metallic(II) salts lead to three novel multidimensional complexes [Cu(HmtpO)(2)(H(2)O)(3)](ClO(4))(2)·H(2)O (1), {[Cu(HmtpO)(2)(H(2)O)(2)](ClO(4))(2)·2HmtpO}(n) (2) and {[Co(HmtpO)(H(2)O)(3)](ClO(4))(2)·2H(2)O}(n) (3). In each compound, the triazolopyrimidine ligand shows a different and unusual coordination mode, giving rise to structures with diverse topologies and dimensionality. Compound 1 is a monomeric complex, in which HmtpO shows both N3-monodentate and N1,O71-bidentate modes. 2 is a bidimensional framework with the ligand showing a N3,O71 bidentate-bridging mode. The structure of 3 consists of 1D chains, in which HmtpO displays a N1,N3,O71-tridentate-bridging mode. It should be noted that these coordination modes of the HmtpO ligand are unique in the case of compounds 2 and 3. On the other hand, the magnetic properties of the polynuclear complexes 2 and 3 have been studied showing weak ferromagnetic and antiferromagnetic behaviour, respectively. PMID:21479329

Caballero, Ana B; Rodríguez-Diéguez, Antonio; Lezama, Luis; Barea, Elisa; Salas, Juan M



Simultaneous determination of Mn2+ and Fe3+ as 4,4'[(4-cholorophenyl)methylene] bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) complexes in some foods, vegetable and water samples by artificial neural networks.  


A simple and sensitive spectrophotometric method to the simultaneous determination of Mn(2+) and Fe(3+) in foods, vegetable and water sample with the aid of artificial neural networks (ANNs) is described. It relies on the complexation of analytes with recently synthesised bis pyrazol base ligand as 4,4'[(4-cholorophenyl)methylene] bis(3-methyl-1-phenyl-1H-pyrazol-5-ol)(CMBPP). The analytical data show that the ratio of ligand to metal in metal complexes is 1:1 and 1:2 for Fe(3+) and Mn(2+), respectively. It was found that the complexation reactions are completed at pH 6.7 and 5 min after mixing. The results showed that Mn(2+) and Fe(3+) could be determined simultaneously in the range of 0.20-7.5 and 0.30-9.0 mgl(-1), respectively. The analytical characteristics of the method such as the detection limit and the relative standard error predictions were calculated. The data obtained from synthetic mixtures of the metal ions were processed by radial basis function networks (RBFNs) and feed forward neural networks (FFNNs). The optimal conditions of the neural networks were obtained by adjusting various parameters by trial-and-error. Under the working conditions, the proposed methods were successfully applied to the simultaneous determination of elements in different water, tablet, rice, tea leaves, tomato, cabbage and lettuce samples. PMID:23411205

Abbasi-Tarighat, Maryam; Shahbazi, Elahe; Niknam, Khodabakhsh



Intramolecular energy transfer in actinide complexes of 6-methyl-2-(2-pyridyl)-benzimidazole (biz): comparison between Cm{sup 3+} and Tb{sup 3+} systems  

SciTech Connect

Coordination of the 6-methyl-2-(2-pyridyl)-benzimidazole ligand with actinide and lanthanide species can produce enhanced emission due to increased efficiency of intramolecular energy transfer to metal centers. A comparison between the curium and terbium systems indicates that the position of the ligand's triplet state is critical for the enhanced emission. The energy gap between the ligand's triplet state and the acceptor level in curium is about 1000cm{sup -1}, as compared to a {approx}600cm{sup -1} gap in the terbium system. Due to the larger gap, the back transfer with curium is reduced and the radiative yield is significantly higher. The quantum yield for this 'sensitized' emission increases to 6.2%, compared to the 0.26% value attained for the metal centered excitation prior to ligand addition. In the terbium case, the smaller donor/acceptor gap enhances back transfer and the energy transfer is less efficient than with the curium system.

Assefa, Zerihun [Transuranium Chemistry Group, Chemical Sciences Division, Oak Ridge National Laboratory, MS 6375, Oak Ridge, TN 37831-6375 (United States)]. E-mail:; Yaita, T. [Department of Materials Science, Japan Atomic Energy Research Institute, Tokai (Japan); Haire, R.G. [Transuranium Chemistry Group, Chemical Sciences Division, Oak Ridge National Laboratory, MS 6375, Oak Ridge, TN 37831-6375 (United States); Tachimori, S. [Department of Materials Science, Japan Atomic Energy Research Institute, Tokai (Japan)



Stereospecific ligands and their complexes IX: Synthesis, characterization and antimicrobial activity of ethyl esters of ( S, S)ethylenediamine N, N?-di-2-propanoic and ( S, S)ethylenediamine N, N?-di-2-(3-methyl)-butanoic acids and corresponding platinum(IV) complexes: Crystal structure of tetrachloride-( O, O?-diethyl-( S, S)ethylenediamine N, N?-di-2-propanoato)-platinum(IV), [PtCl 4(det S, S-eddp)  

Microsoft Academic Search

The synthesis of ethyl esters of (S,S)-ethylenediamine-N,N?-di-2-propanoic and (S,S)-ethylenediamine-N,N?-di-2-(3-methyl)-butanoic acids and corresponding platinum(IV) complexes are reported. The complexes have been prepared by direct reaction of K2[PtCl6] and ethyl esters of the acids mentioned above. The esters and complexes were characterized by elemental microanalysis, infrared, 1H and 13C NMR spectroscopy. The spectroscopically predicted structures of the synthesized complexes were confirmed by

Milena Z. Stankovi?; Gordana P. Radi?; Verica V. Glo?ovi?; Ivana D. Radojevi?; Olgica D. Stefanovi?; Ljiljana R. ?omi?; Olivera R. Klisuri?; Vesna M. Djinovi?; Sre?ko R. Trifunovi?



Highly luminescent poly(methyl methacrylate)-incorporated europium complex supported by a carbazole-based fluorinated ?-diketonate ligand and a 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide co-ligand.  


A novel efficient antenna complex of Eu(3+) [Eu(CPFHP)(3)(DDXPO)] supported by a highly fluorinated carbazole-substituted ?-diketonate ligand, namely, 1-(9H-carbazol-2-yl)-4,4,5,5,5-pentafluoro-3-hydroxypent-2-en-1-one (CPFHP) and the 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide (DDXPO) ancillary ligand, has been synthesized, structurally characterized, and its photoluminescent behavior examined. The single-crystal X-ray diffraction analysis of Eu(CPFHP)(3)(DDXPO) revealed that this complex is mononuclear, and that the central Eu(3+) ion is surrounded by eight oxygen atoms, six of which are provided by the three bidentate ?-diketonate ligands. The remaining two oxygen atoms are furnished by the chelating phosphine oxide ligand. The coordination polyhedron is best described as that of a distorted square antiprism. The photophysical properties of Eu(CPFHP)(3)(DDXPO) benefit from adequate protection of the metal by the ligands with respect to non-radiative deactivation as well as an efficient ligand-to-metal energy transfer process which exceeds 66% in chloroform solution with a quantum yield of 47%. As an integral part of this work, the synthesis, characterization, and luminescent properties of poly(methyl methacrylate) (PMMA) polymer films doped with Eu(CPFHP)(3)(DDXPO) are also reported. The luminescent efficiencies of the doped films (photoluminescence quantum yields 79-84%) are dramatically enhanced in comparison with that of the precursor complex. The new luminescent PMMA-doped Eu(CPFHP)(3)(DDXPO) complex therefore shows considerable promise for polymer light-emitting diode and active polymer optical fiber applications. PMID:20831258

Raj, D B Ambili; Francis, Biju; Reddy, M L P; Butorac, Rachel R; Lynch, Vincent M; Cowley, Alan H



DNA Methylation, Nuclear Structure, Gene Expression and Cancer  

Microsoft Academic Search

DNA methylation, chromatin structure, transcription, and cancer have traditionally been studied as separate phenomena. Recent data provide now direct physical and functional links between these processes revealing a complex network of interactions and mutual dependences. Methylated DNA is bound by methyl-CpG binding protein (MeCP) complexes that include histone deacetylases (HDACs). This recruitment of HDACs is suggested to promote local chromatin

Heinrich Leonhardt; M. Cristina Cardoso



Versatile synthesis of P-chiral (ephedrine) AMPP ligands via their borane complexes. Structural consequences in Rh-catalyzed hydrogenation of methyl ?-acetamidocinnamate  

Microsoft Academic Search

An efficient and versatile synthesis of aminophosphine phosphinite (AMPP) ligands derived from ephedrine, with possible stereogenic P(III)-center(s) is described, using the borane complex methodology. The reaction of oxazaphospholidine borane with an organolithium reagent, leads to the formation of the ring-opened product, which is trapped by a chlorophosphine (borane), to afford the corresponding aminophosphine phosphinite boranes in good yields. Treatment of

Dominique Moulin; Christophe Darcel; Sylvain Jugé



Syntheses of monomeric (. eta. sup 5 -pentamethylcyclopentadienyl)platinum(IV) methyl and bromo complexes and of (hydrotris(3,5-dimethyl-1-pyrazolyl)borato)trimethylplatinum  

SciTech Connect

The reaction of Cp*MgCl{center dot}THF (Cp* = C{sub 5}Me{sub 5}) with 1 equiv of PtMe{sub 3}I and PtMe{sub 2}Br{sub 2} produces Cp*PtMe{sub 3} (1) and Cp*PtMe{sub 2}Br (2), respectively. Reaction of 2 with Br{sub 2} produces Cp*PtMeBr{sub 2} (3) in good yield. The structures of 2 and 3 have been determined by x-ray crystallography, and the crystal structure data are reported. Complex 2 crystallizes in the monoclinic space group, P2{sub 1}/m, and complex 3 crystallizes in the monoclinic space group, P2{sub 1}/m. The molecules reside on mirror planes and are monomeric pseudotetrahedral Pt(IV) complexes with piano stool type geometries and {eta}{sup 5}-Cp* groups. Both molecules have Br atoms on the mirror. This leads to a disorder of the Me and the second Br positions in complex 3. The average Pt-C(Cp*) bond length is 2.25 (7) {angstrom} in 2 and 2.22 (4) {angstrom} in 3. The Pt-C(Me) and Pt-Br bond lengths in 2 are 2.07 (2) and 2.498 (2) {angstrom}, respectively. The ordered Pt-Br bond length in 3 is 2.496 (2) {angstrom}. Treatment of 1 with halogens results in the cleavage of the Pt-Cp* bond. The reaction of PtMe{sub 3}I with KTp* (Tp* = (HB(3,5-dimethylpyrazolyl){sub 3}){sup {minus}}) in thf gives Tp*PtMe{sub 3} (4) in almost quantitative yield. The reaction of 4 with Br{sub 2} brominates the 4-position of the pyrazolyl ring only. 28 refs., 2 figs., 5 tabs.

Roth, S.; Ramamoorthy, V.; Sharp, P.R. (Univ. of Missouri, Columbia (USA))



Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln  

Microsoft Academic Search

Seven Sm proteins, termed B\\/B?, D1, D2, D3, E, F, and G, assemble in an ordered manner onto U snRNAs to form the Sm core of the spliceosomal snRNPs U1, U2, U4\\/U6, and U5 [1–4]. The survival of motor neuron (SMN) protein binds to Sm proteins and mediates in the context of a macromolecular (SMN-) complex the assembly of the

Gunter Meister; Christian Eggert; Dirk Bühler; Hero Brahms; Christian Kambach; Utz Fischer



Crystal structure, DNA binding studies, nucleolytic property and topoisomerase I inhibition of zinc complex with 1,10-phenanthroline and 3-methyl-picolinic acid.  


Crystal structure analysis of the zinc complex establishes it as a distorted octahedral complex, bis(3-methylpicolinato-kappa(2) N,O)(2)(1,10-phenanthroline-kappa(2) N,N)-zinc(II) pentahydrate, [Zn(3-Me-pic)(2)(phen)]x5H(2)O. The trans-configuration of carbonyl oxygen atoms of the carboxylate moieties and orientation of the two planar picolinate ligands above and before the phen ligand plane seems to confer DNA sequence recognition to the complex. It cannot cleave DNA under hydrolytic condition but can slightly be activated by hydrogen peroxide or sodium ascorbate. Circular Dichroism and Fluorescence spectroscopic analysis of its interaction with various duplex polynucleotides reveals its binding mode as mainly intercalation. It shows distinct DNA sequence binding selectivity and the order of decreasing selectivity is ATAT > AATT > CGCG. Docking studies lead to the same conclusion on this sequence selectivity. It binds strongly with G-quadruplex with human tolemeric sequence 5'-AG(3)(T(2)AG(3))(3)-3', can inhibit topoisomerase I efficiently and is cytotoxic against MCF-7 cell line. PMID:19787298

Seng, Hoi-Ling; Von, Sze-Tin; Tan, Kong-Wai; Maah, Mohd Jamil; Ng, Seik-Weng; Rahman, Raja Noor Zaliha Raja Abd; Caracelli, Ignez; Ng, Chew-Hee



MS-377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells.  


MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate) is a antipsychotic agent that binds to sigma-1 receptor. MS-377 showed anti-dopaminergic and anti-serotonergic activities and antagonistic action against phencyclidine (PCP)-induced behaviors in an animal model. These anti-psychotic activities of MS-377 are attributable to association with sigma-1 receptor. However, the mechanism by which the sigma-1 receptor ligands exact those numerous effects remains to be elucidated. In the present study, we evaluated the effect of MS-377 on N-methyl-D-aspartate (NMDA) receptor ion-channel complex in primary cultured rat neuronal cells. First, we examined the effect of MS-377 on NMDA-induced Ca2+ influx with fura-2/ AM loaded cells. MS-377 showed no effects on the basal Ca2+ concentration and NMDA-induced Ca2+ influx by itself PCP and SKF-10047 reduced the NMDA-induced increase in intracellular Ca2+ concentration. Pre-incubation of 1 microM MS-377 was found to significantly block the reduction by PCP or SKF-10047 of the NMDA-induced Ca2+ influx. Second, the effect of MS-377 on [3H]MK-801 intact cell binding was examined. PCP, haloperidol and (+)-pentazocine inhibited [3H]MK-801 binding, although MS-377 showed no effect by itself Pre-treatment of MS-377 markedly reversed the inhibition of [3H]MK-801 binding by PCP in a dose-dependent manner. These effects of MS-377 may depend on its affinity for the sigma-1 receptor, because MS-377 is a selective sigma-1 receptor ligand without any affinity for NMDA receptor ion-channel complex. These observations suggest that the MS-377 indirectly modulated the NMDA receptor ion-channel complex, and the anti-psychotic activities of MS-377, in part, are attributable to such on action via sigma-1 receptor. PMID:11991251

Karasawa, Jun-ichi; Yamamoto, Hideko; Yamamoto, Toshifumi; Sagi, Naoki; Horikomi, Kazutoshi; Sora, Ichiro



DNA-gelatin complex coacervation, UCST and first-order phase transition of coacervate to anisotropic ion gel in 1-methyl-3-octylimidazolium chloride ionic liquid solutions.  


Study of kinetics of complex coacervation occurring in aqueous 1-octyl-3-methylimidazolium chloride ionic liquid solution of low charge density polypeptide (gelatin A) and 200 base pair DNA, and thermally activated coacervate into anisotropic gel transition, is reported here. Associative interaction between DNA and gelatin A (GA) having charge ratio (DNA:GA = 16:1) and persistence length ratio (5:1) was studied at fixed DNA (0.005% (w/v)) and varying GA concentration (C(GA) = 0-0.25% (w/v)). The interaction profile was found to be strongly hierarchical and revealed three distinct binding regions: (i) Region I showed DNA-condensation (primary binding) for C(GA) < 0.10% (w/v), the DNA ? potential decrease from -80 to -5 mV (95%) (partial charge neutralization), and a size decrease by ?60%. (ii) Region II (0.10 < C(GA) < 0.15% (w/v)) indicated secondary binding, a 4-fold turbidity increase, a ? potential decrease from -5 to 0 mV (complete charge neutralization), which resulted in the appearance of soluble complexes and initiation of coacervation. (iii) Region III (0.15 < C(GA) < 0.25% (w/v)) revealed growth of insoluble complexes followed by precipitation. The hydration of coacervate was found to be protein concentration specific in Raman studies. The binding profile of DNA-GA complex with IL concentration revealed optimum IL concentration (=0.05% (w/v)) was required to maximize the interactions. Small angle neutron scattering (SANS) data of coacervates gave static structure factor profiles, I(q) versus wave vector q, that were remarkably similar and invariant of protein concentration. This data could be split into two distinct regions: (i) for 0.0173 < q < 0.0353 Å(-1), I(q) ~ q(-?) with ? = 1.35-1.67, and (ii) for 0.0353 < q < 0.35 Å(-1), I(q) = I(0)/(1 + q(2)?(2)). The correlation length found was ? = 2 ± 0.1 nm independent of protein concentration. The viscoelastic length (?8 nm) was found to have value close to the persistence length of the protein (?10 nm). Rheology data indicated that the coacervate phase resided close to the gelation state of the protein. Thus, on a heating-cooling cycle (heating to 50 °C followed by cooling to 20 °C), the heterogeneous coacervate exhibited an irreversible first-order phase transition to an anisotropic ion gel. This established a coacervate-ion gel phase diagram having a well-defined UCST. PMID:23194173

Rawat, Kamla; Aswal, V K; Bohidar, H B



Synthesis and coordination behaviors of 14-membered tetraaza macrocyclic copper(II) complexes bearing two N-propionic acid or N-propionic methyl ester groups  

Microsoft Academic Search

A di-N-functionalized 14-membered tetraaza macrocycle, [H4L3](ClO4)2 (L3=1,8-bis(2-carboxyethyl)-3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane), has been synthesized by acid hydrolysis of 1,8-bis(2-cyanoethyl)-3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane (L2). The copper(II) complexes [CuL2](ClO4)2 and [Cu(H2L3)](ClO4)2 were prepared and characterized. The complex [Cu(H2L3)]2+ readily reacts with methanol to yield [CuL4]2+ (L4=1,8-bis(2-carbomethoxyethyl)-3,5,7,7,10,12,14,14-octamethyl-1,4,8,11-tetraazacyclotetradecane). The N-CH2CH2COOH groups of [Cu(H2L3)](ClO4)2 are not coordinated to the metal ion in the solid state but are involved in coordination in various

Shin-Geol Kang; Ki-Seok Ryu; Kwanghee Nam; Jinkwon Kim



Deciphering arginine methylation: Tudor tells the tale.  


Proteins can be modified by post-translational modifications such as phosphorylation, methylation, acetylation and ubiquitylation, creating binding sites for specific protein domains. Methylation has pivotal roles in the formation of complexes that are involved in cellular regulation, including in the generation of small RNAs. Arginine methylation was discovered half a century ago, but the ability of methylarginine sites to serve as binding motifs for members of the Tudor protein family, and the functional significance of the protein-protein interactions that are mediated by Tudor domains, has only recently been appreciated. Tudor proteins are now known to be present in PIWI complexes, where they are thought to interact with methylated PIWI proteins and regulate the PIWI-interacting RNA (piRNA) pathway in the germ line. PMID:21915143

Chen, Chen; Nott, Timothy J; Jin, Jing; Pawson, Tony



High Rates of Microbial Methylation of Mercury Bound to Cysteine  

NASA Astrophysics Data System (ADS)

We know that methylation of inorganic mercury is effected by microbes in the anoxic layers of sediments and water columns. But the parameters that control the extent of this methylation are still poorly known. We show that mercury methylation by the versatile bacterium Geobacter sulfurreducens is greatly enhanced in the presence of low concentrations of the amino-acid cysteine. This enhancement results from complexation of inorganic mercury by cysteine, and bacterial uptake of the complex, followed by its efficient methylation and release to the external medium. Those results indicate that mercury uptake and methylation by microbes are under much tighter biological control than heretofore considered and that the formation of specific Hg complexes in anoxic waters likely modulate the efficiency of the microbial methylation of mercury.

Morel, F. M.; Schaefer, J. K.



DNA methylation in insects  

Microsoft Academic Search

Cytosine DNA methylation has been demonstrated in numerous eukaryotic organisms and has been shown to play an important role in human disease. The func- tion of DNA methylation has been studied extensively in vertebrates, but establishing its primary role has proved difficult and controversial. Analysing methyl- ation in insects has indicated an apparent functional diversity that seems to argue against

L. M. Field; F. Lyko; M. Mandrioli; G. Prantera



Comparative study on methyl- and ethylmercury-induced toxicity in C6 glioma cells and the potential role of LAT-1 in mediating mercurial-thiol complexes uptake.  


Various forms of mercury possess different rates of absorption, metabolism and excretion, and consequently, toxicity. Methylmercury (MeHg) is a highly neurotoxic organic mercurial. Human exposure is mostly due to ingestion of contaminated fish. Ethylmercury (EtHg), another organic mercury compound, has received significant toxicological attention due to its presence in thimerosal-containing vaccines. This study was designed to compare the toxicities induced by MeHg and EtHg, as well as by their complexes with cysteine (MeHg-S-Cys and EtHg-S-Cys) in the C6 rat glioma cell line. MeHg and EtHg caused significant (p<0.0001) decreases in cellular viability when cells were treated during 30min with each mercurial following by a washing period of 24h (EC50 values of 4.83 and 5.05?M, respectively). Significant cytotoxicity (p<0.0001) was also observed when cells were treated under the same conditions with MeHg-S-Cys and EtHg-S-Cys, but the respective EC50 values were significantly increased (11.2 and 9.37?M). l-Methionine, a substrate for the l-type neutral amino acid carrier transport (LAT) system, significantly protected against the toxicities induced by both complexes (MeHg-S-Cys and EtHg-S-Cys). However, no protective effects of l-methionine were observed against MeHg and EtHg toxicities. Corroborating these findings, l-methionine significantly decreased mercurial uptake when cells were exposed to MeHg-S-Cys (p=0.028) and EtHg-S-Cys (p=0.023), but not to MeHg and EtHg. These results indicate that the uptake of MeHg-S-Cys and EtHg-S-Cys into C6 cells is mediated, at least in part, through the LAT system, but MeHg and EtHg enter C6 cells by mechanisms other than LAT system. PMID:23727015

Zimmermann, Luciana T; Santos, Danúbia B; Naime, Aline A; Leal, Rodrigo B; Dórea, José G; Barbosa, Fernando; Aschner, Michael; Rocha, João Batista T; Farina, Marcelo



PAF1-complex-mediated histone methylation of FLOWERING LOCUS C chromatin is required for the vernalization-responsive, winter-annual habit in Arabidopsis.  


The winter-annual habit (which typically involves a requirement for exposure to the cold of winter to flower in the spring) in Arabidopsis thaliana is mainly due to the repression of flowering by relatively high levels of FLC expression. Exposure to prolonged cold attenuates FLC expression through a process known as vernalization and thus permits flowering to occur in the spring. Here we show that the elevated FLC expression characteristic of nonvernalized winter annuals requires two genes, EARLY FLOWERING 7 (ELF7) and EARLY FLOWERING 8 (ELF8), that are homologs of components of the PAF1 complex of Saccharomyces cerevisiae. Furthermore, ELF7 and ELF8 are also required for the expression of other genes in the FLC clade of flowering repressors such as MAF2 and FLM. FLC, FLM, and MAF2 are involved in multiple flowering pathways that account for the broad effects of elf7 and elf8 mutations on flowering behavior. ELF7 and ELF8 are required for the enhancement of histone 3 trimethylation at Lys 4 in FLC chromatin. This modification of FLC chromatin appears to be required to elevate FLC expression to levels that can delay flowering in plants that have not been vernalized. A model of the role of ELF7, ELF8, and other previously described genes in the modification of the chromatin of flowering repressors is presented. PMID:15520273

He, Yuehui; Doyle, Mark R; Amasino, Richard M



PAF1-complex-mediated histone methylation of FLOWERING LOCUS C chromatin is required for the vernalization-responsive, winter-annual habit in Arabidopsis  

PubMed Central

The winter-annual habit (which typically involves a requirement for exposure to the cold of winter to flower in the spring) in Arabidopsis thaliana is mainly due to the repression of flowering by relatively high levels of FLC expression. Exposure to prolonged cold attenuates FLC expression through a process known as vernalization and thus permits flowering to occur in the spring. Here we show that the elevated FLC expression characteristic of nonvernalized winter annuals requires two genes, EARLY FLOWERING 7 (ELF7) and EARLY FLOWERING 8 (ELF8), that are homologs of components of the PAF1 complex of Saccharomyces cerevisiae. Furthermore, ELF7 and ELF8 are also required for the expression of other genes in the FLC clade of flowering repressors such as MAF2 and FLM. FLC, FLM, and MAF2 are involved in multiple flowering pathways that account for the broad effects of elf7 and elf8 mutations on flowering behavior. ELF7 and ELF8 are required for the enhancement of histone 3 trimethylation at Lys 4 in FLC chromatin. This modification of FLC chromatin appears to be required to elevate FLC expression to levels that can delay flowering in plants that have not been vernalized. A model of the role of ELF7, ELF8, and other previously described genes in the modification of the chromatin of flowering repressors is presented.

He, Yuehui; Doyle, Mark R.; Amasino, Richard M.



Synthesis, spectroscopic characterization and X-ray structure determinations and packing of tetralkylammonium trans-diamminetetranitrocobaltate(III) complex salts where alkyl=methyl or ethyl  

NASA Astrophysics Data System (ADS)

The two cobalt(III) complex salts [(CH3)4N][trans-Co(NH3)2(NO2)4] (I) and [(C2H5)4N][trans-Co(NH3)2(NO2)4] (II) have been synthesized in high yields by reacting equimolar quantities of [(CH3)4N]Br and [(C2H5)4N]Cl with K[trans-Co(NH3)2(NO2)4], respectively in aqueous medium at room temperature. The salt I crystallized with monoclinic space group P 21/m having cell dimensions a=6.1926(7), b=18.248(3), c=6.2335(6) Å, ?=90.078(7)°, V=704.41(16) Å3, Z=2, R=0.0868 and the salt II crystallized with monoclinic space group P 21/c having cell dimensions a=10.2635(18), b=9.0480(15), c=9.752(2) Å, ?=104.493(12)°, V=876.8(3) Å3, Z=2, R=0.0408. X-ray structure determination revealed the presence of discrete ions, [(CH3)4N]+ and [trans-Co(NH3)2(NO2)4]- in I and [(C2H5)4N]+ and [trans-Co(NH3)2(NO2)4]- in II. In the anion, the central metal atom cobalt(III) is octahedrally surrounded in trans geometry. The crystal lattice is stabilized by electrostatic forces of attractions and hydrogen bonding interactions in I. These are the first X-ray structures of salts containing the tetralkylammonium cations and the anion [trans-Co(NH3)2(NO2)4]-. The packing diagrams show a layered structures in the two salts.

Sharma, Raj Pal; Vermani, Bal Krishan; Sharma, Rajni; Bala, Ritu; Gill, Dip Singh; Salas, Juan M.; Quiros, Miguel



The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation  

PubMed Central

Many steps in gene expression and mRNA biosynthesis are coupled to transcription elongation and organized through the C-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAPII). We showed recently that Spt6, a transcription elongation factor and histone H3 chaperone, binds to the Ser2P CTD and recruits Iws1 and the REF1/Aly mRNA export adaptor to facilitate mRNA export. Here we show that Iws1 also recruits the HYPB/Setd2 histone methyltransferase to the RNAPII elongation complex and is required for H3K36 trimethylation (H3K36me3) across the transcribed region of the c-Myc, HIV-1, and PABPC1 genes in vivo. Interestingly, knockdown of either Iws1 or HYPB/Setd2 also enhanced H3K27me3 at the 5? end of the PABPC1 gene, and depletion of Iws1, but not HYPB/Setd2, increased histone acetylation across the coding regions at the HIV-1 and PABPC1 genes in vivo. Knockdown of HYPB/Setd2, like Iws1, induced bulk HeLa poly(A)+ mRNAs to accumulate in the nucleus. In vitro, recombinant Spt6 binds selectively to a stretch of uninterrupted consensus repeats located in the N-terminal half of the CTD and recruits Iws1. Thus Iws1 connects two distinct CTD-binding proteins, Spt6 and HYPB/Setd2, in a megacomplex that affects mRNA export as well as the histone modification state of active genes.

Yoh, Sunnie M.; Lucas, Joseph S.; Jones, Katherine A.



Five- and Six-Coordinate 2-Methyl-2-propanethiolato Complexes of Zirconium(IV): Synthesis and Structures of [Li(DME)(3)][Zr(SCMe(3))(5)] and [(THF)Li](2)Zr(SCMe(3))(6).  


Five-coordinate and six-coordinate 2-methyl-2-propanethiolato complexes of zirconium, [Li(DME)(3)][Zr(SCMe(3))(5)] (1) and [(THF)Li](2)Zr(SCMe(3))(6) (2), were obtained from the ZrCl(4)/LiSCMe(3) reaction system. The control of the Zr coordination number, by the ether ligands, THF or DME, bound to Li, is demonstrated by the conversion of 2 into 1 upon dissolution in DME. 1 and 2 were crystallographically characterized. The structures are extensively disordered. Crystal data follow: 1, hexagonal P6(3)/m, a = b = 12.496(3) Å, c = 17.561(9) Å, Z = 2, V = 2375(1) Å(3), R = 5.0%, R(w) = 6.8%; 2, trigonal R32, a = b = 11.813(3) Å, c = 28.37(1) Å, Z = 3, V = 3428(1) Å(3), R = 5.2%, R(w) = 6.4%. PMID:11666656

Kawaguchi, Hiroyuki; Tatsumi, Kazuyuki; Cramer, Roger E.



Crystal structures of cytochrome P450 2B4 in complex with the inhibitor 1-biphenyl-4-methyl-1H-imidazole: ligand induced structural response through ?-helical repositioning†‡  

PubMed Central

Two different ligand occupancy structures of cytochrome P450 2B4 (CYP2B4) in complex with 1-biphenyl-4-methyl-1H–imidazole (1-PBI) have been solved by x-ray crystallography. 1-PBI belongs to a series of tight binding, imidazole-based CYP2B4 inhibitors. 1-PBI binding to CYP2B4 yields a type II spectrum with a Ks value of 0.23 µM and inhibits enzyme activity with an IC50 value of 0.035 µM. Previous CYP2B4 structures have shown a large degree of structural movement in response to ligand size. With two phenyl rings, 1-PBI is larger than 1-(4-chlorophenyl)imidazole (1-CPI) and 4-(4-chlorophenyl)imidazole (4-CPI) but smaller than bifonazole, which is branched and contains three phenyl rings. The CYP2B4:1-PBI complex is a structural intermediate to the closed CPI and the open bifonazole structures. The B/C loop reorganizes itself to include two short partial helices while closing one side of the active site. The F-G helix cassette pivots over the I-helix in direct response to the size of the ligand in the active site. A cluster of Phe residues at the fulcrum of this pivot point allows for dramatic repositioning of the cassette with only a relatively small amount of secondary structure rearrangement. Comparisons of ligand bound CYP2B4 structures reveal trends in plastic region mobility that could allow for predictions of their position in future structures based on ligand shape and size.

Gay, Sean C.; Sun, Ling; Maekawa, Keiko; Halpert, James R.; Stout, C. David



On how mammalian transcription factors recognize methylated DNA  

PubMed Central

DNA methylation is an epigenetic mark that is essential for the development of mammals; it is frequently altered in diseases ranging from cancer to psychiatric disorders. The presence of DNA methylation attracts specialized methyl-DNA binding factors that can then recruit chromatin modifiers. These methyl-CpG binding proteins (MBPs) have key biological roles and can be classified into three structural families: methyl-CpG binding domain (MBD), zinc finger, and SET and RING finger-associated (SRA) domain. The structures of MBD and SRA proteins bound to methylated DNA have been previously determined and shown to exhibit two very different modes of methylated DNA recognition. The last piece of the puzzle has been recently revealed by the structural resolution of two different zinc finger proteins, Kaiso and ZFP57, in complex with methylated DNA. These structures show that the two methyl-CpG binding zinc finger proteins adopt differential methyl-CpG binding modes. Nonetheless, there are similarities with the MBD proteins suggesting some commonalities in methyl-CpG recognition across the various MBP domains. These fresh insights have consequences for the analysis of the many other zinc finger proteins present in the genome, and for the biology of methyl-CpG binding zinc finger proteins.

Buck-Koehntop, Bethany A.; Defossez, Pierre-Antoine



Palladium(II) complexes with R(2)edda derived ligands. Part IV. O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid dihydrochloride and their palladium(II) complexes: synthesis, characterization and in vitro antitumoral activity against chronic lymphocytic leukemia (CLL) cells.  


Four novel bidentate N,N'-ligand precursors, including O,O'-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), L1 x 2 HCl-L4 x 2 HCl, of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid dihydrochloride [(S,S)-H(4)eddl]Cl(2) and the corresponding palladium(II) complexes 1-4, were prepared and characterized by IR, (1)H NMR and (13)C NMR spectroscopy and elemental analysis. In vitro cytotoxicity of all compounds was determined against chronic lymphocytic leukemia cells (CLL). The compounds were found to exhibit higher antitumoral activity than cisplatin. The most active compound 2, [PdCl(2){(S,S)-nPr(2)eddl}], was found to be 13.6 times more active than cisplatin on CLL cells. PMID:20570025

Vuji?, Jelena M; Cvijovi?, Milica; Kaluderovi?, Goran N; Milovanovi?, Marija; Zmejkovski, Bojana B; Volarevi?, Vladislav; Arsenijevi?, Nebojsa; Sabo, Tibor J; Trifunovi?, Sre?ko R



Structural Basis for Methyl Transfer by a Radical SAM Enzyme  

SciTech Connect

The radical S-adenosyl-l-methionine (SAM) enzymes RlmN and Cfr methylate 23S ribosomal RNA, modifying the C2 or C8 position of adenosine 2503. The methyl groups are installed by a two-step sequence involving initial methylation of a conserved Cys residue (RlmN Cys{sup 355}) by SAM. Methyl transfer to the substrate requires reductive cleavage of a second equivalent of SAM. Crystal structures of RlmN and RlmN with SAM show that a single molecule of SAM coordinates the [4Fe-4S] cluster. Residue Cys{sup 355} is S-methylated and located proximal to the SAM methyl group, suggesting the SAM that is involved in the initial methyl transfer binds at the same site. Thus, RlmN accomplishes its complex reaction with structural economy, harnessing the two most important reactivities of SAM within a single site.

Boal, Amie K.; Grove, Tyler L.; McLaughlin, Monica I.; Yennawar, Neela H.; Booker, Squire J.; Rosenzweig, Amy C. (NWU); (Penn)



49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.  

Code of Federal Regulations, 2012 CFR

...and methyl bromide or methyl chloride mixtures, etc. 173.193 Section 173.193...and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone must...bromide, chloropicrin and methyl bromide mixtures, chloropicrin and methyl chloride...



Uranyl sequestering agents: Correlation of properties and efficacy with structure for UO{sub 2}{sup 2+} complexes of linear tetradentate 1-methyl-3-hydroxy-2(1H)-pyridinone ligands  

SciTech Connect

A rational design of uranyl sequestering agents based on 3-hydroxy-2(1H)-pyridinone ligands has resulted in the first effective agents for mammalian uranyl decorporation. In this study crystal structures of uranyl complexes with four of these agents are compared and correlated with the chemical and biological properties. These hydroxypyridinone ligands bind the uranyl ion in the equator of a pentagonal prism; a solvent molecule fills the fifth coordination site. The tetradentate ligands are composed of two hydroxypyridonate groups connected by a diamine linker via amide coupling. The dihedral angles between two pyridinone ring planes in these complexes differ as the length of linear backbone changes, giving these molecules a ruffled shape. The physical parameters (such as NMR chemical shifts) of the uranyl complexes with tetradentate Me-3,2-HOPO ligands correlate with the length of the diamine linker, as does the in vivo activity. The ligands are amides of 3-hydroxy-N-methyl-2-(1H)-4-carboxypyridone. For L{sup 1} the amine is propane amine. For the tetradentate bis-amides the linker groups are (L{sup 3}) 1,3-diaminopropane, (L{sup 4}) 1,4-diaminobutane, (L{sup 5}) 1,5-diaminopentane. Crystal data: [UO{sub 2}(L{sup 1}){sub 2}{center_dot}DMF], space group, C2/c, cell constants: a = 37.430(8) {angstrom}, b = 7.0808(14) {angstrom}, c = 26.781(5) {angstrom}, {beta} = 130.17(3){degree}, V = 5424(2) {angstrom}{sup 3}, Z = 8. [UO{sub 2}L{sup 3}{center_dot}DMSO], Pnma, a = 8.4113(1) {angstrom}, b = 16.0140(3) {angstrom}, c = 16.7339(3) {angstrom}, V = 2254.03(5) {angstrom}{sup 3}, Z = 4. [UO{sub 2}L{sup 4}{center_dot}DMSO]{center_dot}DMSO{center_dot}H{sub 2}O{center_dot}0.5C{sub 6}H{sub 12}, P2{sub 1}/n, a = 26.7382(4) {angstrom}, b = 7.4472(1) {angstrom}, c = 31.4876(2) {angstrom}, V = 6209.05(13) {angstrom}{sup 3}, Z = 8. [UO{sub 2}L{sup 5}{center_dot}DMSO]{center_dot}DMSO, Pnma, a = 7.3808(1) {angstrom}, b = 14.7403(3) {angstrom}, c = 23.134(3) {angstrom}, V = 2516.88(8) {angstrom}{sup 3}, Z = 4.

Xu, J. Raymond, K.N. [Lawrence Berkeley National Lab., CA (United States)



Use of electrochemical transient techniques to obtain thermodynamic and kinetic data on aqueous Fe(III)-1,6-dimethyl-4-hydroxy-3-pyridinecarboxylate and Fe(III)-4-hydroxy-2-methyl-3-pyridinecarboxylate complexes.  


Voltammetric experiments were used to demonstrate the possibility to rapidly obtain stability constants, E degrees values and kinetic parameters of Fe(III) complexes with 1,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ716) at pH 2.3 and 4-hydroxy-2-methyl-3-pyridinecarboxylic acid (DQ2) at pH 3. Fe(III) diffusion coefficient (D(Fe)= 5.5.10(-6) cm(2)/s), heterogeneous electron transfer kinetic constant (k degrees = 2.7.10(-4)cm/s), symmetry coefficient (alpha= 0.57) and Fe(III)/Fe(II) standard reduction potential (E degrees = 0.53 V vs. SCE) were determined beforehand and used to obtain all the other results. Digital simulation together with potentiometric data were used to define the whole reaction system in terms of thermodynamic and kinetic parameters. In particular, E degrees and the dissociation kinetic constant, k(b), of the 1:1 (E degrees = 0.22 V vs. SCE, k(b)= 0.032 s(-1)), 1:2 (E degrees = 0.098 V vs. SCE; k(b)= 0.22 s(-1)) and 1:3 (E degrees < or =-0.29 V vs. SCE, k(b)= 157.9 s(-1)) Fe(III)/DQ716 complexes, were estimated. Stability constants of the Fe(II) complexes were computed from these values. The voltammetric data were also interpreted with two independent formalisms: (1) solution of an equation system and (2) a curve fitting method based on the Koutecky-Levich equation. Both approaches allowed us to obtain the speciation of a Fe(III)/DQ716 solution at pH 2.3. Moreover, the second approach allowed the evaluation of the kinetic contributions, the stepwise stability constant of Fe(III)L(2) (7.65 +/- 0.07), and to define the mathematical formalization of the experimental result which link some key-points of the voltammetric curve (inflection points and plateaux) to D(Fe), k degrees , alpha(j) and E degrees . This approach was also successfully applied to obtain the speciation of a Fe(III)/DQ2 solution at pH 3. PMID:19290376

Badocco, Denis; Marcon, Moreno; Mondin, Andrea; Dean, Annalisa; Di Marco, Valerio B; Pastore, Paolo



Employment of methyl 2-pyridyl ketone oxime in 3d/4f-metal chemistry: dinuclear nickel(II)/lanthanide(III) species and complexes containing the metals in separate ions.  


The use of methyl 2-pyridyl ketone oxime (mpkoH) for the synthesis of Ni(II)/Ln(III) (Ln = lanthanide) complexes, using "one-pot" reactions in the absence of an external base, is described. Depending on the reaction and crystallization conditions employed, two families of complexes have been obtained. The first family consists of true heterometallic species and involves complexes [NiLn(mpko)(3)(mpkoH)(3)](ClO(4))(2), where Ln = Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho and Er. The second family contains the pseudo heterometallic complexes [Ni(mpkoH)(3)](2)[Ln(NO(3))(6)](ClO(4)), where Ln = La, Ce, Pr, Nd and Sm. The crystal structures of [NiCe(mpko)(3)(mpkoH)(3)](ClO(4))(2) (1), [NiDy(mpko)(3)(mpkoH)(3)](ClO(4))(2) (8) and [Ni(mpkoH)(3)](2)[La(NO(3))(6)](ClO(4)) (11) have been determined by single-crystal, X-ray crystallography. Complexes 1·1.2MeOH·0.6H(2)O and 8·1.2MeOH·0.6H(2)O crystallise in the monoclinic space group P2(1)/a and are isomorphous; there are two crystallographically independent cations in the unit cell, but their interatomic distances and angles differ little. The Ni(II) and Ln(III) ions are bridged by three oximate groups belonging to the ?(1):?(1):?(1):? mpko(-) ligands. The Ni(II) centre is octahedrally coordinated by the six nitrogen atoms of the mpko(-) ligands in a facial arrangement. The Ln(III) centre is bound to an (O(oximate))(3)N(6) set of donor atoms, the nitrogen atoms belonging to the three N,N'-bidentate chelating mpkoH ligands. The stereochemistry of the Ln(III) atoms has been evaluated by means of continuous shape measures (CShM). The two crystallographically independent Ce(III) atoms in 1 have tricapped trigonal prismatic and capped square antiprismatic coordination geometries, while the polyhedra of the Dy(III) atoms in 8 are both close to a tricapped trigonal prism. The octahedral Ni(II) atoms in 11 are both facially bound to a N(6) set of donor atoms from three N,N'-bidentate chelating mpkoH ligands, while the 12-coordinate La(III) centre in [La(NO(3))(6)](3-) is coordinated by six bidentate chelating nitrato groups. Variable-temperature, solid state dc magnetic susceptibility studies were carried out on complexes 2, 6, 7 and 8. The dc susceptibility data for 6 in the 2.0-300 K range have been fit to a model with one J value, revealing an antiferromagnetic Ni(II)···Gd(III) exchange interaction [J = -1.1 cm(-1) based on H = -J (?(Ni)·?(Gd))]. Antiferromagnetic Ni(II)···Pr(III), Ni(II)···Tb(III) and Ni(II)···Dy(III) exchange interactions have also been suggested for 2, 7 and 8, respectively. The combined work demonstrates the usefulness of mpko(-) in the preparation of interesting Ni(II)/Ln(III) compounds, without requiring the presence of external base and ancillary organic ligands. PMID:23069731

Polyzou, Christina D; Nikolaou, Helen; Papatriantafyllopoulou, Constantina; Psycharis, Vassilis; Terzis, Aris; Raptopoulou, Catherine P; Escuer, Albert; Perlepes, Spyros P



DNA Methylation Profiling Identifies CG Methylation Clusters in Arabidopsis Genes  

Microsoft Academic Search

Cytosine DNA methylation in vertebrates is widespread, but methylation in plants is found almost exclusively at transposable elements and repetitive DNA [1]. Within regions of methylation, methylcytosines are typically found in CG, CNG, and asymmetric contexts. CG sites are maintained by a plant homolog of mammalian Dnmt1 acting on hemi-methylated DNA after replication. Methylation of CNG and asymmetric sites appears

Robert K. Tran; Jorja G. Henikoff; Daniel Zilberman; Renata F. Ditt; Steven E. Jacobsen; Steven Henikoff



Orchestration of DNA Methylation  

Microsoft Academic Search

DNA methylation plays an important role in gene regulation. In order to gain a better understanding of the rules governing\\u000a this epigenetic modification, we have used microarray technology to map DNA methylation in the human genome. This analysis\\u000a has helped decipher the DNA sequences involved in setting up the basic global methylation pattern in the early embryo and\\u000a has revealed

Howard Cedar



H3K36 methylation antagonizes PRC2-mediated H3K27 methylation.  


H3K27 methylation mediated by the histone methyltransferase complex PRC2 is critical for transcriptional regulation, Polycomb silencing, Drosophila segmentation, mammalian X chromosome inactivation, and cancer. PRC2-mediated H3K27 methylation can spread along the chromatin and propagate the repressive chromatin environment; thus, chromatin components that antagonize the activity of PRC2 are important for restraining Polycomb silencing. Here we report that in HeLa cells, H3 histones unmethylated at Lys-36 are mostly methylated at Lys-27, with the exception of newly synthesized H3. In addition, K27me3 rarely co-exists with K36me2 or K36me3 on the same histone H3 polypeptide. Moreover, PRC2 activity is greatly inhibited on nucleosomal substrates with preinstalled H3K36 methylation. These findings collectively identify H3K36 methylation as a chromatin component that restricts the PRC2-mediated spread of H3K27 methylation. Finally, we provide evidence that the controversial histone lysine methyltransferase Ash1, a known Trithorax group protein that antagonizes Polycomb silencing in vivo, is an H3K36-specific dimethylase, not an H3K4 methylase, further supporting the role of H3K36 methylation in antagonizing PRC2-mediated H3K27 methylation. PMID:21239496

Yuan, Wen; Xu, Mo; Huang, Chang; Liu, Nan; Chen, She; Zhu, Bing



Profile of Histone Lysine Methylation across Transcribed Mammalian Chromatin  

Microsoft Academic Search

Complex patterns of histone lysine methylation encode distinct functions within chromatin. We previously reported that trimethylation of lysine 9 of histone H3 (H3K9) occurs at both silent heterochromatin and at the transcribed regions of active mammalian genes, suggesting that the extent of histone lysine methylation involved in mammalian gene activation is not completely defined. To identify additional sites of histone

Christopher R. Vakoc; Mira M. Sachdeva; Hongxin Wang; Gerd A. Blobel



MIRA-Assisted Microarray Analysis, a New Technology for the Determination of DNA Methylation Patterns, Identifies Frequent Methylation of Homeodomain-Containing Genes in Lung Cancer Cells  

Microsoft Academic Search

We present a straightforward and comprehensive approach for DNA methylation analysis in mammalian genomes. The methylated-CpG island recovery assay (MIRA), which is based on the high affinity of the MBD2\\/MBD3L1 complex for methylated DNA, has been used to detect cell type-dependent differences in DNA methylation on a microarray platform. The procedure has been verified and applied to identify a series

Tibor Rauch; Hongwei Li; Xiwei Wu; Gerd P. Pfeifer


Metal complexes of 1-hydroxy-2,3-dimethyl-4-(3?-methyl-4?-amino-5?-mercapto-1?, 2?, 4?-triazole)-1,4-diaza-1, 3-butadiene with manganese(II), cobalt(II), nickel(II) and copper(II)  

Microsoft Academic Search

Summary Binuclear metal complexes of the type [M(HDDB)-(H2O)2]2: where HDDB=1-hydroxy-2,3-dimethyl-4-(3'-methyl-4'-amino-5'-mercapto-1', 2', 4'-triazole)-1,4-diaza-1, 3-butadiene and M=manganese(II), cobalt(II), nickel(II) and copper(II), have been prepared and characterised by elemental and thermal analyses, magnetic measurements, electronic and i.r. spectra. Octahedral geometry around the metal(II) ions is proposed and the crystal field parameters of the cobalt(II) and nickel(II) complexes are also calculated. Fungicidal screening of

Krishna Chandra Satpathy; Ashok Kumar Panda; Rushabha Mishra; Indumati Panda; Aditya Prasad Chopdar



Simultaneous chiral separation of leucovorin and its major metabolite 5-methyl-tetrahydrofolate by capillary electrophoresis using cyclodextrins as chiral selectors: Estimation of the formation constant and mobility of the solute-cyclodextrin complexes  

Microsoft Academic Search

Capillary electrophoresis with an electrolyte containing cyclodextrin was investigated for the simultaneous separation of the diastereoisomers of 6R,S-leucovorin and its active metabolite 6R,S-5-methyl-tetrahydrofolate. ?, ? and ?-cyclodextrin separated the diastereoisomers of 5-methyl-tetrahydrofolate, while only ?-cyclodextrin was found to be effective for the chiral separation of leucovorin. The effect of ?-cyclodextrin concentration was investigated, and subsequently a curve-fitting analysis for the

A. Shibukawa; D. K. Lloyd; I. W. Wainer



Kinetics and mechanism of the reaction of palladium(II) complexes of o-(diphenylphosphino)thioanisole and o-(diphenylphosphino)selenoanisole with nucleophiles thiocyanate and iodide. Carbon-13 NMR spectroscopy of the methyl-heteroatom complexes and x-ray structural characterization of diiodobis(o-(diphenylphosphino)benzenethiolato)dipalladium(II)  

SciTech Connect

The kinetics of the reaction of the nucleophiles thiocyanate and iodide with complexes PdX/sub 2/(o-MeSC/sub 6/H/sub 4/PPh/sub 2/) (X = SCN, I) show a rate law rate = k/sub 2/(PdX/sub 2/(o-MeSC/sub 6/H/sub 4/PPh/sub 2/))(X/sup -/). Second-order rate constants k/sub 2/ for the thiocyanate reaction have been measured, and the activation parameters + +/ and + +/ are 22.9 +- 1.0 kcal/mol and -9.2 +- 2.1 cal/mol. For the selenium analogue complex these respective values are 18.9 +- 1.3 kcal/mol and -12.9 +- 2.3 cal/mol. With iodide as nucleophile an equilibrium condition is established. Rates are calculated from the data both for the demethylation and for the reverse addition of methyl iodide. The alkylation reaction is approximately 50 times faster. The product from the iodide demethylation reaction is considered to be the anion (PdI/sub 2/(o-SC/sub 6/H/sub 4/PPh/sub 2/))/sup -/ on the basis of visible spectroscopy. The mechanism of the nucleophile-induced demethylation reaction resembles the Zeisel ether cleavage.

Roundhill, D.M.; Roundhill, S.G.N.; Beaulieu, W.B.; Bagchi, U.



Genome-scale DNA methylation analysis  

PubMed Central

The haploid human genome contains approximately 29 million CpGs that exist in a methylated, hydroxymethylated or unmethylated state, collectively referred to as the DNA methylome. The methylation status of cytosines in CpGs and occasionally in non-CpG cytosines influences protein–DNA interactions, gene expression, and chromatin structure and stability. The degree of DNA methylation at particular loci may be heritable transgenerationally and may be altered by environmental exposures and diet, potentially contributing to the development of human diseases. For the vast majority of normal and disease methylomes however, less than 1% of the CpGs have been assessed, revealing the formative stage of methylation mapping techniques. Thus, there is significant discovery potential in new genome-scale platforms applied to methylome mapping, particularly oligonucleotide arrays and the transformative technology of next-generation sequencing. Here, we outline the currently used methylation detection reagents and their application to microarray and sequencing platforms. A comparison of the emerging methods is presented, highlighting their degrees of technical complexity, methylome coverage and precision in resolving methylation. Because there are hundreds of unique methylomes to map within one individual and interindividual variation is likely to be significant, international coordination is essential to standardize methylome platforms and to create a full repository of methylome maps from tissues and unique cell types.

Fouse, Shaun D; Nagarajan, Raman P; Costello, Joseph F



Inhibition of methylation and changes in gene expression in relation to neural tube defects  

Microsoft Academic Search

BACKGROUND: An impaired DNA methylation has been suggested to underlie the complex etiology of neural tube defects (NTDs). Previously, we have demonstrated that inhibition of methylation by periodate oxidized adenosine (Adox) results in a widening of the anterior neuropore (ANP) in our in vitro chick embryo model. Since DNA methylation is the chief regulator of gene expression, we hypothesize that

Ivon J. M. van der Linden; Sandra G. Heil; Egmont-Petersen van M; Henny W. van Straaten; Martin den Heijer; Henk J. Blom



Methylation of DNA  

PubMed Central

The methylated bases of DNA are formed by the transfer of the methyl group from S-adenosylmethionine to a polynucleotide acceptor. This transfer is catalyzed by highly specific enzymes which recognize a limited number of available sites in the DNA. The mechanism for the recognition is presently unknown. In some instances, there is evidence that other cellular components, such as lipopolysaccharides, can influence the methylation reaction. Certain bacteriophages induce new methylases upon infection of their hosts. Phage T3 is unique in establishing an environment in which methylation of neither the phage nor the host nucleic acid can occur. By superinfecting T3-infected cells with other phages, the latter can be obtained with methyl-deficient DNA. Although a great deal is known about the enzymology of the methylation reaction, and there appears to be a strong correlation between the in vitro and in vivo reactions, studies in which DNA is either supermethylated or totally unmethylated have not yielded any insight as to what the possible function of the methylated bases may be.

Gold, Marvin; Gefter, Malcolm; Hausmann, Rudolph; Hurwitz, Jerard



Recognition of methylated DNA through methyl-CpG binding domain proteins  

PubMed Central

DNA methylation is a key regulatory control route in epigenetics, involving gene silencing and chromosome inactivation. It has been recognized that methyl-CpG binding domain (MBD) proteins play an important role in interpreting the genetic information encoded by methylated DNA (mDNA). Although the function of MBD proteins has attracted considerable attention and is well characterized, the mechanism underlying mDNA recognition by MBD proteins is still poorly understood. In this article, we demonstrate that the methyl-CpG dinucleotides are recognized at the MBD–mDNA interface by two MBD arginines through an interplay of hydrogen bonding and cation-? interaction. Through molecular dynamics and quantum-chemistry calculations we investigate the methyl-cytosine recognition process and demonstrate that methylation enhances MBD–mDNA binding by increasing the hydrophobic interfacial area and by strengthening the interaction between mDNA and MBD proteins. Free-energy perturbation calculations also show that methylation yields favorable contribution to the binding free energy for MBD–mDNA complex.

Zou, Xueqing; Ma, Wen; Solov'yov, Ilia A.; Chipot, Christophe; Schulten, Klaus



49 CFR 173.193 - Bromoacetone, methyl bromide, chloropicrin and methyl bromide or methyl chloride mixtures, etc.  

Code of Federal Regulations, 2011 CFR

...chloropicrin and methyl bromide or methyl chloride mixtures, etc. 173.193 Section...chloropicrin and methyl bromide or methyl chloride mixtures, etc. (a) Bromoacetone...bromide mixtures, chloropicrin and methyl chloride mixtures, and chloropicrin...



Reactions of Ionized Methyl Benzoate with Methyl Isocyanide in the Gas Phase: Nucleophilic Aromatic Substitutions vs Hydrogen Migrations  

NASA Astrophysics Data System (ADS)

The chemistry leading to the competitive eliminations of H, CH3, and OCOCH3 from adducts of ionized methyl benzoate and neutral methyl isocyanide has been explored using density functional theory molecular orbital calculations. The energies of the various reactants and transition structures were estimated at the B3LYP/6-31+G(d,p) level of theory. Nucleophilic aromatic substitution is proposed to account for the H and OCOCH3 eliminations. The corresponding ?-complex intermediates, B1ipso and B1ortho, are stable species lying in deep energy wells situated 70 and 120 kJ/mol, respectively, below the reactants, ionized methyl benzoate and methyl isocyanide. The latter complex, B1ortho, may be also at the origin of a multistep rearrangement involving hydrogen migrations and methyl elimination from the original methoxy group of the benzoate moiety.

Bouchoux, Guy; Flammang, Robert; Winter, Julien De; Gerbaux, Pascal



Smyd2 controls cytoplasmic lysine methylation of Hsp90 and myofilament organization  

PubMed Central

Protein lysine methylation is one of the most widespread post-translational modifications in the nuclei of eukaryotic cells. Methylated lysines on histones and nonhistone proteins promote the formation of protein complexes that control gene expression and DNA replication and repair. In the cytoplasm, however, the role of lysine methylation in protein complex formation is not well established. Here we report that the cytoplasmic protein chaperone Hsp90 is methylated by the lysine methyltransferase Smyd2 in various cell types. In muscle, Hsp90 methylation contributes to the formation of a protein complex containing Smyd2, Hsp90, and the sarcomeric protein titin. Deficiency in Smyd2 results in the loss of Hsp90 methylation, impaired titin stability, and altered muscle function. Collectively, our data reveal a cytoplasmic protein network that employs lysine methylation for the maintenance and function of skeletal muscle.

Donlin, Laura T.; Andresen, Christian; Just, Steffen; Rudensky, Eugene; Pappas, Christopher T.; Kruger, Martina; Jacobs, Erica Y.; Unger, Andreas; Zieseniss, Anke; Dobenecker, Marc-Werner; Voelkel, Tobias; Chait, Brian T.; Gregorio, Carol C.; Rottbauer, Wolfgang; Tarakhovsky, Alexander; Linke, Wolfgang A.




EPA Science Inventory

Enzymology of Arsenic Methylation David J. Thomas, Pharmacokinetics Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park...


Favoritism in DNA methylation.  


This perspective on Candiloro and Dobrovic (beginning on p. 862 in this issue of the journal) highlights the interplay between epigenetic aberrations and underlying DNA sequence changes and illustrates how these alterations may predispose individuals to cancer. Candiloro and Dobrovic clearly show that particular genotypes of the MGMT gene are associated with its methylation in healthy individuals. Aberrant MGMT methylation may identify individuals who could be targeted for cancer screening and chemoprevention strategies. PMID:19789293

Hitchins, Megan P; Ward, Robyn L



DNA methylation and differentiation.  

PubMed Central

The methylation of specific cytosine residues in DNA has been implicated in regulating gene expression and facilitating functional specialization of cellular phenotypes. Generally, the demethylation of certain CpG sites correlates with transcriptional activation of genes. 5-Azacytidine is an inhibitor of DNA methylation and has been widely used as a potent activator of suppressed genetic information. Treatment of cells with 5-azacytidine results in profound phenotypic alterations. The drug-induced hypomethylation of DNA apparently perturbs DNA-protein interactions that may consequently alter transcriptional activity and cell determination. The inhibitory effect of cytosine methylation may be exerted via altered DNA-protein interactions specifically or may be transduced by a change in the conformation of chromatin. Recent studies have demonstrated that cytosine methylation also plays a central role in parental imprinting, which in turn determines the differential expression of maternal and paternal genomes during embryogenesis. In other words, methylation is the mechanism whereby the embryo retains memory of the gametic origin of each component of genetic information. A memory of this type would probably persist during DNA replication and cell division as methylation patterns are stable and heritable.

Michalowsky, L A; Jones, P A



Selective targeting of histone methylation.  


Histones are post-translationally modified by multiple histone-modifying enzymes, which in turn influences gene expression. Much of the work in the field to date has focused on genetic, biochemical and structural characterization of these enzymes. The most recent genome-wide methods provide insights into specific recruitment of histone-modifying enzymes in vivo and, therefore, onto mechanisms of establishing a differential expression pattern. Here we focus on the recruitment mechanisms of the enzymes involved in the placement of two contrasting histone marks, histone H3 lysine 4 (H3K4) methylation and histone H3 lysine 27 (H3K27) methylation. We describe distribution of their binding sites and show that recruitment of different histone-modifying proteins can be coordinated, opposed, or alternating. Specifically, genomic sites of the H3K4 histone demethylase KDM5A become accessible to its homolog KDM5B in cells with a lowered KDM5A level. The currently available data on recruitment of H3K4/H3K27 modifying enzymes suggests that the formed protein complexes are targeted in a sequential and temporal manner, but that additional, still unknown, interactions contribute to targeting specificity. PMID:21270517

Islam, Abul B M M K; Richter, William F; Lopez-Bigas, Nuria; Benevolenskaya, Elizaveta V



Selective targeting of histone methylation  

PubMed Central

Histones are post-translationally modified by multiple histonemodifying enzymes, which in turn influences gene expression. Much of the work in the field to date has focused on genetic, biochemical and structural characterization of these enzymes. The most recent genome-wide methods provide insights into specific recruitment of histone-modifying enzymes in vivo and, therefore, onto mechanisms of establishing a differential expression pattern. Here we focus on the recruitment mechanisms of the enzymes involved in the placement of two contrasting histone marks, histone H3 lysine 4 (H3K4) methylation and histone H3 lysine 27 (H3K27) methylation. We describe distribution of their binding sites and show that recruitment of different histone-modifying proteins can be coordinated, opposed or alternating. Specifically, genomic sites of the H3K4 histone demethylase KDM5A become accessible to its homolog KDM5B in cells with a lowered KDM5A level. The currently available data on recruitment of H3K4/H3K27 modifying enzymes suggests that the formed protein complexes are targeted in a sequential and temporal manner, but that additional, still unknown, interactions contribute to targeting specificity.

Islam, Abul BMMK; Richter, William F; Lopez-Bigas, Nuria



Effects of Methylated Albumin on Infectious RNA: Reversible Infectivity Loss and Resistance to Nuclease Digestion.  

National Technical Information Service (NTIS)

It has been shown that methylated bovine serum albumin (MBSA) forms a complex with infectious ribonucleic acid (IRNA) from Venezuelan equine encephalitis virus. Formation of the complex is reversible, depending upon salt concentration. In physiological co...

S. A. Norrell R. D. Costlow



2,5-Bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole and its one-dimensional polymeric complex with ZnCl2.  


2,5-Bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole (L), C26H20N4O, forms one-dimensional chains via two types of intermolecular ?-? interactions. In catena-poly[[dichloridozinc(II)]-?-2,5-bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole], [ZnCl2(C26H20N4O)]n, synthesized by the combination of L with ZnCl2, the Zn(II) centres are coordinated by two Cl atoms and two N atoms from two L ligands. [ZnCl2L]n forms one-dimensional P (plus) and M (minus) helical chains, where the L ligand has different directions of twist. The helical chains stack together via interchain ?-? and C-H...? interactions. PMID:24096495

Hou, Shan; Liu, Qi Kui; Li, Yan An; Ma, Jian Ping; Dong, Yu Bin



Formation of stacking complexes between caffeine (1,2,3-trimethylxanthine) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine may attenuate biological effects of this neurotoxin  

Microsoft Academic Search

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin causing symptoms that may resemble those observed in patients suffering from Parkinson’s disease. Therefore, MPTP-treated laboratory animals are currently the most favored models to study therapeutic intervention strategies in this disease. It was demonstrated recently that caffeine (1,2,3-trimethylxanthine) intake decreases the risk of Parkinson’s disease in various human populations and attenuates MPTP-induced neurological effects in

Katarzyna Ulanowska; Jacek Piosik; Anna Gwizdek-Wi?niewska



Simultaneous hyper- and hypomethylation at imprinted loci in a subset of patients with GNAS epimutations underlies a complex and different mechanism of multilocus methylation defect in pseudohypoparathyroidism type 1b.  


Most patients with pseudohypoparathyroidism type 1b (PHP-1b) display a loss of imprinting (LOI) encompassing the GNAS locus resulting in PTH resistance. In other imprinting disorders, such as Russell-Silver or Beckwith-Wiedemann syndrome, we and others have shown that the LOI is not restricted to one imprinted locus but may affect other imprinted loci for some patients. Therefore, we hypothesized that patients with PHP-1b might present multilocus imprinting defects. We investigated, in 63 patients with PHP-1b, the methylation pattern of eight imprinted loci: GNAS, ZAC1, PEG1/MEST, ICR1, and ICR2 on chromosome 11p15, SNRPN, DLK1/GTL2 IG-DMR, and L3MBTL1. We found multilocus imprinting defects in four PHP-1b patients carrying broad LOI at the GNAS locus (1) simultaneous hypermethylation at L3MBTL1 differentially methylated region 3 (DMR3), and hypomethylation at PEG1/MEST DMR (n = 1), (2) hypermethylation at the L3MBTL1 (DMR3) (n = 1) and at the DLK1/GTL2 IG-DMR (n = 1), and (3) hypomethylation at the L3MBTL1 DMR3 (n = 1). We suggest that mechanisms underlying multilocus imprinting defects in PHP-1b differ from those of other imprinting disorders having only multilocus loss of methylation. Furthermore, our results favor the hypothesis of "epidominance", that is, the phenotype is controlled by the most severely affected imprinted locus. PMID:23649963

Maupetit-Méhouas, Stéphanie; Azzi, Salah; Steunou, Virginie; Sakakini, Nathalie; Silve, Caroline; Reynes, Christelle; Perez de Nanclares, Guiomar; Keren, Boris; Chantot, Sandra; Barlier, Anne; Linglart, Agnès; Netchine, Irène



Neurotoxicity of methyl chloride.  


Methyl chloride is encountered in the chemical industry as a methylating agent in the production of butyl rubber, tetramethyl lead, and other products as well as a blowing agent for some polystyrene foams. It is a potent CNS depressant whose principal route of absorption is by inhalation, although it can be absorbed through the skin. Symptoms of the neurotoxicity include headache, drowsiness, giddiness, ataxia, convulsion, and coma. This review focuses on the human case reports of acute and chronic exposures as well as some of the more important inhalation studies conducted with animals. The chemical and physical properties and the more important industrial uses are also discussed. PMID:7038527

Repko, J D



On the bromination of methyl 2-methyl-3-furoate  

Microsoft Academic Search

Methyl 2-methyl-3-furoate was subjected to bromination with N-bromosuccinimide (NBS), a milder brominating reagent, under different reaction conditions to obtain a variety of selective brominated products.

Haripada Khatuya



4-(Di-methyl-amino)-pyridinium trichlorido[4-(di-methyl-amino)-pyridine-?N]cobaltate(II)  

PubMed Central

In the anion of the title compound, (C7H11N2)[CoCl3(C7H10N2)], the CoII ion is coordinated by one N atom from a 4-(di­methyl­amino)­pyridine (DMAP) ligand and three Cl atoms, forming a CoNCl3 polyhedron with a distorted tetra­hedral geometry. In the crystal, cations and anions are linked via weak N—H?Cl and C—H?Cl hydrogen bonds. Double layers of complex anions stack along the b- axis direction, which alternate with double layers of 4-(di­methyl­amino)-pyridinium cations.

Guenifa, Fatiha; Hadjadj, Nasreddine; Zeghouan, Ouahida; Bendjeddou, Lamia; Merazig, Hocine



Alkene and Alkyne Reactivity Towards a Bisruthenium (II) µ2Dinitrogen Complex Containing the 'Pincer' ligand 2,6Bis[(dimethylamino)methyl]pyridine(NN'N). The X-ray Crystal Structures of [Ru(=C=CHPh)Cl2(NN'N)] and [Ru(=C=CHPh)(OTf)(NN'N)(PPh3)][OTf] (OTf =Trifluoromethane Sulfonate)  

Microsoft Academic Search

The binuclear Ru(II) 2-dinitrogen complex [{RuCl2(3-NN'N)}2(-N2)] (1, NN'N = 2,6-bis[(dimethylamino)methyl]pyridine) is an excellent starting material for the synthesis of mononuclear 2-alkene complexes: mer,trans-[RuCl2(3-NN'N)(2-H2C=CHR)] (R = H, CH=CH2, Ph, CH2Ph, CH2Br, CH2OH, CHO, CN, CO2Me; yields 73-93%). These new 2-alkene Ru(II) compounds are stable at room temperature even when the alkene carbon atoms are substituted with potentially reactive functional groups. Of

G. van Koten; I. del Rio; R. A. Gossage; M. S. Hannu; M. H. Lutz; A. L. Spek



Metabolic production of methylated selenium species requires adequate methylation status  

Technology Transfer Automated Retrieval System (TEKTRAN)

Obesity negatively impacts methylation status and markers of methylation status vary according to selenium status in supplemented subjects. We have proposed that disruptions in methylation capacity induced by obesity compromise demonstrable anti-cancer effects of Se supplementation. In order to addr...


Methyl salicylate overdose  


Deep heating rubs overdose; Oil of wintergreen overdose ... Deep-heating creams (Ben Gay, Icy Hot) used to relieve sore muscles and joints Oil of wintergreen Solutions for vaporizers Note: This list may not include all products that contain methyl salicylate.


DNA Methylation and Cancer Diagnosis  

PubMed Central

DNA methylation is a major epigenetic modification that is strongly involved in the physiological control of genome expression. DNA methylation patterns are largely modified in cancer cells and can therefore be used to distinguish cancer cells from normal tissues. This review describes the main technologies available for the detection and the discovery of aberrantly methylated DNA patterns. It also presents the different sources of biological samples suitable for DNA methylation studies. We discuss the interest and perspectives on the use of DNA methylation measurements for cancer diagnosis through examples of methylated genes commonly documented in the literature. The discussion leads to our consideration for why DNA methylation is not commonly used in clinical practice through an examination of the main requirements that constitute a reliable biomarker. Finally, we describe the main DNA methylation inhibitors currently used in clinical trials and those that exhibit promising results.

Delpu, Yannick; Cordelier, Pierre; Cho, William C.; Torrisani, Jerome



EDTA bis-(Methyl tyrosinate): A chelating peptoid peroxynitrite scavenger  

Microsoft Academic Search

Conjugation of ethylenediaminetetra-acetic acid (EDTA) to methyl tyrosinate generates a chelating peptoid EDTA bis-(methyl tyrosinate), (EBMT). Peroxynitrite-mediated nitration was studied for the free peptoid and its ferric and cupric complexes. The nitration products were monitored by electronic absorption spectroscopy at ?max of 420nm (mono-nitrated) and 440nm (di-nitrated). Peak deconvolution was effected by pH manipulation as the mono-nitrated analogue of tyrosine

Anna E. O. Fisher; Declan P. Naughton



Cancer DNA Methylation: Molecular Mechanisms and Clinical Implications  

PubMed Central

DNA methylation plays a crucial role in the regulation of gene expression and chromatin organization within normal eukaryotic cells. In cancer, however, global patterns of DNA methylation are altered with global hypomethylation of repeat-rich intergenic regions and hypermethylation of a subset of CpG-dense gene-associated regions (CpG islands). Extensive research has revealed the cellular machinery that catalyzes DNA methylation, as well as several large protein complexes that mediate the transcriptional repression of hypermethylated genes. However, research is only just beginning to uncover the molecular mechanisms underlying the origins of cancer-specific DNA methylation. Herein, we present several recent advances regarding these mechanisms and discuss the relationship between histone modifications (i.e. H3K4me2/3, H4K16Ac, H3K9me2/3, H3K27me3, H4K20me3), chromatin-modifying enzymes (G9a, EZH2, hMOF, SUV4?20H), and aberrant DNA methylation. Additionally, the role played by inflammation, DNA damage, and miRNAs in the etiology of aberrant DNA methylation is considered. Finally, we discuss the clinical implications of aberrant DNA methylation and the utility of methylated biomarkers in cancer diagnosis and management.

McCabe, Michael T.; Brandes, Johann C.; Vertino, Paula M.



40 CFR 721.6920 - Butyl acrylate, polymer with substituted methyl styrene, methyl methacrylate, and substituted...  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Butyl acrylate, polymer with substituted methyl styrene, methyl...Substances § 721.6920 Butyl acrylate, polymer with substituted methyl styrene, methyl...substance identified as butyl acrylate, polymer with substituted methyl styrene,...



DNA methylation and transcriptional noise  

PubMed Central

Background DNA methylation is one of the most phylogenetically widespread epigenetic modifications of genomic DNA. In particular, DNA methylation of transcription units (‘gene bodies’) is highly conserved across diverse taxa. However, the functional role of gene body methylation is not yet fully understood. A long-standing hypothesis posits that gene body methylation reduces transcriptional noise associated with spurious transcription of genes. Despite the plausibility of this hypothesis, an explicit test of this hypothesis has not been performed until now. Results Using nucleotide-resolution data on genomic DNA methylation and abundant microarray data, here we investigate the relationship between DNA methylation and transcriptional noise. Transcriptional noise measured from microarrays scales down with expression abundance, confirming findings from single-cell studies. We show that gene body methylation is significantly negatively associated with transcriptional noise when examined in the context of other biological factors. Conclusions This finding supports the hypothesis that gene body methylation suppresses transcriptional noise. Heavy methylation of vertebrate genomes may have evolved as a global regulatory mechanism to control for transcriptional noise. In contrast, promoter methylation exhibits positive correlations with the level of transcriptional noise. We hypothesize that methylated promoters tend to undergo more frequent transcriptional bursts than those that avoid DNA methylation.



Production of methyl-oxonium ion and its complexes in the core-excited (HC(O)OCH{sub 3}){sub n} clusters: H/H{sup +} transfer from the {alpha} carbonyl  

SciTech Connect

Dissociation of free methyl-formate (MF), HC(O)OCH{sub 3}, and its clusters (MF){sub n}, (HC(O)OCH{sub 3}){sub n}, induced by core-level excitation was studied near the oxygen K edge by time-of-flight fragment-mass spectroscopy. Besides the protonated clusters, (MF){sub n}H{sup +} with nIE15, we identified the production for another series of (MF){sub m}CH{sub 3}OH{sub 2}{sup +} with mIE14 as well as methyl-oxonium ion, CH{sub 3}OH{sub 2}{sup +}, characteristic of hydrogen transfer reactions in the cationic clusters. Here, specifically labeled methyl-formate-d (MFD), DC(O)OCH{sub 3} was also used to examine the core-excited dissociation mechanisms. Deuterium-labeled experiments indicated that MFD{sup +} with low internal energies, partially generated after the core excitation, produces CH{sub 3}OD{sup +} via a site-specific deuterium transfer from the {alpha} carbonyl in the molecular cation and that CH{sub 3}OD{sub 2}{sup +} can be formed via the successive transfer of another deuterium from the neighbor molecule in the clusters. The deuteron (proton) transfer was also found to take place preferentially from the {alpha} carbonyl of the neighbor molecule for the production of deuteronated (MFD){sub n}D{sup +}, (protonated (MF){sub n}H{sup +}), clusters. The minimal energy requirement paths were examined for dimer (MF){sub 2}{sup +} cation to support the present dissociation mechanisms of core-excited (MF){sub n} clusters using ab initio molecular-orbital calculations.

Tada, S.; Harada, C.; Yoshida, H.; Wada, S.; Hiraya, A.; Tanaka, K.; Tabayashi, K. [Department of Chemistry, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526 (Japan); Department of Physical Science, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan and Hiroshima Synchrotron Radiation Center (HSRC), Hiroshima University, Higashi-Hiroshima 739-8526 (Japan); Department of Chemistry, Graduate School of Science, Hiroshima University, Higashi-Hiroshima 739-8526, Japan and Hiroshima Synchrotron Radiation Center (HSRC), Hiroshima University, Higashi-Hiroshima 739-8526 (Japan)



MS377, a selective sigma receptor ligand, indirectly blocks the action of PCP in the N-methyl-D-aspartate receptor ion-channel complex in primary cultured rat neuronal cells  

Microsoft Academic Search

MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate) is a antipsychotic agent that binds to sigma-1 receptor. MS-377 showed anti-dopaminergic and anti-serotonergic activities and antagonistic action against phencyclidine (PCP)-induced behaviors in an animal model. These anti-psychotic activities of MS-377 are attributable to association with sigma-1 receptor. However, the mechanism by which the sigma-1 receptor ligands exact those numerous effects remains to be elucidated. In the

Jun-ichi Karasawa; Hideko Yamamoto; Toshifumi Yamamoto; Naoki Sagi; Kazutoshi Horikomi; Ichiro Sora



Copper(II)- and iron(II)-complexes of methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), a peptide mimicking the metal-chelating moiety of bleomycin. An ESR investigation.  


Methyl 2-(2-aminoethyl)-aminomethyl-pyridine-6-carboxyl-histidinate (AMPHIS), a synthetic analogue of the chelating part of bleomycin (BLM), has been studied for its metal binding properties. Electron spin resonance parameters of AMPHIS-Cu(II) and BLM-Cu(II) have been found to be closely similar likewise spectra of oxygen radicals spin-adducts induced by AMPHIS-Fe(II)-O2 and BLM-Fe(II)-O2 systems. Thus, AMPHIS could constitute a very useful tool for the study of BLM mode of action. PMID:2579645

Hénichart, J P; Bernier, J L; Houssin, R; Lohez, M; Kenani, A; Catteau, J P



Electrophysiological Study, Biodistribution in Mice, and Preliminary PET Evaluation in a Rhesus Monkey of 1Amino3-(18F)fluoromethyl-5-methyl-adamantane (18F-MEM): A Potential Radioligand for Mapping the NMDA-Receptor Complex  

Microsoft Academic Search

The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that 19F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added

Samuel Samnick; Simon Ametamey; Klaus L. Leenders; Peter Vontobel; Guenter Quack; Chris G. Parsons; Henrik Neu; Pius A. Schubiger


Electrophysiological Study, Biodistribution in Mice, and Preliminary PET Evaluation in a Rhesus Monkey of 1Amino3-[ 18F]fluoromethyl-5-methyl-adamantane ( 18F-MEM): A Potential Radioligand for Mapping the NMDA-Receptor Complex  

Microsoft Academic Search

The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that 19F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added

Samuel Samnick; Simon Ametamey; Klaus L Leenders; Peter Vontobel; Guenter Quack; Chris G Parsons; Henrik Neu; Pius A Schubiger



Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein.  

PubMed Central

Repression of transcription from densely methylated genes can be mediated by the methyl-CpG binding protein MeCP-1 (Boyes and Bird, 1991). Here we have investigated the effect of methylation on genes with a low density of methyl-CpG. We found that sparse methylation could repress transfected genes completely, but the inhibition was fully overcome by the presence in cis of an SV40 enhancer. Densely methylated genes, however, could not be reactivated by the enhancer. In vitro studies showed that the sparsely methylated genes bound weakly to MeCP-1 and that binding interfered with transcription. In the absence of available MeCP-1, methylation had minimal effects on transcription. From these and other results we propose that sparsely methylated genes form an unstable complex with MeCP-1 which prevents transcription when the promoter is weak. This complex can be disrupted by a strong promoter, thereby allowing the methylated gene to be transcribed. Images

Boyes, J; Bird, A



A genome-wide methylation study on obesity: differential variability and differential methylation.  


Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14-20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances. PMID:23644594

Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Hidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling



Synthesis, Spectroscopic Studies, and In Vitro Antifungal Activity of Organosilicon(IV) and Organotin(IV) Complexes of 4Amino5-mercapto-3-methyl-S-triazole Schiff Bases  

Microsoft Academic Search

The Schiff bases derived from condensation of s-triazole with heterocyclic aldehydes and their 1:1 and 1:2 complexes have been synthesized. These complexes have been characterized by elemental analyses, molar conductance and spectroscopic studies, including UV, IR, H, C, Si, and Sn NMR spectroscopy. On the basis of these studies, the resulting complexes have been proposed to have trigonal bipyramidal and

Kiran Singh; Dharampal; Vipin Parkash



DNA methylation profiling in nanochannels  

PubMed Central

We report the profiling of the 5-methyl cytosine distribution within single genomic-sized DNA molecules at a gene-relevant resolution. This method linearizes and stretches DNA molecules by confinement to channels with a dimension of about 250×200 nm2. The methylation state is detected using fluorescently labeled methyl-CpG binding domain proteins (MBD), with high signal contrast and low background. DNA barcodes consisting of methylated and non-methylated segments are generated, with both short and long concatemers demonstrating spatially resolved MBD binding. The resolution of the technique is better than 10 kbp, and single-molecule read-lengths exceeding 140 kbp have been achieved.

Fang Lim, Shuang; Karpusenko, Alena; Sakon, John J.; Hook, Joseph A.; Lamar, Tyra A.; Riehn, Robert



3,5-Bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine and its one-dimensional polymeric complex with HgCl2.  


The molecule of 3,5-bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine (L), C(30)H(24)N(8), has an antiperiplanar conformation of the two terminal benzimidazole groups and forms two-dimensional networks along the crystallographic b axis via two types of intermolecular hydrogen bonds. However, in catena-poly[[[dichloridomercury(II)]-?-3,5-bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine] dichloromethane hemisolvate], {[HgCl(2)(C(30)H(24)N(8))]·0.5CH(2)Cl(2)}(n), synthesized by the combination of L with HgCl(2), the L ligand adopts a synperiplanar conformation. The Hg(II) cation lies in a distorted tetrahedral environment, which is defined by two N atoms and two Cl atoms to form a one-dimensional zigzag chain. These zigzag chains stack via hydrogen bonds which expand the dimensionality of the structure from one to two. PMID:22669186

Li, Yan-an; Liu, Qi-Kui; Ma, Jian-Ping; Dong, Yu-Bin



Selectivity in metal-carbon bond protonolysis in p-tolyl- (or methyl)-cycloplatinated(II) complexes: kinetics and mechanism of the uncatalyzed isomerization of the resulting Pt(II) products.  


Reaction of each of the known starting complexes [PtR(C^N)(SMe2)], 1, in which R = Me or p-MeC6H4 and C^N is either ppy (deprotonated 2-phenylpyridine) or bhq (deprotonated benzo[h]quinoline), with one equivalent of CF3CO2H, gave the complexes [Pt(C^N)(CF3CO2)(SMe2)], 3 (C^N = ppy, 3a; bhq, 3b). The bis-chelate complexes [Pt(C^N)(P^P)](CF3CO2), 4, were obtained by reaction of complexes 3 with one equivalent of either of the P^P bisphosphine reagents, dppf = 1,1'-bis(diphenylphosphino)ferrocene or dppe = bis(diphenylphosphino)ethane. Complexes 4 were alternatively made by reaction of the complexes [PtMe(?(1)C-C^N)(P^P)], 2, with one equivalent of CF3CO2H. When the complex 3b was reacted with 0.5 equivalents of dppe, 0.5 equivalents of the related bis-chelate product, 4d, formed along with 0.5 equivalents of the unreacted starting complex 3b. In contrast, when the complex 3b was reacted with 0.5 equivalents of dppf, then the dimeric complex [Pt2(bhq)2(CF3CO2)2(?-dppf)], 5, formed in pure form. In all the above-mentioned acid reactions, the M-R bond rather than the M-C bond of the cycloplatinated complex is cleaved. When the PPh3 analogues of complexes 1, i.e. the complexes [PtR(C^N)(PPh3)], 6, in which C^N is ppy or tpy = deprotonated 2-p-tolylpyridine, were reacted with one equivalent of CF3CO2H, the course of the reaction reversed and the M-C bonds of the cycloplatinated complexes are cleaved rather than the M-R bonds. The latter reaction gave [PtR(?(1)N-HC^N)(PPh3)(CF3CO2)], as an equilibrium mixture of two isomers 7 and 8. Crystal structures of the typical complexes show a variety of extensive intermolecular hydrogen bonding involving C-H bonds from the different ligands and electronegative atoms (O or F) from the CF3CO2 moiety. On the basis of data obtained from kinetic studies (using (1)H NMR spectroscopy), a dissociative mechanism is proposed for the case of the 7c/8c isomerization process, involving dissociation of the ?(1)N-Htpy neutral ligand, rather than the alternative route of PPh3 or CF3CO2 ligand dissociation. PMID:23887622

Haghighi, Mohsen Golbon; Nabavizadeh, S Masoud; Rashidi, Mehdi; Kubicki, Maciej



Altered DNA Methylation in Leukocytes with Trisomy 21  

PubMed Central

The primary abnormality in Down syndrome (DS), trisomy 21, is well known; but how this chromosomal gain produces the complex DS phenotype, including immune system defects, is not well understood. We profiled DNA methylation in total peripheral blood leukocytes (PBL) and T-lymphocytes from adults with DS and normal controls and found gene-specific abnormalities of CpG methylation in DS, with many of the differentially methylated genes having known or predicted roles in lymphocyte development and function. Validation of the microarray data by bisulfite sequencing and methylation-sensitive Pyrosequencing (MS-Pyroseq) confirmed strong differences in methylation (p<0.0001) for each of 8 genes tested: TMEM131, TCF7, CD3Z/CD247, SH3BP2, EIF4E, PLD6, SUMO3, and CPT1B, in DS versus control PBL. In addition, we validated differential methylation of NOD2/CARD15 by bisulfite sequencing in DS versus control T-cells. The differentially methylated genes were found on various autosomes, with no enrichment on chromosome 21. Differences in methylation were generally stable in a given individual, remained significant after adjusting for age, and were not due to altered cell counts. Some but not all of the differentially methylated genes showed different mean mRNA expression in DS versus control PBL; and the altered expression of 5 of these genes, TMEM131, TCF7, CD3Z, NOD2, and NPDC1, was recapitulated by exposing normal lymphocytes to the demethylating drug 5-aza-2?deoxycytidine (5aza-dC) plus mitogens. We conclude that altered gene-specific DNA methylation is a recurrent and functionally relevant downstream response to trisomy 21 in human cells.

Kerkel, Kristi; Schupf, Nicole; Hatta, Kota; Pang, Deborah; Salas, Martha; Kratz, Alexander; Minden, Mark; Murty, Vundavalli; Zigman, Warren B.; Mayeux, Richard P.; Jenkins, Edmund C.; Torkamani, Ali; Schork, Nicholas J.; Silverman, Wayne; Croy, B. Anne; Tycko, Benjamin



Targeting DNA Methylation  

PubMed Central

Two nucleoside inhibitors of DNA methylation, azacitidine and decitabine, are now standard of care for the treatment of the myelodysplastic syndrome, a deadly form of leukemia. These old drugs, developed as cytotoxic agents and nearly abandoned decades ago were resurrected by the renewed interest in DNA methylation. They have now provided proof of principle for epigenetic therapy, the final chapter in the long saga to provide legitimacy to the field of epigenetics in cancer. But challenges remain; we don’t understand precisely how or why the drugs work or stop working after an initial response. Extending these promising findings to solid tumors face substantial hurdles from drug uptake to clinical trial design. We do not know yet how to select patients for this therapy and how to move it from life extension to cure. The epigenetic potential of DNA methylation inhibitors may be limited by other epigenetic mechanisms that are also worth exploring as therapeutic targets. But the idea of stably changing gene expression in-vivo has transformative potential in cancer therapy and beyond.

Issa, Jean-Pierre J.; Kantarjian, Hagop M.



Direct DNA Methylation Profiling Using Methyl Binding Domain Proteins  

PubMed Central

Methylation of DNA is responsible for gene silencing by establishing heterochromatin structure that represses transcription, and studies have shown that cytosine methylation of CpG islands in promoter regions acts as a precursor to early cancer development. The naturally occurring methyl binding domain (MBD) proteins from mammals are known to bind to the methylated CpG dinucleotide (mCpG), and subsequently recruit other chromatin-modifying proteins to suppress transcription. Conventional methods of detection for methylated DNA involve bisulfite treatment or immunoprecipitation prior to performing an assay. We focus on proof-of-concept studies for a direct microarray-based assay using surface-bound methylated probes. The recombinant protein 1xMBD-GFP recognizes hemi-methylation and symmetric methylation of the CpG sequence of hybridized dsDNA, while displaying greater affinity for the symmetric methylation motif, as evaluated by SPR. From these studies, for symmetric mCpG, the KD for 1xMBD-GFP ranged from 106 nM to 870 nM, depending upon the proximity of the methylation site to the sensor surface. The KD values for non-symmetrical methylation motifs were consistently greater (> 2 µM), but the binding selectivity between symmetric and hemi-methylation motifs ranged from 4 to 30, with reduced selectivity for sites close to the surface or multiple sites in proximity, which we attribute to steric effects. Fitting skew normal probability density functions to our data, we estimate an accuracy of 97.5% for our method in identifying methylated CpG loci, which can be improved through optimization of probe design and surface density.

Yu, Yinni; Blair, Steve; Gillespie, David; Jensen, Randy; Myszka, David G.; Badran, Ahmed H.; Ghosh, Indraneel; Chagovetz, Alexander



Effects of coadministered sodium selenite on short-term distribution on methyl mercury in the rat  

SciTech Connect

Adult male Sprague-Dawley rats received iv injections of 1 of methyl mercury/kg alone or coadministered with 5 of sodium selenite/kg. Tissue concentrations of methyl mercury were determined at 5, 20, and 60 min after treatment. Selenite treatment produced a significant increase in cerebral methyl mercury concentrations and a significant decrease in kidney methyl mercury concentrations at all time points. The concentration of methyl mercury in liver was significantly increased by selenite coadministration at 5 and 20 min but at 60 min after injection the concentration was not significantly different from that found in rats receiving methyl mercury alone. Selenite treatment also significantly lowered blood methyl mercury concentrations at all time points. This decrease was associated with a significant decrease in the concentration of methyl mercury in erythrocytes at 5, 20, and 60 min. Plasma methyl mercury levels at 5 min postinjection were slightly higher in selenite-treated rats but were significantly lower in treated animals at 20 and 60 min. Treatment of rats with selenite did not specifically alter the extent of methyl mercury binding to glutathione in the 108,000 g supernatant of cerebrum of in erythrocyte hemolysates. In rats receiving either methyl mercury alone or with selenite, low-molecular-weight methyl mercury complexes could not be detected in plasma 5 min after iv injection.

Thomas, D.J.; Smith, J.C.



Identification of differentially methylated regions using streptavidin bisulfite ligand methylation enrichment (SuBLiME), a new method to enrich for methylated DNA prior to deep bisulfite genomic sequencing  

PubMed Central

We have developed a method that enriches for methylated cytosines by capturing the fraction of bisulfite-treated DNA with unconverted cytosines. The method, called streptavidin bisulfite ligand methylation enrichment (SuBLiME), involves the specific labeling (using a biotin-labeled nucleotide ligand) of methylated cytosines in bisulfite-converted DNA. This step is then followed by affinity capture, using streptavidin-coupled magnetic beads. SuBLiME is highly adaptable and can be combined with deep sequencing library generation and/or genomic complexity-reduction. In this pilot study, we enriched methylated DNA from Csp6I-cut complexity-reduced genomes of colorectal cancer cell lines (HCT-116, HT-29 and SW-480) and normal blood leukocytes with the aim of discovering colorectal cancer biomarkers. Enriched libraries were sequenced with SOLiD-3 technology. In pairwise comparisons, we scored a total of 1,769 gene loci and 33 miRNA loci as differentially methylated between the cell lines and leukocytes. Of these, 516 loci were differently methylated in at least two promoter-proximal CpG sites over two discrete Csp6I fragments. Identified methylated gene loci were associated with anatomical development, differentiation and cell signaling. The data correlated with good agreement to a number of published colorectal cancer DNA methylation biomarkers and genomic data sets. SuBLiME is effective in the enrichment of methylated nucleic acid and in the detection of known and novel biomarkers.

Ross, Jason P.; Shaw, Jan M.; Molloy, Peter L.



Identification of O-methyl-(-)-epicatechin-O-sulphate metabolites by mass-spectrometry after O-methylation with trimethylsilyldiazomethane.  


(-)-Epicatechin, an abundant dietary polyphenol found mainly in cocoa and tea, is known to extensively undergo metabolism after ingestion giving rise to a complex series of conjugated metabolites including numerous isomers. In the present study, the combination of fractionation, chemical derivatization and various mass spectrometric approaches is described to determine the exact position of sulphate group in methylated epicatechin metabolites. Four O-methyl-(-)-epicatechin-O-sulphate metabolites isolated from human urine samples were derivatized under mild condition using trimethylsilyldiazomethane (TMSD) in the presence of methanol. The resulting methylated reaction products were then analyzed by high resolution and multistage mass spectrometry for the subsequent identification of the sulphate positional isomers. Results show that O-methylation affects the charge delocalization in negatively charged ions and hereby the fragmentation pattern of the sulphate isomers allowing the identification of diagnostic ions. In addition, this study demonstrates that methoxy derivatives of polyphenol metabolites can be prepared using TMSD. Subsequently, the localization of the sulphate group in the polyphenol metabolites can be achieved by analyzing the methoxy derivatives by multistage mass spectrometry. Using an enzymatic reaction for identification of the O-methyl position, and a chemical O-methylation with TMSD follow by high resolution and multistage tandem MS for the identification of the sulphate group position, we were able to identify the previously unknown O-methyl-(-)-epicatechin-O-sulphate. Accordingly, we identified 3'-O-methyl-(-)-epicatechin-5-O-sulphate and 3'-O-methyl-(-)-epicatechin-7-O-sulphate as the main O-methyl-(-)-epicatechin-sulfates(-)-epicatechin metabolites in humans. PMID:22663977

Actis-Goretta, Lucas; Lévèques, Antoine; Giuffrida, Francesca; Destaillats, Frédéric; Nagy, Kornél



A facile method for the synthesis of partially O-methylated alditol acetate standards for GC-MS analysis of galactofuranose-containing structures.  


Mixtures of partially O-methylated alditol acetate standards of galactofuranose were synthesized rapidly. Methyl galactofuranosides were obtained with a yield of 79.9% within 4h under optimized reaction conditions. Methylation of methyl glycosides was carried out in the presence of BaO/Ba(OH)2·8H2O, giving rise to mixtures of partially methylated glycosides. The batch containing the most diverse structures of methyl ethers was converted into partially O-methylated alditol acetates (PMAAs) and then subjected to GC-MS. These PMAAs could be used as GC-MS standards for simultaneous identification of galactofuranose units with diverse linkages in complex carbohydrates. PMID:23835470

He, Jian-yu; Guo, Yu-na; Zhang, Ling-ling; Huang, Lin-hong



Synthesis, spectroscopy and thermal behavior of new lead(II) complexes derived from S-methyl\\/benzyldithiocarbazates (SMDTC\\/SBDTC): X-ray crystal structure of [Pb(SMDTC)(NO 3) 2  

Microsoft Academic Search

Lead(II) complexes of S-methyldithiocarbazate (SMDTC), [Pb(SMDTC)(NO3)2] (1) and S-benzyldithiocarbazate (SBDTC), [Pb(SBDTC)(NO3)2] (2) have been synthesized for the first time and characterized by elemental analysis, IR and TGA techniques. The complexes were obtained by addition of the appropriate ligand to an aqueous ethanolic solution of lead(II) nitrate in 1:1 molar ratio. The X-ray crystal structure of complex 1 has been determined

Pulakesh Bera; Chong-Hyeak Kim; Sang Il Seok



Event extraction for DNA methylation  

PubMed Central

Background We consider the task of automatically extracting DNA methylation events from the biomedical domain literature. DNA methylation is a key mechanism of epigenetic control of gene expression and implicated in many cancers, but there has been little study of automatic information extraction for DNA methylation. Results We present an annotation scheme for DNA methylation following the representation of the BioNLP shared task on event extraction, select a set of 200 abstracts including a representative sample of all PubMed citations relevant to DNA methylation, and introduce manual annotation for this corpus marking nearly 3000 gene/protein mentions and 1500 DNA methylation and demethylation events. We retrain a state-of-the-art event extraction system on the corpus and find that automatic extraction of DNA methylation events, the methylated genes, and their methylation sites can be performed at 78% precision and 76% recall. Conclusions Our results demonstrate that reliable extraction methods for DNA methylation events can be created through corpus annotation and straightforward retraining of a general event extraction system. The introduced resources are freely available for use in research from the GENIA project homepage



Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation  

PubMed Central

Modifications on histones or on DNA recruit proteins that regulate chromatin function. Here we use nucleosomes methylated on DNA and on histone H3 in an affinity assay, in conjunction with a SILAC-based proteomic analysis, to identify “cross-talk” between these two distinct classes of modification. Our analysis reveals proteins whose binding to nucleosomes is regulated by methylation of CpGs, H3K4, H3K9, and H3K27 or a combination thereof. We identify the Origin Recognition Complex (ORC), including LRWD1 as a subunit, to be a methylation-sensitive nucleosome interactor which is recruited cooperatively by DNA and histone methylation. Other interactors, such as the lysine demethylase Fbxl11/KDM2A, recognise nucleosomes methylated on histones but their recruitment is disrupted by DNA methylation. These data establish SILAC nucleosome affinity purifications (SNAP) as a tool for studying the dynamics between different chromatin modifications and provide a modification binding “profile” for proteins regulated by DNA and histone methylation.

Bartke, Till; Vermeulen, Michiel; Xhemalce, Blerta; Robson, Samuel C.; Mann, Matthias; Kouzarides, Tony



Conductometric study of charge transfer complexes  

Microsoft Academic Search

A conductometric titration technique has been used for determining the stoichio-metry of charge-transfer complexes which ionise\\u000a in polar media. The systems studied are: Iodine complexes of acetone, methyl ethyl ketone,iso-butyl methyl ketone, dimethylsulphoxide triphenyl phosphine, triphenyl arsine, triphenyl stibene, methanol, ethanol andn-propanol. The stoichiometry of the above complexes (in highly polar media) were found to be?2:3 (except in the cases

Bharati Bhattacharjee; S N Bhat



DNA methylation in mouse testes.  


DNA methylation of retrotransposons and imprinted genes is accurately regulated in spermatogenesis. In particular, CpG methylation of long interspersed elements-1 (LINE1 or L1) and intracisternal A-particle (IAP) retrotransposons during spermatogenesis has been well characterized. CpG methylation of the regulatory regions of retrotransposons is acquired during embryonic testis development; however, reductions of DNA methylation in LINE1 and/or IAP and/or Rasgrf1, which is an imprinted gene, are observed in deficient mice of piRNA biogenesis concerning. Here, we describe two methods, bisulfite sequencing and Southern blotting using a methylation-sensitive restriction enzyme, for analysis of DNA methylation of LINE1, IAP, and imprinted genes in mouse testes. PMID:24178559

Kuramochi-Miyagawa, Satomi; Kita-Kojima, Kanako; Shiromoto, Yusuke; Ito, Daisuke; Koshima, Hirotaka; Nakano, Toru



Diphenyl-methyl benzoate.  


In the title mol-ecule, C20H16O2, the dihedral angle between the phenyl rings of the diphenyl-methyl group is 68.3?(2)°. The benzoate group is essentially planar, with a maximum deviation of 0.017?(2)?Å for the carbonyl O atom, and the two phenyl rings are twisted by 27.5?(4) and 85.6?(9)° from this plane. In the crystal, weak C-H?O hydrogen bonds link mol-ecules along [100]. PMID:23476463

Kaur, Manpreet; Jasinski, Jerry P; Keeley, Amanda C; Yathirajan, H S; Siddegowda, M S



Triphenyl-methyl benzoate.  


The title compound, C(26)H(20)O(2), has long been known, but was not structurally characterized until now. It adopts the Z conformation and the atoms comprising the ester linkage are essentially coplanar (r.m.s. deviation of 0.0234?Å). The acyl C-O bond length of 1.470?(2)?Å falls within the normal range seen for esters of tertiary alcohols and is below the value of 1.496?Å found in tri-tert-butyl-methyl 4-nitro-benzoate. PMID:21583694

Sykora, Richard E; McDonald, Lane; Spyridis, Greg T



Triphenyl-methyl benzoate  

PubMed Central

The title compound, C26H20O2, has long been known, but was not structurally characterized until now. It adopts the Z conformation and the atoms comprising the ester linkage are essentially coplanar (r.m.s. deviation of 0.0234?Å). The acyl C—O bond length of 1.470?(2)?Å falls within the normal range seen for esters of tertiary alcohols and is below the value of 1.496?Å found in tri-tert-butyl­methyl 4-nitro­benzoate.

Sykora, Richard E.; McDonald, Lane; Spyridis, Greg T.



Novel mixed ligand complexes of bioactive Schiff base (E)-4-(phenyl (phenylimino) methyl) benzene-1,3-diol and 2-aminophenol/2-aminobenzoic acid: Synthesis, spectral characterization, antimicrobial and nuclease studies.  


A novel bidentate Schiff base ligand has been synthesized using 2,4-dihydroxybenzophenone and aniline. Its mixed ligand complexes of MAB type [M=Mn(II), Co(II), Ni(II), Cu(II) and Zn(II); HA=Schiff base and B=2-aminophenol/2-aminobenzoic acid] have been synthesized and characterized on the basis of spectral data UV-Vis, IR, (1)H NMR, FAB-Mass, EPR, SEM and magnetic studies. All the complexes were soluble in DMF and DMSO. Elemental analysis and molar conductance values indicate that the complexes are non-electrolytes. HA binds with M(II) ions through azomethine and deprotonated phenolic group and B binds through the primary amine group and deprotonated phenolic/carboxylic groups. Using FAB-Mass the cleavage pattern of the ligand (HA) has been established. All the complexes adopt octahedral geometry around the metal ions. It has been confirmed with the help of UV-Vis, IR, (1)H NMR and FAB-Mass spectral data. DNA binding activities of the complexes 1d and 2d are studied by UV-Vis spectroscopy and cleavage studies of Schiff base ligand and its complexes 1d and 2d have been by agarose gel electrophoresis method. In vitro biological activities of the free ligand (HA) and their metal complexes (1a-1e and 2a-2e) were screened against few bacteria, Escherichia coli, Staphylococcus saphyphiticus, Staphylococcus aureus, Pseudomonas aeruginosa and fungi Aspergillus niger, Enterobacter species, Candida albicans by well diffusion technique. PMID:23981416

Subbaraj, P; Ramu, A; Raman, N; Dharmaraja, J



O-Carbonyl-Assisted Alkaline Hydrolyses of Methyl Benzoates.  

National Technical Information Service (NTIS)

The rates of alkaline hydrolysis of methyl 6-methyl-2-benzoylbenzoate, methyl 6-methyl-2-acetylbenzoate, methyl 6-chloro-2-benzoylbenzoate, methyl 6-chloro-2-acetylbenzoate, and the 6-unsubstituted analogs have been measured. In each case the 6-substitute...

M. S. Newman A. L. Leegwater



Synthesis of Methylated Ethanolamine Moieties  

PubMed Central

The results of experiments in which intact plants of Lemna paucicostata were labeled with either l-[3H3C]methionine, l-[14CH3]methionine, or [1,2-14C]ethanolamine support the conclusion that growth in concentrations of choline of 3.0 micromolar or above brings about marked decreases in the rate of biosynthesis of methylated forms of ethanolamine (normally present chiefly as phosphatidylcholine, with lesser amounts of choline and phosphocholine). The in vivo locus of the block is at the committing step in the biosynthetic sequence at which phosphoethanolamine is methylated by S-adenosylmethionine to form phosphomethylethanolamine. The block is highly specific: flow of methyl groups originating in methionine continues into S-adenosylmethionine, S-methylmethionine, the methyl moieties of pectin methyl ester, and other methylated metabolites. When choline uptake is less than the total that would be synthesized by control plants, phosphoethanolamine methylation is down-regulated to balance the uptake; total plant content of choline and its derivatives remains essentially constant. At maximum down-regulation, phosphoethanolamine methylation continues at 5 to 10% of normal. A specific decrease in the total available activity of AdoMet: phosphoethanolamine N-methyltransferase, as well as feedback inhibition of this enzyme by phosphocholine, and prevention of accumulation of phosphoethanolamine by down-regulation of ethanolamine synthesis may each contribute to effective control of phosphoethanolamine methylation. This down-regulation may necessitate major changes in S-adenosylmethionine metabolism. Such changes are discussed.

Mudd, S. Harvey; Datko, Anne H.



Electrochemical strategy for sensing DNA methylation and DNA methyltransferase activity.  


The present work demonstrates a novel signal-off electrochemical method for the determination of DNA methylation and the assay of methyltransferase activity using the electroactive complex [Ru(NH3)6](3+) (RuHex) as a signal transducer. The assay exploits the electrostatic interactions between RuHex and DNA strands. Thiolated single strand DNA1 was firstly self-assembled on a gold electrode via Au-S bonding, followed by hybridization with single strand DNA2 to form double strand DNA containing specific recognition sequence of DNA adenine methylation MTase and methylation-responsive restriction endonuclease Dpn I. The double strand DNA may adsorb lots of electrochemical species ([Ru(NH3)6](3+)) via the electrostatic interaction, thus resulting in a high electrochemical signal. In the presence of DNA adenine methylation methyltransferase and S-adenosyl-l-methionine, the formed double strand DNA was methylated by DNA adenine methylation methyltransferase, then the double strand DNA can be cleaved by methylation-responsive restriction endonuclease Dpn I, leading to the dissociation of a large amount of signaling probes from the electrode. As a result, the adsorption amount of RuHex reduced, resulting in a decrease in electrochemical signal. Thus, a sensitive electrochemical method for detection of DNA methylation is proposed. The proposed method yielded a linear response to concentration of Dam MTase ranging from 0.25 to 10UmL(-1) with a detection limit of 0.18UmL(-1) (S/N=3), which might promise this method as a good candidate for monitoring DNA methylation in the future. PMID:23473252

Wang, Gang Lin; Zhou, Long Yin; Luo, Hong Qun; Li, Nian Bing



Antagonism between DNA and H3K27 Methylation at the Imprinted Rasgrf1 Locus  

PubMed Central

At the imprinted Rasgrf1 locus in mouse, a cis-acting sequence controls DNA methylation at a differentially methylated domain (DMD). While characterizing epigenetic marks over the DMD, we observed that DNA and H3K27 trimethylation are mutually exclusive, with DNA and H3K27 methylation limited to the paternal and maternal sequences, respectively. The mutual exclusion arises because one mark prevents placement of the other. We demonstrated this in five ways: using 5-azacytidine treatments and mutations at the endogenous locus that disrupt DNA methylation; using a transgenic model in which the maternal DMD inappropriately acquired DNA methylation; and by analyzing materials from cells and embryos lacking SUZ12 and YY1. SUZ12 is part of the PRC2 complex, which is needed for placing H3K27me3, and YY1 recruits PRC2 to sites of action. Results from each experimental system consistently demonstrated antagonism between H3K27me3 and DNA methylation. When DNA methylation was lost, H3K27me3 encroached into sites where it had not been before; inappropriate acquisition of DNA methylation excluded normal placement of H3K27me3, and loss of factors needed for H3K27 methylation enabled DNA methylation to appear where it had been excluded. These data reveal the previously unknown antagonism between H3K27 and DNA methylation and identify a means by which epigenetic states may change during disease and development.

McLean, Chelsea M.; Dokshin, Gregoriy A.; Persson, Jenna M.; Herman, Herry; Pasini, Diego; Miro, Xavier; Donohoe, Mary E.; Lee, Jeannie T.; Helin, Kristian; Soloway, Paul D.



Copolymers of Methyl Alpha-N-Alkylacrylate and Methyl Methacrylate.  

National Technical Information Service (NTIS)

This patent relates to methyl methacrylate and methyl alpha-n-alkylacrylate wherein the alkyl group, which may vary from 10 to 22 carbon atoms, copolymerize at about 50C in the presence of azobisisobutyronitrile to form polymers having low coefficients of...

H. Gisser H. E. Mertwoy



Differential Subnuclear Localization and Replication Timing of Histone H3 Lysine 9 Methylation States  

Microsoft Academic Search

ABSTRACT Mono-, di- and tri-methylation of specific histone residues adds an additional level of complexity tothe range of histone modifications that may contribute to a histone code. However, it has not been clear whether different methylated states reside stably at different chromatin sites, or whether they represent dynamic intermediates at the same chromatin sites. Here, we have used recently developed

Rong Wu; Anna V. Terry; Prim B. Singh; David M. Gilbert



Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues  

Microsoft Academic Search

Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation

Susan K. Murphy; Zhiqing Huang; Cathrine Hoyo



Phospholipid Methylation and Biological Signal Transmission  

Microsoft Academic Search

Many types of cells methylate phospholipids using two methyl-transferase enzymes that are asymmetrically distributed in membranes. As the phospholipids are successively methylated, they are translocated from the inside to the outside of the membrane. When catecholamine neurotransmitters, lectins, immunoglobulins or chemotaxic peptides bind to the cell surface, they stimulate the methyl-transferase enzymes and reduce membrane viscosity. The methylation of phospholipids

Fusao Hirata; Julius Axelrod



21 CFR 177.2000 - Vinylidene chloride/methyl acrylate/methyl methacrylate polymers.  

Code of Federal Regulations, 2010 CFR

...methyl acrylate/methyl methacrylate polymers. 177.2000 Section 177.2000...CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components...methyl acrylate/methyl methacrylate polymers. The vinylidene...



21 CFR 177.2000 - Vinylidene chloride/methyl acrylate/methyl methacrylate polymers.  

Code of Federal Regulations, 2010 CFR

...methyl acrylate/methyl methacrylate polymers. 177.2000 Section 177.2000...CONTINUED) INDIRECT FOOD ADDITIVES: POLYMERS Substances for Use as Basic Components...methyl acrylate/methyl methacrylate polymers. The vinylidene...



Methylation oligonucleotide microarray: a novel tool to analyze methylation patterns  

NASA Astrophysics Data System (ADS)

A new technique to analyze methylation patterns in several adjacent CpG sites was developed and reported here. We selected a 336bp segment of the 5"-untranslated region and the first exon of the p16Ink4a gene, which include the most densely packed CpG fragment of the islands containing 32 CpG dinucleotides, as the investigated target. The probes that include all types of methylation patterns were designed to fabricate a DNA microarray to determine the methylation patterns of seven adjacent CpG dinucleotides sites. High accuracy and reproducibility were observed in several parallel experiments. The results led us to the conclusion that the methylation oligonucleotide microarray can be applied as a novel and powerful tool to map methylation patterns and changes in multiple CpG island loci in a variety of tumors.

Hou, Peng; Ji, Meiju; He, Nongyao; Lu, Zuhong



4,4'-, 5,5'-, and 6,6'-dimethyl-2,2'-bipyridyls: the structures, phase transitions, vibrations, and methyl group tunneling of their complexes with chloranilic acid.  


The crystal and molecular structures of 4,4(')- and 6,6(')-dimethyl-2,2(')-bipyridyl complexes with 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (chloranilic acid, CLA) have been determined and compared with those of the complex with the 5,5(')-derivative, which is known to possess interesting antiferroelectric properties. In the crystalline state, all three compounds form hydrogen bonded chains with N(+)-H···O(-) and O-H···N bridges on both sides of the bipyridyl constituent. The comparison of three derivatives indicates that the N(+)-H···O(-) hydrogen bonds are shortest for the 5,5(')-dimethyl complex. The 4,4(')- and 6,6(')-derivatives do not show any ferroelectric feature. The 6,6(')-one is, however, characterized by a continuous phase transition, revealed in the differential scanning calorimetry, dilatometric, and dielectric characteristics. The tunneling splitting measured by neutron backscattering in the energy range ±30 ?eV for the neat dimethyl bipyridyls and their complexes with CLA indicates that the different splittings are primarily due to the crystal packing effect and that charge transfer between interacting compounds plays only a minor role. PMID:21806140

Bator, G; Sawka-Dobrowolska, W; Sobczyk, L; Grech, E; Nowicka-Scheibe, J; Pawlukoj?, A; Wuttke, J; Baran, J; Owczarek, M



Identification of methylation sites and effects of phototaxis stimuli on transducer methylation in Halobacterium salinarum.  


The two transducers in the phototaxis system of the archaeon Halobacterium salinarum, HtrI and HtrII, are methyl-accepting proteins homologous to the chemotaxis transducers in eubacteria. Consensus sequences predict three glutamate pairs containing potential methylation sites in HtrI and one in HtrII. Mutagenic substitution of an alanine pair for one of these, Glu265-Glu266, in HtrI and for the homologous Glu513-Glu514 in HtrII eliminated methylation of these two transducers, as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autofluorography. Photostimulation of the repellent receptor sensory rhodopsin II (SRII) induced reversible demethylation of HtrII, while no detectable change in the extent of methylation of HtrI was observed in response to stimulation of its cognate sensory rhodopsin, the attractant receptor SRI. Cells containing HtrI or HtrII with all consensus sites replaced by alanine still exhibited phototaxis responses and behavioral adaptation, and methanol release assays showed that methyl group turnover was still induced in response to photostimulation of SRI or SRII. By pulse-chase experiments with in vivo L-[methyl-(3)H]methionine-labeled cells, we found that repetitive photostimulation of SRI complexed with wild-type (or nonmethylatable) HtrI induced methyl group turnover in transducers other than HtrI to the same extent as in wild-type HtrI. Both attractant and repellent stimuli cause a transient increase in the turnover rate of methyl groups in wild-type H. salinarum cells. This result is unlike that obtained with Escherichia coli, in which attractant stimuli decrease and repellent stimuli increase turnover rate, and is similar to that obtained with Bacillus subtilis, which also shows turnover rate increases regardless of the nature of the stimulus. We found that a CheY deletion mutant of H. salinarum exhibited the E. coli-like asymmetric pattern, as has recently also been observed in B. subtilis. Further, we demonstrate that the CheY-dependent feedback effect does not require the stimulated transducer to be methylatable and operates globally on other transducers present in the cell. PMID:10482508

Perazzona, B; Spudich, J L



Neural Tube Defects, Folic Acid and Methylation  

PubMed Central

Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

Imbard, Apolline; Benoist, Jean-Francois; Blom, Henk J.



DNA methylation and human disease  

Microsoft Academic Search

DNA methylation is a crucial epigenetic modification of the genome that is involved in regulating many cellular processes. These include embryonic development, transcription, chromatin structure, X chromosome inactivation, genomic imprinting and chromosome stability. Consistent with these important roles, a growing number of human diseases have been found to be associated with aberrant DNA methylation. The study of these diseases has

Keith D. Robertson



Fluorometric Assay of Methyl Ketones.  

National Technical Information Service (NTIS)

A quantitative kinetic fluorescence method is reported for alpha-methyl ketones, e.g., acetone and acetophenone. The reaction involves the condensation of o-nitrobenzaldehyde with the alpha-methyl ketones at pH 12.5 to form the fluorescent indoxyl. The ra...

D. N. Kramer E. B. Hackley L. U. Tolentino



Biogeochemistry: Mercury methylation made easy  

NASA Astrophysics Data System (ADS)

The exact mechanism used by microorganisms to produce the neurotoxin methyl mercury is unclear. The latest laboratory studies point to the amino acid cysteine as an important aid for the uptake of inorganic mercury and its transformation to methyl mercury in Geobacter sulfurreducens.

Sparling, Richard



Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease  

PubMed Central

The enzymes catalyzing lysine and arginine methylation of histones are essential for maintaining transcriptional programs and determining cell fate and identity. Until recently, histone methylation was regarded irreversible. However, within the last few years, several families of histone demethylases erasing methyl marks associated with gene repression or activation have been identified, underscoring the plasticity and dynamic nature of histone methylation. Recent discoveries have revealed that histone demethylases take part in large multiprotein complexes synergizing with histone deacetylases, histone methyltransferases, and nuclear receptors to control developmental and transcriptional programs. Here we review the emerging biochemical and biological functions of the histone demethylases and discuss their potential involvement in human diseases, including cancer.

Cloos, Paul A.C.; Christensen, Jesper; Agger, Karl; Helin, Kristian



Absolute configuration of methyl isoeichlerialactone  

PubMed Central

The title compound, C28H44O4·0.56H2O, is a co-crystal of methyl isoeichlerialactone monohydrate as the major component and methyl isoeichlerialactone as the minor component in a 0.55778?(3):0.44222?(3) ratio. The conformations of both components are identical except for that of the –COOCH3 group of the methyl propanoate side chain on the cyclo­hexane ring which is positionally disordered over two orientations. The mol­ecule of methyl isoeichlerialactone has three fused rings and all rings are trans-fused. The two cyclo­hexane rings are in standard chair conformations and the cyclo­pentane ring adopts an envelope conformation. In the crystal, weak C—H?O inter­actions link methyl isoeichlerialactone mol­ecules into screw chains along [010]. The crystal structure is further stabilized by O—H?O hydrogen bonds and weak C—H?O inter­actions.

Fun, Hoong-Kun; Joycharat, Nantiya; Voravuthikunchai, Supayang Piyawan; Chantrapromma, Suchada



Desoxyhemigossypol 6-methyl ether  

PubMed Central

The title sesquiterpene [systematic name: 6-methoxy-10-methyl-7-(propan-2-yl)-2-oxatricyclo[,12]dodeca-1(11),4,6,8(12),9-pentaen-5-ol], C16H18O3, was isolated from pathogen-infected stele tissue of Gossypium barbadense. There are two mol­ecules in the asymmetric unit and the dihedral angle between their naphtho­furan systems is 86.48?(2)°. In the crystal, O—H?O hydrogen bonds between the hy­droxy groups and etheric O atoms link the mol­ecules into centrosymmetric tetra­mers. These tetra­mers are assembled into (010) layers via stacking inter­actions between the naphtho­furan systems [inter­planar distance 3.473?(3)?Å] and short C—H?O contacts.

Uzbekov, Vyacheslav V.; Talipov, Samat A.; Ibragimov, Bakhtiyar T.; Stipanovic, Robert D.; Liu, Jinggao



Methyl Halide Production by Fungi  

NASA Astrophysics Data System (ADS)

Methyl chloride (CH3Cl), methyl bromide (CH3Br) and methyl iodide (CH3I) are methyl halide gases that contribute significant amounts of halogen radicals to the atmosphere. In an effort to better understand the global budget of methyl halides and their impact on the atmosphere, we need to identify the natural sources in addition to the known anthropogenic sources of these compounds. We are investigating the role of fungi in the production of methyl halides in the soils and wetlands in southern New Hampshire, USA. Previous research has shown that wood decay fungi and ectomycorrhizal fungi, which are within a group of fungi called basidiomycetes, emit methyl halides. In our study, measurements of headspace gas extracted from flasks containing fungi grown in culture demonstrate that a variety of fungi, including basidiomycetes and non-basidiomycetes, emit methyl halides. Our research sites include four ecosystems: an agricultural field, a temperate forest, a fresh water wetland, and coastal salt marshes. We have collected and isolated fungi at each site by culturing tissue samples of fruiting bodies and plant material, by using wood baits, and from the direct culture of soil. We compared the rates of methyl halide emissions from the fungi in the four ecosystems. In addition, we measured emissions from previously assayed fungal isolates after reintroducing them to sterilized soils that were collected from their original environments. Fungal biomass was determined by substrate-induced respiration (SIR). The emission rate by the fungus was determined by a linear regression of the concentration of methyl halide in the sample headspace over time divided by the fungal biomass.

Dailey, G. D.; Varner, R. K.; Blanchard, R. O.; Sive, B. C.; Crill, P. M.



Factors underlying variable DNA methylation in a human community cohort  

PubMed Central

Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression. We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated.

Lam, Lucia L.; Emberly, Eldon; Fraser, Hunter B.; Neumann, Sarah M.; Chen, Edith; Miller, Gregory E.; Kobor, Michael S.



The 'golden age' of DNA methylation in neurodegenerative diseases.  


DNA methylation reactions are regulated, in the first instance, by enzymes and the intermediates that constitute the 'so called' one-carbon metabolism. This is a complex biochemical pathway, also known as the homocysteine cycle, regulated by the presence of B vitamins (folate, B6, B12) and choline, among other metabolites. One of the intermediates of this metabolism is S-adenosylmethionine, which represent the methyl donor in all the DNA methyltransferase reactions in eukaryotes. The one-carbon metabolism therefore produces the substrate necessary for the transferring of a methyl group on the cytosine residues of DNA; S-adenosylmethionine also regulates the activity of the enzymes that catalyze this reaction, namely the DNA methyltransferases (DNMTs). Alterations of this metabolic cycle can therefore be responsible for aberrant DNA methylation processes possibly leading to several human diseases. As a matter of fact, increasing evidences indicate that a number of human diseases with multifactorial origin may have an epigenetic basis. This is also due to the great technical advances in the field of epigenetic research. Among the human diseases associated with epigenetic factors, aging-related and neurodegenerative diseases are probably the object of most intense research. This review will present the main evidences linking several human diseases to DNA methylation, with particular focus on neurodegenerative diseases, together with a short description of the state-of-the-art of methylation assays. PMID:23183753

Fuso, Andrea



Iridium-catalyzed oxidative methyl esterification of primary alcohols and diols with methanol.  


Oxidative methyl esterification of primary alcohols and diols with methanol was successfully achieved, using acetone as a hydrogen acceptor, under the influence of an iridium complex combined with 2-(methylamino)ethanol (MAE) as catalyst. PMID:21413815

Yamamoto, Nobuyuki; Obora, Yasushi; Ishii, Yasutaka



Differentially Methylated Regions of Imprinted Genes in Prenatal, Perinatal and Postnatal Human Tissues  

PubMed Central

Epigenetic plasticity in relation to in utero exposures may mechanistically explain observed differences in the likelihood of developing common complex diseases including hypertension, diabetes and cardiovascular disease through the cumulative effects of subtle alterations in gene expression. Imprinted genes are essential mediators of growth and development and are characterized by differentially methylated regulatory regions (DMRs) that carry parental allele-specific methylation profiles. This theoretical 50% level of methylation provides a baseline from which endogenously- or exogenously-induced deviations in methylation can be detected. We quantified DNA methylation at imprinted gene DMRs in a large panel of human conceptal tissues, in matched buccal cell specimens collected at birth and at one year of age, and in the major cell fractions of umbilical cord blood to assess the stability of methylation at these regions. DNA methylation was measured using validated pyrosequencing assays at seven DMRs regulating the IGF2/H19, DLK1/MEG3, MEST, NNAT and SGCE/PEG10 imprinted domains. DMR methylation did not significantly differ for the H19, MEST and SGCE/PEG10 DMRs across all conceptal tissues analyzed (ANOVA p>0.10). Methylation differences at several DMRs were observed in tissues from brain (IGF2 and MEG3-IG DMRs), liver (IGF2 and MEG3 DMRs) and placenta (both DLK1/MEG3 DMRs and NNAT DMR). In most infants, methylation profiles in buccal cells at birth and at one year of age were comparable, as was methylation in the major cell fractions of umbilical cord blood. Several infants showed temporal deviations in methylation at multiple DMRs. Similarity of inter-individual and intra-individual methylation at some, but not all of the DMRs analyzed supports the possibility that methylation of these regions can serve as useful biosensors of exposure.

Murphy, Susan K.; Huang, Zhiqing; Hoyo, Cathrine



Epigenome-wide inheritance of cytosine methylation variants in a recombinant inbred population.  


Cytosine DNA methylation is one avenue for passing information through cell divisions. Here, we present epigenomic analyses of soybean recombinant inbred lines (RILs) and their parents. Identification of differentially methylated regions (DMRs) revealed that DMRs mostly cosegregated with the genotype from which they were derived, but examples of the uncoupling of genotype and epigenotype were identified. Linkage mapping of methylation states assessed from whole-genome bisulfite sequencing of 83 RILs uncovered widespread evidence for local methylQTL. This epigenomics approach provides a comprehensive study of the patterns and heritability of methylation variants in a complex genetic population over multiple generations, paving the way for understanding how methylation variants contribute to phenotypic variation. PMID:23739894

Schmitz, Robert J; He, Yupeng; Valdés-López, Oswaldo; Khan, Saad M; Joshi, Trupti; Urich, Mark A; Nery, Joseph R; Diers, Brian; Xu, Dong; Stacey, Gary; Ecker, Joseph R



A mobility shift detection method for DNA methylation analysis using phosphate affinity polyacrylamide gel electrophoresis.  


We describe a procedure for DNA methylation analysis using the bisulfite-mediated cytosine-to-uracil conversion of a target DNA followed by methylation-specific polymerase chain reaction (MSP) and phosphate affinity polyacrylamide gel electrophoresis (PAGE). The MSP was performed using a 1:1 mixture of 5'-phosphorylated methylation-specific and 5'-OH non-methylation-specific primers. The PAGE using an immobilized phosphate-binding tag molecule (i.e., a polyacrylamide-bound dizinc(II) complex, Zn(2+)-Phos-tag), which selectively captures the 5'-phosphorylated DNA fragment, enabled the mobility shift detection of the methylation-specific product as a slower migration band. Using this novel procedure, we demonstrated the detection of a methylated cytosine base in a pUC19 plasmid. PMID:18394999

Kinoshita-Kikuta, Emiko; Kinoshita, Eiji; Koike, Tohru



Cytosine methylation inhibits replication of African cassava mosaic virus by two distinct mechanisms.  

PubMed Central

Extrachromosomally replicating viral DNA is usually free of cytosine methylation and viral templates methylated in vitro are poor substrates when used in replication assays. We have investigated the mechanism of inhibition of viral replication by DNA methylation using as a model the DNA A of African cassava mosaic virus. We have constructed two component helper systems which allow for separation of the transcriptional inhibition of viral genes necessary for replication from replication inhibition due to altered interaction between the replication complex and methylated viral DNA. Our results suggest that methylation-mediated reduction of viral replication is due to both repression mechanisms and that this provides two independent selection pressures for the maintenance of methylation-free replicons in infected cells. Images

Ermak, G; Paszkowski, U; Wohlmuth, M; Scheid, O M; Paszkowski, J



Genome-wide screening for understanding the role of DNA methylation in colorectal cancer.  


DNA methylation analysis methods have undergone an impressive revolution over the past 15 years. Regarding colorectal cancer (CRC), the localization and distribution of several differently methylated genes have been determined by genome-wide DNA methylation assays. These genes do not just influence the pathogenesis of CRC, but can be used further as diagnostic or prognostic markers. Moreover, the identified four DNA methylation-based subgroups of CRC have important clinical and therapeutic merit. Since genome-wide DNA methylation analyzes result in a large amount of data, there is a need for complex bioinformatic and pathway analysis. Future challenges in epigenetic alterations of CRC include the demand for comprehensive identification and experimental validation of gene abnormalities. By introduction of genome-wide DNA methylation profiling into clinical practice not only the patients' risk stratification but development of targeted therapies will also be possible. PMID:24059802

Sipos, Ferenc; M?zes, Györgyi; Patai, Arpád V; F?ri, István; Péterfia, Bálint; Hollósi, Péter; Molnár, Béla; Tulassay, Zsolt



Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing  

Microsoft Academic Search

Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate

Ru Cao; Liangjun Wang; Hengbin Wang; Li Xia; Hediye Erdjument-Bromage; Paul Tempst; Richard S. Jones; Yi Zhang



A rapid low temperature method for preparation of methyl esters of fatty acids  

Microsoft Academic Search

A rapid method for preparation of methyl esters of fatty acids in lipids has been accomplished by forming the sulfuric acid\\u000a complex of the lipid in ethyl ether at the temp of a dry ice-acetone bath. Decomposition of the complex with methanol results\\u000a in direct formation of methyl esters of the fatty acids. A comparison was made of gas liquid

Gertrude W. McGinnis; L. R. Dugan



Eukaryotic Methyl-CpG-Binding Domain Proteins and Chromatin Modification  

Microsoft Academic Search

Gene regulation in eukaryotic cells is in part mediated through programs of chromatin methylation. On the DNA level, the presence of m5C, mostly at the CpG positions in the vertebrate genomes, allows the recruitment of multisubunit complex(es) consisting of the histone deacetylases and the so-called methyl-CpG-binding domain (MBD) proteins (2). These proteins each contain the MBD motif. Previously, a group

Ming-Shiu Hung; C.-K. J. Shen



Penta-aqua-(di-methyl-formamide)-cobalt(II) sulfate di-methyl-formamide monosolvate.  


The title compound, [Co(C3H7NO)(H2O)5]SO4·C3H7NO, contains five aqua ligands, a Co(II) atom, a sulfate ion and both a coordinating and a non-coordinating di-methyl-formamide (DMF) mol-ecule. The DMF solvent mol-ecule lies between the complex units, which are located along the b axis. The sulfate ion is for charge balance. The Co(II) atom has distorted octa-hedral coordination geometry, being ligated by five aqua ligands and the O atom of the DMF ligand. O-H?O hydrogen bonds between the aqua ligands and the sulfate anion and non-coordinating DMF molecule lead to the formation of a three-dimensional network. Since all constituents lie on a mirror plane, the H atoms of all methyl groups and of one of the aqua ligands are equally disordered over two positions. PMID:24046556

Ta?, Murat; Camur, Seval; Topal, Sevim



Reactions of ?-dichlorobis(? 3-allyl)palladium(II) with bis(1 -H-benzo-triazolyl-methyl) selenide: Formation of unexpected polymeric structure with dormant Se donor site. Applications of the polymeric Pd-complexes in Heck coupling  

Microsoft Academic Search

Bis(1-H-benzotriazolylmethyl)selenide (L) has been synthesized by reacting Se2? generated in situ with 1-(chloromethyl)-1H-benzotriazole. Proton, C-13 and Se-77 NMR spectra of L are characteristic. ?-Dichlorobis(?3-allyl)palladium(II) reacts with L resulting in polymeric complexes which give single crystals of stoichiometry [Pd(?3-C3H5)(L)]·ClO4\\/PF6·CH3CN (1\\/2). The single crystal X-ray diffraction analyses of these polymeric species reveal that they have chain type of structures, and anions through

Dipanwita Das; Monika Singh; Ajai K. Singh



Detection of altered global DNA methylation in coronary artery disease patients.  


Epigenetic modifications, especially alteration in DNA methylation, are increasingly being recognized as a key factor in the pathogenesis of complex disorders, including atherosclerosis. However, there are limited data on the epigenetic changes in the coronary artery disease (CAD) patients. In the present study we evaluated the methylation status of genomic DNA from peripheral lymphocytes in a cohort of 287 individuals: 137 angiographically confirmed CAD patients and 150 controls. The differential susceptibility of genomic DNA to methylation-sensitive restriction enzymes was utilized to assess the methylation status of the genome. We observed that the genomic DNA methylation in CAD patients is significantly higher than in controls (p < 0.05). Since elevated homocysteine levels are known to be an independent risk factor for CAD and a key modulator of macromolecular methylation, we investigated the probable correlation between plasma homocysteine levels and global DNA methylation. We observed a significant positive correlation of global DNA methylation with plasma homocysteine levels in CAD patients (p = 0.001). Further, within a higher range of serum homocysteine levels (>/=12-50 muM), global DNA methylation was significantly higher in CAD patients than in controls. The alteration in genomic DNA methylation associated with cardiovascular disease per se appears to be further accentuated by higher homocysteine levels. PMID:18613790

Sharma, Priyanka; Kumar, Jitender; Garg, Gaurav; Kumar, Arun; Patowary, Ashok; Karthikeyan, Ganesan; Ramakrishnan, Lakshmy; Brahmachari, Vani; Sengupta, Shantanu



Forms of CDDO methyl ester  

US Patent & Trademark Office Database

A triterpenoid compound, methyl 2-cyano-3,12-dioxoleana-1,9(11)-dien-28-oate (CDDO methyl ester), has a non-crystalline, glassy solid form and a non-hydrous crystalline form that can prepared, for example, from a saturated methanol solution. The glassy form displays an enhanced bioavailability over the non-hydrous crystalline form. Each form of CDDO methyl ester is a superior candidate for use, typically in solid dosage form, for treating a variety of disease states, generally associated with inflammation.



Rice Allelopathy Induced by Methyl Jasmonate and Methyl Salicylate  

Microsoft Academic Search

Methyl jasmonate (MeJA) and methyl salicylate (MeSA) are important signaling molecules that induce plant defense against insect\\u000a herbivores and microbial pathogens. We tested the hypothesis that allelopathy is an inducible defense mechanism, and that\\u000a the JA and SA signaling pathways may activate allelochemicals release. Exogenous application of MeJA and MeSA to rice (Oryza sativa L.) enhanced rice allelopathic potential and

Hai Hong Bi; Ren Sen Zeng; Li Ming Su; Min An; Shi Ming Luo




PubMed Central

The title compound, C9H9ClN2, was prepared from the reaction of N-methyl­benzene-1,2-diamine and 2-chloro­acetic acid in boiling 6 M hydro­chloric acid. The benzimidazole unit is approximately planar, the largest deviation from the mean plane being 0.008?(1)?Å. The Cl atom is displaced by 1.667?(2)?Å from this plane. The methyl group is statistically disordered with equal occupancy.

Han, Jie; Zhang, Jun; Yang, Qi; Zhao, Ming-gao; Fan, Guang



Proton magnetic resonance in methyl alcohol and methyl mercaptan  

Microsoft Academic Search

Measurements are reported of the nuclear magnetic resonance parameters of methyl alcohol and methyl mercaptan (CH3SH). The spin-lattice relaxation time T1 and the chemical shift delta have been measured for both liquids, and for both types of proton for T1 from the supercooled liquid up to the critical temperature. The variations of both T1 and delta reflect the considerable difference

K. Krynicki; J. G. Powles



Photodissociation of Methyl Chloride and Methyl Bromide in the Atmosphere  

Microsoft Academic Search

Methyl chloride (CHâCl) and methyl bromide (CHâBr) have been suggested to be significant sources of the stratospheric halogens. The breakup of these compounds in the stratosphere by photodissociation or reaction with OH releases halogen atoms which catalytically destroy ozone. Experimental results are presented for ultra-violet photoabsorption cross sections of CHâCl and CHâBr. Calculations are presented of loss rates for the

Donald E. Robbins



Bis[mu-2-[(1,5-diaza-1-cyclooctyl)-methyl]phenolato-N,N',O:O]bis-[chlorozinc(II)]diacetone solvate: design of a square-pyramidal ZnN2O2Cl complex.  


The title complex, [Zn(2)(C(13)H(19)N(2)O)(2)Cl(2)].2C(3)H(6)O, resides on a crystallographic inversion center. The two Zn(II) centers bridged by the phenoxo groups are in pentacoordinated distorted square-pyramidal coordination environments with an intramolecular Zn...Zn distance of 3.175 (3) A. The mesocyclic ligand takes a boat-chair conformation and an H atom from the 1,5-diazacyclooctane ring effectively blocks the axial coordination site opposite the Cl ligand to form the ZnN(2)O(2)Cl geometry. The crystal structure is stabilized by a N-H...O hydrogen bond between the amino group and an acetone molecule. PMID:11498603

Xu, Q; Du, M; Guo, Y M; Bu, X H



Protein methylation and DNA repair.  


DNA is under constant attack from intracellular and external mutagens. Sites of DNA damage need to be pinpointed so that the DNA repair machinery can be mobilized to the proper location. The identification of damaged sites, recruitment of repair factors, and assembly of repair "factories" is orchestrated by posttranslational modifications (PTMs). These PTMs include phosphorylation, ubiquitination, sumoylation, acetylation, and methylation. Here we discuss recent data surrounding the roles of arginine and lysine methylation in DNA repair processes. PMID:17306845

Lake, Aimee N; Bedford, Mark T



Adenine Methylation in Eukaryotic DNA  

Microsoft Academic Search

N6-Methyladenine (m6A) has been found in DNAs of various eukaryotes (algae, fungi, protozoa, and higher plants). Like bacterial DNA, DNAs of these organisms are subject to enzymatic modification (methylation) not only at cytosine, but also at adenine bases. There is indirect evidence that adenine methylation of the genome occurs in animals as well. In plants, m6A was detected in total,

B. F. Vanyushin



Vibrational absorption, vibrational circular dichroism, and theoretical studies of methyl lactate self-aggregation and methyl lactate-methanol intermolecular interactions  

NASA Astrophysics Data System (ADS)

The infrared vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of methyl lactate in carbon tetrachloride and methanol have been measured in the 1000-1800 cm-1 region. Noticeable changes due to the solute self-aggregation and solvent-solute intermolecular hydrogen-bonding interactions have been detected in the reported spectra of the 2M methyl lactate solution in CCl4 and in methanol, respectively. Molecular dynamics simulations and a series of density functional theory (DFT) B3LYP/6-311++G**) and single point MP2/6-311++G** energy calculations have been performed to identify and to model the explicit hydrogen-bonding interactions between the methanol solvent and the methyl lactate solute and among the methyl lactate molecules. Geometry search and optimization have been performed for the most stable conformers of the methyl lactate dimer and the methyl lactate-(methanol)N clusters, with N=1, 2, and 3. The relative single point MP2 energies among conformers are noticeably different from those obtained with DFT for the larger methyl lactate-methanol complexes. The VA and VCD spectra of these complexes have been simulated and compared to the corresponding experimental spectra. From the combined experimental and theoretical VA and VCD studies, it has been identified that both the methyl lactate monomer and dimer are the main species in the 2M CCl4 solution with 65% and 35% relative abundances, respectively, while the binary (55%) and quaternary (30%) methyl lactate-methanol clusters dominate in the 2M methanol solution, together with a smaller amount (15%) of the methyl lactate monomer. The effects of solute self-aggregation and solute-solvent interactions have been investigated in detail.

Liu, Yang; Yang, Guochun; Losada, Martin; Xu, Yunjie



DNA Methylation, Cancer Susceptibility, and Nutrient Interactions  

Microsoft Academic Search

DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated




Thermodynamic analysis of arsenic methylation.  


The Challenger mechanism for the methylation of arsenic is a repeating sequence of a two-electron reduction of pentavalent arsenic As(V) species to trivalent arsenic As(III) species followed by a methylation-oxidation reaction forming the successive methyl As(V) species. This unusual oxidation-reduction sequence prompted an examination of the thermodynamics of these reactions. Quantum chemical methods are employed to estimate the thermodynamic parameters for the methyl arsenic species. The sequence is thermodynamically favored at neutral pH for redox potentials with pe < 0 and methyl cation activities pCH3+ < -3 to -7 depending on the precise situation analyzed. The observed distribution of methyl arsenic species in human urine, which is remarkably constant across many studied populations, can be reproduced using an equilibrium model if the formation of TMA species is prevented. The estimated thermodynamic parameters are sufficiently accurate to evaluate questions of thermodynamic plausibility but not the precise details of speciation. PMID:15871252

Dombrowski, Paul M; Long, Wei; Farley, Kevin J; Mahony, John D; Capitani, Joseph F; Di Toro, Dominic M



Water Mediated Ligand Functional Group Cooperativity: The Contribution of a Methyl Group to Binding Affinity is Enhanced by a COO? Group Through Changes in the Structure and Thermo dynamics of the Hydration Waters of Ligand-Thermolysin Complexes  

PubMed Central

Ligand functional groups can modulate the contributions of one another to the ligand-protein binding thermodynamics, producing either positive or negative cooperativity. Data presented for four thermolysin phosphonamidate inhibitors demonstrate that the differential binding free energy and enthalpy caused by replacement of a H with a Me group, which binds in the well-hydrated S2? pocket, are more favorable in presence of a ligand carboxylate. The differential entropy is however less favorable. Dissection of these differential thermodynamic parameters, X-ray crystallography, and density-functional theory calculations suggest that these cooperativities are caused by variations in the thermodynamics of the complex hydration shell changes accompanying the H?Me replacement. Specifically, the COO? reduces both the enthalpic penalty and the entropic advantage of displacing water molecules from the S2? pocket, and causes a subsequent acquisition of a more enthalpically, less entropically, favorable water network. This study contributes to understanding the important role water plays in ligand-protein binding.

Nasief, Nader N; Tan, Hongwei; Kong, Jing; Hangauer, David



A genome-wide methylation study on obesity  

PubMed Central

Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14–20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances.

Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A.; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Huidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling



DNA methylation and epigenetic inheritance during plant gametogenesis.  


In plants, newly acquired epigenetic states of transcriptional gene activity are readily transmitted to the progeny. This is in contrast to mammals, where only rare cases of transgenerational inheritance of new epigenetic traits have been reported (FASEB J 12:949-957, 1998; Nat Genet 23:314-318, 1999; Proc Natl Acad Sci U S A 100:2538-2543, 2003). Epigenetic inheritance in plants seems to rely on cytosine methylation maintained through meiosis and postmeiotic mitoses, giving rise to gametophytes. In particular, maintenance of CpG methylation ((m)CpG) appears to play a central role, guiding the distribution of other epigenetic signals such as histone H3 methylation and non-CpG DNA methylation. The evolutionarily conserved DNA methyltransferase MET1 is responsible for copying (m)CpG patterns through DNA replication in the gametophytic phase. The importance of gametophytic MET1 activity is illustrated by the phenotypes of met1 mutants that are severely compromised in the accuracy of epigenetic inheritance during gametogenesis. This includes elimination of imprinting at paternally silent loci such as FWA or MEDEA (MEA). The importance of DNA methylation in gametophytic imprinting has been reinforced by the discovery of DEMETER (DME), encoding putative DNA glycosylase involved in the removal of (m)C. DME opposes transcriptional silencing associated with imprinting activities of the MEA/FIE polycomb group complex. PMID:16249938

Takeda, Shin; Paszkowski, Jerzy



Tissue-specific dysregulation of DNA methylation in aging  

PubMed Central

SUMMARY The normal aging process is a complex phenomenon associated with physiological alterations in the function of cells and organs over time. Although an attractive candidate for mediating transcriptional dysregulation, the contribution of epigenetic dysregulation to these progressive changes in cellular physiology remains unclear. In this study, we employed the genome-wide HELP assay to define patterns of cytosine methylation throughout the rat genome, and the LUMA assay to measure global levels of DNA methylation in the same samples. We studied both liver and visceral adipose tissue, and demonstrated significant differences in DNA methylation with age at >5% of sites analyzed. Furthermore, we showed that epigenetic dysregulation with age is a highly tissue-dependent phenomenon. The most distinctive loci were located at intergenic sequences and conserved non-coding elements, and not at promoters nor at CG-dinucleotide dense loci. Despite this, we found that there was a subset of genes at which cytosine methylation and gene expression changes were concordant. Finally, we demonstrated that changes in methylation occur consistently near genes that are involved in metabolism and metabolic regulation, implicating their potential role in the pathogenesis of age-related diseases. We conclude that different patterns of epigenetic dysregulation occur in each tissue over time and may cause some of the physiological changes associated with normal aging.

Thompson, Reid F.; Atzmon, Gil; Gheorghe, Ciprian; Liang, Hong Qian; Lowes, Christina; Greally, John M.; Barzilai, Nir



Anticancer Activity of Methyl-Substituted Oxaliplatin Analogs†  

PubMed Central

Oxaliplatin is successfully used in systemic cancer therapy. However, resistance development and severe adverse effects are limiting factors for curative cancer treatment with oxaliplatin. The purpose of this study was to comparatively investigate in vitro and in vivo anticancer properties as well as the adverse effects of two methyl-substituted enantiomerically pure oxaliplatin analogs [[(1R,2R,4R)-4-methyl-1,2-cyclohexanediamine] oxalatoplatinum(II) (KP1537), and [(1R,2R,4S)-4-methyl-1,2-cyclohexanediamine]oxalatoplatinum(II) (KP1691)] and to evaluate the impact of stereoisomerism. Although the novel oxaliplatin analogs demonstrated in multiple aspects activities comparable with those of the parental compound, several key differences were discovered. The analogs were characterized by reduced vulnerability to resistance mechanisms such as p53 mutations, reduced dependence on immunogenic cell death induction, and distinctly attenuated adverse effects including weight loss and cold hyperalgesia. Stereoisomerism of the substituted methyl group had a complex and in some aspects even contradictory impact on drug accumulation and anticancer activity both in vitro and in vivo. To summarize, methyl-substituted oxaliplatin analogs harbor improved therapeutic characteristics including significantly reduced adverse effects. Hence, they might be promising metal-based anticancer drug candidates for further (pre)clinical evaluation.

Jungwirth, Ute; Xanthos, Dimitris N.; Gojo, Johannes; Bytzek, Anna K.; Korner, Wilfried; Heffeter, Petra; Abramkin, Sergey A.; Jakupec, Michael A.; Hartinger, Christian G.; Windberger, Ursula; Galanski, Markus; Keppler, Bernhard K.; Berger, Walter



Anticancer activity of methyl-substituted oxaliplatin analogs.  


Oxaliplatin is successfully used in systemic cancer therapy. However, resistance development and severe adverse effects are limiting factors for curative cancer treatment with oxaliplatin. The purpose of this study was to comparatively investigate in vitro and in vivo anticancer properties as well as the adverse effects of two methyl-substituted enantiomerically pure oxaliplatin analogs [[(1R,2R,4R)-4-methyl-1,2-cyclohexanediamine] oxalatoplatinum(II) (KP1537), and [(1R,2R,4S)-4-methyl-1,2-cyclohexanediamine]oxalatoplatinum(II) (KP1691)] and to evaluate the impact of stereoisomerism. Although the novel oxaliplatin analogs demonstrated in multiple aspects activities comparable with those of the parental compound, several key differences were discovered. The analogs were characterized by reduced vulnerability to resistance mechanisms such as p53 mutations, reduced dependence on immunogenic cell death induction, and distinctly attenuated adverse effects including weight loss and cold hyperalgesia. Stereoisomerism of the substituted methyl group had a complex and in some aspects even contradictory impact on drug accumulation and anticancer activity both in vitro and in vivo. To summarize, methyl-substituted oxaliplatin analogs harbor improved therapeutic characteristics including significantly reduced adverse effects. Hence, they might be promising metal-based anticancer drug candidates for further (pre)clinical evaluation. PMID:22331606

Jungwirth, Ute; Xanthos, Dimitris N; Gojo, Johannes; Bytzek, Anna K; Körner, Wilfried; Heffeter, Petra; Abramkin, Sergey A; Jakupec, Michael A; Hartinger, Christian G; Windberger, Ursula; Galanski, Markus; Keppler, Bernhard K; Berger, Walter



Polymerization of 4-methyl-1-pentene catalyzed by ?-diimine nickel catalysts: Living\\/controlled behavior, branch structure, and mechanism  

Microsoft Academic Search

Branched ?-olefin, 4-methyl-1-pentene (4 MP), was polymerized with classical ?-diimine nickel complexes in the presence of MAO. Influences of structure of ?-diimine nickel catalysts and polymerization parameters including temperature and [Al]\\/[Ni] mole ratio were evaluated. At 0 °C, 4-methyl-1-pentene can be polymerized in a living\\/controlled manner. The obtained poly(4-methyl-1-pentene)s are amorphous elastomers with low glass transition temperature (Tg). Nuclear magnetic resonance (NMR)

Haiyang Gao; Jin Pan; Lihua Guo; Dongjie Xiao; Qing Wu



Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism.  


DNA methylation of CpG dinucleotides is an important epigenetic modification of mammalian genomes and is essential for the regulation of chromatin structure, of gene expression and of genome stability. Differences in DNA methylation patterns underlie a wide range of biological processes, such as genomic imprinting, inactivation of the X chromosome, embryogenesis, and carcinogenesis. Inheritance of the epigenetic methylation pattern is mediated by the enzyme DNA methyltransferase 1 (Dnmt1), which methylates newly synthesized CpG sequences during DNA replication, depending on the methylation status of the template strands. The protein UHRF1 (also known as Np95 and ICBP90) recognizes hemi-methylation sites via a SET and RING-associated (SRA) domain and directs Dnmt1 to these sites. Here we report the crystal structures of the SRA domain in free and hemi-methylated DNA-bound states. The SRA domain folds into a globular structure with a basic concave surface formed by highly conserved residues. Binding of DNA to the concave surface causes a loop and an amino-terminal tail of the SRA domain to fold into DNA interfaces at the major and minor grooves of the methylation site. In contrast to fully methylated CpG sites recognized by the methyl-CpG-binding domain, the methylcytosine base at the hemi-methylated site is flipped out of the DNA helix in the SRA-DNA complex and fits tightly into a protein pocket on the concave surface. The complex structure suggests that the successive flip out of the pre-existing methylated cytosine and the target cytosine to be methylated is associated with the coordinated transfer of the hemi-methylated CpG site from UHRF1 to Dnmt1. PMID:18772891

Arita, Kyohei; Ariyoshi, Mariko; Tochio, Hidehito; Nakamura, Yusuke; Shirakawa, Masahiro



CHH islands: de novo DNA methylation in near-gene chromatin regulation in maize  

PubMed Central

Small RNA-mediated regulation of chromatin structure is an important means of suppressing unwanted genetic activity in diverse plants, fungi, and animals. In plants specifically, 24-nt siRNAs direct de novo methylation to repetitive DNA, both foreign and endogenous, in a process known as RNA-directed DNA methylation (RdDM). Many components of the de novo methylation machinery have been identified recently, including multiple RNA polymerases, but specific genetic features that trigger methylation remain poorly understood. By applying whole-genome bisulfite sequencing to maize, we found that transposons close to cellular genes (particularly within 1 kb of either a gene start or end) are strongly associated with de novo methylation, as evidenced both by 24-nt siRNAs and by methylation specifically in the CHH sequence context. In addition, we found that the major classes of transposons exhibited a gradient of CHH methylation determined by proximity to genes. Our results further indicate that intergenic chromatin in maize exists in two major forms that are distinguished based on proximity to genes—one form marked by dense CG and CHG methylation and lack of transcription, and one marked by CHH methylation and activity of multiple forms of RNA polymerase. The existence of the latter, which we call CHH islands, may have implications for how cellular gene expression could be coordinated with immediately adjacent transposon repression in a large genome with a complex organization of genes interspersed in a landscape of transposons.

Gent, Jonathan I.; Ellis, Nathanael A.; Guo, Lin; Harkess, Alex E.; Yao, Yingyin; Zhang, Xiaoyu; Dawe, R. Kelly



Corruption of the intra-gene DNA methylation architecture is a hallmark of cancer.  


Epigenetic processes--including DNA methylation--are increasingly seen as having a fundamental role in chronic diseases like cancer. It is well known that methylation levels at particular genes or loci differ between normal and diseased tissue. Here we investigate whether the intra-gene methylation architecture is corrupted in cancer and whether the variability of levels of methylation of individual CpGs within a defined gene is able to discriminate cancerous from normal tissue, and is associated with heterogeneous tumour phenotype, as defined by gene expression. We analysed 270985 CpGs annotated to 18272 genes, in 3284 cancerous and 681 normal samples, corresponding to 14 different cancer types. In doing so, we found novel differences in intra-gene methylation pattern across phenotypes, particularly in those genes which are crucial for stem cell biology; our measures of intra-gene methylation architecture are a better determinant of phenotype than measures based on mean methylation level alone (K-S test [Formula: see text] in all 14 diseases tested). These per-gene methylation measures also represent a considerable reduction in complexity, compared to conventional per-CpG beta-values. Our findings strongly support the view that intra-gene methylation architecture has great clinical potential for the development of DNA-based cancer biomarkers. PMID:23874574

Bartlett, Thomas E; Zaikin, Alexey; Olhede, Sofia C; West, James; Teschendorff, Andrew E; Widschwendter, Martin



Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes  

PubMed Central

In different eukaryotic model systems, chromatin and gene expression are modulated by post-translational modification of histone tails. In this in vivo study, histone methylation and acetylation are investigated along the imprinted mouse genes Snrpn, Igf2r and U2af1-rs1. These imprinted genes all have a CpG-rich regulatory element at which methylation is present on the maternal allele, and originates from the female germ line. At these ‘differentially methylated regions’ (DMRs), histone H3 on the paternal allele has lysine-4 methylation and is acetylated. On the maternally inherited allele, in contrast, chromatin is marked by hypermethylation on lysine-9 of H3. Allele-specific patterns of lysine-4 and lysine-9 methylation are also detected at other regions of the imprinted loci. For the DMR at the U2af1-rs1 gene, we establish that the methyl-CpG-binding-domain (MBD) proteins MeCP2, MBD1 and MBD3 are associated with the maternal allele. These data support the hypothesis that MBD protein-associated histone deacetylase/chromatin-remodelling complexes are recruited to the parental allele that has methylated DNA and H3-K9 methylation, and are prevented from binding to the opposite allele by H3 lysine-4 methylation.

Fournier, Cecile; Goto, Yuji; Ballestar, Esteban; Delaval, Katia; Hever, Ann M.; Esteller, Manel; Feil, Robert



Synthesis and characterization of rhenium(V) oxo complexes with N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine methyl ester. X-ray crystal structure of (ReO[Ph(2)P(CH(2))(2)C(O)-Gly-Cys-OMe(P,N,N,S)]).  


The PN(2)S chelate N-[N-(3-diphenylphosphinopropionyl)glycyl]-S-tritylcysteine methyl ester [PN(2)S(Trt)-OMe] was synthesized and reacted with ReOCl(3)(PPh(3))(2) and Ph(4)P[ReOCl(4)]. The reactions of both tritylated and detritylated ligands with Re(V)O precursors gave two diastereomers, 9a and 9b, of the ReO(PN(2)S-OMe) complex. The two isomers, produced in a 1:1 molar ratio, are stable and do not interconvert. They were separated by reverse-phase HPLC and characterized by NMR, FT-IR, and UV-visible spectroscopy and electrospray mass spectrometry. X-ray analysis established for 9a the presence in the solid of the syn isomer. Compound 9a, C(21)H(23)N(2)O(5)PSRe, crystallized from warm acetonitrile in the triclinic space group Ponemacr;, a = 9.828(2) A, b = 11.163(2) A, c = 11.641(2) A, alpha = 106.48(3) degrees, beta = 109.06(3) degrees, gamma = 102.81(3) degrees, V = 1085.7(4) A(3), Z = 2. The PN(2)S coordination set is in the equatorial plane, and the complex shows a distorted square pyramidal coordination. The anti configuration assigned to 9b is consistent with all the available physicochemical data. Follow-up of the reaction of the detritylated ligand with Ph(4)P[ReOCl(4)] in ethanol or acetonitrile indicated that the phosphorus atom of the chelate binds first to the metal and that this bond acts as the driving force for coordination. PMID:12588125

Visentin, Roberta; Rossin, Raffaella; Giron, Maria Cecilia; Dolmella, Alessandro; Bandoli, Giuliano; Mazzi, Ulderico



Effect of the methylation of uracil and/or glycine on their mutual interaction.  


In order to simulate the hydrogen bonding and proton transfer (PT) in protein-DNA/RNA interactions, a series of simplified models were employed and investigated in the gas phase. These models included various neutral, anionic and cationic glycine-uracil dimers, and their methylated derivatives generated by the mono- or dimethylation of glycine and/or uracil moieties of the dimer. The results reveal that the only process that can occur in the neutral complexes is a double-PT process leading to proton exchange between the two moieties (i.e., point mutation). The first methyl substitute can reduce the activation energy of the PT process and thus promote the isomerization of the two moieties; further methylation can reduce the isomerization in only some of the cases. In the anionic complexes, only the one-way PT (i.e., amino acid ? nucleic acid base) process is energetically favorable, and this PT process is an interesting barrier-free one (BFPT), with the attached electron locating itself at the base moiety. Methylation will disfavor BFPT, but it cannot alter the nature of BFPT. In the cationic complexes, three different PT processes can occur. These processes can transform mutually by adjusting either or both of the methylated sites and methyl number, indicating that the methylation can regulate the dynamics of these PT processes. PMID:21594761

Ai, Hongqi; Li, Dejie; Zhao, Yongping; Zhang, Chong; Li, Qiang; Feng, Jijun



High methylation rates of mercury bound to cysteine by Geobacter sulfurreducens  

NASA Astrophysics Data System (ADS)

Methylmercury bioaccumulates in aquatic food chains and is able to cross the blood-brain barrier, making this organometallic compound a much more worrisome pollutant than inorganic mercury. We know that methylation of inorganic mercury is carried out by microbes in the anoxic layers of sediments and water columns, but the factors that control the extent of this methylation are poorly known. Mercury methylation is generally thought to be catalysed accidentally by some methylating enzyme, and it has been suggested that cellular mercury uptake results from passive diffusion of neutral mercury complexes. Here, we show that mercury methylation by the bacterium Geobacter sulfurreducens is greatly enhanced in the presence of low concentrations of the amino acid cysteine. The formation of a mercury-cysteine complex promotes both the uptake of inorganic mercury by the bacteria and the enzymatic formation of methylmercury, which is subsequently released to the external medium. Our results suggest that mercury uptake and methylation by microbes are controlled more tightly by biological mechanisms than previously thought, and that the formation of specific mercury complexes in anoxic waters modulates the efficiency of the microbial methylation of mercury.

Schaefer, Jeffra K.; Morel, François M. M.



Methyl donor deficiency induces cardiomyopathy through altered methylation/acetylation of PGC-1? by PRMT1 and SIRT1.  


Cardiomyopathies occur by mechanisms that involve inherited and acquired metabolic disorders. Both folate and vitamin B12 deficiencies are associated with left ventricular dysfunction, but mechanisms that underlie these associations are not known. However, folate and vitamin B12 are methyl donors needed for the synthesis of S-adenosylmethionine, the substrate required for the activation by methylation of regulators of energy metabolism. We investigated the consequences of a diet lacking methyl donors in the myocardium of weaning rats from dams subjected to deficiency during gestation and lactation. Positron emission tomography (PET), microscope and metabolic examinations evidenced a myocardium hypertrophy, with cardiomyocyte enlargement, disturbed mitochondrial alignment, lipid droplets, decreased respiratory activity of complexes I and II and decreased S-adenosylmethionine:S-adenosylhomocysteine ratio. The increased concentrations of triglycerides and acylcarnitines were consistent with a deficit in fatty acid oxidation. These changes were explained by imbalanced acetylation/methylation of PGC-1?, through decreased expression of SIRT1 and PRMT1 and decreased S-adenosylmethionine:S-adenosylhomocysteine ratio, and by decreased expression of PPAR? and ERR?. The main changes of the myocardium proteomic study were observed for proteins regulated by PGC-1?, PPARs and ERR?. These proteins, namely trifunctional enzyme subunit ?-complex, short chain acylCoA dehydrogenase, acylCoA thioesterase 2, fatty acid binding protein-3, NADH dehydrogenase (ubiquinone) flavoprotein 2, NADH dehydrogenase (ubiquinone) 1?-subunit 10 and Hspd1 protein, are involved in fatty acid oxidation and mitochondrial respiration. In conclusion, the methyl donor deficiency produces detrimental effects on fatty acid oxidation and energy metabolism of myocardium through imbalanced methylation/acetylation of PGC-1? and decreased expression of PPAR? and ERR?. These data are of pathogenetic relevance to perinatal cardiomyopathies. PMID:21633959

Garcia, Maira Moreno; Guéant-Rodriguez, Rosa-Maria; Pooya, Shabnam; Brachet, Patrick; Alberto, Jean-Marc; Jeannesson, Elise; Maskali, Fathia; Gueguen, Naig; Marie, Pierre-Yves; Lacolley, Patrick; Herrmann, Markus; Juillière, Yves; Malthiery, Yves; Guéant, Jean-Louis



Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder.  


Borderline personality disorder (BPD) is a complex psychiatric disease of increasing importance. Epigenetic alterations are hallmarks for altered gene expression and could be involved in the etiology of BPD. In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). DNA methylation was analyzed by bisulfite restriction analysis and pyrosequencing in whole blood samples of patients diagnosed with DSM-IV BPD and in controls. Aberrant methylation was not detectable using bisulfite restriction analysis, but a significantly increased methylation of HTR2A, NR3C1, MAOA, MAOB and soluble COMT (S-COMT) was revealed for BPD patients using pyrosequencing. For HTR2A the average methylation of four CpG sites was 0.8% higher in BPD patients compared to controls (p = 0.002). The average methylation of NR3C1 was 1.8% increased in BPD patients compared to controls (p = 0.0003) and was higher at 2 out of 8 CpGs (p ? 0.04). In females, an increased average methylation (1.5%) of MAOA was observed in BPD patients compared to controls (p = 0.046). A similar trend (1.4% higher methylation) was observed for MAOB in female BPD patients and increased methylation was significant for 1 out of 6 CpG sites. For S-COMT, a higher methylation of 2 out of 4 CpG sites was revealed in BPD patients (p ? 0.02). In summary, methylation signatures of several promoter regions were established and a significant increased average methylation (1.7%) occurred in blood samples of BPD patients (p < 0.0001). Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD. PMID:22139575

Dammann, Gerhard; Teschler, Stefanie; Haag, Tanja; Altmüller, Franziska; Tuczek, Frederik; Dammann, Reinhard H



Coordination geometries of bis(4-amino-3-alkyl-1,2,4-triazole-5-thione) complexes of first-row transition metals: crystal structures of complexes with propyl and hydrogen in the 3-position. Relationship to the 3-methyl and 3-ethyl analogs  

Microsoft Academic Search

A series of bis bidentate complexes of 4-amino-3-propyl-1,2,4-triazole-5-thione, SN4C5H10 (apt, 1) of the divalent ions Fe, Co, Ni, and Zn has been crystallized by direct combination of the ligand and metal nitrate or perchlorate hydrate salt in ethanol. The structures were determined by single-crystal X-ray diffraction techniques. In all the complexes, the triazole bonds to the metal ion through the

Robert M McCarrick; Martin J Eltzroth; Philip J Squattrito



Neuropsychiatric manifestations of methyl iodide  

PubMed Central

Methyl iodide is a monohalomethane and with a chemical formula CH3I. Acute exposures to methyl iodide have frequently occurred in the workplace. Predominantly, neuropsychiatric symptoms of acute exposure to monohalomethanes consist of headache, nausea, vomiting, drowsiness, dizziness, giddiness, diarrhea, confusion, ataxia, slurred speech, paralysis, convulsions, delirium, coma, and death. We report two cases who presented to our emergency services after accidental exposure to methyl iodide for a short duration. These case reports highlighted concurrence of frankly psychotic features and acute confusional state in workers vulnerable to industrial exposure to toxic chemicals. Understanding the mechanism of neuro-toxicity will perhaps throw some light on co-existence of both psychiatric and neurological symptoms. Awareness of these toxic effects at vulnerable work places will lead to timely and appropriate interventions. Importance of safety precautions and education of both workers and supervisors cannot be overemphasized here

Parkar, Shubhangi R.; Mayanil, Tushita S.



Dichlorobis(N-Methyl-alpha-(2-Pyridyl)Nitrone) Nickel(II). Synthesis and Proton Magnetic Resonance Spectra.  

National Technical Information Service (NTIS)

The synthesis, properties, and pmr spectra are reported for the new complex dichlorobis (N-methyl-alpha-(2-pyridyl)nitrone)-nickel(II) and its methyl derivatives. The pyridylnitrone ligands represent a new class of bidentate chelating agents. The two rema...

J. R. Hutchison G. N. La Mar W. D. Horrocks



Coordinated methyl and RNA binding is required for heterochromatin localization of mammalian HP1?  

PubMed Central

In mammalian cells, as in Schizosaccharomyces pombe and Drosophila, HP1 proteins bind histone H3 tails methylated on lysine 9 (K9). However, whereas K9-methylated H3 histones are distributed throughout the nucleus, HP1 proteins are enriched in pericentromeric heterochromatin. This observation suggests that the methyl-binding property of HP1 may not be sufficient for its heterochromatin targeting. We show that the association of HP1? with pericentromeric heterochromatin depends not only on its methyl-binding chromo domain but also on an RNA-binding activity present in the hinge region of the protein that connects the conserved chromo and chromoshadow domains. Our data suggest the existence of complex heterochromatin binding sites composed of methylated histone H3 tails and RNA, with each being recognized by a separate domain of HP1?.

Muchardt, Christian; Guilleme, Marie; Seeler, Jacob-S.; Trouche, Didier; Dejean, Anne; Yaniv, Moshe



Methyl jasmonate induces extracellular pathogenesis-related proteins in cell cultures of Capsicum chinense  

PubMed Central

Suspension cultured cells of Capsicum chinense secrete proteins to the culture medium in both control conditions and under methyl jasmonate treatment. The exogenous application of methyl jasmonate induced the accumulation of putative pathogenesis-related proteins, class I chitinase, leucin-rich repeat protein, NtPRp27-like protein and pectinesterase which were also found in suspension cultured cells of C. annuum elicited with methyl jasmonate. However, a germin-like protein, which has never been described in methyl jasmonate-elicited C. chinense suspension cultured cells, was found. The different effects described as being the result of exogenous application of signalling molecules like methyl jasmonate on the expression of germin-like protein suggest that germin-like proteins may play a variety of roles in protecting plants against pathogen attacks and different stresses. Further studies will be necessary to characterize the differential expression of these pathogenesis-related proteins and to throw light on the complexity of their regulation.

Belchi-Navarro, Sarai; Barcelo, Alfonso Ros



PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130.  


Maintenance of the Golgi apparatus (GA) structure and function depends on Golgi matrix proteins. The posttranslational modification of Golgi proteins such as phosphorylation of members of the golgin and GRASP families is important for determining Golgi architecture. Some Golgi proteins including golgin-84 are also known to be methylated, but the function of golgin methylation remains unclear. Here, we show that the protein arginine methyltransferase 5 (PRMT5) localizes to the GA and forms complexes with several components involved in GA ribbon formation and vesicle tethering. PRMT5 interacts with the golgin GM130, and depletion of PRMT5 causes defects in Golgi ribbon formation. Furthermore, PRMT5 methylates N-terminal arginines in GM130, and such arginine methylation appears critical for GA ribbon formation. Our findings reveal a molecular mechanism by which PRMT5-dependent arginine methylation of GM130 controls the maintenance of GA architecture. PMID:20421892

Zhou, Zhongwei; Sun, Xiaotian; Zou, Zhenhua; Sun, Litao; Zhang, Tao; Guo, Shaoshi; Wen, Ya; Liu, Lin; Wang, Yi; Qin, Jun; Li, Lei; Gong, Weimin; Bao, Shilai



Methyl chloroform and the atmosphere  

SciTech Connect

The atmospheric abundance of methyl chloroform, CH{sub 3}CCl{sub 3}, a compound of only anthropogenic origin, is actually decreasing because of emission reductions in compliance with the United Nations Montreal Protocol and its subsequent amendments. This observation, reported by Prinn and co-workers elsewhere in this issue, is based on data from surface-level monitoring stations. The observed trends in methyl chloroform abundance have a few straightforward scientific consequences and substantial policy relevance as discussed in this article. 6 refs., 1 fig.

Ravishankara, A.R.; Albritton, D.L.




Microsoft Academic Search

Glycoamidophosphites in the pentose series have been synthesized based on 2,3-O-isopropylidene-?-methyl-D-ribofuranoside, 1,2-O-isopropylidene-?-D-xylofuranose, xylitane and 3,5-O-isopropylidenexylitane. Some of these compounds are used as ligands for the synthesis of the palladium complexes. Consideration is given to the behavior of these complexes as catalysts in the asymmetric hydrogenation of itaconic acid.

E. E. Nifantyev; S. A. Rumyantseva; M. P. Koroteyev; E. M. Abbasov; A. T. Teleshev; V. A. Pavlov; E. I. Klabunovsky



Optical bio-sniffer for methyl mercaptan in halitosis  

Microsoft Academic Search

An optical bio-sniffer for methyl mercaptan (MM) one of major odorous chemicals in halitosis (bad breath) was constructed by immobilizing monoamine oxidase type A (MAO-A) onto a tip of a fiber optic oxygen sensor (od: 1.59mm) with an oxygen sensitive ruthenium organic complex (excitation: 470nm, fluorescent: 600nm). A flow cell for circulating buffer solution was applied to rinse and clean

Kohji Mitsubayashi; Takeshi Minamide; Kimio Otsuka; Hiroyuki Kudo; Hirokazu Saito



The relationship between DNA methylation and telomere length in dyskeratosis congenita.  


The regulation of telomere length (TL) is a complex process, requiring the telomerase enzyme complex and numerous regulatory proteins. Epigenetic regulation may also be important in telomere maintenance. Specifically, methylation at subtelomeres is associated with changes in TL in vitro and in mouse models. Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by exceedingly short telomeres and mutations in telomere biology genes. To understand the interaction between methylation and TL in humans, we measured LINE-1, pericentromeric (NBL2), and subtelomeric (D4Z4) methylation in peripheral blood DNA derived from 40 patients with DC and 51 mutation-negative relatives. Pearson's correlation coefficient and linear regression models were used to evaluate the relationship between age-standardized lymphocyte TL measured by flow FISH and % DNA methylation. No differences in % subtelomeric, LINE-1, or pericentromeric methylation between patients with DC and relatives were noted except for an increase in % subtelomeric methylation in DC patients with a telomerase-complex mutation (TERC, TERT, DKC1, or TCAB1) (63.0% in DC vs. 61.8% in relatives, P = 0.03). Positive correlations between TL and DNA methylation at LINE-1 (r = 0.39, P = 0.01) and subtelomeric (r = 0.32, P = 0.05) sites were present in patients with DC. The positive correlation between TL and % LINE-1 methylation was restricted to TINF2 mutations. In contrast, statistically nonsignificant inverse correlations between TL and % LINE-1 (r = -0.17), subtelomeric (r = -0.20) were present in unaffected relatives. This study suggests an interaction between TL and both subtelomeric and LINE-1 methylation, which may be altered based on mutation status of telomere biology genes. PMID:21981348

Gadalla, Shahinaz M; Katki, Hormuzd A; Shebl, Fatma M; Giri, Neelam; Alter, Blanche P; Savage, Sharon A



Hydrogen-bonded network structures in dipyridinium, bis-(2-methyl-pyridinium), bis-(3-methyl-pyridinium) and bis-(4-methyl-pyridinium) dioxidobis(oxydiacetato)uranate(VI)  

PubMed Central

Four complexes containing the [UO2(oda)2]2? anion (oda is oxy­diacetate) are reported, namely dipyridinium dioxidobis(oxydiacetato)uranate(VI), (C5H6N)2[U(C4H4O5)2O2], (I), bis(2-methyl­pyridinium) dioxidobis(oxydiacetato)uranate(VI), (C8H8N)2[U(C4H4O5)2O2], (II), bis­(3-methyl­pyridinium) di­oxido­bis(oxydiacetato)uranate(VI), (C8H8N)2[U(C4H4O5)2O2], (III), and bis­(4-methyl­pyridinium) dioxidobis(oxydiacetato)uranate(VI), (C8H8N)2[U(C4H4O5)2O2], (IV). The anions are achiral and are located on a mirror plane in (I) and on inversion centres in (II)–(IV). The four complexes are assembled into three-dimensional structures via N—H?O and C—H?O inter­actions. Compounds (III) and (IV) are isomorphous; the [UO2(oda)2]2? anions form a porous matrix which is nearly identical in the two structures, and the cations are located in channels formed in this matrix. Compounds (I) and (II) are very different from (III) and (IV): (I) forms a layered structure, while (II) forms ribbons.

Lennartson, Anders; Hakansson, Mikael



Synthesis of Methylated Ethanolamine Moieties  

PubMed Central

Cultured cell suspensions of both carrot (Daucus carota L.) and soybean (Glycine max) take up exogenous choline efficiently from their respective growth media. During sustained growth at a concentration near 50 micromolar choline, this compound was taken up at rates which exceeded those at which phosphatidylcholine, is synthesized by cells growing in standard (i.e. choline-free) media. In 50 micromolar choline, both types of cells metabolized this compound to phosphocholine and phosphatidylcholine, but not to other detected metabolites, and marked accumulations of phosphocholine and choline occurred relative to phosphatidylcholine. Pregrowth in 50 micromolar choline for several doublings decreased the rate at which carrot cells transferred 3H from l-[3H3C] methionine into the network of all methylated derivatives of ethanolamine by some 98%. With soybean cells, a decrease of 77% was observed. In both cell types, transfer of 3H into S-methylmethionine, pectin methyl esters, methylated nucleic acids, and nonpolar lipid continued unabated. Gel-filtered extracts of carrot cells pregrown in 50 micromolar choline had marked decreases in the specific activities of S-adenosylmethionine-dependent phosphoethanolamine, phosphomethylethanolamine, and phosphodimethylethanolamine N-methyltransferases; extracts of soybean cells had a similar decrease in phosphoethanolamine N-methyltransferase. The significance of these findings for regulation of the rate of synthesis of methylated ethanolamine moieties is discussed.

Mudd, S. Harvey; Datko, Anne H.




Microsoft Academic Search

Plant roots may promote the disappearance of organic pollutants from soil solution. We have studied the activity of plants that react with benzotriazole (Bz) and some of its derivatives, such as tolyltriazole (Tz), a commonly used corrosion inhibitor in aircraft deicing formulations, 5-methyl benzotriazole (5-MBz); and 1- hydroxy benzotriazole (HBz). At levels below the toxic threshold (about 100 mg\\/L was

S. Castro; L. C. Davis; L. E. Erickson



Gene Methylation in Prostate Cancer.  

National Technical Information Service (NTIS)

Background: NKX3. 1 is a homeoprotein with prostate-specific expression in adults. Loss of NKX3.1 correlates with prostate cancer progression. Loss of heterozygosity affects NKK3.1 in about 80% of prostate cancers. This project focuses on DNA methylation ...

H. Wen-Xin E. P. Gelmann



Gene Methylation in Prostate Cancer.  

National Technical Information Service (NTIS)

NKX3.l is a homeoprotein with prostate-specific expression in adults. Loss of NKX3.l correlates with prostate cancer progression. Loss of heterozygosity affects NKX3.l in about 80% of prostate cancers. This project focuses on DNA methylation of the NKX3.l...

W. Huang



4-Methyl-anilinium nitrate  

PubMed Central

The asymmetric unit of the title compound, C7H10N+·NO3 ?, consists of a 4-methyl­anilinium cation protonated at the amino group and a nitrate anion. In the crystal, anions and cations are linked through N—H?O and N—H?(O,O) hydrogen bonds, buiding a corrugated layer structure parallel to (001).

Benali-Cherif, Nourredine; Boussekine, Houda; Boutobba, Zina; Dadda, Noureddine



Palladium-catalyzed direct arylation of methyl sulfoxides with aryl halides.  


The palladium-catalyzed ?-arylation of unactivated sulfoxides has been developed. The weakly acidic ?-protons of sulfoxides are reversibly deprotonated by LiOtBu, and a palladium phosphine complex facilitates the arylation. A variety of aryl methyl sulfoxides were coupled with aryl bromides. More challenging coupling partners, such as alkyl methyl sulfoxides (including dimethyl sulfoxide) and aryl chlorides proved to be suitable under the optimized conditions. This method was utilized to synthesize bioactive benzyl sulfoxide intermediates. PMID:23419158

Jia, Tiezheng; Bellomo, Ana; Baina, Kawtar E L; Dreher, Spencer D; Walsh, Patrick J



Role of Histone H3 Lysine 27 Methylation in X Inactivation  

Microsoft Academic Search

The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we

Kathrin Plath; Jia Fang; Susanna K. Mlynarczyk-Evans; Ru Cao; Kathleen A. Worringer; Hengbin Wang; Cecile C. de la Cruz; Arie P. Otte; Barbara Panning; Yi Zhang



Photo-sensitized oxidation of unsaturated fatty acid methyl esters. The identification of different pathways  

Microsoft Academic Search

and Summary  The photo-sensitized oxidation of methyl linolenate and methyl oleate was studied using erythrosine and riboflavin as sensitizers.\\u000a The complex mixtures of hydroperoxides obtained were analyzed for the proportion of conjugated products and, after reduction\\u000a to the corresponding mixtures of hydroxystearates, for the distribution of positional isomers. By comparing the mixtures with\\u000a that obtained from autoxidation, it was shown that

Henry W.-S. Chan



Selenium reduces the retention of methyl mercury in the brown shrimp Crangon crangon.  


Methyl mercury accumulated at the top of aquatic food chains constitutes a toxicological risk to humans and other top predators. Because the methyl mercury enters the aquatic food chains at the lower trophic levels, uptake and elimination processes at these levels affect the methyl mercury content at the higher levels. Selenium modulates the biokinetics of mercury in aquatic organisms in fairly complex ways, increasing mercury retention in some aquatic mammals, but decreasing methyl mercury retention in fish. However, it is not known if selenium modulates methyl mercury accumulation at lower trophic levels in aquatic food chains. Here, we show that selenium administered via the food augments the elimination of methyl mercury from marine shrimp and that the effect is dose-dependent, demonstrable down to natural selenium concentrations in aquatic food items. Selenite, seleno-cystine, and seleno-methionine exert this effect but selenate does not. Our results suggest that the selenium naturally present at the lower trophic levels in marine food chains may play an essential role as a modifier of methyl mercury accumulation at these levels, thereby potentially also affecting biomagnification of methyl mercury toward the higher trophic levels in the aquatic food chains. PMID:22550937

Bjerregaard, Poul; Christensen, Alan



Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.  


Protein methylation is a post-translational modification (PTM) by which a variable number of methyl groups are transferred to lysine and arginine residues within proteins. Despite increased interest in this modification due to its reversible nature and its emerging role in a diverse set of biological pathways beyond chromatin, global identification of protein methylation has remained an unachieved goal. To characterise sites of lysine and arginine methylation beyond histones, we employed an approach that combines heavy methyl stable isotope labelling by amino acids in cell culture (hmSILAC) with high-resolution mass spectrometry-based proteomics. Through a broad evaluation of immuno-affinity enrichment and the application of two classical protein separation techniques prior to mass spectrometry, to nucleosolic and cytosolic fractions separately, we identified a total of 501 different methylation types, on 397 distinct lysine and arginine sites, present on 139 unique proteins. Our results considerably extend the number of known in vivo methylation sites and indicate their significant presence on several protein complexes involved at all stages of gene expression, from chromatin remodelling and transcription to splicing and translation. In addition, we describe the potential of the hmSILAC approach for accurate relative quantification of methylation levels between distinct functional states. PMID:23748837

Bremang, Michael; Cuomo, Alessandro; Agresta, Anna Maria; Stugiewicz, Magdalena; Spadotto, Valeria; Bonaldi, Tiziana



Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene.  


Diesters of phthiocerol and phenolphthiocerol are important virulence factors of Mycobacterium tuberculosis and Mycobacterium leprae, the two main mycobacterial pathogens in humans. They are both long-chain beta-diols, and their biosynthetic pathway is beginning to be elucidated. Although the two classes of molecules share a common lipid core, phthiocerol diesters have been found in all the strains of the M. tuberculosis complex examined although phenolphthiocerol diesters are produced by only a few groups of strains. To address the question of the origin of this diversity 8 reference strains and 10 clinical isolates of M. tuberculosis were analyzed. We report the presence of glycosylated p-hydroxybenzoic acid methyl esters, structurally related to the type-specific phenolphthiocerol glycolipids, in the culture media of all reference strains of M. tuberculosis, suggesting that the strains devoid of phenolphthiocerol derivatives are unable to elongate the putative p-hydroxybenzoic acid precursor. We also show that all the strains of M. tuberculosis examined and deficient in the production of phenolphthiocerol derivatives are natural mutants with a frameshift mutation in pks15/1 whereas a single open reading frame for pks15/1 is found in Mycobacterium bovis BCG, M. leprae, and strains of M. tuberculosis that produce phenolphthiocerol derivatives. Complementation of the H37Rv strain of M. tuberculosis, which is devoid of phenolphthiocerol derivatives, with the fused pks15/1 gene from M. bovis BCG restored phenolphthiocerol glycolipids production. Conversely, disruption of the pks15/1 gene in M. bovis BCG led to the abolition of the synthesis of type-specific phenolphthiocerol glycolipid. These data indicate that Pks15/1 is involved in the elongation of p-hydroxybenzoic acid to give p-hydroxyphenylalkanoates, which in turn are converted, presumably by the PpsA-E synthase, to phenolphthiocerol derivatives. PMID:12138124

Constant, Patricia; Perez, Esther; Malaga, Wladimir; Lanéelle, Marie-Antoinette; Saurel, Olivier; Daffé, Mamadou; Guilhot, Christophe



Diffusivity of methyl bromide in water  

Microsoft Academic Search

The oceans are important in the geochemical cycle of methyl bromide, as both a source of natural methyl bromide and a sink for anthropogenic methyl bromide. Air-sea exchange rate calculations are based on measured concentration differences across the air-sea surface, on various gas exchange-wind speed relationships, and on the diffusivity of methyl bromide in seawater. In this study, the diffusivity

Warren J. De Bruyn; Eric S. Saltzman



Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription  

Microsoft Academic Search

Cytosine methylation, a common form of DNA modification that antagonizes transcription, is found at transposons and repeats in vertebrates, plants and fungi. Here we have mapped DNA methylation in the entire Arabidopsis thaliana genome at high resolution. DNA methylation covers transposons and is present within a large fraction of A. thaliana genes. Methylation within genes is conspicuously biased away from

Daniel Zilberman; Mary Gehring; Robert K Tran; Tracy Ballinger; Steven Henikoff



Protein methylation in pea chloroplasts. [Pisum sativum  

SciTech Connect

The methylation of chloroplast proteins has been investigated by incubating intact pea (Pisum sativum) chloroplasts with ({sup 3}H-methyl)-S-adenosylmethionine. Incubation in the light increases the amount of methylation in both the thylakoid and stromal fractions. Numerous thylakoid proteins serve as substrates for the methyltransfer reactions. Three of these thylakoid proteins are methylated to a significantly greater extent in the light than in the dark. The primary stromal polypeptide methylated is the large subunit of ribulose bisphosphate carboxylase/oxygenase. One other stromal polypeptide is also methylated much more in the light than in the dark. Two distinct types of protein methylation occur. One methylinkage is stable to basic conditions whereas a second type is base labile. The base-stable linkage is indicative of N-methylation of amino acid residues while base-lability is suggestive of carboxymethylation of amino acid residues. Labeling in the light increases the percentage of methylation that is base labile in the thylakoid fraction while no difference is observed in the amount of base-labile methylations in light-labeled and dark-labeled stromal proteins. Also suggestive of carboxymethylation is the detection of volatile ({sup 3}H)methyl radioactivity which increases during the labeling period and is greater in chloroplasts labeled in the light as opposed to being labeled in the dark; this implies in vivo turnover of the ({sup 3}H)methyl group.

Niemi, K.J.; Adler, J.; Selman, B.R. (Univ. of Wisconsin, Madison (USA))



Radical SAM-mediated methylation reactions.  


A subset of enzymes that belong to the radical S-adenosylmethionine (SAM) superfamily is able to catalyze methylation reactions. Substrates of these enzymes are distinct from the nucleophilic substrates that undergo methylation by a polar mechanism. Recently, activities of several radical SAM methylating enzymes have been reconstituted in vitro and their mechanisms of catalysis investigated. The RNA modifying enzymes RlmN and Cfr catalyze methylation via a methyl synthase mechanism. These enzymes use SAM in two distinct roles: as a source of a methyl group transferred to a conserved cysteine and as a source of 5'-deoxyadenosyl radical (5'-dA). Hydrogen atom abstraction by this species generates a thiomethylene radical which adds into the RNA substrate, forming an enzyme-substrate covalent adduct. In another recent study, methylation of the indole moiety of tryptophan by the radical SAM and cobalamin-binding domain enzyme TsrM has been reconstituted. Methylcobalamin serves as an intermediate methyl donor in TsrM, and is proposed to transfer the methyl group as a methyl radical. Interestingly, despite the presence of the radical SAM motif, no reductive cleavage of SAM has been observed in this methylation. These important reconstitutions set the stage for further studies on mechanisms of radical methylation. PMID:23835516

Fujimori, Danica Galoni?




Technology Transfer Automated Retrieval System (TEKTRAN)

Many micronutrients and vitamins are critical for DNA synthesis/repair and maintenance of DNA methylation patterns. Folate has been most extensively investigated in this regard because of its unique function as methyl donor for nucleotide synthesis and biological methylation. Cell culture, animal, a...


Ten members of the Arabidopsis gene family encoding methyl-CpG-binding domain proteins are transcriptionally active and at least one, AtMBD11 ,i s crucial for normal development  

Microsoft Academic Search

Animal proteins that contain a methyl-CpG-binding domain (MBD) are suggested to provide a link between DNA methylation, chromatin remodelling and gene silencing. However, some MBD proteins reside in chromatin remodelling complexes, but do not have specific affinity for methylated DNA. It has recently been shown that the Arabidopsis genome contains 12 putative genes encoding proteins with domains similar to MBD,

Anita Berg; Trine J. Meza; Mirela Mahic; Tage Thorstensen; Kjetil Kristiansen; Reidunn B. Aalen



Chloride and ethyl ester morpholine thiourea derivatives and their Ni(II) complexes. Crystal and molecular structures of the thiourea derivative L-leucine methyl ester and its complexes with Cu(II) and Pt(II). Growth of the pathogenic fungus Botrytis cinerea  

Microsoft Academic Search

We have synthesized a series of ligands (1, 3, 4, 6 and 7) and some of their complexes with Ni (II), Cu (II) and Pt (II) (2, 5, 8 and 9). These compounds were studied and characterized by elemental analysis, IR and UV–Vis spectra, conductivity measurements in solution, FAB+\\/MS, 1H and 13C NMR, ESR, etc. Compound 7 crystallized in the

E. Rodr??guez-Fernández; Eva Garc??a; M. R. Hermosa; A. Jiménez-Sánchez; M. Mar Sánchez; Enrique Monte; Julio J. Criado



DNA methylation alterations exhibit intra-individual stability and inter-individual heterogeneity in prostate cancer metastases  

PubMed Central

Human cancers nearly ubiquitously harbor epigenetic alterations. While such alterations in epigenetic marks, including DNA methylation, are potentially heritable, they can also be dynamically altered. Given this potential for plasticity, the degree to which epigenetic changes can be subject to selection and act as drivers of neoplasia has been questioned. Here, we carried out genome-scale analyses of DNA methylation alterations in lethal metastatic prostate cancer and created DNA methylation “cityscape” plots to visualize these complex data. We show that somatic DNA methylation alterations, despite showing marked inter-individual heterogeneity among men with lethal metastatic prostate cancer, were maintained across all metastases within the same individual. The overall extent of maintenance in DNA methylation changes was comparable to that of genetic copy number alterations. Regions that were frequently hypermethylated across individuals were markedly enriched for cancer and development/differentiation related genes. Additionally, regions exhibiting high consistency of hypermethylation across metastases within individuals, even if variably hypermethylated across individuals, showed enrichment of cancer-related genes. Interestingly, whereas some regions showed intra-individual metastatic tumor heterogeneity in promoter methylation, such methylation alterations were generally not correlated with gene expression. This was despite a general tendency for promoter methylation patterns to be strongly correlated with gene expression, particularly at regions that were variably methylated across individuals. These findings suggest that DNA methylation alterations have the potential for producing selectable driver events in carcinogenesis and disease progression and highlight the possibility of targeting such epigenome alterations for development of longitudinal markers and therapeutic strategies.

Aryee, Martin J; Liu, Wennuan; Engelmann, Julia C; Nuhn, Philipp; Gurel, Meltem; Haffner, Michael C; Esopi, David; Irizarry, Rafael A; Getzenberg, Robert H; Nelson, William G; Luo, Jun; Xu, Jianfeng; Isaacs, William B; Bova, G Steven; Yegnasubramanian, Srinivasan



Small Molecule Ligands of Methyl-Lysine Binding Proteins  

PubMed Central

Proteins which bind methylated lysines (“readers” of the histone code) are important components in the epigenetic regulation of gene expression and can also modulate other proteins that contain methyl-lysine such as p53 and Rb. Recognition of methyl-lysine marks by MBT domains leads to compaction of chromatin and a repressed transcriptional state. Antagonists of MBT domains would serve as probes to interrogate the functional role of these proteins and initiate the chemical biology of methyl-lysine readers as a target class. Small molecule MBT antagonists were designed based on the structure of histone peptide-MBT complexes and their interaction with MBT domains determined using a chemiluminescent assay and ITC. The ligands discovered antagonize native histone peptide binding, exhibiting 5-fold stronger binding affinity to L3MBTL1 than its preferred histone peptide. The first co-crystal structure of a small molecule bound to L3MBTL1 was determined and provides new insights into binding requirements for further ligand design.

Herold, J. Martin; Wigle, Tim J.; Norris, Jacqueline L.; Lam, Robert; Korboukh, Victoria K.; Gao, Cen; Ingerman, Lindsey A.; Kireev, Dmitri B.; Senisterra, Guillermo; Vedadi, Masoud; Tripathy, Ashutosh; Brown, Peter J.; Arrowsmith, Cheryl H.; Jin, Jian; Janzen, William P.; Frye, Stephen V.



Small-molecule ligands of methyl-lysine binding proteins.  


Proteins which bind methylated lysines ("readers" of the histone code) are important components in the epigenetic regulation of gene expression and can also modulate other proteins that contain methyl-lysine such as p53 and Rb. Recognition of methyl-lysine marks by MBT domains leads to compaction of chromatin and a repressed transcriptional state. Antagonists of MBT domains would serve as probes to interrogate the functional role of these proteins and initiate the chemical biology of methyl-lysine readers as a target class. Small-molecule MBT antagonists were designed based on the structure of histone peptide-MBT complexes and their interaction with MBT domains determined using a chemiluminescent assay and ITC. The ligands discovered antagonize native histone peptide binding, exhibiting 5-fold stronger binding affinity to L3MBTL1 than its preferred histone peptide. The first cocrystal structure of a small molecule bound to L3MBTL1 was determined and provides new insights into binding requirements for further ligand design. PMID:21417280

Herold, J Martin; Wigle, Tim J; Norris, Jacqueline L; Lam, Robert; Korboukh, Victoria K; Gao, Cen; Ingerman, Lindsey A; Kireev, Dmitri B; Senisterra, Guillermo; Vedadi, Masoud; Tripathy, Ashutosh; Brown, Peter J; Arrowsmith, Cheryl H; Jin, Jian; Janzen, William P; Frye, Stephen V



Gas phase methylation of methyl acetoacetate. Experimental and theoretical study  

NASA Astrophysics Data System (ADS)

Fourier transform ion cyclotron resonance and tandem mass spectrometry, complemented by semiempirical molecular orbital calculations, have been used to study gas phase methylation of methyl acetoacetate as a mixture of the keto form 1 and the enol form 2. The daughter ion spectra of the ion/molecule reaction products were compared with those of model ions generated by electron impact or chemical ionization, in order to determine the site(s) of nucleophilic reaction for the mixture. The data indicate that the site of attachment in the keto form 1 is the keto-carbonyl oxygen. For the enol form 2, no C-methylation occurs in the gas phase; the only product corresponds to O-alkylation. The results derived from D- and 13C-labelled precursors have been used to study the fragmentation mechanisms of model ions a, CH3C+ (OCH3)CH2CO2CH3; and b, CH3COCH2C+(OCH3)2. Experimental results indicate that an irreversible isomerization a --> b occurs under collisional conditions. Unimolecularly both a and b ions eliminate a neutral molecule of ketene but by different pathways. Calculations of charge distributions in 1 and 2 as well as the enthalpies of the neutral and the adduct ions are discussed.

Morizur, J.-P.; Martigny, I.; Taphanel, M.-H.; Tortajada, J.; Geribaldi, S.; Decouzon, M.



Identification of Differentially Methylated Sequences in Colorectal Cancer by Methylated CpG Island Amplification1  

Microsoft Academic Search

CpG island methylation has been linked to tumor suppressor gene inactivation in neoplasia and may serve as a useful marker to clone novel cancer-related genes. We have developed a novel PCR-based method, methylated CpG island amplification (MCA), which is useful for both methylation analysis and cloning differentially methylated genes. Using restriction enzymes that have differential sensitivity to 5-methyl-cytosine, followed by

Minoru Toyota; Coty Ho; Nita Ahuja; Kam-Wing Jair; Qing Li; Mutsumi Ohe-Toyota; Stephen B. Baylin; Jean-Pierre J. Issa



Structural consequences of two methyl additions in the E. coli trp repressor L-tryptophan binding pocket  

SciTech Connect

The flexibility and specificity of the L-tryptophan corepressor binding pocket of E coli trp repressor are being investigated by high-resolution crystallographic examination of aporepressor/corepressor analog complexes. While addition of a methyl group on the corepressor indole (5-methyl-tryptophan) results in a small but measurable shift in the position of that functional group introduction of a methyl group on a nearby residue in the binding pocket (Val 58 {yields} Ile) leaves the indole position of L-tryptophan essentially unchanged. Careful alignment of these structures with aporepressor/L-tryptophan/operator-DNA complexes reveal why 5-methyltryptophan is a better corepressor than L-tryptophan.

Lawson, C.L.



The superiority of asymmetric alkyl methyl carbonates  

SciTech Connect

The electrochemical behavior of graphite electrodes cycled galvanostatically versus Li metal in electrolyte solutions containing LiPF{sub 6}, LiC(SO{sub 2}CF{sub 3}){sub 3}, and LiN(SO{sub 2}C{sub 2}F{sub 5}){sub 2} in ethyl and methyl alkyl carbonates was studied. The solvents include ethyl methyl, ethyl propyl, methyl propyl, isopropyl methyl, and isopropyl ethyl carbonates. The use of asymmetric, aliphatic alkyl methyl carbonates is shown to be essential to achieve both high capacity and long cycle life with graphite electrodes in Li-ion batteries.

Ein-Eli, Y.; McDevitt, S.F.; Laura, R. [Covalent Associates, Inc., Woburn, MA (United States)



Transgene-induced CCWGG methylation does not alter CG methylation patterning in human kidney cells  

PubMed Central

Several reports suggest that CmCWGG methylation tends not to co-exist with mCG methylation in human cells. We have asked whether or not methylation at CCWGG sites can influence CG methylation. DNA from cells expressing an M.EcoRII–GFP fusion was actively methylated at CCWGG sites. CG methylation as measured by R.HpaII/R.MspI ratios was unchanged in cells expressing the transgene. Cloned representatives of CmCWGG methylated DNA often contained, or were adjacent to an ALU repeat, suggesting that M.EcoRII-GFP actively methylated gene-rich R-band DNA. The transgenic methyltransferase applied CmCWGG methylation to a representative human promoter that was heavily methylated at CG dinucleotides (the SERPINB5 promoter) and to a representative promoter that was essentially unmethylated at CG dinucleotides (the APC promoter). In each case, the CG methylation pattern remained in its original state, unchanged by the presence of neighboring CmCWGG sites. Q-PCR measurements showed that RNA expression from the APC gene was not significantly altered by the presence of CmCWGG in its promoter. Kinetic studies suggested that an adjacent CmCWGG methylation site influences neither the maintenance nor the de novo methylation activities of purified human Dnmt1. We conclude that CmCWGG methylation does not exert a significant effect on CG methylation in human kidney cells.

Shevchuk, Taras; Kretzner, Leo; Munson, Kristofer; Axume, John; Clark, Jarrod; Dyachenko, Olga V.; Caudill, Marie; Buryanov, Yaroslav; Smith, Steven S.



Dnmt3L Antagonizes DNA Methylation at Bivalent Promoters and Favors DNA Methylation at Gene Bodies in ESCs.  


The de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methyltransferase that cooperates with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESCs), but its function in these cells is unknown. Through genome-wide analysis of Dnmt3L knockdown in ESCs, we found that Dnmt3L is a positive regulator of methylation at the gene bodies of housekeeping genes and, more surprisingly, is also a negative regulator of methylation at promoters of bivalent genes. Dnmt3L is required for the differentiation of ESCs into primordial germ cells (PGCs) through the activation of the homeotic gene Rhox5. We demonstrate that Dnmt3L interacts with the Polycomb PRC2 complex in competition with the DNA methyltransferases Dnmt3a and Dnmt3b to maintain low methylation levels at the H3K27me3 regions. Thus, in ESCs, Dnmt3L counteracts the activity of de novo DNA methylases to maintain hypomethylation at promoters of bivalent developmental genes. PMID:24074865

Neri, Francesco; Krepelova, Anna; Incarnato, Danny; Maldotti, Mara; Parlato, Caterina; Galvagni, Federico; Matarese, Filomena; Stunnenberg, Hendrik G; Oliviero, Salvatore



Requirement of rRNA Methylation for 80S Ribosome Assembly on a Cohort of Cellular Internal Ribosome Entry Sites?  

PubMed Central

Protein syntheses mediated by cellular and viral internal ribosome entry sites (IRESs) are believed to have many features in common. Distinct mechanisms for ribosome recruitment and preinitiation complex assembly between the two processes have not been identified thus far. Here we show that the methylation status of rRNA differentially influenced the mechanism of 80S complex formation on IRES elements from the cellular sodium-coupled neutral amino acid transporter 2 (SNAT2) versus the hepatitis C virus mRNA. Translation initiation involves the assembly of the 48S preinitiation complex, followed by joining of the 60S ribosomal subunit and formation of the 80S complex. Abrogation of rRNA methylation did not affect the 48S complex but resulted in impairment of 80S complex assembly on the cellular, but not the viral, IRESs tested. Impairment of 80S complex assembly on the amino acid transporter SNAT2 IRES was rescued by purified 60S subunits containing fully methylated rRNA. We found that rRNA methylation did not affect the activity of any of the viral IRESs tested but affected the activity of numerous cellular IRESs. This work reveals a novel mechanism operating on a cohort of cellular IRESs that involves rRNA methylation for proper 80S complex assembly and efficient translation initiation.

Basu, Abhijit; Das, Priyanka; Chaudhuri, Sujan; Bevilacqua, Elena; Andrews, Joel; Barik, Sailen; Hatzoglou, Maria; Komar, Anton A.; Mazumder, Barsanjit



Molecular Structure of Methyl Acrylate  

NSDL National Science Digital Library

Commercially available since 1944, methyl acrylate is a clear, colorless liquid with a sweet, fruity odor. This lachrymator often found in tobacco smoke, is used in the manufacturing of polymers, leather finishing, resins, textile, paper coatings, and plastic films. It is highly flammable and polymerizes explosively with exposure to light or heat. Inhibition by hydroquinone monomethyl ether, MEHQ, helps to prevent this problem. Because MEHQ functionality is reliant on oxygen, methyl acrylate must never be stored in an inert environment. Contact with skin will lead to severe deep burns, while ingestion or inhalation could lead to nausea, cough and abdominal pain. The liver, lungs, and kidneys are target organs for this compound, and medical attention should be sought immediately upon exposure.



DNA methylation in hepatocellular carcinoma.  


As for many other tumors, development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes (TSG). In the last decades, in addition to genetic alterations, epigenetic inactivation of (tumor suppressor) genes by promoter hypermethylation has been recognized as an important and alternative mechanism in tumorigenesis. In HCC, aberrant methylation of promoter sequences occurs not only in advanced tumors, it has been also observed in premalignant conditions just as chronic viral hepatitis B or C and cirrhotic liver. This review discusses the epigenetic alterations in hepatocellular carcinoma focusing DNA methylation. PMID:18350605

Tischoff, Iris; Tannapfe, Andrea



Exogenous bridging and nonbridging in copper(II) complexes of a binculeating 2,6-bis((N-methylpiperazino)methyl)-4-chlorophenolate ligand. Crystal structures and magnetic properties of Bis(. mu. -acetato), dinitrito, and bis(azido) complexes. Possible relevance to the type 3 depleted laccase active site  

SciTech Connect

As part of a wide study of the structure/magnetism/redox relations {sup 1{minus}5} in binuclear copper(II) complexes, the authors have employed a binucleating ligand, LH, obtained by a Mannich reaction between a para-substituted phenol, formaldehye, and N-methylpiperazine{sup 6,7}. Molecular models are given which show that simultaneous coordination of the phenol oxygen and the four piperazine nitrogen atoms to two Cu(II) ions, in the presence of absence of an exogenous bridging ligand, would be difficult in view of the sterically constrained ligand conformation.

Bertoncello, K.; Fallon, G.D.; Hodgkin, J.H.; Murray, K.S. (Monash Univ., Clayton (Australia))



Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27  

Microsoft Academic Search

Polycomb group (PcG) complexes 2 and 3 are involved in transcriptional silencing. These complexes contain a histone lysine methyltransferase (HKMT) activity that targets different lysine residues on histones H1 or H3 in vitro. However, it is not known if these histones are methylation targets in vivo because the human PRC2\\/3 complexes have not been studied in the context of a

Antonis Kirmizis; Stephanie M. Bartley; Andrei Kuzmichev; Raphael Margueron; Danny Reinberg; Roland Green; Peggy J. Farnham



Meisenheimer Complexes (sigma Complexes).  

National Technical Information Service (NTIS)

Meisenheimer complexes are known to form in aromatic nucleophilic substitution reactions. The purpose of the present study is to collect as much information as possible in this important field of organic chemistry. The interaction of nitro aromatics with ...

A. S. Mirza



Strategies for discovery and validation of methylated and hydroxymethylated DNA biomarkers  

PubMed Central

DNA methylation, consisting of the addition of a methyl group at the fifth-position of cytosine in a CpG dinucleotide, is one of the most well-studied epigenetic mechanisms in mammals with important functions in normal and disease biology. Disease-specific aberrant DNA methylation is a well-recognized hallmark of many complex diseases. Accordingly, various studies have focused on characterizing unique DNA methylation marks associated with distinct stages of disease development as they may serve as useful biomarkers for diagnosis, prognosis, prediction of response to therapy, or disease monitoring. Recently, novel CpG dinucleotide modifications with potential regulatory roles such as 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine have been described. These potential epigenetic marks cannot be distinguished from 5-methylcytosine by many current strategies and may potentially compromise assessment and interpretation of methylation data. A large number of strategies have been described for the discovery and validation of DNA methylation-based biomarkers, each with its own advantages and limitations. These strategies can be classified into three main categories: restriction enzyme digestion, affinity-based analysis, and bisulfite modification. In general, candidate biomarkers are discovered using large-scale, genome-wide, methylation sequencing, and/or microarray-based profiling strategies. Following discovery, biomarker performance is validated in large independent cohorts using highly targeted locus-specific assays. There are still many challenges to the effective implementation of DNA methylation-based biomarkers. Emerging innovative methylation and hydroxymethylation detection strategies are focused on addressing these gaps in the field of epigenetics. The development of DNA methylation- and hydroxymethylation-based biomarkers is an exciting and rapidly evolving area of research that holds promise for potential applications in diverse clinical settings.

Olkhov-Mitsel, Ekaterina; Bapat, Bharati



Aberrant Promoter Methylation of the ABCG2 Gene in Renal Carcinoma?  

PubMed Central

ABCG2 is a ubiquitous ATP-binding cassette transmembrane protein that is important in clinical drug resistance. Little is known about the mechanism(s) regulating the expression of ABCG2. We hypothesized that DNA methylation could play a role in the epigenetic regulation of ABCG2 gene expression. The promoter methylation status of three renal carcinoma cell lines was assessed with restriction enzyme digestion-coupled PCR and bisulfite genomic sequencing. Both UOK121 and UOK143, with known methylation of the VHL promoter, showed induction of ABCG2 expression after 5-aza-2?-deoxycytidine (5-aza-dC) treatment, suggesting that aberrant methylation of the ABCG2 gene was associated with gene silencing. In vitro methylation of the ABCG2 promoter-driven luciferase reporter vector resulted in a significant inhibition of transcription. Our data suggested that the ABCG2 gene is regulated coordinately at both histone and DNA levels. A chromatin immunoprecipitation assay demonstrated that the methylated promoter in UOK121 and UOK143, but not the unmethylated one in UOK181, is associated with the methyl CpG binding domain proteins (MBDs), MBD2 and MeCP2. Histone deacetylase 1 and a corepressor, mSin3A, were identified binding to the promoter region containing the CpG island, thereby suppressing ABCG2 transcription. Reactivation of ABCG2 was achieved by treatment with 5-aza-dC, a demethylating agent, concomitant with the release of MBDs from the promoter. Furthermore, the association of methylated lysine 9 on histone H3, a hallmark of promoter methylation, with the promoter was reduced following 5-aza-dC treatment. These data suggest that DNA methylation-dependent formation of a repressor complex in the CpG island contributes to inactivation of ABCG2.

To, Kenneth K. W.; Zhan, Z.; Bates, Susan E.



40 CFR 721.10326 - 2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...  

Code of Federal Regulations, 2013 CFR

...2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...2-Propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl 2-propenoate...2-propenoic acid, 2-methyl-, methyl ester, polymer with butyl 2-propenoate, ethyl...



Synthesis and solution properties of lanthanum(III), europium(III), and lutetium(III) THP complexes and an X-ray diffraction study of a crystal containing four stereoisomers of a europium(III) THP complex (THP = 1,4,7,10-tetrakis(2-hydroxypropryl)-1,4,7,10-tetraazacyclododecane). Methyl groups impart rigidity to S,S,S,S-THP macrocyclic complexes  

Microsoft Academic Search

The macrocycle 1,4,7,10-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane (THP) prepared from racemic propylene oxide and cyclen (1,4,7,10-tetraazacyclododecane) consists of a mixture of stereoisomers that arise from the chiral α-carbons of the hydroxypropyl groups. ¹³C NMR studies suggest that five different diastereomers are formed. Lanthanum(III), europium(III), and lutetium(III) THP complexes are synthesized from the mixture of THP stereoisomers. Europium(III) THP complexes containing R,R,R,S and S,S,S,R configurations

K. O. Aileen Chin; Janet R. Morrow; Charles H. Lake; Melvyn Rowen Churchill



First evidence of DNA methylation in insect Tribolium castaneum: environmental regulation of DNA methylation within heterochromatin.  


DNA methylation has been studied in many eukaryotic organisms, in particular vertebrates, and was implicated in developmental and phenotypic variations. Little is known about the role of DNA methylation in invertebrates, although insects are considered as excellent models for studying the evolution of DNA methylation. In the red flour beetle, Tribolium castaneum (Tenebrionidae, Coleoptera), no evidence of DNA methylation has been found till now. In this paper, a cytosine methylation in Tribolium castaneum embryos was detected by methylation sensitive restriction endonucleases and immuno-dot blot assay. DNA methylation in embryos is followed by a global demethylation in larvae, pupae and adults. DNA demethylation seems to proceed actively through 5-hydroxymethylcytosine, most probably by the action of TET enzyme. Bisulfite sequencing of a highly abundant satellite DNA located in pericentromeric heterochromatin revealed similar profile of cytosine methylation in adults and embryos. Cytosine methylation was not only restricted to CpG sites but was found at CpA, CpT and CpC sites. In addition, complete cytosine demethylation of heterochromatic satellite DNA was induced by heat stress. The results reveal existence of DNA methylation cycling in T. castaneum ranging from strong overall cytosine methylation in embryos to a weak DNA methylation in other developmental stages. Nevertheless, DNA methylation is preserved within heterochromatin during development, indicating its role in heterochromatin formation and maintenance. It is, however, strongly affected by heat stress, suggesting a role for DNA methylation in heterochromatin structure modulation during heat stress response. PMID:23644818

Feliciello, Isidoro; Parazajder, Josip; Akrap, Ivana; Ugarkovi?, Dur?ica



DNA methylation and diet in cancer.  


The studies reviewed here investigate the association between folate status and DNA methylation in cancer tissues. We evaluated tissue vitamin levels and global DNA methylation, a biomarker of neoplasia, in normal lung and lung cancer tissues. Lung squamous cell carcinoma tissues exhibited global DNA hypomethylation, with decreased folate and vitamin B-12 concentrations, and increased vitamin C concentrations, relative to matched uninvolved control tissues. Breast cancer tissues also had globally hypomethylated DNA and decreased vitamin B-12 and vitamin C levels, but folate concentrations were elevated in breast cancer tissues. Global DNA methylation status in buccal mucosal cells may reflect global methylation status in lung tissues, because there was a significant association between global DNA methylation in buccal mucosal cells and malignant tissues of the lung, but not between methylation in peripheral leukocytes and lung tissues. We found that global DNA hypomethylation, as assessed by a radiolabeled 5-methylcytosine technique, was associated with susceptibility for development of lung cancer, which is involved in the progression of the disease. DNA methylation was also associated with the development of squamous cell carcinomas in whites but not in blacks. Overall, these studies suggest that global DNA methylation patterns may vary depending on the type of cancer, that tissue vitamin levels are associated with global DNA methylation status and that ethnicity should be considered in studies of DNA methylation. PMID:12468630

Johanning, Gary L; Heimburger, Douglas C; Piyathilake, Chandrika J



Nitric oxide modifies global histone methylation by inhibiting Jumonji C domain-containing demethylases.  


Methylation of lysine residues on histone tails is an important epigenetic modification that is dynamically regulated through the combined effects of methyltransferases and demethylases. The Jumonji C domain Fe(II) ?-ketoglutarate family of proteins performs the majority of histone demethylation. We demonstrate that nitric oxide ((•)NO) directly inhibits the activity of the demethylase KDM3A by forming a nitrosyliron complex in the catalytic pocket. Exposing cells to either chemical or cellular sources of (•)NO resulted in a significant increase in dimethyl Lys-9 on histone 3 (H3K9me2), the preferred substrate for KDM3A. G9a, the primary methyltransferase acting on H3K9me2, was down-regulated in response to (•)NO, and changes in methylation state could not be accounted for by methylation in general. Furthermore, cellular iron sequestration via dinitrosyliron complex formation correlated with increased methylation. The mRNA of several histone demethylases and methyltransferases was also differentially regulated in response to (•)NO. Taken together, these data reveal three novel and distinct mechanisms whereby (•)NO can affect histone methylation as follows: direct inhibition of Jumonji C demethylase activity, reduction in iron cofactor availability, and regulation of expression of methyl-modifying enzymes. This model of (•)NO as an epigenetic modulator provides a novel explanation for nonclassical gene regulation by (•)NO. PMID:23546878

Hickok, Jason R; Vasudevan, Divya; Antholine, William E; Thomas, Douglas D



DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees  

PubMed Central

In honey bees (Apis mellifera), the development of a larva into either a queen or worker depends on differential feeding with royal jelly and involves epigenomic modifications by DNA methyltransferases. To understand the role of DNA methylation in this process we sequenced the larval methylomes in both queens and workers. We show that the number of differentially methylated genes (DMGs) in larval head is significantly increased relative to adult brain (2,399 vs. 560) with more than 80% of DMGs up-methylated in worker larvae. Several highly conserved metabolic and signaling pathways are enriched in methylated genes, underscoring the connection between dietary intake and metabolic flux. This includes genes related to juvenile hormone and insulin, two hormones shown previously to regulate caste determination. We also tie methylation data to expressional profiling and describe a distinct role for one of the DMGs encoding anaplastic lymphoma kinase (ALK), an important regulator of metabolism. We show that alk is not only differentially methylated and alternatively spliced in Apis, but also seems to be regulated by a cis-acting, anti-sense non–protein-coding transcript. The unusually complex regulation of ALK in Apis suggests that this protein could represent a previously unknown node in a process that activates downstream signaling according to a nutritional context. The correlation between methylation and alternative splicing of alk is consistent with the recently described mechanism involving RNA polymerase II pausing. Our study offers insights into diet-controlled development in Apis.

Foret, Sylvain; Kucharski, Robert; Pellegrini, Matteo; Feng, Suhua; Jacobsen, Steven E.; Robinson, Gene E.; Maleszka, Ryszard



Methylation-dependent and -independent genomic targeting principles of the MBD protein family.  


To gain insight into the cellular readout of DNA methylation, we established a strategy for systematically profiling the genome-wide distribution of chromatin-interacting factors. This enabled us to create genomic maps for the methyl-CpG-binding domain (MBD) family of proteins, including disease-relevant mutants, deletions, and isoforms. In vivo binding of MBD proteins occurs predominantly as a linear function of local methylation density, requiring functional MBD domains and methyl-CPGs. This interaction directs specificity of MBD proteins to methylated, CpG-dense, and inactive regulatory regions. In contrast, binding to unmethylated sites varies between MBD proteins and is mediated via alternative domains or protein-protein interactions. Such targeting is exemplified by NuRD-complex-mediated tethering of MBD2 to a subset of unmethylated, active regulatory regions. Interestingly, MBD3 also occupies these sites, but like MBD2, binding is independent of the presence of hydroxymethylation. These functional binding maps reveal methylation-dependent and -independent binding modes and revise current models of DNA methylation readout through MBD proteins. PMID:23582333

Baubec, Tuncay; Ivánek, Robert; Lienert, Florian; Schübeler, Dirk



Arginine methylation of SmB is required for Drosophila germ cell development.  


Sm proteins constitute the common core of spliceosomal small nuclear ribonucleoproteins. Although Sm proteins are known to be methylated at specific arginine residues within the C-terminal arginine-glycine dipeptide (RG) repeats, the biological relevance of these modifications remains unknown. In this study, a tissue-specific function of arginine methylation of the SmB protein was identified in Drosophila. Analysis of the distribution of SmB during oogenesis revealed that this protein accumulates at the posterior pole of the oocyte, a cytoplasmic region containing the polar granules, which are necessary for the formation of primordial germ cells. The pole plasm localisation of SmB requires the methylation of arginine residues in its RG repeats by the Capsuléen-Valois methylosome complex. Functional studies showed that the methylation of these arginine residues is essential for distinct processes of the germline life cycle, including germ cell formation, migration and differentiation. In particular, the methylation of a subset of these arginine residues appears essential for the anchoring of the polar granules at the posterior cortex of the oocyte, whereas the methylation of another subset controls germ cell migration during embryogenesis. These results demonstrate a crucial role of arginine methylation in directing the subcellular localisation of SmB and that this modification contributes specifically to the establishment and development of germ cells. PMID:20659974

Anne, Joël



Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1)  

PubMed Central

Methylation of cytosine in DNA plays a crucial role in development through inheritable gene silencing. The DNA methyltransferase Dnmt1 is responsible for the propagation of methylation patterns to the next generation via its preferential methylation of hemimethylated CpG sites in the genome; however, how Dnmt1 maintains methylation patterns is not fully understood. Here we report the crystal structure of the large fragment (291–1620) of mouse Dnmt1 and its complexes with cofactor S-adenosyl-L-methionine and its product S-adenosyl-L-homocystein. Notably, in the absence of DNA, the N-terminal domain responsible for targeting Dnmt1 to replication foci is inserted into the DNA-binding pocket, indicating that this domain must be removed for methylation to occur. Upon binding of S-adenosyl-L-methionine, the catalytic cysteine residue undergoes a conformation transition to a catalytically competent position. For the recognition of hemimethylated DNA, Dnmt1 is expected to utilize a target recognition domain that overhangs the putative DNA-binding pocket. Taking into considerations the recent report of a shorter fragment structure of Dnmt1 that the CXXC motif positions itself in the catalytic pocket and prevents aberrant de novo methylation, we propose that maintenance methylation is a multistep process accompanied by structural changes.

Takeshita, Kohei; Suetake, Isao; Yamashita, Eiki; Suga, Michihiro; Narita, Hirotaka; Nakagawa, Atsushi; Tajima, Shoji



Dynamics of DNA methylation in recent human and great ape evolution.  


DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development, X-chromosome inactivation, genomic imprinting and susceptibility to complex disease. However, the dynamics of DNA methylation changes between humans and their closest relatives are still poorly understood. We performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primate samples including all species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Our analysis identified ?800 genes with significantly altered methylation patterns among the great apes, including ?170 genes with a methylation pattern unique to human. Some of these are known to be involved in developmental and neurological features, suggesting that epigenetic changes have been frequent during recent human and primate evolution. We identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation. In contrast, and supporting the idea that many phenotypic differences between humans and great apes are not due to amino acid differences, our analysis also identified 184 genes that are perfectly conserved at protein level between human and chimpanzee, yet show significant epigenetic differences between these two species. We conclude that epigenetic alterations are an important force during primate evolution and have been under-explored in evolutionary comparative genomics. PMID:24039605

Hernando-Herraez, Irene; Prado-Martinez, Javier; Garg, Paras; Fernandez-Callejo, Marcos; Heyn, Holger; Hvilsom, Christina; Navarro, Arcadi; Esteller, Manel; Sharp, Andrew J; Marques-Bonet, Tomas



Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers.  


In mammalian development, epigenetic modifications, including DNA methylation patterns, play a crucial role in defining cell fate but also represent epigenetic barriers that restrict developmental potential. At two points in the life cycle, DNA methylation marks are reprogrammed on a global scale, concomitant with restoration of developmental potency. DNA methylation patterns are subsequently re-established with the commitment towards a distinct cell fate. This reprogramming of DNA methylation takes place firstly on fertilization in the zygote, and secondly in primordial germ cells (PGCs), which are the direct progenitors of sperm or oocyte. In each reprogramming window, a unique set of mechanisms regulates DNA methylation erasure and re-establishment. Recent advances have uncovered roles for the TET3 hydroxylase and passive demethylation, together with base excision repair (BER) and the elongator complex, in methylation erasure from the zygote. Deamination by AID, BER and passive demethylation have been implicated in reprogramming in PGCs, but the process in its entirety is still poorly understood. In this review, we discuss the dynamics of DNA methylation reprogramming in PGCs and the zygote, the mechanisms involved and the biological significance of these events. Advances in our understanding of such natural epigenetic reprogramming are beginning to aid enhancement of experimental reprogramming in which the role of potential mechanisms can be investigated in vitro. Conversely, insights into in vitro reprogramming techniques may aid our understanding of epigenetic reprogramming in the germline and supply important clues in reprogramming for therapies in regenerative medicine. PMID:23166394

Seisenberger, Stefanie; Peat, Julian R; Hore, Timothy A; Santos, Fátima; Dean, Wendy; Reik, Wolf



Methyl rotational tunneling dynamics of p-xylene confined in a crystalline zeolite host  

NASA Astrophysics Data System (ADS)

The methyl rotational tunneling spectrum of p-xylene confined in nanoporous zeolite crystals has been measured by inelastic neutron scattering (INS) and proton nuclear magnetic resonance (NMR), and analyzed to extract the rotational potential energy surfaces characteristic of the methyl groups in the host-guest complex. The number and relative intensities of the tunneling peaks observed by INS indicate the presence of methyl-methyl coupling interactions in addition to the methyl-zeolite interactions. The INS tunneling spectra from the crystals (space group P212121 with four crystallographically inequivalent methyl rotors) are quantitatively interpreted as a combination of transitions involving two coupled methyl rotors as well as a transition involving single-particle tunneling of a third inequivalent rotor, in a manner consistent with the observed tunneling energies and relative intensities. Together, the crystal structure and the absence of additional peaks in the INS spectra suggest that the tunneling of the fourth inequivalent rotor is strongly hindered and inaccessible to INS measurements. This is verified by proton NMR measurements of the spin-lattice relaxation time which reveal the tunneling characteristics of the fourth inequivalent rotor.

Nair, Sankar; Dimeo, Robert M.; Neumann, Dan A.; Horsewill, Anthony J.; Tsapatsis, Michael



DNA cytosine methylation in plant development.  


Cytosine bases of the nuclear genome in higher plants are often extensively methylated. Cytosine methylation has been implicated in the silencing of both transposable elements (TEs) and endogenous genes, and loss of methylation may have severe functional consequences. The recent methylation profiling of the entire Arabidopsis genome has provided novel insights into the extent and pattern of cytosine methylation and its relationships with gene activity. In addition, the fresh studies also revealed the more dynamic nature of this epigenetic modification across plant development than previously believed. Cytosine methylation of gene promoter regions usually inhibits transcription, but methylation in coding regions (gene-body methylation) does not generally affect gene expression. Active demethylation (though probably act synergistically with passive loss of methylation) of promoters by the 5-methyl cytosine DNA glycosylase or DEMETER (DME) is required for the uni-parental expression of imprinting genes in endosperm, which is essential for seed viability. The opinion that cytosine methylation is indispensible for normal plant development has been reinforced by using single or combinations of diverse loss-of-function mutants for DNA methyltransferases, DNA glycosylases, components involved in siRNA biogenesis and chromatin remodeling factors. Patterns of cytosine methylation in plants are usually faithfully maintained across organismal generations by the concerted action of epigenetic inheritance and progressive correction of strayed patterns. However, some variant methylation patterns may escape from being corrected and hence produce novel epialleles in the affected somatic cells. This, coupled with the unique property of plants to produce germline cells late during development, may enable the newly acquired epialleles to be inherited to future generations, which if visible to selection may contribute to adaptation and evolution. PMID:20171573

Zhang, Meishan; Kimatu, Josphert N; Xu, Kezhang; Liu, Bao



Combustion characterization of methylal in reciprocating engines  

SciTech Connect

Methylal, CH{sub 3}OCH{sub 2}OCH{sub 3}, also known as dimethoxy-methane, is unique among oxygenates in that it has a low autoignition temperature, no carbon-carbon bonds, and is soluble in middle distillate fuels. Because of these properties, methylal has been shown to be a favorable fuel additive for reducing smoke in diesel engines. Recent measurements of ignition delay times indicate that methylal has a cetane number in the range of 45-50, which is compatible with diesel fuels. Engine tests have shown that adding methylal to diesel fuel significantly reduces smoke emissions. Gaseous emissions and combustion efficiencies obtained with methylal/diesel fuel blends remain essentially the same as those measured using neat diesel fuel. Lubricity measurements of methylal/diesel fuel blends with a ball on cylinder lubrication evaluator (BOCLE) show that methylal improves the lubricity of diesel fuel. Even though additions of methylal lower the fuel viscosity, the results of the BOCLE tests indicate that the methylal/diesel fuel blends cause less pump wear than neat diesel fuel. The one drawback is that methylal has a low boiling point (42{degrees}C) and a relatively high vapor pressure. As a result, it lowers the flash point of diesel fuel and causes a potential fuel tank flammability hazard. One solution to this increased volatility is to make polyoxymethylenes with the general formula of CH{sub 3}O(CH{sub 2}O){sub x}CH{sub 3} where x > 2. The molecules are similar to methylal, but have higher molecular weights and thus higher viscosities and substantially lower vapor pressures. Therefore, their flash points will be compatible with regular diesel fuel. The polyoxymethylenes are expected to have combustion properties similar to methylal. It is theorized that by analogy with hydrocarbons, the ignition quality (i.e., cetane number) of the polyoxymethylenes will be better than that of methylal.

Dodge, L.; Naegeli, D. [Southwest Research Institute, San Antonio, TX (United States)



A Toxicological Evaluation of Certain Heparin-Quaternary Ammonium Complexes.  

National Technical Information Service (NTIS)

Physical and chemical characterizations show that the heparin-quaternary ammonium salt complexes can be reproducibly prepared from a given lot of a quaternary ammonium salt. Local toxicity studies also indicate that both the tridodecyl methyl ammonium chl...

G. A. Grode J. P. Crowley R. D. Falb R. I. Leininger



Methylation-Specific MLPA (MS-MLPA): simultaneous detection of CpG methylation and copy number changes of up to 40 sequences  

PubMed Central

Copy number changes and CpG methylation of various genes are hallmarks of tumor development but are not yet widely used in diagnostic settings. The recently developed multiplex ligation-dependent probe amplification (MLPA) method has increased the possibilities for multiplex detection of gene copy number aberrations in a routine laboratory. Here we describe a novel robust method: the methylation-specific MLPA (MS-MLPA) that can detect changes in both CpG methylation as well as copy number of up to 40 chromosomal sequences in a simple reaction. In MS-MLPA, the ligation of MLPA probe oligonucleotides is combined with digestion of the genomic DNA–probe hybrid complexes with methylation-sensitive endonucleases. Digestion of the genomic DNA–probe complex, rather than double-stranded genomic DNA, allowed the use of DNA derived from the formalin treated paraffin-embedded tissue samples, enabling retrospective studies. To validate this novel method, we used MS-MLPA to detect aberrant methylation in DNA samples of patients with Prader–Willy syndrome, Angelman syndrome or acute myeloid leukemia.

Nygren, Anders O. H.; Ameziane, Najim; Duarte, Helena M. B.; Vijzelaar, Raymon N. C. P.; Waisfisz, Quinten; Hess, Corine J.; Schouten, Jan P.; Errami, Abdellatif



Minireview: Role of Protein Methylation and Demethylation in Nuclear Hormone Signaling  

PubMed Central

Nuclear hormone receptors (NRs) are transcription factors responsible for mediating the biological effects of hormones during development, metabolism, and homeostasis. Induction of NR target genes is accomplished through the assembly of hormone-bound NR complexes at target promoters and coincides with changes in histone modifications that promote transcription. Some coactivators and corepressors of NR can enhance or inhibit NR function by covalently modifying histones. One such modification is methylation, which plays important roles in transcriptional regulation. Histone methylation is catalyzed by histone methyltransferases and reversed by histone demethylases. Recent studies have uncovered the importance of these enzymes in the regulation of NR target genes. In addition to histones, these enzymes have nonhistone substrates and can methylate and demethylate NRs and coregulatory proteins in order to modulate their function. This review discusses recent progress in our understanding of the role of methylation and demethylation of histones, NRs, and their coregulators in NR-mediated transcription.

Wu, Susan C.; Zhang, Yi



Methylation patterns of immunoglobulin genes in lymphoid cells: correlation of expression and differentiation with undermethylation.  

PubMed Central

Different states of eukaryotic gene expression are often correlated with different levels of methylation of DNA sequences containing structural genes and their flanking regions. To assess the potential role of DNA methylation in the expression of immunoglobulin genes, which require complex rearrangements prior to expression, methylation patterns were examined in cell lines representing different stages of lymphocyte maturation. Methylation of the second cytosine in the sequence 5' C-C-G-G 3' was determined by using Hpa II/Msp I endonuclease digestion. Four CH genes (C mu, C delta, C gamma 2b, and C alpha), C kappa, V kappa, C lambda, and V lambda genes were analyzed. The results lead to the following conclusions: (i) transcribed immunoglobulin genes are undermethylated; (ii) the C gene allelic to an expressed C gene is always also undermethylated; and (iii) all immunoglobulin loci tend to become increasingly undermethylated as B cells mature. Images

Storb, U; Arp, B



Normal histone modifications on the inactive X chromosome in ICF and Rett syndrome cells: implications for methyl-CpG binding proteins  

Microsoft Academic Search

BACKGROUND: In mammals, there is evidence suggesting that methyl-CpG binding proteins may play a significant role in histone modification through their association with modification complexes that can deacetylate and\\/or methylate nucleosomes in the proximity of methylated DNA. We examined this idea for the X chromosome by studying histone modifications on the X chromosome in normal cells and in cells from

Kartik R Varadarajan; Ping Luo; Theresa K Canfield; Jeff Traynor; Uta Francke; R Scott Hansen



Wp specific methylation of highly proliferated LCLs  

SciTech Connect

The epigenetic regulation of viral genes may be important for the life cycle of EBV. We determined the methylation status of three viral promoters (Wp, Cp, Qp) from EBV B-lymphoblastoid cell lines (LCLs) by pyrosequencing. Our pyrosequencing data showed that the CpG region of Wp was methylated, but the others were not. Interestingly, Wp methylation was increased with proliferation of LCLs. Wp methylation was as high as 74.9% in late-passage LCLs, but 25.6% in early-passage LCLs. From two Burkitt's lymphoma cell lines, Wp specific hypermethylation was also found (>80%). Interestingly, the expression of EBNA2 gene which located directly next to Wp was associated with its methylation. Our data suggested that Wp specific methylation may be important for the indicator of the proliferation status of LCLs, and the epigenetic viral gene regulation of EBNA2 gene by Wp should be further defined possibly with other biological processes.

Park, Jung-Hoon [Functional Genomics Lab, Graduate School of Life Science and Biotechnology, CHA Research Institute, Bundang Campus, College of Medicine, Pochon CHA University, 222 Yatap-Dong, Bundang-Gu, Sungnam-Si, Kyunggi-Do 436-836, South Korea (Korea, Republic of); Jeon, Jae-Pil [Division of Genome Resources Bank and Reservation, National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea (Korea, Republic of); Shim, Sung-Mi [Division of Genome Resources Bank and Reservation, National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea (Korea, Republic of); Nam, Hye-Young [Division of Genome Resources Bank and Reservation, National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea (Korea, Republic of); Kim, Joon-Woo [Division of Genome Resources Bank and Reservation, National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea (Korea, Republic of); Han, Bok-Ghee [Division of Genome Resources Bank and Reservation, National Genome Research Institute, National Institute of Health, 5 Nokbun-Dong, Eunpyung-Gu, Seoul 122-701, South Korea (Korea, Republic of); Lee, Suman [Functional Genomics Lab, Graduate School of Life Science and Biotechnology, CHA Research Institute, Bundang Campus, College of Medicine, Pochon CHA University, 222 Yatap-Dong, Bundang-Gu, Sungnam-Si, Kyunggi-Do 436-836, South Korea (Korea, Republic of)]. E-mail:



Protein arginine methylation in Saccharomyces cerevisiae.  


Recent research has implicated arginine methylation as a major regulator of cellular processes, including transcription, translation, nucleocytoplasmic transport, signalling, DNA repair, RNA processing and splicing. Arginine methylation is evolutionarily conserved, and it is now thought that it may rival other post-translational modifications such as phosphorylation in terms of its occurrence in the proteome. In addition, multiple recent examples demonstrate an exciting new theme: the interplay between methylation and other post-translational modifications such as phosphorylation. In this review, we summarize our current understanding of arginine methylation and the recent advances made, with a focus on the lower eukaryote Saccharomyces cerevisiae. We cover the types of methylated proteins, their responsible methyltransferases, where and how the effects of arginine methylation are seen in the cell, and, finally, discuss the conservation of the biological function of methylarginines between S. cerevisiae and mammals. PMID:23094907

Low, Jason K K; Wilkins, Marc R




Microsoft Academic Search

The complexation of Hg under sulfidic conditions influences its bioavailability for microbial methylation. Neutral dissolved Hg-sulfide complexes are readily available to Hg-methylating bacteria in culture, and thermodynamic models predict that inorganic Hg-sulfide complexes dominate dissolved Hg speciation under natural sulfidic conditions. However, these models have not been validated in the field. To examine the complexation of Hg in natural sulfidic

Carrie L. Miller; Robert P. Mason; Cynthia C. Gilmour; Andrew Heyes



Molecular Structure of Methyl Cyanide  

NSDL National Science Digital Library

Methyl Cyanide is a toxic, colorless liquid with an aromatic (ether like) odor and forms explosive mixtures with air. It is a critical solvent for several important processes e.g., it is widely used as a mobile phase solvent in chromatography applications, as a wash solvent and in preparing reagent solutions for oligonucleotide synthesis. It is employed in the manufacturing of acrylic fibers, pharmaceuticals, perfumes, nitrile rubber, batteries, pesticides, and inorganic salts. It can be utilized to remove tars, phenols, and coloring matter from petroleum hydrocarbons, to extract fatty acids from fish liver, animal, and vegetable oils, and to recrystallize steroids.



Aspects of Bioavailability of Mercury for Methylation in Pure Cultures of Desulfobulbus propionicus (1pr3)  

PubMed Central

We have previously hypothesized that sulfide inhibits Hg methylation by decreasing its bioavailability to sulfate-reducing bacteria (SRB), the important methylators of Hg in natural sediments. With a view to designing a bioassay to test this hypothesis, we investigated a number of aspects of Hg methylation by the SRB Desulfobulbus propionicus, including (i) the relationship between cell density and methylmercury (MeHg) production, (ii) the time course of Hg methylation relative to growth stage, (iii) changes in the bioavailability of an added inorganic Hg (HgI) spike over time, and (iv) the dependence of methylation on the concentration of dissolved HgI present in the culture. We then tested the effect of sulfide on MeHg production by this microorganism. These experiments demonstrated that under conditions of equal bioavailability, per-cell MeHg production was constant through log-phase culture growth. However, the methylation rate of a new Hg spike dramatically decreased after the first 5 h. This result was seen whether methylation rate was expressed as a fraction of the total added Hg or the filtered HgI concentration, which suggests that Hg bioavailability decreased through both changes in Hg complexation and formation of solid phases. At low sulfide concentration, MeHg production was linearly related to the concentration of filtered HgI. The methylation of filtered HgI decreased about fourfold as sulfide concentration was increased from 10?6 to 10?3 M. This decline is consistent with a decrease in the bioavailability of HgI, possibly due to a decline in the dissolved neutral complex, HgS0.

Benoit, J. M.; Gilmour, C. C.; Mason, R. P.



A Transcriptional Switch Mediated by Cofactor Methylation  

Microsoft Academic Search

We describe a molecular switch based on the controlled methylation of nucleosome and the transcriptional cofactors, the CREB-binding proteins (CBP)\\/p300. The CBP\\/p300 methylation site is localized to an arginine residue that is essential for stabilizing the structure of the KIX domain, which mediates CREB recruitment. Methylation of KIX by coactivator-associated arginine methyltransferase 1 (CARM1) blocks CREB activation by disabling the

Wei Xu; Hongwu Chen; Keyong Du; Hiroshi Asahara; Marc Tini; Beverly M. Emerson; Marc Montminy; Ronald M. Evans



Dimethylcarbonate for eco-friendly methylation reactions  

Microsoft Academic Search

Dimethylcarbonate (DMC), an environmentally friendly substitute for dimethylsulfate and methyl halides in methylation reactions, is a very selective reagent. Both under gas–liquid phase transfer catalysis (GL-PTC) and under batch conditions, with potassium carbonate as the catalyst, the reactions of DMC with methylene-active compounds (arylacetonitriles and arylacetoesters, aroxyacetonitriles and methyl aroxyacetates, benzylaryl- and alkylarylsulphones) produce monomethylated derivatives, with a selectivity not

S. Memoli; M. Selva; P. Tundo



Methyl esters in the fatty acid industry  

Microsoft Academic Search

Methyl esters, derived from natural fats or oils, can be used as alternatives to fatty acids in the production of a number\\u000a of derivatives. The derivatives that can be made from methyl esters include fatty alkanolamides, fatty alcohols, isopropyl\\u000a esters, and sucrose polyesters. By using methyl esters as the raw materials, several benefits may be realized, such as, the\\u000a ability

R. D. Farris



Enzymatic methylation of canola oil deodorizer distillate  

Microsoft Academic Search

Methylation of canola oil deodorizer distillate catalyzed by a nonspecific lipase was investigated. The conversion of fatty\\u000a acids to methyl esters has been optimized by using a statistical design. Up to 96.5% conversion of fatty acids to their methyl\\u000a esters has been achieved without the aid of vacuum or any water-removing agent. The effects of temperature, ratio of the reactants

Suresh Ramamurthi; Prakash R. Bhirud; Alan R. McCurdy



Hypoxic radiosensitization by the antimicrobial methyl paraben  

SciTech Connect

The antimicrobial preservative, methyl paraben (methyl-4-hydroxybenzoate) sensitizes anoxic buffered suspensions of Staphylococcus aureus to gamma-radiation. The maximal response at an 0.5 mM concentration represents a 150 percent increase in response over that for deoxygenated suspensions without additive, and 80 percent of the response for aerated suspensions alone. Methyl paraben is not toxic to the test organism under the present test conditions.

Jacobs, G.P.; Sade, N.



Microwave-accelerated methylation of starch.  


A novel microwave-accelerated method for methylating soluble starch is described. Soluble starch could be fully methylated in 72% yield within 4.66 min using iodomethane and 30% potassium hydroxide under microwave irradiation. The completely methylated starch thus obtained was hydrolyzed with 60% HCO(2)H for 1.5 min under 80% MW power, followed by 0.05 M H(2)SO(4) for 2.0 min under 100% MW power. The partially methylated monosaccharides were separated by preparative paper chromatography and identified by their melting points and optical rotations. PMID:17961526

Singh, Vandana; Tiwari, Ashutosh