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Sample records for intramolecular nucleophilic addition

  1. Lewis Acid and Fluoroalcohol Mediated Nucleophilic Addition to the C2 Position of Indoles.

    PubMed

    Morimoto, Naoki; Morioku, Kumika; Suzuki, Hideyuki; Takeuchi, Yasuo; Nishina, Yuta

    2016-05-01

    Indole readily undergoes nucleophilic substitution at the C3 site, and many indole derivatives have been functionalized using this property. Indole also forms indolium, which allows electrophilic addition in acidic conditions, but current examples have been limited to intramolecular reactions. C2 site-selective nucleophilic addition to indole derivatives using fluoroalcohol and a Lewis acid was developed. PMID:27119318

  2. The syn/anti-Dichotomy in the Palladium-Catalyzed Addition of Nucleophiles to Alkenes

    PubMed Central

    Kočovský, Pavel; Bäckvall, Jan-E

    2015-01-01

    In this review the stereochemistry of palladium-catalyzed addition of nucleophiles to alkenes is discussed, and examples of these reactions in organic synthesis are given. Most of the reactions discussed involve oxygen and nitrogen nucleophiles; the Wacker oxidation of ethylene has been reviewed in detail. An anti-hydroxypalladation in the Wacker oxidation has strong support from both experimental and computational studies. From the reviewed material it is clear that anti-addition of oxygen and nitrogen nucleophiles is strongly favored in intermolecular addition to olefin–palladium complexes even if the nucleophile is coordinated to the metal. On the other hand, syn-addition is common in the case of intramolecular oxy- and amidopalladation as a result of the initial coordination of the internal nucleophile to the metal. PMID:25378278

  3. Efficient copper-catalyzed direct intramolecular aminotrifluoromethylation of unactivated alkenes with diverse nitrogen-based nucleophiles.

    PubMed

    Lin, Jin-Shun; Xiong, Ya-Ping; Ma, Can-Liang; Zhao, Li-Jiao; Tan, Bin; Liu, Xin-Yuan

    2014-01-27

    A mild, convenient, and step-economical intramolecular aminotrifluoromethylation of unactivated alkenes with a variety of electronically distinct, nitrogen-based nucleophiles in the presence of a simple copper salt catalyst, in the absence of extra ligands, is described. Many different nitrogen-based nucleophiles (e.g., basic primary aliphatic and aromatic amines, sulfonamides, carbamates, and ureas) can be employed in this new aminotrifluoromethylation reaction. The aminotrifluoromethylation process allows straightforward access to diversely substituted CF3-containing pyrrolidines or indolines, in good to excellent yields, through a direct difunctionalization strategy from the respective acyclic starting materials. Mechanistic studies were conducted and a plausible mechanism was proposed. PMID:24458913

  4. Carbazole Annulation via Cascade Nucleophilic Addition-Cyclization Involving 2-(Silyloxy)pentadienyl Cation.

    PubMed

    Stepherson, Jacob R; Ayala, Caitlan E; Tugwell, Thomas H; Henry, Jeffrey L; Fronczek, Frank R; Kartika, Rendy

    2016-06-17

    We report a new strategy toward the synthesis of highly functionalized carbazoles via 2-(silyloxy)pentadienyl cation intermediates, which were generated upon ionization of vinyl-substituted α-hydroxy silyl enol ethers under Brønsted acid catalysis. These electrophilic species were found to readily undergo cascade reactions with substituted indoles to generate carbazole molecular scaffolds in good yields via a sequence of regioselective nucleophilic addition, followed by intramolecular dehydrative cyclization. PMID:27265237

  5. Exploiting the Bis-Nucleophilicity of α-Aminoboronates: Copper-Catalyzed, Intramolecular Aminoalkylations of Bromobenzoyl Chlorides.

    PubMed

    Dumas, Aaron M; Sieradzki, Adrian J; Donnelly, Liam J

    2016-04-15

    α-Aminoboronate salts are interesting examples of heteroatomic species containing adjacent nucleophilic centers. We have developed an acylation/arylation reaction using 2-bromobenzoyl chlorides as bis-electrophiles that harnesses the nucleophilicity of both positions, leading to isoindolinones. The reactions proceed under mild conditions via an intramolecular, Cu-catalyzed sp(3)-sp(2) coupling, giving products in up to 95% yield. These conditions enable arylation of α,α-disubstituted aminoboronates, which are difficult to accomplish using methods based on less abundant and more expensive transition metals. PMID:27017848

  6. Nucleophilic addition of sulfonamides to bromoacetylenes: facile preparation of pyrroles.

    PubMed

    Yamagishi, Masahito; Nishigai, Ken; Hata, Takeshi; Urabe, Hirokazu

    2011-09-16

    Nucleophilic addition of sulfonamides to 1-bromo-1-alkynes provided (Z)-N-(1-bromo-1-alken-2-yl)-p-toluenesulfonamides in good yield and in a highly regio- and stereoselective manner. Treatment of product (Z)-N-(1-bromo-1-octen-2-yl)-N-allyl-p-toluenesulfonamide with a palladium catalyst under Heck conditions afforded 1-(p-toluenesulfonyl)-2-hexyl-4-methylpyrrole in good yield. Other pyrroles with various substituents can also be prepared in good yield by this method. PMID:21842873

  7. Covalent binding of aniline to humic substances. 2. 15N NMR studies of nucleophilic addition reactions

    USGS Publications Warehouse

    Thorn, K.A.; Pettigrew, P.J.; Goldenberg, W.S.; Weber, E.J.

    1996-01-01

    Aromatic amines are known to undergo covalent binding with humic substances in the environment. Although previous studies have examined reaction conditions and proposed mechanisms, there has been no direct spectroscopic evidence for the covalent binding of the amines to the functional groups in humic substances. In order to further elucidate the reaction mechanisms, the Suwannee River and IHSS soil fulvic and humic acids were reacted with 15N-labeled aniline at pH 6 and analyzed using 15N NMR spectrometry. Aniline underwent nucleophilic addition reactions with the quinone and other carbonyl groups in the samples and became incorporated in the form of anilinohydroquinone, anilinoquinone, anilide, imine, and heterocyclic nitrogen, the latter comprising 50% or more of the bound amine. The anilide and anilinohydroquinone nitrogens were determined to be susceptible to chemical exchange by ammonia. In the case of Suwannee River fulvic acid, reaction under anoxic conditions and pretreatment with sodium borohydride or hydroxylamine prior to reaction under oxic conditions resulted in a decrease in the proportion of anilinohydroquinone nitrogen incorporated. The relative decrease in the incorporation of anilinohydroquinone nitrogen with respect to anilinoquinone nitrogen under anoxic conditions suggested that inter- or intramolecular redox reactions accompanied the nucleophilic addition reactions.

  8. Nucleophilic Addition of Nitrogen to Aryl Cations: Mimicking Titan Chemistry

    NASA Astrophysics Data System (ADS)

    Li, Anyin; Jjunju, Fred P. M.; Cooks, R. Graham

    2013-11-01

    The reactivity of aryl cations toward molecular nitrogen is studied systematically in an ion trap mass spectrometer at 102 Pascal of nitrogen, the pressure of the Titan main haze layer. Nucleophilic addition of dinitrogen occurs and the nature of aryl group has a significant influence on the reactivity, through inductive effects and by changing the ground state spin multiplicity. The products of nitrogen activation, aryldiazonium ions, react with typical nitriles, aromatic amines, and alkynes (compounds that are relevant as possible Titan atmosphere constituents) to form covalently bonded heterocyclic products. Theoretical calculations at the level [DFT(B3LYP)/6-311++G(d,p)] indicate that the N2 addition reaction is exothermic for the singlet aryl cations but endothermic for their triplet spin isomers. The -OH and -NH2 substituted aryl ions are calculated to have triplet ground states, which is consistent with their decreased nitrogen addition reactivity. The energy needed for the generation of the aryl cations from their protonated precursors (ca. 340 kJ/mol starting with protonated aniline) is far less than that required to directly activate the nitrogen triple bond (the lowest energy excited state of N2 lies ca. 600 kJ/mol above the ground state). The formation of aza-aromatics via arene ionization and subsequent reactions provide a conceivable route to the genesis of nitrogen-containing organic molecules in the interstellar medium and Titan haze layers.

  9. Nucleophilic addition of nitrogen to aryl cations: mimicking Titan chemistry.

    PubMed

    Li, Anyin; Jjunju, Fred P M; Cooks, R Graham

    2013-11-01

    The reactivity of aryl cations toward molecular nitrogen is studied systematically in an ion trap mass spectrometer at 10(2) Pascal of nitrogen, the pressure of the Titan main haze layer. Nucleophilic addition of dinitrogen occurs and the nature of aryl group has a significant influence on the reactivity, through inductive effects and by changing the ground state spin multiplicity. The products of nitrogen activation, aryldiazonium ions, react with typical nitriles, aromatic amines, and alkynes (compounds that are relevant as possible Titan atmosphere constituents) to form covalently bonded heterocyclic products. Theoretical calculations at the level [DFT(B3LYP)/6-311++G(d,p)] indicate that the N2 addition reaction is exothermic for the singlet aryl cations but endothermic for their triplet spin isomers. The -OH and -NH2 substituted aryl ions are calculated to have triplet ground states, which is consistent with their decreased nitrogen addition reactivity. The energy needed for the generation of the aryl cations from their protonated precursors (ca. 340 kJ/mol starting with protonated aniline) is far less than that required to directly activate the nitrogen triple bond (the lowest energy excited state of N2 lies ca. 600 kJ/mol above the ground state). The formation of aza-aromatics via arene ionization and subsequent reactions provide a conceivable route to the genesis of nitrogen-containing organic molecules in the interstellar medium and Titan haze layers. PMID:23982933

  10. Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

    PubMed Central

    Seddiqzai, Meriam; Dahmen, Tobias; Sure, Rebecca

    2013-01-01

    Summary The intramolecular radical addition to aniline derivatives was investigated by DFT calculations. The computational methods were benchmarked by comparing the calculated values of the rate constant for the 5-exo cyclization of the hexenyl radical with the experimental values. The dispersion-corrected PW6B95-D3 functional provided very good results with deviations for the free activation barrier compared to the experimental values of only about 0.5 kcal mol−1 and was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of the molecules is important and that a combination of electrophilic radicals with preferably nucleophilic arenes results in the highest rate constants. This is opposite to the Minisci reaction where the radical acts as nucleophile and the arene as electrophile. The substitution at the N-atom of the aniline is crucial. Methyl substitution leads to slower addition than phenyl substitution. Carbamates as substituents are suitable only when the radical center is not too electrophilic. No correlations between free reaction barriers and energies (ΔG ‡ and ΔG R) are found. Addition reactions leading to indanes or dihydrobenzofurans are too slow to be useful synthetically. PMID:24062821

  11. Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines.

    PubMed

    Gansäuer, Andreas; Seddiqzai, Meriam; Dahmen, Tobias; Sure, Rebecca; Grimme, Stefan

    2013-01-01

    The intramolecular radical addition to aniline derivatives was investigated by DFT calculations. The computational methods were benchmarked by comparing the calculated values of the rate constant for the 5-exo cyclization of the hexenyl radical with the experimental values. The dispersion-corrected PW6B95-D3 functional provided very good results with deviations for the free activation barrier compared to the experimental values of only about 0.5 kcal mol(-1) and was therefore employed in further calculations. Corrections for intramolecular London dispersion and solvation effects in the quantum chemical treatment are essential to obtain consistent and accurate theoretical data. For the investigated radical addition reaction it turned out that the polarity of the molecules is important and that a combination of electrophilic radicals with preferably nucleophilic arenes results in the highest rate constants. This is opposite to the Minisci reaction where the radical acts as nucleophile and the arene as electrophile. The substitution at the N-atom of the aniline is crucial. Methyl substitution leads to slower addition than phenyl substitution. Carbamates as substituents are suitable only when the radical center is not too electrophilic. No correlations between free reaction barriers and energies (ΔG (‡) and ΔG R) are found. Addition reactions leading to indanes or dihydrobenzofurans are too slow to be useful synthetically. PMID:24062821

  12. Regioselective nucleophilic addition of organometallic reagents to 3-geminal bis(silyl) N-acyl pyridinium.

    PubMed

    Wu, Ya; Li, Linjie; Li, Hongze; Gao, Lu; Xie, Hengmu; Zhang, Zhigao; Su, Zhishan; Hu, Changwei; Song, Zhenlei

    2014-04-01

    A regioselective nucleophilic addition to 3-geminal bis(silyl) N-acyl pyridinium has been described. Geminal bis(silane) shows contrasting roles that lead to different regioselectivities for the addition of different nucleophiles: its steric effect dominates to favor 1,6-addition of alkyl, vinyl, and aryl organometallic reagents; its directing effect dominates to favor 1,2-addition of less sterically demanding alkynyl Grignard reagents. PMID:24666415

  13. Indolyne Experimental and Computational Studies: Synthetic Applications and Origins of Selectivities of Nucleophilic Additions

    PubMed Central

    Im, G-Yoon J.; Bronner, Sarah M.; Goetz, Adam E.; Paton, Robert S.; Cheong, Paul H.-Y.; Houk, K. N.; Garg, Neil K.

    2010-01-01

    Efficient syntheses of 4,5-, 5,6-, and 6,7-indolyne precursors beginning from commercially available hydroxyindole derivatives are reported. The synthetic routes are versatile and allow access to indolyne precursors that remain unsubstituted on the pyrrole ring. Indolynes can be generated under mild fluoride-mediated conditions, trapped by a variety of nucleophilic reagents, and used to access a number of novel substituted indoles. Nucleophilic addition reactions to indolynes proceed with varying degrees of regioselectivity; distortion energies control regioselectivity and provide a simple model to predict the regioselectivity in the nucleophilic additions to indolynes and other unsymmetrical arynes. This model has led to the design of a substituted 4,5-indolyne that exhibits enhanced nucleophilic regioselectivity. PMID:21114321

  14. Organocatalytic Asymmetric Nucleophilic Addition to o-Quinone Methides by Alcohols.

    PubMed

    Lai, Zengwei; Wang, Zhaobin; Sun, Jianwei

    2015-12-18

    The first catalytic asymmetric intermolecular alcohol conjugate addition to o-quinone methides (o-QMs) is disclosed. Due to reversible C-O bond formation and low nucleophilicity of alcohols, catalytic asymmetric oxa-Michael additions with simple alcohol nucleophiles to establish acyclic oxygenated carbon stereocenters remain scarce. The present reaction represents a rare example of this type. With a suitable chiral acid catalyst, the in situ formation of o-QMs and subsequent conjugate addition proceeded with high efficiency and enantioselectivity. The chiral ether products are versatile precursors to other chiral molecules. PMID:26637015

  15. Reaction of arynes with vinylogous amides: nucleophilic addition to the ortho-quinodimethide intermediate.

    PubMed

    Li, Ran; Wang, Xuemei; Wei, Zhibin; Wu, Chunrui; Shi, Feng

    2013-09-01

    The reaction of arynes with vinylogous amides containing no free N-H bonds proceeds in a [2 + 2] cycloaddition fashion at ambient temperature. The electronic properties of the vinylogous amides allow for the cycloadducts undergoing a facile ring-opening process, leading to electronically biased ortho-quinodimethide intermediates. Subsequent nucleophilic addition with alcohols affords 2-substituted benzaldehydes or ketones. PMID:23957502

  16. Synthesis of a Fluorescent Acridone Using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence

    ERIC Educational Resources Information Center

    Goodrich, Samuel; Patel, Miloni; Woydziak, Zachary R.

    2015-01-01

    A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the…

  17. Benzimidazoles and benzoxazoles via the nucleophilic addition of anilines to nitroalkanes.

    PubMed

    Aksenov, Alexander V; Smirnov, Alexander N; Aksenov, Nicolai A; Bijieva, Asiyat S; Aksenova, Inna V; Rubin, Michael

    2015-04-14

    PPA-induced umpolung triggers efficient nucleophilic addition of unactivated anilines to nitroalkanes to produce N-hydroxyimidamides. The latter undergo sequential acid-promoted cyclocondensation with ortho-OH or ortho-NHR moieties to afford benzoxazoles and benzimidazoles, respectively. PMID:25758157

  18. Annulation of thioimidates and vinyl carbodiimides to prepare 2-aminopyrimidines, competent nucleophiles for intramolecular alkyne hydroamination. Synthesis of (-)-crambidine.

    PubMed

    Perl, Nicholas R; Ide, Nathan D; Prajapati, Sudeep; Perfect, Hahdi H; Durón, Sergio G; Gin, David Y

    2010-02-17

    A convergent synthesis of (-)-crambidine is reported. The sequence capitalizes on two novel key transformations, including a [4+2] annulation of thioimidates with vinyl carbodiimides and an alkyne hydroamination employing 2-aminopyrimidine nucleophiles. PMID:20095555

  19. Rhodium and copper-catalyzed asymmetric conjugate addition of alkenyl nucleophiles.

    PubMed

    Müller, Daniel; Alexakis, Alexandre

    2012-12-25

    Since the initial reports in the mid-90s, metal catalyzed asymmetric conjugate addition (ACA) reactions evolved as an important tool for the synthetic chemist. Most of the research efforts have been done in the field of rhodium and copper catalyzed ACA reactions employing aryl and alkyl nucleophiles. Despite the great synthetic value of the double bond, the addition of alkenyl nucleophiles remains insufficiently explored. In this account, an overview of the developments in the field of rhodium and copper catalyzed ACA reactions with organometallic alkenyl reagents (B, Mg, Al, Si, Zr, Sn) will be provided. The account is intended to give a comprehensive overview of all the existing methods. However, in many cases only selected examples are displayed in order to facilitate comparison of different ligands and methodologies. PMID:23096501

  20. 4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions

    NASA Astrophysics Data System (ADS)

    Dong, Jinhuan; Shi, Lou; Pan, Ling; Xu, Xianxiu; Liu, Qun

    2016-06-01

    In recent years, numerous methods have emerged for the synthesis of trifluoromethylated arenes based on the late-stage introduction of a trifluoromethyl group onto an aryl ring. In sharp comparison, the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon has rarely been addressed. It has been found that 4-trifluoromethyl-p-quinol silyl ethers, the readily available and relatively stable compounds, can act as dielectrophiles to be applied to multi-component reactions for the synthesis of various trifluoromethylated arenes. Catalyzed by In(OTf)3, 4-trifluoromethyl-p-quinol silyl ethers react with C-, N-, and S-nucleophiles, respectively, in a regiospecific 1,2-addition manner to generate the corresponding highly reactive electrophilic intermediates. Further reaction of the in-situ generated electrophiles with a C-nucleophile followed by spontaneous aromatization enables the construction of functionalized trifluoromethyl arenes. This three-component, double nucleophilic addition/aromatization reaction based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon provides a divergent strategy for the synthesis of trifluoromethylated arenes under mild reaction conditions in a single operation.

  1. 4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions

    PubMed Central

    Dong, Jinhuan; Shi, Lou; Pan, Ling; Xu, Xianxiu; Liu, Qun

    2016-01-01

    In recent years, numerous methods have emerged for the synthesis of trifluoromethylated arenes based on the late-stage introduction of a trifluoromethyl group onto an aryl ring. In sharp comparison, the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon has rarely been addressed. It has been found that 4-trifluoromethyl-p-quinol silyl ethers, the readily available and relatively stable compounds, can act as dielectrophiles to be applied to multi-component reactions for the synthesis of various trifluoromethylated arenes. Catalyzed by In(OTf)3, 4-trifluoromethyl-p-quinol silyl ethers react with C-, N-, and S-nucleophiles, respectively, in a regiospecific 1,2-addition manner to generate the corresponding highly reactive electrophilic intermediates. Further reaction of the in-situ generated electrophiles with a C-nucleophile followed by spontaneous aromatization enables the construction of functionalized trifluoromethyl arenes. This three-component, double nucleophilic addition/aromatization reaction based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon provides a divergent strategy for the synthesis of trifluoromethylated arenes under mild reaction conditions in a single operation. PMID:27246540

  2. Recent Developments in Metal-Catalyzed Additions of Oxygen Nucleophiles to Alkenes and Alkynes

    NASA Astrophysics Data System (ADS)

    Hintermann, Lukas

    Progress in the field of metal-catalyzed redox-neutral additions of oxygen nucleophiles (water, alcohols, carboxylic acids, and others) to alkenes, alkynes, and allenes between 2001 and 2009 is critically reviewed. Major advances in reaction chemistry include development of chiral Lewis acid catalyzed asymmetric oxa-Michael additions and Lewis-acid catalyzed hydro-alkoxylations of nonactivated olefins, as well as further development of Markovnikov-selective cationic gold complex-catalyzed additions of alcohols or water to alkynes and allenes.

  3. Effects of Solvent and Residual Water on Enhancing the Reactivity of Six-Membered Silyloxyallyl Cations toward Nucleophilic Addition.

    PubMed

    Malone, Joshua A; Cleveland, Alexander H; Fronczek, Frank R; Kartika, Rendy

    2016-09-01

    A new strategy for the generation of six-membered unsymmetrical silyloxyallyl cations using catalytic mild Brønsted acid is reported. These reactive intermediates were found to readily undergo direct nucleophilic addition with a broad range of nucleophiles to produce various α,α'-disubstituted silyl enol ether structural motifs. The findings also highlight the significance of the solvent effect and residual water in enhancing the reaction rate. PMID:27538538

  4. Phosphonate ester hydrolysis catalyzed by two lanthanum ions. Intramolecular nucleophilic attack of coordinated hydroxide and lewis acid activation

    SciTech Connect

    Tsubouchi, A.; Bruice, T.C.

    1995-07-19

    (8-Hydroxy-2-quinolyl)methyl (8-hydroxy-2-quinolyl)methyl phosphonate (I) has been synthesized as a model compound and investigated in terms of catalysis of hydrolysis by two metal ions in concert. Removal of one of two 8-hydroxyquinoline ligands of I to provide (8-hydroxy-2-quinolyl)methylmethylphosphonate (II) leads to the formation of the 1:1 complex (II)La, which is hydrolytically inert but subject to catalysis by free La{sup 3+}. From thermodynamic studies of metal ion complexation and comparison of the kinetics of hydrolysis of I and II in the presence of metal ions, we conclude the following. The phosphonate ester I forms a hydrolytically active 1:2 complex (I)La{sub 2} with La{sup 3+} but inert 1:1 complexes with Zn{sup 2+}, Ni{sup 2+}, Co{sup 2+}, Cu{sup 2+}, and Al{sup 3+}. The La{sup 3+} in the (I)La{sub 2} complex serve to (i) facilitate the formation of metal ligated hydroxide as an intramolecule nucleophile; (ii) stabilize the transition state of the hydrolysis by neutralization of the phosphonate negative charge; and (iii) interact with an incipient oxyanion of the leaving alcohol. The two La{sup 3+} functions operate in concert and provide nearly 10{sup 13} rate enhancement. Consequently the 1:2 complex (I)La{sub 2}(OH{sub 2}){sub n-1}(OH) may serve as a model for the 3`-5` exonuclease reaction of E. coli DNA polymerase I. 39 refs., 7 figs., 3 tabs.

  5. Nucleophilic addition-triggered lanthanide luminescence allows detection of amines by Eu(thenoyltrifluoroacetone)3.

    PubMed

    Zhou, Zhan; Wang, Qianming; Lin, Jintai; Chen, Yanna; Yang, Chuqin

    2012-01-01

    Herein, a novel fluorescent indicator for the real-time monitoring of amines is described. This probe contains a complex of europium-(thenoyltrifluoroacetone)(3) (Eu(TTA)(3)) that efficiently reacts with primary and secondary amines. The electron-withdrawing trifluoroacetyl undergoes a nucleophilic addition with amines, and the complex was used to selectively detect BuNH(2) and Et(2) NH (quenching concentration for BuNH(2): 10(-4) M, for Et(2)NH: 1.2 × 10(-3) M) by monitoring emission; no changes were observed in the emission spectrum of Eu(TTA)(3) in the presence of Et(3)N, [Bu(4)N]Cl, or PhNH(2) in aqueous solution (THF/H(2)O = 1:1). The ratio of emission intensity to amine concentration was linear by the least-squares fitting method. PMID:22458513

  6. Catalytic generation of arynes and trapping by nucleophilic addition and iodination.

    PubMed

    Hamura, Toshiyuki; Chuda, Yu; Nakatsuji, Yuya; Suzuki, Keisuke

    2012-04-01

    A fair exchange: in the title reaction, alkynyllithium serves as an initiator for benzyne generation through an iodine-lithium exchange. When performed in the presence of stoichiometric amounts of a nucleophile, the generated benzyne undergoes attack by lithio nucleophiles to generate aryllithium, which is then iodinated by iodoalkyne to give the iodoarenes 1. PMID:22359268

  7. REACTIVITIES OF ACRYLIC AND METHACRYLIC ACIDS IN A NUCLEOPHILIC ADDITION MODEL OF THEIR BIOLOGICAL ACTIVITY (JOURNAL VERSION)

    EPA Science Inventory

    The reactivities of derivatives of acrylic and methacrylic acid (AA and MAA) in Michael reactions of nucleophilic addition that have been proposed as the underlying mechanisms for the toxicity of such compounds are evaluated from a study of the mechanism of addition of a nucleoph...

  8. Fluorescent "turn-on" detecting CN- by nucleophilic addition induced Schiff-base hydrolysis

    NASA Astrophysics Data System (ADS)

    Lin, Qi; Cai, Yi; Li, Qiao; Shi, Bing-Bing; Yao, Hong; Zhang, You-Ming; Wei, Tai-Bao

    2015-04-01

    A new chemosensor Sz based on Schiff-base group as recognition site and naphthalene as the fluorescence signal group was designed and synthesised. It could fluorescent "turn-on" detect cyanide (CN-) via a novel mechanism of nucleophilic addition induced Schiff-base hydrolysis. Adding the CN- into the solution of Sz could induce Sz to emit blue fluorescence at 435 nm instantly. Moreover, Sz could also colorimetric detect CN-. Upon the addition of CN-, the Sz showed dramatic color change from yellow to colorless. These sensing procedures could not be interfered by other coexistent competitive anions such as F-, AcO-, H2PO4- and SCN-. In addition, Sz showed high sensitivity for CN-, the detection limits is 3.42 × 10-8 M of CN-, which is far lower than the WHO guideline of CN- in drinking water (less than 1.9 × 10-6 M). The CN- test strips based on Sz could act as a convenient CN- test kits.

  9. Bifunctional reactivity of amidoximes observed upon nucleophilic addition to metal-activated nitriles.

    PubMed

    Bolotin, Dmitrii S; Demakova, Marina Ya; Novikov, Alexander S; Avdontceva, Margarita S; Kuznetsov, Maxim L; Bokach, Nadezhda A; Kukushkin, Vadim Yu

    2015-04-20

    Treatment of the aromatic nitrile complexes trans-[PtCl2(RC6H4CN)2] (R = p-CF3 NC1, H NC2, o-Cl NC3) with the aryl amidoximes p-R'C6H4C(NH2)=NOH (R' = Me AO1, H AO2, Br AO3, CF3 AO4, NO2 AO5) in all combinations, followed by addition of 1 equiv of AgOTf and then 5 equiv of Et3N, leads to the chelates [PtCl{HN=C(RC6H4)ON=C(C6H4R'-p)NC(RC6H4)═NH}] (1-15; 15 examples; yields 71-88% after column chromatography) derived from the platinum(II)-mediated coupling between metal-activated nitriles and amidoximes. The mechanism of this reaction was studied experimentally by trapping and identification of the reaction intermediates, and it was also investigated theoretically at the DFT level of theory. The combined experimental and theoretical results indicate that the coupling with the nitrile ligands involves both the HON and monodeprotonated NH2 groups of the amidoximes, whereas in the absence of the base, the NH2 functionality is inactive toward the coupling. The observed reaction represents the first example of bifunctional nucleophilic behavior of amidoximes. The complexes 1-16 were characterized by elemental analyses (C, H, N), high-resolution ESI(+)-MS, FTIR, and (1)H NMR techniques, whereas unstable 17 was characterized by HRESI(+)-MS and FTIR. In addition, 8·C4H8O2, 12, and 16·CHCl3 were studied by single-crystal X-ray diffraction. PMID:25822628

  10. Effect of Conformational Rigidity on the Stereoselectivity of Nucleophilic Additions to Five-membered Ring Bicyclic Oxocarbenium Ion Intermediates

    PubMed Central

    Lavinda, O.; Tran, Vi Tuong

    2014-01-01

    Nucleophilic substitution reactions of five-membered ring acetals bearing fused rings reveal that subtle changes in the structure of the fused ring can exert dramatic influences on selectivity. If the fused ring did not constrain the five-membered ring undergoing substitution, selectivity was comparable to what was observed for an unconstrained system (≥92% diastereoselectivity, favoring the product of inside attack on the oxocarbenium ion). If the ring were more constrained by including at least one oxygen atom in the ring, selectivity dropped considerably (to 60% diastereoselectivity in one case). Transition states of the nucleophilic addition of allyltrimethylsilane to selected oxocarbenium ions were calculated using DFT methods. These computational models reproduced the correlation between additional conformational rigidity and selectivity. PMID:25087588

  11. Mechanistic study of secondary organic aerosol components formed from nucleophilic addition reactions of methacrylic acid epoxide

    NASA Astrophysics Data System (ADS)

    Birdsall, A. W.; Miner, C. R.; Mael, L. E.; Elrod, M. J.

    2014-08-01

    Recently, methacrylic acid epoxide (MAE) has been proposed as a precursor to an important class of isoprene-derived compounds found in secondary organic aerosol (SOA): 2-methylglyceric acid (2-MG) and a set of oligomers, nitric acid esters and sulfuric acid esters related to 2-MG. However, the specific chemical mechanisms by which MAE could form these compounds have not been previously studied. In order to determine the relevance of these processes to atmospheric aerosol, MAE and 2-MG have been synthesized and a series of bulk solution-phase experiments aimed at studying the reactivity of MAE using nuclear magnetic resonance (NMR) spectroscopy have been performed. The present results indicate that the acid-catalyzed MAE reaction is more than 600 times slower than a similar reaction of an important isoprene-derived epoxide, but is still expected to be kinetically feasible in the atmosphere on more acidic SOA. The specific mechanism by which MAE leads to oligomers was identified, and the reactions of MAE with a number of atmospherically relevant nucleophiles were also investigated. Because the nucleophilic strengths of water, sulfate, alcohols (including 2-MG), and acids (including MAE and 2-MG) in their reactions with MAE were found to be of a similar magnitude, it is expected that a diverse variety of MAE + nucleophile product species may be formed on ambient SOA. Thus, the results indicate that epoxide chain reaction oligomerization will be limited by the presence of high concentrations of non-epoxide nucleophiles (such as water); this finding is consistent with previous environmental chamber investigations of the relative humidity-dependence of 2-MG-derived oligomerization processes and suggests that extensive oligomerization may not be likely on ambient SOA because of other competitive MAE reaction mechanisms.

  12. Mechanistic study of secondary organic aerosol components formed from nucleophilic addition reactions of methacrylic acid epoxide

    NASA Astrophysics Data System (ADS)

    Birdsall, A. W.; Miner, C. R.; Mael, L. E.; Elrod, M. J.

    2014-12-01

    Recently, methacrylic acid epoxide (MAE) has been proposed as a precursor to an important class of isoprene-derived compounds found in secondary organic aerosol (SOA): 2-methylglyceric acid (2-MG) and a set of oligomers, nitric acid esters, and sulfuric acid esters related to 2-MG. However, the specific chemical mechanisms by which MAE could form these compounds have not been previously studied with experimental methods. In order to determine the relevance of these processes to atmospheric aerosol, MAE and 2-MG have been synthesized and a series of bulk solution-phase experiments aimed at studying the reactivity of MAE using nuclear magnetic resonance (NMR) spectroscopy have been performed. The present results indicate that the acid-catalyzed MAE reaction is more than 600 times slower than a similar reaction of an important isoprene-derived epoxide, but is still expected to be kinetically feasible in the atmosphere on more acidic SOA. The specific mechanism by which MAE leads to oligomers was identified, and the reactions of MAE with a number of atmospherically relevant nucleophiles were also investigated. Because the nucleophilic strengths of water, sulfate, alcohols (including 2-MG), and acids (including MAE and 2-MG) in their reactions with MAE were found to be of similar magnitudes, it is expected that a diverse variety of MAE + nucleophile product species may be formed on ambient SOA. Thus, the results indicate that epoxide chain reaction oligomerization will be limited by the presence of high concentrations of non-epoxide nucleophiles (such as water); this finding is consistent with previous environmental chamber investigations of the relative humidity dependence of 2-MG-derived oligomerization processes and suggests that extensive oligomerization may not be likely on ambient SOA because of other competitive MAE reaction mechanisms.

  13. Semifluorinated polymers via cycloaddition and nucleophilic addition reactions of aromatic trifluorovinyl ethers

    NASA Astrophysics Data System (ADS)

    Iacono, Scott Thomas

    This dissertation encompasses the synthesis, characterization, and properties of semifluorinated polymers derived from thermal polymerization of aryl trifluorovinyl ether (TFVE) monomers. This work is divided into two parts based on the methodology of thermal polymerization using aryl TFVE monomers. The first part of this work involves the thermal [2 + 2] cyclodimerization of aryl TFVE monomers affording perfluorocyclobutyl (PFCB) aryl ether polymers. Chapter 1 provides an overview of PFCB aryl ether polymers as a next-generation class of high performance fluoropolymers that have been successfully employed for a myriad of technologies. PFCB aryl ether polymers are highly desired because of their high thermal stability, processability, and tailorability for specific material applications. Chapter 2 introduces a general perspective of polyhedral oligomeric silsesquioxanes (POSS) that were modified with PFCB aryl ether polymer for property enhancement, specifically for low surface energy materials. Chapter 3 and 4 show the synthesis, characterization, and properties of POSS modified PFCB aryl ether polymers as blends and a variety of copolymer architectures, respectively. The second portion of this dissertation focuses on the development of a new, facile step-growth polymerization of diols/bisphenols and aryl TFVEs to afford fluoroethylene/vinylene alkyl/aryl ether (FAE) polymers. Chapter 5 is a prelude to the development of FAE polymers which entails optimizing the methodology and mechanistic rationale of nucleophile addition to aryl TFVEs. Chapter 6 details the FAE polymerization kinetics, physical properties, and strategy for functionalization. Chapter 7 illustrates the modular modification of FAE polymers for the development of tunable light emissive materials for potential use as transport layer material for organic light emitting diodes (OLEDs) and also chemical sensors. Chapter 8 introduces postfunctionaliztion of FAE polymers resulting with sulfonated biaryl

  14. Gold(I)-Catalyzed Inter- and Intramolecular Additions of Carbonyl Compounds to Allenenes

    PubMed Central

    2016-01-01

    The gold(I)-catalyzed intramolecular reaction of allenes with oxoalkenes leads to bicyclo[6.3.0]undecane ring systems, although in the case of terminally disubstituted allenes, seven-membered rings are formed. The related intermolecular addition of aldehydes to allenenes also gives seven-membered rings. PMID:26918852

  15. Templated assembly of medium cyclic ethers via exo-trig nucleophilic cyclization of cyclopropenes.

    PubMed

    Alnasleh, Bassam K; Rubina, Marina; Rubin, Michael

    2016-06-14

    A novel method for the assembly of medium heterocycles via an intramolecular nucleophilic addition to cyclopropenes generated in situ from the corresponding bromocyclopropanes is described. The exo-trig nucleophilic cyclizations were shown to proceed very efficiently and in a highly diastereoselective fashion affording cis-fused bicyclic products possessing 7 to 10-membered medium rings; starting from a diastereomeric mixtures of bromocyclopropanes. PMID:27210442

  16. EVAPORATION: a new vapour pressure estimation methodfor organic molecules including non-additivity and intramolecular interactions

    NASA Astrophysics Data System (ADS)

    Compernolle, S.; Ceulemans, K.; Müller, J.-F.

    2011-09-01

    We present EVAPORATION (Estimation of VApour Pressure of ORganics, Accounting for Temperature, Intramolecular, and Non-additivity effects), a method to predict (subcooled) liquid pure compound vapour pressure p0 of organic molecules that requires only molecular structure as input. The method is applicable to zero-, mono- and polyfunctional molecules. A simple formula to describe log10p0(T) is employed, that takes into account both a wide temperature dependence and the non-additivity of functional groups. In order to match the recent data on functionalised diacids an empirical modification to the method was introduced. Contributions due to carbon skeleton, functional groups, and intramolecular interaction between groups are included. Molecules typically originating from oxidation of biogenic molecules are within the scope of this method: aldehydes, ketones, alcohols, ethers, esters, nitrates, acids, peroxides, hydroperoxides, peroxy acyl nitrates and peracids. Therefore the method is especially suited to describe compounds forming secondary organic aerosol (SOA).

  17. A colorimetric detection of acrylamide in potato chips based on nucleophile-initiated thiol-ene Michael addition.

    PubMed

    Hu, Qinqin; Fu, Yingchun; Xu, Xiahong; Qiao, Zhaohui; Wang, Ronghui; Zhang, Ying; Li, Yanbin

    2016-02-01

    Acrylamide (AA), a neurotoxin and a potential carcinogen, has been found in various thermally processed foods such as potato chips, biscuits, and coffee. Simple, cost-effective, and sensitive methods for the rapid detection of AA are needed to ensure food safety. Herein, a novel colorimetric method was proposed for the visual detection of AA based on a nucleophile-initiated thiol-ene Michael addition reaction. Gold nanoparticles (AuNPs) were aggregated by glutathione (GSH) because of a ligand-replacement, accompanied by a color change from red to purple. In the presence of AA, after the thiol-ene Michael addition reaction between GSH and AA with the catalysis of a nucleophile, the sulfhydryl group of GSH was consumed by AA, which hindered the subsequent ligand-replacement and the aggregation of AuNPs. Therefore, the concentration of AA could be determined by the visible color change caused by dispersion/aggregation of AuNPs. This new method showed high sensitivity with a linear range from 0.1 μmol L(-1) to 80 μmol L(-1) and a detection limit of 28.6 nmol L(-1), and especially revealed better selectivity than the fluorescence sensing method reported previously. Moreover, this new method was used to detect AA in potato chips with a satisfactory result in comparison with the standard methods based on chromatography, which indicated that the colorimetric method can be expanded for the rapid detection of AA in thermally processed foods. PMID:26699696

  18. New Insights into the Detection of Sulfur Trioxide Anion Radical by Spin Trapping: Radical Trapping versus Nucleophilic Addition

    PubMed Central

    Ranguelova, Kalina; Mason, Ronald P.

    2009-01-01

    It has recently been proposed that (bi)sulfite (hydrated sulfur dioxide) reacts with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) in biological systems via a nonradical, nucleophilic reaction, implying that the radical adduct (DMPO/•SO3−) formation in these systems is an artifact and not the result of spin trapping of sulfur trioxide anion radical (•SO3−). Here, the one-electron oxidation of (bi)sulfite catalyzed by horseradish peroxidase/H2O2 has been re-investigated by ESR spin trapping with DMPO and oxygen uptake studies in order to obtain further evidence for the radical reaction mechanism. In the case of ESR experiments, the signal of DMPO/•SO3− radical adduct was detected, and the initial rate of its formation was calculated. Support for the radical pathway via •SO3− was obtained from the stoichiometry between the amount of consumed molecular oxygen and the amount of (bi)sulfite oxidized to sulfate (SO42−). When DMPO was incubated with (bi)sulfite, oxygen consumption was completely inhibited due to the efficiency of DMPO trapping. In the absence of DMPO, the initial rate of oxygen and H2O2 consumption was determined to be half of the initial rate of DMPO/•SO3− radical adduct formation as determined by ESR, demonstrating that DMPO forms the radical adduct by trapping the •SO3− exclusively. We conclude that DMPO is not susceptible to artifacts arising from nonradical chemistry (nucleophilic addition) except when both (bi)sulfite and DMPO concentrations are at nonphysiological levels of at least 0.1 M and the incubations are for longer time periods. PMID:19362142

  19. NUCLEOPHILIC ADDITION TO ACTIVATED DOUBLE BONDS: PREDICTION OF REACTIVITY FROM THE LAPLACIAN OF CHARGE DENSITY

    EPA Science Inventory

    The reactivities of a series of molecules in a Michael addition reaction are analyzed on the basis of properties expressed in the Laplacian of the charge density distribution. he charge densities of structurally optimized acrylic acid (AA), methacrylic acid (MAA), acrylonitrile (...

  20. Nucleophilic additions of primary and secondary amines to pentacyclo[5.4.0.0{sup 2,6}.0{sup 3,10}.0{sup 5,9}]undecane-8,11-dione

    SciTech Connect

    Bott, S.G.; Marchand, A.P.; Kumar, K.A.

    1995-10-01

    The crystal structures of three compounds formed via nucleophilic attack of a heterocyclic secondary amine on PCU-8,11-dione, with the concomitant intramolecular attack of one keto oxygen on the carbon of the other ketone, are presented. In all three compounds, the bridging oxygen contains substantial p-character, and the bonds to the {open_quotes}attacking{close_quotes} nitrogen are significantly shorter than would be expected.

  1. Definition of a nucleophilicity scale.

    PubMed

    Jaramillo, Paula; Pérez, Patricia; Contreras, Renato; Tiznado, William; Fuentealba, Patricio

    2006-07-01

    This work deals with exploring some empirical scales of nucleophilicity. We have started evaluating the experimental indices of nucleophilicity proposed by Legon and Millen on the basis of the measure of the force constants derived from vibrational frequencies using a probe dipole H-X (X = F,CN). The correlation among some theoretical parameters with this experimental scale has been evaluated. The theoretical parameters have been chosen as the minimum of the electrostatic potential V(min), the binding energy (BE) between the nucleophile and the H-X dipole, and the electrostatic potential measured at the position of the hydrogen atom V(H) when the complex nucleophile and dipole H-X is in the equilibrium geometry. All of them present good correlations with the experimental nucleophilicity scale. In addition, the BEs of the nucleophiles with two other Lewis acids (one hard, BF(3), and the other soft, BH(3)) have been evaluated. The results suggest that the Legon and Millen nucleophilicity scale and the electrostatic potential derived scales can describe in good approximation the reactivity order of the nucleophiles only when the interactions with a probe electrophile is of the hard-hard type. For a covalent interaction that is orbital controlled, a new nucleophilicity index using information of the frontier orbitals of both, the nucleophile and the electrophile has been proposed. PMID:16805506

  2. Citrus Peel Additives for One-Pot Triazole Formation by Decarboxylation, Nucleophilic Substitution, and Azide-Alkyne Cycloaddition Reactions

    ERIC Educational Resources Information Center

    Mendes, Desiree E.; Schoffstall, Allen M.

    2011-01-01

    This undergraduate organic laboratory experiment consists of three different reactions occurring in the same flask: a cycloaddition reaction, preceded by decarboxylation and nucleophilic substitution reactions. The decarboxylation and cycloaddition reactions occur using identical Cu(I) catalyst and conditions. Orange, lemon, and other citrus fruit…

  3. Mutual Cooperation in the Formal Allyl Alcohol Nucleophilic Substitution and Hydration of Alkynes for the Construction of γ-Substituted Ketones.

    PubMed

    Huang, Kaimeng; Wang, Hongkai; Liu, Lingyan; Chang, Weixing; Li, Jing

    2016-05-01

    Mutual cooperation in the formal allyl alcohol nucleophilic substitution reaction and hydration of an alkyne has been utilized in the presence of a gold catalyst to give a series of γ-functionalized ketones with high to excellent yields. This reaction actually involved an intramolecular O-H insertion cyclization of an alkyne to form the dihydrofuran intermediate, which was followed by the nucleophilic addition ring-opening of a dihydrofuran to give the target compound. PMID:26946315

  4. Additional Nucleophile-Free FeCl3-Catalyzed Green Deprotection of 2,4-Dimethoxyphenylmethyl-Protected Alcohols and Carboxylic Acids.

    PubMed

    Sawama, Yoshinari; Masuda, Masahiro; Honda, Akie; Yokoyama, Hiroki; Park, Kwihwan; Yasukawa, Naoki; Monguchi, Yasunari; Sajiki, Hironao

    2016-01-01

    The deprotection of the methoxyphenylmethyl (MPM) ether and ester derivatives can be generally achieved by the combinatorial use of a catalytic Lewis acid and stoichiometric nucleophile. The deprotections of 2,4-dimethoxyphenylmethyl (DMPM)-protected alcohols and carboxylic acids were found to be effectively catalyzed by iron(III) chloride without any additional nucleophile to form the deprotected mother alcohols and carboxylic acids in excellent yields. Since the present deprotection proceeds via the self-assembling mechanism of the 2,4-DMPM protective group itself to give the hardly-soluble resorcinarene derivative as a precipitate, the rigorous purification process by silica-gel column chromatography was unnecessary and the sufficiently-pure alcohols and carboxylic acids were easily obtained in satisfactory yields after simple filtration. PMID:27373632

  5. EVAPORATION: a new vapor pressure estimation method for organic molecules including non-additivity and intramolecular interactions

    NASA Astrophysics Data System (ADS)

    Compernolle, S.; Ceulemans, K.; Müller, J.-F.

    2011-04-01

    We present EVAPORATION (Estimation of VApour Pressure of ORganics, Accounting for Temperature, Intramolecular, and Non-additivity effects), a method to predict vapour pressure p0 of organic molecules needing only molecular structure as input. The method is applicable to zero-, mono- and polyfunctional molecules. A simple formula to describe log10p0(T) is employed, that takes into account both a wide temperature dependence and the non-additivity of functional groups. In order to match the recent data on functionalised diacids an empirical modification to the method was introduced. Contributions due to carbon skeleton, functional groups, and intramolecular interaction between groups are included. Molecules typically originating from oxidation of biogenic molecules are within the scope of this method: carbonyls, alcohols, ethers, esters, nitrates, acids, peroxides, hydroperoxides, peroxy acyl nitrates and peracids. Therefore the method is especially suited to describe compounds forming secondary organic aerosol (SOA).

  6. Nucleophile-catalyzed additions to activated triple bonds. Protection of lactams, imides, and nucleosides with MocVinyl and related groups.

    PubMed

    Mola, Laura; Font, Joan; Bosch, Lluís; Caner, Joaquim; Costa, Anna M; Etxebarría-Jardí, Gorka; Pineda, Oriol; de Vicente, David; Vilarrasa, Jaume

    2013-06-21

    Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations. PMID:23713491

  7. Spectroscopic Evidence for Covalent Binding of Sulfadiazine to Natural Soils via 1,4-nucleophilic addition (Michael Type Addition) studied by Spin Labeling ESR

    NASA Astrophysics Data System (ADS)

    Aleksandrova, Olga

    2015-04-01

    with different polarity. As shown by the spin labeling ESR experiment, molecules modeling SDZ were promptly bound to non-hydrolysable network of soil organic matter only via the aromatic amines that was accompanied by a prompt enlargement of humic particles binding aromatic amines, whereas binding of decomposition products of SDZ to humic acids of soil via the aliphatic amines was not observable. The ESR spectra obviously showed a single-phase process of covalent binding of the aromatic amines. Repeated washouts of labeled soil samples using distil water and ultrafiltration through the membrane of 5000 MWCO PES confirmed irreversible binding of the aromatic amines, and showed that via the aliphatic amines, binding of SDZ or decomposition products of SDZ to soil might also occur but reversibly and only to small soil molecules, which don't enter into the composition of non-hydrolysable part of soil organic matter. SL ESR experiments of different soils at the presence of Laccase highlighted that covalent binding of the aromatic amines to humic particles occurred in the specific hydrophobic areas of soil found as depleted in oxygen. All measured data evidenced that first, SDZ might be decomposed that allowed for measuring the same change of a paramagnetic signal of soil organic matter influenced by both aromatic and aliphatic amines as in the experiment of the interaction of soil with SDZ. Second, a decomposition product of SDZ with the aromatic amine might be bound to non-hydrolysable parts of soil organic matter under specific anaerobic conditions only via 1,4 - nucleophilic addition, Michael-type addition. Gulkowska, A., Thalmann, B., D., Hollender, J., & Krauss, M. (2014). Chemosphere, 107, 366 - 372. Müller, T., Rosendahl, I., Focks, A., Siemens, J., Klasmeier, J., & Matthies. (2013). Environmental Pollution, 172,180 - 185. Nowak, K.M., Miltner, A., Gehre, M., Schaeffer, A., & Kaestner, M. (2011). Environmental Science & Technology 45, 999 - 1006. Weber, E.J., Spidle

  8. Spectroscopic Evidence for Covalent Binding of Sulfadiazine to Natural Soils via 1,4-nucleophilic addition (Michael Type Addition) studied by Spin Labeling ESR

    NASA Astrophysics Data System (ADS)

    Aleksandrova, Olga

    2015-04-01

    with different polarity. As shown by the spin labeling ESR experiment, molecules modeling SDZ were promptly bound to non-hydrolysable network of soil organic matter only via the aromatic amines that was accompanied by a prompt enlargement of humic particles binding aromatic amines, whereas binding of decomposition products of SDZ to humic acids of soil via the aliphatic amines was not observable. The ESR spectra obviously showed a single-phase process of covalent binding of the aromatic amines. Repeated washouts of labeled soil samples using distil water and ultrafiltration through the membrane of 5000 MWCO PES confirmed irreversible binding of the aromatic amines, and showed that via the aliphatic amines, binding of SDZ or decomposition products of SDZ to soil might also occur but reversibly and only to small soil molecules, which don't enter into the composition of non-hydrolysable part of soil organic matter. SL ESR experiments of different soils at the presence of Laccase highlighted that covalent binding of the aromatic amines to humic particles occurred in the specific hydrophobic areas of soil found as depleted in oxygen. All measured data evidenced that first, SDZ might be decomposed that allowed for measuring the same change of a paramagnetic signal of soil organic matter influenced by both aromatic and aliphatic amines as in the experiment of the interaction of soil with SDZ. Second, a decomposition product of SDZ with the aromatic amine might be bound to non-hydrolysable parts of soil organic matter under specific anaerobic conditions only via 1,4 - nucleophilic addition, Michael-type addition. Gulkowska, A., Thalmann, B., D., Hollender, J., & Krauss, M. (2014). Chemosphere, 107, 366 - 372. Müller, T., Rosendahl, I., Focks, A., Siemens, J., Klasmeier, J., & Matthies. (2013). Environmental Pollution, 172,180 - 185. Nowak, K.M., Miltner, A., Gehre, M., Schaeffer, A., & Kaestner, M. (2011). Environmental Science & Technology 45, 999 - 1006. Weber, E.J., Spidle

  9. Photochemically induced intramolecular six-electron reductive elimination and oxidative addition of nitric oxide by the nitridoosmate(VIII) anion.

    PubMed

    Thornley, Wyatt A; Bitterwolf, Thomas E

    2015-02-01

    UV photolysis of the nitridoosmate(VIII) anion, OsO3 N(-) , in low-temperature frozen matrices results in nitrogen-oxygen bond formation to give the Os(II) nitrosyl complex OsO2 (NO)(-) . Photolysis of the Os(II) nitrosyl product with visible wavelengths results in reversion to the parent Os(VIII) complex. Formally a six-electron reductive elimination and oxidative addition, respectively, this represents the first reported example of such an intramolecular transformation. DFT modelling of this reaction proceeds through a step-wise mechanism taking place through a side-on nitroxyl Os(VI) intermediate, OsO2 (η(2) -NO)(-) . PMID:25537499

  10. Gallium(III)- and calcium(II)-catalyzed Meyer-Schuster rearrangements followed by intramolecular aldol condensation or endo-Michael addition.

    PubMed

    Presset, M; Michelet, B; Guillot, R; Bour, C; Bezzenine-Lafollée, S; Gandon, V

    2015-03-28

    The first gallium- and calcium-catalyzed Meyer-Schuster rearrangements are described. Under substrate control, the incipient conjugated ketones can be trapped intramolecularly by β-keto esters or amides to yield cyclic products after aldol condensation or endo-Michael addition. An interesting additive effect that promotes the latter tandem process with calcium has been found. PMID:25503868

  11. Chiral phosphines in nucleophilic organocatalysis

    PubMed Central

    Xiao, Yumei; Sun, Zhanhu

    2014-01-01

    Summary This review discusses the tertiary phosphines possessing various chiral skeletons that have been used in asymmetric nucleophilic organocatalytic reactions, including annulations of allenes, alkynes, and Morita–Baylis–Hillman (MBH) acetates, carbonates, and ketenes with activated alkenes and imines, allylic substitutions of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols. PMID:25246969

  12. Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines Enabled by Ligand-Controlled Chemoselective Hydrocupration.

    PubMed

    Yang, Yang; Perry, Ian B; Buchwald, Stephen L

    2016-08-10

    The copper-catalyzed intermolecular enantioselective addition of styrenes to imines has been achieved under mild conditions at ambient temperature. This process features the use of styrenes as latent carbanion equivalents via the intermediacy of catalytically generated benzylcopper derivatives, providing an effective means for accessing highly enantiomerically enriched amines bearing contiguous stereocenters. Mechanistic studies shed light on the origin of the preferential styrene hydrocupration in the presence of an imine with the Ph-BPE-derived copper catalyst. PMID:27454393

  13. Studies on the synthesis of 1-substituted uracils, radical-induced cyclization of 1,6-diolefins, and the addition of nucleophiles to fullerenes

    SciTech Connect

    Naim, A.

    1992-01-01

    The reaction of 2-propanol solution of 1,6-diolefins was investigated. The gamma radiolysis of 2-propanol generates 2-hydroxy-2-propyl radical and a hydrogen atom. The addition of 2-hydroxy-2-propyl radical to a double bond forms a 5-hexenyl radical, which subsequently cyclizes to generate the methylcyclopentyl radical. The formation of product in the gamma radiolysis of 2-propanol + 1,6-diolefins is the same as the photolysis of a mixture of 2-propanol + acetone + 1,6-diolefins. On the basis of experimental findings, the major isomer concluded was cis. The monomer diallyldimethylammonium bromide, which undergoes facile polymerization in the presence of free radicals, was also cyclized to give monomeric products. The addition of a variety of nucleophiles to fullerenes was also studied. Both C[sub 60]/C[sub 70] react with KOH and degrade in contact with air. Their reactions are reversible under vacuum. Regeneration of C[sub 60] is quantitative while C[sub 70] in only 72%. The C[sub 70] is more reactive toward KOH than C[sub 60], which led to development of a method to obtain pure C[sub 60] from C[sub 60]/C[sub 70]. Besides KOH, the reaction of KF, NaNH[sub 2], N[sub 2]CHCO[sub 2]CH[sub 2]CH[sub 3] and CH[sub 2]N[sub 2] with the fullerenes were also investigated.

  14. Addition-Elimination or Nucleophilic Substitution? Understanding the Energy Profiles for the Reaction of Chalcogenolates with Dichalcogenides.

    PubMed

    Bortoli, Marco; Wolters, Lando P; Orian, Laura; Bickelhaupt, F Matthias

    2016-06-14

    We have quantum chemically explored the mechanism of the substitution reaction between CH3X(-) and the homo- and heterodichalcogenides CH3X'X″CH3 (X, X', X″ = S, Se, Te) using relativistic density functional theory at ZORA-OLYP/TZ2P and COSMO for simulating the effect of aqueous solvation. In the gas phase, all substitution reactions proceed via a triple-well addition-elimination mechanism that involves a stable three-center intermediate. Aqueous solvation, in some cases, switches the character of the mechanism to double-well SN2 in which the stable three-center intermediate has become a labile transition state. We rationalize reactivity trends and some puzzling aspects of these elementary reactions, in particular, vanishing activation energies and ghost three-center intermediates, using the activation strain model (ASM). PMID:27096625

  15. Stereodivergent Organocatalytic Intramolecular Michael Addition/Lactonization for the Asymmetric Synthesis of Substituted Dihydrobenzofurans and Tetrahydrofurans

    PubMed Central

    Belmessieri, Dorine; de la Houpliere, Alix; Calder, Ewen D D; Taylor, James E; Smith, Andrew D

    2014-01-01

    A stereodivergent asymmetric Lewis base catalyzed Michael addition/lactonization of enone acids into substituted dihydrobenzofuran and tetrahydrofuran derivatives is reported. Commercially available (S)-(−)-tetramisole hydrochloride gives products with high syn diastereoselectivity in excellent enantioselectivity (up to 99:1 d.r.syn/anti, 99 % eesyn), whereas using a cinchona alkaloid derived catalyst gives the corresponding anti-diastereoisomers as the major product (up to 10:90 d.r.syn/anti, 99 % eeanti). PMID:24989672

  16. A Dual Colorimetric/Fluorescence System for Determining pH Based on the Nucleophilic Addition Reaction of an o-Hydroxymerocyanine Dye.

    PubMed

    Yue, Yongkang; Huo, Fangjun; Lee, Songyi; Yin, Caixia; Yoon, Juyoung; Chao, Jianbin; Zhang, Yongbin; Cheng, Fangqin

    2016-01-22

    Owing to their ability to monitor pH in a precise and rapid manner, optical probes have widely been developed for biological and nonbiological applications. The strategies thus far employed to determine pH rely on two types of processes including reversible protonation of amine nitrogen atoms and deprotonation of phenols. We have developed a novel dual, colorimetric/fluorescence system for determining the pH of a solution. This system utilizes an o-hydroxymerocyanine dye that undergoes a nucleophilic addition reaction that subsequently causes reversible structural changes interconverting a merocyanine to a spirocyanine and a spirocyanine to a spiropyran. It was demonstrated that the dye can be employed to measure the pH of solutions in the 2.5-5.75 and 9.6-11.8 ranges with color changes from yellow to dark blue and then to lavender. Moreover, the fluorescence response associated with the spirocyanine-spiropyran transformation of the dye occurring in alkaline solutions provides a precise method. PMID:26603952

  17. Half-pseudoferrocene cations from nucleophilic addition of o-carboranyl anions to the [(η6-mesitylene)2Fe](2+) dication.

    PubMed

    Bakardjiev, Mario; Štíbr, Bohumil; Holub, Josef; Růžička, Aleš; Padělková, Zdeňka

    2012-06-21

    Reactions between the mesitylene (mes) dication [(η(6)-mes)(2)Fe](2+) (1a) [(PF(6)(-))(2) salt] and lithium o-carboranes Li[1-R-1,2-C(2)B(10)H(11)] (2) (R = H, 2a; Me, 2b; Ph, 2c) at low temperature (-60 °C, 1 h, followed by stirring for 2 h at r.t.) in THF resulted in a clean addition of the corresponding carborane anions to one of the unsubstituted arene sites in 1a, forming a series of orange monocations of general structure [(η(5)-mes-exo-6-{2-R-1,2-C(2)B(10)H(11)})Fe(η(6)-mes)](+) (3) (R = H, 3a; Me, 3b; Ph, 3c) which were isolated as PF(6)(-) salts (3PF(6)) in yields ranging 50-75%. Individual complexes were obtained on purification by LC or preparative TLC on a silica gel substrate, using MeCN-CH(2)Cl(2) mixtures as the mobile phase. Interestingly, the room-temperature reaction between 2a (threefold excess) and 1a(PF(6))(2) with a reverse order of addition of the reaction components yielded an orange salt [(η(5)-mes-exo-6-{1,2-C(2)B(10)H(11)})Fe(η(6)-mes)](+)[closo-nido-H(11)B(10)C(2)-C(2)B(10)H(12)](-) (3acCA) (cCA = conjucto-carborane anion = [closo-nido-H(11)B(10)C(2)-C(2)B(10)H(12)](-)) as a sole product in 71% yield. The formation of this conjucto anion can be taken as a strong support for the participation of a radical-chain mechanism in the ostensible nucleophilic addition which we suppose to be initiated by the formation of the [(mes)(2)Fe(+)]˙ radical cation. The structures of both 3PF(6) and 3acCA have been established by X-ray diffraction and the constitution of all compounds isolated is in agreement with elemental analyses, multinuclear NMR data, and MS spectra. PMID:22569925

  18. Nucleophilic Aromatic Substitution.

    ERIC Educational Resources Information Center

    Avila, Walter B.; And Others

    1990-01-01

    Described is a microscale organic chemistry experiment which demonstrates one feasible route in preparing ortho-substituted benzoic acids and provides an example of nucleophilic aromatic substitution chemistry. Experimental procedures and instructor notes for this activity are provided. (CW)

  19. Study of quinones reactions with wine nucleophiles by cyclic voltammetry.

    PubMed

    Oliveira, Carla M; Barros, António S; Ferreira, António C S; Silva, Artur M S

    2016-11-15

    Quinones are electrophilic species which can react with various nucleophiles, like wine antioxidants, such as sulfur dioxide or ascorbic acid, thiols, amino acids, and numerous polyphenols. These reactions are very important in wine aging because they mediate oxygen reactions during both production and bottle aging phases. In this work, the major challenge was to determine the interaction between ortho-quinones and wine nucleophiles (amino acids, thiols, and the antioxidants SO2 and ascorbic acid), by cyclic voltammetry. Wine-model solutions with gallic acid, caffeic acid, or (+)-catechin and nucleophilic compounds were used. To understand the effect of nucleophilic addition in wine, a white wine with the same added nucleophiles was also analysed. Cyclic voltammograms were taken with glassy carbon electrode or screen-printed carbon electrodes, respectively, for wine-model and white wines solutions, in the absence and in the presence of nucleophiles. A nucleophilic order profile related to the cathodic current intensity decrease was observed. PMID:27283600

  20. Iridium-Catalyzed Intramolecular Methoxy C-H Addition to Carbon-Carbon Triple Bonds: Direct Synthesis of 3-Substituted Benzofurans from o-Methoxyphenylalkynes.

    PubMed

    Torigoe, Takeru; Ohmura, Toshimichi; Suginome, Michinori

    2016-07-18

    Catalytic hydroalkylation of an alkyne with methyl ether was accomplished. Intramolecular addition of the C-H bond of a methoxy group in 1-methoxy-2-(arylethynyl)benzenes across a carbon-carbon triple bond took place efficiently either in toluene at 110 °C or in p-xylene at 135 °C in the presence of an iridium catalyst. The initial 5-exo cyclization products underwent double-bond migration during the reaction to give 3-(arylmethyl)benzofurans in high yields. PMID:27168516

  1. Indole synthesis by conjugate addition of anilines to activated acetylenes and an unusual ligand-free copper(II)-mediated intramolecular cross-coupling.

    PubMed

    Gao, Detian; Back, Thomas G

    2012-11-12

    A versatile new synthesis of indoles was achieved by the conjugate addition of N-formyl-2-haloanilines to acetylenic sulfones, ketones, and esters followed by a copper-catalyzed intramolecular C-arylation. The conjugate addition step was conducted under exceptionally mild conditions at room temperature in basic, aqueous DMF. Surprisingly, the C-arylation was performed most effectively by employing copper(II) acetate as the catalyst in the absence of external ligands, without the need for protection from air or water. An unusual feature of this process, for the case of acetylenic ketones, is the ability of the initial conjugate-addition product to serve as a ligand for the catalyst, which enables it to participate in the catalysis of its further transformation to the final indole product. Mechanistic studies, including EPR experiments, indicated that copper(II) is reduced to the active copper(I) species by the formate ion that is produced by the base-catalyzed hydrolysis of DMF. This process also served to recycle any copper(II) that was produced by the adventitious oxidation of copper(I), thereby preventing deactivation of the catalyst. Several examples of reactions involving acetylenic sulfones attached to a modified Merrifield resin demonstrated the feasibility of solid-phase synthesis of indoles by using this protocol, and tricyclic products were obtained in one pot by employing acetylenic sulfones that contain chloroalkyl substituents. PMID:23019064

  2. Concise Enantioselective Synthesis of Oxygenated Steroids via Sequential Copper(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions

    PubMed Central

    Cichowicz, Nathan R.; Kaplan, Will; Khomutnyk, Yaroslav; Bhattarai, Bijay; Sun, Zhankui; Nagorny, Pavel

    2015-01-01

    A new scalable enantioselective approach to functionalized oxygenated steroids is described. This strategy is based on chiral bis(oxazoline) copper(II) complex-catalyzed enantioselective and diastereoselective Michael reactions of cyclic ketoesters and enones to install vicinal quaternary and tertiary stereocenters. In addition, the utility of copper(II) salts as highly active catalysts for the Michael reactions of traditionally unreactive ββ′-enones and substituted ββ′-ketoesters that results in unprecedented Michael adducts containing vicinal all-carbon quaternary centers is also demonstrated. The Michael adducts subsequently undergo base-promoted diastereoselective aldol cascade reactions resulting in the natural or unnatural steroid skeletons. The experimental and computational studies suggest that the torsional strain effects arising from the presence of the Δ5-unsaturation are key controling elements for the formation of the natural cardenolide scaffold. The described method enables expedient generation of polycyclic molecules including modified steroidal scaffolds as well as challenging-to-synthesize Hajos-Parrish and Wieland-Miescher ketones. PMID:26491886

  3. Aqueous oxidation of sulfonamide antibiotics: aromatic nucleophilic substitution of an aniline radical cation.

    PubMed

    Tentscher, Peter R; Eustis, Soren N; McNeill, Kristopher; Arey, J Samuel

    2013-08-19

    Sulfonamide antibiotics are an important class of organic micropollutants in the aquatic environment. For several, sulfur dioxide extrusion products have been previously reported upon photochemical or dark oxidation. Using quantum chemical modeling calculations and transient absorption spectroscopy, it is shown that single-electron oxidation from sulfadiazine produces the corresponding aniline radical cation. Density functional theory calculations indicate that this intermediate can exist in four protonation states. One species exhibits a low barrier for an intramolecular nucleophilic attack at the para position of the oxidized aniline ring, in which a pyrimidine nitrogen acts as a nucleophile. This attack can lead to a rearranged structure, which exhibits the same connectivity as the SO2 -extruded oxidation product that was previously observed in the aquatic environment and characterized by NMR spectroscopy. We report a detailed reaction mechanism for this intramolecular aromatic nucleophilic substitution, and we discuss the possibility of this reaction pathway for other sulfonamide drugs. PMID:23828254

  4. Lithium-stabilized nucleophilic addition of thiamin to a ketone provides an efficient route to mandelylthiamin, a critical pre-decarboxylation intermediate.

    PubMed

    Bielecki, Michael; Howe, Graeme W; Kluger, Ronald

    2015-10-01

    Mandelylthiamin (MTh) is an accurate model of the covalent intermediate derived from the condensation of thiamin diphosphate and benzoylformate in benzoylformate decarboxylase. The properties and catalytic susceptibilities of mandelylthiamin are the subjects of considerable interest. However, the existing synthesis gives only trace amounts of the precursor to MTh as it is conducted under reversible conditions. An improved approach derives from the unique ability of lithium ions to drive to completion the otherwise unfavorable condensation of the conjugate base of thiamin and methyl benzoylformate. The unique efficiency of the condensation reaction in the presence of lithium ions is established in contrast to the effects of other Lewis acids. Interpretation of the pattern of the results indicates that the condensation of the ketone and thiamin is thermodynamically controlled. It is proposed that the addition of lithium ions displaces the equilibrium toward the product through formation of a stable lithium-alkoxide. PMID:26333207

  5. Nucleophilic Substitution by Benzodithioate Anions.

    ERIC Educational Resources Information Center

    Bonnans-Plaisance, Chantal; Gressier, Jean-Claude

    1988-01-01

    Describes a two-session experiment designed to provide a good illustration of, and to improve student knowledge of, the Grignard reaction and nucleophilic substitution. Discusses the procedure, experimental considerations, and conclusion of this experiment. (CW)

  6. Nucleophilic arylation with tetraarylphosphonium salts

    PubMed Central

    Deng, Zuyong; Lin, Jin-Hong; Xiao, Ji-Chang

    2016-01-01

    Organic phosphonium salts have served as important intermediates in synthetic chemistry. But the use of a substituent on the positive phosphorus as a nucleophile to construct C–C bond remains a significant challenge. Here we report an efficient transition-metal-free protocol for the direct nucleophilic arylation of carbonyls and imines with tetraarylphosphonium salts in the presence of caesium carbonate. The aryl nucleophile generated from phosphonium salt shows low basicity and good nucleophilicity, as evidenced by the successful conversion of enolizable aldehydes and ketones. The reaction is not particularly sensitive to water, shows wide substrate scope, and is compatible with a variety of functional groups including cyano and ester groups. Compared with the arylmetallic reagents that are usually moisture sensitive, the phosphonium salts are shelf-stable and can be easily handled. PMID:26822205

  7. Polyimidazoles Via Aromatic Nucleophilic Displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W.; Hergenrother, Paul M.

    1990-01-01

    Experiments show variety of polyimidazoles prepared by aromatic nucleophilic displacement, from reactions of bisphenol imidazoles with activated difluoro compounds. Polyimidazoles have good mechanical properties making them suitable for use as films, moldings, and adhesives.

  8. Modeling the Active Sites in Metalloenzymes 5. The Heterolytic Bond Cleavage of H2 in the [NiFe] Hydrogenase of DesulfoWibrio gigas by a Nucleophilic Addition Mechanism

    SciTech Connect

    Niu, Shuqiang; Hall, Michael B.

    2001-11-19

    The H2 activation catalyzed by an Fe(II)-Ni(III) model of the [NiFe] hydrogenase of DesulfoVibrio gigas has been investigated by density functional theory (DFT/B3LYP) calculations on the neutral and anionic active site complexes, [(CO)(CN)2Fe(Mu-SH)2Ni(SH)(SH2)]0 and [(CO)(CN)2Fe(Mu-SH)2Ni(SH)2]-. The results suggest that the reaction proceeds by a nucleophilic addition mechanism that cleaves the H-H bond heterolytically. The terminal cysteine residue Cys530 in the [NiFe] hydrogenase active site of the D. gigas enzyme plays a crucial role in the catalytic process by accepting the proton. The active site is constructed to provide access by this cysteine residue, and this role explains the change in activity observed when this cysteine is replaced by a selenocysteine. Furthermore, the optimized geometry of the transition state in the model bears a striking resemblance to the geometry of the active site as determined by X-ray crystallography.

  9. Inter- and intramolecular annulation strategies to a cyclopentanone building block containing an all-carbon quaternary stereogenic center.

    PubMed

    Penrose, Stephen D; Stott, Andrew J; Breccia, Perla; Haughan, Alan F; Bürli, Roland W; Jarvis, Rebecca E; Dominguez, Celia

    2015-03-20

    Synthesis of (S)-2-methyl-3-fluorophenyl cyclopentanone methyl ester (1S)-1 has been achieved by both inter- and intramolecular alkylation reactions on multigram scale, using chiral pool reagents. The intramolecular variant is a novel example of a chiral bis-electrophile reacting with a carbon nucleophile to form an enantiomerically pure all-carbon quaternary center. PMID:25720587

  10. Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent.

    PubMed

    Ashtekar, Kumar Dilip; Vetticatt, Mathew; Yousefi, Roozbeh; Jackson, James E; Borhan, Babak

    2016-07-01

    Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the AdE3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted AdE3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile-alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized "sophomore textbook" image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions. PMID:27284808

  11. Synthesis of 9H-Pyrrolo[1,2-a]indole and 3H-Pyrrolizine Derivatives via a Phosphine-Catalyzed Umpolung Addition/Intramolecular Wittig Reaction.

    PubMed

    Saleh, Nidal; Voituriez, Arnaud

    2016-05-20

    The first umpolung addition/intramolecular Wittig reaction, catalytic in phosphine, is described. The in situ phosphine oxide reduction was accomplished by the use of silane and a catalytic amount of bis(4-nitrophenyl)phosphate. This catalytic protocol is applicable to the synthesis of a wide range of functionalized 9H-pyrrolo[1,2-a]indoles and pyrrolizines (18 examples, 70-98% yields). PMID:27080174

  12. Bond formations by intermolecular and intramolecular trappings of acylketenes and their applications in natural product synthesis†

    PubMed Central

    Reber, Keith P.; Tilley, S. David

    2011-01-01

    The reactive intermediates known as acylketenes exhibit a rich chemistry and have been extensively utilized for many types of inter- and intramolecular bond-forming reactions within the field of organic synthesis. Characteristic reactions of acylketenes include cycloadditions, carbon–carbon bond-forming reactions, and nucleophilic capture with alcohols or amines to give β-keto acid derivatives. In particular, the intramolecular capture of acylketene intermediates with pendant nucleophiles represents a powerful method for forming both medium-sized rings and macrocycles, often in high yield. This tutorial review examines the history, generation, and reactivity of acylketenes with a special focus on their applications in the synthesis of natural products. PMID:19847338

  13. Highly nucleophilic acetylide, vinyl, and vinylidene complexes. Progress report

    SciTech Connect

    Not Available

    1992-06-15

    The research was divided into the following: studies of nucleophilic and chiral acetylide complex [Cp(CO)(PPh{sub 3})Mn-C{triple_bond}CR]{sup {minus}}; nucleophilic addition of carbene anions to organic ligands on electrophilic complexes; halide-promoted carbonylation of imido ligands; binuclear Fe{sub 2} complexes with bridging organonitrogen ligands; addition and cycloaddition reactions of carbyne complex [Cp(CO){sub 2}Re{triple_bond}CTol]{sup +}; addition and cycloaddition reactions of methylcarbyne complexes [Cp(CO){sub 2}M{triple_bond}CCH{sub 3}]{sup +} and vinylidene complexes Cp(CO){sub 2}M{double_bond}C{double_bond}CH{sub 2} (M=Mn, Re); studies of generation and reactivity of vinylcarbene complexes formed from reaction of manganese carbene anions and aldehydes; and addition of oxo ligands of nucleophilic oxo complexes to organic ligands on electrophilic metal centers.

  14. Polybenzimidazoles Via Aromatic Nucleophilic Displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W.; Hergenrother, Paul M.; Smith, Joseph G.

    1994-01-01

    Soluble polybenzimidazoles (PBI's) synthesized by nucleophilic displacement reaction of di(hydroxyphenyl)-benzimidazole monomers with activated aromatic difluoride compounds in presence of anhydrous potassium carbonate. These polymers exhibit good thermal, thermo-oxidative, and chemical stability, and high mechanical properties. Using benzimidazole monomers, more economical, and new PBI's processed more easily than commercial PBI, without loss of desirable physical properties.

  15. Anomalous ligand effect in gold(I)-catalyzed intramolecular hydroamination of alkynes.

    PubMed

    Gaggioli, Carlo Alberto; Ciancaleoni, Gianluca; Biasiolo, Luca; Bistoni, Giovanni; Zuccaccia, Daniele; Belpassi, Leonardo; Belanzoni, Paola; Tarantelli, Francesco

    2015-04-01

    We analyzed the ligand electronic effect in a gold(I)-catalyzed intramolecular alkyne hydroamination, through a DFT and charge-displacement function (CDF) study. We found that, in the presence of π-electron conjugation between the alkyne and the nucleophilic functionality, electron poor ligands modify the coordination mode and the geometric parameters of the substrate in such a way that, contrary to expectations, the activation barrier of the nucleophilic attack increases. This remarkable effect is due to the competition between alkyne activation and nucleophile deactivation. The general relevance of these findings is highlighted. PMID:25738820

  16. Electrophilicity and nucleophilicity index for radicals.

    PubMed

    De Vleeschouwer, Freija; Van Speybroeck, Veronique; Waroquier, Michel; Geerlings, Paul; De Proft, Frank

    2007-07-01

    Radicals can be regarded as electrophilic/nucleophilic, depending on their tendency to attack sites of relatively higher/lower electron density. In this paper, an electrophilicity scale, global as well as local, and a nucleophilicity scale for 35 radicals is reported. The global electrophilicity scale correlates well with the nucleophilicity scale, suggesting that these concepts are inversely related. PMID:17559221

  17. Nucleophilic fluorination of aromatic compounds

    DOEpatents

    Satyamurthy, Nagichettiar; Barrio, Jorge R

    2014-03-18

    Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO.sub.2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me.sub.4NF, Et.sub.4NF, n-Bu.sub.4NF, (PhCH.sub.2).sub.4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

  18. Preparation of 1,7- and 3,9-dideazapurines from 2-amino-3-iodo- and 3-amino-4-iodopyridines and activated acetylenes by conjugate addition and copper-catalyzed intramolecular arylation.

    PubMed

    Zhu, Ying; Back, Thomas G

    2014-11-21

    The conjugate addition of N-formyl derivatives of 2-amino-3-iodo- and 3-amino-4-iodopyridines to acetylenes activated by sulfone, ester, or ketone groups, followed by intramolecular arylation, affords variously substituted 1,7- and 3,9-dideazapurines. The method employs DMF-water as the solvent and copper(II) acetate as the catalyst for the cyclization step. Neither added ligands nor the exclusion of oxygen is necessary. The process therefore provides a simple, convenient, and inexpensive route to this biologically interesting class of products. PMID:25333726

  19. Multicapillary Flow Reactor: Synthesis of 1,2,5-Thiadiazepane 1,1-Dioxide Library Utilizing One-Pot Elimination and Inter-/Intramolecular Double aza-Michael Addition Via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS)

    PubMed Central

    Ullah, Farman; Zang, Qin; Javed, Salim; Zhou, Aihua; Knudtson, Christopher A.; Bi, Danse; Hanson, Paul R.; Organ, Michael G.

    2013-01-01

    A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of functionalized 1,2,5-thiadiazepane 1,1-dioxide library, utilizing a one-pot elimination and inter-/intramolecular double aza-Michael addition strategy is reported. The optimized protocol in MACOS was utilized for scale-out and further extended for library production using a multicapillary flow reactor. A 50-member library of 1,2,5-thiadiazepane 1,1-dioxides was prepared on a 100- to 300-mg scale with overall yields between 50 and 80% and over 90 % purity determined by proton nuclear magnetic resonance (1H-NMR) spectroscopy. PMID:24244871

  20. Polybenzimidazole via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G. (Inventor)

    1994-01-01

    Di(hydroxyphenyl)benzimidazole monomers were prepared from phenyl-4-hydroxybenzoate and aromatic bis(o-diamine)s. These monomers were used in the synthesis of soluble polybenzimidazoles. The reaction involved the aromatic nucleophilic displacement of various di(hydroxyphenyl)benzimidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds in the presence of an alkali metal base. These polymers exhibited lower glass transition temperatures, improved solubility, and better compression moldability over their commercial counterparts.

  1. A Convenient Synthesis of γ–Amino-Ynamides via Additions of Lithiated Ynamides to Aryl Imines. Observation of an Aza-Meyer-Schuster Rearrangement.†

    PubMed Central

    Qi, Rui; Wang, Xiao-Na; Wang, Chao-Chao; Li, Qian; Li, Hui; Lv, Ming-Can; Yu, Qing

    2013-01-01

    Efforts in developing an expeditious and convenient method for synthesizing γ–amino-ynamides via nucleophilic addition of lithiated ynamides to aryl imines are described. This work also features an aza-variant of a Meyer-Schuster rearrangement of γ–amino-ynamides and the synthetic utility of γ–amino-ynamides in an intramolecular ketenimine-[2 + 2] cycloaddition. PMID:23976795

  2. Nucleophilic substitution reaction for post-functionalization of polyoxometalates

    DOE PAGESBeta

    Yin, Panchao; Li, Qiang; Zhang, Jin; Wang, Longsheng; Hao, Jian; Wei, Yongge

    2015-07-06

    In this study, a hexamolybdate-based organic inorganic hybrid molecule containing a chloralkane fragment is synthesized and its Cl atom can be substituted by iodine and nitrate through nucleophilic substitution reactions in high yields, which provide a post-functionalization protocol to bring in various additional functional groups into polyoxometalate-based hybrid materials under mild conditions.

  3. The nucleophilicity N index in organic chemistry.

    PubMed

    Domingo, Luis R; Pérez, Patricia

    2011-10-21

    The nucleophilicity N index (J. Org. Chem. 2008, 73, 4615), the inverse of the electrophilicity, 1/ω, and the recently proposed inverse of the electrodonating power, 1/ω⁻, (J. Org. Chem. 2010, 75, 4957) have been checked toward (i) a series of single 5-substituted indoles for which rate constants are available, (ii) a series of para-substituted phenols, and for (iii) a series of 2,5-disubstituted bicyclic[2.2.1]hepta-2,5-dienes which display concurrently electrophilic and nucleophilic behaviors. While all considered indices account well for the nucleophilic behavior of organic molecules having a single substitution, the nucleophilicity N index works better for more complex molecules. Unlike, the inverse of the electrophilicity, 1/ω, (R(2) = 0.71), and the inverse of the electrodonating power, 1/ω⁻ (R(2) = 0.83), a very good correlation of the nucleophilicity N index of twelve 2-substituted-6-methoxy-bicyclic[2.2.1]hepta-2,5-dienes versus the activation energy associated with the nucleophilic attack on 1,1-dicyanoethylene is found (R(2) = 0.99). This comparative study allows to assert that the nucleophilicity N index is a measure of the nucleophilicity of complex organic molecules displaying concurrently electrophilic and nucleophilic behaviors. PMID:21842104

  4. Detection of Electrophilic and Nucleophilic Chemical Agents

    SciTech Connect

    McElhanon, James R.; Shepodd, Timothy J.

    2008-11-11

    A "real time" method for detecting electrophilic and nucleophilic species generally by employing tunable, precursor sensor materials that mimic the physiological interaction of these agents to form highly florescent berberine-type alkaloids that can be easily and rapidly detected. These novel precursor sensor materials can be tuned for reaction with both electrophilic (chemical species, toxins) and nucleophilic (proteins and other biological molecules) species.

  5. Polyimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor)

    1991-01-01

    Polyimidazoles (Pl) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl)imidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions are carried out in polar aprotic solvents such as N,N-dimethylacetamide, sulfolane, N-methylpyrroldinone, dimethylsulfoxide, or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperature under nitrogen. The di(hydroxyphenyl)imidazole monomers are prepared by reacting an aromatic aldehyde with a dimethoxybenzil or by reacting an aromatic dialdehyde with a methoxybenzil in the presence of ammonium acetate. The di(methoxyphenyl)imidazole is subsequently treated with aqueous hydrobromic acid to give the di(hydroxyphenyl)imidazole monomer. This synthetic route has provided high molecular weight Pl of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides and dinitro compounds.

  6. Polyimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor)

    1992-01-01

    Polyimidazoles (PI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl) imidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions are carried out in polar aprotic solvents such as N,N-dimethyl acetamide, sulfolane, N-methylpyrrolidinone, dimethylsulfoxide, or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl) imidazole monomers are prepared by reacting an aromatic aldehyde with a dimethoxybenzil or by reacting an aromatic dialdehyde with a methoxybenzil in the presence of ammonium acetate. The di(methoxyphenyl) imidazole is subsequently treated with aqueous hydrobromic acid to give the di(hydroxphenyl) imidazole monomer. This synthetic route has provided high molecular weight PI of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides and dinitro compounds.

  7. Tuning the Nucleophilicity in Cyclopropenylidenes

    PubMed Central

    Schoeller, Wolfgang W.; Frey, Guido D.; Bertrand, Guy

    2008-01-01

    Cyclopropenylidenes are Hückel aromatic π-systems in which one of the ring atoms is a carbene center. Quantum chemical calculations at density functional level, supplemented by coupled-cluster calculations, indicate that these species have a sizeable energy separation between the lowest energy singlet and triplet states. Amino groups considerably increase the energy difference between these two states, while electron-withdrawing substituents decrease it. The 1.1-dimerization products of cyclopropenylidenes, namely triafulvalenes, are investigated. The calculations show that, without steric hindrance and considerable electronic stabilization, cyclopropenylidenes are kinetically not stable and dimerize. Different substituents (alkyl, silyl, terphenyl, amino, and posphaneiminato) were probed to tune the energy levelling of the frontier orbitals in cyclopropenylidenes. Accordingly, it is predicted that by a suitable choice of substituents at the olefinic positions, cyclopropenylidenes can be more nucleophilic than their five-membered ring congeners, namely imidazol-2-ylidenes. PMID:18404754

  8. Polybenzimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1995-01-01

    Novel molecular weight controlled and endcapped polybenzimidazoles (PBI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The PBI are endcapped with mono(hydroxyphenyl) benzimidazoles. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. Mono(hydroxyphenyl) benzimidazoles are synthesizedby reacting phenyl-4-hydroxybenzoate with aromatic (o-diamine)s in diphenylsulfone. Molecular weight controlled and endcapped PBI of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

  9. Polybenzimidazoles Via Aromatic Nucleophilic Displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergerrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1997-01-01

    Novel molecular weight controlled and endcapped polybenzimidazoles (PBI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenylbenzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The PBI are endcapped with mono(hydroxyphenyl)benzimidazoles. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. Mono(hydroxyphenyl)benzimidazoles are synthesized by reacting phenyl-4-hydroxybenzoate with aromatic (o-diamine)s in diphenylsulfone. Molecular weight controlled and endcapped PBI of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

  10. Covalent adduction of nitrogen mustards to model protein nucleophiles.

    PubMed

    Thompson, Vanessa R; DeCaprio, Anthony P

    2013-08-19

    Protein adducts have the potential to serve as unique biomarkers of exposure to compounds of interest. Many xenobiotics (or their metabolites) are electrophilic and therefore reactive with nucleophilic amino acid residues on proteins. Nitrogen mustards are reactive xenobiotics with potential use as chemical warfare agents (CWA) or agents of terrorist attack, in addition to being employed as chemotherapeutic agents. The present study utilized cysteine-, lysine-, and histidine-containing model peptides to characterize in vitro adduction of the nitrogen mustards mechloroethamine (HN-2) and tris-(2-chlorethyl)amine (HN-3) to these nucleophilic amino acid residues by means of liquid chromatography-tandem mass spectrometry. The study assessed the structure of adducts formed, the time course of adduct formation, concentration-response relationships, and temporal stability of adducts. Adduction was hypothesized to occur on all three model peptides via initial formation of a reactive aziridinium intermediate for both mechloroethamine and tris-(2-chlorethyl)amine, followed by covalent adduction to nucleophilic residues. While adduction was found to occur most readily with cysteine, it was also observed at lysine and histidine, demonstrating that adduction by mechloroethamine and tris-(2-chlorethyl)amine is possible at multiple nucleophilic sites. Following solid phase extraction cleanup, adducts formed with mechloroethamine were stable for up to three weeks. Adducts formed with tris-(2-chlorethyl)amine were less stable; however, hydrolyzed secondary adducts were observed throughout the three week period. This study demonstrates that the nitrogen mustards mechloroethamine and tris-(2-chlorethyl)amine form stable adducts with reactive protein nucleophiles other than cysteine. PMID:23859065

  11. Global and local reactivity indices for electrophilic/nucleophilic free radicals.

    PubMed

    Domingo, Luis R; Pérez, Patricia

    2013-07-14

    A set of five DFT reactivity indices, namely, the global electrophilicity ω° and nucleophilicity N° indices, the radical Parr function P, and the local electrophilicity ω and nucleophilicity N indices, for the study of free radicals (FRs) are proposed. Global indices have been tested for a series of 32 FRs having electrophilic and/or nucleophilic activations. As expected, no correlation between the proposed global electrophilicity ω° and global nucleophilicity N° has been found. Analysis of the local electrophilicity ω and nucleophilicity N indices for FRs, together with analysis of the local electrophilicity ωk and nucleophilicity Nk indices for alkenes, allows for an explanation of the regio- and chemoselectivity in radical additions of FRs to alkenes. Finally, an ELF bonding analysis for the C-C bond formation along the nucleophilic addition of 2-hydroxyprop-2-yl FR 28 to methyl acrylate 35 evidences that the new C-C bond is formed by C-to-C coupling of two radical centres, which are properly characterized through the use of the Parr functions. PMID:23685829

  12. Oxidative nucleophilic aromatic amination of nitrobenzenes.

    PubMed

    Khutorianskyi, V V; Sonawane, M; Pošta, M; Klepetářová, B; Beier, P

    2016-06-01

    Nitrobenzenes substituted with electron-acceptor groups such as halogen, nitro, trifluoromethyl, pentafluorosulfanyl, or cyano underwent oxidative nucleophilic substitution with lithium salts of arylamines to afford N-aryl-2-nitroanilines. PMID:27152372

  13. Intramolecular and nonlinear dynamics

    SciTech Connect

    Davis, M.J.

    1993-12-01

    Research in this program focuses on three interconnected areas. The first involves the study of intramolecular dynamics, particularly of highly excited systems. The second area involves the use of nonlinear dynamics as a tool for the study of molecular dynamics and complex kinetics. The third area is the study of the classical/quantum correspondence for highly excited systems, particularly systems exhibiting classical chaos.

  14. Carbon nanotube intramolecular junctions

    NASA Astrophysics Data System (ADS)

    Yao, Zhen; Postma, Henk W. Ch.; Balents, Leon; Dekker, Cees

    1999-11-01

    The ultimate device miniaturization would be to use individual molecules as functional devices. Single-wall carbon nanotubes (SWNTs) are promising candidates for achieving this: depending on their diameter and chirality, they are either one-dimensional metals or semiconductors. Single-electron transistors employing metallic nanotubes and field-effect transistors employing semiconducting nanotubes have been demonstrated. Intramolecular devices have also been proposed which should display a range of other device functions. For example, by introducing a pentagon and a heptagon into the hexagonal carbon lattice, two tube segments with different atomic and electronic structures can be seamlessly fused together to create intramolecular metal-metal, metal-semiconductor, or semiconductor-semiconductor junctions. Here we report electrical transport measurements on SWNTs with intramolecular junctions. We find that a metal-semiconductor junction behaves like a rectifying diode with nonlinear transport characteristics that are strongly asymmetric with respect to bias polarity. In the case of a metal-metal junction, the conductance appears to be strongly suppressed and it displays a power-law dependence on temperatures and applied voltage, consistent with tunnelling between the ends of two Luttinger liquids. Our results emphasize the need to consider screening and electron interactions when designing and modelling molecular devices. Realization of carbon-based molecular electronics will require future efforts in the controlled production of these intramolecular nanotube junctions.

  15. Functionally Diverse Nucleophilic Trapping of Iminium Intermediates Generated Utilizing Visible Light

    PubMed Central

    Freeman, David B.; Furst, Laura; Condie, Allison G.

    2011-01-01

    Our previous studies into visible light-mediated aza-Henry reactions demonstrated that molecular oxygen played a vital role in catalyst turnover as well as the production of base to facilitate the nucleophilic addition of nitroalkanes. Herein, improved conditions for the generation of iminium ions from tetrahydroisoquinolines that allow for versatile nucleophilic trapping are reported. The new conditions provide access to a diverse range of functionality under mild, anaerobic reaction conditions as well as mechanistic insights into the photoredox cycle. PMID:22148974

  16. Frustrated Lewis pair modification by 1,1-carboboration: disclosure of a phosphine oxide triggered nitrogen monoxide addition to an intramolecular P/B frustrated Lewis pair.

    PubMed

    Liedtke, René; Scheidt, Felix; Ren, Jinjun; Schirmer, Birgitta; Cardenas, Allan Jay P; Daniliuc, Constantin G; Eckert, Hellmut; Warren, Timothy H; Grimme, Stefan; Kehr, Gerald; Erker, Gerhard

    2014-06-25

    The vicinal frustrated Lewis pair (FLP) mes2P-CH2CH2-B(C6F5)2 (3) reacts with phenyl(trimethylsilyl)acetylene by 1,1-carboboration to give the extended C3-bridged FLP 6 featuring a substituted vinylborane subunit. The FLP 6 actively cleaves dihydrogen. The FLP 3 also undergoes a 1,1-carboboration reaction with diphenylphosphino(trimethylsilyl)acetylene to give the P/B/P FLP 11 that features a central unsaturated four-membered heterocyclic P/B FLP and a pendant CH2CH2-Pmes2 functional group. Compound 11 reacts with nitric oxide (NO) by oxidation of the pendant Pmes2 unit to the P(O)mes2 phosphine oxide and N,N-addition of the P/B FLP unit to NO to yield the persistent P/B/PO FLPNO aminoxyl radical 14. This reaction is initiated by P(O)mes2 formation and opening of the central Ph2P···B(C6F5)2 linkage triggered by the pendant CH2CH2-P(O)mes2 group. PMID:24850528

  17. Detection of electrophilic and nucleophilic chemical agents

    DOEpatents

    McElhanon, James R.; Shepodd, Timothy J.

    2014-08-12

    A "real time" method for detecting chemical agents generally and particularly electrophilic and nucleophilic species by employing tunable, precursor sensor materials that mimic the physiological interaction of these agents to form highly florescent berberine-type alkaloids that can be easily and rapidly detected. These novel precursor sensor materials can be tuned for reaction with both electrophilic (chemical species, toxins) and nucleophilic (proteins and other biological molecules) species. By bonding or otherwise attaching these precursor molecules to a surface or substrate they can be used in numerous applications.

  18. Nucleotides as nucleophiles: reactions of nucleotides with phosphoimidazolide activated guanosine

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Rosenbach, M. T.; Hurley, T. B.

    1991-01-01

    An earlier study of the reaction of phosphoimidazolide activated nucleosides (ImpN) in aqueous phosphate buffers indicated two modes of reaction of the phosphate monoanion and dianion. The first mode is catalysis of the hydrolysis of the P-N bond in ImpN's which leads to imidazole and nucleoside 5'-monophosphate. The second represents a nucleophilic substitution of the imidazole to yield the nucleoside 5'-diphosphate. This earlier study thus served as a model for the reaction of ImpN with nucleoside monophosphates (pN) because the latter can be regarded as phosphate derivatives. In the present study we investigated the reaction of guanosine 5'-phosphate-2-methylimidazolide, 2-MeImpG, in the presence of pN (N = guanosine, adenosine and uridine) in the range 6.9 less than or equal to pH less than or equal to 7.7. We observed that pN's do act as nucleophiles to form NppG, and as general base to enhance the hydrolysis of the P-N bond in 2-MeImpG, i.e. pN show the same behavior as inorganic phosphate. The kinetic analysis yields the following rate constants for the dianion pN2-: knpN = 0.17 +/- 0.02 M-1 h-1 for nucleophilic attack and khpN = 0.11 +/- 0.07 M-1 h-1 for general base catalysis of the hydrolysis. These rate constants which are independent of the nucleobase compare with kp.2 = 0.415 M-1 h-1 and khp2. = 0.217 M-1 h-1 for the reactions of HPO4(2-). In addition, this study shows that under conditions where pN presumably form stacks, the reaction mechanism remains unchanged although in quantitative terms stacked pN are somewhat less reactive. Attack by the 2'-OH and 3'-OH groups of the ribose moiety in amounts greater than or equal to 1% is not observed; this is attributed to the large difference in nucleophilicity in the neutral pH range between the phosphate group and the ribose hydroxyls. This nucleophilicity rank is not altered by stacking.

  19. The Remarkable Reactivity of Aryl Halides with Nucleophiles

    ERIC Educational Resources Information Center

    Bunnett, Joseph F.

    1974-01-01

    Discusses the reactivity of aryl halides with nucleophilic or basic reagents, including nucleophilic attacks on carbon, hydrogen, halogen, and arynes. Suggestions are made concerning revisions of the sections on aryl halide chemistry courses and the corresponding chapters in textbooks. (CC)

  20. 1,3,5-Triazapentadienes by Nucleophilic Addition to 1,3- and 1,4-Dinitriles-Sterically Constrained Examples by Incorporation into Cyclic Peripheries: Synthesis, Aggregation, and Photophysical Properties.

    PubMed

    Wrobel, Agnes Johanna; Lucchesi, Ralph; Wibbeling, Birgit; Daniliuc, Constantin-Gabriel; Fröhlich, Roland; Würthwein, Ernst-Ulrich

    2016-04-01

    1,3,5-Triazapentadienes usually show U- or twisted S-shaped conformations along the N-C-N-C-N skeleton due to dominating n/π* interactions. If, however, the 1,3,5-triazapentadiene unit is part of a ring, its W conformation might be restricted to the plane. Here, we describe the synthesis of 13 new 1,3,5-triazapentadienes 10-12, which are sterically restrained by incorporation into six- or seven-membered ring systems, by addition of a lithiated primary amine or hydrazine 5 to a dinitrile 7, 8, or 9 with the two cyano groups in 1,3 or 1,4 distance. These novel compounds show very strong tendency for aggregation due to hydrogen bonding, especially to form homodimers as seen from X-ray data in the solid state. Additional hydrogen bonding generates also linear chains in the crystal. Several of the new compounds show fluorescence in solution. Quantum chemical DFT calculations were used for evaluation of the dimerization energies and for interpretation of the photophysical properties. PMID:26987891

  1. Addition of nucleophiles on cyanoacetylene N≡CCH=CH-X (X = NH2, OH, SH, …). Synthesis and Physico-chemical Properties of Potential Prebiotic Compounds or Interstellar Molecules.

    NASA Astrophysics Data System (ADS)

    Guillemin, Jean-Claude

    Among the molecules detected to date in the interstellar medium (ISM), cyanopolyynes constitute a rich and important subset. These robust compounds exhibit special properties with respect to their reactivity and kinetic stability, and some have been found in other astrochemical environments, such as comets or in lab simulations of planetary atmospheres.[1] These systems are supposed to be good starting materials for the formation of new, more complex, astrochemical species, or amino acids on primitive Earth. The formal addition of water, hydrogen sulfur or ammonia on cyanoacetylene (H-C≡C-C≡N) gives the corresponding heterosubstitued acrylonitriles. We have extensively investigated the study of such adducts. With water, the formed cyanovinylalcohol (NC-CH=CH-OH) is in a tautomeric equilibrium with the kinetically more stable cyanoacetaldehyde (NC-CH2 CH(=O)). Isolation of these compounds in pure form is challenging but the gas phase infrared spectrum has been recorded. Reaction of ammonia with cyanoacetylene gives aminoacrylonitrile (H2 N-CH=CH-CN), a stable enamine; microwave and infrared spectra were obtained.[2] Similarly the MW spectrum of 3-mercapto-2-propenenitrile (HS-CH=CH-CN) has been recorded.[3] Attempts to detect both species in the ISM have been performed. A combined experimental and theoretical study on the gas-phase basicity and acidity of a series of cyanovinyl derivatives is also presented.[4] We will demonstrate that many particular physicochemical properties are associated to these simple adducts of cyanoacetylene, compounds often proposed as prebiotic molecules or components of the ISM. 1] S. W. Fow, K. Dose, Molecular Evolution and the Origin of Life, Marcel Dekker, Stateplace- New York, metricconverterProductID1977. A1977. A. Coustenis, T. Encrenaz, B. BJzard, B. Bjoraker, G. Graner, G. Dang-Nhu, E. AriJ, Icarus 1993, 102, 240 - 269. [2] Benidar, A. ; Guillemin, J.-C. ; M—, O. ; Y‡-ez, M. J. Phys. Chem. A. 2005, 109, 4705-4712. E

  2. Base-controlled selectivity in the synthesis of linear and angular fused quinazolinones by a palladium-catalyzed carbonylation/nucleophilic aromatic substitution sequence.

    PubMed

    Chen, Jianbin; Natte, Kishore; Spannenberg, Anke; Neumann, Helfried; Langer, Peter; Beller, Matthias; Wu, Xiao-Feng

    2014-07-14

    A new approach for the facile synthesis of fused quinazolinone scaffolds through a palladium-catalyzed carbonylative coupling followed by an intramolecular nucleophilic aromatic substitution is described. The base serves as the key modulator: Whereas DBU gives rise to the linear isomers, Et3N promotes the preferential formation of angular products. Interestingly, a light-induced 4+4 reaction of the product was also observed. PMID:24891190

  3. Kinetic isotope effects for RNA cleavage by 2'-O- transphosphorylation: Nucleophilic activation by specific base

    PubMed Central

    Harris, Michael E; Dai, Qing; Gu, Hong; Kellerman, Dan; Piccirilli, Joseph A; Anderson, Vernon E

    2010-01-01

    To better understand the interactions between catalysts and transition states during RNA strand cleavage, primary 18O kinetic isotope effects and solvent D2O isotope effects were measured to probe the mechanism of base-catalyzed 2'-O-transphosphorylation of the RNA dinucleotide 5'-UpG-3'. The observed 18O KIEs for the nucleophilic 2'-O and in the 5'-O leaving group at pH 14 are both large relative to reactions of phosphodiesters with good leaving groups, indicating that the reaction catalyzed by hydroxide has a transition state (TS) with advanced phosphorus-oxygen bond fission to the leaving group (18kLG = 1.034 ± 0.004) and phosphorous-nucleophile bond formation (18kNUC = 0.984 ± 0.004). A breakpoint in the pH dependence of the 2'-O-transphosphorylation rate to a pH independent phase above pH 13 has been attributed to the pKa of the 2'-OH nucleophile. A smaller nucleophile KIE is observed at pH 12 (18kNUC = 0.995 ± 0.004) that is interpreted as the combined effect of the equilibrium isotope effect (~1.02) on deprotonation of the 2′-hydroxyl nucleophile and the intrinsic KIE on the nucleophilic addition step (ca. 0.981). An alternative mechanism in which the hydroxide ion acts as a general base is considered unlikely given the lack of a solvent deuterium isotope effect above the breakpoint in the pH versus rate profile. These results represent the first direct analysis of the transition state for RNA strand cleavage. The primary 18O KIE results and the lack of a kinetic solvent deuterium isotope effect together provide strong evidence for a late transition state and 2'-O nucleophile activation by specific base catalysis. PMID:20669950

  4. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  5. Intramolecular Aminoboration of Unfunctionalized Olefins.

    PubMed

    Yang, Chun-Hua; Zhang, Yu-Shi; Fan, Wen-Wen; Liu, Gong-Qing; Li, Yue-Ming

    2015-10-19

    A direct and catalyst-free method for the intramolecular aminoboration of unfunctionalized olefins is reported. In the presence of BCl3 (1 equiv) as the sole boron source, intramolecular aminoboration of sulfonamide derivatives of 4-penten-1-amines, 5-hexen-1-amines, and 2-allylanilines proceeded readily without the use of any catalyst. The boronic acids obtained after hydrolysis could be converted into the corresponding pinacol borates in a straightforward manner by treatment with pinacol under anhydrous conditions. PMID:26331979

  6. Advances in Nucleophilic Phosphine Catalysis of Alkenes, Allenes, Alkynes, and MBHADs

    PubMed Central

    Fan, Yi Chiao

    2014-01-01

    In nucleophilic phosphine catalysis, tertiary phosphines undergo conjugate additions to activated carbon–carbon multiple bonds to form β-phosphonium enolates, β-phosphonium dienolates, β-phosphonium enoates, and vinyl phosphonium ylides as intermediates. When these reactive zwitterionic species react with nucleophiles and electrophiles, they may generate carbo- and heterocycles with multifarious molecular architectures. This Article describes the reactivities of these phosphonium zwitterions, the applications of phosphine catalysis in the syntheses of biologically active compounds and natural products, and recent developments in the enantioselective phosphine catalysis. PMID:24196409

  7. Synthesis of 4H-chromenes by an unexpected, K3PO4-mediated intramolecular Rauhut-Currier type reaction.

    PubMed

    Bhunia, Anup; Yetra, Santhivardhana Reddy; Gonnade, Rajesh G; Biju, Akkattu T

    2016-06-28

    In an attempt to develop the umpolung of Michael acceptors using chalcones having an enoate moiety under N-heterocyclic carbene (NHC) catalysis, a K3PO4-mediated intramolecular Rauhut-Currier type reaction was observed. This C(sp(2))-C(sp(2)) coupling reaction afforded the biologically important 4H-chromenes in moderate to good yields. It is likely that the enol ether functionality acts as the nucleophilic trigger in this reaction. PMID:27109318

  8. Catalytic, Enantioselective, Intramolecular Carbosulfenylation of Olefins. Preparative and Stereochemical Aspects

    PubMed Central

    Denmark, Scott E.; Jaunet, Alex

    2014-01-01

    The first catalytic, enantioselective, intramolecular carbosulfenylation of isolated alkenes with aromatic nucleophiles is described. The combination of N-phenylsulfenylphthalimide, a chiral selenophosphoramide derived from BINAM, and ethanesulfonic acid as a co-catalytic Brønsted acid induced an efficient and selective cyclofunctionalization of various alkenes (aliphatic and aromatic) tethered to a 3,4-methylenedioxyphenyl ring. Under these conditions, 6-phenylthio-5,6,7,8-tetrahydronaphthalenes are formed diastereospecifically in good yields (50–92%) and high enantioselectivities (71:29 – 97:3 er). E-Alkenes reacted much more rapidly and with much higher selectivity than Z-alkenes, whereas electron rich alkenes reacted more rapidly but with comparable selectivity to electron-neutral alkenes and electron deficient alkenes. The Brønsted acid played a critical role in effecting reproducible enantioselectivity. A model for the origin of enantioselectivity and the dependence of rate and selectivity on alkene structure is proposed along with a rationale for the site selectivity in reactions with mono-activated arene nucleophiles. PMID:24328051

  9. Aptamer switch probe based on intramolecular displacement.

    PubMed

    Tang, Zhiwen; Mallikaratchy, Prabodhika; Yang, Ronghua; Kim, Youngmi; Zhu, Zhi; Wang, Hui; Tan, Weihong

    2008-08-27

    A novel aptamer-based molecular probe design employing intramolecular signal transduction is demonstrated. The probe is composed of three elements: an aptamer, a short, partially cDNA sequence, and a PEG linker conjugating the aptamer with the short DNA strand. We have termed this aptamer probe an "aptamer switch probe", or ASP. The ASP design utilizes both a fluorophore and a quencher which are respectively modified at the two termini of the ASP. In the absence of the target molecule, the short DNA will hybridize with the aptamer, keeping the fluorophore and quencher in close proximity, thus switching off the fluorescence. However, when the ASP meets its target, the binding between the aptamer and the target molecule will disturb the intramolecular DNA hybridization, move the quencher away from the fluorophore, and, in effect, switch on the fluorescence. Both ATP and human alpha-thrombin aptamers were engineered to demonstrate this design, and both showed that fluorescence enhancement could be quantitatively mediated by the addition of various amounts of target molecules. Both of these ASPs presented excellent selectivity and prompt response toward their targets. With intrinsic advantages resulting from its intramolecular signal transduction architecture, the ASP design holds promising potential for future applications, such as biochip and in situ imaging, which require reusability, excellent stability, prompt response, and high sensitivity. PMID:18680291

  10. Intramolecular cyclopropanation and C-H insertion reactions with metal carbenoids generated from cyclopropenes.

    PubMed

    Archambeau, Alexis; Miege, Frédéric; Meyer, Christophe; Cossy, Janine

    2015-04-21

    Activation of unsaturated carbon-carbon bonds by means of transition metal catalysts is an exceptionally active research field in organic synthesis. In this context, due to their high ring strain, cyclopropenes constitute an interesting class of substrates that displays a versatile reactivity in the presence of transition metal catalysts. Metal complexes of vinyl carbenes are involved as key intermediates in a wide variety of transition metal-catalyzed ring-opening reactions of cyclopropenes. Most of the reported transformations rely on intermolecular or intramolecular addition of nucleophiles to these latter reactive species. This Account focuses specifically on the reactivity of carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation and C-H insertion reactions, which are arguably two of the most representative transformations of metal complexes of carbenes. Compared with the more conventional α-diazo carbonyl compounds, the use of cyclopropenes as precursors of metal carbenoids in intramolecular cyclopropanation or C-H insertion reactions has been largely underexploited. One of the challenges is to devise appropriately substituted and readily available cyclopropenes that would not only undergo regioselective ring-opening under mild conditions but also trigger the subsequent desired transformations with a high level of chemoselectivity and stereoselectivity. These goals were met by considering several substrates derived from the readily available 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective gold(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as a route to diversely substituted heterocycles and carbocycles possessing a bicyclo[4.1.0]heptane framework. The use of rhodium(II) catalysts enabled us to widen the scope of this transformation for the synthesis of medium-sized heterocyclic scaffolds

  11. Nucleophilic Substitution Reactions Using Phosphine Nucleophiles: An Introduction to Phosphorus-31 NMR

    ERIC Educational Resources Information Center

    Sibbald, Paul A.

    2015-01-01

    Nuclear magnetic resonance (NMR) spectroscopy is commonly used in modern synthetic chemistry to monitor the conversion of reactants to products. Since instruction in the use of NMR spectroscopy typically does not occur until after the introduction of nucleophilic substitution reactions, organic chemistry students are not able to take advantage of…

  12. Solvolyses of Benzoyl Chlorides in Weakly Nucleophilic Media

    PubMed Central

    Bentley, Thomas William; Harris, Haldon Carl

    2011-01-01

    Rate constants and activations parameters are reported for solvolyses of p-Z-substituted benzoyl chlorides (1, Z = OMe, Me, H, and Cl) in 97% w/w hexafluoroisopropanol-water (97H). Additional kinetic data are reported for solvolyses in acetic and formic acids. Plots of log k vs. σp in 97H are consistent with previous research showing that a cationic reaction channel is dominant, even for solvolyses of 1, Z = NO2. A benzoyl cation intermediate was trapped by Friedel-Crafts reaction with 1,3,5-trimethoxybenzene in hexafluoroisopropanol. The results are explained by an SN2-SN1 spectrum of mechanisms with variations in nucleophilic solvent assistance. Ab initio calculations of heterolytic bond dissociation energies of various chloro- and fluoro-substituted and other benzoyl chlorides are correlated with log k for solvolyses. PMID:21954326

  13. Hyperbranched Polycarbosilanes via Nucleophilic Substitution Reactions

    NASA Astrophysics Data System (ADS)

    Interrante, L.; Shen, Q.

    Nucleophilic substitution reactions involving organomagnesium (Grignard) [1] and organolithium reagents have been used extensively for many years to form Si—C bonds (see Reaction Scheme 12.1). However, their use for the construction of hyperbranched polymers whose backbone contains, as a major structural component, silicon—carbon bonds, i.e., polycarbosilanes [2] is relatively more recent. (12.1) begin{array}{l} {{R}}_3 {{SiX + MR'}} to {{R}}_3 {{SiR' + MX}} \\ left({{{R,R' = alkyl}} {{or aryl;}} {{M = Mg(X),}} {{Li,}} {{Na}};{{X = halogen, OR''}}} right) \\ This chapter focuses on the application of such nucleophilic substitution reactions toward the synthesis of hyperbranched polycarbosilanes, with particular emphasis on those preparations that have resulted in relatively well characterized products. These syntheses are organized by the type of ABn monomer unit used (see Section 1.2), where A and B refer to the (C)X and (Si)Xn, respectively, functional ends of the monomer unit and where the nature of the coupling reaction leads to entirely or primarily Si—C bond formation. In most cases, these are “one-pot” reactions that employ monomers that bear halogen or alkoxy groups on the C and Si ends of the unit. Indeed, hyperbranched polycarbosilanes have been described, in general, as “obtained in one synthetic step via a random, one-pot polymerization of multifunctional monomers of AB n type” [2]. Treatment of the ABn monomer with either elemental Mg or an organolithium reagent, ideally (but not always) forms a complexed carbanion (the nucleophile) by reaction with the C-X end of the monomer unit, resulting in an intermediate of the type, (XxM)CSiXn, where M = Mg or Li, X = halogen or alkoxy, and x = 1 (Mg) or 0 (Li). Self-coupling of this reagent via reactions of the type shown in Reaction Scheme 12.1 leads to oligomeric and polymeric products that are connected primarily through Si—C bonds and yield an inorganic MXx by-product.

  14. An O-to-N intramolecular acyl migration in C₁₉-diterpenoid alkaloids.

    PubMed

    Chen, Qi-Feng; Jian, Xi-Xian; Chen, Qiao-Hong; Wang, Feng-Peng

    2012-01-01

    The O-acyl group at C-1 of two C₁₉-diterpenoid alkaloids 2 and 5 was transferred to the secondary amine nitrogen to form amides 3 and 6 in the basic condition. This kind of O-to-N intramolecular acyl migration could be caused by the near distance between the nucleophilic nitrogen atom and the carbonyl group of the ester at C-1 in the C₁₉-diterpenoid alkaloids, which is consistent with the conformation of rings A and E in the C₁₉-diterpenoid alkaloids. PMID:22568819

  15. Femtosecond laser studies of ultrafast intramolecular processes

    SciTech Connect

    Hayden, C.

    1993-12-01

    The goal of this research is to better understand the detailed mechanisms of chemical reactions by observing, directly in time, the dynamics of fundamental chemical processes. In this work femtosecond laser pulses are used to initiate chemical processes and follow the progress of these processes in time. The authors are currently studying ultrafast internal conversion and subsequent intramolecular relaxation in unsaturated hydrocarbons. In addition, the authors are developing nonlinear optical techniques to prepare and monitor the time evolution of specific vibrational motions in ground electronic state molecules.

  16. A Safer, Discovery-Based Nucleophilic Substitution Experiment

    ERIC Educational Resources Information Center

    Horowitz, Gail

    2009-01-01

    A discovery-based nucleophilic substitution experiment is described in which students compare the reactivity of chloride and iodide ions in an S[subscript N]2 reaction. This experiment improves upon the well-known "Competing Nucleophiles" experiment in that it does not involve the generation of hydrogen halide gas. The experiment also introduces…

  17. Electrophilicity and nucleophilicity of commonly used aldehydes.

    PubMed

    Pratihar, Sanjay

    2014-08-14

    The present approach for determining the electrophilicity (E) and nucleophilicity (N) of aldehydes includes a kinetic study of KMNO4 oxidation and NaBH4 reduction of aldehydes. A transition state analysis of the KMNO4 promoted aldehyde oxidation reaction has been performed, which shows a very good correlation with experimental results. The validity of the experimental method has been tested using the experimental activation parameters of the two reactions. The utility of the present approach is further demonstrated by the theoretical versus experimental relationship, which provides easy access to E and N values for various aldehydes and offers an at-a-glance assessment of the chemical reactivity of aldehydes in various reactions. PMID:24979574

  18. Solvent isotope effects on nucleophilic displacement reactions

    SciTech Connect

    Spiegel, G.W.

    1981-01-01

    The kinetic solvent isotope effect, KSIE, (k/sub H/sub 2/O//k/sub D/sub 2/O/), at 25.0/sup 0/C and ionic strength, I, equal to 0.20 +- 0.02 M was measured for the nucleophilic displacement of iodine ion from iodomethane, iodoacetamide, and iodoacetate ion, thiophene from S-Methylthiophenium ion, and tosylate ion from methyl tosylate by bromide ion, chloride ion, acetate ion, hydroxide ion, water, ammonia, ethylenediamine, n-butylamine, piperazine, piperidine, quinuclidine, and 1,4-Diazabicyclo(2.2.2)octane (DABCO), and the monoprotonated cations of ethylenediamine, piperazine, and DABCO. By means of solvent partition measurements at 25.0/sup 0/C and I = 0.02 M between H/sub 2/O and D/sub 2/O and a common immiscible organic solvent, the ground state activity coefficients in D/sub 2/O, the solution in H/sub 2/O being chosen as the reference state, were determined for the nitrogen-containing nucleophiles (except ammonia) and the substrates methyl tosylate, iodoacetamide, and iodoacetic acid. The solubilities at 25.0/sup 0/C of the picrate and tetraphenylborate salts of the monoprotonated cationic forms of ethylenediamine, piperazine, and DABCO were measured to determine the activity coefficients in D/sub 2/O of these ions relative to an H/sub 2/O reference state. Applying the Eyring equation, the activity coefficients of the transition states in D/sub 2/O, reference state H/sub 2/O, were calculated.

  19. The Element Effect Revisited: Factors Determining Leaving Group Ability in Activated Nucleophilic Aromatic Substitution Reactions

    PubMed Central

    Senger, Nicholas A.; Bo, Bo; Cheng, Qian; Keeffe, James R.; Gronert, Scott; Wu, Weiming

    2012-01-01

    The “element effect” in nucleophilic aromatic substitution reactions (SNAr) is characterized by the leaving group order, F > NO2 > Cl ≈ Br > I, in activated aryl halides. Multiple causes for this result have been proposed. Experimental evidence shows that the element effect order in the reaction of piperidine with 2,4-dinitrophenyl halides in methanol is governed by the differences in enthalpies of activation. Computational studies of the reaction of piperidine and dimethylamine with the same aryl halides using the polarizable continuum model (PCM) for solvation indicate that polar, polarizability, solvation, and negative hyperconjugative effects are all of some importance in producing the element effect in methanol. In addition, a reversal of polarity of the C–X bond from reactant to transition state in the case of ArCl and ArBr compared to ArF also contributes to their difference in reactivity. The polarity reversal, and hyperconjugative influences have received little or no attention in the past. Nor has differential solvation of the different transition states been strongly emphasized. An anionic nucleophile, thiolate, gives very early transition states and negative activation enthalpies with activated aryl halides. The element effect is not established for these reactions. We suggest that the leaving group order in the gas phase will be dependent on the exact combination of nucleophile, leaving group, and substrate framework. The geometry of the SNAr transition state permits useful, qualitative conceptual distinctions to be made between this reaction and other modes of nucleophilic attack. PMID:23057717

  20. Cyclic disulfide C8 iminoporfiromycin: nucleophilic activation of a porfiromycin.

    PubMed

    Lee, Sang Hyup; Kohn, Harold

    2004-04-01

    The clinical success of mitomycin C (1) and its associated toxicities and resistance have led to efforts to prepare semisynthetic analogues (i.e., KW-2149 (3), BMS-181174 (4)) that have improved pharmacological profiles. In this study, we report the preparation and evaluation of the novel 7-N-(1'-amino-4',5'-dithian-2'-yl)porfiromycin C(8) cyclized imine (6) and its reference compound, 7-N-(1'-aminocyclohex-2'-yl)porfiromycin C(8) cyclized imine (13). Porfiromycin 6 contains a disulfide unit that, upon cleavage, may provide thiol(s) that affect drug reactivity. We demonstrated that phosphines dramatically accelerated 6 activation and solvolysis in methanolic solutions ("pH 7.4") compared with 13. Porfiromycins 6 and 13 efficiently cross-linked EcoRI-linearized pBR322 DNA upon addition of Et3P. We found enhanced levels of interstrand cross-link (ISC) adducts for 6 and 13 compared with porfiromycin (7) and that 6 was more efficient than 13. The large Et3P-mediated rate enhancements for the solvolysis of 6 compared with 13 and a N(7)-substituted analogue of 1, and the increased levels of ISC adducts for 6 compared with 13 and 7 are attributed to a nucleophile-assisted disulfide cleavage process that permits porfiromycin activation and nucleophile (MeOH, DNA) adduction. The in vitro antiproliferative activities of 6 and 13 using the A549 tumor cell line (lung adenocarcinoma) were determined under aerobic and hypoxic conditions and then compared with 7. Both 6 and 13 were more cytotoxic than 7, with 13 being more potent than 6. The C(8) iminoporfiromycins 6 and 13 displayed anticancer profiles similar to 3. PMID:15053618

  1. Substituent effects and chemoselectivity of the intramolecular Buchner reaction of diazoacetamide derivatives catalyzed by the di-Rh(ii)-complex.

    PubMed

    Li, Hui; Ma, Xuelu; Lei, Ming

    2016-05-28

    A density functional theory (DFT) study was performed to reveal that the substituent effects in the α-site have an effect on the chemoselectivity of the intramolecular Buchner reaction of diazoacetamide catalyzed by Rh2(OAc)4. The substituent effect is investigated considering five different groups (Z = -Me, -OMe, -H, -CN and -C(O)Me) in the substrates. The substituent group in the α-site changes the electronegativity of the C-atom in carbene and affects the chemoselectivity. The basis of chemoselectivity is the distribution of products that was analyzed by DFT calculations. The barrier energy of the favorable pathway is clearly lower than that of the other pathways. Nucleophilic substituent groups, such as -H, -OMe and -Me, are regarded as electron-donating groups, which increase the electropositivity of the C-atom in carbene compounds and improve the reactivity of the aromatic addition reaction. Electrophilic substituent groups, such as -CN and -C(O)Me, are regarded as electron-withdrawing groups, which decrease the electropositivity of the C-atom in carbene compounds and favor the C-H activation step. The computational results showed that the main product is cycloheptatriene when Z = -H/-OMe. The main product is β-lactam when the substituent group is -CN/-C(O)Me. When the substituent group is -Me, the products are a mixture of γ-lactams, β-lactams and cycloheptatriene. PMID:27116043

  2. Further studies on cation clock reactions in glycosylation: observation of a configuration specific intramolecular sulfenyl transfer and isolation and characterization of a tricyclic acetal.

    PubMed

    Huang, Min; Furukawa, Takayuki; Retailleau, Pascal; Crich, David; Bohé, Luis

    2016-06-01

    The use of the 2-O-(2-trimethylsilylmethallyl) group as intramolecular nucleophile and cation clock reaction in the glucopyranose series depends on the nature of the glycosyl donor. As previously reported, with trichloroacetimidates the anticipated intramolecular Sakurai reaction proceeds efficiently and is an effective clock, whereas with sulfoxides complications arise. The source of these complications is now shown to be an intramolecular sulfenyl transfer reaction between the tethered allylsilane and the activated sulfoxide. These results illustrate how a different unimolecular clock reaction may be required for a given cation when it is generated from different donors in order to avoid side reactions. The synthesis and cyclization of a 2-O-(3-hydroxypropyl) glucopyranosyl sulfoxide leading on activation to the formation of a trans-fused acetal is also described. The formation of this crystallographically-established trans-fused acetal is discussed in terms of the high effective concentration of the intramolecular nucleophile which leads to a high degree of a SN2 character in the displacement of the α-glucosyl triflate or at the level of the corresponding α-CIP. The possible use of such intramolecular alcohols as clock reactions and their limitations is discussed. PMID:27085740

  3. The activation of electrophile, nucleophile and leaving group during the reaction catalysed by pI258 arsenate reductase.

    PubMed

    Roos, Goedele; Loverix, Stefan; Brosens, Elke; Van Belle, Karolien; Wyns, Lode; Geerlings, Paul; Messens, Joris

    2006-06-01

    The reduction of arsenate to arsenite by pI258 arsenate reductase (ArsC) combines a nucleophilic displacement reaction with a unique intramolecular disulfide cascade. Within this reaction mechanism, the oxidative equivalents are translocated from the active site to the surface of ArsC. The first reaction step in the reduction of arsenate by pI258 ArsC consists of a nucleophilic displacement reaction carried out by Cys10 on dianionic arsenate. The second step involves the nucleophilic attack of Cys82 on the Cys10-arseno intermediate formed during the first reaction step. The onset of the second step is studied here by using quantum chemical calculations in a density functional theory context. The optimised geometry of the Cys10-arseno adduct in the ArsC catalytic site (sequence motif: Cys10-Thr11-Gly12-Asn13-Ser14-Cys15-Arg16-Ser17) forms the starting point for all subsequent calculations. Thermodynamic data and a hard and soft acids and bases (HSAB) reactivity analysis show a preferential nucleophilic attack on a monoanionic Cys10-arseno adduct, which is stabilised by Ser17. The P-loop active site of pI258 ArsC activates first a hydroxy group and subsequently arsenite as the leaving group, as is clear from an increase in the calculated nucleofugality of these groups upon going from the gas phase to the solvent phase to the enzymatic environment. Furthermore, the enzymatic environment stabilises the thiolate form of the nucleophile Cys82 by 3.3 pH units through the presence of the eight-residue alpha helix flanked by Cys82 and Cys89 (redox helix) and through a hydrogen bond with Thr11. The importance of Thr11 in the pKa regulation of Cys82 was confirmed by the observed decrease in the kcat value of the Thr11Ala mutant as compared to that of wild-type ArsC. During the final reaction step, Cys89 is activated as a nucleophile by structural alterations of the redox helix that functions as a pKa control switch for Cys89; this final step is necessary to expose a Cys82-Cys

  4. Intramolecular Tetrylene Lewis Adducts: Synthesis and Reactivity.

    PubMed

    Schneider, Julia; Krebs, Kilian M; Freitag, Sarah; Eichele, Klaus; Schubert, Hartmut; Wesemann, Lars

    2016-07-01

    A series of benzyl(diphenylphosphino) and o-phenyl(diphenlyphosphino) substituted germylenes and plumbylenes were synthesized by nucleophilic substitution between the respective lithium reagent and tetrylene halide. The Lewis pairs were characterized by X-ray crystallography and NMR spectroscopy. The reactivity of the tetrylenes was investigated with respect to azide addition. In the germylene case, the germaniumimide was formed as the kinetically controlled product, which rearranges upon heating to give the phosphinimide. The stannylene and plumbylene derivatives react with adamantylazide to give the azide adducts. 1-Pentene reacts diastereoselectively with the phosphagermirane to give a cyclic addition product. Trimethysilylacetylene shows an addition with the benzylphosphino-substituted germylene and plumbylene to give the cycloheteropentene molecules. The addition product between phenylacetylene and the four membered Ge-P adduct shows after addition at room temperature a 1,4-phenylmigration to give a cyclic phosphine. Alkylnitrene insertion into a Ge-C bond of the alkyne addition product of the phosphagermirane was found in reaction with adamantylazide. PMID:27273819

  5. Silver-catalysed intramolecular hydroamination of alkynes with trichloroacetimidates.

    PubMed

    Wong, Valerie H L; Hor, T S Andy; Hii, King Kuok Mimi

    2013-10-18

    Silver(I) complexes catalyse the intramolecular addition of trichloroacetimidates to alkynes. In the absence of a ligand, the selectivity of the reaction is dependent upon the nature of the counter-anion and solvent. The introduction of non-chelating nitrogeneous ligands suppresses competitive Brønsted acid catalysis, improving the yield and selectivity of the reaction. PMID:23999555

  6. How Does Nucleophilic Aromatic Substitution Really Proceed in Nitroarenes? Computational Prediction and Experimental Verification.

    PubMed

    Błaziak, Kacper; Danikiewicz, Witold; Mąkosza, Mieczysław

    2016-06-15

    The aim of this paper is to present a correct and complete mechanistic picture of nucleophilic substitution in nitroarenes based on the results obtained by theoretical calculations and experimental observations coming from numerous publications, reviews, and monographs. This work gives the theoretical background to the very well documented experimentally yet still ignored observations that the addition of nucleophiles to halo nitroarenes resulting in the formation of σ(H) adducts, which under proper reaction conditions can be transformed into the product of the SNArH reaction, is faster than the competing process of addition to the carbon atom bearing a nucleofugal group (usually a halogen atom) resulting in the "classic" SNAr reaction. Only when the σ(H) adduct cannot be transformed into the SNArH reaction product, SNAr reaction is observed. PMID:27218876

  7. Nucleophilic Aromatic Substitution Between Halogenated Benzene Dopants and Nucleophiles in Atmospheric Pressure Photoionization

    NASA Astrophysics Data System (ADS)

    Kauppila, Tiina J.; Haack, Alexander; Kroll, Kai; Kersten, Hendrik; Benter, Thorsten

    2016-03-01

    In a preceding work with dopant assisted-atmospheric pressure photoionization (DA-APPI), an abundant ion at [M + 77]+ was observed in the spectra of pyridine and quinoline with chlorobenzene dopant. This contribution aims to reveal the identity and route of formation of this species, and to systematically investigate structurally related analytes and dopants. Compounds containing N-, O-, and S-lone pairs were investigated with APPI in the presence of fluoro-, chloro-, bromo-, and iodobenzene dopants. Computational calculations on a density functional theory (DFT) level were carried out to study the reaction mechanism for pyridine and the different halobenzenes. The experimental and computational results indicated that the [M + 77]+ ion was formed by nucleophilic aromatic ipso-substitution between the halobenzene radical cation and nucleophilic analytes. The reaction was most efficient for N-heteroaromatic compounds, and it was weakened by sterical effects and enhanced by resonance stabilization. The reaction was most efficient with chloro-, bromo-, and iodobenzenes, whereas with fluorobenzene the reaction was scarcely observed. The calculated Gibbs free energies for the reaction between pyridine and the halobenzenes were shown to increase in the order I < Br < Cl < F. The reaction was found endergonic for fluorobenzene due to the strong C-F bonding, and exergonic for the other halobenzenes. For fluoro- and chlorobenzenes the reaction was shown to proceed through an intermediate state corresponding to [M + dopant]+, which was highly stable for fluorobenzene. For the bulkier bromine and iodine, this intermediate did not exist, but the halogens were shown to detach already during the approach by the nucleophile.

  8. Nucleophilic Aromatic Substitution Between Halogenated Benzene Dopants and Nucleophiles in Atmospheric Pressure Photoionization.

    PubMed

    Kauppila, Tiina J; Haack, Alexander; Kroll, Kai; Kersten, Hendrik; Benter, Thorsten

    2016-03-01

    In a preceding work with dopant assisted-atmospheric pressure photoionization (DA-APPI), an abundant ion at [M + 77](+) was observed in the spectra of pyridine and quinoline with chlorobenzene dopant. This contribution aims to reveal the identity and route of formation of this species, and to systematically investigate structurally related analytes and dopants. Compounds containing N-, O-, and S-lone pairs were investigated with APPI in the presence of fluoro-, chloro-, bromo-, and iodobenzene dopants. Computational calculations on a density functional theory (DFT) level were carried out to study the reaction mechanism for pyridine and the different halobenzenes. The experimental and computational results indicated that the [M + 77](+) ion was formed by nucleophilic aromatic ipso-substitution between the halobenzene radical cation and nucleophilic analytes. The reaction was most efficient for N-heteroaromatic compounds, and it was weakened by sterical effects and enhanced by resonance stabilization. The reaction was most efficient with chloro-, bromo-, and iodobenzenes, whereas with fluorobenzene the reaction was scarcely observed. The calculated Gibbs free energies for the reaction between pyridine and the halobenzenes were shown to increase in the order I < Br < Cl < F. The reaction was found endergonic for fluorobenzene due to the strong C-F bonding, and exergonic for the other halobenzenes. For fluoro- and chlorobenzenes the reaction was shown to proceed through an intermediate state corresponding to [M + dopant](+), which was highly stable for fluorobenzene. For the bulkier bromine and iodine, this intermediate did not exist, but the halogens were shown to detach already during the approach by the nucleophile. Graphical Abstract ᅟ. PMID:26637323

  9. Nucleophilic reactivity of a copper(II)-superoxide complex.

    PubMed

    Pirovano, Paolo; Magherusan, Adriana M; McGlynn, Ciara; Ure, Andrew; Lynes, Amy; McDonald, Aidan R

    2014-06-01

    Metal-bound superoxide intermediates are often implicated as electrophilic oxidants in dioxygen-activating metalloenzymes. In the nonheme iron α-ketoglutarate dependent oxygenases and pterin-dependent hydroxylases, however, Fe(III)-superoxide intermediates are postulated to react by nucleophilic attack on electrophilic carbon atoms. By reacting a Cu(II)-superoxide complex (1) with acyl chloride substrates, we have found that a metal-superoxide complex can be a very reactive nucleophile. Furthermore, 1 was found to be an efficient nucleophilic deformylating reagent, capable of Baeyer-Villiger oxidation of a number of aldehyde substrates. The observed nucleophilic chemistry represents a new domain for metal-superoxide reactivity. Our observations provide support for the postulated role of metal-superoxide intermediates in nonheme iron α-ketoglutarate dependent and pterin-dependent enzymes. PMID:24753290

  10. Nucleophilic Aromatic Substitution Reactions in Water Enabled by Micellar Catalysis.

    PubMed

    Isley, Nicholas A; Linstadt, Roscoe T H; Kelly, Sean M; Gallou, Fabrice; Lipshutz, Bruce H

    2015-10-01

    Given the huge dependence on dipolar, aprotic solvents such as DMF, DMSO, DMAc, and NMP in nucleophilic aromatic substitution reactions (SNAr), a simple and environmentally friendly alternative is reported. Use of a "benign-by-design" nonionic surfactant, TPGS-750-M, in water enables nitrogen, oxygen, and sulfur nucleophiles to participate in SNAr reactions. Aromatic and heteroaromatic substrates readily participate in this micellar catalysis, which takes place at or near ambient temperatures. PMID:26368348

  11. Selective copper(II)-mediated oxidative coupling of a nucleophilic reagent to the para-methyl group of 2,4,6-trimethylphenol.

    PubMed

    Boldron, Christophe; Ozalp-Yaman, Seniz; Gamez, Patrick; Tooke, Duncan M; Spek, Anthony L; Reedijk, Jan

    2005-11-01

    A copper(II) neocuproine system has been developed for the efficient and very selective 1,6-addition of a nucleophile to the para-methyl group of 2,4,6-trimethylphenol. Crystallographic and spectroscopic data point towards the involvement of a micro-methoxo-micro-phenoxo-bridged copper species which appears to generate a highly reactive quinone methide intermediate that can be attacked by a nucleophilic reagent. PMID:16234935

  12. A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

    PubMed Central

    Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

    2014-01-01

    Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

  13. Intramolecular interactions in the polar headgroup of sphingosine: serinol† †Electronic supplementary information (ESI) available: Ab initio parameters for serinol conformers within 1000 cm–1, measured transition frequencies, typical a-type transition for conformer aa1, interconversion barriers and possible tunnelling pathways. See DOI: 10.1039/c5cc09423b Click here for additional data file.

    PubMed Central

    Loru, Donatella; Peña, Isabel; Alonso, José L.

    2016-01-01

    The intramolecular interactions in the lipid sphingosine have been elucidated through the investigation of the amino alcohol serinol which mimics its polar headgroup. Intricate networks of intramolecular hydrogen bonds involving the hydroxyl groups and the amino group contribute to the stabilisation of five different conformations observed in the broadband rotational spectrum. PMID:26727395

  14. Nucleophilic Aromatic Substitution, A Guided Inquiry Laboratory Experiment.

    PubMed

    Winfield, Leyte L

    2010-01-01

    Inquiry-based learning is a unique student-centered alternative to traditional instruction. This form of active learning is ideal for the organic chemistry laboratory as it encourages critical thinking and hands on problem solving to complete an experiment. Electrophilic Aromatic Substitution is immediately associated with the undergraduate organic chemistry course. However, nucleophilic aromatic substitution is not. The N-arylation of aniline derivatives is a useful reaction for implementing nucleophilic aromatic substitution into the undergraduate curriculum. Under the framework of inquiry-based learning, a straightforward procedure has been developed for the undergraduate laboratory. This experiment explores the reaction rate of the nucleophilic aromatic substitution using various electrophiles. The reaction is conducted under microwave irradiation and the experiment is completed in one laboratory setting. PMID:21197138

  15. Copper(I)-Catalyzed Allylic Substitutions with a Hydride Nucleophile.

    PubMed

    Nguyen, T N Thanh; Thiel, Niklas O; Pape, Felix; Teichert, Johannes F

    2016-05-20

    An easily accessible copper(I)/N-heterocyclic carbene (NHC) complex enables a regioselective hydride transfer to allylic bromides, an allylic reduction. The resulting aryl- and alkyl-substituted branched α-olefins, which are valuable building blocks for synthesis, are obtained in good yields and regioselectivity. A commercially available silane, (TMSO)2Si(Me)H, is employed as hydride source. This protocol offers a unified alternative to the established metal-catalyzed allylic substitutions with carbon nucleophiles, as no adaption of the catalyst to the nature of the nucleophile is required. PMID:27151495

  16. Highly nucleophilic dipropanolamine chelated boron reagents for aryl-transmetallation to iron complexes.

    PubMed

    Dunsford, Jay J; Clark, Ewan R; Ingleson, Michael J

    2015-12-21

    New aryl- and heteroarylboronate esters chelated by dipropanolamine are synthesised directly from boronic acids. The corresponding anionic borates are readily accessible by deprotonation and demonstrate an increase in hydrocarbyl nucleophilicity in comparison to other common borates. The new borates proved competent for magnesium or zinc additive-free, direct boron-to-iron hydrocarbyl transmetallations with well-defined iron(II) (pre)catalysts. The application of the new borate reagents in representative Csp(2)-Csp(3) cross-coupling led to almost exclusive homocoupling unless coupling is performed in the presence of a zinc additive. PMID:26554484

  17. Chlorine isotope effects from isotope ratio mass spectrometry suggest intramolecular C-Cl bond competition in trichloroethene (TCE) reductive dehalogenation.

    PubMed

    Cretnik, Stefan; Bernstein, Anat; Shouakar-Stash, Orfan; Löffler, Frank; Elsner, Martin

    2014-01-01

    Chlorinated ethenes are prevalent groundwater contaminants. To better constrain (bio)chemical reaction mechanisms of reductive dechlorination, the position-specificity of reductive trichloroethene (TCE) dehalogenation was investigated. Selective biotransformation reactions (i) of tetrachloroethene (PCE) to TCE in cultures of Desulfitobacterium sp. strain Viet1; and (ii) of TCE to cis-1,2-dichloroethene (cis-DCE) in cultures of Geobacter lovleyi strain SZ were investigated. Compound-average carbon isotope effects were -19.0‰ ± 0.9‰ (PCE) and -12.2‰ ± 1.0‰ (TCE) (95% confidence intervals). Using instrumental advances in chlorine isotope analysis by continuous flow isotope ratio mass spectrometry, compound-average chorine isotope effects were measured for PCE (-5.0‰ ± 0.1‰) and TCE (-3.6‰ ± 0.2‰). In addition, position-specific kinetic chlorine isotope effects were determined from fits of reactant and product isotope ratios. In PCE biodegradation, primary chlorine isotope effects were substantially larger (by -16.3‰ ± 1.4‰ (standard error)) than secondary. In TCE biodegradation, in contrast, the product cis-DCE reflected an average isotope effect of -2.4‰ ± 0.3‰ and the product chloride an isotope effect of -6.5‰ ± 2.5‰, in the original positions of TCE from which the products were formed (95% confidence intervals). A greater difference would be expected for a position-specific reaction (chloride would exclusively reflect a primary isotope effect). These results therefore suggest that both vicinal chlorine substituents of TCE were reactive (intramolecular competition). This finding puts new constraints on mechanistic scenarios and favours either nucleophilic addition by Co(I) or single electron transfer as reductive dehalogenation mechanisms. PMID:24853618

  18. Understanding thio-effects in simple phosphoryl systems: role of solvent effects and nucleophile charge† †Electronic supplementary information (ESI) available: A breakdown of calculated activation free energies shown in Table 1, as well as absolute energies and Cartesian coordinates of all key species in this work are presented as ESI. See DOI: 10.1039/c5ob00309a Click here for additional data file.

    PubMed Central

    Carvalho, Alexandra T. P.; O'Donoghue, AnnMarie C.; Hodgson, David R. W.

    2015-01-01

    Recent experimental work (J. Org. Chem., 2012, 77, 5829) demonstrated pronounced differences in measured thio-effects for the hydrolysis of (thio)phosphodichloridates by water and hydroxide nucleophiles. In the present work, we have performed detailed quantum chemical calculations of these reactions, with the aim of rationalizing the molecular bases for this discrimination. The calculations highlight the interplay between nucleophile charge and transition state solvation in SN2(P) mechanisms as the basis of these differences, rather than a change in mechanism. PMID:25797408

  19. Approach to the synthesis of natural and modified oligonucleotides by the phosphotriester method using O-nucleophilic intramolecular catalysis.

    PubMed

    Efimov, Vladimir A; Molchanova, Natalia S; Chakhmakhcheva, Oksana G

    2007-01-01

    An approach to the solid phase synthesis of natural and modified oligonucleotides using phosphotriester technique has been developed. Particularly, this method allows the synthesis of ribo- and deoxyribo-oligonucleotides containing various 2'-modified mononucleotides as well as stereodefined nucleotide phosphorothioate analogues. PMID:18058542

  20. Bi(OTf)3–, TfOH–, and TMSOTf–Mediated, One-Pot Epoxide Rearrangement, Addition and Intramolecular Silyl-Modified Sakurai (ISMS) Cascade Toward Dihydropyrans: Comparison of Catalysts and Role of Bi(OTf)3

    PubMed Central

    Lambert, R. Frederick; Hinkle, Robert J.; Ammann, Stephen E.; Lian, Yajing; Liu, Jia; Lewis, Shane E.; Pike, Robert D.

    2011-01-01

    Catalytic quantities of bismuth(III) triflate efficiently initiate the rearrangement of epoxides to aldehydes which subsequently react with (Z)-δ-hydroxyalkenylsilanes to afford 2,6-disubstituted-3,6-dihydro-2H-pyrans. Isolated yields of desired products using Bi(OTf)3 were compared with yields when the reactions were run with TfOH and TMSOTf in the presence and absence of several additives. These studies, as well as NMR spectroscopic analyses, indicate an initial Lewis acid/base interaction between Bi(OTf)3 and substrates providing TfOH in situ. PMID:21916500

  1. Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular Benzoin Reaction.

    PubMed

    Wen, Genfa; Su, Yingpeng; Zhang, Guoxiang; Lin, Qiqiao; Zhu, Yujin; Zhang, Qianqian; Fang, Xinqiang

    2016-08-19

    The strategy of stereodivergent reactions on racemic mixtures (stereodivergent RRM) was employed for the first time in intramolecular benzoin reactions and led to the rapid access of chromanones/flavanones with two consecutive stereocenters. The easily separable stereoisomers of the products were obtained with moderate to excellent enantioselectivities in a single step. Catechol type additives proved crucial in achieving the desired diastereo- and enantioselectivities. PMID:27490010

  2. Nucleophilic Polymers and Gels in Hydrolytic Degradation of Chemical Warfare Agents.

    PubMed

    Bromberg, Lev; Creasy, William R; McGarvey, David J; Wilusz, Eugene; Hatton, T Alan

    2015-10-01

    Water- and solvent-soluble polymeric materials based on polyalkylamines modified with nucleophilic groups are introduced as catalysts of chemical warfare agent (CWA) hydrolysis. A comparative study conducted at constant pH and based on the criteria of the synthetic route simplicity, aqueous solubility, and rate of hydrolysis of CWA mimic, diisopropylfluorophosphate (DFP), indicated that 4-aminopyridine-substituted polyallylamine (PAAm-APy) and polyvinylamine substituted with 4-aminopyridine (PVAm-APy) were advantageous over 4-pyridinealdoxime-modified PVAm and PAAm, poly(butadiene-co-pyrrolidinopyridine), and PAAm modified with bipyridine and its complex with Cu(II). The synthesis of PVAm-APy and PAAm-APy involved generation of a betaine derivative of acrylamide and its covalent attachment onto the polyalkylamine chain followed by basic hydrolysis. Hydrogel particles of PAAm-APy and PVAm-APy cross-linked by epichlorohydrin exhibited pH-dependent swelling and ionization patterns that affected the rate constants of DFP nucleophilic hydrolysis. Deprotonation of the aminopyridine and amine groups increased the rates of the nucleophilic hydrolysis. The second-order rate of nucleophilic hydrolysis was 5.5- to 10-fold higher with the nucleophile-modified gels compared to those obtained by cross-linking of unmodified PAAm, throughout the pH range. Testing of VX and soman (GD) was conducted in 2.5-3.7 wt % PVAm-APy suspensions or gels swollen in water or DMSO/water mixtures. The half-lives of GD in aqueous PVAm-APy were 12 and 770 min at pH 8.5 and 5, respectively. Addition of VX into 3.5-3.7 wt % suspensions of PVAm-APy in DMSO-d6 and D2O at initial VX concentration of 0.2 vol % resulted in 100% VX degradation in less than 20 min. The unmodified PVAm and PAAm were 2 orders of magnitude less active than PVAm-APy and PAAm-APy, with VX half-lives in the range of 24 h. Furthermore, the PVAm-APy and PAAm-APy gels facilitated the dehydrochlorination reaction of sulfur mustard

  3. Concerted nucleophilic aromatic substitution with (19)F(-) and (18)F(-).

    PubMed

    Neumann, Constanze N; Hooker, Jacob M; Ritter, Tobias

    2016-06-16

    Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain (18)F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a 'leaving group' leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong π-acceptors in the ortho and/or para position(s). Here we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group-tolerant (18)F-deoxyfluorination reaction of phenols, which can be used to synthesize (18)F-PET probes. Selective (18)F introduction, without the need for the common, but cumbersome, azeotropic drying of (18)F, can now be accomplished from phenols as starting materials, and provides access to (18)F-labelled compounds not accessible through conventional chemistry. PMID:27281221

  4. Concerted nucleophilic aromatic substitution with 19F‑ and 18F‑

    NASA Astrophysics Data System (ADS)

    Neumann, Constanze N.; Hooker, Jacob M.; Ritter, Tobias

    2016-06-01

    Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain 18F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a ‘leaving group’ leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong π-acceptors in the ortho and/or para position(s). Here we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group-tolerant 18F-deoxyfluorination reaction of phenols, which can be used to synthesize 18F-PET probes. Selective 18F introduction, without the need for the common, but cumbersome, azeotropic drying of 18F, can now be accomplished from phenols as starting materials, and provides access to 18F-labelled compounds not accessible through conventional chemistry.

  5. Nucleophilic substitution in ionizable Fischer thiocarbene complexes: steric effect of the alkyl substituent on the heteroatom.

    PubMed

    Andrada, Diego M; Zoloff Michoff, Martin E; de Rossi, Rita H; Granados, Alejandro M

    2015-03-28

    A detailed kinetic study has been carried out for the aminolysis of ionizable Fischer thiocarbene complexes (CO)5M[double bond, length as m-dash]C(SR)CH3 (M = Cr, W; R = iPr, nBu, cHex, tBu) with five primary amines and one secondary amine in aqueous acetonitrile solutions (50% MeCN-50% water (v/v)). The observed rate constants for the reaction with primary amines showed a first-order dependence on the amine concentration, while with morpholine, the rate constant has second-order dependence. The general base catalysis process was confirmed by the variation of the rate constants with the concentration of an external catalyst and the pH. The results agree with a stepwise mechanism where the nucleophilic addition to the carbene carbon to produce a tetrahedral intermediate (T±) is the first step, followed by a rapid deprotonation of to form the anion T- which leads to the products by general-acid catalysed leaving group (-SR) expulsion. In general, it was found that the chromium complexes are less reactive than the tungsten analogues. The obtained Brønsted parameters for the nucleophilic addition (βnuc) indicate that C-N bond formation has made little progress at the transition state. By using Charton's correlation, the role that the steric factor plays throughout the mechanism has been unraveled. The nucleophilic addition to the thiocarbenes is less sensitive to steric effects than the alkoxycarbenes regardless of the nature of the metal centre. Conversely, the steric effects on the general-base catalysis can be strong depending on the volume of the catalyst and the metal centre. On the basis of the structure-reactivity coefficients β and ψ and comparison with alkoxycarbene complexes, esters and thiolesters, insights into the main factors ruling the reactivity in terms of transition state imbalances are discussed. PMID:25698135

  6. Intramolecular Aminocyanation of Alkenes via N–CN Bond Cleavage**

    PubMed Central

    Pan, Zhongda; Pound, Sarah M.; Rondla, Naveen R.; Douglas, Christopher J.

    2014-01-01

    A metal-free, Lewis acid-promoted intramolecular aminocyanation of alkenes was developed. B(C6F5)3 activates N-sulfonyl cyanamides, leading an formal cleavage of the N-CN bonds in conjunction with vicinal addition of sulfonamide and nitrile groups across an alkene. This method enables atom-economical access to indolines and tetrahydroquinolines in excellent yields, and provides a complementary strategy for regioselective alkene difunctionalizations with sulfonamide and nitrile groups. Labeling experiments with 13C suggest a fully intramolecular cyclization pattern due to lack of label scrambling in double crossover experiments. Catalysis with Lewis acid is realized and the reaction can be conducted under air. PMID:24719371

  7. V-type nerve agents phosphonylate ubiquitin at biologically relevant lysine residues and induce intramolecular cyclization by an isopeptide bond.

    PubMed

    Schmidt, Christian; Breyer, Felicitas; Blum, Marc-Michael; Thiermann, Horst; Worek, Franz; John, Harald

    2014-08-01

    Toxic organophosphorus compounds (e.g., pesticides and nerve agents) are known to react with nucleophilic side chains of different amino acids (phosphylation), thus forming adducts with endogenous proteins. Most often binding to serine, tyrosine, or threonine residues is described as being of relevance for toxicological effects (e.g., acetylcholinesterase and neuropathy target esterase) or as biomarkers for post-exposure analysis (verification, e.g., albumin and butyrylcholinesterase). Accordingly, identification of novel protein targets might be beneficial for a better understanding of the toxicology of these compounds, revealing new bioanalytical verification tools, and improving knowledge on chemical reactivity. In the present study, we investigated the reaction of ubiquitin (Ub) with the V-type nerve agents Chinese VX, Russian VX, and VX in vitro. Ub is a ubiquitous protein with a mass of 8564.8 Da present in the extra- and intracellular space that plays an important physiological role in several essential processes (e.g., proteasomal degradation, DNA repair, protein turnover, and endocytosis). Reaction products were analyzed by matrix-assisted laser desorption/ionization-time-of-flight- mass spectrometry (MALDI-TOF MS) and μ-high-performance liquid chromatography online coupled to UV-detection and electrospray ionization MS (μHPLC-UV/ESI MS). Our results originally document that a complex mixture of at least mono-, di, and triphosphonylated Ub adducts was produced. Surprisingly, peptide mass fingerprint analysis in combination with MALDI and ESI MS/MS revealed that phosphonylation occurred with high selectivity in at least 6 of 7 surface-exposed lysine residues that are essential for the biological function of Ub. These reaction products were found not to age. In addition, we herein report for the first time that phosphonylation induced intramolecular cyclization by formation of an isopeptide bond between the ε-amino group of a formerly phosphonylated

  8. All intermediates of the arsenate reductase mechanism, including an intramolecular dynamic disulfide cascade

    PubMed Central

    Messens, Joris; Martins, José C.; Van Belle, Karolien; Brosens, Elke; Desmyter, Aline; De Gieter, Marjan; Wieruszeski, Jean-Michel; Willem, Rudolph; Wyns, Lode; Zegers, Ingrid

    2002-01-01

    The mechanism of pI258 arsenate reductase (ArsC) catalyzed arsenate reduction, involving its P-loop structural motif and three redox active cysteines, has been unraveled. All essential intermediates are visualized with x-ray crystallography, and NMR is used to map dynamic regions in a key disulfide intermediate. Steady-state kinetics of ArsC mutants gives a view of the crucial residues for catalysis. ArsC combines a phosphatase-like nucleophilic displacement reaction with a unique intramolecular disulfide bond cascade. Within this cascade, the formation of a disulfide bond triggers a reversible “conformational switch” that transfers the oxidative equivalents to the surface of the protein, while releasing the reduced substrate. PMID:12072565

  9. Hydrocarbation of C≡C bonds: quantification of the nucleophilic reactivity of ynamides.

    PubMed

    Laub, Hans A; Evano, Gwilherm; Mayr, Herbert

    2014-05-01

    Donor-substituted diarylcarbenium ions Ar2 CH(+) react with ynamides to give 1-amido-substituted allyl cations (α,β-unsaturated iminium ions). Kinetic studies show that these adducts, which correspond to the addition of a CH bond across the CC bond, are formed stepwise with initial formation of keteniminium ions and subsequent 1,3-hydride shifts. The linear correlations between the second-order rate constants (lg k2 , 20 °C) with the electrophilicity parameters E of the diarylcarbenium ions allow us to include ynamides in our comprehensive nucleophilicity scale and thus predict potential electrophilic reaction partners. PMID:24715471

  10. Intramolecular Hydrogen Bonding in Substituted Aminoalcohols.

    PubMed

    Lane, Joseph R; Schrøder, Sidsel D; Saunders, Graham C; Kjaergaard, Henrik G

    2016-08-18

    The qualifying features of a hydrogen bond can be contentious, particularly where the hydrogen bond is due to a constrained intramolecular interaction. Indeed there is disagreement within the literature whether it is even possible for an intramolecular hydrogen bond to form between functional groups on adjacent carbon atoms. This work considers the nature of the intramolecular interaction between the OH (donor) and NH2 (acceptor) groups of 2-aminoethanol, with varying substitution at the OH carbon. Gas-phase vibrational spectra of 1-amino-2-methyl-2-propanol (BMAE) and 1-amino-2,2-bis(trifluoromethyl)-2-ethanol (BFMAE) were recorded using Fourier transform infrared spectroscopy and compared to literature spectra of 2-aminoethanol (AE). Based on the experimental OH-stretching frequencies, the strength of the intramolecular hydrogen bond appears to increase from AE < BMAE ≪ BFMAE. Non-covalent interaction analysis shows evidence of an intramolecular hydrogen bond in all three molecules, with the order of the strength of interaction matching that of experiment. The experimental OH-stretching vibrational frequencies were found to correlate well with the calculated kinetic energy density, suggesting that this approach can be used to estimate the strength of an intramolecular hydrogen bond. PMID:27447952

  11. Competing intramolecular vs. intermolecular hydrogen bonds in solution.

    PubMed

    Nagy, Peter I

    2014-01-01

    A hydrogen bond for a local-minimum-energy structure can be identified according to the definition of the International Union of Pure and Applied Chemistry (IUPAC recommendation 2011) or by finding a special bond critical point on the density map of the structure in the framework of the atoms-in-molecules theory. Nonetheless, a given structural conformation may be simply favored by electrostatic interactions. The present review surveys the in-solution competition of the conformations with intramolecular vs. intermolecular hydrogen bonds for different types of small organic molecules. In their most stable gas-phase structure, an intramolecular hydrogen bond is possible. In a protic solution, the intramolecular hydrogen bond may disrupt in favor of two solute-solvent intermolecular hydrogen bonds. The balance of the increased internal energy and the stabilizing effect of the solute-solvent interactions regulates the new conformer composition in the liquid phase. The review additionally considers the solvent effects on the stability of simple dimeric systems as revealed from molecular dynamics simulations or on the basis of the calculated potential of mean force curves. Finally, studies of the solvent effects on the type of the intermolecular hydrogen bond (neutral or ionic) in acid-base complexes have been surveyed. PMID:25353178

  12. Competing Intramolecular vs. Intermolecular Hydrogen Bonds in Solution

    PubMed Central

    Nagy, Peter I.

    2014-01-01

    A hydrogen bond for a local-minimum-energy structure can be identified according to the definition of the International Union of Pure and Applied Chemistry (IUPAC recommendation 2011) or by finding a special bond critical point on the density map of the structure in the framework of the atoms-in-molecules theory. Nonetheless, a given structural conformation may be simply favored by electrostatic interactions. The present review surveys the in-solution competition of the conformations with intramolecular vs. intermolecular hydrogen bonds for different types of small organic molecules. In their most stable gas-phase structure, an intramolecular hydrogen bond is possible. In a protic solution, the intramolecular hydrogen bond may disrupt in favor of two solute-solvent intermolecular hydrogen bonds. The balance of the increased internal energy and the stabilizing effect of the solute-solvent interactions regulates the new conformer composition in the liquid phase. The review additionally considers the solvent effects on the stability of simple dimeric systems as revealed from molecular dynamics simulations or on the basis of the calculated potential of mean force curves. Finally, studies of the solvent effects on the type of the intermolecular hydrogen bond (neutral or ionic) in acid-base complexes have been surveyed. PMID:25353178

  13. Silyl Ketene Imines: Highly Versatile Nucleophiles for Catalytic, Asymmetric Synthesis

    PubMed Central

    Denmark, Scott E.; Wilson, Tyler W.

    2012-01-01

    This Minireview provides an overview on the development of silyl ketene imines and their recent applications in catalytic, enantioselective reactions. The unique structure of the ketene imine allows a diverse range of reactivity patterns and provides solutions to existing challenges in the enantioselective construction of quaternary stereogenic carbon centers and cross-benzoin adducts. A variety of reactions for which silyl ketene imines have been applied are presented with an overall goal of inspiring new uses for these underutilized nucleophiles. PMID:22968901

  14. HBF4-Catalysed Nucleophilic Substitutions of Propargylic Alcohols

    PubMed Central

    Barreiro, Elena; Sanz-Vidal, Alvaro; Tan, Eric; Lau, Shing-Hing; Sheppard, Tom D; Díez-González, Silvia

    2015-01-01

    The activity of HBF4 (aqueous solution) as a catalyst in propargylation reactions is presented. Diverse types of nucleophiles were employed in order to form new C–O, C–N and C–C bonds in technical acetone and in air. Good to excellent yields and good chemoselectivities were obtained using low acid loading (typically 1 mol-%) under simple reaction conditions. PMID:26693210

  15. Catalysis of Carboxypeptidase A: Promoted-water vs Nucleophilic Pathways

    PubMed Central

    Wu, Shanshan; Zhang, Chunchun; Xu, Dingguo; Guo, Hua

    2010-01-01

    The catalytic mechanism of carboxypeptidase A (CPA) for the hydrolysis of ester substrates is investigated using hybrid quantum mechanical/molecular mechanical (QM/MM) methods and high-level density functional theory. The prevailing mechanism was found to utilize an active-site water molecule assisted by Glu270 and this so-called promoted-water pathway is similar to that in the CPA catalyzed proteolytic reaction (D. Xu and H. Guo, J. Am. Chem. Soc. 131, 9780 (2009)). On the other hand, our simulations indicated the existence of an alternative pathway due to direct nucleophilic attack of Glu270 on the scissile carbonyl carbon. This so-called nucleophilic pathway, which is not viable in proteolytic reactions, leads to a stable acyl-enzyme complex. However, the nucleophilic pathway is non-productive as it is blocked by a high barrier in the deacylation step. Based on results reported here and in our earlier publication, a unified model is proposed to account for nearly all experimental observations concerning the catalysis of CPA. PMID:20583802

  16. Stereoselective synthesis of 2,3-disubstituted indoline, pyrrolidine and cyclic ether-fused 1,2-dihydroquinoline derivatives using alkyne iminium ion cyclization of vinylogous carbamates: switch of regioselectivity using an internal hydroxy group as a nucleophile.

    PubMed

    Gharpure, Santosh J; Prasath, V; Kumar, Vinod

    2015-09-14

    An intramolecular, alkyne iminium ion cyclization of vinylogous carbamates derived from o-alkynyl anilines and N-protected homopropargyl amines is developed for the stereoselective construction of trans-2,3-disubstituted indolines and pyrrolidine derivatives, respectively. The regioselectivity of the alkyne iminium ion cyclization could be switched using a hydroxy group as an internal nucleophile resulting in cyclic ether-fused 1,2-dihydroquinolines. The entire process of nitrogen heterocycle formation can also be carried out in a 'one-pot' manner starting from o-iodo aniline derivatives. PMID:26226402

  17. Understanding the Origins of Nucleophilic Hydride Reactivity of a Sodium Hydride-Iodide Composite.

    PubMed

    Hong, Zonghan; Ong, Derek Yiren; Muduli, Subas Kumar; Too, Pei Chui; Chan, Guo Hao; Tnay, Ya Lin; Chiba, Shunsuke; Nishiyama, Yusuke; Hirao, Hajime; Soo, Han Sen

    2016-05-17

    Sodium hydride (NaH) has been commonly used as a Brønsted base in chemical syntheses, while it has rarely been employed to add hydride (H(-) ) to unsaturated electrophiles. We previously developed a procedure to activate NaH through the addition of a soluble iodide source and found that the new NaH-NaI composite can effect even stereoselective nucleophilic hydride reductions of nitriles, imines, and carbonyl compounds. In this work, we report that mixing NaH with NaI or LiI in tetrahydrofuran (THF) as a solvent provides a new inorganic composite, which consists of NaI interspersed with activated NaH, as revealed by powder X-ray diffraction, and both solid-state NMR and X-ray photoelectron spectroscopies. DFT calculations imply that this remarkably simple inorganic composite, which is comprised of NaH and NaI, gains nucleophilic hydridic character similar to covalent hydrides, resulting in unprecedented and unique hydride donor chemical reactivity. PMID:27038135

  18. Chloromethyl chlorosulfate: a new, catalytic method of preparation and reactions with some nucleophiles.

    PubMed

    Power, Nicholas P; Bethell, Donald; Proctor, Lee; Latham, Elliot; Dawson, Paul

    2004-05-21

    The reaction of liquid (gamma-) SO3 with CH2Cl2 at room temperature leads to SO3 insertion into the C-Cl bonds, giving the useful chloromethylating agent chloromethyl chlorosulfate (CMCS). The process is very slow but becomes rapid on addition of catalytic quantities of trimethyl borate. The product mixture consists almost entirely of CMCS and the product of further sulfation, methylene bis(chlorosulfate)(MBCS), in a ratio of ca. 2 : 1, but typical yields of CMCS, isolated by distillation, are only 30-35%. The catalysed reaction in the homogeneous liquid phase at -45 degrees C has been followed as a function of time and of reactant concentration by 1H nmr spectroscopy. It is observed that, besides CMCS and MBCS, three additional, transient products (designated A, B and C) are formed. Products A, B and C decompose slowly at -45 degrees C but much more rapidly if the reaction mixture is raised to room temperature, giving additional CMCS and MBCS. From an analysis of the SO3 balance, it is inferred that products A, B and C arise from the reaction of one molecule of CH2Cl2 with respectively two, three and four molecules of SO3; they are suggested to be chloromethyl chloropolysulfates. By measuring initial rates of CMCS formation or total CH2Cl2 consumption, it is shown that the reaction is first order in the catalyst and roughly third order in SO3. A mechanistic scheme is proposed in which SO3 forms equilibrating zwitterionic molecular complexes with CH2Cl2. of 1 : 1, 2 : 1 and higher stoichiometries. The boron-containing catalyst can activate these complexes towards nucleophilic attack at carbon by the negatively charged oxygen of another zwitterion. An analogous mechanism can be written for the conversion of CMCS into MBCS by SO3 in the presence of trimethyl borate. CMCS reacts rapidly with anionic nucleophiles, such as halide or acetate ions (X-), in homogeneous solution of their tetrabutylammonium salts in CD3CN, or in a two-phase system (CDCl3/H2O) using alkali

  19. Substrate Controlled Synthesis of Benzisoxazole and Benzisothiazole Derivatives via PhI(OAc)2-Mediated Oxidation Followed by Intramolecular Oxidative O-N/S-N Bond Formation.

    PubMed

    Anand, Devireddy; Patel, Om P S; Maurya, Rahul K; Kant, Ruchir; Yadav, Prem P

    2015-12-18

    A phenyliodine(III) diacetate (PIDA)-mediated, highly efficient and tandem approach for the synthesis of aryldiazenylisoxazolo(isothiazolo)arenes from simple 2-amino-N'-arylbenzohydrazides has been developed. The reaction proceeds via formation of (E)-(2-aminoaryl)(aryldiazenyl)methanone as the key intermediate, followed by intramolecular oxidative O-N/S-N bond formation in one pot at room temperature. The quiet different reactivity of the substrate is due to the formation of a diazo intermediate which encounters a nucleophilic attack by carbonyl oxygen on the electrophilic amine to produce isoxazole products, as compared to the previous reportsa,b,4 in which an N-acylnitrenium ion intermediate is intramolecularly trapped by an amine group. PMID:26565748

  20. Intramolecular alpha–Glucosaminidation: Synthesis of Mycothiol

    PubMed Central

    Ajayi, Kehinde; Thakur, Vinay V.; Lapo, Robert C.; Knapp, Spencer

    2010-01-01

    A protected cyclitol aglycon was tethered to an (N-arylsulfonyl)glucosamine donor by a methylene linker; the exclusively alpha-selective intramolecular glycosyation reaction was then initiated by electrophilic activation of the thioglycoside donor portion. Further transformations of the glycosylation product to give the M. tuberculosis detoxifier mycothiol and its oxidized congener, the disulfide mycothione, are detailed. PMID:20443569

  1. Organocatalyzed Intramolecular Carbonyl-Ene Reactions.

    PubMed

    Dahlmann, Heidi A; McKinney, Amanda J; Santos, Maria P; Davis, Lindsey O

    2016-01-01

    An organocatalyzed intramolecular carbonyl-ene reaction was developed to produce carbocyclic and heterocyclic 5- and 6-membered rings from a citronellal-derived trifluoroketone and a variety of aldehydes. A phosphoramide derivative was found to promote the cyclization of the trifluoroketone, whereas a less acidic phosphoric acid proved to be a superior catalyst for the aldehyde substrates. PMID:27258238

  2. Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene.

    PubMed

    Ajenjo, Javier; Greenhall, Martin; Zarantonello, Camillo; Beier, Petr

    2016-01-01

    3-Fluoro-5-nitro-1-(pentafluorosulfanyl)benzene was prepared by three different ways: as a byproduct of direct fluorination of 1,2-bis(3-nitrophenyl)disulfane, by direct fluorination of 4-nitro-1-(pentafluorosulfanyl)benzene, and by fluorodenitration of 3,5-dinitro-1-(pentafluorosulfanyl)benzene. The title compound was subjected to a nucleophilic aromatic substitution of the fluorine atom with oxygen, sulfur and nitrogen nucleophiles affording novel (pentafluorosulfanyl)benzenes with 3,5-disubstitution pattern. Vicarious nucleophilic substitution of the title compound with carbon, oxygen, and nitrogen nucleophiles provided 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzenes substituted in position four. PMID:26977178

  3. Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

    PubMed Central

    Ajenjo, Javier; Greenhall, Martin; Zarantonello, Camillo

    2016-01-01

    Summary 3-Fluoro-5-nitro-1-(pentafluorosulfanyl)benzene was prepared by three different ways: as a byproduct of direct fluorination of 1,2-bis(3-nitrophenyl)disulfane, by direct fluorination of 4-nitro-1-(pentafluorosulfanyl)benzene, and by fluorodenitration of 3,5-dinitro-1-(pentafluorosulfanyl)benzene. The title compound was subjected to a nucleophilic aromatic substitution of the fluorine atom with oxygen, sulfur and nitrogen nucleophiles affording novel (pentafluorosulfanyl)benzenes with 3,5-disubstitution pattern. Vicarious nucleophilic substitution of the title compound with carbon, oxygen, and nitrogen nucleophiles provided 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzenes substituted in position four. PMID:26977178

  4. Catalysis of hydrolysis and nucleophilic substitution at the P-N bond of phosphoimidazolide-activated nucleotides in phosphate buffers

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Rosenbach, M. T.

    1991-01-01

    Phosphoimidazolide-activated derivatives of guanosine and cytidine 5'-monophosphates, henceforth called ImpN's, exhibit enhanced rates of degradation in the presence of aqueous inorganic phosphate in the range 4.0 < or = pH < or = 8.6. This degradation is been attributed to (i) nucleophilic substitution of the imidazolide and (ii) catalysis of the P-N bond hydrolysis by phosphate. The first reaction results in the formation of nucleoside 5'-diphosphate and the second in nucleoside 5'-monophosphate. Analysis of the observed rates as well as the product ratios as a function of pH and phosphate concentration allow distinction between various mechanistic possibilities. The results show that both H2PO4- and HPO4(2-) participate in both hydrolysis and nucleophilic substitution. Statistically corrected biomolecular rate constants indicate that the dianion is 4 times more effective as a general base than the monoanion, and 8 times more effective as nucleophile. The low Bronsted value beta = 0.15 calculated for these phosphate species, presumed to act as general bases in facilitating water attack, is consistent with the fact that catalysis of the hydrolysis of the P-N bond in ImpN's has not been detected before. The beta nuc = 0.35 calculated for water, H2PO4-, HPO4(2-), and hydroxide acting as nucleophiles indicates a more associative transition state for nucleotidyl (O2POR- with R = nucleoside) transfers than that observed for phosphoryl (PO3(2-)) transfers (beta nuc = 0.25). With respect to the stability/reactivity of ImpN's under prebiotic conditions, our study shows that these materials would not suffer additional degradation due to inorganic phosphate, assuming the concentrations of phosphate, Pi, on prebiotic Earth were similar to those in the present oceans ([Pi] approximately 2.25 micromoles).

  5. TD-DFT study on electron transfer mobility and intramolecular hydrogen bond of substituted indigo derivatives

    NASA Astrophysics Data System (ADS)

    Ma, Chi; Li, Hui; Yang, Yonggang; Li, Donglin; Liu, Yufang

    2015-10-01

    The density functional theory (DFT) and time-dependent density functional theory (TDDFT) method were carried out to investigate the ground and excited states of indigo and its derivative molecules. The results demonstrate that the intramolecular hydrogen bond I is weakened and the intramolecular hydrogen bond II is strengthened upon photo-excitation to the S1 state. In the absorption spectra, the substitution at R4R4, of indigo causes a significant redshift. In addition, the halogen substitution obviously increases the electron transfer mobility of indigo. It is proved that the halogen substitution may be a new method to design high performance organic semiconductors.

  6. Nickel-Catalyzed Intramolecular C-O Bond Formation: Synthesis of Cyclic Enol Ethers.

    PubMed

    Han, Seo-Jung; Doi, Ryohei; Stoltz, Brian M

    2016-06-20

    An efficient and exceptionally mild intramolecular nickel-catalyzed carbon-oxygen bond-forming reaction between vinyl halides and primary, secondary, and tertiary alcohols has been achieved. Zinc powder was found to be an essential additive for obtaining high catalyst turnover and yields. This operationally simple method allows direct access to cyclic vinyl ethers in high yields in a single step. PMID:27159831

  7. Palladium-catalyzed intramolecular C-H arylation of arenes using tosylates and mesylates as electrophiles.

    PubMed

    Nervig, Christine S; Waller, Peter J; Kalyani, Dipannita

    2012-09-21

    This paper describes a method for the palladium catalyzed intramolecular C-H arylation using tosylates and mesylates as electrophiles. The transformation is efficient for the synthesis of various heterocyclic motifs including furans, carbazoles, indoles, and lactams. Additionally, a protocol for the one-pot sequential tosylation/arylation of phenol derivatives is presented. PMID:22974229

  8. Classification of the Electrophilic Addition Reactions of Olefins and Acetylenes

    ERIC Educational Resources Information Center

    Wilson, Michael A.

    1975-01-01

    Divides addition reactions into molecular, stepwise, or termolecular, depending on whether the reaction is synchronous or multistep; and further into nucleophilic, electrophilic, or concerted, depending on how the electrons are transferred in the initiation step. (MLH)

  9. Enantioselective Michael Addition of Water

    PubMed Central

    Chen, Bi-Shuang; Resch, Verena; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    The enantioselective Michael addition using water as both nucleophile and solvent has to date proved beyond the ability of synthetic chemists. Herein, the direct, enantioselective Michael addition of water in water to prepare important β-hydroxy carbonyl compounds using whole cells of Rhodococcus strains is described. Good yields and excellent enantioselectivities were achieved with this method. Deuterium labeling studies demonstrate that a Michael hydratase catalyzes the water addition exclusively with anti-stereochemistry. PMID:25529526

  10. Synthesis and structural studies of flavin and alloxazine adducts with O-nucleophiles

    NASA Astrophysics Data System (ADS)

    Ménová, Petra; Eigner, Václav; Čejka, Jan; Dvořáková, Hana; Šanda, Miloslav; Cibulka, Radek

    2011-10-01

    Five flavin (isoalloxazine) and alloxazine adducts with O-nucleophiles, 5-ethyl-4a-hydroxy-3,7,8,10-tetramethyl-4a,5-dihydroisoalloxazine ( 1a-OH), 5-ethyl-4a-hydroxy-3,10-dimethyl-4a,5-dihydroisoalloxazine ( 1b-OH), 5-ethyl-4a-methoxy-3,10-dimethyl-4a,5-dihydroisoalloxazine ( 1b-OMe), 5-ethyl-4a-hydroxy-1,3-dimethyl-4a,5-dihydroalloxazine ( 2a-OH) and 5-ethyl-4a-methoxy-1,3-dimethyl-4a,5-dihydroalloxazine ( 2a-OMe) were prepared from the corresponding salts, 5-ethyl-3,7,8,10-tetramethylisoalloxazinium ( 1a), 5-ethyl-3,10-dimethylisoalloxazinium ( 1b) and 5-ethyl-1,3-dimethylalloxazinium ( 2a) perchlorates by the addition of a nucleophile (water or methanol) and triethylamine as a base. The prepared adducts represent artificial analogs of flavin cofactor derivatives which are essential for the functioning of flavoenzymes. They were characterized by 1H and 13C NMR, HR-MS and UV-VIS spectra. In the cases of 1a-OH, 1b-OH, and 2a-OMe, the crystal structures were determined by X-ray diffraction. Flavinium and alloxazinium salts are in rapid equilibria with their adducts in water or methanolic solutions without the presence of a base. It was found that the equilibrium constants for flavin adduct formation is higher by six orders of magnitude than those for alloxazine derivatives. The presence of the sp 3 hybridized C4a atom in the molecule of the adducts causes deviation from planarity. The interplanar angles between benzene and the pyrimidine ring were found to be 31.5°, 23.64° and 15.62° for 1a-OH, 1b-OH and 2a-OMe, respectively, which are much higher than those of previously published adducts of C-nucleophiles. In isoalloxazine adducts, delocalization of π electrons between the N10-C10a and C10a-N1 bonds was detected while the length of the N10-C10a and C10a-N1 bonds in the alloxazine adducts corresponds to a double and single bond, respectively.

  11. Synthesis of β–Heteroaryl Propionates via Trapping of Carbocations with π-Nucleophiles

    PubMed Central

    Fu, Tsung-hao; Bonaparte, Amy; Martin, Stephen F.

    2009-01-01

    A variety of heterocyclic alcohols and acetates were coupled with silyl ketene acetals and other π-nucleophiles in the presence of trimethylsilyl trifluoromethanesulfonate to provide an array of substituted β-heteroaryl propionates, including those with contiguous quaternary centers, as well as vinylogs thereof. This reaction also proceeds with high diastereoselectivity when the π-nucleophile bears a chiral auxiliary. PMID:20161309

  12. Isocyano Enones: Addition-Cyclization Cascade to Oxazoles.

    PubMed

    Chao, Allen; Lujan-Montelongo, J Armando; Fleming, Fraser F

    2016-07-01

    Copper iodide catalyzes the conjugate addition of organometallic and heteroatom nucleophiles to isocyano enones to afford oxazoles. A range of enolates, metalated nitriles, amines, and thiols undergo catalyzed conjugate addition to cyclic and acyclic oxoalkene isocyanides. Mechanistic studies suggest that copper complexation facilitates the nucleophilic attack on the isocyano enone to generate an enolate that cyclizes onto the isocyanide leading to a variety of substituted acyclic or ring-fused oxazoles. PMID:27282173

  13. Transetherification on Polyols by Intra- and Intermolecular Nucleophilic Substitutions

    PubMed Central

    Muraoka, Takahiro; Adachi, Kota; Chowdhury, Rainy; Kinbara, Kazushi

    2014-01-01

    Transetherification on polyols involving intra- and intermolecular nucleophilic substitutions is reported. Di- or trialkoxide formation of propane-1,3-diol or 2-(hydroxymethyl)propane-1,3-diol derivatives by NaH triggers the reaction via oxetanes formation, where the order to add NaH and a polyol significantly influences the yields of products. It was demonstrated that the protective group on the pentaerythritol skeleton is apparently transferred to the hydrophilic and hydrophobic chain molecules bearing a leaving group in one-step, and a protective group conversion from tosyl to benzyl was successful using a benzyl-appending triol to afford a desired product in 67% yield. PMID:24663293

  14. Amination of electrophilic aromatic compounds by vicarious nucleophilic substitution

    SciTech Connect

    Mitchell, A.R.; Pagoria, P.F.; Schmidt, R.D.

    2000-05-30

    The present invention relates to a process to aminate electrophilic aromatic compounds by vicarious nucleophilic substitution of hydrogen using quaternary hydrazinium salts. The use of trialkylhydrazinium halide, e.g., trimethylhydrazinium iodide, as well as hydroxylamine, alkoxylamines, and 4-amino-1,2,4-triazole to produce aminated aromatic structures, such as 1,3-diamino-2,4,6-trinitrobenzene (DATB), 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and 3,5-diamino-2,4,6-trinitrotoluene (DATNT), is described. DATB and TATB are useful insensitive high explosives. TATB is also used for the preparation of benzenehexamine, a starting material for the synthesis of novel materials (optical imaging devices, liquid crystals, ferromagnetic compounds).

  15. Poly(N-arylenbenzimidazoles) via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1995-01-01

    Novel poly(N-arylenebenzimidazole)s (PNABIs) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl N-arylenebenzimidazole) monomers are synthesized by reacting phenyl 4-hydroxybenzoate with bis(2-aminoanilino) arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyl N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

  16. Poly(N-arylenebenzimidazole)s via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Jr., Joseph G. (Inventor)

    1996-01-01

    Novel poly(N-arylenebenzimidazole)s (PNABls) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl-N-arylenebenzimidazole) monomers are synthesized by reacting phenyl-4-hydroxybenzoate with bis(2-aminoanilino)arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyI-N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

  17. Amination of electrophilic aromatic compounds by vicarious nucleophilic substitution

    DOEpatents

    Mitchell, Alexander R.; Pagoria, Philip F.; Schmidt, Robert D.

    2000-01-01

    The present invention relates to a process to aminate electrophilic aromatic compounds by vicarious nucleophilic substitution of hydrogen using quaternary hydrazinium salts. The use of trialkylhydrazinium halide, e.g., trimethylhydrazinium iodide, as well as hydroxylamine, alkoxylamines, and 4-amino-1,2,4-triazole to produce aminated aromatic structures, such as 1,3-diamino-2,4,6-trinitrobenzene (DATB), 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and 3,5-diamino-2,4,6-trinitrotoluene (DATNT), is described. DATB and TATB are useful insensitive high explosives. TATB is also used for the preparation of benzenehexamine, a starting material for the synthesis of novel materials (optical imaging devices, liquid crystals, ferromagnetic compounds).

  18. Nucleophilic substitution at phosphorus centers (SN2@p).

    PubMed

    van Bochove, Marc A; Swart, Marcel; Bickelhaupt, F Matthias

    2007-12-01

    We have studied the characteristics of archetypal model systems for bimolecular nucleophilic substitution at phosphorus (SN2@P) and, for comparison, at carbon (SN2@C) and silicon (SN2@Si) centers. In our studies, we applied the generalized gradient approximation (GGA) of density functional theory (DFT) at the OLYP/TZ2P level. Our model systems cover nucleophilic substitution at carbon in X(-)+CH3Y (SN2@C), at silicon in X(-)+SiH3Y (SN2@Si), at tricoordinate phosphorus in X(-)+PH2Y (SN2@P3), and at tetracoordinate phosphorus in X(-)+POH2Y (SN2@P4). The main feature of going from SN2@C to SN2@P is the loss of the characteristic double-well potential energy surface (PES) involving a transition state [X--CH3--Y]- and the occurrence of a single-well PES with a stable transition complex, namely, [X--PH2--Y]- or [X--POH2--Y](-). The differences between SN2@P3 and SN2@P4 are relatively small. We explored both the symmetric and asymmetric (i.e. X, Y=Cl, OH) SN2 reactions in our model systems, the competition between backside and frontside pathways, and the dependence of the reactions on the conformation of the reactants. Furthermore, we studied the effect, on the symmetric and asymmetric SN2@P3 and S(N)2@P4 reactions, of replacing hydrogen substituents at the phosphorus centers by chlorine and fluorine in the model systems X(-)+PR2Y and X(-)+POR2Y, with R=Cl, F. An interesting phenomenon is the occurrence of a triple-well PES not only in the symmetric, but also in the asymmetric SN2@P4 reactions of X(-)+POCl2--Y. PMID:17990249

  19. Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide.

    PubMed

    Cuevasanta, Ernesto; Lange, Mike; Bonanata, Jenner; Coitiño, E Laura; Ferrer-Sueta, Gerardo; Filipovic, Milos R; Alvarez, Beatriz

    2015-11-01

    Hydrogen sulfide (H2S) is increasingly recognized to modulate physiological processes in mammals through mechanisms that are currently under scrutiny. H2S is not able to react with reduced thiols (RSH). However, H2S, more precisely HS(-), is able to react with oxidized thiol derivatives. We performed a systematic study of the reactivity of HS(-) toward symmetric low molecular weight disulfides (RSSR) and mixed albumin (HSA) disulfides. Correlations with thiol acidity and computational modeling showed that the reaction occurs through a concerted mechanism. Comparison with analogous reactions of thiolates indicated that the intrinsic reactivity of HS(-) is 1 order of magnitude lower than that of thiolates. In addition, H2S is able to react with sulfenic acids (RSOH). The rate constant of the reaction of H2S with the sulfenic acid formed in HSA was determined. Both reactions of H2S with disulfides and sulfenic acids yield persulfides (RSSH), recently identified post-translational modifications. The formation of this derivative in HSA was determined, and the rate constants of its reactions with a reporter disulfide and with peroxynitrite revealed that persulfides are better nucleophiles than thiols, which is consistent with the α effect. Experiments with cells in culture showed that treatment with hydrogen peroxide enhanced the formation of persulfides. Biological implications are discussed. Our results give light on the mechanisms of persulfide formation and provide quantitative evidence for the high nucleophilicity of these novel derivatives, setting the stage for understanding the contribution of the reactions of H2S with oxidized thiol derivatives to H2S effector processes. PMID:26269587

  20. Why does threonine, and not serine, function as the active site nucleophile in proteasomes?

    PubMed

    Kisselev, A F; Songyang, Z; Goldberg, A L

    2000-05-19

    Proteasomes belong to the N-terminal nucleophile group of amidases and function through a novel proteolytic mechanism, in which the hydroxyl group of the N-terminal threonines is the catalytic nucleophile. However, it is unclear why threonine has been conserved in all proteasomal active sites, because its replacement by a serine in proteasomes from the archaeon Thermoplasma acidophilum (T1S mutant) does not alter the rates of hydrolysis of Suc-LLVY-amc (Seemüller, E., Lupas, A., Stock, D., Lowe, J., Huber, R., and Baumeister, W. (1995) Science 268, 579-582) and other standard peptide amide substrates. However, we found that true peptide bonds in decapeptide libraries were cleaved by the T1S mutant 10-fold slower than by wild type (wt) proteasomes. In degrading proteins, the T1S proteasome was 3.5- to 6-fold slower than the wt, and this difference increased when proteolysis was stimulated using the proteasome-activating nucleotidase (PAN) ATPase complex. With mutant proteasomes, peptide bond cleavage appeared to be rate-limiting in protein breakdown, unlike with wt. Surprisingly, a peptide ester was hydrolyzed by both particles much faster than the corresponding amide, and the T1S mutant cleaved it faster than the wt. Moreover, the T1S mutant was inactivated by the ester inhibitor clasto-lactacystin-beta-lactone severalfold faster than the wt, but reacted with nonester irreversible inhibitors at similar rates. T1A and T1C mutants were completely inactive in all these assays. Thus, proteasomes lack additional active sites, and the N-terminal threonine evolved because it allows more efficient protein breakdown than serine. PMID:10809725

  1. Enantioselective addition of boronates to acyl imines catalyzed by chiral biphenols.

    PubMed

    Bishop, Joshua A; Lou, Sha; Schaus, Scott E

    2009-01-01

    On the big screen: A chiral biphenol catalyst screening protocol was developed for the rapid identification of enantioselective nucleophilic boronate reactions with acyl imines (see scheme). The approach successfully identified a unique catalyst for the reaction of aryl, vinyl, and alkynyl boronates. Mechanistic studies demonstrate boronate ligand exchange with the catalyst is necessary for activation towards nucleophilic addition. PMID:19431168

  2. Dual nucleophilic substitution at a W(ii) η(2)-coordinated diiodo acetylene leading to an amidinium carbyne complex.

    PubMed

    Helmdach, Kai; Rüger, Julia; Villinger, Alexander; Seidel, Wolfram W

    2016-02-11

    The synthesis and reactivity of a W(ii) C2I2 complex towards various nucleophiles are described. Soft, aprotic nucleophiles like 4-dimethylaminopyridine (DMAP) lead to substitution of one CO at tungsten, whereas reaction with an excess of benzylamine results in a dual nucleophilic substitution at the alkyne moiety involving the rearrangement to a novel cationic amidinium carbyne complex. PMID:26750261

  3. Intramolecular energy transfer reactions in polymetallic

    SciTech Connect

    Petersen, J.

    1990-11-01

    This report is concerned with intramolecular, energy-transfer reactions. The concept of preparing synthetically a complex molecular species, capable of absorbing a photon at one metal center (antenna fragment), transferring that energy to a second metal center (reactive fragment) via a bridging ligand was first reported by our group in 1979. It is now apparent that a major emphasis in inorganic chemistry in the future will involve these types of molecular ensembles. Complexes discussed include Rh, Ru, and Cu complexes. 23 refs., 14 tabs.

  4. Conjugate addition-enantioselective protonation reactions.

    PubMed

    Phelan, James P; Ellman, Jonathan A

    2016-01-01

    The addition of nucleophiles to electron-deficient alkenes represents one of the more general and commonly used strategies for the convergent assembly of more complex structures from simple precursors. In this review the addition of diverse protic and organometallic nucleophiles to electron-deficient alkenes followed by enantioselective protonation is summarized. Reactions are first categorized by the type of electron-deficient alkene and then are further classified according to whether catalysis is achieved with chiral Lewis acids, organocatalysts, or transition metals. PMID:27559372

  5. Nucleophilic lewis base dependent addition reactions of allenoates with trifluoromethylated cyclic ketimines.

    PubMed

    Yang, Li-Jun; Li, Shen; Wang, Shuai; Nie, Jing; Ma, Jun-An

    2014-04-18

    A detailed investigation on the different reactivity patterns shown by phosphorus- and nitrogen-containing Lewis base catalysts in the reactions of allenoates with cyclic trifluoromethyl ketimines was accomplished. With PPh3, [3 + 2] annulations proceeded smoothly to afford dihydropyrrole derivatives in excellent yields. Under the catalysis of DABCO, [2 + 2] annulations occurred, producing azetidine derivatives in good to high yields. However, in the presence of pyridine, α,α'-disubstituted allenoates were obtained in very high yields via aza-Morita-Baylis-Hillman reactions. These studies provide an opportunity for diverse synthesis of a variety of N-heterocyclic compounds from the same starting materials. PMID:24693927

  6. Solvent gating of intramolecular electron transfer

    SciTech Connect

    Miller, R.M. ); Spears, K.G.; Gong, J.H.; Wach, M. )

    1994-02-03

    The rates for ionic photodissociation of malachite green leucocyanide to form cyanide ion and a malachite green carbonium ion were measured as a function of solvent and temperature. The observed rates in mixtures of polar and nonpolar solvents all had an activation energy of about 1 kcal/mol for a wide range of dielectric constants. This dissociative intramolecular electron transfer (DIET) is unusual because it is the first example where solvent configurational entropy changes are required to enable a large amplitude molecular distortion leading to a nonadiabatic electron transfer and ionic dissociation. This solvent gated intramolecular electron-transfer mechanism is supported by analysis of the preexponential and activation energy trends in dipolar aprotic solven mixtures and alcohol solvents. The large amplitude motion is not separately measurable due to the slow gating rates, but viscosity effects on both the preexponential and the activation energy are analyzed to demonstrate consistency with a barrierless diffusion model having a structural dependence on electron-transfer rate. The rate has an inverse dependence on viscosity raised to the 0.53 power. 36 refs., 6 figs., 4 tabs.

  7. Molecular Structure and Photoinduced Intramolecular Hydrogen Bonding in 2-Pyrrolylmethylidene Cycloalkanones.

    PubMed

    Sigalov, Mark; Shainyan, Bagrat; Chipanina, Nina; Oznobikhina, Larisa; Strashnikova, Natalia; Sterkhova, Irina

    2015-11-01

    The structures of pyrrolylmethylidene derivatives of 2,3-dihydro-1H-inden-1-one (3), 3,4-dihydro-naphthalen-1(2H)-one (4), and cycloalkanones (5-7) were studied for the first time in the solid state and solution by NMR, IR, and UV spectroscopies supported by DFT quantum mechanical calculations. It was shown that all studied compounds except cycloheptanone derivative 7 both in crystal and in solution exist in the form of dimers where single E or E,E configuration with respect to the exocyclic C═C bond is stabilized by intermolecular hydrogen bonds N-H···O═C. UV irradiation at a wavelength of 365 nm of MeCN or DMSO solutions of 3-6 results, depending on the exposition time and solvent, partial to complete isomerization to the Z or Z,E isomers (in the case of 6, also the Z,Z isomer). The NMR and IR spectroscopy data show the existence of a strong intramolecular hydrogen bond N-H···O═C in the Z moieties of isomerized compounds. The studied compounds are protonated by trifluoroacetic acid at the carbonyl oxygen, in spite of the reverse order of basicity and nucleophilicity of the carbonyl group and the pyrrole ring. Investigation of the behavior of compound 6 with respect to acetate and fluoride anions allows one to consider it as a potential fluoride sensor. PMID:26457975

  8. Eco-friendly polyethylene glycol promoted Michael addition reactions of α,β-unsaturated carbonyl compounds

    EPA Science Inventory

    Abstract- Intra- and inter-nucleophilic addition reactions of different unsaturated compounds were found to be highly effective without any additives in PEG-400 as a recyclable reaction medium under neutral conditions.

  9. REVISITING NUCLEOPHILIC SUBSTITUTION REACTIONS: MICROWAVE-ASSISTED SYNTHESIS OF AZIDES, THIOCYANATES AND SULFONES IN AQUEOUS MEDIUM

    EPA Science Inventory

    A practical, rapid and efficient microwave (MW) promoted synthesis of various azides, thiocyanates and sulfones, is described in aqueous medium. This general and expeditious MW-enhanced nucleophilic substitution approach uses easily accessible starting materials such as halides o...

  10. Effects of electron acceptors and radical scavengers on nonchain radical nucleophilic substitution reactions

    SciTech Connect

    Xianman Zhang; Dilun Yang; Youcheng Liu )

    1993-01-01

    The yields of reaction products from thermal nucleophilic substitution reactions in dimethyl sulfoxide (DMSO) of six o- and p-nitrohalobenzenes with the sodium salt of ethyl [alpha]-cyanoacetate carbanion [Na[sup +][sup [minus

  11. Rational design of reversible and irreversible cysteine sulfenic acid-targeted linear C-nucleophiles.

    PubMed

    Gupta, Vinayak; Carroll, Kate S

    2016-02-16

    Concerns about off-target effects has motivated the development of reversible covalent inhibition strategies for targeting cysteine. However, such strategies have not been reported for the unique cysteine oxoform, sulfenic acid. Herein, we have designed and identified linear C-nucleophiles that react selectively with cysteine sulfenic acid. The resulting thioether adducts exhibit reversibility ranging from minutes to days under reducing conditions, showing the feasibility of tuning C-nucleophile reactivity across a wide range of time scales. PMID:26878905

  12. Reactions of electrophiles with nucleophilic thiolate sites: relevance to pathophysiological mechanisms and remediation.

    PubMed

    LoPachin, Richard M; Gavin, Terrence

    2016-01-01

    Electrophiles are electron-deficient species that form covalent bonds with electron-rich nucleophiles. In biological systems, reversible electrophile-nucleophile interactions mediate basal cytophysiological functions (e.g. enzyme regulation through S-nitrosylation), whereas irreversible electrophilic adduction of cellular macromolecules is involved in pathogenic processes that underlie many disease and injury states. The nucleophiles most often targeted by electrophiles are side chains on protein amino acids (e.g. Cys, His, and Lys) and aromatic nitrogen sites on DNA bases (e.g. guanine N7). The sulfhydryl thiol (RSH) side chain of cysteine residues is a weak nucleophile that can be ionized in specific conditions to a more reactive nucleophilic thiolate (RS(-)). This review will focus on electrophile interactions with cysteine thiolates and the pathophysiological consequences that result from irreversible electrophile modification of this anionic sulfur. According to the Hard and Soft, Acids and Bases (HSAB) theory of Pearson, electrophiles and nucleophiles can be classified as either soft or hard depending on their relative polarizability. HSAB theory suggests that electrophiles will preferentially and more rapidly form covalent adducts with nucleophiles of comparable softness or hardness. Application of HSAB principles, in conjunction with in vitro and proteomic studies, have indicated that soft electrophiles of broad chemical classes selectively form covalent Michael-type adducts with soft, highly reactive cysteine thiolate nucleophiles. Therefore, these electrophiles exhibit a common mechanism of cytotoxicity. As we will discuss, this level of detailed mechanistic understanding is a necessary prerequisite for the rational development of effective prevention and treatment strategies for electrophile-based pathogenic states. PMID:26559119

  13. Reactions of adducts of phosphorus pentachloride and oxa-containing nucleophiles with arsenic trifluoride

    SciTech Connect

    Fridland, S.V.; Miftakhov, M.N.; Arkhipov, V.P.

    1987-12-20

    Results are given on the synthesis of phosphonofluoridates by the reactions of arsenic trifluoride with adducts of phosphorus pentachloride with oxa-containing nucleophiles. The nucleophiles used were saturated ethers, dioxolanes, and vinyl ethers. Reaction products were identified by means of NMR spectroscopy using H 1, P 31, and C 13. A full analysis of chemical shift and spin-spin coupling constant behavior as well as the spectral structure is conducted.

  14. Nucleophilic substitution at centers other than carbon: reaction at the chlorine of N-chloroacetanilides with triethylamine as the nucleophile

    SciTech Connect

    Underwood, G.R.; Dietze, P.E.

    1984-12-28

    The reaction between triethylamine (TEA) and a series of para-substituted N-chloroacetanilides has been studied in aqueous solution buffered to pHs between 1 and 5. The exclusive product derived from the aromatic moiety is the corresponding acetanilide. The reaction occurs via two parallel pseudo-second-order paths, one acid catalyzed (the Orton-like mechanism), the other uncatalyzed. The uncatalyzed reaction is accelerated by the presence of electron-withdrawing substituents on the aromatic ring and can best be represented as nucleophilic displacement at chlorine. It therefore appears to be the prototype of a convenient class of reactions for the study of displacement reactions at chlorine. The rho value for this reaction is 3.87, indicating substantial negative charge buildup in the aromatic ring during of the transition state. The acid-catalyzed reaction is more complex, presumable involving a protonation equilibrium for the N-chloroacetanilide prior to the rate-determining step similar to that in the Orton reaction. 15 references, 2 figures, 3 tables.

  15. Quantitative Intramolecular Singlet Fission in Bipentacenes.

    PubMed

    Sanders, Samuel N; Kumarasamy, Elango; Pun, Andrew B; Trinh, M Tuan; Choi, Bonnie; Xia, Jianlong; Taffet, Elliot J; Low, Jonathan Z; Miller, John R; Roy, Xavier; Zhu, X-Y; Steigerwald, Michael L; Sfeir, Matthew Y; Campos, Luis M

    2015-07-22

    Singlet fission (SF) has the potential to significantly enhance the photocurrent in single-junction solar cells and thus raise the power conversion efficiency from the Shockley-Queisser limit of 33% to 44%. Until now, quantitative SF yield at room temperature has been observed only in crystalline solids or aggregates of oligoacenes. Here, we employ transient absorption spectroscopy, ultrafast photoluminescence spectroscopy, and triplet photosensitization to demonstrate intramolecular singlet fission (iSF) with triplet yields approaching 200% per absorbed photon in a series of bipentacenes. Crucially, in dilute solution of these systems, SF does not depend on intermolecular interactions. Instead, SF is an intrinsic property of the molecules, with both the fission rate and resulting triplet lifetime determined by the degree of electronic coupling between covalently linked pentacene molecules. We found that the triplet pair lifetime can be as short as 0.5 ns but can be extended up to 270 ns. PMID:26102432

  16. Ab initio of the intramolecular dynamics trifluoronitromethane

    SciTech Connect

    Roehrig, M.A.; McCarthy, W.J.; Kukolich, S.G.; Adamowicz, L.

    1993-12-31

    Several experimental studies of trifluoronitromethane have indicated that this molecule undergoes a low energy motion corresponding to an internal rotation of the CF{sub 3} relative to the NO{sub 2} group. Values for the V{sub 6} barrier have been obtained by electron diffraction and microwave spectroscopy to be 3 kcal/mol and 74 cal/mol respectively. A theoretical study of this molecule investigating this and possible other low energy motions is currently underway. Results from this study should reveal new information on the low barrier dynamics and shed some light on this large discrepancy on the V{sub 6} barriers. Preliminary calculations seem to indicate that a simple V{sub 6} barrier does not adequately describe the intramolecular dynamics of this molecule.

  17. Simple intramolecular model potentials for water

    SciTech Connect

    Dang, L.X.; Pettitt, B.M.

    1987-06-04

    An effective intramolecular potential is presented for use in conjunction with existing three-site models of water. Two commonly used internal geometries were fit to the same form yielding slightly different parametrizations. By including a Urey-Bradley-like term in an otherwise standard molecular mechanics form it was found that the experimental transition frequencies of water monomer can be reproduced accurately. Good qualitative agreements for spectral shifts were subsequently found for the models in condensed-phase applications. Harmonic analysis of clusters indicates good qualitative agreement with experimental environmental shifts in frequencies at low temperatures for these models. This model should be useful for a wide variety of applications including simulations of biopolymers and ionic solutions.

  18. Are intramolecular frustrated Lewis pairs also intramolecular catalysts? A theoretical study on H2 activation.

    PubMed

    Zeonjuk, Lei Liu; St Petkov, Petko; Heine, Thomas; Röschenthaler, Gerd-Volker; Eicher, Johannes; Vankova, Nina

    2015-04-28

    We investigate computationally a series of intramolecular frustrated Lewis pairs (FLPs), with the general formula Mes2PCHRCH2B(C6F5)2, that are known from the literature to either activate molecular hydrogen (FLPs with R = H (1) or Me (4)), or remain inert (FLPs with R = Ph (2) or SiMe3 (3)). The prototypical system Mes2PCH2CH2B(C6F5)2 (1) has been described in the literature (Grimme et al., Angew. Chem., Int. Ed., 2010; Rokob et al., J. Am. Chem. Soc., 2013) as an intramolecular reactant that triggers the reaction with H2 in a bimolecular concerted fashion. In the current study, we show that the concept of intramolecular H2 activation by linked FLPs is not able to explain the inertness of the derivative compounds 2 and 3 towards H2. To cope with this, we propose an alternative intermolecular mechanism for the investigated reaction, assuming stacking of two open-chain FLP conformers, and formation of a dimeric reactant with two Lewis acid–base domains, that can split up to two hydrogen molecules. Using quantum-chemical methods, we compute the reaction profiles describing these alternative mechanisms, and compare the derived predictions with earlier reported experimental results. We show that only the concept of intermolecular H2 activation could explain both the activity of the FLPs having small substituents in the bridging molecular region, and the inertness of the FLPs with a bulkier substitution, in a consistent way. Importantly, the intermolecular H2 activation driven by intramolecular FLPs indicates the key role of steric factors and noncovalent interactions for the design of metal-free systems that can efficiently split H2, and possibly serve as metal-free hydrogenation catalysts. PMID:25812167

  19. The concerted action of a positive charge and hydrogen bonds dynamically regulates the pKa of the nucleophilic cysteine in the NrdH-redoxin family.

    PubMed

    Van Laer, Koen; Oliveira, Margarida; Wahni, Khadija; Messens, Joris

    2014-02-01

    NrdH-redoxins shuffle electrons from the NADPH pool in the cell to Class Ib ribonucleotide reductases, which in turn provide the precursors for DNA replication and repair. NrdH-redoxins have a CVQC active site motif and belong to the thioredoxin-fold protein family. As for other thioredoxin-fold proteins, the pK(a) of the nucleophilic cysteine of NrdH-redoxins is of particular interest since it affects the catalytic reaction rate of the enzymes. Recently, the pK(a) value of this cysteine in Corynebacterium glutamicum and Mycobacterium tuberculosis NrdH-redoxins were determined, but structural insights explaining the relatively low pK(a) remained elusive. We subjected C. glutamicum NrdH-redoxin to an extensive molecular dynamics simulation to expose the factors regulating the pK(a) of the nucleophilic cysteine. We found that the nucleophilic cysteine receives three hydrogen bonds from residues within the CVQC active site motif. Additionally, a fourth hydrogen bond with a lysine located N-terminal of the active site further lowers the cysteine pK(a). However, site-directed mutagenesis data show that the major contribution to the lowering of the cysteine pK(a) comes from the positive charge of the lysine and not from the additional Lys-Cys hydrogen bond. In 12% of the NrdH-redoxin family, this lysine is replaced by an arginine that also lowers the cysteine pK(a). All together, the four hydrogen bonds and the electrostatic effect of a lysine or an arginine located N-terminally of the active site dynamically regulate the pK(a) of the nucleophilic cysteine in NrdH-redoxins. PMID:24243781

  20. Understanding the mechanism of the intramolecular stetter reaction. A DFT study.

    PubMed

    Domingo, Luis R; Zaragozá, Ramón J; Saéz, Jose A; Arnó, Manuel

    2012-01-01

    The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addition is the stereoselectivity determining step responsible for the configuration of the stereogenic carbon a to the carbonyl of chromanone 3. An ELF analysis at TSs and intermediates involved in the Michael-type addition allows for the characterization of the electronic changes along the C-C bond-formation. PMID:22301721

  1. Nucleophilicity Parameters of Stabilized Iodonium Ylides for Characterizing Their Synthetic Potential.

    PubMed

    Chelli, Saloua; Troshin, Konstantin; Mayer, Peter; Lakhdar, Sami; Ofial, Armin R; Mayr, Herbert

    2016-08-17

    Kinetics and mechanisms of the reactions of the β-dicarbonyl-substituted iodonium ylides 1(a-d) with several π-conjugated carbenium and iminium ions have been investigated. All reactions proceed with rate-determining attack of the electrophile at the nucleophilic carbon center of the ylides to give iodonium ions, which rapidly expel iodobenzene and undergo different subsequent reactions. The second-order rate constants k2 for the reactions of the iodonium ylides with benzhydrylium ions correlate linearly with the electrophilicity parameters E of the benzhydrylium ions and thus follow the linear free energy relationship log k(20 °C) = sN(N + E) (eq 1), where electrophiles are characterized by one parameter (E), while nucleophiles are characterized by two parameters: the nucleophilicity N and the susceptibility sN. The nucleophilicity parameters 4 < N < 8 for iodonium ylides 1(a-d) derived from these correlations show that substituting hydrogen for Ph-I(+) at the carbanionic center of Meldrum's acid or dimedone, respectively, reduces the nucleophilicity by approximately 10 orders of magnitude. The iodonium ylides 1(a-d) thus have nucleophilicities similar to those of pyrroles, indoles, and silylated enol ethers and, therefore, should be suitable substrates in iminium-activated reactions. Good agreement of the measured rate constant for the cyclopropanation of the imidazolidinone-derived iminium ion 10a with the iodonium ylide 1a with the rate constant calculated by eq 1 suggests a stepwise mechanism in which the initial nucleophilic attack of the iodonium ylide at the iminium ion is rate-determining. The reaction of cinnamaldehyde with iodonium ylide 1a catalyzed by (5S)-5-benzyl-2,2,3-trimethyl-imidazolidin-4-one (11a, MacMillan's first-generation catalyst) gives the corresponding cyclopropane with an enantiomeric ratio of 70/30 and, thus, provides proof of principle that iodonium ylides are suitable substrates for iminium-activated cyclopropanations. PMID

  2. Substituents on Quinone Methides Strongly Modulate Formation and Stability of Their Nucleophilic Adducts

    PubMed Central

    Weinert, Emily E.; Dondi, Ruggero; Colloredo-Melz, Stefano; Frankenfield, Kristen N.; Mitchell, Charles H.; Freccero, Mauro; Rokita, Steven E.

    2008-01-01

    Electronic perturbation of quinone methides (QM) greatly influences their stability and in turn alters the kinetics and product profile of QM reaction with deoxynucleosides. Consistent with the electron deficient nature of this reactive intermediate, electron-donating substituents are stabilizing and electron-withdrawing substituents are destabilizing. For example, a dC N3-QM adduct is made stable over the course of observation (7 days) by the presence of an electron-withdrawing ester group that inhibits QM regeneration. Conversely, a related adduct with an electron donating methyl group is very labile and regenerates its QM with a half-life of approximately 5 hr. The generality of these effects is demonstrated with a series of alternative quinone methide precursors (QMP) containing a variety of substituents attached at different positions with respect to the exocyclic methylene. The rates of nucleophilic addition to substituted QMs measured by laser flash photolysis similarly span five orders of magnitude with electron rich species reacting most slowly and electron deficient species reacting most quickly. The reversibility of QM reaction can now be predictably adjusted for any desired application. PMID:16953635

  3. An immunochemical approach to detect oxidized protein tyrosine phosphatases using a selective C-nucleophile tag.

    PubMed

    Garcia, Francisco J; Carroll, Kate S

    2016-05-24

    Protein tyrosine phosphatases are crucial regulators of signal transduction and function as antagonists towards protein tyrosine kinases to control reversible tyrosine phosphorylation, thereby regulating fundamental physiological processes. Growing evidence has supported the notion that reversible oxidative inactivation of the catalytic cysteine residue in protein tyrosine phosphatases serves as an oxidative post-translational modification that regulates its activity to influence downstream signaling by promoting phosphorylation and induction of the signaling cascade. The oxidation of cysteine to the sulfenic acid is often transient and difficult to detect, thus making it problematic in understanding the role that this oxidative post-translational modification plays in redox-biology and pathogenesis. Several methods to detect cysteine oxidation in biological systems have been developed, though targeted approaches to directly detect oxidized phosphatases are still lacking. Herein we describe the development of a novel immunochemical approach to directly profile oxidized phosphatases. This immunochemical approach consists of an antibody designed to recognize the conserved sequence of the PTP active site (VHCDMDSAG) harboring the catalytic cysteine modified with dimedone (CDMD), a nucleophile that chemoselectively reacts with cysteine sulfenic acids to form a stable thioether adduct. Additionally, we provide biochemical and mass spectrometry workflows to be used in conjugation with this newly developed immunochemical approach to assist in the identification and quantification of basal and oxidized phosphatases. PMID:26757830

  4. Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation

    NASA Astrophysics Data System (ADS)

    You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P.

    2015-01-01

    The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of >=50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.

  5. Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation.

    PubMed

    You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P

    2015-01-15

    The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of ≥50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods. PMID:25592541

  6. Carbonylmetallates--A Special Family of Nucleophiles in Aromatic and Vinylic Substitution Reactions.

    PubMed

    Sazonov, Petr K; Beletskaya, Irina P

    2016-03-01

    Carbonylmetallates, [M(CO)(n)L](-), anionic transition-metal carbonyl complexes, represent a large family of metal-centered nucleophiles, and studying carbonylmetallates allows us to understand the differences in the behavior of the metal-centered complexes versus heteroatom-based nucleophiles. The mechanisms of carbonylmetallate reactions with aryl- and alkenyl halides have been examined by employing radical and, especially, carbanion trapping techniques. Carbonylmetallates show a marked preference for halogenophilic attack, and nucleophilic substitution with carbonylmetallates is often not a direct process, but proceeds through the initial attack at halogen with subsequent coupling of carbanion and HalM(CO)(n)L intermediates. Factors governing the competition between the halogenophilic and more common "carbophilic" reaction pathways, as well as the means of predicting the actual course of reaction are discussed. The review also considers other aspects of carbonylmetallate reactivity, including ion-pairing effects, radical-mediated nucleophilic substitution pathways, and the carbonylmetallate nucleophilicity scale in the reactions with π-electrophiles. PMID:26808811

  7. Intramolecular hydrogen bonds in crystals of thiophosphorylbenzopyrane derivatives X-ray and FT-IR studies

    NASA Astrophysics Data System (ADS)

    Rybarczyk-Pirek, Agnieszka J.; Dubis, Alina T.; Grabowski, Sławomir J.; Nawrot-Modranka, Jolanta

    2006-01-01

    The crystal structures of two new benzopyrane derivatives are analyzed and compared with previous X-ray investigations on related compounds. A particular attention is focused on intramolecular interactions. For the chromone derivatives ( 1 and 3) only one kind of interaction is possible, i.e., N-H⋯O, whereas for the coumarine derivatives ( 2 and 4) two types of intramolecular hydrogen bonding are observed - N-H⋯O and O-H⋯N. Two types of H-bond for coumarine derivatives are the result of the existence of two tautomeric forms - enamine and iminoenol. Combined spectroscopic, NMR and IR measurements confirm such tautomeric equilibrium in solution. The influence of the additional intermolecular hydrogen bonds on the stabilization of tautomeric forms in crystals is also discussed here.

  8. Internal Stark effect mediates intramolecular excited-state proton transfer in 3-hydroxyflavone derivatives

    NASA Astrophysics Data System (ADS)

    Klymchenko, Andriy S.; Demchenko, Alexander P.

    2002-12-01

    Internal Stark effect in electronic spectra is the effect that is observed when the electronic bands shift udner the influence of promixal charges. In order to study the possible involvement of this effect in modulating the intramolecular proton transfer reactions in the excited state, we designed and studied several derivatives of 3-hydroxyflavone. They include the species containing neutral and positively charged substituents in 6 position of chromone ring. These compounds were studied in solvents of different polarities. In these experiments the shifts of both normal and tautomer flurosence bands are clearly observed in a manner predicted by Stark effect theory. In addition, a dramatic effect of suppression by introduced charge of intramolecular excited-state proton transfer was observed.

  9. Intramolecular hydrogen bonding and calixarene-like structures in p-cresol/formaldehyde resins

    NASA Astrophysics Data System (ADS)

    Opaprakasit, P.; Scaroni, A.; Painter, P.

    2001-08-01

    The nature of the strong hydrogen bonds found in p-cresol/formaldehyde (PCF) resins, compared to ordinary phenolic compounds, is studied. The evidence from FTIR spectroscopy indicates that this strong interaction is due to intramolecular hydrogen bonding from "calixarene-like" structures. The formation of this structure in PCF is enabled by its "linear" (all- ortho-linkage) structure, which is not present in branched resins. Additionally, a transition is observed at around 175 to 200°C where the intramolecular hydrogen bonded structure is lost. This structure cannot be recovered upon cooling or annealing due to restrictions on conformational rotations that are coupled to a new pattern of intermolecular hydrogen bonding. However, the structure is reformed by dissolving the resin in solution and casting new films.

  10. Asymmetric Synthesis of (-)-Incarvillateine Employing an Intramolecular Alkylation via Rh-Catalyzed Olefinic C-H Bond Activation

    SciTech Connect

    Tsai, Andy; Bergman, Robert; Ellman, Jonathan

    2008-02-18

    An asymmetric total synthesis of (-)-incarvillateine, a natural product having potent analgesic properties, has been achieved in 11 steps and 15.4% overall yield. The key step is a rhodium-catalyzed intramolecular alkylation of an olefinic C-H bond to set two stereocenters. Additionally, this transformation produces an exocyclic, tetrasubstituted alkene through which the bicyclic piperidine moiety can readily be accessed.

  11. Palladium-catalyzed regioselective intramolecular coupling of o-carborane with aromatics via direct cage B-H activation.

    PubMed

    Quan, Yangjian; Xie, Zuowei

    2015-03-18

    Palladium-catalyzed intramolecular coupling of o-carborane with aromatics via direct cage B-H bond activation has been achieved, leading to the synthesis of a series of o-carborane-functionalized aromatics in high yields with excellent regioselectivity. In addition, the site selectivity can also be tuned by the substituents on cage carbon atom. PMID:25747772

  12. Enantioselective Intramolecular C-H Insertion of Donor and Donor/Donor Carbenes by a Nondiazo Approach.

    PubMed

    Zhu, Dong; Ma, Jun; Luo, Kui; Fu, Hongguang; Zhang, Li; Zhu, Shifa

    2016-07-11

    The first enantioselective intramolecular C-H insertion and cyclopropanation reactions of donor- and donor/donor-carbenes by a nondiazo approach are reported. The reactions were conducted in a one-pot manner without slow addition and provided the desired dihydroindole, dihydrobenzofuran, tetrahydrofuran, and tetrahydropyrrole derivatives with up to 99 % ee and 100 % atom efficiency. PMID:27265896

  13. Intramolecular hydrogen bonds in sulfur-containing aminophenols

    NASA Astrophysics Data System (ADS)

    Belkov, M. V.; Harbachova, A. N.; Ksendzova, G. A.; Polozov, G. I.; Skornyakov, I. V.; Sorokin, V. L.; Tolstorozhev, G. B.; Shadyro, O. I.

    2010-07-01

    IR Fourier spectroscopy methods have been adopted to study intramolecular interactions that occur in CCl4 solutions of antiviral derivatives of aminophenol. Analysis of the IR spectra showed that intramolecular bonds O-H···N, O-H···O=C, N-H···O=S=O, and O-H···O=S=O can occur in these compounds depending on the substituent on the amino group. Not only the presence of intramolecular O-H···N, O-H···O=S=O, and N- H···O=S=O hydrogen bonds in 2-amino-4,6-di-tert-butylphenol derivatives containing a sulfonamide fragment but also conformational equilibrium among these types of intramolecular interactions are essential for the manifestation of high efficiency in suppressing HIV-infection in cell culture.

  14. Synchronous intramolecular cycloadditions of the polyene macrolactam polyketide heronamide C.

    PubMed

    Booth, Thomas J; Alt, Silke; Capon, Robert J; Wilkinson, Barrie

    2016-05-11

    A growing number of natural products appear to arise from biosynthetic pathways that involve pericyclic reactions. We show here that for the heronamides this can occur via two spontaneous pathways involving alternative thermal or photochemical intramolecular cycloadditions. PMID:27091090

  15. Exciton Correlations in Intramolecular Singlet Fission.

    PubMed

    Sanders, Samuel N; Kumarasamy, Elango; Pun, Andrew B; Appavoo, Kannatassen; Steigerwald, Michael L; Campos, Luis M; Sfeir, Matthew Y

    2016-06-15

    We have synthesized a series of asymmetric pentacene-tetracene heterodimers with a variable-length conjugated bridge that undergo fast and efficient intramolecular singlet fission (iSF). These compounds have distinct singlet and triplet energies, which allow us to study the spatial dynamics of excitons during the iSF process, including the significant role of exciton correlations in promoting triplet pair generation and recombination. We demonstrate that the primary photoexcitations in conjugated dimers are delocalized singlets that enable fast and efficient iSF. However, in these asymmetric dimers, the singlet becomes more localized on the lower energy unit as the length of the bridge is increased, slowing down iSF relative to analogous symmetric dimers. We resolve the recombination kinetics of the inequivalent triplets produced via iSF, and find that they primarily decay via concerted processes. By identifying different decay channels, including delayed fluorescence via triplet-triplet annihilation, we can separate transient species corresponding to both correlated triplet pairs and uncorrelated triplets. Recombination of the triplet pair proceeds rapidly despite our experimental and theoretical demonstration that individual triplets are highly localized and unable to be transported across the conjugated linker. In this class of compounds, the rate of formation and yield of uncorrelated triplets increases with bridge length. Overall, these constrained, asymmetric systems provide a unique platform to isolate and study transient species essential for singlet fission, which are otherwise difficult to observe in symmetric dimers or condensed phases. PMID:27183040

  16. Femtochemistry of Intramolecular Charge and Proton Transfer Reactions in Solution

    SciTech Connect

    Douhal, Abderrazzak; Sanz, Mikel; Carranza, Maria Angeles; Organero, Juan Angel; Tormo, Laura

    2005-03-17

    We report on the first observation of ultrafast intramolecular charge- and proton-transfer reactions in 4'-dimethylaminoflavonol (DAMF) in solution. Upon femtosecond excitation of a non-planar structure of DMAF in apolar medium, the intramolecular charge transfer (ICT) does not occur, and a slow (2 ps) proton motion takes place. However, in polar solvents, the ICT is very fast (100-200 fs) and the produced structure is stabilized that proton motion takes place in few or tens of ps.

  17. Oxidative nucleophilic strategy for synthesis of thiocyanates and trifluoromethyl sulfides from thiols.

    PubMed

    Yamaguchi, Kazuya; Sakagami, Konomi; Miyamoto, Yumi; Jin, Xiongjie; Mizuno, Noritaka

    2014-12-01

    Thiocyanates and trifluoromethyl sulfides are important compounds and have classically been synthesized via multistep procedures together with the formation of significant amounts of byproducts. Herein, we demonstrate an oxidative nucleophilic strategy for the synthesis of thiocyanates and trifluoromethyl sulfides from thiol starting materials using nucleophilic reagents such as TMSCN and TMSCF3 (TMS = trimethylsilyl). In the presence of a 2 × 2 manganese oxide-based octahedral molecular sieve (OMS-2) and potassium fluoride (KF), various structurally diverse thiocyanates and trifluoromethyl sulfides could be synthesized in almost quantitative yields (typically >90%). The presented cyanation and trifluoromethylation reactions proceed through the OMS-2-catalyzed oxidative homocoupling of thiols to give disulfides followed by nucleophilic bond cleavage to produce the desired compounds and thiolate species (herein S-trimethylsilylated thiols). OMS-2 can catalyze oxidative homocoupling of the thiolate species, thus resulting formally in the quantitative production of thiocyanates and trifluoromethyl sulfides from thiols. PMID:25297894

  18. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase

    SciTech Connect

    Ealy, Julie B.; Sudol, Malgorzata; Krzeminski, Jacek; Amin, Shantu; Katzman, Michael

    2012-11-10

    Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.

  19. Identification of the nucleophile catalytic residue of GH51 α-l-arabinofuranosidase from Pleurotus ostreatus

    DOE PAGESBeta

    Amore, Antonella; Iadonisi, Alfonso; Vincent, Florence; Faraco, Vincenza

    2015-12-21

    In this paper, the recombinant α-l-arabinofuranosidase from the fungus Pleurotus ostreatus (rPoAbf) was subjected to site-directed mutagenesis in order to identify the catalytic nucleophile residue. Based on bioinformatics and homology modelling analyses, E449 was revealed to be the potential nucleophilic residue. Thus, the mutant E449G of PoAbf was recombinantly expressed in Pichia pastoris and its recombinant expression level and reactivity were investigated in comparison to the wild-type. The design of a suitable set of hydrolysis experiments in the presence or absence of alcoholic arabinosyl acceptors and/or formate salts allowed to unambiguously identify the residue E449 as the nucleophile residue involvedmore » in the retaining mechanism of this GH51 arabinofuranosidase. 1H NMR analysis was applied for the identification of the products and the assignement of their anomeric configuration.« less

  20. Microwaves and Aqueous Solvents Promote the Reaction of Poorly Nucleophilic Anilines with a Zincke Salt.

    PubMed

    Zeghbib, Narimane; Thelliere, Paul; Rivard, Michael; Martens, Thierry

    2016-04-15

    The Zincke reaction allows the transformation of primary amines into their respective N-alkylated or N-arylated pyridinium salts. While nucleophilic primary amines (typically, aliphatic primary amines) often lead to quantitative reactions and has been documented profusely, the use of poorly nucleophilic amines still requires an in depth account. To date, the lack of nucleophilicity of the amines is redhibitory. The subject addressed in this article is a series of primary amines deriving from aniline having been engaged in Zincke reactions. Efficient transformations were obtained, even when conducted on electronically deactivated, eventually also sterically hindered, substrates. This was achieved by the combined use of microwave activation and aqueous solvents. Under our conditions, the role of water revealed indeed crucial to avoid the self-degradation of the Zincke salt, the reagent of the reaction. PMID:26986875

  1. Identification of the nucleophile catalytic residue of GH51 α-L-arabinofuranosidase from Pleurotus ostreatus.

    PubMed

    Amore, Antonella; Iadonisi, Alfonso; Vincent, Florence; Faraco, Vincenza

    2015-12-01

    In this study, the recombinant α-L-arabinofuranosidase from the fungus Pleurotus ostreatus (rPoAbf) was subjected to site-directed mutagenesis in order to identify the catalytic nucleophile residue. Based on bioinformatics and homology modelling analyses, E449 was revealed to be the potential nucleophilic residue. Thus, the mutant E449G of PoAbf was recombinantly expressed in Pichia pastoris and its recombinant expression level and reactivity were investigated in comparison to the wild-type. The design of a suitable set of hydrolysis experiments in the presence or absence of alcoholic arabinosyl acceptors and/or formate salts allowed to unambiguously identify the residue E449 as the nucleophile residue involved in the retaining mechanism of this GH51 arabinofuranosidase. (1)H NMR analysis was applied for the identification of the products and the assignement of their anomeric configuration. PMID:26690659

  2. Intramolecular Charge-Assisted Hydrogen Bond Strength in Pseudochair Carboxyphosphate

    PubMed Central

    2015-01-01

    Carboxyphosphate, a suspected intermediate in ATP-dependent carboxylases, has not been isolated nor observed directly by experiment. Consequently, little is known concerning its structure, stability, and ionization state. Recently, carboxyphosphate as either a monoanion or dianion has been shown computationally to adopt a novel pseudochair conformation featuring an intramolecular charge-assisted hydrogen bond (CAHB). In this work, additive and subtractive correction schemes to the commonly employed open–closed method are used to estimate the strength of the CAHB. Truhlar’s Minnesota M06-2X functional with Dunning’s aug-cc-pVTZ basis set has been used for geometry optimization, energy evaluation, and frequency analysis. The CHARMM force field has been used to approximate the Pauli repulsive terms in the closed and open forms of carboxyphosphate. From our additive correction scheme, differential Pauli repulsion contributions between the pseudochair (closed) and open conformations of carboxyphosphate are found to be significant in determining the CAHB strength. The additive correction modifies the CAHB prediction (ΔEclosed–open) of −14 kcal/mol for the monoanion and −12 kcal/mol for the dianion to −22.9 and −18.4 kcal/mol, respectively. Results from the subtractive technique reinforce those from our additive procedure, where the predicted CAHB strength ranges from −17.8 to −25.4 kcal/mol for the monoanion and from −15.7 to −20.9 kcal/mol for the dianion. Ultimately, we find that the CAHB in carboxyphosphate meets the criteria for short-strong hydrogen bonds. However, carboxyphosphate has a unique energy profile that does not result in the symmetric double-well behavior of low-barrier hydrogen bonds. These findings provide deeper insight into the pseudochair conformation of carboxyphosphate, and lead to an improved mechanistic understanding of this intermediate in ATP-dependent carboxylases. PMID:25405523

  3. Synthesis and reactivity of nitrogen nucleophiles-induced cage-rearrangement silsesquioxanes.

    PubMed

    Jaroentomeechai, Thapakorn; Yingsukkamol, Pa-Kwan; Phurat, Chuttree; Somsook, Ekasith; Osotchan, Tanakorn; Ervithayasuporn, Vuthichai

    2012-11-19

    Novel phthalimide and o-sulfobenzimide-functionalized silsesquioxanes were successfully synthesized via nucleophilic substitution reactions from octakis(3-chloropropyl)octasilsesquioxane. Surprisingly, the formation of deca- and dodecasilsesquioxanes cages was discovered during substitution with phthalimide, but only octasilsesquioxane maintained a cage in the o-sulfobenzimide substitution reaction. Moreover, we report the electronic effect of nitrogen nucleophiles to promote cage-rearrangement of inorganic silsesquioxane core for the first time. Structures of products were confirmed by (1)H, (13)C, and (29)Si NMR spectroscopy, ESI-MS analysis, and single-crystal X-ray diffraction. PMID:23134535

  4. Reactivity, Selectivity, and Stability in Sulfenic Acid Detection: A Comparative Study of Nucleophilic and Electrophilic Probes.

    PubMed

    Gupta, Vinayak; Paritala, Hanumantharao; Carroll, Kate S

    2016-05-18

    The comparative reaction efficiencies of currently used nucleophilic and electrophilic probes toward cysteine sulfenic acid have been thoroughly evaluated in two different settings-(i) a small molecule dipeptide based model and (ii) a recombinant protein model. We further evaluated the stability of corresponding thioether and sulfoxide adducts under reducing conditions which are commonly encountered during proteomic protocols and in cell analysis. Powered by the development of new cyclic and linear C-nucleophiles, the unsurpassed efficiency in the capture of sulfenic acid under competitive conditions is achieved and thus holds great promise as highly potent tools for activity-based sulfenome profiling. PMID:27123991

  5. Intramolecular Hydrogen Bonding in Benzoxazines: When Structural Design Becomes Functional.

    PubMed

    Froimowicz, Pablo; Zhang, Kan; Ishida, Hatsuo

    2016-02-18

    The future evolution of benzoxazines and polybenzoxazines as advanced molecular, structural, functional, engineering, and newly commercial materials depends to a great extent on a deeper and more fundamental understanding at the molecular level. In this contribution, the field of benzoxazines is briefly introduced along with a more detailed review of ortho-amide-functional benzoxazines, which are the main subjects of this article. Provided in this article are the detailed and solid scientific evidences of intramolecular five-membered-ring hydrogen bonding, which is supposed to be responsible for the unique and characteristic features exhibited by this ever-growing family of ortho-functionalized benzoxazines. One-dimensional (1D) (1)H NMR spectroscopy was used to study various concentrations of benzoxazines in various solvents with different hydrogen-bonding capability and at various temperatures to investigate in detail the nature of hydrogen bonding in both ortho-amide-functionalized benzoxazine and its para counterpart. These materials were further investigated by two-dimensional (2D) (1)H-(1)H nuclear Overhauser effect spectroscopy (NOESY) to verify and support the conclusions derived during the 1D (1)H NMR experiments. Only highly purified single-crystal benzoxazine samples have been used for this study to avoid additional interactions caused by any impurities. PMID:26797690

  6. Cationic palladium(ii)-catalyzed dehydrative nucleophilic substitutions of benzhydryl alcohols with electron-deficient benzenethiols in water.

    PubMed

    Hikawa, Hidemasa; Machino, Yumo; Toyomoto, Mariko; Kikkawa, Shoko; Azumaya, Isao

    2016-08-01

    An efficient direct nucleophilic substitution of benzhydryl alcohols with electron-deficient benzenethiols using cationic Pd(ii) catalysts as Lewis acids in water is reported. Atom economical and environmentally benign protocols afford S-benzylated products in moderate to excellent yields. Commercially available Pd(MeCN)4(OTf)2, PdCl2(MeCN)2, and Na2PdCl4 are highly efficient catalysts. Notably, this simple protocol can be achieved without any other additives such as acids, bases, or external ligands. A Hammett study on the rate constants of S-benzylation by using various substituted benzhydryl alcohols yielded negative ρ values, suggesting that there is a build-up of positive charge in the transition state. PMID:27363665

  7. Biphenyl-Derived Phosphepines as Chiral Nucleophilic Catalysts: Enantioselective [4+1] Annulations to Form Functionalized Cyclopentenes

    PubMed Central

    Ziegler, Daniel T.; Riesgo, Lorena; Ikeda, Takuya; Fujiwara, Yuji

    2015-01-01

    Due to the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. In this report, we introduce a new family of chiral nucleophilic catalysts, biphenyl-derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation first described by Tong. A range of one-carbon coupling partners can be employed, thereby generating cyclopentenes that bear a fully substituted stereocenter (either all-carbon or heteroatom-substituted (sulfur and phosphorus)). Stereocenters at the other four positions of the cyclopentane ring can also be introduced with good stereoselectivity. An initial mechanistic study indicates that phosphine addition to the electrophilic four-carbon coupling partner is not the turnover-limiting step of the catalytic cycle. PMID:25287684

  8. Bridge- and Solvent-Mediated Intramolecular Electronic Communications in Ubiquinone-Based Biomolecular Wires

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-Yuan; Ma, Wei; Zhou, Hao; Cao, Xiao-Ming; Long, Yi-Tao

    2015-05-01

    Intramolecular electronic communications of molecular wires play a crucial role for developing molecular devices. In the present work, we describe different degrees of intramolecular electronic communications in the redox processes of three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by electrochemistry and Density Functional Theory (DFT) methods in different solvents. We found that the bridges linkers have a significant effect on the electronic communications between the two peripheral ubiquinone moieties and solvents effects are limited and mostly depend on the nature of solvents. The DFT calculations for the first time indicate the intensity of the electronic communications during the redox processes rely on the molecular orbital elements VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1), which is could be affected by the bridges linkers. The DFT calculations also demonstrates the effect of solvents on the latter two-electron transfer of Bis-CoQ0s is more significant than the former two electrons transfer as the observed electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry and theoretical calculations reveal the intramolecular electronic communications vary in the four-electron redox processes of three Bis-CoQ0s.

  9. Bridge- and Solvent-Mediated Intramolecular Electronic Communications in Ubiquinone-Based Biomolecular Wires

    PubMed Central

    Liu, Xiao-Yuan; Ma, Wei; Zhou, Hao; Cao, Xiao-Ming; Long, Yi-Tao

    2015-01-01

    Intramolecular electronic communications of molecular wires play a crucial role for developing molecular devices. In the present work, we describe different degrees of intramolecular electronic communications in the redox processes of three ubiquinone-based biomolecular wires (Bis-CoQ0s) evaluated by electrochemistry and Density Functional Theory (DFT) methods in different solvents. We found that the bridges linkers have a significant effect on the electronic communications between the two peripheral ubiquinone moieties and solvents effects are limited and mostly depend on the nature of solvents. The DFT calculations for the first time indicate the intensity of the electronic communications during the redox processes rely on the molecular orbital elements VL for electron transfer (half of the energy splitting of the LUMO and LUMO+1), which is could be affected by the bridges linkers. The DFT calculations also demonstrates the effect of solvents on the latter two-electron transfer of Bis-CoQ0s is more significant than the former two electrons transfer as the observed electrochemical behaviors of three Bis-CoQ0s. In addition, the electrochemistry and theoretical calculations reveal the intramolecular electronic communications vary in the four-electron redox processes of three Bis-CoQ0s. PMID:25996306

  10. The Identity of the Nucleophile Substitution may Influence Metal Interactions with the Cleavage Site of the Minimal Hammerhead Ribozyme

    PubMed Central

    Osborne, Edith M.; Ward, W. Luke; Ruehle, Max Z.; DeRose, Victoria J.

    2010-01-01

    Potential metal interactions with the cleavage site of a minimal hammerhead ribozyme (mHHRz) were probed using 31P NMR-detected Cd2+ titration studies of HHRz constructs containing a phosphorothioate (PS) modification at the cleavage site. The mHHRz nucleophile position was replaced by either a 2′-F or a 2′-NH2 in order to block cleavage activity during the study. The 2′-F/PS cleavage site mHHRz construct, in which the 2′-F should closely imitate the atom size and electronegativity of a 2′OH, demonstrates low levels of metal ion association (<1 ppm 31P chemical shift changes). This observation indicates that having an atom size and electrostatic properties that are similar to the 2′-OH are not the governing factors in allowing metal interactions with the scissile phosphate of the mHHRz. With a 2′-NH2 substitution, a large upfield change in 31P NMR chemical shift of the phosphorothioate peak (Δ~3 ppm with 6 equivalents added Cd2+) indicates observable Cd2+ interactions with the substituted site. Since a 2′-NH2, but not a 2′-F, can serve as a metal ligand, these data suggest that a metal ion interaction with the HHRz cleavage site may include both the scissile phosphate and the 2′ nucleophile. Control samples in which the 2′-NH2/PS unit is placed either next to the mHHRz cleavage site (at U16.1), in a duplex, or in a amUPSU dinucleotide, show much weaker interactions with Cd2+. Results with these control samples indicate that simply the presence of a 2′-NH2/PS unit does not create a strong metal binding site, reinforcing the possibility that the 2′-NH2-moderated Cd-PS interaction is specific to the mHHRz cleavage site. Upfield chemical shifts of both 31P and H2′ 1H resonances in amUPSU are observed with addition of Cd2+, consistent with the predicted metal coordination to both 2′-NH2 and phosphorothioate ligands. These data suggest that metal ion association with the HHRz cleavage site may include an interaction with the 2

  11. Nucleophilicity and P-C Bond Formation Reactions of a Terminal Phosphanido Iridium Complex.

    PubMed

    Serrano, Ángel L; Casado, Miguel A; Ciriano, Miguel A; de Bruin, Bas; López, José A; Tejel, Cristina

    2016-01-19

    The diiridium complex [{Ir(ABPN2)(CO)}2(μ-CO)] (1; [ABPN2](-) = [(allyl)B(Pz)2(CH2PPh2)](-)) reacts with diphenylphosphane affording [Ir(ABPN2)(CO)(H) (PPh2)] (2), the product of the oxidative addition of the P-H bond to the metal. DFT studies revealed a large contribution of the terminal phosphanido lone pair to the HOMO of 2, indicating nucleophilic character of this ligand, which is evidenced by reactions of 2 with typical electrophiles such as H(+), Me(+), and O2. Products from the reaction of 2 with methyl chloroacetate were found to be either [Ir(ABPN2)(CO)(H)(PPh2CH2CO2Me)][PF6] ([6]PF6) or [Ir(ABPN2)(CO)(Cl)(H)] (7) and the free phosphane (PPh2CH2CO2Me), both involving P-C bond formation, depending on the reaction conditions. New complexes having iridacyclophosphapentenone and iridacyclophosphapentanone moieties result from reactions of 2 with dimethyl acetylenedicarboxylate and dimethyl maleate, respectively, as a consequence of a further incorporation of the carbonyl ligand. In this line, the terminal alkyne methyl propiolate gave a mixture of a similar iridacyclophosphapentanone complex and [Ir(ABPN2){CH═C(CO2Me)-CO}{PPh2-CH═CH(CO2Me)}] (10), which bears the functionalized phosphane PPh2-CH═CH(CO2Me) and an iridacyclobutenone fragment. Related model reactions aimed to confirm mechanistic proposals are also studied. PMID:26695592

  12. Intramolecular energy transfer in fullerene pyrazine dyads

    SciTech Connect

    Guldi, D.M.; Torres-Garcia, G.; Mattay, J.

    1998-11-26

    Excited-state properties of three different pyrazine derivatives 4--6 were probed by emission and transient absorption spectroscopy. They display emission maxima at 464 (4), 417 (5), and 515 nm (6) that are red-shifted with respect to their strong UV ground-state absorption and formed with overall quantum yields ({Phi}) of 0.156, 0.22, and 0.13, respectively. Once photoexcited, these triplet excited pyrazines undergo rapid intermolecular energy transfer to a monofunctionalized fullerene derivative (7) with bimolecular rate constants ranging from 3.64 {times} 10{sup 9} M{sup {minus}1} s{sup {minus}1} (6) to 1.1 {times} 10{sup 10} M{sup {minus}1} s{sup {minus}1} (4). The product of these bimolecular energy-transfer reactions is in all cases the fullerene triplet excited state. Functionalization of pristine C{sub 60} with the investigated pyrazine derivatives promotes the UV-vis absorption characteristics and, in turn, improves the light-harvesting efficiency of the resulting dyads 1--3 relative to pristine C{sub 60}. Photoexcitation of the pyrazine moieties in dyads 1--3 leads to the formation of their singlet excited states. In contrast to the pyrazine models, photoexcitation of dyad 1--3 is followed by rapid intramolecular deactivation processes of the latter via energy transfer to the fullerene ground state with half-lives between 37 and 100 ps. In turn, energy transfer transforms the short-lived and moderately redox-active singlet excited states of pyrazine into the highly reactive fullerene triplet excited state. The latter is found to produce effectively singlet oxygen ({sup 1}O{sub 2}) with quenching rate constants for 1--3 of (1--1.5) {times} 10{sup 9} M{sup {minus}1} s{sup {minus}1}. Similarly, reductive quenching of the triplet excited states in dyads 1--3 via electron transfer with diazabicyclooctane (DABCO) occurs with rate constants of 5.2--9.4 {times} 10{sup 7} M{sup {minus}1} s{sup {minus}1}.

  13. REVISITING CLASSICAL NUCLEOPHILIC SUBSTITUTIONS IN AQUEOUS MEDIUM: MICROWAVE-ASSISTED SYNTHESIS OF ALKYL AZIDES

    EPA Science Inventory

    An efficient and clean synthesis of alkyl azides using microwave (MW) radiation is described in aqueous medium by reacting alkyl halides or tosylates with alkali azides. This general and expeditious MW-enhanced approach to nucleophilic substitution reactions is applicable to the ...

  14. Organic Chemistry Students' Ideas about Nucleophiles and Electrophiles: The Role of Charges and Mechanisms

    ERIC Educational Resources Information Center

    Anzovino, Mary E.; Bretz, Stacey Lowery

    2015-01-01

    Organic chemistry students struggle with reaction mechanisms and the electron-pushing formalism (EPF) used by practicing organic chemists. Faculty have identified an understanding of nucleophiles and electrophiles as one conceptual prerequisite to mastery of the EPF, but little is known about organic chemistry students' knowledge of nucleophiles…

  15. Reactions of heteroatom and carbon nucleophiles with the cationic bridging methylidyne complex

    SciTech Connect

    Casey, C.P.; Crocker, M.; Vosejpka, P.C.; Fagan, P.J.; Marder, S.R.; Gohdes, M.A.

    1988-03-01

    The reaction of the ..mu..-methylidyne complex /((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CO)(..mu..-CH)//sup +/PF/sub 6//sup -/ (1) with NMe/sub 3/ and (C/sub 6/H/sub 5/)/sub 2/C=NH gave the cationic 1:1 adducts /((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CO)(..mu..-CHNMe/sub 3/)//sup +/PF/sub 6//sup -/ (3) and /((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CHNH=C(C/sub 6/H/sub 5/)/sub 2/)//sup +/PF/sub 6//sup -/ (9), respectively, arising from attack of nitrogen on the methylidyne carbon. The reaction of 1 with KOC(CH/sub 3/)/sub 3/ gave the neutral ..mu..-carbene complex ((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CO)(..mu..-CHOC(CH/sub 3/)P/sub 3/) (4). Reaction of 1 with water afforded a 1:1 mixture of ..mu..methylene complex ((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CO)(..mu..-CH/sub 2/) (2) and ((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CO)/sub 2/; these products are proposed to arise from disproportionation of an initially formed hydroxy carbene species. Reaction of 1 with Et/sub 4/N/sup +/Br/sup -/ gave the unstable /sup +/-carbene complex ((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CO)(..mu..-CHBr) (6). Reaction of 1 with the carbon nucleophiles CH/sub 3/Li and Li(C/sub 6/H/sub 5/CuCN) gave the ..mu..-carbene complexes ((C/sub 5/H/sub 5/)(CO)Fe/sub 2/(..mu..-CO)(..mu..-CHCH/sub 3/) (11) and ((C/sub 5/H/sub 5/)(CO)Fe)/sub 2/(..mu..-CO)(..mu..-CHC/sub 6/H/sub 5/ (12), while reaction of 1 with HFe(CO)/sub 4//sup -/ afforded 2. 1 reacted with acetone via nucleophilic addition of the enol affording the neutral ..mu..-carbene complex (C/sub 5/H/sub 5/)-(CO)Fe)/sub 2/(..mu..-CO)(..mu..-CHCH/sub 2/COCH/sub 3/)) (13). 1 also reacted with cyclohexanone, 2-butanone, 4-methyl-2-pentanone, 2,4-pentanedione, 5,5-dimethyl-1,3-cyclohexanedione, ethyl acetoacetate, and the sodium salt of diethyl malonate to give similar ..mu..-carbene products.

  16. Metal-Free Visible Light-Mediated Photocatalysis: Controlling Intramolecular [2 + 2] Photocycloaddition of Enones through Axial Chirality.

    PubMed

    Clay, Anthony; Vallavoju, Nandini; Krishnan, Retheesh; Ugrinov, Angel; Sivaguru, Jayaraman

    2016-08-19

    Atropisomeric enone-imides and enone-amides featuring N-CAryl bond rotation were evaluated for intramolecular [2 + 2] photocycloaddition. Straight addition product was observed over cross-addition product with good control over reactivity. The atropselectivity was found to be dependent on the substituent on the aryl ring. Substitution-dependent atropselectivity was rationalized on the basis of a divergent mechanistic pathway. PMID:27382920

  17. Reaction of perfluoro-2-methylpent-2-ene with oxygen nucleophiles

    SciTech Connect

    Snegirev, V.F.; Makarov, K.N.

    1986-07-10

    Perfluoro-2-methyl-2-pentene reacts with alcohols to give either fluorine substitution products or addition products, depending on the amount of basic catalyst which is used. Alcohols containing branched substituents give another product in addition to those derived from substitution of a vinyl fluorine atom in perfluoro-2-methyl-2-pentene, namely isomeric vinyl ethers which are derivatives of perfluoro-2-methyl-1-pentene. Dehydrofluorination of the addition products, namely 2-hydro-3-alkoxyperfluoropentanes, leads in high yields to fluorine-containing allyl ethers containing terminal double bonds.

  18. Cyclic Triradicals Composed of Iminonitroxide-Gold(I) with Intramolecular Ferromagnetic Interactions.

    PubMed

    Suzuki, Shuich; Wada, Tomoyuki; Tanimoto, Ryu; Kozaki, Masatoshi; Shiomi, Daisuke; Sugisaki, Kenji; Sato, Kazunobu; Takui, Takeji; Miyake, Yota; Hosokoshi, Yuko; Okada, Keiji

    2016-08-26

    A triangular gold(iminonitroxide-2-ide) trimer complex (5) was prepared and investigated to determine its magnetic properties. The results showed that the metalloid triradical is highly stable, even in solution under aerated conditions. The intramolecular exchange interaction of 5 was found to be positive (Jintra /kB ≈+29 K), thus showing that 5 is in a quartet ground state. In addition, a silver sandwich complex (5-Ag(+) -5) was prepared and its electronic and magnetic properties were also clarified. PMID:27490798

  19. An intramolecular charge transfer fluorescent probe: Synthesis and selective fluorescent sensing of Ag +

    NASA Astrophysics Data System (ADS)

    Mu, Honglei; Gong, Rui; Ren, Lin; Zhong, Cheng; Sun, Yimin; Fu, Enqin

    2008-09-01

    An intramolecular charge transfer (ICT) fluorescent probe, in which the thiourea derivative moiety is linked to the fluorescent 4-(dimethylamino) benzamide, has been designed and synthesized. The ions-selective signaling behaviors of the probe were investigated. Upon the addition of Ag +, an overall emission enhancement of 14-fold was observed. Compound 1 displayed highly selective chelation enhanced fluorescence (CHEF) effect with Ag + over alkali, alkali earth metal ions and some transition metal ions in aqueous methanol solutions. The prominent selective and efficient fluorescent enhancing behavior could be utilized as a new chemosensing probe for the analysis of Ag + ion in aqueous environment.

  20. Investigations of acidity and nucleophilicity of diphenyldithiophosphinate ligands using theory and gas-phase dissociation reactions

    SciTech Connect

    Christopher M. Leavitt; Garold L. Gresham; Michael T. Benson; Jean-Jaques Gaumet; Dean Peterman; John Klaehn; Megan Moser; Frederic Aubriet; Michael J. Van Stipdonk; Gary S. Groenewold

    2008-04-01

    Diphenyldithiophosphinate (DTP) ligands modified with electron-withdrawing trifluoromethyl (TFM) substitutents are of high interest because they have demonstrated potential for exceptional separation of Am3+ from lanthanide3+ cations. Specifically, the bis(ortho-TFM) (L1-) and (ortho-TFM)(meta-TFM) (L2-) derivatives have shown excellent separation selectivity, while the bis(meta-TFM) (L3)- and unmodified DTP (Lu-) did not. Factors responsible for selective coordination have been investigated using density functional theory (DFT) calculations in concert with competitive dissociation reactions in the gas phase. To evaluate the role of (DTP+H) acidity, density functional calculations were used to predict pKa values, which followed the trend of L3 < L2 < L1 < Lu. The order of the TFM-modified (DTP+H) acids was opposite of what would be expected based on the e--withdrawing effects of the TFM group, suggesting that secondary factors are influencing the pKa and nucleophilicity. The relative nucleophilicities of the DTP anions were evaluated by forming metal-mixed ligand complexes in a trapped ion mass spectrometer, and then fragmenting them using competitive collision induced dissociation. Relative to Na+, the unmodified Lu- anion was the strongest nucleophile. Comparing the TFM derivatives, the bis(ortho-TFM) derivative L1- was found to be the strongest nucleophile, while the bis(meta-TFM) L3- was the weakest, a trend consistent with the pKa calculations. DFT modeling of the Na+ complexes suggested that the elevated cation affinity of the L1- and L2- anions was due to donation of electron density from fluorine atoms to the metal center, which was occurring in rotational conformers where the TFM moiety was proximate to the Na+-dithiophosphinate group. Competitive dissociation experiments were performed with the dithiophosphinate anions complexed with europium nitrate species; ionic dissociation of these complexes always produced the TFM-modified dithiophosphinate anions

  1. Regio- and Stereoselective 1,2-Dihydropyridine Alkylation/Addition Sequence for the Synthesis of Piperidines with Quaternary Centers**

    PubMed Central

    Duttwyler, Simon; Chen, Shuming; Lu, Colin; Mercado, Brandon Q.; Bergman, Robert G.; Ellman, Jonathan A.

    2014-01-01

    The first example of C-alkylation of 1,2-dihydropyridines with alkyl triflates and Michael acceptors was developed to introduce quaternary carbon centers with high regio- and diastereoselectivity. Hydride or carbon nucleophile addition to the resultant iminium ion also proceeded with high diastereoselectivity. Carbon nucleophile addition results in an unprecedented level of substitution to provide piperidine rings with adjacent tetrasubstituted carbons. PMID:24604837

  2. Exploration of zeroth-order wavefunctions and energies as a first step toward intramolecular symmetry-adapted perturbation theory

    NASA Astrophysics Data System (ADS)

    Gonthier, Jérôme F.; Corminboeuf, Clémence

    2014-04-01

    Non-covalent interactions occur between and within all molecules and have a profound impact on structural and electronic phenomena in chemistry, biology, and material science. Understanding the nature of inter- and intramolecular interactions is essential not only for establishing the relation between structure and properties, but also for facilitating the rational design of molecules with targeted properties. These objectives have motivated the development of theoretical schemes decomposing intermolecular interactions into physically meaningful terms. Among the various existing energy decomposition schemes, Symmetry-Adapted Perturbation Theory (SAPT) is one of the most successful as it naturally decomposes the interaction energy into physical and intuitive terms. Unfortunately, analogous approaches for intramolecular energies are theoretically highly challenging and virtually nonexistent. Here, we introduce a zeroth-order wavefunction and energy, which represent the first step toward the development of an intramolecular variant of the SAPT formalism. The proposed energy expression is based on the Chemical Hamiltonian Approach (CHA), which relies upon an asymmetric interpretation of the electronic integrals. The orbitals are optimized with a non-hermitian Fock matrix based on two variants: one using orbitals strictly localized on individual fragments and the other using canonical (delocalized) orbitals. The zeroth-order wavefunction and energy expression are validated on a series of prototypical systems. The computed intramolecular interaction energies demonstrate that our approach combining the CHA with strictly localized orbitals achieves reasonable interaction energies and basis set dependence in addition to producing intuitive energy trends. Our zeroth-order wavefunction is the primary step fundamental to the derivation of any perturbation theory correction, which has the potential to truly transform our understanding and quantification of non

  3. Exploration of zeroth-order wavefunctions and energies as a first step toward intramolecular symmetry-adapted perturbation theory

    SciTech Connect

    Gonthier, Jérôme F.; Corminboeuf, Clémence

    2014-04-21

    Non-covalent interactions occur between and within all molecules and have a profound impact on structural and electronic phenomena in chemistry, biology, and material science. Understanding the nature of inter- and intramolecular interactions is essential not only for establishing the relation between structure and properties, but also for facilitating the rational design of molecules with targeted properties. These objectives have motivated the development of theoretical schemes decomposing intermolecular interactions into physically meaningful terms. Among the various existing energy decomposition schemes, Symmetry-Adapted Perturbation Theory (SAPT) is one of the most successful as it naturally decomposes the interaction energy into physical and intuitive terms. Unfortunately, analogous approaches for intramolecular energies are theoretically highly challenging and virtually nonexistent. Here, we introduce a zeroth-order wavefunction and energy, which represent the first step toward the development of an intramolecular variant of the SAPT formalism. The proposed energy expression is based on the Chemical Hamiltonian Approach (CHA), which relies upon an asymmetric interpretation of the electronic integrals. The orbitals are optimized with a non-hermitian Fock matrix based on two variants: one using orbitals strictly localized on individual fragments and the other using canonical (delocalized) orbitals. The zeroth-order wavefunction and energy expression are validated on a series of prototypical systems. The computed intramolecular interaction energies demonstrate that our approach combining the CHA with strictly localized orbitals achieves reasonable interaction energies and basis set dependence in addition to producing intuitive energy trends. Our zeroth-order wavefunction is the primary step fundamental to the derivation of any perturbation theory correction, which has the potential to truly transform our understanding and quantification of non

  4. Chemoselective Boron-Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich-Type Reactions.

    PubMed

    Morita, Yuya; Yamamoto, Tomohiro; Nagai, Hideoki; Shimizu, Yohei; Kanai, Motomu

    2015-06-10

    The carboxyl group (COOH) is an omnipresent functional group in organic molecules, and its direct catalytic activation represents an attractive synthetic method. Herein, we describe the first example of a direct catalytic nucleophilic activation of carboxylic acids with BH3·SMe2, after which the acids are able to act as carbon nucleophiles, i.e. enolates, in Mannich-type reactions. This reaction proceeds with a mild organic base (DBU) and exhibits high levels of functional group tolerance. The boron catalyst is highly chemoselective toward the COOH group, even in the presence of other carbonyl moieties, such as amides, esters, or ketones. Furthermore, this catalytic method can be extended to highly enantioselective Mannich-type reactions by using a (R)-3,3'-I2-BINOL-substituted boron catalyst. PMID:26011419

  5. Automated electrophilic radiosynthesis of [¹⁸F]FBPA using a modified nucleophilic GE TRACERlab FXFDG.

    PubMed

    Mairinger, Severin; Stanek, Johann; Wanek, Thomas; Langer, Oliver; Kuntner, Claudia

    2015-10-01

    We modified a commercially available synthesis module for nucleophilic [(18)F]fluorinations (TRACERlab(TM) FXFDG, GE Healthcare) to enable the reliable synthesis of 2-[(18)F]fluoro-4-borono-L-phenylalanine ([(18)F]FBPA) via direct electrophilic substitution of 4-borono-L-phenylalanine with [(18)F]F2 gas. [(18)F]FBPA was obtained with a RCY of 8.5±2.0% and a radiochemical purity of 98±1% in a total synthesis time of 72±7 min (n=22). The modified synthesis module might also be useful for the synthesis of other [(18)F]radiopharmaceuticals via electrophilic substitution reactions while still being suitable for nucleophilic substitution reactions. PMID:26159661

  6. From carbanions to organometallic compounds: quantification of metal ion effects on nucleophilic reactivities.

    PubMed

    Corral-Bautista, Francisco; Klier, Lydia; Knochel, Paul; Mayr, Herbert

    2015-10-12

    The influence of the metal on the nucleophilic reactivities of indenyl metal compounds was quantitatively determined by kinetic investigations of their reactions with benzhydrylium ions (Ar2 CH(+) ) and structurally related quinone methides. With the correlation equation log k2 =sN (N+E), it can be derived that the ionic indenyl alkali compounds are 10(18) to 10(24) times more reactive (depending on the reference electrophile) than the corresponding indenyltrimethylsilane. PMID:25951612

  7. Transition-Metal-Free Stereospecific Cross-Coupling with Alkenylboronic Acids as Nucleophiles.

    PubMed

    Li, Chengxi; Zhang, Yuanyuan; Sun, Qi; Gu, Tongnian; Peng, Henian; Tang, Wenjun

    2016-08-31

    We herein report a transition-metal-free cross-coupling between secondary alkyl halides/mesylates and aryl/alkenylboronic acid, providing expedited access to a series of nonchiral/chiral coupling products in moderate to good yields. Stereospecific SN2-type coupling is developed for the first time with alkenylboronic acids as pure nucleophiles, offering an attractive alternative to the stereospecific transition-metal-catalyzed C(sp(2))-C(sp(3)) cross-coupling. PMID:27515390

  8. A diastereoselective, nucleophile-promoted aldol-lactonization of ketoacids leading to bicyclic-β-lactones.

    PubMed

    Liu, Gang; Shirley, Morgan E; Romo, Daniel

    2012-03-01

    An improved, tandem acid activation/aldol-lactonization process is described. This more practical protocol shortens reaction times for the construction of bicyclic β-lactones from ketoacids and implements the use of commercially available reagents p-toluenesulfonyl chloride (p-TsCl) as activator and 4-dimethylaminopyridine (4-DMAP) as nucleophilic promoter (Lewis base). Substrates with β-substituents, with respect to the carboxylic acid, consistently showed excellent levels of diastereoselectivity during the bis-cyclization event. PMID:22260519

  9. Control of Diastereoselectivity for Iridium-catalyzed Allylation of a Prochiral Nucleophile with a Phosphate Counterion

    PubMed Central

    Chen, Wenyong; Hartwig, John F.

    2013-01-01

    We report a highly diastereo- and enantioselective allylation of azlactones catalyzed by the combination of a metallayclic iridium complex and an optically inactive phosphate anion. The process demonstrates an approach to conduct diastereoselective reactions with prochiral nucleophiles in the presence of metallacyclic allyliridium complexes. The reaction provides access to an array of enantioenriched allylated azlactones containing adjacent tertiary and quaternary carbon centers. Preliminary mechanistic studies suggest that the phosphate and methyl carbonate anions together induce the unusually high diastereoselectivity. PMID:23286279

  10. Catalytic Chemo- and Regioselective Coupling of 1,3-Dicarbonyls with N-Heterocyclic Nucleophiles.

    PubMed

    Kenny, Miles; Kitson, Daniel J; Franckevičius, Vilius

    2016-06-17

    The development of a decarboxylative palladium-catalyzed coupling of 1,3-dicarbonyl compounds with indole, pyrrole, imidazole, and pyrazole nucleophiles via an allylic linker under neutral conditions is disclosed. This process enables the installation of an all-carbon quaternary center and new C-C and C-N bonds in a single operation. Despite the weakly acidic nature of N-heterocycles, the reactions proceed with good efficiency and complete regio- and chemoselectivity. PMID:27211875

  11. Nucleophilic reactivity and electrocatalytic reduction of halogenated organic compounds by nickel o-phenylenedioxamidate complexes.

    PubMed

    Das, Siva Prasad; Ganguly, Rakesh; Li, Yongxin; Soo, Han Sen

    2016-09-14

    A growing number of halogenated organic compounds have been identified as hazardous pollutants. Although numerous advanced oxidative processes have been developed to degrade organohalide compounds, reductive and nucleophilic molecular approaches to dehalogenate organic compounds have rarely been reported. In this manuscript, we employ nickel(ii)-ate complexes bearing the o-phenylenebis(N-methyloxamide) (Me2opba) tetraanionic ligand as nucleophilic reagents that can react with alkyl halides (methyl up to the bulky isobutyl) by O-alkylation to give their respective imidate products. Four new nickel(ii) complexes have been characterized by X-ray crystallography, and the salient structural parameters and FT-IR vibrational bands (∼1655 cm(-1)) concur with their assignment as the imidate tautomeric form. To the best of our knowledge, this is the first report on the nucleophilic reactivity of Ni(II)(Me2opba) with halogenated organic compounds. The parent nickel(ii) Me2opba complex exhibits reversible electrochemical oxidation and reduction behavior. As a proof of concept, Ni(II)(Me2opba) and its alkylated congeners were utilized for the electrocatalytic reduction of chloroform, as a representative, simple polyhalogenated organic molecule that could arise from the oxidative treatment of organic compounds by chlorination. Modest turnover numbers of up to 6 were recorded, with dichloromethane identified as one of the possible products. Future efforts are directed towards bulkier -ate complexes that possess metal-centered instead of ligand-centered nucleophilic activity to create more effective electrocatalysts for the reduction of halogenated organic compounds. PMID:27506275

  12. Novel nucleophiles enhance the human serum paraoxonase 1 (PON1)-mediated detoxication of organophosphates.

    PubMed

    Chambers, Janice E; Chambers, Howard W; Meek, Edward C; Funck, Kristen E; Bhavaraju, Manikanthan H; Gwaltney, Steven R; Pringle, Ronald B

    2015-01-01

    Paraoxonase 1 (PON1) is a calcium-dependent hydrolase associated with serum high-density lipoprotein particles. PON1 hydrolyzes some organophosphates (OPs), including some nerve agents, through nucleophilic attack of hydroxide ion (from water) in the active site. Most OPs are hydrolyzed inefficiently. This project seeks to identify nucleophiles that can enhance PON1-mediated OP degradation. A series of novel nucleophiles, substituted phenoxyalkyl pyridinium oximes, has been synthesized which enhance the degradation of surrogates of sarin (nitrophenyl isopropyl methylphosphonate; NIMP) and VX (nitrophenyl ethyl methylphosphonate; NEMP). Two types of in vitro assays have been conducted, a direct assay using millimolar concentrations of substrate with direct spectrophotometric quantitation of a hydrolysis product (4-nitrophenol) and an indirect assay using submicromolar concentrations of substrate with quantitation by the level of inhibition of an exogenous source of acetylcholinesterase from non-hydrolyzed substrate. Neither NIMP nor NEMP is hydrolyzed effectively by PON1 if one of these novel oximes is absent. However, in the presence of eight novel oximes, PON1-mediated degradation of both surrogates occurs. Computational modeling has created a model of PON1 embedded in phospholipid and has indicated general agreement of the binding enthalpies with the relative efficacy as PON1 enhancers. PON1 enhancement of degradation of OPs could be a unique and unprecedented mechanism of antidotal action. PMID:25304213

  13. Detoxication of sulfur half-mustards by nucleophilic scavengers: robust activity of thiopurines.

    PubMed

    Liu, Jinyun; Powell, K Leslie; Thames, Howard D; MacLeod, Michael C

    2010-03-15

    Sulfur mustard (bis-(2-chloroethyl)sulfide) has been used in chemical warfare since World War I and is well known as an acutely toxic vesicant. It has been implicated as a carcinogen after chronic low-level exposure and is known to form interstrand cross-links in DNA. Sulfur and nitrogen mustards are currently of interest as potential chemical threat agents for terrorists because of ease of synthesis. Sulfur mustard and monofunctional analogues (half-mustards, 2-[chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular macromolecules, and thus are potentially subject to scavenging by nucleophilic agents. We have determined rate constants for the reaction of four purine derivatives that contain nucleophilic thiol moieties with several sulfur-half-mustards. Three of these compounds, 2,6-dithiopurine, 2,6-dithiouric acid, and 9-methyl-6-mercaptopurine, exhibit facile reaction with the electrophilic mustard compounds. At near neutral pH, these thiopurines are much better nucleophilic scavengers of mustard electrophiles than other low molecular weight thiols such as N-acetyl cysteine and glutathione. Progress curves calculated by numerical integration techniques indicate that equimolar concentrations of thiopurine provide significant reductions in the overall exposure to the episulfonium ions, which are the major reactive, electrophiles produced when sulfur mustards are dissolved in aqueous solution. PMID:20050632

  14. Hydrogen-bond promoted nucleophilic fluorination: concept, mechanism and applications in positron emission tomography.

    PubMed

    Lee, Ji-Woong; Oliveira, Maria Teresa; Jang, Hyeong Bin; Lee, Sungyul; Chi, Dae Yoon; Kim, Dong Wook; Song, Choong Eui

    2016-08-22

    Due to the tremendous interest in carbon-fluorine bond-forming reactions, research efforts in this area have been dedicated to the development of facile processes to synthesize small fluorine-containing organic molecules. Among others, PET (Positron Emission Tomography) is one of the most important applications of fluorine chemistry. Recognizing the specific requirements of PET processes, some groups have focused on fluorination reactions using alkali metal fluorides, particularly through SN2-type reactions. However, a common "misconception" about the role of protic solvents and hydrogen bonding interactions in this class of reactions has hampered the employment of these excellent promoters. Herein, we would like to review recent discoveries in this context, showing straightforward nucleophilic fluorination reactions using alkali metal fluorides promoted by protic solvents. Simultaneous dual activation of reacting partners by intermolecular hydrogen bonding and the enhancement of the "effective fluoride nucleophilicity", which is Nature's biocatalytic approach with the fluorinase enzyme, are the key to this unprecedentedly successful nucleophilic fluorination. PMID:27264160

  15. Copper-catalyzed P-arylation via direct coupling of diaryliodonium salts with phosphorus nucleophiles at room temperature.

    PubMed

    Xu, Jian; Zhang, Pengbo; Gao, Yuzhen; Chen, Yiyin; Tang, Guo; Zhao, Yufen

    2013-08-16

    A new method for copper-catalyzed P-C bond formation through reaction of phosphorus nucleophiles with diaryliodonium salts at room temperature is described. Most target products are obtained with this method in high yields within a short reaction time of 10 min. It can be easily adapted to large-scale preparations. When unsymmetrical iodonium salts are employed, nucleophilic substitution occurs preferentially on the sterically hindered aromatic ring or the more electron-deficient ring. PMID:23865378

  16. Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α-Fluorination of Ketenes: Synthetic and Mechanistic Studies

    PubMed Central

    2015-01-01

    The catalytic asymmetric synthesis of alkyl fluorides, particularly α-fluorocarbonyl compounds, has been the focus of substantial effort in recent years. While significant progress has been described in the formation of enantioenriched secondary alkyl fluorides, advances in the generation of tertiary alkyl fluorides have been more limited. Here, we describe a method for the catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C6F5ONa to furnish tertiary α-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C6F5ONa) is critical for turnover, releasing the catalyst (PPY*) from an N-acylated intermediate. The available data can be explained by a reaction pathway wherein the enantioselectivity is determined in the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived from the addition of PPY* to the ketene. The structure and the reactivity of the product of this proposed elementary step, an α-fluoro-N-acylpyridinium salt, have been examined. PMID:24922581

  17. Nucleophilic reactions at a vinylic center. XVI. Investigation of the nucleophilic exchange of fluorine in. beta. -fluoroacrylonitriles by the MINDO/3 method

    SciTech Connect

    Shainyan, B.A.

    1986-01-10

    The potential energy surfaces of the reactions of F/sup -/ with cis- and trans-..beta..-fluoroacrylonitriles were calculated by the MINDO/3 method. It was shown that three reaction paths can be realized in the system, i.e., attack by the nucleophile at the ..beta..-carbon atom, the elimination of a proton from the ..cap alpha.. position, and the elimination of a proton from the ..beta.. position. All three reaction paths are exothermic in the gas phase, and the elimination of the proton from the ..cap alpha.. position is 70 kJ/mole more favorable than from the ..beta.. position. Allowance for the effect of the medium in terms of an unconcerted solvation model modes not lead to the appearance of an activation barrier, in contrast to the reactions of anions with ethylene.

  18. Oligo(p-phenylene-ethynylene)s with backbone conformation controlled by competitive intramolecular hydrogen bonds.

    PubMed

    Hu, Wei; Yan, Qifan; Zhao, Dahui

    2011-06-14

    A series of conjugated oligo(p-phenylene-ethynylene) (OPE) molecules with backbone conformations (that is, the relative orientations of the contained phenylene units) controlled by competitive intramolecular hydrogen bonds to be either co-planar or random were synthesised and studied. In these oligomers, carboxylate and amido substituents were attached to alternate phenylene units in the OPE backbone. These functional groups were able to form intramolecular hydrogen bonds between neighbouring phenylene units. Thereby, all phenylene units in the backbone were confined in a co-planar conformation. This planarised structure featured a more extended effective conjugation length than that of regular OPEs with phenylene units adopting random orientation due to a low rotational-energy barrier. However, if a tri(ethylene glycol) (Tg) side chain was appended to the amido group, it enabled another type of intramolecular hydrogen bond, formed by the Tg chain folding back and the contained ether oxygen atom competing with the ester carbonyl group as the hydrogen-bond acceptor. The outcome of this competition was proven to depend on the length of the alkylene linker joining the ether oxygen atom to the amido group. Specifically, if the Tg chain folded back to form a five-membered cyclic structure, this hydrogen-bonding motif was sufficiently robust to overrule the hydrogen bonds between adjacent phenylene units. Consequently, the oligomers assumed non-planar conformations. However, if the side chain formed a six-membered ring by hydrogen bonding with the amido NH group, such a motif was much less stable and yielded in the competition with the ester carbonyl group from the adjacent phenylene unit. Thus, the hydrogen bonds between the phenylene units remained, and the co-planar conformation was manifested. In our system, the hydrogen bonds formed by the back-folded Tg chain and amido NH group relied on a single oxygen atom as the hydrogen-bond acceptor. The additional oxygen

  19. Intramolecular amide bonds stabilize pili on the surface of bacilli

    SciTech Connect

    Budzik, Jonathan M.; Poor, Catherine B.; Faull, Kym F.; Whitelegge, Julian P.; He, Chuan; Schneewind, Olaf

    2010-01-12

    Gram-positive bacteria elaborate pili and do so without the participation of folding chaperones or disulfide bond catalysts. Sortases, enzymes that cut pilin precursors, form covalent bonds that link pilin subunits and assemble pili on the bacterial surface. We determined the x-ray structure of BcpA, the major pilin subunit of Bacillus cereus. The BcpA precursor encompasses 2 Ig folds (CNA{sub 2} and CNA{sub 3}) and one jelly-roll domain (XNA) each of which synthesizes a single intramolecular amide bond. A fourth amide bond, derived from the Ig fold of CNA{sub 1}, is formed only after pilin subunits have been incorporated into pili. We report that the domains of pilin precursors have evolved to synthesize a discrete sequence of intramolecular amide bonds, thereby conferring structural stability and protease resistance to pili.

  20. Intramolecular interaction and dynamics of the cationic argon trimer

    SciTech Connect

    Ragnetti, F.; Zuhrt, C.; Zuelicke, L.

    1996-12-31

    For the simplest cationic argon cluster, Ar{sub 3}{sup +}, the topographical characteristics of the ground-state potential energy surface (PES), the mode coupling and the claswsical intramolecular dynamics are studied; PES data have been obtained by the diatomics-in-molecules approach of Kuntz et al. The results show that Ar{sub 3}{sup +} s a rather floppy system with rapid vibrational energy redistribution and early onset of classical chaos.

  1. Intramolecular vibrational dephasing obeys a power law at intermediate times

    PubMed Central

    Gruebele, M.

    1998-01-01

    Experimental intramolecular vibrational dephasing transients for several large organic molecules are reanalyzed. Fits to the experimental data, as well as full numerical quantum calculations with a factorized potential surface for all active degrees of freedom of fluorene indicate that power law decays, not exponentials, occur at intermediate times. The results support a proposal that power law decays describe vibrational dephasing dynamics in large molecules at intermediate times because of the local nature of energy flow. PMID:9600900

  2. Mechanism of intramolecular transformations of nickel phosphanido hydride complexes.

    PubMed

    Latypov, Shamil K; Polyancev, Fedor M; Ganushevich, Yulia S; Miluykov, Vasily A; Sinyashin, Oleg G

    2016-02-01

    In solution, nickel phosphanido hydride complexes ([NiH{P(Ar)(H)}(dtbpe)], Ar = Dmp, Mes*) undergo a degenerate intramolecular exchange, with the Ni-H and P-H hydrogens and both halves of the dtbpe moiety interchanging. This intramolecular rearrangement was shown to occur in three steps: first, the hydride proton migrates to phosphorus, then the P-Aryl moiety rotates around the P-Ni bond, and finally the back migration of one proton to Ni completes the process. Both migration and rotation were determined to be characterized by high barriers (on the NMR time scale) and to depend on the type of aryl group at the terminal phosphorus. Compared to that observed for the Ni complexes, the same isomeric preference, but with a slower rate of intramolecular rearrangement, is predicted for the corresponding Pt complexes. An opposite isomeric preference, however, is expected for the corresponding Pd complexes. Thus, it is likely that some of the catalytic reactions of Pd and Pt complexes are driven by the relative thermodynamic stabilities of their main forms. PMID:26407302

  3. Dynamic Kinetic Resolution Enabled by Intramolecular Benzoin Reaction: Synthetic Applications and Mechanistic Insights.

    PubMed

    Zhang, Guoxiang; Yang, Shuang; Zhang, Xiaoyan; Lin, Qiqiao; Das, Deb K; Liu, Jian; Fang, Xinqiang

    2016-06-29

    The highly enantio-, diastereo-, and regioselective dynamic kinetic resolution of β-ketoesters and 1,3-diketones was achieved via a chiral N-heterocyclic carbene catalyzed intramolecular cross-benzoin reaction. A variety of tetralone derivatives bearing two contiguous stereocenters and multiple functionalities were liberated in moderate to excellent yields and with high levels of stereoselectivity (>95% ee and >20:1 dr in most cases). In addition, the excellent regioselectivity control for aryl/alkyl 1,3-diketones, and the superior electronic differentiation of 1,3-diarylketones were highlighted. Moreover, a set of new mechanistic rationale that differs with the currently widely accepted understanding of intramolecular benzoin reactions was established to demonstrate the superior preference of benzoin over aldol transformation: (1) A coexistence of competitive aldol and benzoin reactions was detected, but a retro-aldol-irreversible benzoin process performs a vital role in the generation of predominant benzoin products. (2) The most essential role of an N-electron-withdrawing substituent in triazolium catalysts was revealed to be accelerating the rate of the benzoin transformation, rather than suppressing the aldol process through reducing the inherent basicity of the catalyst. PMID:27270409

  4. Intra-molecular Triplet Energy Transfer is a General Approach to Improve Organic Fluorophore Photostability

    PubMed Central

    Zheng, Qinsi; Jockusch, Steffen; Rodríguez-Calero, Gabriel G.; Zhou, Zhou; Zhao, Hong; Altman, Roger B.; Abruña, Héctor D.; Blanchard, Scott C.

    2015-01-01

    Bright, long-lasting and non-phototoxic organic fluorophores are essential to the continued advancement of biological imaging. Traditional approaches towards achieving photostability, such as the removal of molecular oxygen and the use of small-molecule additives in solution, suffer from potentially toxic side effects, particularly in the context of living cells. The direct conjugation of small-molecule triplet state quenchers, such as cyclooctatetraene (COT), to organic fluorophores has the potential to bypass these issues by restoring reactive fluorophore triplet states to the ground state through intra-molecular triplet energy transfer. Such methods have enabled marked improvement in cyanine fluorophore photostability spanning the visible spectrum. However, the generality of this strategy to chemically and structurally diverse fluorophore species has yet to be examined. Here, we show that the proximal linkage of COT increases the photon yield of a diverse range of organic fluorophores widely used in biological imaging applications, demonstrating that the intra-molecular triplet energy transfer mechanism is a potentially general approach for improving organic fluorophore performance and photostability. PMID:26700693

  5. Multiwall nanotubes with intramolecular junctions (CNx/C): Preparation, rectification, logic gates, and application

    NASA Astrophysics Data System (ADS)

    Hu, Ping'an; Xiao, Kai; Liu, Yunqi; Yu, Gui; Wang, Xianbao; Fu, Lei; Cui, Guanglei; Zhu, Daoben

    2004-06-01

    We prepared a large quantity of multiwall nanotubes with intramolecular junctions (CNx/C) by pyrolysis of iron phthalocyanine with or without an inlet of ammonia gas. The nanotubes consist of two sections, one section made of carbon nitride featuring bamboo-like structure and the other one made of carbon featuring empty hollow cylinder structure, and thus the intramolecular junctions were formed in the middle as a result of being doped or undoped with nitrogen. Nanodiode based on a single CNx/C junction shows reproducible rectifying behavior with a rectification ratio of 1.3×103 at ±2 V. In addition, the nanodiode demonstrated as a half-wave rectifier worked at an input sine wave of 1 kHz. Two CNx/C junctions were configured together to exhibit functions of OR and AND logic gates. Moreover, after substituting the wave-detection silicon diode in common transistor radio set with our nanodiode, the radio set still worked normally, representing an important step toward the potential application for nano-scale devices.

  6. Characteristics of Intramolecular Charge Transfer by J-Aggregates in Merocyanine Dye LB Films.

    PubMed

    Yang, Chang Heon; Kwon, Young-Soo; Shin, Hoon-Kyu

    2016-06-01

    In this study, for the development of future molecular electronic devices, we have investigated the characteristics of the aggregates of Langmuir-Blodgett films. The characteristics of intramolecular charge transfer by J-aggregates in merocyanine dye LB films have been studied experimentally by using UV irradiation and heat treatment. In addition to intramolecular charge transfer, we also studied the conjugation and energy changes of the molecules. In case a dye is thinned by LB method, the alkyl chain is often displaced in order to form a mono-molecular film with ease. Since the molecular association form is often made by self-organization of molecules themselves, in case the dye and the alkyl chain are strongly bonded by the covalent bond, it may be said that the properties of the LB film to be built up are almost determined at the time of synthesis of film-forming molecules. Meanwhile, since, in case LB film is fabricated by the diffusion absorption method, the cohesive force between the water-soluble dye and the surface-active mono-molecular film is electrostatic, the dye molecule can move relatively freely on the air/water interface, which may be regarded as a two-dimensional crystal growth process. PMID:27427711

  7. Highly nucleophilic acetylide, vinyl, and vinylidene complexes. Final progress report, 1 January 1991--31 March 1994

    SciTech Connect

    Geoffroy, G.L.

    1994-10-04

    In the course of this research the authors found that the anionic alkynyl complex [Cp{prime}(CO)(PPh{sub 3})Mn-C{triple_bond}C-CH{sub 3}]{sup {minus}} can be generated in situ by the addition of two equivalents of n-BuLi to a solution of the carbene complex Cp{prime}(CO)(PPh{sub 3})Mn{double_bond}C(OMe)CH{sub 2}CH{sub 3}. It was also found that the highly nucleophilic propynyl complex [Cp(CO)(PPh{sub 3})Mn-C{triple_bond}C-Me]{sup {minus}} reacts with a variety of aldehydes and ketones in the presence of BF{sub 3}{center_dot}Et{sub 2}O to give, after quenching with MeOH, a series of cationic vinylcarbyne complexes of the general form [Cp(CO)(PPh{sub 3})Mn{triple_bond}C-C(Me){double_bond}C(R)(R{prime})]BF{sub 4}. The cationic alkylidyne complexes [Cp(CO){sub 2}M{triple_bond}C-CH{sub 2}R]{sup +} [M = Re, R = H, M = Mn, R = H, Me, Ph] have been found to undergo facile deprotonation to give the corresponding neutral vinylidene complexes Cp(CO){sub 2}M{double_bond}C{double_bond}C(H)R. The authors have also investigated reactions relevant to the halide promoted Fe and Ru catalyzed carbonylation of nitroaromatics. The final part of this work has involved investigations of metal-oxo complexes.

  8. Surface-active ionic liquids in micellar catalysis: impact of anion selection on reaction rates in nucleophilic substitutions.

    PubMed

    Cognigni, Alice; Gaertner, Peter; Zirbs, Ronald; Peterlik, Herwig; Prochazka, Katharina; Schröder, Christian; Bica, Katharina

    2016-05-21

    A series of surface-active ionic liquids based on the 1-dodecyl-3-methylimidazolium cation and different anions such as halides and alkylsulfates was synthesized. The aggregation behavior of these ionic liquids in water was characterized by surface tension, conductivity measurements and UV-Vis spectroscopy in order to determine the critical micelle concentration (CMC) and to provide aggregation parameters. The determination of surface activity and aggregation properties of amphiphilic ionic liquids was accompanied by SAXS studies on selected surface-active ionic liquids. The application of these surface-active ionic liquids with different anions was tested in nucleophilic substitution reactions for the degradation of organophosphorus compounds. Kinetic studies via UV-Vis spectrophotometry showed a strong acceleration of the reaction in the micellar system compared to pure water. In addition, an influence of the anion was observed, resulting in a correlation between the anion binding to the micelle and the reaction rate constants, indicating that the careful choice of the surface-active ionic liquid can considerably affect the outcome of reactions. PMID:27121134

  9. Nucleophilic substitution with two reactive centers: The CN{sup −} + CH{sub 3}I case

    SciTech Connect

    Carrascosa, E.; Bawart, M.; Stei, M.; Carelli, F.; Meyer, J.; Gianturco, F. A.; Wester, R.; Linden, F.; Geppert, W. D.

    2015-11-14

    The nucleophilic substitution reaction CN{sup −} + CH{sub 3}I allows for two possible reactive approaches of the reactant ion onto the methyl halide, which lead to two different product isomers. Stationary point calculations predict a similar shape of the potential and a dominant collinear approach for both attacks. In addition, an H-bonded pre-reaction complex is identified as a possible intermediate structure. Submerged potential energy barriers hint at a statistical formation process of both CNCH{sub 3} and NCCH{sub 3} isomers at the experimental collision energies. Experimental angle- and energy differential cross sections show dominant direct rebound dynamics and high internal excitation of the neutral product. No distinct bimodal distributions can be extracted from the velocity images, which impedes the indication of a specific preference towards any of the product isomers. A forward scattering simulation based on the experimental parameters describes accurately the experimental outcome and shows how the possibility to discriminate between the two isomers is mainly hindered by the large product internal excitation.

  10. Nucleophilic Reactivity of a Nitride-Bridged Diuranium(IV) Complex: CO2 and CS2 Functionalization.

    PubMed

    Falcone, Marta; Chatelain, Lucile; Mazzanti, Marinella

    2016-03-14

    Thermolysis of the nitride-bridged diuranium(IV) complex Cs{(μ-N)[U(OSi(O(t) Bu)3 )3 ]2 } (1) showed that the bridging nitride behaves as a strong nucleophile, promoting N-C bond formation by siloxide ligand fragmentation to yield an imido-bridged siloxide/silanediolate diuranium(IV) complex, Cs{(μ-N(t) Bu)(μ-O2 Si(O(t) Bu)2 )U2 (OSi(O(t) Bu)3 )5 }. Complex 1 displayed reactivity towards CS2 and CO2 at room temperature that is unprecedented in f-element chemistry, affording diverse N-functionalized products depending on the reaction stoichiometry. The reaction of 1 with two equivalents of CS2 yielded the thiocyanate/thiocarbonate complex Cs{(μ-NCS)(μ-CS3 )[U(OSi(O(t) Bu)3 )3 ]2 } via a putative NCS(-) /S(2-) intermediate. The reaction of 1 with one equivalent of CO2 resulted in deoxygenation and N-C bond formation, yielding the cyanate/oxo complex Cs{(μ-NCO)(μ-O)[U(OSi(O(t) Bu)3 )3 ]2 }. Addition of excess CO2 to 1 led to the unprecedented dicarbamate product Cs{(μ-NC2 O4 )[U(OSi(O(t) Bu)3 )3 ]2 }. PMID:26914732

  11. Dithizone as novel and efficient chromogenic probe for cyanide detection in aqueous media through nucleophilic addition into diazenylthione moiety.

    PubMed

    Tavallali, Hossein; Deilamy-Rad, Gohar; Parhami, Abolfath; Kiyani, Sajede

    2014-01-01

    A new selective chemodosimeter probe was developed by the introduction of dithizone (DTZ) as a simple and available dye for detection of cyanide in aqueous media which enables recognition of cyanide over other competing anions such as acetate, dihydrogen phosphate, fluoride and benzoate through covalent bonding. The sensing properties of DTZ were investigated in DMSO/H2O (1:9) and have demonstrated a very high selectivity toward the cyanide anions. A reasonable recognition mechanism was suggested using UV-Vis, (1)H NMR and FTIR spectroscopy techniques. Time dependent density function theory (TDDFT) computations of UV-Vis excitation for DTZ2-CN adduct agreed well with our experimental findings. The detection limit of the new chromogenic probe was measured to be 0.48 μmol L(-1) which is much lower than most recently reported chromogenic probes for cyanide determination. The analytical utility of the method for the analysis of cyanide ions in electroplating wastewater (EPWW), human serum, tap and mineral water samples was demonstrated and the results were compared successfully with the conventional reference method. The short time response and the detection by the naked eye make the method available for the detection and quantitative determination of cyanide in a variety of real samples. PMID:24231750

  12. Dithizone as novel and efficient chromogenic probe for cyanide detection in aqueous media through nucleophilic addition into diazenylthione moiety

    NASA Astrophysics Data System (ADS)

    Tavallali, Hossein; Deilamy-Rad, Gohar; Parhami, Abolfath; Kiyani, Sajede

    2014-03-01

    A new selective chemodosimeter probe was developed by the introduction of dithizone (DTZ) as a simple and available dye for detection of cyanide in aqueous media which enables recognition of cyanide over other competing anions such as acetate, dihydrogen phosphate, fluoride and benzoate through covalent bonding. The sensing properties of DTZ were investigated in DMSO/H2O (1:9) and have demonstrated a very high selectivity toward the cyanide anions. A reasonable recognition mechanism was suggested using UV-Vis, 1H NMR and FTIR spectroscopy techniques. Time dependent density function theory (TDDFT) computations of UV-Vis excitation for DTZ2-CN adduct agreed well with our experimental findings. The detection limit of the new chromogenic probe was measured to be 0.48 μmol L-1 which is much lower than most recently reported chromogenic probes for cyanide determination. The analytical utility of the method for the analysis of cyanide ions in electroplating wastewater (EPWW), human serum, tap and mineral water samples was demonstrated and the results were compared successfully with the conventional reference method. The short time response and the detection by the naked eye make the method available for the detection and quantitative determination of cyanide in a variety of real samples.

  13. Phosphine-Catalyzed Enantioselective Intramolecular [3+2] Annulations To Generate Fused Ring Systems

    PubMed Central

    2015-01-01

    Substantial progress has been described in the development of asymmetric variants of the phosphine-catalyzed intermolecular [3+2] annulation of allenes with alkenes; however, there have not been corresponding advances for the intramolecular process, which can generate a higher level of complexity (an additional ring and stereocenter(s)). In this study, we describe the application of chiral phosphepine catalysts to address this challenge, thereby providing access to useful scaffolds that are found in bioactive compounds, including diquinane and quinolin-2-one derivatives, with very good stereoselectivity. The products of the [3+2] annulation can be readily transformed into structures that are even more stereochemically rich. Mechanistic studies are consistent with β addition of the phosphepine to the allene being the turnover-limiting step of the catalytic cycle, followed by a concerted [3+2] cycloaddition to the pendant olefin. PMID:25815702

  14. Tyrosyl-DNA phosphodiesterase I catalytic mutants reveal an alternative nucleophile that can catalyze substrate cleavage.

    PubMed

    Comeaux, Evan Q; Cuya, Selma M; Kojima, Kyoko; Jafari, Nauzanene; Wanzeck, Keith C; Mobley, James A; Bjornsti, Mary-Ann; van Waardenburg, Robert C A M

    2015-03-01

    Tyrosyl-DNA phosphodiesterase I (Tdp1) catalyzes the repair of 3'-DNA adducts, such as the 3'-phosphotyrosyl linkage of DNA topoisomerase I to DNA. Tdp1 contains two conserved catalytic histidines: a nucleophilic His (His(nuc)) that attacks DNA adducts to form a covalent 3'-phosphohistidyl intermediate and a general acid/base His (His(gab)), which resolves the Tdp1-DNA linkage. A His(nuc) to Ala mutant protein is reportedly inactive, whereas the autosomal recessive neurodegenerative disease SCAN1 has been attributed to the enhanced stability of the Tdp1-DNA intermediate induced by mutation of His(gab) to Arg. However, here we report that expression of the yeast His(nuc)Ala (H182A) mutant actually induced topoisomerase I-dependent cytotoxicity and further enhanced the cytotoxicity of Tdp1 His(gab) mutants, including H432N and the SCAN1-related H432R. Moreover, the His(nuc)Ala mutant was catalytically active in vitro, albeit at levels 85-fold less than that observed with wild type Tdp1. In contrast, the His(nuc)Phe mutant was catalytically inactive and suppressed His(gab) mutant-induced toxicity. These data suggest that the activity of another nucleophile when His(nuc) is replaced with residues containing a small side chain (Ala, Asn, and Gln), but not with a bulky side chain. Indeed, genetic, biochemical, and mass spectrometry analyses show that a highly conserved His, immediately N-terminal to His(nuc), can act as a nucleophile to catalyze the formation of a covalent Tdp1-DNA intermediate. These findings suggest that the flexibility of Tdp1 active site residues may impair the resolution of mutant Tdp1 covalent phosphohistidyl intermediates and provide the rationale for developing chemotherapeutics that stabilize the covalent Tdp1-DNA intermediate. PMID:25609251

  15. Synthesis of Allenamides by Copper-Catalyzed Coupling of Propargylic Bromides and Nitrogen Nucleophiles.

    PubMed

    Demmer, Charles S; Benoit, Emeline; Evano, Gwilherm

    2016-03-18

    An efficient and general synthesis of allenamides derived from oxazolidinones and hydantoins is reported. Upon activation with a combination of a copper catalyst and a 2,2'-bipyridine derivative in the presence of an inorganic base, propargylic bromides were found to be suitable reagents for the direct allenylation of nitrogen nucleophiles by a formal copper-catalyzed S(N)2' reaction. Besides the availability of the starting materials, notable features of this route to allenamides are its mild reaction conditions, the reaction being performed at room temperature in most cases, and its applicability to the preparation of mono-, di-, as well as trisubstituted allenamides. PMID:26936415

  16. tert-Butanesulfinamides as Nitrogen Nucleophiles in Carbon-Nitrogen Bond Forming Reactions.

    PubMed

    Ramirez Hernandez, Johana; Chemla, Fabrice; Ferreira, Franck; Jackowski, Olivier; Oble, Julie; Perez-Luna, Alejandro; Poli, Giovanni

    2016-01-01

    The use of tert-butanesulfinamides as nitrogen nucleophiles in carbon-nitrogen bond forming reactions is reviewed. This field has grown in the shadow of the general interest in N-tert-butanesulfinyl imines for asymmetric synthesis and occupies now an important place in its own right in the chemistry of the chiral amine reagent tert-butanesulfinamide. This article provides an overview of the area and emphasizes recent contributions wherein the tert-butanesulfinamides act as chiral auxiliaries or perform as nitrogen donors in metal-catalyzed amination reactions. PMID:26931222

  17. Enantioselective desymmetrization of prochiral cyclohexanones by organocatalytic intramolecular Michael additions to α,β-unsaturated esters.

    PubMed

    Gammack Yamagata, Adam D; Datta, Swarup; Jackson, Kelvin E; Stegbauer, Linus; Paton, Robert S; Dixon, Darren J

    2015-04-13

    A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99% ee) and in good yields (60-90%). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst. PMID:25727215

  18. Total synthesis of (±)-leuconolam: intramolecular allylic silane addition to a maleimide carbonyl group

    PubMed Central

    Izgu, Enver Cagri

    2014-01-01

    A concise total synthesis of the plant alkaloid (±)-leuconolam (1) has been achieved. A regio- and diastereoselective Lewis-acid mediated allylative cyclization was used to establish, simultaneously, two adjacent tetrasubstituted carbon centers. Furthermore, an essential arene cross-coupling to a hindered haloalkene was enabled by the use of a novel 2-anilinostannane. PMID:25419448

  19. An intramolecular interaction between the FHA domain and a coiled coil negatively regulates the kinesin motor KIF1A

    PubMed Central

    Lee, Jae-Ran; Shin, Hyewon; Choi, Jeonghoon; Ko, Jaewon; Kim, Seho; Lee, Hyun Woo; Kim, Karam; Rho, Seong-Hwan; Lee, Jun Hyuck; Song, Hye-Eun; Eom, Soo Hyun; Kim, Eunjoon

    2004-01-01

    Motor proteins not actively involved in transporting cargoes should remain inactive at sites of cargo loading to save energy and remain available for loading. KIF1A/Unc104 is a monomeric kinesin known to dimerize into a processive motor at high protein concentrations. However, the molecular mechanisms underlying monomer stabilization and monomer-to-dimer transition are not well understood. Here, we report an intramolecular interaction in KIF1A between the forkhead-associated (FHA) domain and a coiled-coil domain (CC2) immediately following the FHA domain. Disrupting this interaction by point mutations in the FHA or CC2 domains leads to a dramatic accumulation of KIF1A in the periphery of living cultured neurons and an enhancement of the microtubule (MT) binding and self-multimerization of KIF1A. In addition, point mutations causing rigidity in the predicted flexible hinge disrupt the intramolecular FHA–CC2 interaction and increase MT binding and peripheral accumulation of KIF1A. These results suggest that the intramolecular FHA–CC2 interaction negatively regulates KIF1A activity by inhibiting MT binding and dimerization of KIF1A, and point to a novel role of the FHA domain in the regulation of kinesin motors. PMID:15014437

  20. Pyrrolidine and Piperidine Formation Via Copper(II) Carboxylate Promoted Intramolecular Carboamination of Unactivated Olefins: Diastereoselectivity and Mechanism

    PubMed Central

    Sherman, Eric S.; Fuller, Peter H.; Kasi, Dhanalakshmi; Chemler, Sherry R.

    2008-01-01

    An expanded substrate scope and in depth analysis of the reaction mechanism of the copper(II) carboxylate promoted intramolecular carboamination of unactivated alkenes is described. This method provides access to N-functionalized pyrrolidines and piperidines. Both aromatic and aliphatic γ- and δ-alkenyl N-arylsulfonamides undergo the oxidative cyclization reaction efficiently. N-Benzoyl-2-allylaniline also underwent the oxidative cyclization. The terminal olefin substrates examined were more reactive than those with internal olefins, and the latter terminated in elimination rather than carbon-carbon bond formation. The efficiency of the reaction was enhanced by the use of more organic soluble copper(II) carboxylate salts, copper(II) neodecanoate in particular. The reaction times were reduced by the use of microwave heating. High levels of diastereoselectivity were observed in the synthesis of 2,5-disubstituted pyrrolidines, wherein the cis substitution pattern predominates. The mechanism of the reaction is discussed in the context of the observed reactivity and in comparison to analogous reactions promoted by other reagents and conditions. Our evidence supports a mechanism wherein the N-C bond is formed via intramolecular syn aminocupration and the C-C bond is formed via intramolecular addition of a primary carbon radical to an aromatic ring. PMID:17428100

  1. Tyrosine-Lipid Peroxide Adducts from Radical Termination: Para-Coupling and Intramolecular Diels-Alder Cyclization

    PubMed Central

    Shchepin, Roman; Möller, Matias N.; Kim, Hye-young H.; Hatch, Duane M.; Bartesaghi, Silvina; Kalyanaraman, Balaraman; Radi, Rafael

    2013-01-01

    Free radical co-oxidation of polyunsaturated lipids with tyrosine or phenolic analogs of tyrosine gave rise to lipid peroxide-tyrosine (phenol) adducts in both aqueous micellar and organic solutions. The novel adducts were isolated and characterized by 1D and 2D NMR as well as by mass spectrometry. The spectral data suggest that the polyunsaturated lipid peroxyl radicals give stable peroxide coupling products exclusively at the para position of the tyrosyl (phenoxy) radicals. These adducts have characteristic 13C chemical shifts at 185 ppm due to the cross-conjugated carbonyl of the phenol-derived cyclohexadienone. The primary peroxide adducts subsequently undergo intramolecular Diels-Alder (IMDA) cyclization, affording a number of diastereomeric tricyclic adducts that have characteristic carbonyl 13C chemical shifts at ~198 ppm. All NMR HMBC and HSQC correlations support the structure assignment of the primary and Diels-Alder adducts, as does MS collision induced dissociation. Kinetic rate constants and activation parameters for the IMDA reaction were determined and the primary adducts were reduced with cuprous ion giving a phenol-derived 4-hydroxycyclohexa-2,5-dienone. No products from adduction of peroxyls at the phenolic ortho position were found either in the primary or the cuprous reduction product mixtures. These studies provide a framework for understanding the nature of lipid-protein adducts formed by peroxyl-tyrosyl radical-radical termination processes. Coupling of lipid peroxyl radicals with tyrosyl radicals leads to cyclohexenone and cyclohexadienone adducts which are of interest in and of themselves since, as electrophiles, they are likely targets for protein nucleophiles. One consequence of lipid peroxyl reactions with tyrosyls may therefore be protein-protein crosslinks via interprotein Michael adducts. PMID:21090613

  2. Intramolecular hydroarylation of aryl propargyl ethers catalyzed by indium: the mechanism of the reaction and identifying the catalytic species.

    PubMed

    Menkir, Mengistu Gemech; Lee, Shyi-Long

    2016-07-01

    The mechanism and regioselectivity of the intramolecular hydroarylation of phenyl propargyl ether catalyzed by indium in gas and solvent phases were investigated by means of the density functional theory method. The computed results revealed that the reaction proceeds through initial π-coordination of the propargyl moiety to the catalyst, which triggers the nucleophilic attack of the phenyl ring via an exo- or endo-dig pathway in a Friedel-Crafts type mechanism. Calculation results obtained employing InI2(+) as the possible catalyst show similar activation energies for the 5-exo-dig and 6-endo-dig pathways. In contrast, the neural catalyst InI3 shows a kinetic preference for 6-endo-dig versus 5-exo-dig cyclizations leading to the experimentally observed product, 2H-chromene. The calculation results suggest that InI3 could be the real catalytic species for this reaction as it shows regioselectivity in agreement with the experimental observation. Furthermore, the 6-endo-dig cyclization through deprotonation/protonation steps is kinetically more favored than the stepwise two consecutive [1,2]-H shift steps. The rate determining step of the whole catalytic cycle is the deprotonation step with an energy barrier of 18.9 kcal mol(-1) in toluene solvent. The effects of substituents on both the phenyl ring and the propargyl moiety on the selectivity and elementary steps of the hydroarylation process were investigated. A methoxy group, particularly at the meta-position, on the phenyl ring largely decreases the energy barrier of the first step for the 6-endo path, though it shows little effect on the activation energies of the second and third steps. Our calculation results are in good agreement with the experimental results. PMID:27298068

  3. Controlling subtilisin activity and selectivity in organic media by imprinting with nucleophilic substrates

    SciTech Connect

    Rich, J.O.; Dordick, J.S.

    1997-04-09

    The activity and substrate specificity of subtilisin-catalyzed acylation of nucleosides in organic solvents can be controlled by lyophilizing the enzyme from an aqueous solution containing the substrate. This `molecular imprinting` technique was examined using thymidine as a model nucleoside, and the resulting subtilisin preparation was up to 50-fold more reactive toward thymidine acylation in nearly anhydrous tetrahydrofuran than subtilisin lyophilized from aqueous buffer in the absence of the nucleoside. Although several compounds lyophilized with subtilisin, including thymine and ribose, improved the rate of thymidine acylation, the thymidine-imprinted enzyme was the most efficient catalyst for this reaction. Furthermore, it was possible to alter the substrate selectivity of subtilisin by lyophilizing the enzyme in the presence of a different nucleophilic substrate. For example, imprinting made possible the discrimination between structurally different (i.e., sucrose versus thymidine) as well as structurally similar (i.e., thymidine versus deoxyadenosine) nucleophiles. Molecular modeling studies of the interaction of thymidine or the unrelated sucrose with subtilisin revealed that structural changes upon imprinting in the serine protease`s catalytic triad may be responsible for the observed activation and selectivity changes. 40 refs., 6 figs., 3 tabs.

  4. Development of Selective Colorimetric Probes for Hydrogen Sulfide Based on Nucleophilic Aromatic Substitution

    PubMed Central

    Montoya, Leticia A.; Pearce, Taylor F.; Hansen, Ryan J.; Zakharov, Lev N.; Pluth, Michael D.

    2013-01-01

    Hydrogen sulfide is an important biological signalling molecule and an important environmental target for detection. A major challenge in developing H2S detection methods is separating the often similar reactivity of thiols and other nucleophiles from H2S. To address this need, the nucleophilic aromatic substitution (SNAr) reaction of H2S with electron-poor aromatic electrophiles was developed as a strategy to separate H2S and thiol reactivity. Treatment of aqueous solutions of nitrobenzofurazan (7-nitro-1,2,3-benzoxadiazole, NBD) thioethers with H2S resulted in thiol extrusion and formation of nitrobenzofurazan thiol (λmax = 534 nm). This reactivity allows for unwanted thioether products to be converted to the desired nitrobenzofurazan thiol upon reaction with H2S. The scope of the reaction was investigated using a Hammett linear free energy relationship study, and the determined ρ = +0.34 is consistent with the proposed SN2Ar reaction mechanism. The efficacy of the developed probes was demonstrated in buffer and in serum with associated sub-micromolar detection limits as low as 190 nM (buffer) and 380 nM (serum). Furthermore, the sigmoidal response of nitrobenzofurazan electrophiles with H2S can be fit to accurately quantify H2S. The developed detection strategy offers a manifold for H2S detection that we foresee being applied in various future applications. PMID:23735055

  5. The second-shell metal ligands of human arginase affect coordination of the nucleophile and substrate.

    PubMed

    Stone, Everett M; Chantranupong, Lynne; Georgiou, George

    2010-12-14

    The active sites of eukaryotic arginase enzymes are strictly conserved, especially the first- and second-shell ligands that coordinate the two divalent metal cations that generate a hydroxide molecule for nucleophilic attack on the guanidinium carbon of l-arginine and the subsequent production of urea and l-ornithine. Here by using comprehensive pairwise saturation mutagenesis of the first- and second-shell metal ligands in human arginase I, we demonstrate that several metal binding ligands are actually quite tolerant to amino acid substitutions. Of >2800 double mutants of first- and second-shell residues analyzed, we found more than 80 unique amino acid substitutions, of which four were in first-shell residues. Remarkably, certain second-shell mutations could modulate the binding of both the nucleophilic water/hydroxide molecule and substrate or product ligands, resulting in activity greater than that of the wild-type enzyme. The data presented here constitute the first comprehensive saturation mutagenesis analysis of a metallohydrolase active site and reveal that the strict conservation of the second-shell metal binding residues in eukaryotic arginases does not reflect kinetic optimization of the enzyme during the course of evolution. PMID:21053939

  6. Reduced Reactivity of Amines against Nucleophilic Substitution via Reversible Reaction with Carbon Dioxide.

    PubMed

    Mohammed, Fiaz S; Kitchens, Christopher L

    2015-01-01

    The reversible reaction of carbon dioxide (CO₂) with primary amines to form alkyl-ammonium carbamates is demonstrated in this work to reduce amine reactivity against nucleophilic substitution reactions with benzophenone and phenyl isocyanate. The reversible formation of carbamates has been recently exploited for a number of unique applications including the formation of reversible ionic liquids and surfactants. For these applications, reduced reactivity of the carbamate is imperative, particularly for applications in reactions and separations. In this work, carbamate formation resulted in a 67% reduction in yield for urea synthesis and 55% reduction for imine synthesis. Furthermore, the amine reactivity can be recovered upon reversal of the carbamate reaction, demonstrating reversibility. The strong nucleophilic properties of amines often require protection/de-protection schemes during bi-functional coupling reactions. This typically requires three separate reaction steps to achieve a single transformation, which is the motivation behind Green Chemistry Principle #8: Reduce Derivatives. Based upon the reduced reactivity, there is potential to employ the reversible carbamate reaction as an alternative method for amine protection in the presence of competing reactions. For the context of this work, CO₂ is envisioned as a green protecting agent to suppress formation of n-phenyl benzophenoneimine and various n-phenyl-n-alky ureas. PMID:26703563

  7. Identification of the nucleophile catalytic residue of GH51 α-l-arabinofuranosidase from Pleurotus ostreatus

    SciTech Connect

    Amore, Antonella; Iadonisi, Alfonso; Vincent, Florence; Faraco, Vincenza

    2015-12-21

    In this paper, the recombinant α-l-arabinofuranosidase from the fungus Pleurotus ostreatus (rPoAbf) was subjected to site-directed mutagenesis in order to identify the catalytic nucleophile residue. Based on bioinformatics and homology modelling analyses, E449 was revealed to be the potential nucleophilic residue. Thus, the mutant E449G of PoAbf was recombinantly expressed in Pichia pastoris and its recombinant expression level and reactivity were investigated in comparison to the wild-type. The design of a suitable set of hydrolysis experiments in the presence or absence of alcoholic arabinosyl acceptors and/or formate salts allowed to unambiguously identify the residue E449 as the nucleophile residue involved in the retaining mechanism of this GH51 arabinofuranosidase. 1H NMR analysis was applied for the identification of the products and the assignement of their anomeric configuration.

  8. Configurationally Stable, Enantioenriched Organometallic Nucleophiles in Stereospecific Pd-Catalyzed Cross-Coupling Reactions: An Alternative Approach to Asymmetric Synthesis

    PubMed Central

    Wang, Chao-Yuan; Derosaa, Joseph

    2015-01-01

    Several research groups have recently developed methods to employ configurationally stable, enantioenriched organometallic nucleophiles in stereospecific Pd-catalyzed cross-coupling reactions. By establishing the absolute configuration of a chiral alkyltin or alkylboron nucleophile prior to its use in cross-coupling reactions, new stereogenic centers may be rapidly and reliably generated with preservation of the known initial stereochemistry. While this area of research is still in its infancy, such stereospecific cross-coupling reactions may emerge as simple, general methods to access diverse, optically active products from common enantioenriched organometallic building blocks. This minireview highlights recent progress towards the development of general, stereospecific Pd-catalyzed cross-coupling reactions using configurationally stable organometallic nucleophiles. PMID:26388985

  9. Catalytic Intramolecular Ketone Alkylation with Olefins by Dual Activation.

    PubMed

    Lim, Hee Nam; Dong, Guangbin

    2015-12-01

    Two complementary methods for catalytic intramolecular ketone alkylation reactions with unactivated olefins, resulting in Conia-ene-type reactions, are reported. The transformations are enabled by dual activation of both the ketone and the olefin and are atom-economical as stoichiometric oxidants or reductants are not required. Assisted by Kool's aniline catalyst, the reaction conditions can be both pH- and redox-neutral. A broad range of functional groups are thus tolerated. Whereas the rhodium catalysts are effective for the formation of five-membered rings, a ruthenium-based system that affords the six-membered ring products was also developed. PMID:26486569

  10. Intramolecular charge transfer in donor-acceptor molecules

    SciTech Connect

    Slama-Schwok, A.; Blanchard-Desce, M.; Lehn, J.M. )

    1990-05-17

    The photophysical properties of donor-acceptor molecules, push-pull polyenes and carotenoids, have been studied by absorption and fluorescence spectroscopy. The compounds bear various acceptor and donor groups, linked together by chains of different length and structure. The position of the absorption and fluorescence maxima and their variation in solvents of increasing polarity are in agreement with long-distance intramolecular charge-transfer processes, the linker acting as a molecular wire. The effects of the linker length and structure and of the nature of acceptor and donor are presented.

  11. Intramolecular Fluorescence Correlation Spectroscopy in a Feedback Tracking Microscope

    NASA Astrophysics Data System (ADS)

    McHale, Kevin; Mabuchi, Hideo

    2010-07-01

    We derive the statistics of the signals generated by shape fluctuations of large molecules studied by feedback tracking microscopy. We account for the influence of intramolecular dynamics on the response of the tracking system, and derive a general expression for the fluorescence autocorrelation function that applies when those dynamics are linear. We show that tracking provides enhanced sensitivity to translational diffusion, molecular size, heterogeneity and long time-scale decays in comparison to traditional fluorescence correlation spectroscopy. We demonstrate our approach by using a three-dimensional tracking microscope to study genomic $\\lambda$-phage DNA molecules with various fluorescence label configurations.

  12. C1-Cx revisited: intramolecular synergism in a cellulase.

    PubMed Central

    Din, N; Damude, H G; Gilkes, N R; Miller, R C; Warren, R A; Kilburn, D G

    1994-01-01

    Endoglucanase A (CenA) from the bacterium Cellulomonas fimi is composed of a catalytic domain and a nonhydrolytic cellulose-binding domain that can function independently. The individual domains interact synergistically in the disruption and hydrolysis of cellulose fibers. This intramolecular synergism is distinct from the well-known intermolecular synergism between individual cellulases. The catalytic domain corresponds to the hydrolytic Cx system and the cellulose-binding domain corresponds to the nonhydrolytic C1 system postulated by Reese et al. [Reese, E. T., Sui, R. G. H. & Levinson, H. S. (1950) J. Bacteriol. 59, 485-497] to be required for the hydrolysis of cellulose. PMID:7972069

  13. Detailed theoretical investigation of excited-state intramolecular proton transfer mechanism of a new chromophore II

    NASA Astrophysics Data System (ADS)

    Cui, Yanling; Li, Yafei; Dai, Yumei; Verpoort, Francis; Song, Peng; Xia, Lixin

    2016-02-01

    In the present work, TDDFT has been used to investigate the excited state intramolecular proton transfer (ESIPT) mechanism of a new chromophore II [Sensors and Actuators B: Chemical. 202 (2014) 1190]. The calculated absorption and fluorescence spectra agree well with experimental results. In addition, two types of II configurations are found in the first excited state (S1), which can be ascribed to the ESIPT reaction. Based on analysis of the calculated infrared (IR) spectra of O-H stretching vibration as well as the hydrogen bonding energies, the strengthening of the hydrogen bond in the S1 state has been confirmed. The frontier molecular orbitals (MOs), Hirshfeld charge distribution and the Natural bond orbital (NBO) have also been analyzed, which displays the tendency of the ESIPT process. Finally, potential energy curves of the S0 and S1 states were constructed, demonstrating that the ESIPT reaction can be facilitated based on the photo-excitation.

  14. Mapping the intramolecular contributions to the inelastic electron tunneling signal of a molecular junction

    NASA Astrophysics Data System (ADS)

    Foti, Giuseppe; Vázquez, Héctor

    2016-07-01

    We present a quantitative analysis of the intramolecular origin of the inelastic electron tunneling signal of a molecular junction. We use density-functional theory to study a representative conjugated molecule with a low degree of symmetry and calculate, for all modes, the different contributions that give rise to the vibrational spectrum. These local contributions involve products of scattering states with electron-phonon matrix elements and thus encode information on both the vibrational modes and the electronic structure. We separate these intra- and interatomic terms and draw a pattern of addition or cancellation of these partial contributions throughout the inelastic spectrum. This allows for a quantitative relation between the degree of symmetry of each vibrational mode, its inelastic signal, and the locality of selection rules.

  15. Total synthesis of Elisabethin A: intramolecular Diels-Alder reaction under biomimetic conditions.

    PubMed

    Heckrodt, Thilo J; Mulzer, Johann

    2003-04-23

    We describe the first total synthesis of the marine diterpenoid elisabethin A. The synthesis uses (S)-hydroxy-2-methyl-propionate as the chiral starting material, which is elaborated into a dienyl-iodide and added to an aryl acetic acid ester via enolate alkylation. The hydroquinoid system is oxidized to the quinone which serves as the dienophile in a highly stereocontrolled intramolecular Diels-Alder addition. This IMDA reaction, which to our knowledge is the first one to employ a terminal (Z)-diene, proceeds under biomimetic conditions (water, ferrichloride as the oxidant, room temperature) with high yield and stereoselectivity. The Diels-Alder adduct is transformed into the natural product via a three-step sequence including selective hydrogenation, base-catalyzed epimerization of the cis- into the trans-decalin system and O-demethylation. PMID:12696865

  16. Effect of. gamma. -cyclodextrin on the intramolecular charge transfer processes in aminocoumarin laser dyes

    SciTech Connect

    Nag, A.; Chakrabarty, T.; Bhattacharyya, K. )

    1990-05-17

    Steady-state and time-resolved studies on the emission properties of three 7-(diethylamino)coumarin laser dyes (I-III) in aqueous {gamma}-cyclodextrin ({gamma}-CD) solutions are reported. On addition of {gamma}-CD, fluorescence maxima of all the three dyes shift to higher energy, with a huge enhancement of the yield of intramolecular charge transfer (ICT) emission for the flexible ones (I and II) and a very slight enhancement for the rigid analogue III. The results are explained in terms of the concept of polarity-dependent twisted ICT rates. It is proposed that twisted ICT, the main nonradiative process in the excited ICT states of these dyes, is severely restricted inside the {gamma}-cyclodextrin cavity because of the reduced polarity. This is responsible for the enhancement of fluorescence from the ICT state.

  17. Corrole and nucleophilic aromatic substitution are not incompatible: a novel route to 2,3-difunctionalized copper corrolates

    PubMed Central

    Stefanelli, M.; Mandoj, F.; Nardis, S.; Raggio, M.; Fronczek, F.R.; McCandless, G.T.; Smith, K. M.; Paolesse, R.

    2015-01-01

    The insertion of a –NO2 group onto the corrole framework represents a key step for subsequent synthetic manipulation of the macrocycle based on the chemical versatility of such a functionality. Here we report results on the investigation of a copper 3-NO2-triarylcorrolate in nucleophilic aromatic substitution reactions with “active” methylene carbanions, namely diethyl malonate and diethyl 2-chloromalonate. Although similar reactions on nitroporphyrins afford chlorin derivatives, nucleophilic attack on carbon-2 of corrole produces 2,3-difunctionalized Cu corrolates in acceptable yields (ca. 30%), evidencing once again the erratic chemistry of this contracted porphyrinoid. PMID:25986693

  18. Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

    PubMed Central

    Schmid, Thibault E; Drissi-Amraoui, Sammy; Crévisy, Christophe; Baslé, Olivier

    2015-01-01

    Summary The copper-catalyzed asymmetric conjugate addition (ACA) of nucleophiles onto polyenic Michael acceptors represents an attractive and powerful methodology for the synthesis of relevant chiral molecules, as it enables in a straightforward manner the sequential generation of two or more stereogenic centers. In the last decade, various chiral copper-based catalysts were evaluated in combination with different nucleophiles and Michael acceptors, and have unambiguously demonstrated their usefulness in the control of the regio- and enantioselectivity of the addition. The aim of this review is to report recent breakthroughs achieved in this challenging field. PMID:26734090

  19. Effects of Intramolecular Distance between Amyloidogenic Domains on Amyloid Aggregation

    PubMed Central

    Ko, Ahra; Kim, Jin Ryoun

    2012-01-01

    Peptide/protein aggregation is implicated in many amyloid diseases. Some amyloidogenic peptides/proteins, such as those implicated in Alzheimer’s and Parkinson’s diseases, contain multiple amyloidogenic domains connected by “linker” sequences displaying high propensities to form turn structures. Recent studies have demonstrated the importance of physicochemical properties of each amino acid contained in the polypeptide sequences in amyloid aggregation. However, effects on aggregation related to the intramolecular distance between amyloidogenic domains, which may be determined by a linker length, have yet to be examined. In the study presented here, we created peptides containing two copies of KFFE, a simple four-residue amyloidogenic domain, connected by GS-rich linker sequences with different lengths yet similar physicochemical properties. Our experimental results indicate that aggregation occurred most rapidly when KFFE domains were connected by a linker of an intermediate length. Our experimental findings were consistent with estimated entropic contribution of a linker length toward formation of (partially) structured intermediates on the aggregation pathway. Moreover, inclusion of a relatively short linker was found to inhibit formation of aggregates with mature fibril morphology. When the results are assimilated, our study demonstrates that intramolecular distance between amyloidogenic domains is an important yet overlooked factor affecting amyloid aggregation. PMID:23202890

  20. Intermediate State Dependence of Intramolecular Vibrations in Photoactive Yellow Protein

    NASA Astrophysics Data System (ADS)

    Deng, Yanting; Xu, Mengyang; Niessen, Katherine; Schmidt, Marius; Markelz, Andrea

    Photoactive proteins provide a testbed for the role of long-range collective motions in protein function. Long-range intramolecular vibrations of the protein scaffold may provide efficient energy relaxation, enhancement of chromophore vibrations that promote structural transitions and assistance in electron energy transfer. Photoactive yellow protein (PYP) is a cytoplasmic photocycling protein associated with the negative phototactic response to blue light in halohodospira halophile. We measure the intramolecular vibrations of PYP using crystal anisotropy terahertz microscopy (CATM) as a function of photoexcitation. Room temperature CATM measurements are performed in the dark and with continuous illumination at 488 nm, which is found to result in an approximately 20% steady photoexcited state (pB). We find a decrease in anisotropic absorption in frequency range 20-60 cm-1 with photoexcitation. This result may be due to an increase in sample disorder associated with the structural change in pB state. We compare the measured and calculated spectra using molecular dynamics and normal mode/quasiharmonic analysis to identify the nature of the motions giving rise to the resonant absorption bands.

  1. One pot synthesis of Curcumin-NSAIDs prodrug, spectroscopic characterization, conformational analysis, chemical reactivity, intramolecular interactions and first order hyperpolarizability by DFT method

    NASA Astrophysics Data System (ADS)

    Srivastava, Sangeeta; Gupta, Preeti; Sethi, Arun; Singh, Ranvijay Pratap

    2016-08-01

    A novel Curcumin-NSAIDs prodrug 4-((1E, 3Z, 6E)-3-hydroxy-(4-hydroxy-3-methoxyphenyl)-5-oxohepta-1,3,3-trienyl)-2-methoxyphenyl-2-(4-isobutylphenyl) propanoate (2) derivative was synthesized by Steglich esterification in high yield and characterized with the help of 1H, 13C NMR, 1H-1H COSY, UV, FT-IR spectroscopy and mass spectrometry. The molecular geometry of synthesized compound was calculated in ground state by Density functional theory (DFT/B3LYP) using two different basis set 6-31G (d, p) and 6-311G (d, p). Conformational analysis of 2 was carried out to determine the most stable conformation. Stability of the molecule as a result of hyperconjugative interactions and electron delocalization were analysed using Natural bond orbital (NBO) analysis. Intramolecular interactions were analysed by AIM (Atom in molecule) approach. Global and local reactivity descriptors were calculated to study the reactive site within molecule. The electronic properties such as HOMO and LUMO energies were calculated using time dependent Density Functional Theory (TD-DFT). The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). First hyperpolarizability value has been calculated to describe the nonlinear optical (NLO) property of the synthesized compound. Molecular electrostatic potential (MEP) for synthesized compounds have also been determined to check their electrophilic or nucleophilic reactivity.

  2. Lithium choreography: intramolecular arylations of carbamate-stabilised carbanions and their mechanisms probed by in situ IR spectroscopy and DFT calculations.

    PubMed

    Fournier, Anne M; Nichols, Christopher J; Vincent, Mark A; Hillier, Ian H; Clayden, Jonathan

    2012-12-14

    Deprotonation of O-allyl, O-propargyl or O-benzyl carbamates in the presence of a lithium counterion leads to carbamate-stabilised organolithium compounds that may be quenched with electrophiles. We now report that when the allylic, propargylic or benzylic carbamate bears an N-aryl substituent, an aryl migration takes place, leading to stereochemical inversion and C-arylation of the carbamate α to oxygen. The aryl migration is an intramolecular S(N) Ar reaction, despite the lack of anion-stabilising aryl substituents. Our in situ IR studies reveal a number of intermediates along the rearrangement pathway, including a "pre-lithiation complex," the deprotonated carbamate, the rearranged anion, and the final arylated carbamate. No evidence was obtained for a dearomatised intermediate during the aryl migration. DFT calculations predict that during the reaction the solvated Li cation moves from the carbanion centre, thus freeing its lone pair for nucleophilic attack on the remote phenyl ring. This charge separation leads to several alternative conformations. The one having Li(+) bound to the carbamate oxygen gives rise to the lowest-energy transition structure, and also leads to inversion of the configuration. In agreement with the IR studies, the DFT calculations fail to locate a dearomatised intermediate. PMID:23097264

  3. Novel synthetic ester of Brassicasterol, DFT investigation including NBO, NLO response, reactivity descriptor and its intramolecular interactions analyzed by AIM theory

    NASA Astrophysics Data System (ADS)

    Sethi, Arun; Prakash, Rohit

    2015-03-01

    In the present work, Brassicasterol (compound 1) isolated from Allamanda Violacea reacted with the well known NSAID ibuprofen by Steglich esterification yielding a novel steroidal ester, 3β-(2-(4-isobutyl phenyl) propionoxy) 24 methyl cholest-5, 22-dien (compound 2). Identity of synthetic derivative (compound 2) was done with the help of modern spectroscopic techniques like, 1H NMR, IR and UV as well as mass spectrometry. Molecular geometry and vibrational frequencies of compound 2 were calculated using density functional method (DFT/B3LYP) and 6-31(d,p) basis set. NMR chemical shifts of the compound were calculated with GIAO method. Electronic properties such as HOMO-LUMO energies were measured with the help of time dependent DFT method. Natural bond orbital (NBO) analysis was carried out to study hyperconjugative interactions. Non linear optical (NLO) response of compound 2 was also evaluated. Molecular electrostatic potential (MEP) surface has been used to indicate nucleophilic and electrophilic sites. Global reactivity descriptors of compound 1 and 2 were also calculated. Intramolecular interactions were analyzed using Atoms in molecule (AIM) theory.

  4. Taming of fluoroform: direct nucleophilic trifluoromethylation of Si, B, S, and C centers.

    PubMed

    Prakash, G K Surya; Jog, Parag V; Batamack, Patrice T D; Olah, George A

    2012-12-01

    Fluoroform (CF(3)H), a large-volume by-product of the manufacture of Teflon, refrigerants, polyvinylidene fluoride (PVDF), fire-extinguishing agents, and foams, is a potent and stable greenhouse gas that has found little practical use despite the growing importance of trifluoromethyl (CF3) functionality in more structurally elaborate pharmaceuticals, agrochemicals, and materials. Direct nucleophilic trifluoromethylation using CF(3)H has been a challenge. Here, we report on a direct trifluoromethylation protocol using close to stoichiometric amounts of CF(3)H in common organic solvents such as tetrahydrofuran (THF), diethyl ether, and toluene. The methodology is widely applicable to a variety of silicon, boron, and sulfur-based electrophiles, as well as carbon-based electrophiles. PMID:23224551

  5. Conversion of the rocket propellant UDMH to a reagent useful in vicarious nucleophilic substitution reactions

    SciTech Connect

    Mitchell, A.R.; Pagoria, P.F.; Schmidt, R.D.

    1995-11-10

    The objective of our program is to develop novel, innovative solutions for the disposal of surplus energetic materials resulting from the demilitarization of conventional and nuclear munitions. In this report we describe the use of surplus propellant (UDMH) and explosives (TNT, Explosive D) as chemical precursors for higher value products. The conversion of UDMH to 1,1,1-trimethylhydrazinium iodide (TMHI) provides a new aminating reagent for use in Vicarious Nucleophilic Substitution (VNS) reactions. When TMHI is reacted with various nitroarenes the amino functionality is introduced in good to excellent yields. Thus, 2,4,6-trinitroaniline (picramide) reacts with TMHI to give 1,3,5-triamino-2,4,6-trinitroaniline (TATB) while 2,4,6-trinitrotoluene (TNT) reacts with TMHI to give 3,5-diamino-2,4,6-trinitrotoluene (DATNT). The advantages, scope and limitations of the VNS approach and the use of TMHI are discussed.

  6. Bis-tert-Alcohol-Functionalized Crown-6-Calix[4]arene: An Organic Promoter for Nucleophilic Fluorination.

    PubMed

    Jadhav, Vinod H; Choi, Wonsil; Lee, Sung-Sik; Lee, Sungyul; Kim, Dong Wook

    2016-03-18

    A bis-tert-alcohol-functionalized crown-6-calix[4]arene (BACCA) was designed and prepared as a multifunctional organic promoter for nucleophilic fluorinations with CsF. By formation of a CsF/BACCA complex, BACCA could release a significantly active and selective fluoride source for SN2 fluorination reactions. The origin of the promoting effects of BACCA was studied by quantum chemical methods. The role of BACCA was revealed to be separation of the metal fluoride to a large distance (>8 Å), thereby producing an essentially "free" F(-). The synergistic actions of the crown-6-calix[4]arene subunit (whose O atoms coordinate the counter-cation Cs(+)) and the terminal tert-alcohol OH groups (forming controlled hydrogen bonds with F(-)) of BACCA led to tremendous efficiency in SN2 fluorination of base-sensitive substrates. PMID:26880350

  7. Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine.

    PubMed

    Li, Jing; Lear, Martin J; Kwon, Eunsang; Hayashi, Yujiro

    2016-04-11

    Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I(+) under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion. PMID:26938791

  8. Diverse Reactivity of an Electrophilic Phosphasilene towards Anionic Nucleophiles: Substitution or Metal-Amino Exchange.

    PubMed

    Willmes, Philipp; Junk, Lukas; Huch, Volker; Yildiz, Cem B; Scheschkewitz, David

    2016-08-26

    The reaction of MesLi (Mes=2,4,6-trimethylphenyl) with the electrophilic phosphasilene R2 (NMe2 )Si-RSi=PNMe2 (2, R=Tip=2,4,6-triisopropylphenyl) cleanly affords R2 (NMe2 )Si-RSi=PMes and thus provides the first example of a substitution reaction at an unperturbed Si=P bond. In toluene, the reaction of 2 with lithium disilenide, R2 Si=Si(R)Li (1), apparently proceeds via an initial nucleophilic substitution step as well (as suggested by DFT calculations), but affords a saturated bicyclo[1.1.0]butane analogue as the final product, which was further characterized as its Fe(CO)4 complex. In contrast, in 1,2-dimethoxyethane the reaction of 1 with 2 results in an unprecedented metal-amino exchange reaction. PMID:27509901

  9. Synthesis and intramolecular cyclization of methylenediphosphorus bisalkylamides containing one or two 4-coordinate phosphorus atoms

    SciTech Connect

    Novikova, Z.S.; Monin, E.A.; Kabachnik, M.M.; Lutsenko, I.F.

    1987-10-10

    We have previously reported on the synthesis of methylenediphosphorus bisalkylamides containing two 3-coordinate phosphorus atoms and their intramolecular cyclization into 1,2,4-azadiphosphetidines. In this work we have synthesized methylenediphosphorus bisalkylamides containing one or two 4-coordinate phosphorus atoms and have studied their intramolecular cyclization. The bisalkylamides were characterized in ether solution by their /sup 31/ NMR spectra.

  10. Direct Observation of Cascade of Photoinduced Ultrafast Intramolecular Charge Transfer Dynamics in Diphenyl Acetylene Derivatives: Via Solvation and Intramolecular Relaxation.

    PubMed

    Karunakaran, Venugopal; Das, Suresh

    2016-07-21

    Interaction of light with electron donor-acceptor π-conjugated systems leading to intramolecular charge transfer (ICT) plays an essential role in transformation of light energy. Here the cascade of photoinduced ICT processes is directly observed by investigating the excited state relaxation dynamics of cyano and mono/di methoxy substituted diphenyl acetylene derivatives using femtosecond pump-probe spectroscopy and nanosecond laser flash photolysis. The femtosecond transient absorption spectra of the chromophores upon ultrafast excitation reveal the dynamics of intermediates involved in transition from initially populated Frank-Condon state to local excited state (LE). It also provides the dynamic details of the transition from the LE to the charge transfer state yielding the formation of the radical ions. Finally, the charge transfer state decays to the triplet state by geminate charge recombination. The latter dynamics are observed in the nanosecond transient absorption spectra. It is found that excited state relaxation pathways are controlled by different stages of solvation and intramolecular relaxation depending on the solvent polarity. The twisted ICT state is more stabilized (978 ps) in acetonitrile than cyclohexane where major components of transient absorption originate from the S1 state. PMID:27347705

  11. Online Measurement of the Intramolecular Isotopic Composition of Acetate in Natural Porewater Samples

    NASA Astrophysics Data System (ADS)

    Thomas, R. B.; Arthur, M. A.; Freeman, K. H.

    2006-12-01

    Carbon dioxide and methane are traditionally considered to be the dominant end products of anaerobic metabolism while acetate is thought to be a rapidly consumed intermediate. However, in some settings, recent evidence has grown to suggest that, at least transiently, acetate can be a major metabolic end product. In natural systems, isotopic mass balances can be used to partition the flow of carbon to methane, CO2, and acetate. However, these isotopic estimates require intramolecular measurements of acetate in addition to isotopic measurements of the gaseous species, CO2 and CH4. In practice, the intramolecular isotopic composition of acetate is rarely measured because the analysis is technically challenging and traditionally requires prior separation and offline pyrolysis of purified acetate. As a result of these technical challenges, acetate methyl carbon is usually assumed to be a few permil depleted relative to the carbon isotopic composition of bulk organic matter. In environments where acetate may be produced by autotrophic acetogens this assumption can be devastatingly false. This work describes the use of an online method for the analysis of the intramolecular carbon isotopic composition of dissolved acetate from dilute surface water samples with a detection limit of injected sample down to 500uM. Preconcentration of samples via lyophilization has resulted in detection limits as low as 30uM. In 2002, at Penn State, Dias et al. (Organic Geochemistry Vol. 33, p161-168) reported a technique to examine the intramolecular isotopic composition of acetate from oil-prone source rocks using SPME extraction with an online GC-pyrolysis-IRMS. We have adapted the Dias method to be used with direct injection of dilute natural water samples. Briefly, this procedure protonates acetate with a .1M addition of oxalic acid and vaporizes the sample in the GC inlet at low temperatures. This prevents oxalic acid decomposition and provides sufficient separation of acetate from

  12. The kinetics and mechanisms of aromatic nucleophilic substitution reactions in liquid ammonia.

    PubMed

    Ji, Pengju; Atherton, John H; Page, Michael I

    2011-05-01

    The rates of aromatic nucleophilic substitution reactions in liquid ammonia are much faster than those in protic solvents indicating that liquid ammonia behaves like a typical dipolar aprotic solvent in its solvent effects on organic reactions. Nitrofluorobenzenes (NFBs) readily undergo solvolysis in liquid ammonia and 2-nitrofluorobenzene is about 30 times more reactive than the 4-substituted isomer. Oxygen nucleophiles, such as alkoxide and phenoxide ions, readily displace fluorine of 4-NFB in liquid ammonia to give the corresponding substitution product with little or no competing solvolysis product. Using the pK(a) of the substituted phenols in liquid ammonia, the Brønsted β(nuc) for the reaction of 4-NFB with para-substituted phenoxides is 0.91, indicative of the removal of most of the negative charge on the oxygen anion and complete bond formation in the transition state and therefore suggests that the decomposition of the Meisenheimer σ-intermediate is rate limiting. The aminolysis of 4-NFB occurs without general base catalysis by the amine and the second-order rate constants generate a Brønsted β(nuc) of 0.36 using either the pK(a) of aminium ion in acetonitrile or in water, which is also interpreted in terms of rate limiting breakdown of the Meisenheimer σ-intermediate. Nitrobenzene and diazene are formed as unusual products from the reaction between sodium azide and 4-NFB, which may be due to the initially formed 4-nitroazidobenzene decomposing to give a nitrene intermediate, which may then give diazene or be trapped by ammonia to give the unstable hydrazine which then yields nitrobenzene. PMID:21417418

  13. Use of phosphoimidazolide-activated guanosine to investigate the nucleophilicity of spermine and spermidine

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Baird, E. E.; Smith, P. J.

    1995-01-01

    Guanosine 5'-phosphate 2-methylimidazolide (2-MeImpG), a labile phosphoimidazolide analog of guanosine triphosphate, was used to test the reactivity of the natural polyamines (PAs), spermine (spm) and spermidine (spd). The products are the guanosine 5'-phosphate-polyamine derivatives (PA-pG: spd-pG and spm-pG) which are quite stable in the range 4 < pH < 11. Our study is the first of which we are aware that reports on the nucleophilicity of these amines. The main findings are as follows. (i) HPLC analysis of the products indicates the formation of only two of the three possible spd products and only one of the two possible spm products. These results can be explained if only the primary amino groups of the two polyamines are reactive, while the secondary amino groups are rendered unreactive by a steric effect. The reactions of 2-MeImpG and other phosphoimidazolide derivatives of nucleosides (ImpNs) with primary and secondary monoamines support this interpretation (Kanavarioti et al. J. Org. Chem. 1995, 60, 632). (ii) The product ratio of the two spd-pG adducts derived from the primary amino groups varies between 2.40 and 0.71 in the range 6.1 < or equal to pH < or equal to 11.9. Such small variation in the product ratio can only be rationalized by the similar, but not identical, basicity of the two primary amino groups and provides strong support for a previously reported model for polyamine ionization (Onasch et. al. Biophys. Chem. 1984, 19, 245). (iii) On the basis of our kinetic determinations conditions at which the nucleophilicity of these amines is at a minimum and at which other interactions with ImpNs could be tested can be chosen.

  14. Ground State Destabilization by Anionic Nucleophiles Contributes to the Activity of Phosphoryl Transfer Enzymes

    PubMed Central

    Andrews, Logan D.; Fenn, Tim D.; Herschlag, Daniel

    2013-01-01

    Enzymes stabilize transition states of reactions while limiting binding to ground states, as is generally required for any catalyst. Alkaline Phosphatase (AP) and other nonspecific phosphatases are some of Nature's most impressive catalysts, achieving preferential transition state over ground state stabilization of more than 1022-fold while utilizing interactions with only the five atoms attached to the transferred phosphorus. We tested a model that AP achieves a portion of this preference by destabilizing ground state binding via charge repulsion between the anionic active site nucleophile, Ser102, and the negatively charged phosphate monoester substrate. Removal of the Ser102 alkoxide by mutation to glycine or alanine increases the observed Pi affinity by orders of magnitude at pH 8.0. To allow precise and quantitative comparisons, the ionic form of bound Pi was determined from pH dependencies of the binding of Pi and tungstate, a Pi analog lacking titratable protons over the pH range of 5–11, and from the 31P chemical shift of bound Pi. The results show that the Pi trianion binds with an exceptionally strong femtomolar affinity in the absence of Ser102, show that its binding is destabilized by ≥108-fold by the Ser102 alkoxide, and provide direct evidence for ground state destabilization. Comparisons of X-ray crystal structures of AP with and without Ser102 reveal the same active site and Pi binding geometry upon removal of Ser102, suggesting that the destabilization does not result from a major structural rearrangement upon mutation of Ser102. Analogous Pi binding measurements with a protein tyrosine phosphatase suggest the generality of this ground state destabilization mechanism. Our results have uncovered an important contribution of anionic nucleophiles to phosphoryl transfer catalysis via ground state electrostatic destabilization and an enormous capacity of the AP active site for specific and strong recognition of the phosphoryl group in the transition

  15. Blue organic light-emitting devices with an oxadiazole-containing emitting layer exhibiting excited state intramolecular proton transfer

    NASA Astrophysics Data System (ADS)

    Ma, Dongge; Liang, Fushun; Wang, Lixiang; Lee, S. T.; Hung, L. S.

    2002-05-01

    We report a blue organic light-emitting device having an emissive layer of 2-(2-hydroxyphenyl)-5-phenyl-1,3,4-oxadiazole (HOXD), that exhibits excited state intramolecular proton transfer (ESIPT). The device had a luminance efficiency of 0.8 cd/A and a maximum brightness of 870 cd/ m2. Electroluminescence spectra revealed a dominating peak at 450 nm and two additional peaks at 480 and 515 nm with a full width at half maximum of 50 nm. Our studies indicate that some EL may originate from the triplet excitation state of the enol form of HOXD.

  16. Reactivity of endohedral metallofullerene la2@c80 in nucleophilic and electrophilic attacks: vibronic coupling density approach.

    PubMed

    Haruta, Naoki; Sato, Tohru; Tanaka, Kazuyoshi

    2015-01-01

    The regioselectivities of La2@C80 in thermal nucleophilic and electrophilic attacks were theoretically investigated using vibronic coupling density (VCD) analysis. Nucleophilic and electrophilic cycloadditions to La2@C80 were experimentally reported to yield [6,6] and [6,5] adducts, respectively, as major products. VCD analysis provided a clear explanation for these experimental results. For nucleophilic reactions, it was found that the reactive [6,6] bonds did not have a large lowest unoccupied molecular orbital (LUMO) density and Fukui function but a large potential derivative with respect to a reaction mode. The VCD illustrates the origin of the interaction between the electronic and vibrational states. On the other hand, conventional reactivity indices such as frontier orbital density take only the electronic state into account. The result suggested that the stabilization due to vibronic couplings plays an important role in the regioselectivity of nucleophilic cycloadditions. The VCD with respect to the effective mode could provide a picture of the functional groups, which are the double bonds of ethylene moieties. VCD analysis with respect to hypothetical localized modes enabled the quantitative prediction of regioselectivities. PMID:25389657

  17. Mechanism of phenol oxidation by heterodinuclear Ni Cu bis(μ-oxo) complexes involving nucleophilic oxo groups

    PubMed Central

    Kundu, Subrata; Miceli, Enrico; Farquhar, Erik R.

    2014-01-01

    Oxidation of phenols by heterodinuclear CuIII(μ-O)2NiIII complexes containing nucleophilic oxo groups occurs by both proton coupled electron transfer (PCET) and hydrogen atom transfer (HAT) mechanisms; the exact mechanism depends on the nature of the phenol as well as the substitution pattern of the ligand bound to Cu. PMID:24362244

  18. Determination of gas-phase nucleophilicities and electrophilicities using B⋯HX bond critical point properties of AIM analysis

    NASA Astrophysics Data System (ADS)

    Ebrahimi, Ali; Roohi, Hosein; Habibi, Mostafa; Hasannejad, Mehdi

    2006-09-01

    The values of nucleophilicity and electrophilicity have been established in gas phase for some nucleophiles (B = CH 3CN, CO, H 2O, H 2S, HCN, N 2, NH 3, PH 3) and electrophiles (HX = HF, HCl, HBr, HCN HCF 3) from properties of bond critical points of atoms in molecules (AIM) analysis. On the basis of the meaningful relationship, the recent method has been applied to electron density ( ρ), Laplacian of electron density (∇ρ2), and electronic kinetic energy density ( G), of B⋯HX bond critical point. AIM analysis has been performed on the obtained wave functions at MP2/6-311++G(d,p) level of theory. The correlation between averaged calculated values of nucleophilicity (or electrophilicity), using different properties of B⋯HX bond critical points, and complexation energies (Δ Ecomp) is satisfactory. The best correlation coefficient between nucleophilicity and Δ Ecomp is related to ρ values of bond critical points. But, the best correlation coefficient between electrophilicity and Δ Ecomp is allied to ∇ρ2 and G values of bond critical points.

  19. Catalytic Nucleophilic Fluorination of Secondary and Tertiary Propargylic Electrophiles with a Copper-N-Heterocyclic Carbene Complex.

    PubMed

    Cheng, Li-Jie; Cordier, Christopher J

    2015-11-01

    A catalytic method for the nucleophilic fluorination of propargylic electrophiles is described. Our protocol involves the use of a Cu(NHC) complex as the catalyst and is suitable for the preparation of secondary and tertiary propargylic fluorides without the formation of isomeric fluoroallenes. Preliminary mechanistic investigations suggest that fluorination proceeds via copper acetylides and that cationic species are involved. PMID:26403935

  20. Catalytic Nucleophilic Fluorination of Secondary and Tertiary Propargylic Electrophiles with a Copper–N-Heterocyclic Carbene Complex

    PubMed Central

    Cheng, Li-Jie; Cordier, Christopher J

    2015-01-01

    A catalytic method for the nucleophilic fluorination of propargylic electrophiles is described. Our protocol involves the use of a Cu(NHC) complex as the catalyst and is suitable for the preparation of secondary and tertiary propargylic fluorides without the formation of isomeric fluoroallenes. Preliminary mechanistic investigations suggest that fluorination proceeds via copper acetylides and that cationic species are involved. PMID:26403935

  1. Intramolecular strain coordinates kinesin stepping behavior along microtubules

    PubMed Central

    Yildiz, Ahmet; Tomishige, Michio; Gennerich, Arne; Vale, Ronald D.

    2008-01-01

    SUMMARY Kinesin advances 8 nm along a microtubule per ATP hydrolyzed, but the mechanism responsible for coordinating the enzymatic cycles of kinesin’s two identical motor domains remains unresolved. Here, we have tested whether such coordination is mediated by intramolecular tension generated by the “neck linkers”, mechanical elements that span between the motor domains. When tension is reduced by extending the neck linkers with artificial peptides, the coupling between ATP hydrolysis and forward stepping is impaired and motor’s velocity decreases as a consequence. However, speed recovers to nearly normal levels when external tension is applied by an optical trap. Remarkably, external load also induces bidirectional stepping of an immotile kinesin that lacks its mechanical element (neck linker) and fuel (ATP). Our results indicate that the kinesin motor domain senses and responds to strain in a manner that facilitates its plus-end-directed stepping and communication between its two motor domains. PMID:18805095

  2. Intramolecular dynamics of structure of alkaline phosphatase from Escherichia coli

    NASA Astrophysics Data System (ADS)

    Mazhul, Vladimir M.; Mjakinnik, Igor V.; Volkova, Alena N.

    1995-01-01

    The luminescent analysis with nano- and millisecond time resolution of intramolecular dynamics of Escherichia coli alkaline phosphatase was carried out. The effect of pH within the range 7.2 - 9.0, thermal inactivation, limited proteolysis by trypsin, binding of pyrophosphate, interconversion of enzyme and apoenzyme, the replacement of Zn2+ and Mg2+ in the active site by Cd2+ and Ni2+ on the spectral and kinetic parameters of luminescence was investigated. The essential changes of the level of nano- and millisecond dynamics of protein structure were found to correlate with the shift of enzymatic activity. The importance of small- and large-scale flexibility of protein structure for the act of enzymatic catalysis realization was shown.

  3. Universal prediction of intramolecular hydrogen bonds in organic crystals.

    PubMed

    Galek, Peter T A; Fábián, László; Allen, Frank H

    2010-04-01

    A complete exploration of intramolecular hydrogen bonds (IHBs) has been undertaken using a combination of statistical analyses of the Cambridge Structural Database and computation of ab initio interaction energies for prototypical hydrogen-bonded fragments. Notable correlations have been revealed between computed energies, hydrogen-bond geometries, donor and acceptor chemistry, and frequencies of occurrence. Significantly, we find that 95% of all observed IHBs correspond to the five-, six- or seven-membered rings. Our method to predict a propensity for hydrogen-bond occurrence in a crystal has been adapted for such IHBs, applying topological and chemical descriptors derived from our findings. In contrast to intermolecular hydrogen bonding, it is found that IHBs can be predicted across the complete chemical landscape from a single optimized probability model, which is presented. Predictivity of 85% has been obtained for generic organic structures, which can exceed 90% for discrete classes of IHB. PMID:20305358

  4. Gold‐Catalyzed Intramolecular Cyclizations of Cyclopropenes with Propargylic Esters

    PubMed Central

    Zhu, Peng‐Long

    2015-01-01

    Abstract Homogeneous gold catalysts are interesting as they can act as potent carbophilic Lewis acids to activate the π bonds of alkynes, allenes, and alkenes. Many impressive applications for the formation of C−C or C−heteroatom bonds have been found due to the excellent functional group compatibility of these catalysts and the air and moisture tolerance of their reactions. Here, we have developed gold‐catalyzed novel intramolecular cycloisomerizations of nitrogen or oxygen‐tethered cyclopropenes with propargylic esters. The reaction proceeded through different pathways according to different substituent styles, affording 5‐azaspiro[2.5]oct‐7‐enes and bicyclo[4.1.0]heptanes. PMID:27308208

  5. Sequence and intramolecular distance scoring analyses of microbial rhodopsins

    PubMed Central

    Asano, Miki; Ide, Shunta; Kamata, Atsushi; Takahasi, Kiyohiro; Okada, Tetsuji

    2016-01-01

    Recent accumulation of sequence and structural data, in conjunction with systematical classification into a set of families, has significantly advanced our understanding of diverse and specific protein functions. Analysis and interpretation of protein family data requires comprehensive sequence and structural alignments. Here, we present a simple scheme for analyzing a set of experimental structures of a given protein or family of proteins, using microbial rhodopsins as an example. For a data set comprised of around a dozen highly similar structures to each other (overall pairwise root-mean-squared deviation < 2.3 Å), intramolecular distance scoring analysis yielded valuable information with respect to structural properties, such as differences in the relative variability of transmembrane helices. Furthermore, a comparison with recent results for G protein-coupled receptors demonstrates how the results of the present analysis can be interpreted and effectively utilized for structural characterization of diverse protein families in general. PMID:26998236

  6. Solvent reorganizational red-edge effect in intramolecular electron transfer.

    PubMed Central

    Demchenko, A P; Sytnik, A I

    1991-01-01

    Polar solvents are characterized by statistical distributions of solute-solvent interaction energies that result in inhomogeneous broadening of the solute electronic spectra. This allows photoselection of the high interaction energy part of the distribution by excitation at the red (long-wavelength) edge of the absorption bands. We observe that intramolecular electron transfer in the bianthryl molecule from the locally excited (LE) to the charge-transfer (CT) state, which requires solvent relaxation and does not occur in vitrified polar solutions, is dramatically facilitated in low-temperature propylene glycol glass by the red-edge excitation. This allows one to obtain spectroscopically the pure CT form and observe its dependence upon the relaxational properties of the solvent. A qualitative potential model of this effect is presented. PMID:11607224

  7. Estimating the energy of intramolecular hydrogen bonds in chitosan oligomers

    NASA Astrophysics Data System (ADS)

    Mikhailov, G. P.; Lazarev, V. V.

    2016-07-01

    The effect the number of chitosan monomer units CTS n ( n = 1-5), the protonation of chitosan dimers, and the interaction between CTS n ( n = 1-3) and acetate ions have on the energy of intramolecular hydrogen bonds is investigated by means of QTAIM analysis and solving the vibrational problem within the cluster-continuum model. It is established that the number of H-bonds in CTS n is 2 n - 1 and the total energy of H-bonds grows by ~20 kJ/mol. It is concluded that the hydrogen bonds between CTS and acetate ions play a major role in the stabilization of polyelectrolyte complexes in dilute acetic acid solutions of CTS.

  8. Intramolecular diffusion controls aggregation of the PAPf39 peptide.

    PubMed

    Srivastava, Kinshuk R; French, Kinsley C; Tzul, Franco O; Makhatadze, George I; Lapidus, Lisa J

    2016-09-01

    The 39-residue fragment of human prostatic acidic phosphatase (PAP) is found in high concentrations in semen and easily form fibrils. Previous work has shown that fibrillization is accelerated with a deletion of the first 8, mostly charged residues and it was hypothesized that fibrillization depended on the dynamics of these peptides. To test this hypothesis we have measured the intramolecular diffusion of the full length and 8-residue deletion peptides at two different pHs and found a correlation with fibrillization lag time. These results can be explained by a simple kinetic model of the early stages of aggregation in which oligomerization is controlled by the rate of peptide reconfiguration. PMID:27393931

  9. Intramolecular Long-Distance Electron Transfer in Organic Molecules

    NASA Astrophysics Data System (ADS)

    Closs, Gerhard L.; Miller, John R.

    1988-04-01

    Intramolecular long-distance electron transfer (ET) has been actively studied in recent years in order to test existing theories in a quantitative way and to provide the necessary constants for predicting ET rates from simple structural parameters. Theoretical predictions of an ``inverted region,'' where increasing the driving force of the reaction will decrease its rate, have begun to be experimentally confirmed. A predicted nonlinear dependence of ET rates on the polarity of the solvent has also been confirmed. This work has implications for the design of efficient photochemical charge-separation devices. Other studies have been directed toward determining the distance dependence of ET reactions. Model studies on different series of compounds give similar distance dependences. When different stereochemical structures are compared, it becomes apparent that geometrical factors must be taken into account. Finally, the mechanism of coupling between donor and acceptor in weakly interacting systems has become of major importance. The theoretical and experimental evidence favors a model in which coupling is provided by the interaction with the orbitals of the intervening molecular fragments, although more experimental evidence is needed. Studies on intramolecular ET in organic model compounds have established that current theories give an adequate description of the process. The separation of electronic from nuclear coordinates is only a convenient approximation applied to many models, but in long-distance ET it works remarkably well. It is particularly gratifying to see Marcus' ideas finally confirmed after three decades of skepticism. By obtaining the numbers for quantitative correlations between rates and distances, these experiments have shown that saturated hydrocarbon fragments can ``conduct'' electrons over tens of angstroms. A dramatic demonstration of this fact has recently been obtained by tunneling electron microscopy on Langmuir-Blodgett films, showing in a

  10. Structural studies of photoinduced intramolecular electron transfer in cyclopentadienylnickelnitrosyl

    SciTech Connect

    Chen, L.X.; Bowman, M.K.; Wang, Zhiyu; Norris, J.R. |; Montano, P.A. |

    1994-03-01

    A structural study based on EXAFS, FTIR, and optical absorption spectroscopies has been conducted on a photogenerated, metastable state of cyclopentadienylnickelnitrosyl (CpNiNO) produced by a reversible photochemical reaction. The photogenerated, metastable state with distinctively different EXAFS, IR, and optical absorption spectra from those of the ground state molecules was created by irradiating the sample with the 365 nm line of a mercury lamp at 20K . At the same temperature, the reverse reaction was induced by irradiation with the 313 nm line from the mercury lamp. Based on the analysis of the EXAFS data, the photogenerated, metastable state of CpNiNO has undergone considerable nuclear rearrangements compared to its ground state. The nuclear movement is characterized by a 0.12{angstrom} elongation of Ni-N bond and by a bending of Ni-N-O. A shift of the N-O stretching frequency from 1824 to 1387 cm{sup {minus}1} was observed in the photoinduced reaction with 365 nm light, implying that a NO{sup {minus}} like species results from intramolecular electron transfer from Ni to NO. The changes in the absorption spectra for the same reaction showed reduced absorption of the 385 nm band and a newly generated broad band near IR region. Temperature dependence of the Debye-Waller factor of CpNiNO was in good agreement with the diatomic harmonic oscillator for the Ni-N bond, but deviated for the Ni-O and the Ni-C bonds. Based on the structures obtained from EXAFS, ZINDO calculations for both the ground state and the photogenerated, metastable state of CpNiNO reproduced the general features of the observed absorption spectra and qualitatively explained the wavelength dependence of the reaction. The calculated partial charges on each atom in the ground state and the photogenerated, metastable state of CpNiNO are consistent with intramolecular electron transfer upon photoexcitation by 365 nm light.

  11. Liquid ammonia as a dipolar aprotic solvent for aliphatic nucleophilic substitution reactions.

    PubMed

    Ji, Pengju; Atherton, John; Page, Michael I

    2011-03-01

    The rate constants for the reactions of a variety of nucleophiles reacting with substituted benzyl chlorides in liquid ammonia (LNH(3)) have been determined. To fully interpret the associated linear free-energy relationships, the ionization constants of phenols ions in liquid ammonia were obtained using UV spectra. These equilibrium constants are the product of those for ion-pair formation and dissociation to the free ions, which can be separated by evaluating the effect of added ammonium ions. There is a linear relationship between the pK(a) of phenols in liquid ammonia and those in water of slope 1.68. Aminium ions exist in their unprotonated free base form in liquid ammonia and their ionization constants could not be determined by NMR. The rates of solvolysis of substituted benzyl chlorides in liquid ammonia at 25 °C show a Hammett ρ of zero, having little or no dependence upon ring substituents, which is in stark contrast with the hydrolysis rates of substituted benzyl halides in water, which vary 10(7) fold. The rate of substitution of benzyl chloride by substituted phenoxide ions is first order in the concentration of the nucleophile indicative of a S(N)2 process, and the dependence of the rate constants on the pK(a) of the phenol in liquid ammonia generates a Brønsted β(nuc) = 0.40. Contrary to the solvolysis reaction, the reaction of phenoxide ion with 4-substituted benzyl chlorides gives a Hammett ρ = 1.1, excluding the 4-methoxy derivative, which shows the normal positive deviation. The second order rate constants for the substitution of benzyl chlorides by neutral and anionic amines show a single Brønsted β(nuc) = 0.21 (based on the aqueous pK(a) of amine), but their dependence on the substituent in substituted benzyl chlorides varies with a Hammett ρ of 0 for neutral amines, similar to that seen for solvolysis, whereas that for amine anions is 0.93, similar to that seen for phenoxide ion. PMID:21348532

  12. Ground state destabilization by anionic nucleophiles contributes to the activity of phosphoryl transfer enzymes.

    PubMed

    Andrews, Logan D; Fenn, Tim D; Herschlag, Daniel

    2013-07-01

    Enzymes stabilize transition states of reactions while limiting binding to ground states, as is generally required for any catalyst. Alkaline Phosphatase (AP) and other nonspecific phosphatases are some of Nature's most impressive catalysts, achieving preferential transition state over ground state stabilization of more than 10²²-fold while utilizing interactions with only the five atoms attached to the transferred phosphorus. We tested a model that AP achieves a portion of this preference by destabilizing ground state binding via charge repulsion between the anionic active site nucleophile, Ser102, and the negatively charged phosphate monoester substrate. Removal of the Ser102 alkoxide by mutation to glycine or alanine increases the observed Pi affinity by orders of magnitude at pH 8.0. To allow precise and quantitative comparisons, the ionic form of bound P(i) was determined from pH dependencies of the binding of Pi and tungstate, a P(i) analog lacking titratable protons over the pH range of 5-11, and from the ³¹P chemical shift of bound P(i). The results show that the Pi trianion binds with an exceptionally strong femtomolar affinity in the absence of Ser102, show that its binding is destabilized by ≥10⁸-fold by the Ser102 alkoxide, and provide direct evidence for ground state destabilization. Comparisons of X-ray crystal structures of AP with and without Ser102 reveal the same active site and P(i) binding geometry upon removal of Ser102, suggesting that the destabilization does not result from a major structural rearrangement upon mutation of Ser102. Analogous Pi binding measurements with a protein tyrosine phosphatase suggest the generality of this ground state destabilization mechanism. Our results have uncovered an important contribution of anionic nucleophiles to phosphoryl transfer catalysis via ground state electrostatic destabilization and an enormous capacity of the AP active site for specific and strong recognition of the phosphoryl group in

  13. Vibrational spectroscopy and intramolecular energy transfer in isocyanic acid (HNCO)

    SciTech Connect

    Coffey, M.J.; Berghout, H.L.; Woods, E. III; Crim, F.F.

    1999-06-01

    Room temperature photoacoustic spectra in the region of the first through the fourth overtones (2{nu}{sub 1} to 5{nu}{sub 1}) and free-jet action spectra of the second through the fourth overtones (3{nu}{sub 1} to 5{nu}{sub 1}) of the N{endash}H stretching vibration permit analysis of the vibrational and rotational structure of HNCO. The analysis identifies the strong intramolecular couplings that control the early stages of intramolecular vibrational energy redistribution (IVR) and gives the interaction matrix elements between the zero-order N{endash}H stretching states and the other zero-order states with which they interact. The experimentally determined couplings and zero-order state separations are consistent with {ital ab initio} calculations of East, Johnson, and Allen [J. Chem. Phys. {bold 98}, 1299 (1993)], and comparison with the calculation identifies the coupled states and likely interactions. The states most strongly coupled to the pure N{endash}H stretching zero-order states are ones with a quantum of N{endash}H stretching excitation ({nu}{sub 1}) replaced by different combinations of N{endash}C{endash}O asymmetric or symmetric stretching excitation ({nu}{sub 2} or {nu}{sub 3}) and {ital trans}-bending excitation ({nu}{sub 4}). The two strongest couplings of the n{nu}{sub 1} state are to the states (n{minus}1){nu}{sub 1}+{nu}{sub 2}+{nu}{sub 4} and (n{minus}1){nu}{sub 1}+{nu}{sub 3}+2{nu}{sub 4}, and sequential couplings through a series of low order resonances potentially play a role. The analysis shows that if the pure N{endash}H stretch zero-order state were excited, energy would initially flow out of that mode into the strongly coupled mode in 100 fs to 700 fs, depending on the level of initial excitation. {copyright} {ital 1999 American Institute of Physics.}

  14. 1,3,2,5-Diazadiborinine featuring nucleophilic and electrophilic boron centres.

    PubMed

    Wu, Di; Kong, Lingbing; Li, Yongxin; Ganguly, Rakesh; Kinjo, Rei

    2015-01-01

    The seminal discovery in 1865 by Kekulé that benzene nucleus exists with cyclic skeleton is considered to be the beginning of aromatic chemistry. Since then, a myriad of cyclic molecules displaying aromatic property have been synthesized. Meanwhile, borazine (B3N3H6), despite the isostructural and isoelectronic relationships with benzene, exhibits little aromaticity. Herein, we report the synthesis of a 1,3,2,5-diazadiborinine (B2C2N2R6) derivative, a hybrid inorganic/organic benzene, and we present experimental and computational evidence for its aromaticity. In marked contrast to the reactivity of benzene, borazine, and even azaborinines previously reported, 1,3,2,5-diazadiborinine readily forms the adducts with methyl trifluoromethanesulfonate and phenylacetylene without any catalysts. Moreover, 1,3,2,5-diazadiborine activates carbon dioxide giving rise to a bicycle[2,2,2] product, and the binding process was found to be reversible. These results, thus, demonstrate that 1,3,2,5-diazadiborinine features both nucleophilic and electrophilic boron centres, with a formal B(+I)/B(+III) mixed valence system, in the aromatic six-membered B2C2N2 ring. PMID:26073993

  15. Routes to covalent catalysis by reactive selection for nascent protein nucleophiles.

    PubMed

    Reshetnyak, Andrey V; Armentano, Maria Francesca; Ponomarenko, Natalia A; Vizzuso, Domenica; Durova, Oxana M; Ziganshin, Rustam; Serebryakova, Marina; Govorun, Vadim; Gololobov, Gennady; Morse, Herbert C; Friboulet, Alain; Makker, Sudesh P; Gabibov, Alexander G; Tramontano, Alfonso

    2007-12-26

    Reactivity-based selection strategies have been used to enrich combinatorial libraries for encoded biocatalysts having revised substrate specificity or altered catalytic activity. This approach can also assist in artificial evolution of enzyme catalysis from protein templates without bias for predefined catalytic sites. The prevalence of covalent intermediates in enzymatic mechanisms suggests the universal utility of the covalent complex as the basis for selection. Covalent selection by phosphonate ester exchange was applied to a phage display library of antibody variable fragments (scFv) to sample the scope and mechanism of chemical reactivity in a naive molecular library. Selected scFv segregated into structurally related covalent and noncovalent binders. Clones that reacted covalently utilized tyrosine residues exclusively as the nucleophile. Two motifs were identified by structural analysis, recruiting distinct Tyr residues of the light chain. Most clones employed Tyr32 in CDR-L1, whereas a unique clone (A.17) reacted at Tyr36 in FR-L2. Enhanced phosphonylation kinetics and modest amidase activity of A.17 suggested a primitive catalytic site. Covalent selection may thus provide access to protein molecules that approximate an early apparatus for covalent catalysis. PMID:18044899

  16. Gramicidin S: a peptide model for protein glycation and reversal of glycation using nucleophilic amines.

    PubMed

    Shakkottai, V G; Sudha, R; Balaram, P

    2002-08-01

    Nonenzymatic glycation of proteins has been implicated in various diabetic complications and age-related disorders. Proteins undergo glycation at the N-terminus or at the epsilon-amino group of lysine residues. Glycation of proteins proceeds through the stages of Schiff base formation, conversion to ketoamine product and advanced glycation end products. Gramicidin S, which has two ornithine residues, was used as a model system to study the various stages of glycation of proteins using electrospray ionization mass spectrometry. The proximity of two ornithine residues in the peptide favors the glycation reaction. Formation of advanced glycation end products and diglycation on ornithine residues in gramicidin S were observed. The formation of Schiff base adduct is reversible, whereas the Amadori rearrangement to the ketoamine product is irreversible. Nucleophilic amines and hydrazines can deglycate the Schiff base adduct of glucose with peptides and proteins. Hydroxylamine, isonicotinic acid hydrazide and aminoguanidine effectively removed glucose from the Schiff base adduct of gramicidin S. Hydroxylamine is more effective in deglycating the adduct compared with isonicotinic acid hydrazide and aminoguanidine. The observation that the hydrazines are effective in deglycating the Schiff base adduct even in the presence of high concentrations of glucose, may have a possible therapeutic application in preventing complications of diabetes mellitus. Hydrazines may be used to distinguish between the Schiff base and the ketoamine products formed at the initial stages of glycation. PMID:12102724

  17. 1,3,2,5-Diazadiborinine featuring nucleophilic and electrophilic boron centres

    PubMed Central

    Wu, Di; Kong, Lingbing; Li, Yongxin; Ganguly, Rakesh; Kinjo, Rei

    2015-01-01

    The seminal discovery in 1865 by Kekulé that benzene nucleus exists with cyclic skeleton is considered to be the beginning of aromatic chemistry. Since then, a myriad of cyclic molecules displaying aromatic property have been synthesized. Meanwhile, borazine (B3N3H6), despite the isostructural and isoelectronic relationships with benzene, exhibits little aromaticity. Herein, we report the synthesis of a 1,3,2,5-diazadiborinine (B2C2N2R6) derivative, a hybrid inorganic/organic benzene, and we present experimental and computational evidence for its aromaticity. In marked contrast to the reactivity of benzene, borazine, and even azaborinines previously reported, 1,3,2,5-diazadiborinine readily forms the adducts with methyl trifluoromethanesulfonate and phenylacetylene without any catalysts. Moreover, 1,3,2,5-diazadiborine activates carbon dioxide giving rise to a bicycle[2,2,2] product, and the binding process was found to be reversible. These results, thus, demonstrate that 1,3,2,5-diazadiborinine features both nucleophilic and electrophilic boron centres, with a formal B(+I)/B(+III) mixed valence system, in the aromatic six-membered B2C2N2 ring. PMID:26073993

  18. Nucleophile-dependent regio- and stereoselective ring opening of 1-azoniabicyclo[3.1.0]hexane tosylate.

    PubMed

    Ji, Mi-Kyung; Hertsen, Dietmar; Yoon, Doo-Ha; Eum, Heesung; Goossens, Hannelore; Waroquier, Michel; Van Speybroeck, Veronique; D'hooghe, Matthias; De Kimpe, Norbert; Ha, Hyun-Joon

    2014-04-01

    1-[(1R)-(1-Phenylethyl)]-1-azoniabicyclo[3.1.0]hexane tosylate was generated as a stable bicyclic aziridinium salt from the corresponding 2-(3-hydroxypropyl)aziridine upon reaction with p-toluenesulfonyl anhydride. This bicyclic aziridinium ion was then treated with various nucleophiles including halides, azide, acetate, and cyanide in CH3CN to afford either piperidines or pyrrolidines through regio- and stereoselective ring opening, mediated by the characteristics of the applied nucleophile. On the basis of DFT calculations, ring-opening reactions under thermodynamic control yield piperidines, whereas reactions under kinetic control can yield both piperidines and pyrrolidines depending on the activation energies for both pathways. PMID:24488926

  19. Synthesis and Late-Stage Functionalization of Complex Molecules through C–H Fluorination and Nucleophilic Aromatic Substitution

    PubMed Central

    2015-01-01

    We report the late-stage functionalization of multisubstituted pyridines and diazines at the position α to nitrogen. By this process, a series of functional groups and substituents bound to the ring through nitrogen, oxygen, sulfur, or carbon are installed. This functionalization is accomplished by a combination of fluorination and nucleophilic aromatic substitution of the installed fluoride. A diverse array of functionalities can be installed because of the mild reaction conditions revealed for nucleophilic aromatic substitutions (SNAr) of the 2-fluoroheteroarenes. An evaluation of the rates for substitution versus the rates for competitive processes provides a framework for planning this functionalization sequence. This process is illustrated by the modification of a series of medicinally important compounds, as well as the increase in efficiency of synthesis of several existing pharmaceuticals. PMID:24918484

  20. sp(2)-sp(3) diboranes: astounding structural variability and mild sources of nucleophilic boron for organic synthesis.

    PubMed

    Dewhurst, Rian D; Neeve, Emily C; Braunschweig, Holger; Marder, Todd B

    2015-06-14

    Despite the widespread use of organoborane reagents in organic synthesis and catalysis, a major challenge still remains: very few boron-centered nucleophiles exist for the direct construction of B-C bonds. Perhaps the most promising emerging solution to this problem is the use of sp(2)-sp(3) diboranes, in which one boron atom of a conventional diborane(4) is quaternised by either a neutral or anionic nucleophile. These compounds, either isolated or generated in situ, serve as relatively mild and convenient sources of the boryl anion [BR2](-) for use in organic synthesis and have already proven their efficacy in metal-free as well as metal-catalysed borylation reactions. This Feature article documents the history of sp(2)-sp(3) diborane synthesis, their properties and surprising structural variability, and their burgeoning utility in organic synthesis. PMID:25912808

  1. A Substrate-Assisted Mechanism of Nucleophile Activation in a Ser-His-Asp Containing C-C Bond Hydrolase

    SciTech Connect

    Ruzzini, Antonio C.; Bhowmik, Shiva; Ghosh, Subhangi; Yam, Katherine C.; Bolin, Jeffrey T.; Eltis, Lindsay D.

    2013-11-12

    The meta-cleavage product (MCP) hydrolases utilize a Ser–His–Asp triad to hydrolyze a carbon–carbon bond. Hydrolysis of the MCP substrate has been proposed to proceed via an enol-to-keto tautomerization followed by a nucleophilic mechanism of catalysis. Ketonization involves an intermediate, ESred, which possesses a remarkable bathochromically shifted absorption spectrum. We investigated the catalytic mechanism of the MCP hydrolases using DxnB2 from Sphingomonas wittichii RW1. Pre-steady-state kinetic and LC ESI/MS evaluation of the DxnB2-mediated hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid to 2-hydroxy-2,4-pentadienoic acid and benzoate support a nucleophilic mechanism catalysis. In DxnB2, the rate of ESred decay and product formation showed a solvent kinetic isotope effect of 2.5, indicating that a proton transfer reaction, assigned here to substrate ketonization, limits the rate of acylation. For a series of substituted MCPs, this rate was linearly dependent on MCP pKa2nuc ~ 1). Structural characterization of DxnB2 S105A:MCP complexes revealed that the catalytic histidine is displaced upon substrate-binding. The results provide evidence for enzyme-catalyzed ketonization in which the catalytic His–Asp pair does not play an essential role. The data further suggest that ESred represents a dianionic intermediate that acts as a general base to activate the serine nucleophile. This substrate-assisted mechanism of nucleophilic catalysis distinguishes MCP hydrolases from other serine hydrolases.

  2. Synthesis, characterization and intramolecular proton transfer of 3,3";-dihydroxy-4,4";-[5-methyl-1,3-phenylenebis(nitrilomethylidyne)]-bis-phenol

    NASA Astrophysics Data System (ADS)

    Eshtiagh-Hosseini, Hossein; Beyramabadi, S. Ali; Morsali, Ali; Mirzaei, Masoud; Chegini, Hamed; Elahi, Morteza; Naseri, Mohammad Ali

    2014-08-01

    A newly synthesized Schiff base, 3,3";-dihydroxy-4,4";-[5-methyl-1,3-phenylenebis(nitrilomethylidyne)]-bis-phenol, was characterized experimentally. Its geometries optimization, tautomerization, assignment of the IR bands and NMR chemical shifts were calculated by using density functional theory (DFT) method. In addition, the atoms in molecules (AIM) analysis was employed for investigation of its tautomerization. Four possible tautomers of the investigated Schiff base were optimized in both of the gas and solution phases. The Schiff base has no planar structure, but each of the benzene rings is in a separate plane. In the most stable tautomer, the phenolic protons of the two sbnd OH groups are engaged in the intramolecular-hydrogen bond with the azomethine nitrogens. Good consistency between the theoretical and experimental results confirms validity of the optimized geometry. Also, kinetics and mechanism of the intramolecular-proton transfer of the studied Schiff base was demonstrated theoretically.

  3. Synthesis of 2-Cyclopentenone Derivatives via Palladium-Catalyzed Intramolecular Carbonyl α-Alkenylation.

    PubMed

    Chen, Panpan; Meng, Yinggao; Wang, Han; Han, Feipeng; Wang, Yulong; Song, Chuanjun; Chang, Junbiao

    2016-08-01

    2-Cyclopentenone derivatives have been efficiently synthesized from 5-bromo-5-hexen-2-ones via palladium-catalyzed intramolecular carbonyl α-alkenylation followed by double-bond migration under mild reaction conditions. PMID:27463262

  4. Light induced catalytic intramolecular hydrofunctionalization of allylphenols mediated by porphyrin rhodium(iii) complexes.

    PubMed

    Liu, Xu; Wang, Zikuan; Fu, Xuefeng

    2016-09-14

    Catalytic intramolecular hydrofunctionalization of allylphenols to heterocyclic compounds mediated by rhodium(iii) porphyrin complexes was described. The Wacker-type intermediate β-heterocyclic alkyl rhodium complex was independently synthesized and crystallized. PMID:27482840

  5. Intramolecular Hydrogen-Bonding Effects on the Fluorescence of PRODAN Derivatives.

    PubMed

    Alty, Isaac G; Cheek, Douglas W; Chen, Tao; Smith, David B; Walhout, Emma Q; Abelt, Christopher J

    2016-05-26

    The effects of intramolecular hydrogen-bonding on the fluorescence behavior of three derivatives of 6-propionyl-2-dimethylaminonaphthalene are reported. The H-bonding effects are revealed through comparisons with corresponding reference compounds in which the H-bond-donating hydroxyl groups are replaced with methoxy groups. In toluene, intramolecular H bonding gives rise to a dramatic increase in the fluorescence intensity but only a slight red shift in the position. This behavior is attributed to decreased efficiency in intersystem crossing due to an increase in the energy of the n → π* triplet state. The intramolecular H bond does not induce quenching in acetonitrile; however, in the presence of a very small concentration of methanol, a dual intramolecular, intermolecular H-bonding arrangement does lead to partial quenching as revealed by preferential solvation studies. PMID:27127907

  6. Thermal selectivity of intermolecular versus intramolecular reactions on surfaces

    NASA Astrophysics Data System (ADS)

    Cirera, Borja; Giménez-Agulló, Nelson; Björk, Jonas; Martínez-Peña, Francisco; Martin-Jimenez, Alberto; Rodriguez-Fernandez, Jonathan; Pizarro, Ana M.; Otero, Roberto; Gallego, José M.; Ballester, Pablo; Galan-Mascaros, José R.; Ecija, David

    2016-03-01

    On-surface synthesis is a promising strategy for engineering heteroatomic covalent nanoarchitectures with prospects in electronics, optoelectronics and photovoltaics. Here we report the thermal tunability of reaction pathways of a molecular precursor in order to select intramolecular versus intermolecular reactions, yielding monomeric or polymeric phthalocyanine derivatives, respectively. Deposition of tetra-aza-porphyrin species bearing ethyl termini on Au(111) held at room temperature results in a close-packed assembly. Upon annealing from room temperature to 275 °C, the molecular precursors undergo a series of covalent reactions via their ethyl termini, giving rise to phthalocyanine tapes. However, deposition of the tetra-aza-porphyrin derivatives on Au(111) held at 300 °C results in the formation and self-assembly of monomeric phthalocyanines. A systematic scanning tunnelling microscopy study of reaction intermediates, combined with density functional calculations, suggests a [2+2] cycloaddition as responsible for the initial linkage between molecular precursors, whereas the monomeric reaction is rationalized as an electrocyclic ring closure.

  7. Thiol dependent intramolecular locking of Orai1 channels.

    PubMed

    Alansary, Dalia; Schmidt, Barbara; Dörr, Kathrin; Bogeski, Ivan; Rieger, Heiko; Kless, Achim; Niemeyer, Barbara A

    2016-01-01

    Store-operated Ca(2+) entry mediated by STIM1-gated Orai1 channels is essential to activate immune cells and its inhibition or gain-of-function can lead to immune dysfunction and other pathologies. Reactive oxygen species interacting with cysteine residues can alter protein function. Pretreatment of the Ca(2+) selective Orai1 with the oxidant H2O2 reduces ICRAC with C195, distant to the pore, being its major redox sensor. However, the mechanism of inhibition remained elusive. Here we combine experimental and theoretical approaches and show that oxidation of Orai1 leads to reduced subunit interaction, slows diffusion and that either oxidized C195 or its oxidomimetic mutation C195D located at the exit of transmembrane helix 3 virtually eliminates channel activation by intramolecular interaction with S239 of transmembrane helix 4, thereby locking the channel in a closed conformation. Our results demonstrate a novel mechanistic model for ROS-mediated inhibition of Orai1 and identify a candidate residue for pharmaceutical intervention. PMID:27624281

  8. Thermal selectivity of intermolecular versus intramolecular reactions on surfaces

    PubMed Central

    Cirera, Borja; Giménez-Agulló, Nelson; Björk, Jonas; Martínez-Peña, Francisco; Martin-Jimenez, Alberto; Rodriguez-Fernandez, Jonathan; Pizarro, Ana M.; Otero, Roberto; Gallego, José M.; Ballester, Pablo; Galan-Mascaros, José R.; Ecija, David

    2016-01-01

    On-surface synthesis is a promising strategy for engineering heteroatomic covalent nanoarchitectures with prospects in electronics, optoelectronics and photovoltaics. Here we report the thermal tunability of reaction pathways of a molecular precursor in order to select intramolecular versus intermolecular reactions, yielding monomeric or polymeric phthalocyanine derivatives, respectively. Deposition of tetra-aza-porphyrin species bearing ethyl termini on Au(111) held at room temperature results in a close-packed assembly. Upon annealing from room temperature to 275 °C, the molecular precursors undergo a series of covalent reactions via their ethyl termini, giving rise to phthalocyanine tapes. However, deposition of the tetra-aza-porphyrin derivatives on Au(111) held at 300 °C results in the formation and self-assembly of monomeric phthalocyanines. A systematic scanning tunnelling microscopy study of reaction intermediates, combined with density functional calculations, suggests a [2+2] cycloaddition as responsible for the initial linkage between molecular precursors, whereas the monomeric reaction is rationalized as an electrocyclic ring closure. PMID:26964764

  9. Chirally selective, intramolecular interaction observed in an aminoacyl adenylate anhydride

    NASA Astrophysics Data System (ADS)

    Lacey, James C.; Hall, Leo M.; Mullins, Dail W.; Watkins, Charles L.

    1985-06-01

    All earthly creatures use only L-amino acids in template directed protein synthesis. The reason for this exclusive use of the L-isomer is not yet apparent, although recent experiments by Usher and his colleagues have shown some stereoselctivity in the aminoacylation of di- and polynucleotides [1 3]. We have separately reported on intramolecular interactions between hydrophobic amino acid side chains and the adenine ring in aminoacyl adenylates [4]. There was a preferential association of Phe > Leu = Ile > Val with the adenine in these studies, but we made no attempts to address the question of D, L selectivity. Recently, in1H NMR studies of N-acetylphenylalanyl adenylate anhydride, we noticed evidence that both D- and L-isomers of the amino acid were present and, furthermore, that one isomer seemed to be associating with the adenine ring more strongly than the other. Using HPLC, we have separated the two diastereoisomers and have enzymatically determined that the isomer which associates more strongly is the biologically important one, the L-isomer. We present those studies here and discuss the evolutionary significance of this finding.

  10. Intramolecular phenotypic capacitance in a modular RNA molecule

    PubMed Central

    Hayden, Eric J.; Bendixsen, Devin P.; Wagner, Andreas

    2015-01-01

    Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mechanisms behind capacitance are mostly limited to complex, multicomponent systems often involving several interacting protein molecules. Here we demonstrate phenotypic capacitance within a much simpler system, an individual RNA molecule with catalytic activity (ribozyme). This naturally occurring RNA molecule has a modular structure, where a scaffold module acts as an intramolecular chaperone that facilitates folding of a second catalytic module. Previous studies have shown that the scaffold module is not absolutely required for activity, but dramatically decreases the concentration of magnesium ions required for the formation of an active site. Here, we use an experimental perturbation of magnesium ion concentration that disrupts the folding of certain genetic variants of this ribozyme and use in vitro selection followed by deep sequencing to identify genotypes with altered phenotypes (catalytic activity). We identify multiple conditional mutations that alter the wild-type ribozyme phenotype under a stressful environmental condition of low magnesium ion concentration, but preserve the phenotype under more relaxed conditions. This conditional buffering is confined to the scaffold module, but controls the catalytic phenotype, demonstrating how modularity can enable phenotypic capacitance within a single macromolecule. RNA’s ancient role in life suggests that phenotypic capacitance may have influenced evolution since life’s origins. PMID:26401020

  11. Thermal selectivity of intermolecular versus intramolecular reactions on surfaces.

    PubMed

    Cirera, Borja; Giménez-Agulló, Nelson; Björk, Jonas; Martínez-Peña, Francisco; Martin-Jimenez, Alberto; Rodriguez-Fernandez, Jonathan; Pizarro, Ana M; Otero, Roberto; Gallego, José M; Ballester, Pablo; Galan-Mascaros, José R; Ecija, David

    2016-01-01

    On-surface synthesis is a promising strategy for engineering heteroatomic covalent nanoarchitectures with prospects in electronics, optoelectronics and photovoltaics. Here we report the thermal tunability of reaction pathways of a molecular precursor in order to select intramolecular versus intermolecular reactions, yielding monomeric or polymeric phthalocyanine derivatives, respectively. Deposition of tetra-aza-porphyrin species bearing ethyl termini on Au(111) held at room temperature results in a close-packed assembly. Upon annealing from room temperature to 275 °C, the molecular precursors undergo a series of covalent reactions via their ethyl termini, giving rise to phthalocyanine tapes. However, deposition of the tetra-aza-porphyrin derivatives on Au(111) held at 300 °C results in the formation and self-assembly of monomeric phthalocyanines. A systematic scanning tunnelling microscopy study of reaction intermediates, combined with density functional calculations, suggests a [2+2] cycloaddition as responsible for the initial linkage between molecular precursors, whereas the monomeric reaction is rationalized as an electrocyclic ring closure. PMID:26964764

  12. Intramolecular phenotypic capacitance in a modular RNA molecule.

    PubMed

    Hayden, Eric J; Bendixsen, Devin P; Wagner, Andreas

    2015-10-01

    Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mechanisms behind capacitance are mostly limited to complex, multicomponent systems often involving several interacting protein molecules. Here we demonstrate phenotypic capacitance within a much simpler system, an individual RNA molecule with catalytic activity (ribozyme). This naturally occurring RNA molecule has a modular structure, where a scaffold module acts as an intramolecular chaperone that facilitates folding of a second catalytic module. Previous studies have shown that the scaffold module is not absolutely required for activity, but dramatically decreases the concentration of magnesium ions required for the formation of an active site. Here, we use an experimental perturbation of magnesium ion concentration that disrupts the folding of certain genetic variants of this ribozyme and use in vitro selection followed by deep sequencing to identify genotypes with altered phenotypes (catalytic activity). We identify multiple conditional mutations that alter the wild-type ribozyme phenotype under a stressful environmental condition of low magnesium ion concentration, but preserve the phenotype under more relaxed conditions. This conditional buffering is confined to the scaffold module, but controls the catalytic phenotype, demonstrating how modularity can enable phenotypic capacitance within a single macromolecule. RNA's ancient role in life suggests that phenotypic capacitance may have influenced evolution since life's origins. PMID:26401020

  13. Intramolecular Hydrogen Bonds in Low-Molecular-Weight Polyethylene Glycol.

    PubMed

    Kozlowska, Mariana; Goclon, Jakub; Rodziewicz, Pawel

    2016-04-18

    We used static DFT calculations to analyze, in detail, the intramolecular hydrogen bonds formed in low-molecular-weight polyethylene glycol (PEG) with two to five repeat subunits. Both red-shifted O-H⋅⋅⋅O and blue-shifting C-H⋅⋅⋅O hydrogen bonds, which control the structural flexibility of PEG, were detected. To estimate the strength of these hydrogen bonds, the quantum theory of atoms in molecules was used. Car-Parrinello molecular dynamics simulations were used to mimic the structural rearrangements and hydrogen-bond breaking/formation in the PEG molecule at 300 K. The time evolution of the H⋅⋅⋅O bond length and valence angles of the formed hydrogen bonds were fully analyzed. The characteristic hydrogen-bonding patterns of low-molecular-weight PEG were described with an estimation of their lifetime. The theoretical results obtained, in particular the presence of weak C-H⋅⋅⋅O hydrogen bonds, could serve as an explanation of the PEG structural stability in the experimental investigation. PMID:26864943

  14. Intramolecular electronic energy transfer in bichromophoric molecular macrocyclic systems

    NASA Astrophysics Data System (ADS)

    Speiser, Shammai

    1993-01-01

    The structures and spectral properties of several bichromophoric molecules, suitable for optical data processing, are presented. The bichromophoric molecules are composed of an aromatic ring connected by two methylene chains to an (alpha) -diketone moiety. Both the absorption and emission spectra of these compounds can be attributed to a superposition of the individual spectra of the separate chromophores. The critical transfer radia for electronic energy transfer from the aromatic (donor) chromophore to the (alpha) -diketone (acceptor) chromophore was calculated from the spectral overlap between the fluorescence spectrum of the aromatic ring with the absorption spectrum of the (alpha) -diketone chromophore. The results show that this series of molecules is well suited for a mechanistic study of short-range intramolecular electronic energy transfer (intra-EET). The temperature and the molecular structure dependence of the intra-EET efficiency in this series was measured and analyzed for both singlet-singlet and triplet-triplet routes. The results show that the transfer efficiency is strongly temperature and structure dependent, indicating that exchange interaction is responsible for intra-EET between close chromophores in a bichromophoric molecule. The relative contributions of interchromophoric distance and that of the relative orientation of the two chromophores to exchange interaction are discussed.

  15. Intramolecular Interactions That Induce Helical Rearrangement upon Rhodopsin Activation

    PubMed Central

    Yamazaki, Yoichi; Nagata, Tomoko; Terakita, Akihisa; Kandori, Hideki; Shichida, Yoshinori; Imamoto, Yasushi

    2014-01-01

    Rhodopsin undergoes rearrangements of its transmembrane helices after photon absorption to transfer a light signal to the G-protein transducin. To investigate the mechanism by which rhodopsin adopts the transducin-activating conformation, the local environmental changes in the transmembrane region were probed using the cysteine S-H group, whose stretching frequency is well isolated from the other protein vibrational modes. The S-H stretching modes of cysteine residues introduced into Helix III, which contains several key residues for the helical movements, and of native cysteine residues were measured by Fourier transform infrared spectroscopy. This method was applied to metarhodopsin IIa, a precursor of the transducin-activating state in which the intramolecular interactions are likely to produce a state ready for helical movements. No environmental change was observed near the ionic lock between Arg-135 in Helix III and Glu-247 in Helix VI that maintains the inactive conformation. Rather, the cysteine residues that showed environmental changes were located around the chromophore, Ala-164, His-211, and Phe-261. These findings imply that the hydrogen bond between Helix III and Helix V involving Glu-122 and His-211 and the hydrophobic packing between Helix III and Helix VI involving Gly-121, Leu-125, Phe-261, and Trp-265 are altered before the helical rearrangement leading toward the active conformation. PMID:24692562

  16. Intramolecular Alkene Aminocarbonylation Using Concerted Cycloadditions of Amino-Isocyanates.

    PubMed

    Ivanovich, Ryan A; Clavette, Christian; Vincent-Rocan, Jean-François; Roveda, Jean-Grégoire; Gorelsky, Serge I; Beauchemin, André M

    2016-06-01

    The ubiquity of nitrogen heterocycles in biologically active molecules challenges synthetic chemists to develop a variety of tools for their construction. While developing metal-free hydroamination reactions of hydrazine derivatives, it was discovered that carbazates and semicarbazides can also lead to alkene aminocarbonylation products if nitrogen-substituted isocyanates (N-isocyanates) are formed in situ as reactive intermediates. At first this reaction required high temperatures (150-200 °C), and issues included competing hydroamination and N-isocyanate dimerization pathways. Herein, improved conditions for concerted intramolecular alkene aminocarbonylation with N-isocyanates are reported. The use of βN-benzyl carbazate precursors allows the effective minimization of N-isocyanate dimerization. Diminished dimerization leads to higher yields of alkene aminocarbonylation products, to reactivity at lower temperatures, and to an improved scope for a reaction sequence involving alkene aminocarbonylation followed by 1,2-migration of the benzyl group. Furthermore, fine-tuning of the blocking (masking) group on the N-isocyanate precursor, and reaction conditions relying on base catalysis for N-isocyanate formation from simpler precursors resulted in room temperature reactivity, consequently minimizing the competing hydroamination pathway. Collectively, this work highlights that controlled reactivity of aminoisocyanates is possible, and provides a broadly applicable alkene aminocarbonylation approach to heterocycles possessing the β-aminocarbonyl motif. PMID:27112602

  17. Who Activates the Nucleophile in Ribozyme Catalysis? An Answer from the Splicing Mechanism of Group II Introns.

    PubMed

    Casalino, Lorenzo; Palermo, Giulia; Rothlisberger, Ursula; Magistrato, Alessandra

    2016-08-24

    Group II introns are Mg(2+)-dependent ribozymes that are considered to be the evolutionary ancestors of the eukaryotic spliceosome, thus representing an ideal model system to understand the mechanism of conversion of premature messenger RNA (mRNA) into mature mRNA. Neither in splicing nor for self-cleaving ribozymes has the role of the two Mg(2+) ions been established, and even the way the nucleophile is activated is still controversial. Here we employed hybrid quantum-classical QM(Car-Parrinello)/MM molecular dynamics simulations in combination with thermodynamic integration to characterize the molecular mechanism of the first and rate-determining step of the splicing process (i.e., the cleavage of the 5'-exon) catalyzed by group II intron ribozymes. Remarkably, our results show a new RNA-specific dissociative mechanism in which the bulk water accepts the nucleophile's proton during its attack on the scissile phosphate. The process occurs in a single step with no Mg(2+) ion activating the nucleophile, at odds with nucleases enzymes. We suggest that the novel reaction path elucidated here might be an evolutionary ancestor of the more efficient two-metal-ion mechanism found in enzymes. PMID:27309711

  18. Laboratory determination of the carbon kinetic isotope effects (KIEs) for reactions of methyl halides with various nucleophiles in solution

    USGS Publications Warehouse

    Baesman, S.M.; Miller, L.G.

    2005-01-01

    Large carbon kinetic isotope effects (KIEs) were measured for reactions of methyl bromide (MeBr), methyl chloride (MeCl), and methyl iodide (MeI) with various nucleophiles at 287 and 306 K in aqueous solutions. Rates of reaction of MeBr and MeI with H2O (neutral hydrolysis) or Cl- (halide substitution) were consistent with previous measurements. Hydrolysis rates increased with increasing temperature or pH (base hydrolysis). KIEs for hydrolysis were 51 ?? 6??? for MeBr and 38 ?? 8??? for MeI. Rates of halide substitution increased with increasing temperature and greater reactivity of the attacking nucleophile, with the fastest reaction being that of MeI with Br-. KIEs for halide substitution were independent of temperature but varied with the reactant methyl halide and the attacking nucleophile. KIEs were similar for MeBr substitution with Cl- and MeCl substitution with Br- (57 ?? 5 and 60 ?? 9??? respectively). The KIE for halide exchange of MeI was lower overall (33 ?? 8??? and was greater for substitution with Br- (46 ?? 6???) than with Cl- (29 ?? 6???). ?? Springer Science + Business Media, Inc. 2005.

  19. Asymmetric Intramolecular Alkylation of Chiral Aromatic Imines via Catalytic C-H Bond Activation

    SciTech Connect

    Watzke, Anja; Wilson, Rebecca; O'Malley, Steven; Bergman, Robert; Ellman, Jonathan

    2007-04-16

    The asymmetric intramolecular alkylation of chiral aromatic aldimines, in which differentially substituted alkenes are tethered meta to the imine, was investigated. High enantioselectivities were obtained for imines prepared from aminoindane derivatives, which function as directing groups for the rhodium-catalyzed C-H bond activation. Initial demonstration of catalytic asymmetric intramolecular alkylation also was achieved by employing a sterically hindered achiral imine substrate and catalytic amounts of a chiral amine.

  20. Enthalpy difference between conformations of normal alkanes: effects of basis set and chain length on intramolecular basis set superposition error

    NASA Astrophysics Data System (ADS)

    Balabin, Roman M.

    2011-03-01

    The quantum chemistry of conformation equilibrium is a field where great accuracy (better than 100 cal mol-1) is needed because the energy difference between molecular conformers rarely exceeds 1000-3000 cal mol-1. The conformation equilibrium of straight-chain (normal) alkanes is of particular interest and importance for modern chemistry. In this paper, an extra error source for high-quality ab initio (first principles) and DFT calculations of the conformation equilibrium of normal alkanes, namely the intramolecular basis set superposition error (BSSE), is discussed. In contrast to out-of-plane vibrations in benzene molecules, diffuse functions on carbon and hydrogen atoms were found to greatly reduce the relative BSSE of n-alkanes. The corrections due to the intramolecular BSSE were found to be almost identical for the MP2, MP4, and CCSD(T) levels of theory. Their cancelation is expected when CCSD(T)/CBS (CBS, complete basis set) energies are evaluated by addition schemes. For larger normal alkanes (N > 12), the magnitude of the BSSE correction was found to be up to three times larger than the relative stability of the conformer; in this case, the basis set superposition error led to a two orders of magnitude difference in conformer abundance. No error cancelation due to the basis set superposition was found. A comparison with amino acid, peptide, and protein data was provided.

  1. Food additives

    MedlinePlus

    Food additives are substances that become part of a food product when they are added during the processing or making of that food. "Direct" food additives are often added during processing to: Add nutrients ...

  2. Thiol-ene "click" reaction triggered by neutral ionic liquid: the "ambiphilic" character of [hmim]Br in the regioselective nucleophilic hydrothiolation.

    PubMed

    Kumar, Rajesh; Saima; Shard, Amit; Andhare, Nitin H; Richa; Sinha, Arun K

    2015-01-12

    Thiol-ene "click" chemistry has emerged as a powerful strategy to construct carbon-heteroatom (C-S) bonds, which generally results in the formation of two regioisomers. To this end, the neutral ionic liquid [hmim]Br has been explored as a solvent cum catalyst for the synthesis of linear thioethers from activated and inactivated styrene derivatives or secondary benzyl alcohols and thiols without the requirement of using a metal complex, base, or free radical initiator. Furthermore, detailed mechanistic investigations using (1)H NMR spectroscopy and quadrupole time-of-flight electrospray ionization mass spectrometry (Q-TOF ESI-MS) revealed that the "ambiphilic" character of the ionic liquid promotes the nucleophilic addition of thiol to styrene through an anti-Markovnikov pathway. The catalyst recyclability and the extension of the methodology for thiol-yne click chemistry are additional benefits. A competitive study among thiophenol, styrene, and phenyl acetylene revealed that the rate of reaction is in the order of thiol-yne>thiol-ene>dimerization of thiol in [hmim]Br. PMID:25430704

  3. Substrate-controlled Michael additions of chiral ketones to enones.

    PubMed

    Fàbregas, Mireia; Gómez-Palomino, Alejandro; Pellicena, Miquel; Reina, Daniel F; Romea, Pedro; Urpí, Fèlix; Font-Bardia, Mercè

    2014-12-01

    Substrate-controlled Michael additions of the titanium(IV) enolate of lactate-derived ketone 1 to acyclic α,β-unsaturated ketones in the presence of a Lewis acid (TiCl4 or SnCl4) provide the corresponding 2,4-anti-4,5-anti dicarbonyl compounds in good yields and excellent diastereomeric ratios. Likely, the nucleophilic species involved in such additions are bimetallic enolates that may add to enones through cyclic transition states. Finally, further studies indicate that a structurally related β-benzyloxy chiral ketone can also participate in such stereocontrolled conjugate additions. PMID:25423031

  4. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  5. Intra-molecular cross-linking of acidic residues for protein structure studies.

    PubMed

    Novak, Petr; Kruppa, Gary H

    2008-01-01

    Intra-molecular cross-linking has been suggested as a method of obtaining distance constraints that would help to develop structural models of proteins. Recent work published on intra-molecular cross-linking for protein structural studies has employed commercially available primary amine (lysine, the amino terminus) selective reagents. Previous work using these cross-linkers has shown that for several proteins of known structure, the number of cross-links that can be obtained experimentally may be small compared to what would be expected from the known structure, due to the relative reactivity, distribution and solvent accessibility of the lysines in the protein sequence. To overcome these limitations, we have investigated the use of cross-linking reagents that can react with other reactive side chains in proteins. We used 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to activate the carboxylic acid containing residues, aspartic acid (D), glutamic acid (E) and the carboxy terminus (O), for cross-linking reactions. Once activated, the DEO side chains can react to form "zero-length" cross-links with nearby primary amine containing residues, lysines (K) and the amino terminus (X), via the formation of a new amide bond. We also show that the EDC-activated DEO side chains can be cross-linked to each other using dihydrazides, two hydrazide moieties connected by an alkyl cross-linker arm of variable length. Using these reagents, we have found three new "zero-length" cross-links in ubiquitin consistent with its known structure (M1-E16, M1-E18 and K63-E64). Using the dihydrazide cross-linkers, we have identified two new cross-links (D21-D32 and E24-D32) unambiguously. Using a library of dihydrazide cross-linkers with varying arm length, we have shown that there is a minimum arm length required for the DEO-DEO cross-links of 5.8 A. These results show that additional structural information can be obtained by exploiting new cross-linker chemistry

  6. Intra-molecular cross-linking of acidic residues for protein structure studies.

    SciTech Connect

    Kruppa, Gary Hermann; Young, Malin M.; Novak, Petr; Schoeniger, Joseph S.

    2005-03-01

    Intra-molecular cross-linking has been suggested as a method of obtaining distance constraints that would be useful in developing structural models of proteins. Recent work published on intra-molecular cross-linking for protein structural studies has employed commercially available primary amine selective reagents that can cross-link lysine residues to other lysine residues or the amino terminus. Previous work using these cross-linkers has shown that for several proteins of known structure, the number of cross-links that can be obtained experimentally may be small compared to what would be expected from the known structure, due to the relative reactivity, distribution, and solvent accessibility of the lysines in the protein sequence. To overcome these limitations we have investigated the use of cross-linking reagents that can react with other reactive sidechains in proteins. We used 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to activate the carboxylic acid containing residues, aspartic acid (D), glutamic acid (E), and the carboxy terminus (O), for cross-linking reactions. Once activated, the DEO sidechains can react to form 'zero-length' cross-links with nearby primary amine containing resides, lysines (K) and the amino terminus (X), via the formation of a new amide bond. We also show that the EDC-activated DEO sidechains can be cross-linked to each other using dihydrazides, two hydrazide moieties connected by an alkyl cross-linker ann of variable length. Using these reagents, we have found three new 'zero-length' cross-links in ubiquitin consistent with its known structure (M1-E16, M1-E18, and K63-E64). Using the dihydrazide cross-linkers, we have identified 2 new cross-links (D21-D32 and E24-D32) unambiguously. Using a library of dihydrazide cross-linkers with varying arm length, we have shown that there is a minimum arm length required for the DEO-DEO cross-links of 5.8 angstroms. These results show that additional structural information

  7. A theoretical study on the structure, intramolecular interactions, and detonation performance of hydrazinium dinitramide.

    PubMed

    Zhang, Xueli; Liu, Yan; Wang, Fang; Gong, Xuedong

    2014-01-01

    The structures of hydrazinium dinitramide (HDN) in the gas phase and in aqueous solution have been studied at different levels of theory by using quantum chemistry. The intramolecular hydrogen-bond interactions in HDN were studied by employing the quantum theory of atoms in molecules (QTAIM), as well as those in ammonium dinitramide (ADN), hydrazinium nitroformate (HNF), and ammonium nitroformate (ANF) for comparison. The results showed that HDN possessed the strongest hydrogen bonds, with the largest hydrogen-bond energy (-47.95 kJ mol(-1)) and the largest total hydrogen-bond energy (-60.29 kJ mol(-1)). In addition, the charge transfer between the cation and the anion, the binding energy, the energy difference between the frontier orbitals, and the second-order perturbation energy of HDN were all the largest among the investigated compounds. These strongest intramolecular interactions accounted for the highest decomposition temperature of HDN among all four compounds. The IR spectra in the gas phase and in aqueous solution were very different and showed the significant influence of the solvent. The UV spectrum showed the strongest absorption at about 253 nm. An orbital-interaction diagram demonstrated that the transition of electrons mainly happened inside the anion of HDN. The detonation velocity (D=8.34 km s(-1)) and detonation pressure (P=30.18 GPa) of HDN were both higher than those of ADN (D=7.55 km s(-1) and P=24.83 GPa). The composite explosive HDN/CL-20 with the weight ratio wCL-20 /wHDN =0.388:0.612 showed the best performance (D=9.36 km s(-1) , P=39.82 GPa), which was close to that of CL-20 (D=9.73 km s(-1), P=45.19 GPa) and slightly better than that of the composite explosive ADN/CL-20 (wCL-20 /wADN =0.298:0.702, D=9.34 km s(-1), P=39.63 GPa). PMID:24108480

  8. Nucleophilic substitution in preparation and surface modification of hypercrosslinked stationary phases.

    PubMed

    Janků, Simona; Škeříková, Veronika; Urban, Jiří

    2015-04-01

    Four linear diaminoalkanes (1,2-diaminoethane, 1,4-diaminobutane, 1,6-diaminohexane, and 1,8-diaminooctane) have been used to hypercrosslink poly(styrene-co-vinylbenzyl chloride-co-divinylbenzene) monolithic stationary phases by nucleophilic substitution reaction. The column efficiency of polymer monoliths improved with longer diaminoalkane with 1,8-diaminoctane providing the highest efficiency. The concentration of 1,8-diaminoctane, together with hypercrosslinking time and temperature has been optimized. To improve the permeability of prepared columns, the hypercrosslinking modification has been combined with an early termination of polymerization reaction and decrease in polymerization temperature. The optimal column has been prepared by a polymerization reaction for 2h at 65°C and hypercrosslinked in the presence of 3% 1,8-diaminooctane for 2h at 95°C. The repeatability study of the presented protocol provided relative standard deviation for nine columns prepared independently out of three individual polymerization mixtures in between 2.0-12.0% for retention factors and 1.5-6.5% for plate heights, respectively. Further, we have modified residual chloromethyl groups with 2-aminoethanesulfonic acid (taurine) to prepare monolithic columns suitable for separation of small polar molecules in hydrophilic interaction chromatography. The highest retention of polar thiourea showed the column modified at 70°C for 20 h. Taurine-modified hypercrosslinked column showed the minimum of van Deemter curve of 20 μm. The prepared column provided dual-retention mechanism, including hydrophilic interaction and reversed-phase liquid chromatography that can be controlled by the composition of the mobile phase. The prepared column has been successfully used for an isocratic separation of low-molecular phenolic acids. PMID:25728663

  9. Probing the critical residues for intramolecular fructosyl transfer reaction of a levan fructotransferase.

    PubMed

    Moon, Keum-Ok; Choi, Kyoung-Hwa; Kang, Ho-Young; Oh, Jeong-Il; Jang, Se Bok; Park, Cheon-Seok; Lee, Jong-Hoon; Cha, Jaeho

    2008-06-01

    Levan fructotransferase (LFTase) preferentially catalyzes the transfructosylation reaction in addition to levan hydrolysis, whereas other levan-degrading enzymes hydrolyze levan into a levan-oligosaccharide and fructose. Based on sequence comparisons and enzymatic properties, the fructosyl transfer activity of LFTase is proposed to have evolved from levanase. In order to probe the residues that are critical to the intramolecular fructosyl transfer reaction of the Microbacterium sp. AL-210 LFTase, an error-prone PCR mutagenesis process was carried out, and the mutants that led to a shift in activity from transfructosylation towards hydrolysis of levan were screened by the DNS method. After two rounds of mutagenesis, TLC and HPLC analyses of the reaction products by the selected mutants revealed two major products; one is a di-D-fructose- 2,6':6,2'-dianhydride (DFAIV) and the other is a levanbiose. The newly detected levanbiose corresponds to the reaction product from LFTase lacking transferring activity. Two mutants (2-F8 and 2-G9) showed a high yield of levanbiose (38-40%) compared with the wild-type enzyme, and thus behaved as levanases. Sequence analysis of the individual mutants responsible for the enhanced hydrolytic activity indicated that Asn-85 was highly involved in the transfructosylation activity of LFTase. PMID:18600048

  10. Mechanistic Analysis and Optimization of the Copper-Catalyzed Enantioselective Intramolecular Alkene Aminooxygenation

    PubMed Central

    Paderes, Monissa C.; Keister, Jerome B.; Chemler, Sherry R.

    2013-01-01

    The catalytic asymmetric aminooxygenation of alkenes provides an efficient and straightforward approach to prepare chiral vicinal amino alcohols. We have reported a copper(II)-catalyzed enantioselective intramolecular alkene aminooxygenation, using (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as the oxygen source, which results in the synthesis of chiral indolines and pyrrolidines. Herein we disclose that kinetics studies indicate the reaction is first order both in substrate and the [Cu(R,R)-Ph-bis(oxazoline)]OTf2 catalyst, and zero order in TEMPO. Furthermore, kinetic isotope effect studies support that the cis aminocupration step, the addition of N-Cu across the alkene, is the rate-limiting step. Subsequent formation of a carbon radical intermediate, and direct carbon radical trapping with TEMPO is the indicated mechanism for the C-O bond formation as suggested by a deuterium labeling experiment. A ligand screen revealed that C(4)-phenyl substitution on the bis(oxazoline) is optimal for high asymmetric induction. The size of the substrate’s N-sulfonyl group also influences the enantioselectivity of the reaction. The preparative scale catalytic aminooxygenation reaction (gram scale) was demonstrated and an unexpected dependence on reaction temperature was uncovered on the larger scale reaction. PMID:23244027

  11. Mechanistic analysis and optimization of the copper-catalyzed enantioselective intramolecular alkene aminooxygenation.

    PubMed

    Paderes, Monissa C; Keister, Jerome B; Chemler, Sherry R

    2013-01-18

    The catalytic asymmetric aminooxygenation of alkenes provides an efficient and straightforward approach to prepare chiral vicinal amino alcohols. We have reported a copper(II)-catalyzed enantioselective intramolecular alkene aminooxygenation, using (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as the oxygen source, which results in the synthesis of chiral indolines and pyrrolidines. Herein we disclose that kinetics studies indicate the reaction is first order both in substrate and the [Cu(R,R)-Ph-bis(oxazoline)]OTf(2) catalyst and zero order in TEMPO. Furthermore, kinetic isotope effect studies support that the cis-aminocupration step, the addition of N-Cu across the alkene, is the rate-limiting step. Subsequent formation of a carbon radical intermediate and direct carbon radical trapping with TEMPO is the indicated mechanism for the C-O bond formation as suggested by a deuterium labeling experiment. A ligand screen revealed that C(4)-phenyl substitution on the bis(oxazoline) is optimal for high asymmetric induction. The size of the substrate's N-sulfonyl group also influences the enantioselectivity of the reaction. The preparative-scale catalytic aminooxygenation reaction (gram scale) was demonstrated, and an unexpected dependence on reaction temperature was uncovered on the larger scale reaction. PMID:23244027

  12. Photophysical Properties of Intramolecular Charge Transfer in a Tribranched Donor-π-Acceptor Chromophore.

    PubMed

    Hu, Jiangpu; Li, Yang; Zhu, Huaning; Qiu, Shuhai; He, Guiying; Zhu, Xiaozhang; Xia, Andong

    2015-08-01

    The photophysical properties of intramolecular charge transfer (ICT) in a novel tribranched donor-π-acceptor chromophore, triphenoxazine-2,4,6-triphenyl-1,3,5-triazine (tri-PXZ-TRZ), with thermally activated delayed fluorescence character was investigated in different aprotic solvents by steady-state spectroscopy and femtosecond and nanosecond transient absorption spectroscopy measurements. Increasing the solvent polarity led to a significant increase in the Stokes shift. The large Stokes shift in highly polar solvents was attributed to ICT properties upon excitation; this resulted in a strong interaction between the tri-PXZ-TRZ molecule and the surrounding solvent, which led to a strong solvation process. Quantum-chemical calculations and changes in the dipole moment showed that this compound has a large degree of ICT. Furthermore, an apolar environment helped to preserve the symmetry of tri-PXZ-TRZ and to enhance its emission efficiency. The femtosecond and nanosecond transient absorption spectroscopy results indicated that the excited-state dynamics of this push-pull molecule were strongly influenced by solvent polarity through the formation of a solvent-stabilized ICT state. The excited-state relaxation mechanism of tri-PXZ-TRZ was proposed by performing target model analysis on the femtosecond transient absorption spectra. In addition, the delayed fluorescence of tri-PXZ-TRZ was significantly modulated by a potential competition between solvation and intersystem crossing processes. PMID:26018143

  13. Suppression of human immunodeficiency virus type 1 activity in vitro by oligonucleotides which form intramolecular tetrads.

    PubMed

    Rando, R F; Ojwang, J; Elbaggari, A; Reyes, G R; Tinder, R; McGrath, M S; Hogan, M E

    1995-01-27

    An oligonucleotide (I100-15) composed of only deoxyguanosine and thymidine was able to inhibit human immunodeficiency virus type-1 (HIV-1) in culture assay systems. I100-15 did not block virus entry into cells but did reduce viral-specific transcripts. As assessed by NMR and polyacrylamide gel methods, I100-15 appears to form a structure in which two stacked guanosine tetrads are connected by three two-base long loops. Structure/activity experiments indicated that formation of intramolecular guanosine tetrads was necessary to achieve maximum antiviral activity. The single deoxyguanosine nucleotide present in each loop was found to be extremely important for the overall antiviral activity. The toxicity of I100-15 was determined to be well above the 50% effective dose (ED50) in culture which yielded a high therapeutic index (> 100). The addition of a cholesterol moiety to the 3' terminus of I100-15 (I100-23) reduced the ED50 value to less than 50 nM (from 0.12 microM for I100-15) and increased the duration of viral suppression to greater than 21 days (versus 7-10 days for I100-15) after removal of the drug from infected cell cultures. The favorable therapeutic index of such molecules coupled with the prolonged suppression of HIV-1, suggest that such compounds further warrant investigation as potential therapeutic agents. PMID:7829511

  14. Intramolecular hydrogen bond in biologically active o-carbonyl hydroquinones.

    PubMed

    Martínez-Cifuentes, Maximiliano; Weiss-López, Boris E; Santos, Leonardo S; Araya-Maturana, Ramiro

    2014-01-01

    Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and antioxidant activity. Experimental NMR data were correlated with theoretical calculations at the DFT and ab initio levels. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) calculations were used to study the electronic characteristics of these IHB. As expected, our results show that NBO calculations are better than MEP to describe the strength of the IHBs. NBO energies (∆Eij(2)) show that the main contributions to energy stabilization correspond to LP-->σ* interactions for IHBs, O1…O2-H2 and the delocalization LP-->π* for O2-C2=Cα(β). For the O1…O2-H2 interaction, the values of ∆Eij(2) can be attributed to the difference in the overlap ability between orbitals i and j (Fij), instead of the energy difference between them. The large energy for the LP O2-->π* C2=Cα(β) interaction in the compounds 9-Hydroxy-5-oxo-4,8, 8-trimethyl-l,9(8H)-anthracenecarbolactone (VIII) and 9,10-dihydroxy-4,4-dimethylanthracen-1(4H)-one (VII) (55.49 and 60.70 kcal/mol, respectively) when compared with the remaining molecules (all less than 50 kcal/mol), suggests that the IHBs in VIII and VII are strongly resonance assisted. PMID:24995921

  15. New bimetallic palladium(ii) and platinum(ii) complexes: studies of the nucleophilic substitution reactions, interactions with CT-DNA, bovine serum albumin and cytotoxic activity.

    PubMed

    Jovanović, Snežana; Obrenčević, Katarina; Bugarčić, Živadin D; Popović, Iva; Žakula, Jelena; Petrović, Biljana

    2016-08-01

    Two new dinuclear bimetallic complexes, [{PdCl(bipy)}{μ-(pyrazine)}{PtCl(bipy)}]Cl(ClO4) (1) (bipy is 2,2'-bipyridine) and [{PdCl(en)}{μ-(pyrazine)}{PtCl(en)}]Cl(ClO4) (2) (en is ethylenediamine), have been synthesized and characterized by elemental microanalysis, IR, (1)H NMR spectroscopy and MALDI-TOF mass spectrometry. The pKa values of the coordinated water molecules of the diaqua species were determined as well. Substitution reactions of complexes (1) and (2) with thiourea (Tu), l-methionine (l-Met), l-cysteine (l-Cys), l-histidine (l-His) and guanosine-5'-monophosphate (5'-GMP) were studied under the pseudo-first order conditions as a function of nucleophile concentration and temperature. The order of reactivity of nucleophiles was: Tu > l-Met > l-Cys > l-His > 5'-GMP. Substitution reactions with Tu, l-Cys and l-His were followed by decomposition of bimetallic complexes to the corresponding substituted mononuclear complexes [Pd(N-N)(Nu)2] and [Pt(N-N)(Nu)2] (N-N = bipy, en), releasing the bridging ligand. However, the structures of starting bimetallic complexes were preserved during the reactions with l-Met and 5'-GMP. The absorption spectroscopic study of interactions of calf-thymus DNA (CT-DNA) with complexes (1), (2) and [{PdCl(bipy)}{μ-(NH2(CH2)6H2N)} {PtCl(bipy)}]Cl(ClO4) (3), has shown that all the complexes exhibit high intrinsic binding constants (Kb = 10(4)-10(5) M(-1)). DNA-ethidium bromide (DNA-EB) fluorescence was quenched after addition of complexes (1), (2) or (3), indicating displacement of intercalating EB by complexes. All complexes have shown good binding affinity to bovine serum albumin protein (BSA). Chemosensitivity of A375 (human melanoma) and HeLa (human cervical cancer) cell lines toward complexes (1), (2) and (3) was analyzed by SRB assay. Complex (1) displayed significant inhibitory effect on the growth of both cell lines. PMID:27431616

  16. Hg/Pt-catalyzed conversion of bromo alkynamines/alkynols to saturated and unsaturated γ-butyrolactams/lactones via intramolecular electrophilic cyclization.

    PubMed

    Kiran Kumar, Yalla; Ranjith Kumar, Gadi; Sridhar Reddy, Maddi

    2016-01-28

    Convenient and general Hg(ii)/Pt(iv) catalyzed syntheses of γ-butyrolactams and α,β-unsaturated γ-butyrolactones/lactams are described via intramolecular electrophilic cyclizations of bromoalkynes with tosylamino and hydroxyl tethers. The reaction features the use of wet solvents, the exclusion of any base and additive, mild conditions and practical yields. We also synthesised few chiral lactams through this pathway. Additionally, it is shown that the NHTs group distanced further from the homopropargylic position assists regioselective bromoalkyne hydration to yield useful α-bromoketones. Furthermore, Boc protected bromo homo propargyl amines undergo 6-endo-dig cyclization through Boc oxygen to give bromomethylene substituted oxazinones. PMID:26647118

  17. Trade-Offs in Capacity and Rechargeability in Nonaqueous Li-O2 Batteries: Solution-Driven Growth versus Nucleophilic Stability.

    PubMed

    Khetan, Abhishek; Luntz, Alan; Viswanathan, Venkatasubramanian

    2015-04-01

    The development of high-capacity rechargeable Li-O2 batteries requires the identification of stable solvents that can promote a solution-based discharge mechanism, which has been shown to result in higher discharge capacities. Solution-driven discharge product growth requires dissolution of the adsorbed intermediate LiO2*, thus generating solvated Li+ and O2(-) ions. Such a mechanism is possible in solvents with high Gutmann donor or acceptor numbers. However, O2(-) is a strong nucleophile and is known to attack solvents via proton/hydrogen abstraction or substitution. This kind of a parasitic process is extremely detrimental to the battery's rechargeability. In this work, we develop a thermodynamic model to describe these two effects and demonstrate an anticorrelation between solvents’ stability and their ability to enhance capacity via solution-mediated discharge product growth. We analyze the commonly used solvents in the same framework and describe why solvents that can promote higher discharge capacity are also prone to degradation. Solvating additives for practical Li-O2 batteries will have to be outliers to this observed anticorrelation. PMID:26262983

  18. Signatures of field-induced intramolecular quantum interference in high-order harmonic generation by laser-irradiated homonuclear diatomics

    NASA Astrophysics Data System (ADS)

    Usachenko, Vladimir; Kim, Vyacheslav; Pyak, Pavel

    2015-05-01

    We report about the results of our theoretical study of the strong-field phenomenon of high-order harmonic generation (HHG) in homonuclear diatomics H2+ andH2 irradiated by a high-intensity laser field of mid-infrared wavelengths corresponding to intermediate values of the so-called Keldysh parameter (γ <= 1). The problem is addressed within the length-gauge (LG) formulation of strong-field approximation (SFA) additionally exploiting the density-functional-theory (DFT) method for numerical composition of initial (laser-free) molecular state using the routines of GAUSSIAN-03 code. The results of our present LG-VGA calculation well reproduce a pronounced interference-related minimum arising in high-frequency region of respective molecular HHG spectra and suggesting clear signatures of the field-induced intramolecular interference corresponding to photoelectron emission to intermediate continuum states from different atomic centers.

  19. Copper(I)-catalyzed enantioselective nucleophilic borylation of aldehydes: an efficient route to enantiomerically enriched α-alkoxyorganoboronate esters.

    PubMed

    Kubota, Koji; Yamamoto, Eiji; Ito, Hajime

    2015-01-14

    The first catalytic enantioselective nucleophilic borylation of a C═O double bond has been achieved. A series of aldehydes reacted with a diboron reagent in the presence of a copper(I)/DTBM-SEGPHOS complex catalyst using MeOH as a proton source to give the corresponding optically active α-alkoxyorganoboronate esters with excellent enantioselectivities. Furthermore, the products could be readily converted to the corresponding functionalized chiral alcohol derivatives through stereospecific C-C bond forming reactions involving the stereogenic C-B bond. PMID:25494834

  20. Food additives.

    PubMed

    Berglund, F

    1978-01-01

    The use of additives to food fulfils many purposes, as shown by the index issued by the Codex Committee on Food Additives: Acids, bases and salts; Preservatives, Antioxidants and antioxidant synergists; Anticaking agents; Colours; Emulfifiers; Thickening agents; Flour-treatment agents; Extraction solvents; Carrier solvents; Flavours (synthetic); Flavour enhancers; Non-nutritive sweeteners; Processing aids; Enzyme preparations. Many additives occur naturally in foods, but this does not exclude toxicity at higher levels. Some food additives are nutrients, or even essential nutritents, e.g. NaCl. Examples are known of food additives causing toxicity in man even when used according to regulations, e.g. cobalt in beer. In other instances, poisoning has been due to carry-over, e.g. by nitrate in cheese whey - when used for artificial feed for infants. Poisonings also occur as the result of the permitted substance being added at too high levels, by accident or carelessness, e.g. nitrite in fish. Finally, there are examples of hypersensitivity to food additives, e.g. to tartrazine and other food colours. The toxicological evaluation, based on animal feeding studies, may be complicated by impurities, e.g. orthotoluene-sulfonamide in saccharin; by transformation or disappearance of the additive in food processing in storage, e.g. bisulfite in raisins; by reaction products with food constituents, e.g. formation of ethylurethane from diethyl pyrocarbonate; by metabolic transformation products, e.g. formation in the gut of cyclohexylamine from cyclamate. Metabolic end products may differ in experimental animals and in man: guanylic acid and inosinic acid are metabolized to allantoin in the rat but to uric acid in man. The magnitude of the safety margin in man of the Acceptable Daily Intake (ADI) is not identical to the "safety factor" used when calculating the ADI. The symptoms of Chinese Restaurant Syndrome, although not hazardous, furthermore illustrate that the whole ADI

  1. Unexpected Michael Additions on the Way to 2.3,8.9-Dibenzanthanthrenes with Interesting Structural Properties.

    PubMed

    Reus, Christian; Lechner, Marc P; Schulze, Matthias; Lungerich, Dominik; Diner, Colin; Gruber, Marco; Stryker, Jeffrey M; Hampel, Frank; Jux, Norbert; Tykwinski, Rik R

    2016-06-27

    The synthesis and properties of a new polycyclic aromatic hydrocarbon containing eight annulated rings and based on the anthanthrene core is described. An unexpected, nucleophile-dependent Michael addition to a dibenzanthanthrene-1,7-dione is found, giving a product with three triisopropylsilylacetylene units and a remarkable solid-state structure (as determined by X-ray crystallography). PMID:27140668

  2. Mean-Field Theory of Intra-Molecular Charge Ordering in (TTM--TTP)I3

    NASA Astrophysics Data System (ADS)

    Omori, Yukiko; Tsuchiizu, Masahisa; Suzumura, Yoshikazu

    2011-02-01

    We examine an intra-molecular charge-ordered (ICO) state in the multi-orbital molecular compound (TTM--TTP)I3 on the basis of an effective two-orbital model derived from ab initio calculations. Representing the model in terms of the fragment molecular-orbital (MO) picture, the ICO state is described as the charge disproportionation on the left and right fragment MOs. By applying the mean-field theory, the phase diagram of the ground state is obtained as a function of the inter-molecular Coulomb repulsion and the intra-molecular transfer integral. The ICO state is stabilized by large inter-fragment Coulomb interactions, and the small intra-molecular transfer energy between two fragment MOs. Furthermore, we examine the finite-temperature phase diagram. The relevance to the experimental observations in the molecular compound of (TTM--TTP)I3 is also discussed.

  3. Laser-Induced Dynamical Chirality and Intramolecular Energy Flow in the CH Chromophore

    SciTech Connect

    Thanopulos, Ioannis

    2007-11-29

    We review the quantum dynamics of intramolecular energy flow during and after coherent infrared multiphoton excitation of the CH organic chromophore. The understanding of the underlying dynamics is of central importance for a wide range of systems in molecular physics, chemistry and biology, due to the experimentally supported assumption that the chromophore dynamics is weakly-dependent on a specific environment, in particular on sub-picosecond time scale. The excitation process due to the interaction with the laser field is studied by computationally monitoring the wave packet motion in the configuration sub-space relevant to femtosecond dynamics, using global analytical potential energy and electric dipole functions previously developed. The features of the intramolecular vibrational energy redistribution and the related dynamical time scales are investigated. In particular, we discuss the generation of dynamical chirality in methane istopomers, the corresponding stereomutation and racemization phenomena on the femtosecond time scale, and their relation to intramolecular vibrational energy redistribution.

  4. Investigating the Disordered States of Two Proteins Using Intramolecular Contact Formation

    NASA Astrophysics Data System (ADS)

    Singh, Vijay; Kopka, Michaela; Chen, Yujie; Wedemeyer, William; Lapidus, Lisa

    2007-03-01

    Using the quenching of the triplet state of tryptophan by cysteine, we investigate the unfolded states of two structurally similar but sequentially non-homologous proteins, the IgG binding domain of proteins L and G, under a range of denaturing conditions. These proteins show remarkably similar dynamics of intramolecular diffusion marked by a decrease in contact formation at denaturant conditions that favor folding. A reaction limited rate and the diffusion limited rate are obtained by measuring the viscosity dependence of the intramolecular contact rate. To further investigate the polymer dynamics of the unfolded state under folding conditions, we modeled the proteins as a worm-like chain with excluded volume using Szabo, Schulten and Schulten (SSS) theory to estimate the effective persistence length and intramolecular diffusion constant at various concentrations of GdnHCl. The results reveal an unfolded state under folding conditions that is significantly more compact and less diffusive than the fully denatured state.

  5. Intramolecular circuits connected to N electrodes using a scattering matrix approach

    NASA Astrophysics Data System (ADS)

    Ami, S.; Joachim, C.

    2002-04-01

    The scattering matrix technique is extended to describe the electronic transport characteristics of intramolecular circuits driven in a ballistic or a tunnel transport regime. The circuit is assumed to be connected by N electrodes. As a working example, the electronic properties of a T-node circuit are presented leading to the design of an OR logic gate working in a ballistic regime. In the tunnel regime, only the ``node'' Kirchhoff law of circuit remains valid at the nodes of an intramolecular tunnel circuit and the electronic characteristics of the branches composing the circuit are mutually independent. It results in a difficult design of a logic OR intramolecular gate of high performance and stability, pointing out the urge for new architectures to implement complex logic functions inside a single molecule.

  6. Electrophilic, Ambiphilic, and Nucleophilic C-H bond Activation. Understanding the electronic continuum of C-H bond activation through transition-state and reaction pathway interaction energy decompositions

    SciTech Connect

    Ess, Daniel H.; Goddard, William A.; Periana, Roy A.

    2010-10-29

    The potential energy and interaction energy profiles for metal- and metal-ligand-mediated alkane C-H bond activation were explored using B3LYP density functional theory (DFT) and the absolutely localized molecular orbital energy decomposition analysis (ALMO-EDA). The set of complexes explored range from late transition metal group 10 (Pt and Pd) and group 11 (Au) metal centers to group 7-9 (Ir, Rh, Ru, and W) metal centers as well as a group 3 Sc complex. The coordination geometries, electron metal count (d8, d6, d4, and d0), and ligands (N-heterocycles, O-donor, phosphine, and Cp*) are also diverse. Quantitative analysis using ALMO-EDA of both directions of charge-transfer stabilization (occupied to unoccupied orbital stabilization) energies between the metal-ligand fragment and the coordinated C-H bond in the transition state for cleavage of the C-H bond allows classification of C-H activation reactions as electrophilic, ambiphilic, or nucleophilic on the basis of the net direction of charge-transfer energy stabilization. This bonding pattern transcends any specific mechanistic or bonding paradigm, such as oxidative addition, σ-bond metathesis, or substitution. Late transition metals such as Au(III), Pt(II), Pd(II), and Rh(III) metal centers with N-heterocycle, halide, or O-donor ligands show electrophilically dominated reaction profiles with forward charge-transfer from the C-H bond to the metal, leading to more stabilization than reverse charge transfer from the metal to the C-H bond. Transition states and reaction profiles for d6 Ru(II) and Ir(III) metals with Tp and acac ligands were found to have nearly equal forward and reverse charge-transfer energy stabilization. This ambiphilic region also includes the classically labeled electrophilic cationic species Cp*(PMe3)Ir(Me). Nucleophilic character, where the metal to C-H bond charge-transfer interaction is most stabilizing, was found in

  7. Photophysics of 2-(4'-amino-2'-hydroxyphenyl)-1H-imidazo-[4,5-c]pyridine and its analogues: intramolecular proton transfer versus intramolecular charge transfer.

    PubMed

    Behera, Santosh Kumar; Karak, Ananda; Krishnamoorthy, G

    2015-02-12

    Photophysical characteristics of 2-(4'-amino-2'-hydroxyphenyl)-1H-imidazo-[4,5-c]pyridine (AHPIP-c) have been studied in various aprotic and protic solvents using UV-visible, steady state fluorescence and time-resolved fluorescence spectroscopic techniques. To comprehend the competition between the intramolecular charge transfer (ICT) and the excited state intramolecular proton transfer (ESIPT) processes, the photophysical properties of 2-(4'-amino-2'-methoxyphenyl)-1H-imidazo-[4,5-c]pyridine (AMPIP-c) and 2-(4'-aminophenyl)-1H-imidazo-[4,5-c]pyridine (APIP-c) were also investigated. Though APIP-c displays twisted ICT (TICT) emission in protic solvents, AHPIP-c exhibits normal and tautomer emissions in aprotic as well as in protic solvents due to ESIPT. However, the methoxy derivative, AMPIP-c, emits weak TICT fluorescence in methanol. PMID:25337987

  8. A novel non-fluorescent excited state intramolecular proton transfer phenomenon induced by intramolecular hydrogen bonds: an experimental and theoretical investigation

    PubMed Central

    Yin, Hang; Li, Hui; Xia, Guomin; Ruan, Chengyan; Shi, Ying; Wang, Hongming; Jin, Mingxing; Ding, Dajun

    2016-01-01

    Two molecules, 1-hydroxypyrene-2-carbaldehyde (HP) and 1-methoxypyrene-2-carbaldehyde (MP) were explored. We investigated their photophysical properties, using experimental transient absorption and theoretical density functional theory/time-dependent density functional theory (DFT/TDDFT). HP and MP have similar geometric conformations but exhibit entirely different photophysical properties upon excitation into the S1 state. In contrast to traditional excited state intramolecular proton transfer (ESIPT) in molecules that exhibit either single or dual fluorescence, HP has an unusual non-fluorescent property. Specifically, the ultrafast ESIPT process occurs in 158 fs and is followed by an intersystem crossing (ISC) component of 11.38 ps. In contrast to HP, MP undergoes only an 8 ps timescale process, which was attributed to interactions between solute and solvent. We concluded that this difference arises from intramolecular hydrogen bonds (IMHBs), which induce drastic structural alterntion upon excitation. PMID:26790961

  9. A DFT study on PBu3-catalyzed intramolecular cyclizations of N-allylic substituted α-amino nitriles for the formation of functionalized pyrrolidines: mechanisms, selectivities, and the role of catalysts.

    PubMed

    Zheng, Linjie; Tang, Mingsheng; Wang, Yang; Guo, Xiaokang; Wei, Donghui; Qiao, Yan

    2016-03-21

    The mechanisms and chemo- and stereo-selectivities of PBu3-catalyzed intramolecular cyclizations of N-allylic substituted α-amino nitriles leading to functionalized pyrrolidines (5-endo-trig cyclization, Mechanism A) and their competing reaction leading to another kind of pyrrolidine (5-exo-trig cyclization, Mechanism B) have been investigated using density functional theory (DFT). Multiple possible reaction pathways associated with four different isomers (RR, SR, RS, and SS) for Mechanism A, and two isomers (R and S) for Mechanism B have been studied. The calculated results indicate that the Gibbs free energy barriers of Mechanism A are remarkably lower than those of Mechanism B, and the reaction pathway leading to the RS-configured product has the lowest Gibbs free energy barrier, which is in agreement with the experiments. A C-Hπ interaction has been identified to be responsible for the favorability of RS isomers by non-covalent interaction (NCI) analysis. Moreover, global reaction indexes (GRIs) and NBO analyses confirm that PBu3 acts as a Lewis base to strengthen the nucleophilicity of the reaction active site. The mechanistic insights gained in the present study should be valuable for the rational design of effective organocatalysts for this kind of reaction with high chemo- and stereo-selectivities. PMID:26911423

  10. Intramolecular Dehydrogenative Coupling of 2,3-Diaryl Acrylic Compounds: Access to Substituted Phenanthrenes.

    PubMed

    Gupta, Vijay; Rao, V U Bhaskara; Das, Tamal; Vanka, Kumar; Singh, Ravi P

    2016-07-01

    A simple, facile, and environmentally benign intramolecular dehydrogenative coupling of various 1,2-diarylethylenes for the synthesis of phenanthrenes in excellent yield has been described. This new methodology uses ceric ammonium nitrate (CAN) as a promoter at room temperature and has been extended to intermolecular synthesis of biaryl compounds. The electron transfer from methoxyarene to cerium leads to cationic radical formation, which further proceeds to intramolecular coupling. Preliminary mechanistic investigation by EPR spectroscopy and density functional theory calculation suggested a similar view. PMID:27232691

  11. Intra-molecular enantiomerism in R-(+)-Limonene as evidenced by the differential bond polarizabilities

    NASA Astrophysics Data System (ADS)

    Shen, Hongxia; Wu, Guozhen; Wang, Peijie

    2014-07-01

    We propose an algorithm to obtain the differential bond polarizabilities from the Raman and Raman optical activity (ROA) spectral intensities. The signs of the differential bond polarizabilities of R-Limonene demonstrate that there is intra-molecular enantiomerism in its six membered ring structure. That is, the signs of the differential bond polarizabilities around the six membered ring are inversed under an intra-molecular mirror reflection. This is similar to what happens in the right and left handed chiral isomers under a mirror conversion.

  12. Reversible Tuning of Interfacial and Intramolecular Charge Transfer in Individual MnPc Molecules.

    PubMed

    Zhong, Jian-Qiang; Wang, Zhunzhun; Zhang, Jia Lin; Wright, Christopher A; Yuan, Kaidi; Gu, Chengding; Tadich, Anton; Qi, Dongchen; Li, He Xing; Lai, Min; Wu, Kai; Xu, Guo Qin; Hu, Wenping; Li, Zhenyu; Chen, Wei

    2015-12-01

    The reversible selective hydrogenation and dehydrogenation of individual manganese phthalocyanine (MnPc) molecules has been investigated using photoelectron spectroscopy (PES), low-temperature scanning tunneling microscopy (LT-STM), synchrotron-based near edge X-ray absorption fine structure (NEXAFS) measurements, and supported by density functional theory (DFT) calculations. It is shown conclusively that interfacial and intramolecular charge transfer arises during the hydrogenation process. The electronic energetics upon hydrogenation is identified, enabling a greater understanding of interfacial and intramolecular charge transportation in the field of single-molecule electronics. PMID:26528623

  13. Synthesis of high specific activity (+)- and (-)-6-( sup 18 F)fluoronorepinephrine via the nucleophilic aromatic substitution reaction

    SciTech Connect

    Ding, Y.S.; Fowler, J.S.; Gatley, S.J.; Dewey, S.L.; Wolf, A.P. )

    1991-02-01

    The first example of a no-carrier-added {sup 18}F-labeled catecholamine, 6-({sup 18}F)fluoronorepinephrine (6-({sup 18}F)FNE), has been synthesized via nucleophilic aromatic substitution. The racemic mixture was resolved on a chiral HPLC column to obtain pure samples of (-)-6-({sup 18}F)FNE and (+)6-({sup 18}F)FNE. Radiochemical yields of 20% at the end of bombardment (EOB) for the racemic mixture (synthesis time 93 min), 6% for each enantiomer (synthesis time 128 min) with a specific activity of 2-5 Ci/mumol at EOB were obtained. Chiral HPLC peak assignment for the resolved enantiomers was achieved by using two independent methods: polarimetric determination and reaction with dopamine beta-hydroxylase. Positron emission tomography (PET) studies with racemic 6-({sup 18}F)FNE show high uptake and retention in the baboon heart. This work demonstrates that nucleophilic aromatic substitution by ({sup 18}F)fluoride ion is applicable to systems having electron-rich aromatic rings, leading to high specific activity radiopharmaceuticals. Furthermore, the suitably protected dihydroxynitrobenzaldehyde 1 may serve as a useful synthetic precursor for the radiosynthesis of other complex {sup 18}F-labeled radiotracers.

  14. Porous coordination polymers of diverse topologies based on a twisted tetrapyridylbiaryl: application as nucleophilic catalysts for acetylation of phenols.

    PubMed

    Seth, Saona; Venugopalan, Paloth; Moorthy, Jarugu Narasimha

    2015-01-26

    Porous coordination polymers (CPs) with partially uncoordinated pyridyl rings based on rationally designed polypyridyl linkers are appealing from the point of view of their application as nucleophilic catalysts. A D2d -symmetric tetradentate organic linker L, that is, 2,2',6,6'-tetramethoxy-3,3',5,5'-tetrakis(4-pyridyl)biphenyl, was designed and synthesized for metal-assisted self-assembly aimed at porous CPs. Depending on the nature of the metal ion and the counter anion, the ligand L is found to function as a 3- or 4-connecting building block leading to porous CPs of diverse topologies. The reaction of L with Zn(NO3 )2 and Cd(NO3 )2 yields porous 2 D CPs of "fes" topology, in which the tetrapyridyl linker L serves as a 3-connecting unit with its free pyridyl rings well exposed into the pores. The functional utility of these porous CPs containing uncoordinated pyridyl rings is demonstrated by employing them as efficient heterogeneous nucleophilic catalysts for acetylation of a number of phenols with varying electronic properties and reactivities. PMID:25430673

  15. Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate

    PubMed Central

    He, Qinggang; Wang, Ying; Alfeazi, Ines; Sadeghi, Saman

    2015-01-01

    An electrochemical method with the ability to conduct 18F-fluorination of aromatic molecules through direct nucleophilic fluorination of cationic intermediates is presented in this paper. The reaction was performed on a remote-controlled automatic platform. Nucleophilic electrochemical fluorination of tert-butyloxycarbonyl (Boc) protected catechol, an intermediate model molecule for the positron emission tomography (PET) probe (3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine), was performed. Fluorination was achieved under potentiostatic anodic oxidation in acetonitrile containing Et3N · 3HF and other supporting electrolytes. Radiofluorination efficiency was influenced by a number of variables, including the concentration of the precursor, concentration of Et3N · 3HF, type of supporting electrolyte, temperature and time, as well as applied potentials. Radiofluorination efficiency of 10.4 ± 0.6% (n = 4) and specific activity of up to 43 GBq/mmol was obtained after 1 h electrolysis of 0.1 M of 4-tert-butyl-diboc-catechol in the acetonitrile solution of Et3N · 3HF (0.033 M) and NBu4PF6 (0.05 M). Density functional theory (DFT) was employed to explain the tert-butyl functional group facilitation of electrochemical oxidation and subsequent fluorination. PMID:25000498

  16. How Do Nutritional Antioxidants Really Work: Nucleophilic Tone and Para-Hormesis Versus Free Radical Scavenging in vivo

    PubMed Central

    Forman, Henry Jay; Davies, Kelvin J. A.; Ursini, Fulvio

    2013-01-01

    We present arguments for an evolution in our understanding of how antioxidants in fruits and vegetables exert their health-protective effects. There is much epidemiological evidence for disease prevention by dietary antioxidants and chemical evidence that such compounds react in one-electron reactions with free radicals in vitro. Nonetheless, kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. Instead, enzymatic removal of non-radical electrophiles, such as hydroperoxides, in two-electron redox reactions is the major antioxidant mechanism. Furthermore, we propose that a major mechanism of action for nutritional antioxidants is the paradoxical oxidative activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which maintains protective oxidoreductases and their nucleophilic substrates. This maintenance of ‘Nucleophilic Tone,’ by a mechanism that can be called ‘Para-Hormesis,’ provides a means for regulating physiological non-toxic concentrations of the non-radical oxidant electrophiles that boost antioxidant enzymes, and damage removal and repair systems (for proteins, lipids, and DNA), at the optimal levels consistent with good health. PMID:23747930

  17. Solvent effects on kinetics of an heteroatomic nucleophilic substitution reaction in ionic liquid and molecular solvents mixtures

    NASA Astrophysics Data System (ADS)

    Salari, Hadi; Pedervand, Mohsen; Sadeghzadeh-Darabi, Faramarz; Gholami, Mohammad Reza

    2013-12-01

    Rate constants, k A, for the aromatic nucleophilic substitution reaction of 2-chloro-3,5-dinitropyridine with aniline were determined in different compositions of 2-propanol mixed with hexane, benzene, and 2-methylpropan-2-ol and 1-ethyl-3-methylimidazolium ethylsulfate ([Emim][EtSO4]) with dimethyl sulfoxide at 25°C. The obtained rate constants of the reaction in pure solvents are in the following order: 2-methylpropan-2-ol > dimethyl sulfoxide > 2-propanol > hexane > benzene > [Emim][EtSO4]. Molecularmicroscopic solvent parameters corresponding to the selected binary mixtures were utilized to study the kinetics of a nucleophilic substitution reaction in order to investigate and compare the effects of the solvents on a chemical process. The influence of solvent parameters including normalized polarity ( E {/T N }), dipolarity/polarizability (π*), hydrogen bond donor acidity (α), and hydrogen bond acceptor basicity (β) on the second-order rate constants were investigated and multiple linear regressions gave much better results with regard to single parameter regressions. The dipolarity/polarizability of media has a positive effect in all mixtures regarding zwitterionic character of the reaction intermediate and the hydrogen bond acceptor basicity of the solvent by stabilizing of activated complex increases the reaction rate.

  18. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  19. Phosphazene additives

    SciTech Connect

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  20. Silver(I)-Catalyzed Addition of Phenols to Alkyne Cobalt Cluster Stabilized Carbocations.

    PubMed

    Valderas, Carolina; Casarrubios, Luis; Lledos, Agusti; Ortuño, Manuel A; de la Torre, María C; Sierra, Miguel A

    2016-06-20

    A smooth catalytic method to use phenols as the nucleophilic partner in the Nicholas reaction has been developed. The method uses either Ag(I) or Au(I) catalysts with AgClO4 or AgBF4 as the most efficient catalysts tested. Neither additional additives nor cocatalysts were required and the formation of the corresponding phenol adducts occurred in excellent yields. The process has the single limitation of the inability of less nucleophilic phenols (4-nitrophenol) to generate the corresponding adducts. Additionally, the reaction is highly diastereoselective. DFT calculations allow a catalytic cycle to be proposed that involves trimetallic intermediates; the rate-determining step of the reaction is hydroxy-group elimination in a cobalt-silver trimetallic intermediate. PMID:27187529

  1. Application of the intramolecular vinylogous Morita-Baylis-Hillman reaction toward the synthesis of the spinosyn A tricyclic nucleus.

    PubMed

    Mergott, Dustin J; Frank, Scott A; Roush, William R

    2002-09-01

    [reaction: see text] A concise synthesis of the spinosyn A tricyclic nucleus 27 has been developed by a route featuring a one-pot tandem intramolecular Diels-Alder reaction and intramolecular vinylogous Morita-Baylis-Hillman cyclization in which five stereocenters in tricycle 10 are set with excellent selectivity. PMID:12201741

  2. Excited state intramolecular charge transfer reaction in nonaqueous electrolyte solutions: Temperature dependence

    SciTech Connect

    Pradhan, Tuhin; Gazi, Harun Al Rasid; Biswas, Ranjit

    2009-08-07

    Temperature dependence of the excited state intramolecular charge transfer reaction of 4-(1-azetidinyl)benzonitrile (P4C) in ethyl acetate (EA), acetonitrile (ACN), and ethanol at several concentrations of lithium perchlorate (LiClO{sub 4}) has been investigated by using the steady state and time resolved fluorescence spectroscopic techniques. The temperature range considered is 267-343 K. The temperature dependent spectral peak shifts and reaction driving force (-{Delta}G{sub r}) in electrolyte solutions of these solvents can be explained qualitatively in terms of interaction between the reactant molecule and ion-atmosphere. Time resolved studies indicate that the decay kinetics of P4C is biexponential, regardless of solvents, LiClO{sub 4} concentrations, and temperatures considered. Except at higher electrolyte concentrations in EA, reaction rates in solutions follow the Arrhenius-type temperature dependence where the estimated activation energy exhibits substantial electrolyte concentration dependence. The average of the experimentally measured activation energies in these three neat solvents is found to be in very good agreement with the predicted value based on data in room temperature solvents. While the rate constant in EA shows a electrolyte concentration induced parabolic dependence on reaction driving force (-{Delta}G{sub r}), the former in ethanol and ACN increases only linearly with the increase in driving force (-{Delta}G{sub r}). The data presented here also indicate that the step-wise increase in solvent reorganization energy via sequential addition of electrolyte induces the ICT reaction in weakly polar solvents to crossover from the Marcus inverted region to the normal region.

  3. High-resolution electronic spectroscopy of the doorway states to intramolecular charge transfer.

    PubMed

    Fleisher, Adam J; Bird, Ryan G; Zaleski, Daniel P; Pate, Brooks H; Pratt, David W

    2013-04-25

    Reported here are several of the ground, first, and second excited state structures and dipole moments of three benchmark intramolecular charge transfer (ICT) systems; 4-(1H-pyrrol-1-yl)benzonitrile (PBN), 4,4'-dimethylaminobenzonitrile (DMABN), and 4-(1-pyrrolidinyl)benzonitrile (PYRBN), isolated in the gas phase and probed by rotationally resolved spectroscopy in a molecular beam. The related molecules 1-phenylpyrrole (PP) and 4-aminobenzonitrile (ABN) also are discussed. We find that the S1 electronic state is of B symmetry in all five molecules. In PBN, a second excited state (S2) of A symmetry is found only ~400 cm(-1) above the presumed origin of the S1 state. The change in dipole moment upon excitation to the A state is measured to be Δμ ≈ 3.0 D, significantly smaller than the value predicted by theory and also smaller than that observed for the "anomalous" ICT band of PBN in solution. The B state dipole moments of DMABN and PYRBN are large, ~10.6 D, slightly larger than those attributed to "normal" LE fluorescence in solution. In addition, we find the unsaturated donor molecules (PP, PBN) to be twisted in their ground states and to become more planar upon excitation, even in the A state, whereas the saturated donor molecules (ABN, DMABN, PYRBN), initially planar, either remain planar or become more twisted in their excited states. It thus appears that the model that is appropriate for describing ICT in these systems depends on the geometry of the ground state. PMID:22913563

  4. Highly selective colorimetric sensing of Cu(II) ions in aqueous solution via modulation of intramolecular charge transfer transition of aminonaphthoquinone chemosensor.

    PubMed

    Madhupriya, Selvaraj; Elango, Kuppanagounder P

    2012-11-01

    An aminonaphthoquinone based colorimetric chemosensor has been developed and demonstrated for the highly selective detection of Cu(II) ions in aqueous solution. The intramolecular charge transfer (ICT) transition exits in amine moiety directly attached to the quinone ring is modulated by the d-d transition of a square planar Cu(II)-receptor complex resulting in a change of color from yellow to blue. No significant color change was observed upon addition of other selected metal ions. The sensing property has been investigated using various spectral techniques (UV-Vis, fluorescence) and product analysis (Elemental analysis, magnetic moment, UV-Vis, FT-IR, EPR). PMID:22750343

  5. Using Open-Ended Questions to Diagnose Students' Understanding of Inter- and Intramolecular Forces

    ERIC Educational Resources Information Center

    Rompayom, Patcharee; Tambunchong, Chinda; Wongyounoi, Somson; Dechsri, Precharn

    2011-01-01

    The purpose of this study was to investigate Grade 10 Thai students about their understanding on inter- and intramolecular forces. Sixty four students were elicited by administered open-ended questions after finishing normal instruction on chemical bonding topics. The instrument was in a set of open-ended questions which contained a number of…

  6. Assembly of the Isoindolinone Core of Muironolide A by Asymmetric Intramolecular Diels-Alder Cycloaddition

    PubMed Central

    Flores, Beatris; Molinski, Tadeusz F.

    2011-01-01

    The hexahydro-1H-isoindolin-1-one core of muironolide A was prepared by asymmetric intramolecular Diels Alder cycloaddition using a variant of the MacMillan organocatalyst which sets the C4,C5 and C11 stereocenters. PMID:21751773

  7. Homoallylic amines by reductive inter- and intramolecular coupling of allenes and nitriles

    PubMed Central

    Manojlovic, Marija D

    2011-01-01

    Summary The one-pot hydrozirconation of allenes and nitriles followed by an in situ transmetalation of the allylzirconocene with dimethylzinc or zinc chloride provides functionalized homoallylic amines. An intramolecular version of this process leads to 3-aminotetrahydrofurans and 3-aminotetrahydropyrans. PMID:21804878

  8. Intramolecular glycosylation under neutral conditions for synthesis of 1,4-linked disaccharides.

    PubMed

    Laursen, J B; Petersen, L; Jensen, K J

    2001-03-01

    [structure: see text]. A new method for intramolecular glycosylation, in which the donor and acceptor were linked via a 3,5-dinitrosalicylic acid derivative, was developed. Simply dissolving the tethered glycoside in CH3NO2 and warming to 40-60 degrees C led to formation of 1,4-linked disaccharides under neutral, hence, exceptionally mild, conditions. PMID:11259037

  9. Enantioselective Carbocycle Formation through Intramolecular Pd-Catalyzed Allyl–Aryl Cross-Coupling

    PubMed Central

    2015-01-01

    Aryl electrophiles containing tethered allylboronate units undergo efficient intramolecular coupling in the presence of a chiral palladium catalyst to give enantioenriched carbocyclic products. The reaction is found to be quite general, affording 5, 6, and 7-membered carbocyclic products as single regioisomers and with moderate enantioselectivities. Examination of differential coupling partners points to rapid allyl-equilibration as a key stereodefining feature. PMID:25105510

  10. Intramolecular reorganization energy in zinc phthalocyanine and its fluorinated derivatives: a joint experimental and theoretical study.

    PubMed

    da Silva Filho, Demetrio A; Coropceanu, Veaceslav; Gruhn, Nadine E; de Oliveira Neto, Pedro Henrique; Brédas, Jean-Luc

    2013-07-11

    We report a high-resolution gas-phase UPS spectrum of zinc phthalocyanine (ZnPc) together with a detailed analysis of the vibronic structure of the first ionization band, showing that presents the lowest value of the intramolecular reorganization energy experimentally reported for a molecular organic semiconductor. PMID:23722445

  11. Stereochemically Rich Polycyclic Amines from the Kinetic Resolution of Indolines through Intramolecular Povarov Reactions.

    PubMed

    Min, Chang; Seidel, Daniel

    2016-07-25

    Under control of a chiral Brønsted acid catalyst, racemic indolines undergo intramolecular Povarov reactions with achiral aromatic aldehydes bearing a pendent dienophile. One enantiomer of the indoline reacts preferentially, resulting in the highly enantio- and diastereoselective formation of polycyclic heterocycles with four stereogenic centers. This kinetic resolution approach exploits the differential formation/reactivity of diastereomeric ion pairs. PMID:27346876

  12. Deciphering DNA-based asymmetric catalysis through intramolecular Friedel-Crafts alkylations.

    PubMed

    Park, Soyoung; Ikehata, Keiichi; Watabe, Ryo; Hidaka, Yuta; Rajendran, Arivazhagan; Sugiyama, Hiroshi

    2012-10-28

    We describe asymmetric intramolecular Friedel-Crafts alkylations with a DNA-based hybrid catalyst and propose a plausible binding model. This study shows promise for studying relationships between the helical chirality of DNA and enantioselectivity of the chemical reaction. PMID:22986468

  13. Usnic Acid and the Intramolecular Hydrogen Bond: A Computational Experiment for the Organic Laboratory

    ERIC Educational Resources Information Center

    Green, Thomas K.; Lane, Charles A.

    2006-01-01

    A computational experiment is described for the organic chemistry laboratory that allows students to estimate the relative strengths of the intramolecular hydrogen bonds of usnic and isousnic acids, two related lichen secondary metabolites. Students first extract and purify usnic acid from common lichens and obtain [superscript 1]H NMR and IR…

  14. Solvent-induced reversible solid-state colour change of an intramolecular charge-transfer complex.

    PubMed

    Li, Ping; Maier, Josef M; Hwang, Jungwun; Smith, Mark D; Krause, Jeanette A; Mullis, Brian T; Strickland, Sharon M S; Shimizu, Ken D

    2015-10-11

    A dynamic intramolecular charge-transfer (CT) complex was designed that displayed reversible colour changes in the solid-state when treated with different organic solvents. The origins of the dichromatism were shown to be due to solvent-inclusion, which induced changes in the relative orientations of the donor pyrene and acceptor naphthalenediimide units. PMID:26299357

  15. Conversion of oxazolidinediones to isoindoloisoquinolinones via intramolecular Friedel–Crafts reaction.

    PubMed

    Min, Ji-Young; Kim, Guncheol

    2014-02-01

    Treatment of oxazolidinediones with TiCl4 in CH2Cl2 resulted in conversion to isoindoloisoquinolinones via intramolecular Friedel–Crafts reaction with extrusion of CO2 in the transformation. The alkaloid nuevamine has been synthesized under these conditions in a regiospecific manner. PMID:24400908

  16. Palladium-catalyzed synthesis of dibenzophosphole oxides via intramolecular dehydrogenative cyclization.

    PubMed

    Kuninobu, Yoichiro; Yoshida, Takuya; Takai, Kazuhiko

    2011-09-16

    Dibenzophosphole oxides were obtained from secondary hydrophosphine oxides with a biphenyl group by dehydrogenation via phosphine-hydrogen and carbon-hydrogen bond cleavage in the presence of a catalytic amount of palladium(II) acetate, Pd(OAc)(2). By using this reaction, a ladder-type dibenzophosphole oxide could also be synthesized by double intramolecular dehydrogenative cyclization. PMID:21819045

  17. Organocatalytic Enantioselective Intramolecular Oxa-Michael Reaction of Enols: Synthesis of Chiral Isochromenes.

    PubMed

    Parhi, Biswajit; Gurjar, Jitendra; Pramanik, Suman; Midya, Abhisek; Ghorai, Prasanta

    2016-06-01

    An unprecedented enantioselective intramolecular oxa-Michael reaction of enols has been described. A squaramide-containing tertiary amine based bifunctional organocatalyst efficiently activates the o-homoformyl chalcones to provide the chiral isochromenes in moderate yields and good to excellent enantioselectivities. Further, late-stage functionalizations of the vinyl ether moiety of the chiral isochromene products have also been exemplified. PMID:27176883

  18. Construction of erythrinane skeleton via Pd(0)-catalyzed intramolecular dearomatization of para-aminophenols.

    PubMed

    Xu, Ren-Qi; Gu, Qing; Wu, Wen-Ting; Zhao, Zhuo-An; You, Shu-Li

    2014-11-01

    A novel Pd(0)-catalyzed intramolecular arylative dearomatization of para-aminophenol derivatives is described. In the presence of 1.25 mol % [Pd(C3H5)Cl]2 and 3.75 mol % RuPhos, the arylative dearomatization reaction proceeds smoothly for a broad range of substrates, offering an efficient synthetic route to erythrinane derivatives in excellent yields. PMID:25308898

  19. Intramolecular σ-bond metathesis between carbon-carbon and silicon-silicon bonds.

    PubMed

    Ishida, Naoki; Ikemoto, Wataru; Murakami, Masahiro

    2012-06-15

    An intramolecular σ-bond metathesis between carbon-carbon and silicon-silicon bonds took place on treatment of a disilane tethered to a cyclobutanone with a palladium(0) catalyst, furnishing a silaindane skeleton as well as an acylsilane functionality at once. PMID:22651103

  20. Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups.

    PubMed

    Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold; Reissig, Hans-Ulrich

    2016-01-01

    Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID:27559374

  1. Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

    PubMed Central

    Saadi, Jakub; Bentz, Christoph; Redies, Kai; Lentz, Dieter; Zimmer, Reinhold

    2016-01-01

    Summary Starting from γ-ketoesters with an o-iodobenzyl group we studied a palladium-catalyzed cyclization process that stereoselectively led to bi- and tricyclic compounds in moderate to excellent yields. Four X-ray crystal structure analyses unequivocally defined the structure of crucial cyclization products. The relative configuration of the precursor compounds is essentially transferred to that of the products and the formed hydroxy group in the newly generated cyclohexane ring is consistently in trans-arrangement with respect to the methoxycarbonyl group. A transition-state model is proposed to explain the observed stereochemical outcome. This palladium-catalyzed Barbier-type reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. PMID:27559374

  2. Regioselectivity of radical additions to substituted alkenes: insight from conceptual density functional theory.

    PubMed

    De Vleeschouwer, Freija; Jaque, Pablo; Geerlings, Paul; Toro-Labbé, Alejandro; De Proft, Frank

    2010-08-01

    Radical additions to substituted alkenes are among the most important reactions in radical chemistry. Nonetheless, there is still some controversy in the literature about the factors that affect the rate and regioselectivity in these addition reactions. In this paper, the orientation of (nucleophilic) radical additions to electron-rich, -neutral, and -poor monosubstituted substrates (11 reactions in total) is investigated through the use of chemical concepts and reactivity descriptors. The regioselectivity of the addition of nucleophilic radicals on electron-rich and -neutral alkenes is thermodynamically controlled. An excellent correlation of 94% is found between the differences in activation barriers and in product stabilities (unsubstituted versus substituted site attack). Polar effects at the initial stage of the reaction play a significant role when electron-poor substrates are considered, lowering the extent of regioselectivity toward the unsubstituted sites, as predicted from the stability differences. This is nicely confirmed through an analysis for each of the 11 reactions using the spin-polarized dual descriptor, matching electrophilic and nucleophilic regions. PMID:20614876

  3. Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids.

    PubMed

    Hayama, Noboru; Azuma, Takumi; Kobayashi, Yusuke; Takemoto, Yoshiji

    2016-01-01

    The first intermolecular asymmetric Michael addition of nitrogen-nucleophiles to α,β-unsaturated carboxylic acids was achieved through a new type of arylboronic acid equipped with chiral aminothiourea. The use of BnONH2 as a nucleophile gives a range of enantioenriched β-(benzyloxy)amino acid derivatives in good yields and with high enantioselectivity (up to 90% yield, 97% enantiomeric excess (ee)). The obtained products are efficiently converted to optically active β-amino acid and 1,2-diamine derivatives. PMID:27373626

  4. Native functionality in triple catalytic cross-coupling: sp³ C-H bonds as latent nucleophiles.

    PubMed

    Shaw, Megan H; Shurtleff, Valerie W; Terrett, Jack A; Cuthbertson, James D; MacMillan, David W C

    2016-06-10

    The use of sp(3) C-H bonds--which are ubiquitous in organic molecules--as latent nucleophile equivalents for transition metal-catalyzed cross-coupling reactions has the potential to substantially streamline synthetic efforts in organic chemistry while bypassing substrate activation steps. Through the combination of photoredox-mediated hydrogen atom transfer (HAT) and nickel catalysis, we have developed a highly selective and general C-H arylation protocol that activates a wide array of C-H bonds as native functional handles for cross-coupling. This mild approach takes advantage of a tunable HAT catalyst that exhibits predictable reactivity patterns based on enthalpic and bond polarity considerations to selectively functionalize α-amino and α-oxy sp(3) C-H bonds in both cyclic and acyclic systems. PMID:27127237

  5. E-H (E = B, Si, Ge) bond activation of pinacolborane, silanes, and germanes by nucleophilic palladium carbene complexes.

    PubMed

    Comanescu, Cezar C; Iluc, Vlad M

    2016-07-12

    The reactivity of two nucleophilic palladium carbenes, [PC(sp(2))P]Pd(PMe3) and [PC(sp(2))P]Pd(PPh3), where [PC(sp(2))P] = bis[2-(di-iso-propylphosphino)phenyl]methylene, toward the E-H bond activation of Ph4-nEHn (E = Si, Ge; n = 1-3) and pinacolborane (HBpin) is discussed. Unlike previous reports, both types of isomer species, hydride [PC(EHn-1Ph4-n)P]PdH or [PC(Bpin)P]PdH and silyl/germyl [PC(H)P]Pd(EHn-1Ph4-n), were observed depending on the substrate and the phosphine ligand, showing that the polarity of the Pd-C bond can be tuned by the phosphine substituents. PMID:26830660

  6. An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

    DOE PAGESBeta

    So Jeong Lee; Fowler, Joanna S.; Alexoff, David; Schueller, Michael; Kim, Dohyun; Nauth, Alexander; Weber, Carina; Kim, Sung Won; Hooker, Jacob M.; Ma, Ling; et al

    2015-09-21

    We developed a rapid method for the synthesis of carbon-11 radiolabeled indole using a sub-nanomolar quantity of no-carrier-added [11C]cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (2), a highly reactive substrate 2-nitrobenzyl bromide (1) was evaluated for nucleophilic [11C]cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-11C]acetonitrile ([11C]-2) while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-11C]propanenitrile ([11C]-3). Next, a Raney Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-11C]indole with hydrazinium monoformate as the active reducing agent. Extensive and iterative screening of basicity, temperature and stoichiometry was required tomore » overcome the large stoichiometry bias that favored 2-nitrobenzylbromide (1) over [11C]cyanide, which both caused further alkylation of the desired nitrile and poisoned the Raney Nickel catalyst. The result is an efficient two-step, streamlined method to reliably synthesize [2-11C]indole with an entire radiochemical yield of 21 ± 2.2% (n = 5, ranging from 18 – 24%). The radiochemical purity of the final product was > 98% and specific activity was 176 ± 24.8 GBq/μmol (n = 5, ranging from 141 – 204 GBq/μmol). The total radiosynthesis time including product purification by semi-preparative HPLC was 50 – 55 min from end of cyclotron bombardment.« less

  7. An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

    SciTech Connect

    So Jeong Lee; Fowler, Joanna S.; Alexoff, David; Schueller, Michael; Kim, Dohyun; Nauth, Alexander; Weber, Carina; Kim, Sung Won; Hooker, Jacob M.; Ma, Ling; Qu, Wenchao

    2015-09-21

    We developed a rapid method for the synthesis of carbon-11 radiolabeled indole using a sub-nanomolar quantity of no-carrier-added [11C]cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (2), a highly reactive substrate 2-nitrobenzyl bromide (1) was evaluated for nucleophilic [11C]cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-11C]acetonitrile ([11C]-2) while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-11C]propanenitrile ([11C]-3). Next, a Raney Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-11C]indole with hydrazinium monoformate as the active reducing agent. Extensive and iterative screening of basicity, temperature and stoichiometry was required to overcome the large stoichiometry bias that favored 2-nitrobenzylbromide (1) over [11C]cyanide, which both caused further alkylation of the desired nitrile and poisoned the Raney Nickel catalyst. The result is an efficient two-step, streamlined method to reliably synthesize [2-11C]indole with an entire radiochemical yield of 21 ± 2.2% (n = 5, ranging from 18 – 24%). The radiochemical purity of the final product was > 98% and specific activity was 176 ± 24.8 GBq/μmol (n = 5, ranging from 141 – 204 GBq/μmol). The total radiosynthesis time including product purification by semi-preparative HPLC was 50 – 55 min from end of cyclotron bombardment.

  8. Oxygen-Atom Transfer Reactivity of Axially Ligated Mn(V)–Oxo Complexes: Evidence for Enhanced Electrophilic and Nucleophilic Pathways

    PubMed Central

    2015-01-01

    Addition of anionic donors to the manganese(V)–oxo corrolazine complex MnV(O)(TBP8Cz) has a dramatic influence on oxygen-atom transfer (OAT) reactivity with thioether substrates. The six-coordinate anionic [MnV(O)(TBP8Cz)(X)]− complexes (X = F–, N3–, OCN–) exhibit a ∼5 cm–1 downshift of the Mn–O vibrational mode relative to the parent MnV(O)(TBP8Cz) complex as seen by resonance Raman spectroscopy. Product analysis shows that the oxidation of thioether substrates gives sulfoxide product, consistent with single OAT. A wide range of OAT reactivity is seen for the different axial ligands, with the following trend determined from a comparison of their second-order rate constants for sulfoxidation: five-coordinate ≈ thiocyanate ≈ nitrate < cyanate < azide < fluoride ≪ cyanide. This trend correlates with DFT calculations on the binding of the axial donors to the parent MnV(O)(TBP8Cz) complex. A Hammett study was performed with p-X-C6H4SCH3 derivatives and [MnV(O)(TBP8Cz)(X)]− (X = CN– or F–) as the oxidant, and unusual “V-shaped” Hammett plots were obtained. These results are rationalized based upon a change in mechanism that hinges on the ability of the [MnV(O)(TBP8Cz)(X)]− complexes to function as either an electrophilic or weak nucleophilic oxidant depending upon the nature of the para-X substituents. For comparison, the one-electron-oxidized cationic MnV(O)(TBP8Cz•+) complex yielded a linear Hammett relationship for all substrates (ρ = −1.40), consistent with a straightforward electrophilic mechanism. This study provides new, fundamental insights regarding the influence of axial donors on high-valent MnV(O) porphyrinoid complexes. PMID:25238495

  9. Identification of Glu-519 as the catalytic nucleophile in beta-mannosidase 2A from Cellulomonas fimi.

    PubMed Central

    Stoll, D; He, S; Withers, S G; Warren, R A

    2000-01-01

    Incubation of the beta-mannosidase Man2A from Cellulomonas fimi with 2-deoxy-2-fluoro-beta-D-mannosyl fluoride (2FMan beta F) resulted in time-dependent inactivation of the enzyme (inactivation rate constant k(i)=0.57 min(-1), dissociation constant for the inactivator K(i)=0.41 mM) through the accumulation of a covalent 2-deoxy-2-fluoro-alpha-D-mannosyl-beta-mannosidase 2A (2FMan-Man2A) enzyme intermediate, as observed by electrospray ionization mass spectrometry. The stoichiometry of inactivation was 1:1. Removal of excess inactivator and regeneration of active enzyme by transglycosylation of the covalently attached inhibitor to gentiobiose [Glc beta(1-6)Glc] demonstrated that the covalent intermediate was catalytically competent. Comparison by MS of the peptic digests of 2FMan-Man2A with peptic digests of native Man2A revealed a peptide of m/z 1520 that was unique to 2FMan-Man2A, and one of m/z 1036.5 that was unique to a Man2A peptide. Their sequences, determined by collision-induced fragmentation, were CSEFGFQGPPTW and FGFQGPPTW, corresponding to residues 517-528 and 520-528 of Man2A respectively. The difference in mass of 483.5 between the two peptides equals the sum of the masses of the tripeptide CSE plus that of 2-fluoromannose. It was concluded that in 2FMan-Man2A, the 2-fluoromannose esterified to Glu-519 blocks hydrolysis of the Glu-519-Phe-520 peptide bond, and that Glu-519 is the catalytic nucleophile in this enzyme. This residue is conserved in all members of family 2 of the glycosyl hydrolases. This represents the first ever labelling and identification of an active-site nucleophile in a beta-mannosidase. PMID:11042141

  10. Distributions of intramolecular distances in the reduced and denatured states of bovine pancreatic ribonuclease A. Folding initiation structures in the C-terminal portions of the reduced protein.

    PubMed

    Navon, A; Ittah, V; Landsman, P; Scheraga, H A; Haas, E

    2001-01-01

    The purpose of this investigation is to characterize the reduced state of RNase A (r-RNase A) in terms of (i) intramolecular distances, (ii) the sequence of formation of stable loops in the initial stages of folding, and (iii) the unfolding transitions induced by GdnHCl. This is accomplished by identifying specific subdomain structures and local and long-range interactions that direct the folding process of this protein and lead to the native fold and formation of the disulfide bonds. Eleven pairs of dispersed sites in the RNase A molecule were labeled with fluorescent donor and acceptor probes, and the distributions of intramolecular distances (IDDs) were determined by means of time-resolved dynamic nonradiative excitation energy transfer (TR-FRET) measurements. The mutants were designed to search for (a) a possible nonrandom fold of the backbone in the collapsed state and (b) possible loops stabilized by long-range interactions. It was found that, under folding conditions, (i) the labeled mutants of r-RNase A in refolding buffer (the R(N) state) exhibit features of specific (nonrandom) compact but very dispersed subdomain structures (indicated by short mean distances, broad IDDs, and a weak dependence of the mean distances on segment length), (ii) the backbone fold in the C-terminal beta-like portion of the molecule appears to adopt a native-like overall fold, (iii) the N-terminal alpha-like portion of the chain is separated from the C-terminal core by very large intramolecular distances, larger than those in the crystal structure, and (iv) perturbations by addition of GdnHCl reveal several conformational transitions in different sections of the chain. Addition of GdnHCl to the native disulfide-intact protein provided a reference state for the extent of expansion of intramolecular distances under denaturing conditions. In conclusion, r-RNase A under folding conditions (the R(N) state) is poised for the final folding step(s) with a native-like trace of the chain

  11. Synthesis of Aryl-Substituted 2,4-Dinitrophenylamines: Nucleophilic Aromatic Substitution as a Problem-Solving and Collaborative-Learning Approach

    ERIC Educational Resources Information Center

    Santos, Elvira Santos; Garcia, Irma Cruz Gavilan; Gomez, Eva Florencia Lejarazo; Vilchis-Reyes, Miguel Angel

    2010-01-01

    A series of experiments based on problem-solving and collaborative-learning pedagogies are described that encourage students to interpret results and draw conclusions from data. Different approaches including parallel library synthesis, solvent variation, and leaving group variation are used to study a nucleophilic aromatic substitution of…

  12. Long-Lived Triplet Excited States of Bent-Shaped Pentacene Dimers by Intramolecular Singlet Fission.

    PubMed

    Sakuma, Takao; Sakai, Hayato; Araki, Yasuyuki; Mori, Tadashi; Wada, Takehiko; Tkachenko, Nikolai V; Hasobe, Taku

    2016-03-24

    Intramolecular singlet fission (ISF) is a promising photophysical process to construct more efficient light energy conversion systems as one excited singlet state converts into two excited triplet states. Herein we synthesized and evaluated bent-shaped pentacene dimers as a prototype of ISF to reveal intrinsic characters of triplet states (e.g., lifetimes of triplet excited states). In this study, meta-phenylene-bridged TIPS-pentacene dimer (PcD-3Ph) and 2,2'-bipheynyl bridged TIPS-pentacene dimer (PcD-Biph) were newly synthesized as bent-shaped dimers. In the steady-state spectroscopy, absorption and emission bands of these dimers were fully characterized, suggesting the appropriate degree of electronic coupling between pentacene moieties in these dimers. In addition, the electrochemical measurements were also performed to check the electronic interaction between two pentacene moieties. Whereas the successive two oxidation peaks owing to the delocalization were observed in a directly linked-pentacene dimer (PcD) by a single bond, the cyclic voltammograms in PcD-Biph and PcD-3Ph implied the weaker interaction compared to that of p-phenylene-bridged TIPS-pentacene dimer (PcD-4Ph) and PcD. The femtosecond and nanosecond transient absorption spectra clearly revealed the slower ISF process in bent-shaped pentacene dimers (PcD-Biph and PcD-3Ph), more notably, the slower relaxation of the excited triplet states in PcD-Biph and PcD-3Ph. Namely, the quantum yields of triplet states (ΦT) by ISF approximately remain constant (ca. 180-200%) in all dimer systems, whereas the lifetimes of the triplet excited states became much longer (up to 360 ns) in PcD-Biph as compared to PcD-4Ph (15 ns). Additionally, the lifetimes of the corresponding triplet states in PcD-Biph and PcD-3Ph were sufficiently affected by solvent viscosity. In particular, the lifetimes of PcD-Biph triplet state in THF/paraffin (1.0 μs) increased up to approximately three times as compared to that in THF

  13. A DFT study on the NHC catalysed Michael addition of enols to α,β-unsaturated acyl-azoliums. A base catalysed C-C bond-formation step.

    PubMed

    Domingo, Luis R; Sáez, José A; Arnó, Manuel

    2014-02-14

    The NHC catalysed nucleophilic additions of enols to α,β-unsaturated acyl-azolium intermediates have been investigated using DFT methods at the MPWB1K/6-31G** computational level. In the direct and the conjugate additions, formation of a hydrogen bond (HB) with the carboxyl oxygen is not sufficient to favour the C-C bond formation as a consequence of the low nucleophilic character of enols. Interestingly, when enols form a HB with the chloride counterion, the activation energies associated with the conjugate addition decrease as a consequence of the increased nucleophilic character of enols and the increased electrophilic character of the 'acyl-azolium + Cl' ion pair. Analysis of the DFT reactivity indices allows establishing a base catalysed C-C bond-formation step promoted by the chloride counterion. PMID:24343422

  14. The scaffold protein PDZK1 undergoes a head-to-tail intramolecular association that negatively regulates its interaction with EBP50

    PubMed Central

    LaLonde, David P.; Bretscher, Anthony

    2009-01-01

    PDZK1 (also known as CAP70, NHERF3, NaPi-Cap1) is a scaffolding protein composed of four PDZ (Post-Synaptic Density-95, Discs Large, Zonula Occludens-1) domains followed by a short carboxyl-terminal tail. This scaffold acts as a mediator of localization and expression levels of multiple receptors in the kidney, liver and endothelium. Here, we characterize the self-association properties of the protein. PDZK1 can undergo modest homo-dimerization in vivo and in vitro through self-association involving its third PDZ domain. In addition, the tail of PDZK1 interacts in an intramolecular fashion with the first PDZ domain, but this interaction does not contribute to dimer formation. The interaction between the tail of PDZK1 and its first PDZ domain induces the protein to adopt a more compact conformation. A head-to-tail association has also been reported for EBP50/NHERF1, a two PDZ domain member of the same scaffolding protein family as PDZK1, and shown to regulate binding of target proteins to the EBP50 PDZ domains. As opposed to EBP50, the association of PDZK1 with specific ligands for its PDZ domains is unaffected by the intramolecular association, establishing a different mode of interaction among these two members of the same scaffolding family. However, the tail of PDZK1 interacts with the PDZ domains of EBP50, and this interaction is negatively regulated by the intramolecular association of PDZK1. Thus, we have uncovered a regulated association between the two PDZ-containing scaffolding molecules, PDZK1 and EBP50. PMID:19173579

  15. Mutagenesis of Nucleophilic Residues near the Orthosteric Binding Pocket of M1 and M2 Muscarinic receptors: Effect on the Binding of Nitrogen Mustard Analogs of Acetylcholine and McN-A-343

    PubMed Central

    Suga, Hinako; Sawyer, Gregory W.

    2010-01-01

    Investigating how a test drug alters the reaction of a site-directed electrophile with a receptor is a powerful method for determining whether the drug acts competitively or allosterically, provided that the binding site of the electrophile is known. In this study, therefore, we mutated nucleophilic residues near and within the orthosteric pockets of M1 and M2 muscarinic receptors to identify where acetylcholine mustard and 4-[(2-bromoethyl)methyl-amino]-2-butynyl-N-(3-chlorophenyl)carbamate (BR384) bind covalently. BR384 is the nitrogen mustard analog of [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343). Mutation of the highly conserved aspartic acid in M1 (Asp105) and M2 (Asp103) receptors to asparagine largely prevented receptor alkylation by acetylcholine mustard, although modest alkylation still occurred at M2 D103N at high concentrations of the mustard. Receptor alkylation by BR384 was also greatly inhibited in the M1 D105N mutant, but some alkylation still occurred at high concentrations of the compound. In contrast, BR384 rapidly alkylated the M2 D103N mutant. Its affinity was reduced to one tenth, however. The alkylation of M2 D103N by BR384 was competitively inhibited by N-methylscopolamine and allosterically inhibited by gallamine. Mutation of a variety of other nucleophilic residues, some in combination with D103N, had little effect on M2 receptor alkylation by BR384. Our results suggest that BR384 alkylates at least one residue other than the conserved aspartic acid at the ligand-binding site of M1 and M2 receptors. This additional residue seems to be located within or near the orthosteric-binding pocket and is not part of the allosteric site for gallamine. PMID:20643905

  16. Gas-phase intramolecular elimination reaction studies of steviol glycosides in positive electrospray and tandem mass spectrometry.

    PubMed

    Upreti, Mani; Clos, John F; Somayajula, Kasi V; Milanowski, Dennis J; Mocek, Ulla; Dubois, Grant E; Prakash, Indra

    2009-01-01

    This paper reports the first study of the gas-phase intramolecular elimination reaction of steviol glycosides in positive electrospray mass spectrometry. The observed glycosylated product ions are proposed to be formed via an intramolecular elimination of sugar units from the parent molecule ion. It was further proven by MS/MS studies and deuterium labeling experiments with one of the steviol glycosides, rebaudioside A. These mass spectrometric results confirmed that the new glycosylated product ions observed are most likely formed by the combination of glucose moieties (Glu) II-IV and Glu I via a gas-phase intramolecular elimination reaction. PMID:19174590

  17. The addition of disilanes to cumulenes

    SciTech Connect

    Chen, Y.

    1997-10-08

    The syntheses of silicon-containing compounds and the studies of their rearrangements have been active research areas in the Barton research group. Previously, the addition of disilanes to acetylenes was studied in the group and an intramolecular 2S + 2A mechanism has been proposed. In this thesis, the work is focused on the addition of disilanes to cumulenes. The syntheses of the precursors are discussed and the possible mechanisms for their thermal, photochemical and catalytic rearrangements are proposed. Conjugated organic polymers have been studied in the group since 1985 because of their potential for exhibiting high electroconductivity, photoconductivity, strong non-linear optical response and intense fluorescence. In the second section of this dissertation, the synthesis and property studies of poly(phenylene vinylene) analogues are discussed.

  18. Nucleophilic index value: implication in the protection by indole-3-carbinol from N-nitrosodimethylamine cyto and genotoxicity in mouse liver.

    PubMed

    Shertzer, H G; Tabor, M W

    1988-04-01

    A novel assay system was developed in order to quantitate the nucleophilicity of pure chemicals or tissue extracts. This Nucleophilic Index Value (NIV) assay was based on the ability of putative nucleophiles to inhibit the methylation of cysteine by limiting concentrations of the electrophilic source, N-methyl-N-nitrosourea (MNU). Efficacy of model and cellular nucleophiles was quantitated as nmol cysteine protected by the nucleophile from methylation by MNU/h/mM compound. The NIVs of the pure compounds ascorbate, glutathione, 4-(4-nitrobenzyl)-pyridine (NBP) and indole-3-carbinol (I-3-C) were 2400, 1600, 3 and 0, respectively. When mice were treated with I-3-C by gavage at dosages of 0, 25, 50, 75 or 100 mg/kg body wt, the NIV for ethyl acetate extracts of the livers 1 h after treatment were 0, 33, 47, 52 and 92 nmol cysteine preserved/h/g tissue, respectively. The I-3-C enhancement of NIV was not attributable to ascorbate or glutathione, neither of which were present in the ethyl extracts of liver. When mice were treated with 10 mg N-nitrosodimethylamine (NDMA)/kg body wt 1 h after the varying dosages of I-3-C, the 24 h post-NDMA plasma alanine transaminase (ALT) values were decreased by I-3-C pretreatment in a dose-dependent fashion. Plasma ALT values were used in this study as an indicator of hepatotoxicity. The coefficient of determination, r2, computed from the linear least squares correlation coefficient between NIV and ALT values, was 0.80 (0-100 mg I-3-C/kg) and 0.97 (0-75 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3379233

  19. Conformational stability and intramolecular hydrogen bonding in 1,2-ethanediol and 1,4-butanediol.

    PubMed

    Das, Prasanta; Das, Puspendu K; Arunan, E

    2015-04-23

    The gas-phase infrared spectra of 1,2-ED and 1,4-BD have been recorded at three different temperatures using a multipass gas cell of 6 m optical path length. DFT calculation has also been carried out using 6-311++G** and aug-cc-pVDZ basis sets to look for the existence of intramolecular hydrogen bonding in them from the red shift and infrared absorption intensity enhancement of the bonded O-H band compared to that of the free O-H band. Equilibrium population analysis with 10 conformers of 1,2-ED and 1,4-BD at experimental temperatures were carried out for the reconstruction of the observed vibrational spectra at that temperature using standard statistical relationships. The most abundant conformer at experimental temperatures was identified. In 1,2-ED a red shift of 45 cm(-1) in the intramolecularly interacting O-H stretching vibrational band position and no significant intensity enhancement compared to that of the free O-H have been observed. On the contrary, in one of the hydrogen-bonded conformers of 1,4-BD, a 124 cm(-1) red shift in the O-H stretching frequency and a 8.5 times intensity enhancement for the "bonded" O-H compared to that of the "free" O-H is seen. On the basis of this comparative study, we have concluded that strong intramolecular hydrogen bonding exists in 1,4-BD. But there appears to be weak intramolecular hydrogen bonding in 1,2-ED at temperatures of 303, 313, and 323 K in the gas phase. We have found that most stable hydrogen-bonded conformers of 1,4-BD are less populated than some of the non-hydrogen-bonded conformers. Even for the 1,4-BD, the relative population of the g'GG'Gt conformer, which has a strong intramolecular hydrogen bond, is less than what is predicted. Perhaps the intramolecular hydrogen bond plays a less significant role in the relative stability of the various conformers than what has been predicted from calculations and prevails in the literature. PMID:25839224

  20. Basic-functionalized recyclable ionic liquid catalyst: A solvent-free approach for Michael addition of 1,3-dicarbonyl compounds to nitroalkenes under ultrasound irradiation.

    PubMed

    Narayanaperumal, Senthil; da Silva, Rodrigo César; Feu, Karla Santos; de la Torre, Alexander Fernández; Corrêa, Arlene G; Paixão, Márcio Weber

    2013-05-01

    A task-specific ionic liquid (TSIL) has been introduced as a recyclable catalyst in Michael addition. A series of nitroalkenes and various C-based nucleophiles were reacted in the presence of 30mol% of recyclable basic-functionalized ionic liquid. Good to excellent yields were obtained in 30min under ultrasound irradiation. PMID:23218731

  1. Rh-Catalyzed Domino Addition-Enolate Arylation: Generation of 3-Substituted Oxindoles via a Rh(lll) Intermediate.

    PubMed

    Jang, Young Jin; Yoon, Hyung; Lautens, Mark

    2015-08-01

    A Rh-catalyzed domino conjugate addition-arylation sequence via a Rh(III) intermediate is reported. This process involving a proposed intramolecular oxidative addition of a rhodium enolate was utilized to achieve the synthesis of 3-substituted oxindole derivatives in moderate to excellent yields. PMID:26158867

  2. Evidence for excited-state intramolecular proton transfer in 4-chlorosalicylic acid from combined experimental and computational studies: Quantum chemical treatment of the intramolecular hydrogen bonding interaction

    NASA Astrophysics Data System (ADS)

    Paul, Bijan Kumar; Guchhait, Nikhil

    2012-07-01

    The photophysical study of a pharmaceutically important chlorine substituted derivative of salicylic acid viz., 4-chlorosalicylic acid (4ClSA) has been carried out by steady-state absorption, emission and time-resolved emission spectroscopy. A large Stokes shifted emission band with negligible solvent polarity dependence marks the spectroscopic signature of excited-state intramolecular proton transfer (ESIPT) reaction in 4ClSA. Theoretical calculation by ab initio and Density Functional Theory methods yields results consistent with experimental findings. Theoretical potential energy surfaces predict the occurrence of proton transfer in S1-state. Geometrical and energetic criteria, Atoms-In-Molecule topological parameters, Natural Bond Orbital population analysis have been exploited to evaluate the intramolecular hydrogen bond (IMHB) interaction and to explore its directional nature. The inter-correlation between aromaticity and resonance assisted H-bond is also discussed in this context. Our results unveil that the quantum chemical treatment is a more accurate tool to assess hydrogen bonding interaction in comparison to geometrical criteria.

  3. Inequivalence of substitution pairs in hydroxynaphthaldehyde: A theoretical measurement by intramolecular hydrogen bond strength, aromaticity, and excited-state intramolecular proton transfer reaction.

    PubMed

    Mahanta, Subrata; Paul, Bijan Kumar; Balia Singh, Rupashree; Guchhait, Nikhil

    2011-01-15

    The inequivalence of substitution pair positions of naphthalene ring has been investigated by a theoretical measurement of hydrogen bond strength, aromaticity, and excited state intramolecular proton transfer (ESIPT) reaction as the tools in three substituted naphthalene compounds viz 1-hydroxy-2-naphthaldehyde (HN12), 2-hydroxy-1-naphthaldehyde (HN21), and 2-hydroxy-3-naphthaldehyde (HN23). The difference in intramolecular hydrogen bond (IMHB) strength clearly reflects the inequivalence of substitution pairs where the calculated IMHB strength is found to be greater for HN12 and HN21 than HN23. The H-bonding interactions have been explored by calculation of electron density ρ(r) and Laplacian ∇(2) ρ(r) at the bond critical point using atoms in molecule method and by calculation of interaction between σ* of OH with lone pair of carbonyl oxygen atom using NBO analysis. The ground and excited state potential energy surfaces (PESs) for the proton transfer reaction at HF (6-31G**) and DFT (B3LYP/6-31G**) levels are similar for HN12, HN21 and different for HN23. The computed aromaticity of the two rings of naphthalene moiety at B3LYP/6-31G** method also predicts similarity between HN12 and HN21, but different for HN23. PMID:20623648

  4. Direct asymmetric vinylogous Michael addition of cyclic enones to nitroalkenes via dienamine catalysis

    PubMed Central

    Bencivenni, Giorgio; Galzerano, Patrizia; Mazzanti, Andrea; Bartoli, Giuseppe; Melchiorre, Paolo

    2010-01-01

    In spite of the many catalytic methodologies available for the asymmetric functionalization of carbonyl compounds at their α and β positions, little progress has been achieved in the enantioselective carbon–carbon bond formation γ to a carbonyl group. Here, we show that primary amine catalysis provides an efficient way to address this synthetic issue, promoting vinylogous nucleophilicity upon selective activation of unmodified cyclic α,β-unsaturated ketones. Specifically, we document the development of the unprecedented direct and vinylogous Michael addition of β-substituted cyclohexenone derivatives to nitroalkenes proceeding under dienamine catalysis. Besides enforcing high levels of diastereo- and enantioselectivity, chiral primary amine catalysts derived from natural cinchona alkaloids ensure complete γ-site selectivity: The resulting, highly functionalized vinylogous Michael adducts, having two stereocenters at the γ and δ positions, are synthesized with very high fidelity. Finally, we describe the extension of the dienamine catalysis-induced vinylogous nucleophilicity to the asymmetric γ-amination of cyclohexene carbaldehyde. PMID:20566884

  5. Direct asymmetric vinylogous Michael addition of cyclic enones to nitroalkenes via dienamine catalysis.

    PubMed

    Bencivenni, Giorgio; Galzerano, Patrizia; Mazzanti, Andrea; Bartoli, Giuseppe; Melchiorre, Paolo

    2010-11-30

    In spite of the many catalytic methodologies available for the asymmetric functionalization of carbonyl compounds at their α and β positions, little progress has been achieved in the enantioselective carbon-carbon bond formation γ to a carbonyl group. Here, we show that primary amine catalysis provides an efficient way to address this synthetic issue, promoting vinylogous nucleophilicity upon selective activation of unmodified cyclic α,β-unsaturated ketones. Specifically, we document the development of the unprecedented direct and vinylogous Michael addition of β-substituted cyclohexenone derivatives to nitroalkenes proceeding under dienamine catalysis. Besides enforcing high levels of diastereo- and enantioselectivity, chiral primary amine catalysts derived from natural cinchona alkaloids ensure complete γ-site selectivity: The resulting, highly functionalized vinylogous Michael adducts, having two stereocenters at the γ and δ positions, are synthesized with very high fidelity. Finally, we describe the extension of the dienamine catalysis-induced vinylogous nucleophilicity to the asymmetric γ-amination of cyclohexene carbaldehyde. PMID:20566884

  6. Enantioselective Intramolecular Hydroarylation of Alkenes via Directed C-H Bond Activation

    SciTech Connect

    Harada, Hitoshi; Thalji, Reema; Bergman, Robert; Ellman, Jonathan

    2008-05-22

    Highly enantioselective catalytic intramolecular ortho-alkylation of aromatic imines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using [RhCl(coe){sub 2}]{sub 2} and chiral phosphoramidite ligands. Cyclization of substrates containing 1,1- and 1,2-disubstituted as well as trisubstituted alkenes were achieved with enantioselectivities >90% ee for each substrate class. Cyclization of substrates with Z-alkene isomers proceeded much more efficiently than substrates with E-alkene isomers. This further enabled the highly stereoselective intramolecular alkylation of certain substrates containing Z/E-alkene mixtures via a Rh-catalyzed alkene isomerization with preferential cyclization of the Z-isomer.

  7. Design of Small Intramolecular Singlet Fission Chromophores: An Azaborine Candidate and General Small Size Effects.

    PubMed

    Zeng, Tao; Goel, Prateek

    2016-04-01

    We report the first attempt to design small intramolecular singlet fission chromophores, with the aid of quantum chemistry and explicitly simulating the time evolution of state populations using quantum dynamics method. We start with three previously proposed azaborine-substituted intermolecular singlet fission chromophores. Through analyzing their frontier orbital amplitudes, we select a BN-substituted azulene as the building block. Covalently connecting two such monomers and tuning their relative configuration, we examine three dimers. One dimer is found to be an eminent candidate: the triplet-pair state is quickly formed within 1 ps, and the two triplets are ready to be disentangled. We elucidate the general small size effects in intramolecular singlet fission and focus on specific aspects which should be taken care of when manipulating the fission rate through steric hindrance. PMID:27007577

  8. Intramolecular symmetry-adapted perturbation theory with a single-determinant wavefunction

    NASA Astrophysics Data System (ADS)

    Pastorczak, Ewa; Prlj, Antonio; Gonthier, Jérôme F.; Corminboeuf, Clémence

    2015-12-01

    We introduce an intramolecular energy decomposition scheme for analyzing non-covalent interactions within molecules in the spirit of symmetry-adapted perturbation theory (SAPT). The proposed intra-SAPT approach is based upon the Chemical Hamiltonian of Mayer [Int. J. Quantum Chem. 23(2), 341-363 (1983)] and the recently introduced zeroth-order wavefunction [J. F. Gonthier and C. Corminboeuf, J. Chem. Phys. 140(15), 154107 (2014)]. The scheme decomposes the interaction energy between weakly bound fragments located within the same molecule into physically meaningful components, i.e., electrostatic-exchange, induction, and dispersion. Here, we discuss the key steps of the approach and demonstrate that a single-determinant wavefunction can already deliver a detailed and insightful description of a wide range of intramolecular non-covalent phenomena such as hydrogen bonds, dihydrogen contacts, and π - π stacking interactions. Intra-SAPT is also used to shed the light on competing intra- and intermolecular interactions.

  9. Broadband Tunable Microlasers Based on Controlled Intramolecular Charge-Transfer Process in Organic Supramolecular Microcrystals.

    PubMed

    Dong, Haiyun; Wei, Yanhui; Zhang, Wei; Wei, Cong; Zhang, Chunhuan; Yao, Jiannian; Zhao, Yong Sheng

    2016-02-01

    Wavelength tunable micro/nanolasers are indispensable components for various photonic devices. Here, we report broadband tunable microlasers built by incorporating a highly polarized organic intramolecular charge-transfer (ICT) compound with a supramolecular host. The spatial confinement of the ICT dye generates an optimized energy level system that favors controlled population distribution between the locally excited (LE) state and the twisted intramolecular charge-transfer (TICT) state, which is beneficial for significantly broadening the tailorable gain region. As a result, we realized a wide tuning of lasing wavelength in the organic supramolecular microcrystals based on temperature-controlled population transfer from the LE to TICT state. The results will provide a useful enlightenment for the rational design of miniaturized lasers with desired performances. PMID:26756966

  10. Intramolecular Crystal Nucleation Favored by Polymer Crystallization: Monte Carlo Simulation Evidence.

    PubMed

    Zhang, Rong; Zha, Liyun; Hu, Wenbing

    2016-07-14

    We performed dynamic Monte Carlo simulations of half-half binary blends of symmetric (double and mutual) crystallizable polymers. We separately enhanced the driving forces for polymer-uniform and polymer-staggered crystals. Under parallel enhancements, polymer-uniform crystals exhibit faster nucleation and growth, with more chain folding and less lamellar thickening, than those in polymer-staggered crystals. We attributed the results to intramolecular crystal nucleation, ruined by enhanced polymer-staggered crystallization. Our observations provide direct molecular-level evidence to support the fact that intramolecular crystal nucleation is favored by polymer crystallization in quiescent solutions and melt, which yields chain folding for the characteristic β-sheet or lamellar morphology of macromolecular crystals. PMID:27300471

  11. Impact of Stereospecific Intramolecular Hydrogen Bonding on Cell Permeability and Physicochemical Properties

    PubMed Central

    2014-01-01

    Profiling of eight stereoisomeric T. cruzi growth inhibitors revealed vastly different in vitro properties such as solubility, lipophilicity, pKa, and cell permeability for two sets of four stereoisomers. Using computational chemistry and NMR spectroscopy, we identified the formation of an intramolecular NH→NR3 hydrogen bond in the set of stereoisomers displaying lower solubility, higher lipophilicity, and higher cell permeability. The intramolecular hydrogen bond resulted in a significant pKa difference that accounts for the other structure–property relationships. Application of this knowledge could be of particular value to maintain the delicate balance of size, solubility, and lipophilicity required for cell penetration and oral administration for chemical probes or therapeutics with properties at, or beyond, Lipinski’s rule of 5. PMID:24524242

  12. Intramolecular and Intermolecular Interactions in Hybrid Organic-Inorganic Alucone Films Grown by Molecular Layer Deposition.

    PubMed

    Park, Yi-Seul; Kim, Hyein; Cho, Boram; Lee, Chaeyun; Choi, Sung-Eun; Sung, Myung Mo; Lee, Jin Seok

    2016-07-13

    Investigation of molecular interactions in polymeric films is crucial for understanding and engineering multiscale physical phenomena correlated to device function and performance, but this often involves a compromise between theoretical and experimental data, because of poor film uniformity. Here, we report the intramolecular and intermolecular interactions inside the ultrathin and conformal hybrid organic-inorganic alucone films grown by molecular layer deposition, based on sequential and self-limiting surface reactions. Varying the carbon chain length of organic precursors, which affects their molecular flexibility, caused intramolecular interactions such as double reactions by bending of the molecular backbone, resulting in formation of hole vacancies in the films. Furthermore, intermolecular interactions in alucone polymeric films are dependent on the thermal kinetics of molecules, leading to binding failures and cross-linking at low and high growth temperatures, respectively. We illustrate these key interactions and identify molecular geometries and potential energies by density functional theory calculations. PMID:27314844

  13. Design Principles of Electronic Couplings for Intramolecular Singlet Fission in Covalently-Linked Systems.

    PubMed

    Ito, Soichi; Nagami, Takanori; Nakano, Masayoshi

    2016-08-11

    We theoretically investigate the singlet fission in three types of covalently-linked systems, that is, ortho-, meta- and para-linked pentacene dimers, where these are shown to have significantly different singlet fission rates. Each molecule is composed of two chromophores (pentacenes), which are active sites for singlet fission, and covalent bridges linking them. We clarify the origin of the difference in the electronic couplings in these systems, which are found to well support a recent experimental observation. It is also found that the next-nearest-neighbor interaction is indispensable for intramolecular singlet fission in these systems. On the basis of these results, we present design principles for efficient intramolecular singlet fission in covalently-linked systems and demonstrate the performance by using several novel conjugated linkers. PMID:27448100

  14. Identification of intramolecular hydrogen bonds as the origin of malfunctioning of multitopic receptors

    NASA Astrophysics Data System (ADS)

    Dolenský, Bohumil; Konvalinka, Roman; Jakubek, Milan; Král, Vladimír

    2013-03-01

    Several trisamides of N,N-bis(2-aminoethyl)ethane-1,2-amine are prepared as potential saccharide receptors. Surprisingly low or even nil affinity to n-octyl-glucose is found by 1H NMR titration, and explained as a consequence of intramolecular hydrogen bonds of trisamides, (Rsbnd COsbnd NHsbnd C2H4)3N. The hydrogen bonds are identified by combination of 1H NMR and infrared spectra, and 1H NMR temperature coefficients. Results demonstrate that even small molecule can has a rather strong secondary structure, which can cause their malfunctioning in certain applications. Results also point out that the amide temperature coefficients should not be used as the only parameter for the consideration a hydrogen bond is intermolecular or intramolecular, particularly, in the case of furcated hydrogen bonds, and in the cases were a couple of signals are averaged.

  15. Intramolecular symmetry-adapted perturbation theory with a single-determinant wavefunction

    SciTech Connect

    Pastorczak, Ewa; Prlj, Antonio; Corminboeuf, Clémence; Gonthier, Jérôme F.

    2015-12-14

    We introduce an intramolecular energy decomposition scheme for analyzing non-covalent interactions within molecules in the spirit of symmetry-adapted perturbation theory (SAPT). The proposed intra-SAPT approach is based upon the Chemical Hamiltonian of Mayer [Int. J. Quantum Chem. 23(2), 341–363 (1983)] and the recently introduced zeroth-order wavefunction [J. F. Gonthier and C. Corminboeuf, J. Chem. Phys. 140(15), 154107 (2014)]. The scheme decomposes the interaction energy between weakly bound fragments located within the same molecule into physically meaningful components, i.e., electrostatic-exchange, induction, and dispersion. Here, we discuss the key steps of the approach and demonstrate that a single-determinant wavefunction can already deliver a detailed and insightful description of a wide range of intramolecular non-covalent phenomena such as hydrogen bonds, dihydrogen contacts, and π − π stacking interactions. Intra-SAPT is also used to shed the light on competing intra- and intermolecular interactions.

  16. Intramolecular cycloaddition in 6,6-spiroepoxycyclohexa-2,4-dienone: simple aromatics to (+/-)-platencin.

    PubMed

    Singh, Vishwakarma; Sahu, Bharat Chandra; Bansal, Varsha; Mobin, Shaikh M

    2010-10-01

    A formal total synthesis of platencin from a simple aromatic precursor is described. Transformation of the aromatic compound into reactive spiroepoxycyclohexa-2,4-dienone and intramolecular cycloaddition are the key features of our methodology. 2-Hydroxymethyl-6-(3-hydroxy-hex-5-enyl)-phenol was oxidized with NaIO(4) to give a dimer that, upon a retro-Diels-Alder reaction, generated the spiroepoxycyclohexa-2,4-dienone that underwent intramolecular Diels-Alder reaction to give a tricyclic adduct having a core structure of platencin and appropriately disposed functional groups in a single step. Reduction of the double bond present in the ethano-bridge, manipulation of the oxirane ring and introduction of a double bond in the six-membered ring furnished a tricyclic intermediate which has already been converted into platencin. PMID:20683538

  17. Intramolecular complex formation and triplet energy transfer in polynorbornenes incorporating benzophenone

    SciTech Connect

    Fossum, R.D.; Fox, M.A.

    1997-02-12

    The photophysical properties of homopolymers (2) and block copolymers (3) prepared by ring-opening metathesis polymerization of norbornenes substituted with benzophenone, naphthalene, and phenanthrene groups (1) have been investigated. When benzophenone is attached to this polynorbornene backbone, its excited state behavior differs from that observed for monomeric benzophenone. A new intramolecular excited state complex can be observed in the transient absorption and emission measurements of the benzophenone-substituted homopolymer. In copolymers bearing benzophenone and naphthalene or phenanthrene substituent blocks, triplet energy transfer from the sensitizer (benzophenone) to the arene is observed. This energy transfer dominates over the intramolecular complexation that characterizes group interactions in the homopolymer. 41 refs., 14 figs., 7 tabs.

  18. Intramolecular nitrone dipolar cycloadditions: control of regioselectivity and synthesis of naturally-occurring spirocyclic alkaloids.

    PubMed

    Hodges, Alastair J; Adams, Joseph P; Bond, Andrew D; Holmes, Andrew B; Press, Neil J; Roughley, Stephen D; Ryan, John H; Saubern, Simon; Smith, Catherine J; Turnbull, Michael D; Newton, Annabella F

    2012-12-01

    The intramolecular nitrone dipolar cycloaddition of in situ-generated nitrones such as compound 26 has been used for the synthesis of cyclic isoxazolidines 27 and 29. The regioselectivity of the intramolecular cycloaddition depends on the nature of the terminal substituent on the dipolarophile. The influence of the substituent on the regioselectivity of the cycloaddition has been examined using several model systems and two methods of nitrone formation. These studies demonstrated that the cyano-substituent plays a special role in favouring the formation of the 6,6,5-ring fused adduct 27 under thermodynamically controlled conditions. The utility of the cyclo-adduct 57 (see Scheme 12) as a precursor for the naturally occurring histrionicotoxins is illustrated by the synthesis of three "unsymmetrical" (i.e. with each side chain bearing different functional groups) members of the histrionicotoxin family HTX-259A, HTX-285C and HTX-285E (2, 3 and 4 respectively). PMID:23051904

  19. Theoretical Investigation of Intramolecular Hydrogen Shift Reactions in 3-Methyltetrahydrofuran (3-MTHF) Oxidation.

    PubMed

    Parab, Prajakta R; Sakade, Naoki; Sakai, Yasuyuki; Fernandes, Ravi; Heufer, K Alexander

    2015-11-01

    3-Methyltetrahydrofuran (3-MTHF) is proposed to be a promising fuel component among the cyclic oxygenated species. To have detailed insight of its combustion kinetics, intramolecular hydrogen shift reactions for the ROO to QOOH reaction class are studied for eight ROO isomers of 3-MTHF. Rate constants of all possible reaction paths that involve formation of cyclic transition states are computed by employing the CBS-QB3 composite method. A Pitzer-Gwinn-like approximation has been applied for the internal rotations in reactants, products, and transition states for the accurate treatment of hindered rotors. Calculated relative barrier heights highlight that the most favorable reaction channel proceeds via a six membered transition state, which is consistent with the computed rate constants. Comparing total rate constants in ROO isomers of 3-MTHF with the corresponding isomers of methylcyclopentane depicts faster kinetics in 3-MTHF than methylcyclopentane reflecting the effect of ring oxygen on the intramolecular hydrogen shift reactions. PMID:26444499

  20. Vibrational spectrum and intramolecular coordination of silicon in 1-hydrosilatrane

    SciTech Connect

    Ignat'ev, I.S.; Lazarev, A.N.; Shevchenko, S.G.; Baryshok, V.P.

    1987-01-10

    An investigation of the IR and Raman spectra of 1-hydrosilatrane and its deuterated analog HSi(OCD/sub 2/CD/sub 2/)/sub 3/N makes it possible to identify most of the fundamental vibrations of the skeletons of these molecules. A calculation of the normal coordinates demonstrates the existence of two totally symmetric vibrations, whose frequencies depend on the Si...N interaction. The additive block construction of the potential-energy matrix in dependent internal coordinates permits the evaluation of the contribution of the Si...N interaction to the force field of the molecule.

  1. Molecular Orbital Study of the Formation of Intramolecular Hydrogen Bonding of a Ligand Molecule in a Protein Aromatic Hydrophobic Pocket.

    PubMed

    Koseki, Jun; Gouda, Hiroaki; Hirono, Shuichi

    2016-01-01

    The natural product argadin is a cyclopentapeptide chitinase inhibitor that binds to chitinase B (ChiB) from the pathogenic bacteria Serratia marcescens. N(ω)-Acetyl-L-arginine and L-aminoadipic acid of argadin form intramolecular ionic hydrogen bonds in the aromatic hydrophobic pocket of ChiB. We performed ab initio molecular orbital and density functional theory calculations to elucidate the role of this intramolecular hydrogen bonding on intermolecular interactions between argadin and ChiB. We found that argadin accrues large stabilization energies from the van der Waals dispersion interactions, such as CH-π, π-π, and π-lone pair interactions, in the aromatic hydrophobic pocket of ChiB, although intramolecular hydrogen bonding within argadin might result in loss of entropy. The intramolecular ionic hydrogen bonding formation canceled local molecular charges and provided good van der Waals interactions with surrounding aromatic residues. PMID:27373666

  2. Copper-catalyzed intramolecular N-arylation of quinazolinones: facile convergent approach to (-)-circumdatins H and J.

    PubMed

    Kshirsagar, Umesh A; Argade, Narshinha P

    2010-08-20

    A copper-catalyzed intramolecular N-arylation of a quinazolinone nucleus that furnished the central benzodiazepine core unit has been demonstrated to accomplish an efficient convergent total synthesis of (-)-circumdatins H and J. PMID:20669978

  3. Indium-Mediated Intramolecular Reaction of N-(2-Iodobenzoyl)azabenzonorbornadienes: A General Access to Dihydrobenzo[c]phenanthridinones.

    PubMed

    Liu, Yang; Lei, Kang; Liu, Na; Sun, Dong-Wei; Hua, Xue-Wen; Li, Ya-Juan; Xu, Xiao-Hua

    2016-07-01

    An efficient synthesis of dihydrobenzo[c]phenanthridinones was achieved by utilizing an indium(0)-mediated intramolecular cyclization reaction under ligand- and base-free conditions. A variety of functional groups were tolerated in the present protocol. PMID:27243934

  4. Intramolecular transport of small-molecule cargo in a nanoscale device operated by light.

    PubMed

    Chen, Jiawen; Wezenberg, Sander J; Feringa, Ben L

    2016-05-21

    An intramolecular cargo transport device, based on a light-driven molecular motor, is presented. Detailed UV-vis and (1)H NMR studies demonstrate that the gripper attached to the upper half of the molecular motor is able to pick up an acetyl group from one side of the lower stator and, after a photochemical Z-E isomerization, drop it on the opposite side. PMID:27068214

  5. Stable Blue Phosphorescence Iridium(III) Cyclometalated Complexes Prompted by Intramolecular Hydrogen Bond in Ancillary Ligand.

    PubMed

    Yi, Seungjun; Kim, Jin-Hyoung; Cho, Yang-Jin; Lee, Jiwon; Choi, Tae-Sup; Cho, Dae Won; Pac, Chyongjin; Han, Won-Sik; Son, Ho-Jin; Kang, Sang Ook

    2016-04-01

    Improvement of the stability of blue phosphorescent dopant material is one of the key factors for real application of organic light-emitting diodes (OLEDs). In this study, we found that the intramolecular hydrogen bonding in an ancillary ligand from a heteroleptic Ir(III) complex can play an important role in the stability of blue phosphorescence. To rationalize the role of intramolecular hydrogen bonding, a series of Ir(III) complexes is designed and prepared: Ir(dfppy)2(pic-OH) (1a), Ir(dfppy)2(pic-OMe) (1b), Ir(ppy)2(pic-OH) (2a), and Ir(ppy)2(pic-OMe) (2b). The emission lifetime of Ir(dfppy)2(pic-OH) (1a) (τem = 3.19 μs) in dichloromethane solution was found to be significantly longer than that of Ir(dfppy)2(pic-OMe) (1b) (τem = 0.94 μs), because of a substantial difference in the nonradiative decay rate (knr = 0.28 × 10(5) s(-1) for (1a) vs 2.99 × 10(5) s(-1) for (1b)). These results were attributed to the intramolecular OH···O═C hydrogen bond of the 3-hydroxy-picolinato ligand. Finally, device lifetime was significantly improved when 1a was used as the dopant compared to FIrpic, a well-known blue dopant. Device III (1a as dopant) achieved an operational lifetime of 34.3 h for an initial luminance of 400 nits compared to that of device IV (FIrpic as dopant), a value of 20.1 h, indicating that the intramolecular hydrogen bond in ancillary ligand is playing an important role in device stability. PMID:26991672

  6. A Concomitant Allylic Azide Rearrangement/Intramolecular Azide–Alkyne Cycloaddition Sequence

    PubMed Central

    2015-01-01

    An intramolecular Huisgen cycloaddition of an interconverting set of isomeric allylic azides with alkynes affords substituted triazoles in high yield. The stereoisomeric vinyl-substituted triazoloxazines formed depend on the rate of cycloaddition of the different allylic azide precursors when the reaction is carried out under thermal conditions. In contrast, dimerized macrocyclic products were obtained when the reaction was done using copper(I)-catalyzed conditions, demonstrating the ability to control the reaction products through changing conditions. PMID:24635056

  7. Intramolecular electron transfer reactions in meso-(4-nitrophenyl)-substituted subporphyrins.

    PubMed

    Copley, Graeme; Oh, Juwon; Yoshida, Kota; Shimizu, Daiki; Kim, Dongho; Osuka, Atsuhiro

    2016-01-25

    A2B-type meso-(4-nitrophenyl)-substituted subporphyrins have been synthesized and shown to undergo very fast photoinduced intramolecular charge separation (CS) and charge recombination (CR) between the subporphyrin core and the meso-4-nitrophenyl group in CH2Cl2 as probed by femtosecond time-resolved transient absorption spectroscopy. Red-shifted emissions were detected from charge-separated states as a rare case for porphyrinoids. PMID:26645430

  8. Ruthenium Catalyzed Intramolecular C-S Coupling Reactions: Synthetic Scope and Mechanistic Insight.

    PubMed

    Sharma, Shivani; Pathare, Ramdas S; Maurya, Antim K; Gopal, Kandasamy; Roy, Tapta Kanchan; Sawant, Devesh M; Pardasani, Ram T

    2016-02-01

    A ruthenium catalyzed intramolecular C-S coupling reaction of N-arylthioureas for the synthesis of 2-aminobenzothiazoles has been developed. Kinetic, isotope labeling, and computational studies reveal the involvement of an electrophilic ruthenation pathway instead of a direct C-H activation. Stereoelectronic effect of meta-substituents on the N-arylthiourea dictates the final regioselective outcome of the reaction. PMID:26761401

  9. A Chiral Thiourea as a Template for Enantioselective Intramolecular [2 + 2] Photocycloaddition Reactions

    PubMed Central

    2016-01-01

    A chiral (1R,2R)-diaminocyclohexane-derived bisthiourea was found to exhibit a significant asymmetric induction in the intramolecular [2 + 2] photocycloaddition of 2,3-dihydropyridone-5-carboxylates. Under optimized conditions, the reaction was performed with visible light employing 10 mol % of thioxanthone as triplet sensitizer. Due to the different electronic properties of its carbonyl oxygen atoms, a directed binding of the substrate to the template is possible, which in turn enables an efficient enantioface differentiation. PMID:27258626

  10. Utilising tetraphenylethene as a dual activator for intramolecular charge transfer and aggregation induced emission.

    PubMed

    Zhang, Guo-Feng; Aldred, Matthew P; Gong, Wen-Liang; Li, Chong; Zhu, Ming-Qiang

    2012-08-11

    We report a simple design and synthesis of a donor-acceptor tetraphenylethene-naphthalimide (TPE-NI) dyad, in which TPE acts both as an electron-donor for intramolecular charge transfer (ICT) and activator for aggregation induced emission (AIE). Strong solvent-dependent photoluminescence covering almost the whole visible spectrum and AIE in its nanoparticle state compared to its solution state are demonstrated. PMID:22745935

  11. An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

    PubMed Central

    Ma, Zhiyuan; Ni, Feng; Woo, Grace H C; Lo, Sie-Mun; Roveto, Philip M; Schaus, Scott E

    2012-01-01

    Summary Intramolecular inverse electron demand cycloadditions of isatin-derived 1,2,4-triazines with acetylenic dienophiles tethered by amidations or transesterifications proceed in excellent yields to produce lactam- or lactone-fused α-carbolines. Beginning with various isatins and alkynyl dienophiles, a pilot-scale library of eighty-eight α-carbolines was prepared by using this robust methodology for biological evaluation. PMID:23015831

  12. A near infrared colorimetric and fluorometric probe for organophosphorus nerve agent mimics by intramolecular amidation.

    PubMed

    Hu, Xiao-Xiao; Su, Yue-Ting; Ma, Yun-Wei; Zhan, Xin-Qi; Zheng, Hong; Jiang, Yun-Bao

    2015-10-21

    A near infrared probe for sensitive colorimetric and fluorimetric detection of nerve agent mimics, DCP and DCNP, was reported based on the activation of a carboxylic acid group by the mimics to conduct an intramolecular amidation reaction in the heptamethine chromophore, where its absorption or excitation maximum wavelength could be greatly red-shifted by attenuating the electron-donating ability of the amine group in the bridgehead site of heptamethine cyanine. PMID:26323249

  13. Synthesis of an ABCD-Type Phthalocyanine by Intramolecular Cyclization Reaction.

    PubMed

    Chow, Sun Y S; Ng, Dennis K P

    2016-07-01

    Unsymmetrical phthalocyanines with a low symmetry can exhibit unique and intriguing properties that can facilitate their applications in certain disciplines. The synthesis of these compounds, however, has posed a great difficulty. A novel and unprecedented approach for phthalocyanine synthesis is reported that involves intramolecular cyclization of prelinked tetrakisphthalonitriles. By using this strategy, the first ABCD-type phthalocyanine has been prepared in 7.2% yield. PMID:27309120

  14. Synthesis of carbazoles by copper-catalyzed intramolecular C-H/N-H coupling.

    PubMed

    Takamatsu, Kazutaka; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro

    2014-06-01

    A Cu-catalyzed intramolecular C-H amination for the synthesis of carbazoles has been developed. The key to success is the installation of the picolinamide-based directing group, which is spontaneously removed after the coupling event. The Cu catalysis proceeded smoothly under Pd- and I(III)-free conditions, and its mild oxidation aptitude enables the rapid and concise construction of heteroatom-incorporated carbazole core π-systems. PMID:24813821

  15. Auger electron spectroscopy as a tool for measuring intramolecular charges of adsorbed molecules

    NASA Astrophysics Data System (ADS)

    Magkoev, T. T.

    A way for the determination of the values of intramolecular charges of adsorbed molecules of some binary dielectrics, based on Auger electron spectroscopy (AES), is proposed. These values can be obtained from the coverage dependences of the ratios of intensities of anion KL 23L 23 and KL 1L 1 Auger transitions, which are sensitive to the amount of charge at the 2p-orbitals. As an example, MgO adsorbed on Mo(110) is presented.

  16. Auger electron spectroscopy as a tool for measuring intramolecular charges of adsorbed molecules

    NASA Astrophysics Data System (ADS)

    Magkoev, T. T.

    1993-10-01

    A way for the determination of the values of intramolecular charges of adsorbed molecules of some binary dielectrics, based on Auger electron spectroscopy (AES), is proposed. These values can be obtained from the coverage dependences of the ratios of intensities of anion KL 23L 23 and KL 1L 1 Auger transitions, which are sensitive to the amount of charge at the 2p-orbitals. As an example, MgO adsorbed on Mo(110) is presented.

  17. An Iridium(I) N-Heterocyclic Carbene Complex Catalyzes Asymmetric Intramolecular Allylic Amination Reactions.

    PubMed

    Ye, Ke-Yin; Cheng, Qiang; Zhuo, Chun-Xiang; Dai, Li-Xin; You, Shu-Li

    2016-07-01

    A chiral iridium(I) N-heterocyclic carbene complex was reported for the first time as the catalyst in the highly enantioselective intramolecular allylic amination reaction. The current method provides facile access to biologically important enantioenriched indolopiperazinones and piperazinones in good yields (74-91 %) and excellent enantioselectivities (92-99 % ee). Preliminary mechanistic investigations reveal that the C-H activation occurs at the position ortho to the N-aryl group of the ligand. PMID:27162135

  18. Vibrationally highly excited molecules and intramolecular mode coupling through high-overtone spectroscopy

    SciTech Connect

    Wong, J.S.; Moore, C.B.

    1981-08-01

    High overtone spectra of organic molecules can be interpreted using the local mode model for absorptions by the inequivalent C-H bonds. The spectra can be assigned using either observed C-H bond lengths or isolated fundamental frequencies. The spectra of trihalomethanes indicate that the dominant intramolecular mode coupling for the C-H stretching overtones is Fermi resonance with combination states with one less C-H stretching quantum plus two quanta of the C-H bending vibrations.

  19. Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives

    PubMed Central

    2015-01-01

    Methods have recently been developed for the phosphine-catalyzed asymmetric γ-addition of nucleophiles to readily available allenoates and alkynoates to generate useful α,β-unsaturated carbonyl compounds that bear a stereogenic center in either the γ or the δ position (but not both) with high stereoselectivity. The utility of this approach would be enhanced considerably if the stereochemistry at both termini of the new bond could be controlled effectively. In this report, we describe the achievement of this objective, specifically, that a chiral phosphepine can catalyze the stereoconvergent γ-addition of a racemic nucleophile to a racemic electrophile; through the choice of an appropriate heterocycle as the nucleophilic partner, this new method enables the synthesis of protected α,α-disubstituted α-amino acid derivatives in good yield, diastereoselectivity, and enantioselectivity. PMID:26192217

  20. Characterization of intramolecular hydrogen bonds by atomic charges and charge fluxes.

    PubMed

    Baranović, Goran; Biliškov, Nikola; Vojta, Danijela

    2012-08-16

    The electronic charge redistribution and the infrared intensities of the two types of intramolecular hydrogen bonds, O-H···O and O-H···π, of o-hydroxy- and o-ethynylphenol, respectively, together with a set of related intermolecular hydrogen bond complexes are described in terms of atomic charges and charge fluxes derived from atomic polar tensors calculated at the B3LYP/cc-pVTZ level of theory. The polarizable continuum model shows that both the atomic charges and charge fluxes are strongly dependent on solvent. It is shown that their values for the OH bond in an intramolecular hydrogen bond are not much different from those for the "free" OH bond, but the changes are toward the values found for an intermolecular hydrogen bond. The intermolecular hydrogen bond is characterized not only by the decreased atomic charge but also by the enlarged charge flux term of the same sign producing thus an enormous increase in IR intensity. The overall behavior of the charges and fluxes of the hydrogen atom in OH and ≡CH bonds agree well with the observed spectroscopic characteristics of inter- and intramolecular hydrogen bonding. The main reason for the differences between the two types of the hydrogen bond lies in the molecular structure because favorable linear proton donor-acceptor arrangement is not possible to achieve within a small molecule. The calculated intensities (in vacuo and in polarizable continuum) are only in qualitative agreement with the measured data. PMID:22809455

  1. Regulation of interleukin-4 signaling by extracellular reduction of intramolecular disulfides

    SciTech Connect

    Curbo, Sophie; Gaudin, Raphael; Carlsten, Mattias; Malmberg, Karl-Johan; Troye-Blomberg, Marita; Ahlborg, Niklas; Karlsson, Anna; Johansson, Magnus; Lundberg, Mathias

    2009-12-25

    Interleukin-4 (IL-4) contains three structurally important intramolecular disulfides that are required for the bioactivity of the cytokine. We show that the cell surface of HeLa cells and endotoxin-activated monocytes can reduce IL-4 intramolecular disulfides in the extracellular space and inhibit binding of IL-4 to the IL-4R{alpha} receptor. IL-4 disulfides were in vitro reduced by thioredoxin 1 (Trx1) and protein disulfide isomerase (PDI). Reduction of IL-4 disulfides by the cell surface of HeLa cells was inhibited by auranofin, an inhibitor of thioredoxin reductase that is an electron donor to both Trx1 and PDI. Both Trx1 and PDI have been shown to be located at the cell surface and our data suggests that these enzymes are involved in catalyzing reduction of IL-4 disulfides. The pro-drug N-acetylcysteine (NAC) that promotes T-helper type 1 responses was also shown to mediate the reduction of IL-4 disulfides. Our data provides evidence for a novel redox dependent pathway for regulation of cytokine activity by extracellular reduction of intramolecular disulfides at the cell surface by members of the thioredoxin enzyme family.

  2. Molecular dynamics of excited state intramolecular proton transfer: 3-hydroxyflavone in solution

    SciTech Connect

    Bellucci, Michael A.; Coker, David F.

    2012-05-21

    The ultrafast enol-keto photoisomerization in the lowest singlet excited state of 3-hydroxyflavone is investigated using classical molecular dynamics in conjunction with empirical valence bond (EVB) potentials for the description of intramolecular interactions, and a molecular mechanics and variable partial charge model, dependent on transferring proton position, for the description of solute-solvent interactions. A parallel multi-level genetic program was used to accurately fit the EVB potential energy surfaces to high level ab initio data. We have studied the excited state intramolecular proton transfer (ESIPT) reaction in three different solvent environments: methylcyclohexane, acetonitrile, and methanol. The effects of the environment on the proton transfer time and the underlying mechanisms responsible for the varied time scales of the ESIPT reaction rates are analyzed. We find that simulations with our EVB potential energy surfaces accurately reproduce experimentally determined reaction rates, fluorescence spectra, and vibrational frequency spectra in all three solvents. Furthermore, we find that the ultrafast ESIPT process results from a combination of ballistic transfer, and intramolecular vibrational redistribution, which leads to the excitation of a set of low frequency promoting vibrational modes. From this set of promoting modes, we find that an O-O in plane bend and a C-H out of plane bend are present in all three solvents, indicating that they are fundamental to the ultrafast proton transfer. Analysis of the slow proton transfer trajectories reveals a solvent mediated proton transfer mechanism, which is diffusion limited.

  3. An intramolecular disulfide bond designed in myoglobin fine-tunes both protein structure and peroxidase activity.

    PubMed

    Wu, Lei-Bin; Yuan, Hong; Zhou, Hu; Gao, Shu-Qin; Nie, Chang-Ming; Tan, Xiangshi; Wen, Ge-Bo; Lin, Ying-Wu

    2016-06-15

    Disulfide bond plays crucial roles in stabilization of protein structure and in fine-tuning protein functions. To explore an approach for rational heme protein design, we herein rationally introduced a pair of cysteines (F46C/M55C) into the scaffold of myoglobin (Mb), mimicking those in native neuroglobin. Molecular modeling suggested that it is possible for Cys46 and Cys55 to form an intramolecular disulfide bond, which was confirmed experimentally by ESI-MS analysis, DTNB reaction and CD spectrum. Moreover, it was shown that the spontaneously formed disulfide bond of Cys46-Cys55 fine-tunes not only the heme active site structure, but also the protein functions. The substitution of Phe46 with Ser46 in F46S Mb destabilizes the protein while facilitates H2O2 activation. Remarkably, the formation of an intramolecular disulfide bond of Cys46-Cys55 in F46C/M55C Mb improves the protein stability and regulates the heme site to be more favorable for substrate binding, resulting in enhanced peroxidase activity. This study provides valuable information of structure-function relationship for heme proteins regulated by an intramolecular disulfide bond, and also suggests that construction of such a covalent bond is useful for design of functional heme proteins. PMID:27117233

  4. The interplay between inter- and intra-molecular dynamics in a series of alkylcitrates

    SciTech Connect

    Kipnusu, Wycliffe Kiprop; Kossack, Wilhelm; Iacob, Ciprian; Zeigermann, Philipp; Jasiurkowska, Malgorzata; Sangoro, Joshua R; Valiullin, Rustem; Kremer, Friedrich

    2013-01-01

    The inter- and intra-molecular dynamics in a series of glass-forming alkylcitrates is studied by a combination of Broadband Dielectric Spectroscopy (BDS), Pulsed Field Gradient Nuclear Magnetic Resonance (PFG NMR), Fourier-Transform Infrared (FTIR) spectroscopy and Differential Scanning Calorimetry (DSC). Analyzing the temperature dependencies of specific IR absorption bands in terms of their spectral position and the corresponding oscillator strengths enables one to unravel the intramolecular dynamics of specific molecular moieties and to compare them with the (primarily dielectrically) determined intermolecular dynamics. With decreasing temperature, the IR band positions of carbonyls (part of the core units) and H-bonded moieties of citrates show a red shift with a kink at the calorimetric glass transition temperature (Tg) while other moieties, whose dynamics are decoupled from those of the core units, exhibit a blue shift with nominal changes at Tg. The oscillator strength of all units in citrates depicts stronger temperature dependencies above Tg and in some, the ester linkage and H-bonded units show a change of slope at a temperature where structural and faster secondary relaxations merge. By that, a wealth of novel information is obtained proving the fundamental importance of intramolecular mobility in the process of glass formation, beyond coarse-grained descriptions.

  5. Conformational analysis and intramolecular hydrogen bonding of cis-3-aminoindan-1-ol: a quantum chemical study.

    PubMed

    Kheffache, Djaffar; Guemmour, Hind; Dekhira, Azzedine; Benaboura, Ahmed; Ouamerali, Ourida

    2013-11-01

    In the present work, we carried out a conformational analysis of cis-3-aminoindan-1-ol and evaluated the role of the intramolecular hydrogen bond in the stabilization of various conformers using quantum mechanical DFT (B3LYP) and MP2 methods. On the basis of relative energies, we have found nine conformational minima, which can interchange through the ring-puckering and the internal rotation of the OH and NH2 groups on the five-membered ring. The intramolecular hydrogen bonds such as OH∙∙∙∙π, NH∙∙∙∙π, NH∙∙∙∙OH and HN∙∙∙∙HO are expected to be of critical importance for the conformational stabilities. The intramolecular interactions of the minima have been analyzed by calculation of electron density (ρ) and Laplacian (ρ) at the bond critical points (BCPs) using atoms-in-molecule (AIM) theory. The existence or absence of OH∙∙∙∙π and NH∙∙∙∙π in cis-3-aminoindan-1-ol remains unclear since the geometrical investigation has not been confirmed by topological criteria. The results of theoretical calculations demonstrate that this compound exists predominantly in one ring-puckering form stabilized by strong hydrogen bond HN∙∙∙∙HO Interaction. PMID:24026578

  6. Copper-Catalyzed Intramolecular Oxidative Amination of Unactivated Internal Alkenes.

    PubMed

    Xiong, Peng; Xu, Fan; Qian, Xiang-Yang; Yohannes, Yared; Song, Jinshuai; Lu, Xin; Xu, Hai-Chao

    2016-03-18

    A copper-catalyzed oxidative amination of unactivated internal alkenes has been developed. The Wacker-type oxidative alkene amination reaction is traditionally catalyzed by a palladium through a mechanism involving aminopalladation and β-hydride elimination. Replacing the precious and scarce palladium with a cheap and abundant copper for this transformation has been challenging because of the difficulty associated with the aminocupration of internal alkenes. The combination of a simple copper salt, without additional ligand, as the catalyst and Dess-Martin periodinane as the oxidant, promotes efficiently the oxidative amination of allylic carbamates and ureas bearing di- and trisubstituted alkenes leading to oxazolidinones and imidazolidinones. Preliminary mechanistic studies suggested a hybrid radical-organometallic mechanism involving an amidyl radical cyclization to form the key C-N bond. PMID:26878987

  7. 1-(2-biphenyl)-3-methyltriazenide-N-oxide as a template for intramolecular copper(II)⋯arene-π interactions

    NASA Astrophysics Data System (ADS)

    Paraginski, Gustavo Luiz; Hörner, Manfredo; Back, Davi Fernando; Wohlmuth Alves dos Santos, Aline Joana Rolina; Beck, Johannes

    2016-01-01

    Deprotonated triazene N-oxides are able to chelate metal ions resulting in five-membered rings without carbon atoms. A new ligand 1-(2-biphenyl)-3-methyltriazenide-N-oxide (1) and its mononuclear Cu(II) complex (2) were synthesized to verify the capability of this ligand to promote Cu(II)⋯arene-π interactions. Ligand 1 and complex 2 have been characterized by elemental analysis, mass spectrometry (ESI(+)-TOF), IR, and UV-Vis spectroscopy. In addition, ligand 1 was characterized by 1H and 13C NMR and complex 2 by X-ray diffraction on single crystal. The crystal structure of complex 2 reveals a distorted tetrahedral geometry of Cu(II) in the first coordination sphere, which expands to a distorted octahedral environment by two symmetrically independent intramolecular metal⋯arene-π interactions. These interactions are provided by ortho-phenyl rings of both triazene N-oxide ligands 1. The aim of this work was to contribute to the architecture of new Cu(II)⋯arene-π complexes based on the synthesis of appropriated ligand for intramolecular interactions

  8. Probing Intramolecular versus Intermolecular CO2 Adsorption on Amine-Grafted SBA-15.

    PubMed

    Yoo, Chun-Jae; Lee, Li-Chen; Jones, Christopher W

    2015-12-15

    A mesoporous silica SBA-15 is modified with an array of amine-containing organosilanes including (i) propylamine, SiCH2CH2CH2NH2 (MONO), (ii) propylethylenediamine, SiCH2CH2CH2NHCH2CH2NH2 (DI), (iii) propyldiethylenetriamine, SiCH2CH2CH2NHCH2CH2NHCH2CH2NH2 (TRI), and (iv) propyltriethylenetetramine, SiCH2CH2CH2NHCH2CH2N(CH2CH2NH2)2 (TREN) and the low loading silane adsorbents (∼0.45 mmol silane/g) are evaluated for their CO2 adsorption properties, with a focus on gaining insight into the propensity for intramolecular vs intermolecular CO2 adsorption. Adsorption isotherms at low CO2 coverages are measured while simultaneously recording the heat evolved via a Tian-Calvet calorimeter. The results are compared on a silane molecule efficiency basis (mol CO2 adsorbed/mol silane) to assess the potential for intramolecular CO2 adsorption, employing two amine groups in a single silane molecule. As the number of amines in the silane molecule increases (MONO < DI < TREN ∼ TRI), the silane molecule efficiency is enhanced owing to the ability to intramolecularly capture CO2. Analysis of the CO2 uptake for samples with the surface silanols removed by capping demonstrates that cooperative uptake due to amine-CO2-silanol interactions is also possible over these adsorbents and is the primary mode of sorption for the MONO material at the studied low silane loading. As the propensity for intramolecular CO2 capture increases due to the presence of multiple amines in a single silane molecule (MONO < DI < TREN ∼ TRI), the measured heat of adsorption also increases. This study of various amine-containing silanes at low coverage is the first to provide significant, direct evidence for intramolecular CO2 capture in a single silane molecule. Furthermore, it provides evidence for the relative heats of adsorption for physisorption on a silanol laden surface (ca. 37 kJ/mol), a silanol-capped surface (ca. 25 kJ/mol), via amine-CO2-silanol interactions (ca. 46 kJ/mol), and via amine-CO2

  9. Escherichia coli lipoprotein binds human plasminogen via an intramolecular domain

    PubMed Central

    Gonzalez, Tammy; Gaultney, Robert A.; Floden, Angela M.; Brissette, Catherine A.

    2015-01-01

    Escherichia coli lipoprotein (Lpp) is a major cellular component that exists in two distinct states, bound-form and free-form. Bound-form Lpp is known to interact with the periplasmic bacterial cell wall, while free-form Lpp is localized to the bacterial cell surface. A function for surface-exposed Lpp has yet to be determined. We hypothesized that the presence of C-terminal lysinses in the surface-exposed region of Lpp would facilitate binding to the host zymogen plasminogen (Plg), a protease commandeered by a number of clinically important bacteria. Recombinant Lpp was synthesized and the binding of Lpp to Plg, the effect of various inhibitors on this binding, and the effects of various mutations of Lpp on Lpp–Plg interactions were examined. Additionally, the ability of Lpp-bound Plg to be converted to active plasmin was analyzed. We determined that Lpp binds Plg via an atypical domain located near the center of mature Lpp that may not be exposed on the surface of intact E. coli according to the current localization model. Finally, we found that Plg bound by Lpp can be converted to active plasmin. While the consequences of Lpp binding Plg are unclear, these results prompt further investigation of the ability of surface exposed Lpp to interact with host molecules such as extracellular matrix components and complement regulators, and the role of these interactions in infections caused by E. coli and other bacteria. PMID:26500634

  10. Intramolecular stable isotope distributions detect plant metabolic responses on century time scales

    NASA Astrophysics Data System (ADS)

    Schleucher, Jürgen; Ehlers, Ina; Augusti, Angela; Betson, Tatiana

    2014-05-01

    Plants respond to environmental changes on a vast range of time scales, and plant gas exchanges constitute important feedback mechanisms in the global C cycle. Responses on time scales of decades to centuries are most important for climate models, for prediction of crop productivity, and for adaptation to climate change. Unfortunately, responses on these timescale are least understood. We argue that the knowledge gap on intermediate time scales is due to a lack of adequate methods that can bridge between short-term manipulative experiments (e.g. FACE) and paleo research. Manipulative experiments in plant ecophysiology give information on metabolism on time scales up to years. However, this information cannot be linked to results from retrospective studies in paleo research, because little metabolic information can be derived from paleo archives. Stable isotopes are prominent tools in plant ecophysiology, biogeochemistry and in paleo research, but in all applications to date, isotope ratios of whole molecules are measured. However, it is well established that stable isotope abundance varies among intramolecular groups of biochemical metabolites, that is each so-called "isotopomer" has a distinct abundance. This intramolecular variation carries information on metabolic regulation, which can even be traced to individual enzymes (Schleucher et al., Plant, Cell Environ 1999). Here, we apply intramolecular isotope distributions to study the metabolic response of plants to increasing atmospheric [CO2] during the past century. Greenhouse experiments show that the deuterium abundance among the two positions in the C6H2 group of photosynthetic glucose depends on [CO2] during growth. This is observed for all plants using C3 photosynthesis, and reflects the metabolic flux ratio between photorespiration and photosynthesis. Photorespiration is a major C flux that limits assimilation in C3 plants, which encompass the overwhelming fraction of terrestrial photosynthesis and the

  11. Cp2ZrMeCl: A Reagent for Asymmetric Methyl Addition.

    PubMed

    Garrec, Kilian; Fletcher, Stephen P

    2016-08-01

    The use of Cp2ZrMeCl is described as a source of nucleophilic methyl in asymmetric catalysis. This easily prepared reagent is bench stable, weighable in air, and generally useful in highly enantioselective copper-catalyzed addition reactions at room temperature. Methyl is successfully (generally >90% ee) added in 1,4-additions to cyclic and acyclic α,β-unsaturated ketones to provide tertiary and quaternary centers. Examples of catalyst controlled diastereoselective 1,6-addition and dynamic kinetic asymmetric allylic alkylation reactions are also reported. The reagent is used in the catalytic asymmetric synthesis of naturally occurring fragrance (R)-(-)-muscone (82% yield, 91% ee). PMID:27458650

  12. Nucleophilic ring opening of bridging thietane ligands in trirhenium carbonyl cluster complexes

    SciTech Connect

    Adams, R.D.; Cortopassi, J.E.; Falloon, S.B.

    1992-11-01

    The reactions of 3,3-dimethylthietane, SCH{sub 2}CMe{sub 2}CH{sub 2} (3,3-DMT), and thietane, SCH{sub 2}CH{sub 2}CH{sub 2}, with Re{sub 3}(CO){sub 10}[{mu}-SCH{sub 2}CH{sub 2}CH{sub 2}]({mu}-H){sub 3}, 2b. Compound 2a was characterized crystallographically and was found to consist of a trirhenium cluster with three bridging hydride ligands and a bridging thietane ligand coordinated through its sulfur atom. 2a and 2b react with halide ions by ring-opening additions to the 3,3-DMT ligand to yield the complex anions [Re{sub 3}(CO){sub 10}({mu}-SCH{sub 2}CMe{sub 2}CH{sub 2}x)({mu}-h){sub 3}]{sup -} 3A-6A, X = F (71%), Cl(71%), Br(84%), I(87%) and [Re{sub 3}(CO){sub 10}({mu}-SCH{sub 2}CH{sub 2}CH{sub 2}Cl)({mu}-H){sub 3}]{sup -}, 4b (67%). Similarly, addition of NMe{sub 3} to 2a and 2b yielded the ring-opened zwitterions Re{sub 3}(CO){sub 10}({mu}-SCH{sub 2}CMe{sub 2}CH{sub 2}NMe{sub 3})({mu}-H){sub 3}, 7 a crystographically. They are zwitterions positively charged at the nitrogen atoms and negatively charged on the trirhenium clusters. Complex 7b was also obtained in a 48% yield from the reaction of Re{sub 3}(C){sub 12}({mu}-H){sub 3} with Me{sub 3}NO in the presence of thietane, but the corresponding reaction using 3,3-DMT yielded only 2a and Re{sub 3}(CO){sub 11}(SCH{sub 2}CMe{sub 2}CH{sub 2})({mu}-H){sub 3}, 8. Attempts to obtain a ring-opening addition to 2a by reaction with PMe{sub 2}Ph yielded only Re{sub 3}(CO){sub 10}(PMe{sub 2}PH){sub 2}({mu}-H){sub 3} by ligand substitution. Attempts to obtain ring opening addition to 8 by reaction with I{sup -} yielded only [Re{sub 3}(CO){sub 11}I({mu}-H){sub 3}]{sup -} by ligand substitution. 20 refs., 3 figs., 10 tabs.

  13. Preparation and characterization of poly (arylene ether isoxazole)s by fluoride ion-mediated aromatic nucleophilic displacement reactions

    NASA Technical Reports Server (NTRS)

    Herbert, C. G.; Bass, R. G.

    1994-01-01

    As part of a continuing effort to prepare novel thermally stable high-performance polymers, poly(arylene ether isoxazole)s have been prepared by fluoride ion-catalyzed aromatic nucleophilic substitution reactions with bis(trimethylsiloxyphenyl) isoxazoles and activated bisarylhalides in diphenyl sulfone. Initial investigation involving the preparation of these materials with isoxazole bisphenols and activated bisarylhalides in the presence of potassium carbonate indicated that, under reaction conditions necessary to prepare high-molecular-weight materials, the isoxazole monomer was converted to an enamino ketone. This side reaction was avoided by using fluoride as a base. However, trimethylsilyl ether derivatives of the isoxazole bisphenols were required in these polymerizations for the preparation of high-molecular-weight materials. Moderate to high inherent viscosity eta(sub inh): 0.43-0.87 dl/g) materials with good thermal stability (air: 409-477 C, helium: 435-512 C) can be prepared by the silyl ether method. Glass transition temperatures ranged from 182 to 225 C for polymers with phenyl pendants and from 170 to 214 C for those without. Molecular weight control by 2% endcapping and the incorporation of a phenyl pendant at the 4 position of the isoxazole is necessary to yield polymers soluble in polar aprotic solvents at room temperature. There is evidence, however, indicating the existence of crosslinks between the polymer chains when the silyl ether approach is utilized.

  14. Enantioconvergent Nucleophilic Substitution Reaction of Racemic Alkyne-Dicobalt Complex (Nicholas Reaction) Catalyzed by Chiral Brønsted Acid.

    PubMed

    Terada, Masahiro; Ota, Yusuke; Li, Feng; Toda, Yasunori; Kondoh, Azusa

    2016-08-31

    Catalytic enantioselective syntheses enable a practical approach to enantioenriched molecules. While most of these syntheses have been accomplished by reaction at the prochiral sp(2)-hybridized carbon atom, little attention has been paid to enantioselective nucleophilic substitution at the sp(3)-hybridized carbon atom. In particular, substitution at the chiral sp(3)-hybridized carbon atom of racemic electrophiles has been rarely exploited. To establish an unprecedented enantioselective substitution reaction of racemic electrophiles, enantioconvergent Nicholas reaction of an alkyne-dicobalt complex derived from racemic propargylic alcohol was developed using a chiral phosphoric acid catalyst. In the present enantioconvergent process, both enantiomers of the racemic alcohol were transformed efficiently to a variety of thioethers with high enantioselectivity. The key to achieving success is dynamic kinetic asymmetric transformation (DYKAT) of enantiomeric cationic intermediates generated via dehydroxylation of the starting racemic alcohol under the influence of the chiral phosphoric acid catalyst. The present fascinating DYKAT involves the efficient racemization of these enantiomeric intermediates and effective resolution of these enantiomers through utilization of the chiral conjugate base of the phosphoric acid. PMID:27490239

  15. Oxidative group transfer to a triiron complex to form a nucleophilic μ(3)-nitride, [Fe3(μ(3)-N)]-.

    PubMed

    Powers, Tamara M; Fout, Alison R; Zheng, Shao-Liang; Betley, Theodore A

    2011-03-16

    Utilizing a hexadentate ligand platform, a high-spin trinuclear iron complex of the type ((tbs)L)Fe(3)(thf) was synthesized and characterized ([(tbs)L](6-) = [1,3,5-C(6)H(9)(NPh-o-NSi(t)BuMe(2))(3)](6-)). The silyl-amide groups only permit ligation of one solvent molecule to the tri-iron core, resulting in an asymmetric core wherein each iron ion exhibits a distinct local coordination environment. The triiron complex ((tbs)L)Fe(3)(thf) rapidly consumes inorganic azide ([N(3)]NBu(4)) to afford an anionic, trinuclear nitride complex [((tbs)L)Fe(3)(μ(3)-N)]NBu(4). The nearly C(3)-symmetric complex exhibits a highly pyramidalized nitride ligand that resides 1.205(3) Å above the mean triiron plane with short Fe-N (1.871(3) Å) distances and Fe-Fe separation (2.480(1) Å). The nucleophilic nitride can be readily alkylated via reaction with methyl iodide to afford the neutral, trinuclear methylimide complex ((tbs)L)Fe(3)(μ(3)-NCH(3)). Alkylation of the nitride maintains the approximate C(3)-symmetry in the imide complex, where the imide ligand resides 1.265(9) Å above the mean triiron plane featuring lengthened Fe-N(imide) bond distances (1.892(3) Å) with nearly equal Fe-Fe separation (2.483(1) Å). PMID:21332160

  16. Tandem Synthesis of 10-Dimethylaminobenzo[h]quinazolines from 2-Ketimino-1,8-bis(dimethylamino)naphthalenes via Nucleophilic Replacement of the Unactivated Aromatic NMe2 Group.

    PubMed

    Mikshiev, Vladimir Y; Antonov, Alexander S; Pozharskii, Alexander F

    2016-06-17

    It has been found that 2-bromo-1,8-bis(dimethylamino)naphthalene on sequential treatment with n-BuLi and 2 equiv of the same or different aryl(hetaryl) cyanide as a result of [2 + 2 + 2] nucleophilic cascade annulation produces 10-dimethylaminobenzo[h]quinazolines, as yet unknown NMe2/-N═ analogues of the proton sponge. It is even more convenient to use preliminarily prepared 2-ketimino-1,8-bis(dimethylamino)naphthalenes as starting material. The substitution of both peri-NMe2 groups furnishing quinazolino[7,8-h]quinazoline derivatives is also possible. The process is remarkable by surprisingly mild nucleophilic displacement of an unactivated aromatic NMe2 group. PMID:27258556

  17. Time-Resolved Crystallography of the Reaction Intermediate of Nitrile Hydratase: Revealing a Role for the Cysteinesulfenic Acid Ligand as a Catalytic Nucleophile.

    PubMed

    Yamanaka, Yasuaki; Kato, Yuki; Hashimoto, Koichi; Iida, Keisuke; Nagasawa, Kazuo; Nakayama, Hiroshi; Dohmae, Naoshi; Noguchi, Keiichi; Noguchi, Takumi; Yohda, Masafumi; Odaka, Masafumi

    2015-09-01

    The reaction mechanism of nitrile hydratase (NHase) was investigated using time-resolved crystallography of the mutant NHase, in which βArg56, strictly conserved and hydrogen bonded to the two post-translationally oxidized cysteine ligands, was replaced by lysine, and pivalonitrile was the substrate. The crystal structures of the reaction intermediates were determined at high resolution (1.2-1.3 Å). In combination with FTIR analyses of NHase following hydration in H2 (18) O, we propose that the metal-coordinated substrate is nucleophilically attacked by the O(SO(-) ) atom of αCys114-SO(-) , followed by nucleophilic attack of the S(SO(-) ) atom by a βArg56-activated water molecule to release the product amide and regenerate αCys114-SO(-) . PMID:26333053

  18. A versatile approach to Ullmann C-N couplings at room temperature: new families of nucleophiles and electrophiles for photoinduced, copper-catalyzed processes.

    PubMed

    Ziegler, Daniel T; Choi, Junwon; Muñoz-Molina, José María; Bissember, Alex C; Peters, Jonas C; Fu, Gregory C

    2013-09-01

    The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C-N bond formation to occur under unusually mild conditions. In this study, we substantially expand the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C-N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups. PMID:23968565

  19. Nucleophilic Participation in the Solvolyses of (Arylthio)methyl Chlorides and Derivatives: Application of Simple and Extended Forms of the Grunwald-Winstein Equations.

    PubMed

    Kevill, Dennis N; Park, Young Hoon; Park, Byoung-Chun; D'Souza, Malcolm J

    2012-06-01

    The specific rates of solvolysis of chloromethyl phenyl sulfide [(phenylthio)methyl chloride] and its p-chloro-derivative have been determined at 0.0 °C in a wide range of hydroxylic solvents, including several containing a fluroalcohol. Treatment in terms of a two-term Grunwald-Winstein equation, incorporating terms based on solvent ionizing power (Y(Cl)) and solvent nucleophilicity (N(T)) suggest a mechanism similar to that for the solvolyses of tert-butyl chloride, involving in the rate-determining step a nucleophilic solvation of the incipient carbocation in an ionization process. A previous suggestion, that a third-term governed by the aromatic ring parameter (I) is required, is shown both for the new and for the previously studied related substrates to be an artifact, resulting from an appreciable degree of multicollinearity between I values and a linear combination of N(T) and Y(Cl) values. PMID:22711999

  20. The Palladium Catalyzed Asymmetric Addition of Oxindoles and Allenes: an Atom-Economical Versatile Method for the Construction of Chiral Indole Alkaloids

    PubMed Central

    Trost, Barry M.; Xie, Jia; Sieber, Joshua D.

    2011-01-01

    The Pd-catalyzed asymmetric allylic alkylation (AAA) is one of the most useful and versatile methods for asymmetric synthesis known in organometallic chemistry. Development of this reaction over the past 30 years has typically relied on the use of an allylic electrophile bearing an appropriate leaving group to access the reactive Pd(π-allyl) intermediate that goes on to the desired coupling product after attack by the nucleophile present in the reaction. Our group has been interested in developing alternative approaches to access the reactive Pd(π-allyl) intermediate that does not require the use of an activated electrophile, which ultimately generates a stoichiometric byproduct in the reaction that is derived from the leftover leaving group. Along these lines, we have demonstrated that allenes can be used to generate the reactive Pd(π-allyl) intermediate in the presence of an acid cocatalyst, and this system is compatible with nucleophiles to allow for formation of formal AAA products by Pd-catalyzed additions to allenes. This article describes our work regarding the use of oxindoles as carbon-based nucleophiles in a Pd-catalyzed asymmetric addition of oxindoles to allenes (Pd-catalyzed hydrocarbonation of allenes). By using the chiral standard Trost ligand (L1) and 3-aryloxindoles as nucleophiles, this hydrocarbonation reaction provides products with two vicinal stereocenters, with one being quaternary, in excellent chemo-, regio-, diastereo-, and enantioselectivities in high chemical yields. PMID:22070545