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Sample records for intramolecular nucleophilic addition

  1. 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

  2. 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

  3. A new approach to cyclic hydroxamic acids: Intramolecular cyclization of N-benzyloxy carbamates with carbon nucleophiles

    PubMed Central

    Liu, Yuan; Jacobs, Hollie K.

    2011-01-01

    N-Alkyl-N-benzyloxy carbamates, 2, undergo facile intramolecular cyclization with a variety of carbon nucleophiles to give functionalized 5- and 6-membered protected cyclic hydroxamic acids, 3, in good to excellent yields. This method can be extended to prepare seven-membered cyclic hydroxamic acids in moderate yields. The sulfone intermediates 3 from this study can be alkylated while the corresponding phosphonates have been shown to undergo HWE reaction. The α,β-unsaturated synthon, 8, prepared by thermal elimination of sulfoxide 3m, undergoes Michael addition with secondary amines. The usefulness of this approach to prepare polydentate chelators has been demonstrated by the synthesis of bis cyclic hydroxamic acids 12, 14, and 15. PMID:21499514

  4. Nucleophilic addition of reactive dyes on amidoximated acrylic fabrics.

    PubMed

    El-Shishtawy, Reda M; El-Zawahry, Manal M; Abdelghaffar, Fatma; Ahmed, Nahed S E

    2014-01-01

    Seven reactive dyes judiciously selected based on chemical structures and fixation mechanisms were applied at 2% of of shade on amidoximated acrylic fabrics. Amidoximated acrylic fabric has been obtained by a viable amidoximation process. The dyeability of these fabrics was evaluated with respect to the dye exhaustion, fixation, and colour strength under different conditions of temperature and dyeing time. Nucleophilic addition type reactive dyes show higher colour data compared to nucleophilic substitution ones. FTIR studies further implicate the binding of reactive dyes on these fabrics. A tentative mechanism is proposed to rationalize the high fixation yield obtained using nucleophilic addition type reactive dyes. Also, the levelling and fastness properties were evaluated for all dyes used. Excellent to good fastness and levelling properties were obtained for all samples irrespective of the dye used. The result of investigation offers a new method for a viable reactive dyeing of amidoximated acrylic fabrics.

  5. Nucleophilic Addition of Thiols to Deoxynivalenol.

    PubMed

    Stanic, Ana; Uhlig, Silvio; Solhaug, Anita; Rise, Frode; Wilkins, Alistair L; Miles, Christopher O

    2015-09-01

    Conjugation of deoxynivalenol (DON) with sulfur compounds is recognized as a significant reaction pathway, and putative DON-glutathione (DON-GSH) conjugates have been reported in planta. To understand and control the reaction of trichothecenes with biologically important thiols, we studied the reaction of DON, T-2 tetraol, and de-epoxy-DON with a range of model thiols. Reaction conditions were optimized for DON with 2-mercaptoethanol. Major reaction products were identified using HRMS and NMR spectroscopy. The results indicate that thiols react reversibly with the double bond (Michael addition) and irreversibly with the epoxide group in trichothecenes. These reactions occurred at different rates, and multiple isomers were produced including diconjugated forms. LC-MS analyses indicated that glutathione and cysteine reacted with DON in a similar manner to the model thiols. In contrast to DON, none of the tested mercaptoethanol adducts displayed toxicity in human monocytes or induced pro-inflammatory cytokines in human macrophages.

  6. Steric Effects Compete with Aryne Distortion to Control Regioselectivities of Nucleophilic Additions to 3-Silylarynes

    PubMed Central

    Bronner, Sarah M.; Mackey, Joel L.

    2012-01-01

    We report an experimental and computational study of 3-silylarynes. The addition of nucleophiles yield ortho-substituted products as a result of aryne distortion, but meta-substituted products form predominately when the nucleophile is large. Computations correctly predict the preferred site of attack observed in both nucleophilic addition and cycloaddition experiments. Nucleophilic additions to 3-t-butylbenzyne, which is not significantly distorted, give meta-substituted products. PMID:22876797

  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.

  10. 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.

  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. 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

  13. The oxidation of Ni(II) N-confused porphyrins (NCPs) with azo radical initiators and an unexpected intramolecular nucleophilic substitution reaction via a proposed Ni(III) NCP intermediate.

    PubMed

    Jiang, Hua-Wei; Chen, Qing-Yun; Xiao, Ji-Chang; Gu, Yu-Cheng

    2009-07-01

    The oxidation of Ni(II) N-confused porphyrins (NCPs) with azo radical initiators resulted in an unexpected intramolecular nucleophilic substitution reaction via a proposed Ni(III) NCP intermediate, which could be detected by HRMS.

  14. 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…

  15. Diethyl fluoronitromethylphosphonate: synthesis and application in nucleophilic fluoroalkyl additions.

    PubMed

    Opekar, Stanislav; Pohl, Radek; Beran, Pavel; Rulíšek, Lubomír; Beier, Petr

    2014-01-27

    Diethyl fluoronitromethylphosphonate (3), a previously unknown compound, was synthesized by electrophilic fluorination of diethyl nitromethylphosphonate with Selectfluor. Base-induced decomposition of 3 was studied by NMR spectroscopy, which identified diethyl fluorophosphate and fluoronitromethane as the main decomposition products. C-H acidities [pK(a) values in dimethyl sulfoxide (DMSO)] of 3, 1-fluoro-1-phenylsulfonylmethanephosphonate (1; McCarthy's reagent), tetraethyl fluoromethylenebisphosphonate (2), and some nonfluorinated phosphonates were computed, and a good correlation between calculated and experimental pK(a) values was found. The calculated C-H acidities increased in the sequence 2<1<3. Diethyl fluoronitromethylphosphonate (3) was applied in the Horner-Wadsworth-Emmons reaction with aldehydes and trifluoromethyl ketones to provide new 1-fluoro-1-nitroalkenes with good to high stereoselectivities. Alkylation of 3 was successful only with iodomethane, however, conjugate additions of 3 to Michael acceptors such as α,β-unsaturated carbonyl compounds, sulfones, and nitro compounds allowed access to variously modified diethyl 1-fluoro-1-nitrophosphonates.

  16. 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

  17. 4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions.

    PubMed

    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.

  18. 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.

  19. Improved Synthesis of and Nucleophilic Addition to 2-Formyl-2-Cyclohexenone

    PubMed Central

    Adary, Elan M.; Chang, Chih-wei; Auria, Damian T. D’; Nguyen, Phuc M.; Polewacz, Klaudyna; Reinicke, Justin A.; Seo, Hannah; Berger, Gideon O.

    2014-01-01

    A preparation of 2-formyl-2-cyclohexenone in nearly quantitative yield and purity of approximately 95% is described. It is scalable and has been extended to the synthesis of the 5- and 7-membered ring homologs with comparable yields. Conditions have also been developed for the successful conjugate addition of dimethylmalonate to 2-formyl-2-cyclohexenone, in good and scalable yield (60%). This result has been extended to 5 other nucleophile classes, and the dimethylmalonate conjugate addition has been demonstrated with 2-formyl-2-cyclopentenone and 2-formyl-2-cycloheptenone. PMID:25593375

  20. 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

  1. Enantioselective addition of silicon nucleophiles to aldimines using a preformed NHC-Copper(I) complex as the catalyst.

    PubMed

    Hensel, Alexander; Nagura, Kazuhiko; Delvos, Lukas B; Oestreich, Martin

    2014-05-01

    A remaining major challenge in the asymmetric addition of silicon nucleophiles to typical prochiral acceptors, the enantioselective 1,2-addition to aldimines, is addressed. Activation of the SiB bond in the silicon pronucleophile by a copper(I) alkoxide with McQuade's chiral six-membered N-heterocyclic carbene as a supporting ligand releases the silicon nucleophile, which adds to various aldimines with high levels of enantioselectivity. The new method provides a catalytic asymmetric access to α-silylated amines.

  2. 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.

  3. 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

  4. 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

  5. Facile synthesis of enantioenriched Cγ-tetrasubstituted α-amino acid derivatives via an asymmetric nucleophilic addition/protonation cascade.

    PubMed

    Duan, Shu-Wen; An, Jing; Chen, Jia-Rong; Xiao, Wen-Jing

    2011-05-01

    An asymmetric nucleophilic addition/protonation reaction of 3-substituted oxindoles and ethyl 2-phthalimidoacrylate has been described. This strategy can give direct access to C(γ)-tetrasubstituted α-amino acid derivatives bearing 1,3-nonadjacent stereocenters with up to 98% yield, 94:6 dr, and >99% ee. Dual activation is proposed in the transition state, and the opposite enantiomers can be obtained simply by changing cinchonidine-derived catalyst to the cinchonine analogue.

  6. 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.

  7. 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.

  8. 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

  9. Highly efficient "on water" catalyst-free nucleophilic addition reactions using difluoroenoxysilanes: dramatic fluorine effects.

    PubMed

    Yu, Jin-Sheng; Liu, Yun-Lin; Tang, Jing; Wang, Xin; Zhou, Jian

    2014-09-01

    A remarkable fluorine effect on "on water" reactions is reported. The CF⋅⋅⋅HO interactions between suitably fluorinated nucleophiles and the hydrogen-bond network at the phase boundary of oil droplets enable the formation of a unique microstructure to facilitate on water catalyst-free reactions, which are difficult to realize using nonfluorinated substrates. Accordingly, a highly efficient on water, catalyst-free reaction of difluoroenoxysilanes with aldehydes, activated ketones, and isatylidene malononitriles was developed, thus leading to the highly efficient synthesis of a variety of α,α-difluoro-β-hydroxy ketones and quaternary oxindoles.

  10. Organocatalytic Michael addition/intramolecular Julia-Kocienski olefination for the preparation of nitrocyclohexenes.

    PubMed

    Rodrigo, Eduardo; García Ruano, José Luis; Cid, M Belén

    2013-11-01

    An asymmetric organocatalytic [3 + 3] annulation strategy based on a Michael addition/intramolecular Julia-Kocienski olefination sequence has been developed for the synthesis of 4-substituted-5-nitrocyclohex-1-ene compounds. The strategy is an alternative to the direct reluctant enantioselective Diels-Alder approach. The potential of the methodology has been demonstrated with a concise enantioselective formal synthesis of trandolapril.

  11. 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

  12. Direct inter- and intramolecular addition of amides to arylalkenes promoted by KOt-Bu/DMF.

    PubMed

    Wang, Wei-juan; Zhao, Xu; Tong, Lang; Chen, Jia-hua; Zhang, Xue-jing; Yan, Ming

    2014-09-19

    Direct addition of tetrahydroisoquinoline derived amides to arylalkenes has been achieved in the presence of KOt-Bu/DMF. Both intermolecular and intramolecular reactions could occur in good yields. α-Amido alkyl radicals are proposed to be generated under the reaction conditions. The reaction is efficient for the synthesis of seven-membered nitrogen heterocycles. A homoprotoberberine was prepared conveniently via this method.

  13. 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

  14. A combined QM/MM study of the nucleophilic addition reaction of methanethiolate and N-methylacetamide.

    PubMed

    Byun, K; Gao, J

    2000-02-01

    A combined quantum mechanical (QM) and molecular mechanical (MM) method was used to study the nucleophilic addition reaction of methanethiolate to N-methylacetamide (NMA) in the gas phase and aqueous solution. At the B3LYP/aug-cc-pVDZ//HF/6-31 + G(d) level, the ion-dipole complex was found to be the global minimum on the potential energy surface in the gas phase with a binding energy of 21.2 kcal/mol. The complex has a C-S distance of 4.33 A, and no stabilized tetrahedral intermediate was located. The computed potential of mean force in water shows that solvent effects stabilize the reactants over the tetrahedral adduct by 36.5 kcal/mol, and that the tetrahedral intermediate does not exist for the present reaction in water. The present study provides an initial step for modeling the cysteine protease hydrolysis reactions in enzymes.

  15. Intramolecular addition of diarylmethanols to imines promoted by KOt-Bu/DMF: a new synthetic approach to indole derivatives.

    PubMed

    Chen, Jia-Hua; Chen, Zi-Cong; Zhao, Hong; Zhang, Ting; Wang, Wei-Juan; Zou, Yong; Zhang, Xue-Jing; Yan, Ming

    2016-04-26

    KOt-Bu/DMF promoted intramolecular addition of diarylmethanols to imines was developed. A series of 2,3-disubstituted indoles was obtained in good yields. A reaction mechanism of radical cyclization and subsequent dehydration is proposed. PMID:27055383

  16. Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel-Crafts-Type 1,4-Addition.

    PubMed

    Yoshida, Keisuke; Itatsu, Yukihiro; Fujino, Yuta; Inoue, Hiroki; Takao, Ken-Ichi

    2016-06-01

    The highly enantioselective organocatalytic construction of spiroindanes containing an all-carbon quaternary stereocenter by intramolecular Friedel-Crafts-type 1,4-addition is described. The reaction was catalyzed by a cinchonidine-based primary amine and accelerated by water and p-bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (-)-cannabispirenones A and B. PMID:27111396

  17. Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel-Crafts-Type 1,4-Addition.

    PubMed

    Yoshida, Keisuke; Itatsu, Yukihiro; Fujino, Yuta; Inoue, Hiroki; Takao, Ken-Ichi

    2016-06-01

    The highly enantioselective organocatalytic construction of spiroindanes containing an all-carbon quaternary stereocenter by intramolecular Friedel-Crafts-type 1,4-addition is described. The reaction was catalyzed by a cinchonidine-based primary amine and accelerated by water and p-bromophenol. A variety of spiro compounds containing quaternary stereocenters were obtained with excellent enantioselectivity (up to 95 % ee). The reaction was applied to the asymmetric formal synthesis of the spirocyclic natural products (-)-cannabispirenones A and B.

  18. Toward a mechanism for biliprotein lyases: revisiting nucleophilic addition to phycocyanobilin.

    PubMed

    Tu, Jun-Ming; Zhou, Ming; Haessner, Rainer; Plöscher, Matthias; Eichacker, Lutz; Scheer, Hugo; Zhao, Kai-Hong

    2009-04-22

    Biliprotein lyases attach linear-tetrapyrrolic bilins covalently to apoproteins, which is a prerequisite for the assembly of phycobiliproteins into phycobilisomes, the light-harvesting complexes of cyanobacteria. On the basis of the addition of thiol and imidazole to phycocyanobilin, we propose a generalized lyase reaction mechanism. The adducts contain isomerized phycocyanobilin that can be transferred by the lyase to apoproteins by either back-isomerization, generating phycocyanobilin-containing proteins, or direct transfer, generating phycoviolobilin-containing proteins.

  19. Conducting Polymers: Insights Into Reduced Polyparaphenylene Vinylene Materials via Nucleophilic Addition, Proton Abstraction, and Electron Transfer Reactions.

    NASA Astrophysics Data System (ADS)

    Hilker, Brian Lee

    Grignard routes were investigated as methods to produce poly paraphenylene vinylene polymers. Because of coupling problems with these reactions, high molecular weight unsubstituted and dimethyl and dimethoxy substituted poly paraphenylene vinylene polymers were prepared via a literature-proven synthetic route: the sodium hydride dehydrochlorination addition polymerization route. Both the Grignard reactions and the sodium hydride method required dichloromethyl compounds monomers. The syntheses of these dichloromethyl monomers were studied extensively. The three high molecular weight poly paraphenylene vinylene polymer systems prepared in this work were charged with the traditional electron transfer reducing agent potassium/naphthalide. They were also charged via the novel nucleophilic addition of n-butyllithium across the alkenes and subjected to proton abstraction charging in the presence of a strong, complexed base mixture of n-butyllithium and potassium-t-butoxide. Conductivities were obtained via standard four point probe techniques. Characterization of these polymers and their quenched anion derivatives was via FTIR and acid titration. Results of these topics are presented and discussed.

  20. Synthesis of N-allylideneamines and their use for the double nucleophilic addition of ketene silyl (thio)acetals and trimethylsilyl cyanide.

    PubMed

    Mizota, Isao; Matsuda, Yuri; Hachiya, Iwao; Shimizu, Makoto

    2008-09-18

    N-Allylideneamines 1a, b were prepared from acrolein and diphenylethyl or trityl amine in the presence of Ti(OEt)4. Double nucleophilic addition of various ketene silyl (thio)acetals and trimethylsilyl cyanide to these imines proceeded efficiently to give, after workup with TFA, homoglutamic acid derivatives 3 and valerolactam 5.

  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.

  2. 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.

  3. 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…

  4. Tandem sequence of phenol oxidation and intramolecular addition as a method in building heterocycles.

    PubMed

    Ratnikov, Maxim O; Farkas, Linda E; Doyle, Michael P

    2012-11-16

    A tandem phenol oxidation-Michael addition furnishing oxo- and -aza-heterocycles has been developed. Dirhodium caprolactamate [Rh(2)(cap)(4)] catalyzed oxidation by T-HYDRO of phenols with alcohols, ketones, amides, carboxylic acids, and N-Boc protected amines tethered to their 4-position afforded 4-(tert-butylperoxy)cyclohexa-2,5-dienones that undergo Brønsted acid catalyzed intramolecular Michael addition in one-pot to produce oxo- and -aza-heterocycles in moderate to good yields. The scope of the developed methodology includes dipeptides Boc-Tyr-Gly-OEt and Boc-Tyr-Phe-Me and provides a pathway for understanding the possible transformations arising from oxidative stress of tyrosine residues. A novel method of selective cleavage of O-O bond in hindered internal peroxide using TiCl(4) has been discovered in efforts directed to the construction of cleroindicin F, whose synthesis was completed in 50% yield over just 3 steps from tyrosol using the developed methodology.

  5. Dehalogenation of aromatics by nucleophilic aromatic substitution.

    PubMed

    Sadowsky, Daniel; McNeill, Kristopher; Cramer, Christopher J

    2014-09-16

    Nucleophilic aromatic substitution has been implicated as a mechanism for both the biotic and abiotic hydrodehalogenation of aromatics. Two mechanisms for the aqueous dehalogenation of aromatics involving nucleophilic aromatic substitution with hydride as a nucleophile are investigated using a validated density functional and continuum solvation protocol. For chlorinated and brominated aromatics, nucleophilic addition ortho to carbon-halogen bonds via an anionic intermediate is predicted to be the preferred mechanism in the majority of cases, while concerted substitution is predicted to be preferred for most fluorinated aromatics. Nucleophilic aromatic substitution reactions with the hydroxide and hydrosulfide anions as nucleophiles are also investigated and compared.

  6. 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.

  7. [Asymmetric intramolecular conjugate addition of chiral enolates via non-equilibrium].

    PubMed

    Monguchi, Daiki

    2006-08-01

    Optically active alpha,alpha-disubstituted alpha-amino acids belong to an important class of unnatural amino acids. Since the synthesis of such amino acids involves the creation of a quaternary stereocenter, methods for their synthesis have been extensively studied. We have reported that N-t-butoxycarbonyl(Boc)-N-methoxymethyl(MOM)-amino acid derivatives undergo asymmetric alpha-alkylation in up to 93% ee. Original chiral information on an amino acid is preserved in axially chiral enolate intermediates, and thus asymmetric induction is achieved without the aid of external chiral sources (i.e., memory of chirality). Recently, we have reported a new protocol for the asymmetric cyclization of amino acid derivatives, which enables straightforward synthesis of cyclic amino acids with a tetrasubstituted carbon center from the usual alpha-amino acids in up to 98% ee. Here we report the asymmetric construction of highly substituted chiral nitrogen heterocycles via intramolecular conjugate addition of chiral enolates generated from N-Boc-N-alkylylamino acid derivatives. This method is applicable to the asymmetric construction of pyrrolidine, piperidine, tetrahydroisoquinoline, and indoline derivatives with contiguous quaternary and tertiary stereocenters.

  8. Nucleophilic addition to a p-benzyne derived from an enediyne: a new mechanism for halide incorporation into biomolecules.

    PubMed

    Perrin, Charles L; Rodgers, Betsy L; O'Connor, Joseph M

    2007-04-18

    Biosynthesis of haloaromatics ordinarily occurs by electrophilic attack of an activated halogen species on an electron-rich aromatic ring. We now present the discovery of a new reaction whereby a nucleophilic halide anion can be attached even to an aromatic ring without activating substituents. We show that the enediyne cyclodeca-1,5-diyn-3-ene, in the presence of lithium halide and a weak acid, is converted to 1-halotetrahydronaphthalene. The kinetics are consistent with rate-limiting cyclization to a p-benzyne biradical that rapidly adds halide and is then protonated. This reaction has interesting mechanistic features and important implications for incorporation of halide into biomolecules.

  9. Distance dependence in photoinduced intramolecular electron transfer. Additional remarks and calculations

    NASA Astrophysics Data System (ADS)

    Larsson, Sven; Volosov, Andrey

    1987-12-01

    Rate constants for photoinduced intramolecular electron transfer are calculated for four of the molecules studied by Hush et al. The electronic factor is obtained in quantum chemical calculations using the CNDO/S method. The results agree reasonably well with experiments for the forward reaction. Possible reasons for the disagreement for the charge recombination process are offered.

  10. Intramolecular 1,1-carboboration versus intermolecular FLP addition in reactions of boranes and bis(phenylethynyl)telluroether.

    PubMed

    Tsao, Fu An; Lough, Alan J; Stephan, Douglas W

    2015-03-11

    Reactions of boranes with Te(CCPh)2 proceed via initial intermolecular 1,1-carboboration followed by either an intramolecular carboboration or an FLP addition to a second molecule of the intermediate, yielding 1-bora-4-tellurocyclohexa-2,5-diene heterocycles or tricylic derivatives of 1,4-ditellurocyclohexa-2,5-diene, respectively. The latter species is also shown to convert to the former upon heating.

  11. Scandium triflate-catalyzed nucleophilic additions to indolylmethyl Meldrum's acid derivatives via a gramine-type fragmentation: synthesis of substituted indolemethanes.

    PubMed

    Armstrong, Erin L; Grover, Huck K; Kerr, Michael A

    2013-10-18

    Treatment of indolylmethyl Meldrum's acids with catalytic scandium triflate and a variety of nucleophiles results in the nucleophilic displacement of the Meldrum's acid moiety via a gramine-type fragmentation. The reaction is useful for the generation of heterocyclic compounds of significant molecular complexity.

  12. 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

  13. 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

  14. 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

  15. Copper(I)-catalyzed regioselective addition of nucleophilic silicon across terminal and internal carbon-carbon triple bonds.

    PubMed

    Hazra, Chinmoy K; Fopp, Carolin; Oestreich, Martin

    2014-10-01

    The copper(I) alkoxide-catalyzed release of a silicon-based cuprate reagent from a silicon-boron pronucleophile is applied to the addition across carbon-carbon triple bonds. Commercially available CuBr⋅Me2S was found to be a general precatalyst that secures high regiocontrol for both aryl- and alkyl-substituted terminal as well as internal alkynes. The solvent greatly influences the regioisomeric ratio, favoring the linear regioisomer with terminal acceptors. This facile protocol even allows for the transformation of internal acceptors with remarkable levels of regio- and diastereocontrol.

  16. A Tin(IV) Chloride Promoted Tandem C-O Bond Cleavage/Nazarov Cyclization/Nucleophilic Addition Reaction of 1,1-Disubstituted Allylic Ethers toward the Synthesis of Multisubstituted Indenes.

    PubMed

    Yang, Chao; Xu, Zheng-Liang; Shao, Hui; Mou, Xue-Qing; Wang, Jie; Wang, Shao-Hua

    2015-11-01

    A novel SnCl4-promoted tandem reaction toward multisubstituted indenes via a sequential C-O bond cleavage/Nazarov cyclization/nucleophilic addition reaction has been developed to afford a series of multisubstituted indenes with an all-carbon quaternary center in moderate to good yields. PMID:26465205

  17. 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

  18. Secondary deuterium kinetic isotope effects in irreversible additions of hydride and carbon nucleophiles to aldehydes: A spectrum of transition states from complete bond formation to single electron transfer

    SciTech Connect

    Gajewski, J.J.; Bocian, W.; Harris, N.J.; Olson, L.P.; Gajewski, J.P.

    1999-01-20

    The competitive kinetics of hydride and organometallic additions to benzaldehyde-H and -D were determined at {minus}78 C using LiAlH{sub 4}, LiBEt{sub 3}H, NaBH{sub 4}, LiBH{sub 4}, LiAl(O-tert-butoxy){sub 3}H, NaB(OMe){sub 3}H, NaB-(Ac){sub 3}H (at 20 C) methyl, phenyl, and allyl Grignard, and methyl-, phenyl-, n-butyl-, tert-butyl-, and allyllithium. The additions of hydride were found to have an inverse secondary deuterium kinetic isotope effects in all cases, but the magnitude of the effect varied inversely with the apparent reactivity of the hydride. In the additions of methyl Grignard reagent and of methyllithium and phenyllithium, inverse secondary deuterium isotope effects were observed; little if any isotope effect was observed with phenyl Grignard or n-butyl- and tert-butyllithium. With allyl Grignard and allyllithium, a normal secondary deuterium kinetic isotope effect was observed. The results indicate that rate-determining single-electron transfer occurs with allyl reagents, but direct nucleophilic reaction occurs with all of the other reagents, with the extent of bond formation dependent on the reactivity of the reagent. In the addition of methyllithium to cyclohexanecarboxyaldehyde, a less inverse secondary deuterium kinetic isotope effect was observed than that observed in the addition of methyllithium to benzaldehyde, and allyllithium addition to cyclohexanecarboxaldehyde had a kinetic isotope effect near unity. The data with organometallic additions, which are not incompatible with observations of carbonyl carbon isotope effects, suggest that electrochemically determined redox potentials which indicate endoergonic electron transfer with energies less than ca. 13 kcal/mol allow electron-transfer mechanisms to compete well with direct polar additions to aldehydes, provided that the reagent is highly stabilized, like allyl species. Methyllithium and phenyllithium and methyl and phenyl Grignard reagents are estimated to undergo electron transfer with

  19. 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

  20. 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)

  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. Enantioselective synthesis of primary 1-(aryl)alkylamines by nucleophilic 1,2-addition of organolithium reagents to hydroxyoxime ethers and application to asymmetric synthesis of G-protein-coupled receptor ligands.

    PubMed

    Atobe, Masakazu; Yamazaki, Naoki; Kibayashi, Chihiro

    2004-08-20

    (E)-Arylaldehyde oxime ethers bearing a (1S)-2-hydroxy-1-phenylethyl or (2R)-1-hydroxy-2-phenylethyl group as a chiral auxiliary, both derived from a single precursor, methyl (R)-mandelate, underwent nucleophilic addition with organolithium reagents via six-membered chelates to give the diastereomerically enriched (R)- and (S)-adducts, respectively, which, after chiral auxiliary removal by reductive N-O bond cleavage, led to the corresponding (R)- and (S)-1-(aryl)ethylamines. This organolithium addition protocol using methyllithium was applied in an enantiodivergent fashion to the preparation of both enantiomers of 1-(2-hydroxyphenyl)ethylamine, which has been previously used as an efficient chiral auxiliary for the synthesis of natural products in this laboratory. The synthetic utility of this methodology involving diastereoselective methyl addition was demonstrated by further application to the asymmetric synthesis of a new type of calcium receptor agonist (calcimimetics), (R)-(+)-NPS R-568 and its thio analogue. Furthermore, diastereoselective vinylation was accomplished by application of the hydroxy oxime ether-based protocol using vinyllithium, which allowed the development of the enantioselective synthesis of the NK-1 receptor antagonists, (+)-CP-99,994 and (+)-CP-122,721.

  3. Transition states and energetics of nucleophilic additions of thiols to substituted α,β-unsaturated ketones: substituent effects involve enone stabilization, product branching, and solvation.

    PubMed

    Krenske, Elizabeth H; Petter, Russell C; Zhu, Zhendong; Houk, K N

    2011-06-17

    CBS-QB3 enthalpies of reaction have been computed for the conjugate additions of MeSH to six α,β-unsaturated ketones. Compared with addition to methyl vinyl ketone, the reaction becomes 1-3 kcal mol(-1) less exothermic when an α-Me, β-Me, or β-Ph substituent is present on the C=C bond. The lower exothermicity for the substituted enones occurs because the substituted reactant is stabilized more by hyperconjugation or conjugation than the product is stabilized by branching. Substituent effects on the activation energies for the rate-determining step of the thiol addition (reaction of the enone with MeS(-)) were also computed. Loss of reactant stabilization, and not steric hindrance, is the main factor responsible for controlling the relative activation energies in the gas phase. The substituent effects are further magnified in solution; in water (simulated by CPCM calculations), the addition of MeS(-) to an enone is disfavored by 2-6 kcal mol(-1) when one or two methyl groups are present on the C=C bond (ΔΔG(‡)). The use of CBS-QB3 gas-phase energies in conjunction with CPCM solvation corrections provides kinetic data in good agreement with experimental substituent effects. When the energetics of the thiol additions were calculated with several popular density functional theory and ab initio methods (B3LYP, MPW1PW91, B1B95, PBE0, B2PLYP, and MP2), some substantial inaccuracies were noted. However, M06-2X (with a large basis set), B2PLYP-D, and SCS-MP2 gave results within 1 kcal mol(-1) of the CBS-QB3 benchmark values.

  4. 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

  5. Controlling the ambiphilic nature of σ-arylpalladium intermediates in intramolecular cyclization reactions.

    PubMed

    Solé, Daniel; Fernández, Israel

    2014-01-21

    the metal center with the carbonyl group. Second, the additive phenol exchanges the iodide ligand to give an arylpalladium(II) phenoxide complex, which has a beneficial effect on the arylation. The formation of this transient intermediate not only stabilizes the arylpalladium moiety, thus preventing the nucleophilic attack at the carbonyl group, but also assists the enolization reaction, which takes place in a more favorable intramolecular manner. The azapalladacycle intermediate is, in the words of J. R. R. Tolkien, "the one ring to bring them all and in the darkness to bind them." With this intermediate, we can easily achieve the synthesis of a variety of heterocyclic systems by selectively promoting electrophilic α-arylation or nucleophilic addition reactions from the same precursors. PMID:23957464

  6. 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.

  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. 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)

  9. 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

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

    PubMed

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

    2015-11-18

    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 β,β'-enones and substituted β,β'-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 Δ(5)-unsaturation are key controlling 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.

  11. 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

  12. 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.

  13. Implications of dynamic imine chemistry for the sustainable synthesis of nitrogen heterocycles via transimination followed by intramolecular cyclisation.

    PubMed

    Laha, Joydev K; Tummalapalli, K S Satyanarayana; Jethava, Krupal P

    2016-02-28

    An exploration of a tandem approach to the sustainable synthesis of N-heterocycles from readily available N-aryl benzylamines or imines and ortho-substituted anilines is described, which demonstrates, for the first time, an important synthetic application of dynamic imine chemistry. The key features to the successful development of this protocol include the utilisation of N-aryl benzylamines as imine precursors in transimination, the occurrence of transimination in acetonitrile in the absence of any catalysts, an intramolecular nucleophilic addition occurring in the newly formed imine causing irreversible transimination, and the tandem event occurring under green conditions.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. A general overview of the organocatalytic intramolecular aza-Michael reaction.

    PubMed

    Sánchez-Roselló, María; Aceña, José Luis; Simón-Fuentes, Antonio; del Pozo, Carlos

    2014-11-01

    The organocatalytic intramolecular aza-Michael reaction gives access to enantiomerically enriched nitrogen-containing heterocycles in a very simple manner. Enals, enones, conjugated esters and nitro olefins have been employed as Michael acceptors, while moderate nitrogen nucleophiles such as sulphonamides, carbamates and amides have been shown to be appropriate Michael donors in this type of reaction. Additionally, the process has been performed under both covalent and non-covalent catalysis, with diaryl prolinols, imidazolidinones, thioureas and chiral binol phosphoric acids being the most frequently used catalysts. The level of efficiency reached with this protocol is demonstrated by the implementation of numerous tandem processes, as well as the total synthesis of several natural products.

  1. 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

  2. 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

  3. Nucleophilic substitution reaction for post-functionalization of polyoxometalates

    SciTech Connect

    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.

  4. 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

  5. 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.

  6. Detection of Electrophilic and Nucleophilic Chemical Agents

    DOEpatents

    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.

  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. 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.

  10. 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.

  11. 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.

  12. Nucleophilic substitution as a mechanism of atrazine sequestration in soil.

    PubMed

    Lu, Junhe; Shao, Juan; Kong, Deyang

    2015-03-01

    Formation of nonextractable residue was widely observed as a sink of atrazine (ATZ) in soil. However, the mechanisms by which ATZ binds to soil organic matter remain unclear. In this study, we demonstrated that neucleophilic substitution could serve an important pathway causing ATZ sequestration. The carbon bonded to the chlorine in ATZ molecule is partially positively charged due to the strong electronegativity of chlorine and is susceptible to the attack of nucleophiles such as aniline. Since aromatic amines are relatively rare in natural soils, amino acids/peptides were hypothesized to act as the main nucleophiles in real environment. However, substantially ATZ transformation was only observed in the presence of those species containing thiol functionality. Thus, we speculated that it was the thiol group in amino acids/peptides acting as the nucleophile. Nitrogen in amino acids was in fact not an active nucleophile toward ATZ. In addition to the sulfur-containing amino acids, other thiol compounds, and sulfide were also proved to be reactive to ATZ. Thus, the sequestration potential of ATZ probably correlates to the availability of thiol compounds in soil.

  13. Base-dependent stereodivergent intramolecular aza-Michael reaction: asymmetric synthesis of 1,3-disubstituted isoindolines.

    PubMed

    Fustero, Santos; Herrera, Lidia; Lázaro, Ruben; Rodríguez, Elsa; Maestro, Miguel A; Mateu, Natalia; Barrio, Pablo

    2013-08-26

    The nucleophilic addition (A(N)) / intramolecular aza-Michael reaction (IMAMR) process on Ellman's tert-butylsulfinyl imines, bearing a Michael acceptor in the ortho position, is studied. This reaction affords 1,3-disubstituted isoindolines with a wide range of substituents in good yields and diastereoselectivities. Interestingly, careful choice of the base for the aza-Michael step allows either the cis or the trans diastereoisomers to be exclusively obtained. This stereodivergent cyclization has enabled the synthesis of C2-symmetric bisacetate-substituted isoindolines. In addition, bisacetate isoindolines bearing two well-differentiated ester moieties are also noteworthy because they may allow for the orthogonal synthesis of β,β'-dipeptides using a single nitrogen atom as a linchpin.

  14. A spontaneously blinking fluorophore based on intramolecular spirocyclization for live-cell super-resolution imaging.

    PubMed

    Uno, Shin-Nosuke; Kamiya, Mako; Yoshihara, Toshitada; Sugawara, Ko; Okabe, Kohki; Tarhan, Mehmet C; Fujita, Hiroyuki; Funatsu, Takashi; Okada, Yasushi; Tobita, Seiji; Urano, Yasuteru

    2014-08-01

    Single-molecule localization microscopy is used to construct super-resolution images, but generally requires prior intense laser irradiation and in some cases additives, such as thiols, to induce on-off switching of fluorophores. These requirements limit the potential applications of this methodology. Here, we report a first-in-class spontaneously blinking fluorophore based on an intramolecular spirocyclization reaction. Optimization of the intramolecular nucleophile and rhodamine-based fluorophore (electrophile) provide a suitable lifetime for the fluorescent open form, and equilibrium between the open form and the non-fluorescent closed form. We show that this spontaneously blinking fluorophore is suitable for single-molecule localization microscopy imaging deep inside cells and for tracking the motion of structures in living cells. We further demonstrate the advantages of this fluorophore over existing methodologies by applying it to nuclear pore structures located far above the coverslip with a spinning-disk confocal microscope and for repetitive time-lapse super-resolution imaging of microtubules in live cells for up to 1 h. PMID:25054937

  15. 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

  16. 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.

  17. 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

  18. Nucleophilic fluorination of triflates by tetrabutylammonium bifluoride.

    PubMed

    Kim, Kyu-Young; Kim, Bong Chan; Lee, Hee Bong; Shin, Hyunik

    2008-10-17

    Careful examination of nucleophilicity, basicity, and leaving group ability led us to discover the nucleophilic fluorination of triflates by weakly basic tetrabutylammonium bifluoride, which provides excellent yields with minimal formation of elimination-derived side products. Primary hydroxyl groups as well as secondary hydroxyl groups in acyclic chains or in five-membered rings are excellent substrates, whereas benzylic and aldol-type secondary hydroxyl groups give poor yields as a result of the instability of their triflates.

  19. Nucleophilic Iododifluoromethylation of Aldehydes Using Bromine/Iodine Exchange.

    PubMed

    Levin, Vitalij V; Smirnov, Vladimir O; Struchkova, Marina I; Dilman, Alexander D

    2015-09-18

    A method for the iododifluoromethylation of aromatic aldehydes using (bromodifluoromethyl)trimethylsilane (Me3SiCF2Br) is described. The selective formation of the CF2I group is based on using sodium iodide, with the sodium serving as a scavenger of bromide and iodide serving as a nucleophile with respect to difluorocarbene. The primary CF2I-addition products can undergo HI-elimination or iodine/zinc exchange followed by allylation in a one-pot manner.

  20. 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

  1. 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.

  2. Detection of electrophilic and nucleophilic chemical agents

    SciTech Connect

    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.

  3. 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.

  4. 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)

  5. Lewis Acid-Catalyzed Indole Synthesis via Intramolecular Nucleophilic Attack of Phenyldiazoacetates to Iminium Ions

    PubMed Central

    Zhou, Lei; Doyle, Michael P.

    2009-01-01

    Lewis acids catalyze the cyclization of methyl phenyldiazoacetates with an ortho-imino group, prepared from o-aminophenylacetic acid, to give 2,3-substituted indoles in quantitative yields. PMID:19904905

  6. Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S,S)-(+)-pseudoephedrine as chiral auxiliary; enantioselective synthesis of 3-substituted pyrrolidines.

    PubMed

    Alonso, Beatriz; Ocejo, Marta; Carrillo, Luisa; Vicario, Jose L; Reyes, Efraim; Uria, Uxue

    2013-01-18

    We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.

  7. 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

  8. Formation of amides, their intramolecular reactions for the synthesis of N-heterocycles, and preparation of a marketed drug, sildenafil: a comprehensive coverage.

    PubMed

    Laha, Joydev K; Patel, Ketul V; Tummalapalli, K S Satyanarayana; Dayal, Neetu

    2016-08-11

    A unified approach to the tandem preparation of diverse nitrogen heterocycles via decarboxylative acylation of ortho-substituted amines with α-oxocarboxylic acids and subsequent intramolecular cyclizations has been developed. The key features of this work include: the first example of transition-metal-free decarboxylative amidation of α-oxocarboxylic acids with ortho-substituted amines, realization of intramolecular cyclization of amides employing nucleophiles that have previously been unexplored, mechanistic investigation of an unprecedented K2S2O8 promoted amide formation and its subsequent intramolecular cyclizations, and application to the synthesis of a best-selling marketed drug. PMID:27430326

  9. Intramolecular thermal stepwise [2 + 2] cycloadditions: investigation of a stereoselective synthesis of [n.2.0]-bicyclolactones† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ob01661h Click here for additional data file. Click here for additional data file.

    PubMed Central

    Throup, Adam; Patterson, Laurence H.

    2016-01-01

    Fused cyclobutanes are found in a range of natural products and formation of these motifs in a straightforward and easy manner represents an interesting synthetic challenge. To this end we investigated an intramolecular variant of the thermal enamine [2 + 2] cyclisation, developing a diastereoselective intramolecular enamine [2 + 2] cyclisation furnishing δ lactone and lactam fused cyclobutenes in good yield and excellent diastereoselectivity. PMID:27722445

  10. Reactivity umpolung in intramolecular ring closure of 3,4-disubstituted butenolides: diastereoselective total synthesis of paeonilide.

    PubMed

    Deore, Prashant S; Argade, Narshinha P

    2013-11-15

    Remarkable reactivity reversal stratagem in 3,4-disubstituted butenolides under acidic conditions is described. Design of a suitably substituted multifunctional butenolide followed by an acid-catalyzed chemo- and diastereoselective intramolecular ring closure via the reactivity umpolung has been demonstrated to accomplish a concise total synthesis of paeonilide. Overall, the present protocol involves one-pot reduction of an α,β-unsaturated carbon-carbon double bond and intramolecular nucleophilic insertion of oxygen function at the electron-rich γ-position of butenolide. The involved mechanistic aspects have also been discussed. PMID:24175675

  11. 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.

  12. 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…

  13. 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

  14. 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

  15. 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.

  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. 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.

  18. Electrochemical intramolecular aminooxygenation of unactivated alkenes.

    PubMed

    Xu, Fan; Zhu, Lin; Zhu, Shaobin; Yan, Xiaomei; Xu, Hai-Chao

    2014-09-26

    An electrochemical approach to the intramolecular aminooxygenation of unactivated alkenes has been developed. This process is based on the addition of nitrogen-centered radicals, generated through electrochemical oxidation, to alkenes followed by trapping of the cyclized radical intermediate with 2,2,6,6-tetramethylpiperidine-N-oxyl radical (TEMPO). Difunctionalization of a variety of alkenes with easily available carbamates/amides and TEMPO affords aminooxygenation products in high yields and with excellent trans selectivity for cyclic systems (d.r. up to>20:1). The approach provides a much-needed complementary route to existing cis-selective methods.

  19. 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.

  20. 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.

  1. The Nucleophilicity of Persistent α-Monofluoromethide Anions.

    PubMed

    Zhang, Zhe; Puente, Ángel; Wang, Fang; Rahm, Martin; Mei, Yuncai; Mayr, Herbert; Prakash, G K Surya

    2016-10-01

    α-Fluorocarbanions are key intermediates in nucleophilic fluoroalkylation reactions. Although frequently discussed, the origin of the fluorine effect on the reactivity of α-fluorinated CH acids has remained largely unexplored. We have now investigated the kinetics of a series of reactions of α-substituted carbanions with reference electrophiles to elucidate the effects of α-F, α-Cl, and α-OMe substituents on the nucleophilic reactivities of carbanions. PMID:27628935

  2. Fluorinated alcohols as promoters for the metal-free direct substitution reaction of allylic alcohols with nitrogenated, silylated, and carbon nucleophiles.

    PubMed

    Trillo, Paz; Baeza, Alejandro; Nájera, Carmen

    2012-09-01

    The direct allylic substitution reaction using allylic alcohols in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) and 2,2,2-trifluoroethanol (TFE) as reaction media is described. The developed procedure is simple, works under mild conditions (rt, 50 and 70 °C), and proves to be very general, since different nitrogenated nucleophiles and carbon nucleophiles can be used achieving high yields, especially when HFIP is employed as solvent and aromatic allylic alcohols are the substrates. Thus, sulfonamides, carbamates, carboxamides, and amines can be successfully employed as nitrogen-based nucleophiles. Likewise, silylated nucleophiles such as trimethylsilylazide, allyltrimethylsilane, trimethylsilane, and trimethylsilylphenylacetylene give the corresponding allylic substitution products in high yields. Good results for the Friedel-Crafts adducts are also achieved with aromatic compounds (phenol, anisole, indole, and anilines) as nucleophiles. Particularly interesting are the results obtained with electron-rich anilines, which can behave as nitrogenated or carbon nucleophiles depending on their electronic properties and the solvent employed. In addition, 1,3-dicarbonyl compounds (acetylacetone and Meldrum's acid) are also successfully employed as soft carbon nucleophiles. Studies for mechanism elucidation are also reported, pointing toward the existence of carbocationic intermediates and two working reaction pathways for the obtention of the allylic substitution product.

  3. Intramolecular ketene-allene cycloadditions.

    PubMed

    McCaleb, K L; Halcomb, R L

    2000-08-24

    [reaction: see text]This report describes intramolecular thermal [2 + 2] cycloadditions between ketenes and allenes. The formation of ketenes and the subsequent cycloadditions occurred under a variety of conditions, affording 7-methylidinebicyclo[3.2.0]heptanones and 7-methylidinebicyclo[3.1.1]heptanones in 45-78% yields. The regioselectivity of the cycloaddition varied with the substitution of the allene, and the yield of cyclized products varied with reaction conditions.

  4. Enantioselective Nucleophilic β-Carbon-Atom Amination of Enals: Carbene-Catalyzed Formal [3+2] Reactions.

    PubMed

    Wu, Xingxing; Liu, Bin; Zhang, Yuexia; Jeret, Martin; Wang, Honglin; Zheng, Pengcheng; Yang, Song; Song, Bao-An; Chi, Yonggui Robin

    2016-09-26

    An enantioselective β-carbon amination for enals is disclosed. The nitrogen atom from a protected hydrazine with suitable electronic properties readily behaves as a nucleophile. Addition of the nitrogen nucleophile to a catalytically generated N-heterocyclic-carbene-bound α,β-unsaturated acyl azolium intermediate constructs a new carbon-nitrogen bond asymmetrically. The pyrazolidinone products from our catalytic reactions are common scaffolds in bioactive molecules, and can be easily transformed into useful compounds such as β(3) -amino-acid derivatives. PMID:27596365

  5. Nucleophilic Hydroxylation in Water Media Promoted by a Hexa-Ethylene Glycol-Bridged Dicationic Ionic Liquid.

    PubMed

    Jadhav, Vinod H; Kim, Jin Gwan; Jeong, Hyeon Jin; Kim, Dong Wook

    2015-07-17

    Hexaethylene glycol bis(3-hexaethylene glycol imidazolium) dimesylate ionic liquid (hexaEG-DHIM) was designed and prepared as a highly efficient promoter for the nucleophilic hydroxylation of alkyl halides to the corresponding alcohol products in neat water media. It was observed that hexaEG-DHIM promoter enhanced the nucleophilicity of water significantly in the reaction. In addition, the hexaEG-DHIM could be reused several times without loss of activity. Moreover, the hydroxylation reactions of base-sensitive and/or polar alkyl halide substrates proceeded highly chemoselectively in excellent yields. PMID:26115388

  6. 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

  7. Activation of dinitrogen-derived hafnium nitrides for nucleophilic N-C bond formation with a terminal isocyanate.

    PubMed

    Semproni, Scott P; Chirik, Paul J

    2013-12-01

    Better by Hf: Anion coordination to a bridging hafnocene nitride complex, prepared from CO-induced N2 cleavage, increases the nucleophilicity of the nitrogen atom, thus promoting additional NC bond formation with a typically inert terminal isocyanate ligand. This cascade sequence allows synthesis of otherwise challenging mono-substituted ureas using N2 , CO, and an appropriate electrophile.

  8. Fluorotrimethylsilane affinities of anionic nucleophiles: a study of fluoride-induced desilylation.

    PubMed

    Krouse, Ian H; Wenthold, Paul G

    2005-05-01

    In this study, preparation and decomposition of five novel pentavalent fluorosiliconates, RSi(CH3)3F- (R = CH3CH2O, CF3CH2O, (CH3)2CHO, (CH3)3SiO, and (CH3)3SiNH) is used to investigate the process of fluoride-induced desilylation. The siliconates were characterized by collision-induced dissociation and energy-resolved mass spectrometry. Decomposition of RSi(CH3)3F- leads to loss of the nucleophile R- and FSi(CH3)3, except in the case of (CH3)3SiNHSi(CH3)3F-, where HF loss is also observed. Ion affinities for FSi(CH3)3 have been measured for all five nucleophiles, and compare well with computational predictions. The observed trend of the bond dissociation energies resembles the trend of deltaH(acid) values for the corresponding conjugate acids, RH. Additionally, this data has been incorporated with existing thermochemistry to derive fluoride affinities for four of the silanes (R = CH3CH2O, (CH3)2CHO, (CH3)3SiO, and (CH3)3SiNH). We use the fluoride affinity of the silanes and the FSi(CH3)3 affinity of the departing nucleophilic anion to assess the feasibility of fluoride-induced desilylation of the silanes examined in this work. PMID:15862771

  9. An insight into the Lewis acid-catalyzed intramolecular aminocyanation and oxycyanation of alkenes: a concerted or stepwise mechanism.

    PubMed

    Zhao, Jiyang; Wang, Guoqiang; Li, Shuhua

    2015-10-28

    Density functional theory investigations reveal that the intramolecular additions of N-CN bonds to alkenes proceed in a novel asynchronous and concerted mechanism, while the intramolecular addition of O-CN bonds to alkenes may occur by both concerted and stepwise pathways.

  10. Transition-metal catalyzed oxidative cross-coupling reactions to form C-C bonds involving organometallic reagents as nucleophiles.

    PubMed

    Shi, Wei; Liu, Chao; Lei, Aiwen

    2011-05-01

    Transition-metal-catalyzed coupling reactions have become a versatile tool for chemical bond formation. From the variation of the coupling partners, coupling reactions can be classified into three models: traditional coupling, reductive coupling and oxidative coupling. The oxidative coupling, which is different from the traditional coupling, occurs between two nucleophiles. This critical review focuses on transition-metal-catalyzed oxidative coupling reactions involving organometallic reagents as nucleophiles. Since the scope of the oxidative coupling is highly diversified, this paper only reviews the oxidative coupling reactions concerning C-C bond formation, including the coupling between organometal reagents and hydrocarbons as well as coupling between two organometal reagents. Since terminal alkynes are normally activated by metal salts and in situ form the alkynyl metal reagents in coupling reactions, they are directly considered as organometal reagents in this review. Intramolecular oxidative couplings and oxidative cyclizations are not included in this critical review. Moreover, there are many examples of oxidative coupling leading to the formation of functional materials, such as the oxidative polymerization of thiophenes. Since several reviews in these areas have been published they are not included in this review either (99 references).

  11. 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

  12. Palladium Catalyzed Intramolecular Acylcyanation of Alkenes Using α-Iminonitriles

    PubMed Central

    Rondla, Naveen R.; Ogilvie, Jodi M.; Pan, Zhongda

    2014-01-01

    Reported here is a palladium catalyzed intramolecular acylcyanation of alkenes using α-iminonitriles. Through this method, highly functionalized indanones are synthesized in moderate to high yields using Pd(PPh3)4, without need for any additional ligands, and a common Lewis acid (ZnCl2). Additionally, the reaction tolerates substitution at various positions on the aromatic ring including electron donating, and electron withdrawing groups. PMID:24980625

  13. 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

  14. 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

  15. 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

  16. 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

  17. Nucleophilic substitution by grignard reagents on sulfur mustards.

    PubMed

    Converso, Antonella; Saaidi, Pierre-Loïc; Sharpless, K Barry; Finn, M G

    2004-10-15

    With proper activation of the leaving group, sulfur mustards react with Grignard reagents with neighboring group participation of the sulfur atom. 2,6-Dichloro-9-thiabicyclo[3.3.1]nonane is especially useful in this regard, providing clean reactivity with organomagnesium nucleophiles on a topologically constrained scaffold.

  18. 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.

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

    PubMed

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

    2016-05-18

    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.

  20. Nucleophilicity-periodic trends and connection to basicity.

    PubMed

    Uggerud, Einar

    2006-01-23

    The potential energy profiles of 18 identity S(N)2 reactions have been estimated by using G2-type quantum-chemical calculations. The reactions are: X- + CH3-X --> X-CH3 + X- and XH + CH3-XH+ --> +HX-CH3 + XH (X = NH2, OH, F, PH2, SH, Cl, AsH2, SeH, Br). Despite the charge difference, the barrier heights and the geometrical requirements upon going from the reactant to the transition structure are surprisingly similar for X- and XH. The barrier heights decrease on going from left to right in the periodic table, and increasing ionization energy (of X- and XH) is correlated with decreasing barrier. The observed trends are explained in terms of substrates with stronger electrostatic character giving rise to lower energetic barriers due to decreased electron repulsion in the transition structure. On the basis of this study, the relationship between the kinetic concept of nucleophilicity and the thermodynamic concept of basicity has been analyzed and clarified. Since the trends in intrinsic nucleophilicity (only defined for identity reactions) and basicity are opposite, overall nucleophilicity (defined for any reaction) will be determined by the relative contribution of the two factors. Only for strongly exothermic reactions will basicity and nucleophilicity be matching.

  1. 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

  2. A general phosphoric acid-catalyzed desymmetrization of meso-aziridines with silylated selenium nucleophiles.

    PubMed

    Senatore, Matilde; Lattanzi, Alessandra; Santoro, Stefano; Santi, Claudio; Della Sala, Giorgio

    2011-09-21

    The first example of meso-aziridine desymmetrization with selenium nucleophiles is reported. The reaction, promoted by VAPOL-hydrogen phosphate using (phenylseleno)trimethylsilane as the nucleophile, proves to be very general and highly enantioselective (84-99% ee).

  3. Benzyl anion transfer in the fragmentation of N-(phenylsulfonyl)-benzeneacetamides: a gas-phase intramolecular S(N)Ar reaction.

    PubMed

    Shen, Shanshan; Chai, Yunfeng; Liu, Yaqin; Li, Chang; Pan, Yuanjiang

    2015-10-28

    In this study, we report a gas-phase benzyl anion transfer via intramolecular aromatic nucleophilic substitution (SNAr) during the course of tandem mass spectrometry of deprotonated N-(phenylsulfonyl)-benzeneacetamide. Upon collisional activation, the formation of the initial ion/neutral complex ([C6H5CH2(-)/C6H5SO2NCO]), which was generated by heterolytic cleavage of the CH2-CO bond, is proposed as the key step. Subsequently, the anionic counterpart, benzyl anion, is transferred to conduct the intra-complex SNAr reaction. After losing neutral HNCO, the intermediate gives rise to product ion B at m/z 231, whose structure is confirmed by comparing the multistage spectra with those of deprotonated 2-benzylbenzenesulfinic acid and (benzylsulfonyl)benzene. In addition, intra-complex proton transfer is also observed within the complex [C6H5CH2(-)/C6H5SO2NCO] to generate product ion C at m/z 182. The INC-mediated mechanism was corroborated by theoretical calculations, isotope experiments, breakdown curve, substituent experiments, etc. This work may provide further understanding of the physicochemical properties of the gaseous benzyl anion. PMID:26309220

  4. 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

  5. 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

  6. 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

  7. 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

  8. Intramolecular cycloadditions of cyclobutadiene with olefins.

    PubMed

    Limanto, John; Tallarico, John A; Porter, James R; Khuong, Kelli S; Houk, K N; Snapper, Marc L

    2002-12-11

    Intramolecular cycloadditions between cyclobutadiene and olefins can provide highly functionalized cyclobutene-containing products. The outcome of the reaction depends on the nature of the tether connecting the two reactive partners in the cycloaddition. Electronically unactivated olefins attached to cyclobutadiene through a three-atom, heteroatom-containing tether yield successfully the desired cycloadducts, whereas the corresponding substrates without a heteroatom linkage or with a longer tether are less prone to undergo the intramolecular cycloaddition. Calculations were used to help uncover some of the factors that influence the course of the cycloaddition. Successful intramolecular reactions usually require either electronic activation of the dienophile, conformational restriction of the tether, or a slower oxidation protocol. In general, a facile intermolecular dimerization of cyclobutadiene is the major process that competes with the intramolecular cycloaddition.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Synthesis and nucleophilic reactivity of a series of glutathione analogues, modified at the gamma-glutamyl moiety.

    PubMed Central

    Adang, A E; Duindam, A J; Brussee, J; Mulder, G J; van der Gen, A

    1988-01-01

    A series of GSH analogues with modifications at the gamma-glutamyl moiety was synthesized and purified by following peptide chemistry methodology. Benzyl, benzyloxycarbonyl and t-butyloxycarbonyl protective groups were used to protect individual amino acid functional groups. The formation of peptide bonds was accomplished through coupling of free amino groups with active esters, generated by reaction of the carboxylate functions with dicyclohexylcarbodi-imide and 1-hydroxybenzotriazole. The protecting groups in the tripeptides were removed in a single step by using Na in liquid NH3. Precautions were taken in order to prevent oxidation of the thiol function in the cysteine residue. Thus GSH analogues containing both L- and D-glutamic acid and L- and D-aspartic acid, coupled to cysteinylglycine through both the alpha- and the omega-carboxylate group, were synthesized. Also, decarboxy-GSH and deamino-GSH, lacking one functional group in the glutamate moiety, were prepared. The spontaneous non-enzyme-catalysed nucleophilic reaction of these GSH analogues with the electrophilic model substrate 1-chloro-2,4-dinitrobenzene showed appreciable rate differences, indicating the importance of intramolecular interactions in determining the nucleophilic reactivity of the thiol function in the cysteine residue. In particular, the free amino group in the gamma-L-glutamic acid residue appears to play a crucial role in activating the thiol group in GSH. In an adjacent paper [Adang, Brussee, Meyer, Coles, Ketterer, van der Gen & Mulder (1988) Biochem. J. 255, 721-724] these results are compared with those obtained in a study on the ability of these GSH analogues to act as a co-substrate in the glutathione S-transferase-catalysed conjugation reaction with 1-chloro-2,4-dinitrobenzene. PMID:2904808

  15. 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

  16. Intramolecular screening of intermolecular forces

    NASA Astrophysics Data System (ADS)

    Liang, Ying Q.; Hunt, K. L. C.

    1993-03-01

    By use of nonlocal polarizability densities, we analyze the intramolecular screening of intermolecular fields. For two interacting molecules A and B with weak or negligible charge overlap, we show that the reaction field and the field due to the unperturbed charge distribution of the neighboring molecule are screened identically via the Sternheimer shielding tensor and its generalizations to nonuniform fields and nonlinear response. The induction force on nucleus I in molecule A, derived from perturbation theory, results from linear screening of the reaction field due to B and nonlinear screening of the field from the permanent charge distribution of B. In general, at first or second order in the molecular interaction, the screening-tensor expressions for the force on nucleus I involve susceptibilities of one order higher than the expressions derived from perturbation theory. The first-order force from perturbation theory involves permanent charge moments, while the first-order screened force involves linear response tensors; and the second-order screened force depends on hyperpolarizabilities, while second-order induction effects are specified in terms of static, lowest-order susceptibilities. The equivalence of the two formulations for these forces, order by order, is a new illustration of the interrelations we have found among permanent moments, linear-response tensors, and nonlinear response. This work also provides new insight into the dispersion forces on an individual nucleus I in molecule A by separating the forces into two distinct terms—the first term results from changes in the reaction of A to the fluctuating charge distribution of the neighboring molecule B, when nucleus I shifts infinitesimally, and the second term stems from changes in correlations of the fluctuating charge distribution of A itself. Changes in the fluctuation correlations are determined by changes in the classical Coulomb field of nucleus I and by the imaginary part of the

  17. Temporary silicon connection strategies in intramolecular allylation of aldehydes with allylsilanes.

    PubMed

    Beignet, Julien; Jervis, Peter J; Cox, Liam R

    2008-07-18

    Three gamma-(amino)silyl-substituted allylsilanes 14a-c have been prepared in three steps from the corresponding dialkyldichlorosilane. The aminosilyl group has been used to link this allylsilane nucleophile to a series of beta-hydroxy aldehydes through a silyl ether temporary connection. The size of the alkyl substituents at the silyl ether tether governs the outcome of the reaction on exposure to acid. Thus, treatment of aldehyde (E)-9aa, which contains a dimethylsilyl ether connection between the aldehyde and allylsilane, with a range of Lewis and Brønsted acid activators provides an (E)-diene product. The mechanism of formation of this undesired product is discussed. Systems containing a sterically more bulky diethylsilyl ether connection react differently: thus in the presence of TMSOTf and a Brønsted acid scavenger, intramolecular allylation proceeds smoothly to provide two out of the possible four diastereoisomeric oxasilacycles, 23 (major) and 21 (minor). A diene product again accounts for the remaining mass balance in the reaction. This side product can be completely suppressed by using a sterically even more bulky diisopropylsilyl ether connection in the cyclization precursor, although this is now at the expense of a slight erosion in the 1,3-stereoinduction in the allylation products. The sense of 1,3-stereoinduction observed in these intramolecular allylations has been rationalized by using an electrostatic argument, which can also explain the stereochemical outcome of a number of related reactions. Levels of 1,4-stereoinduction in the intramolecular allylation are more modest but can be significantly improved in some cases by using a tethered (Z)-allylsilane in place of its (E)-stereoisomer. Oxidation of the major diastereoisomeric allylation product 23 under Tamao-Kumada conditions provides an entry into stereodefined 1,2-anti-2,4-syn triols 28.

  18. The efficiency of the metal catalysts in the nucleophilic substitution of alcohols is dependent on the nucleophile and not on the electrophile.

    PubMed

    Biswas, Srijit; Samec, Joseph S M

    2013-05-01

    In this study, we investigate the effect of the electrophiles and the nucleophiles for eight catalysts in the catalytic SN 1 type substitution of alcohols with different degree of activation by sulfur-, carbon-, oxygen-, and nitrogen-centered nucleophiles. The catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols and follow the trend of alcohol reactivity. However, when it comes to the nucleophile, the eight catalysts show general and specific variances in the efficiency and selectivity to perform the desired substitution. Interestingly, the selectivity of the alcohols to produce the desired substitution products was found to be independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation. Catalysts based on iron(III), bismuth(III), and gold(III) show higher conversions for S-, C-, and N-centered nucleophiles, and Bi(III) was the most efficient catalyst in all combinations. Catalysts based on rhenium(I) or rhenium(VII), palladium(II), and lanthanum(III) were the most efficient in performing the nucleophilic substitution on the various alcohols with the O-centered nucleophiles. These catalysts generate the symmetrical ether as a by-product from the reactions of S-, C-, and N-centered nucleophiles as well, resulting in lower chemoselectivity. PMID:23471850

  19. 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

  20. Palladium-catalyzed Allylic Substitution with (η6-arene–CH2Z)Cr(CO)3-based Nucleophiles

    PubMed Central

    Zhang, Jiadi; Stanciu, Corneliu; Wang, Beibei; Hussain, Mahmud M.; Da, Chao-Shan; Carroll, Patrick J.; Dreher, Spencer D.; Walsh, Patrick J.

    2011-01-01

    Although the palladium-catalyzed Tsuji-Trost allylic substitution reaction has been intensively studied, there is a lack of general methods to employ simple benzylic nucleophiles. Such a method would facilitate access to “α-2-propenyl benzyl” motifs, which are common structural motifs in bioactive compounds and natural products. We report herein the palladium-catalyzed allylation reaction of toluene-derived pronucleophiles activated by tricarbonylchromium. A variety of cyclic and acyclic allylic electrophiles can be employed with in situ generated (η6-C6H5–CHLiR)Cr(CO)3 nucleophiles. Catalyst identification was performed by high throughput experimentation (HTE) and led to the Xantphos/palladium hit, which proved to be a general catalyst for this class of reactions. In addition to η6-toluene complexes, benzyl amine and ether derivatives (η6-C6H5–CH2Z)Cr(CO)3 (Z=NR2, OR) are also viable pronucleophiles, allowing C–C bond-formation alpha to heteroatoms with excellent yields. Finally, a tandem allylic substitution/demetallation procedure is described that affords the corresponding metal-free allylic substitution products. This method will be a valuable complement to the existing arsenal of nucleophiles with applications in allylic substitution reactions. PMID:22047504

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

    PubMed

    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). PMID:11538282

  2. 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).

  3. Aromatic nucleophilic substitution reactions in high temperature, high pressure water

    SciTech Connect

    Le Lacheur, R.M.; Tumas, W.

    1995-12-01

    Aromatic nucleophilic substitution reactions in anoxic supercritical water were examined both for their synthetic and waste remediation potential. The substrates were halogenated aromatic compounds, and the nucleophiles were hydroxide and halide salts. Hydroxide reacts rapidly with bromo-, chloro-, and fluorobenzene at 400{degrees}C and 5300 psi, and phenol is produced almost quantitatively. In batch studies, the reaction rate order was bromo > fluoro > chlorobenzene. Mechanistic studies using halogenated toluenes showed that fluorotoluenes yield ipso substitution, possibly via the S{sub N}Ar mechanism, Chlorotoluenes and bromotoluenes yield cine substitution, likely via the benzyne mechanism. Sodium chloride reacts with bromotoluenes to yield ipso-substituted chlorotoluenes as the major product; cesium fluoride yields cine substituted cresols as the major products, with small amounts of cine substituted fluorotoluenes. The results indicate that fluoride is a very strong base under supercritical conditions, and that the benzyne mechanism results. Chloride is a weaker base and reacts by a direct substitution mechanism such as S{sub N}Ar.

  4. Organocatalyzed Intramolecular Carbonyl-Ene Reactions.

    PubMed

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

    2016-05-31

    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.

  5. Poly(1,3,4-oxadiazoles) via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    Poly(1,3,4-oxadiazoles) (POX) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl) 1,3,4-oxadiazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl) 1,3,4-oxadiazole monomers are synthesized by reacting 4-hydroxybenzoic hydrazide with phenyl 4-hydrobenzoate in the melt and also by reacting aromatic dihydrazides with two moles of phenyl 4-hydroxybenzoate in the melt. This synthetic route has provided high molecular weight POX of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the large variety of activated aromatic dihalides which are available.

  6. 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.

  7. 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).

  8. 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

  9. 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).

  10. 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.

  11. 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

  12. 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)

  13. 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

  14. Intramolecular Tsuji-Trost-type Allylation of Carboxylic Acids: Asymmetric Synthesis of Highly π-Allyl Donative Lactones.

    PubMed

    Suzuki, Yusuke; Seki, Tomoaki; Tanaka, Shinji; Kitamura, Masato

    2015-08-01

    Tsuji-Trost-type asymmetric allylation of carboxylic acids has been realized by using a cationic CpRu complex with an axially chiral picolinic acid-type ligand (Cl-Naph-PyCOOH: naph = naphthyl, py = pyridine). The carboxylic acid and allylic alcohol intramolecularly condense by the liberation of water without stoichiometric activation of either nucleophile or electrophile part, thereby attaining high atom- and step-economy, and low E factor. This success can be ascribed to the higher reactivity of allylic alcohols as compared with the allyl ester products in soft Ru/hard Brønstead acid combined catalysis, which can function under slightly acidic conditions unlike the traditional Pd-catalyzed system. Detailed analysis of the stereochemical outcome of the reaction using an enantiomerically enriched D-labeled substrate provides an intriguing view of enantioselection. PMID:26199057

  15. 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

  16. Enantioselective Michael addition of water.

    PubMed

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

    2015-02-01

    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.

  17. 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.

  18. 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

  19. 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.

  20. Bismuth-catalyzed addition of silyl nucleophiles to carbonyl compounds and imines.

    PubMed

    Ollevier, Thierry

    2012-01-01

    Bismuth triflate was found to be an efficient catalyst both in the Mannich-type reaction of silyl enolates and in the Sakurai reaction of allyltrimethylsilane with N-alkoxycarbonylamino sulfones. The reactions proceeded smoothly with a low catalyst loading of Bi(OTf)(3)·4H(2)O (0.5-5.0 mol%) to afford the corresponding protected β-amino carbonyl compounds and homoallylic amines in very good yields (up to 96%). The latter compounds could also be obtained via a bismuth-mediated three-component reaction. We have also developed an efficient vinylogous Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan with various aromatic aldehydes mediated by bismuth triflate in a low catalyst loading (1 mol%). The reaction proceeds rapidly and affords the corresponding 5-[hydroxy(aryl)methyl]furan-2(5H)-ones in high yields with good to very good diastereoselectivities (diastereoisomeric ratios>98:2). Such selectivities, although previously reported with other Lewis acids, could be achieved with a much lower catalyst loading. 5-[Hydroxy(alkyl)methyl]furan-2(5H)-ones derived from ketones could also be obtained with good diastereoselectivities. The vinylogous Mukaiyama aldol reaction has also been extended to 2,2-dimethyl-6-methylene-4-(trimethyl-silyloxy)-1,3-diox-4-ene using 1 mol% of Bi(OTf)(3)·4H(2)O. PMID:22048688

  1. Is nucleophilic cleavage chemistry practical for 4-membered heterocycles?

    PubMed

    Banks, Harold D

    2009-11-01

    A computational study at the MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level of the ammonolysis of halogen substituted azetidines, oxetanes and thietanes was performed in the gas phase and in the commonly used solvent, acetonitrile. Using the free energy of activation of a benchmark reaction for evaluation of synthetic viability, several haloazetidines and oxetanes that possessed the required reactivity were identified; however, no substituted thietane investigated herein was determined to be synthetically useful under the mild conditions selected for this study. In the case of the azetidines, the side reaction of displacement of halide ion was determined to be the preferred reaction course in acetonitrile; however, the amino product of the reactions of the 2-haloazetidines cleaved at an acceptable rate under mild conditions. For the oxetane derivatives investigated, 2-fluorooxetane proved to be a direct source of ring cleavage product. Nucleophilic cleavage of halogen-substituted azetidines and oxetanes is predicted to be a viable source of functionalized three-carbon moieties under mild conditions in organic synthesis.

  2. 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

  3. Analysis of solvent nucleophile isotope effects: evidence for concerted mechanisms and nucleophilic activation by metal coordination in nonenzymatic and ribozyme-catalyzed phosphodiester hydrolysis.

    PubMed

    Cassano, Adam G; Anderson, Vernon E; Harris, Michael E

    2004-08-17

    Heavy atom isotope effects are a valuable tool for probing chemical and enzymatic reaction mechanisms; yet, they are not widely applied to examine mechanisms of nucleophilic activation. We developed approaches for analyzing solvent (18)O nucleophile isotope effects ((18)k(nuc)) that allow, for the first time, their application to hydrolysis reactions of nucleotides and nucleic acids. Here, we report (18)k(nuc) for phosphodiester hydrolysis catalyzed by Mg(2+) and by the Mg(2+)-dependent RNase P ribozyme and deamination by the Zn(2+)-dependent protein enzyme adenosine deaminase (ADA). Because ADA incorporates a single solvent molecule into the product inosine, this reaction can be used to monitor solvent (18)O/(16)O ratios in complex reaction mixtures. This approach, combined with new methods for analysis of isotope ratios of nucleotide phosphates by whole molecule mass spectrometry, permitted determination of (18)k(nuc) for hydrolysis of thymidine 5'-p-nitrophenyl phosphate and RNA cleavage by the RNase P ribozyme. For ADA, an inverse (18)k(nuc) of 0.986 +/- 0.001 is observed, reflecting coordination of the nucleophile by an active site Zn(2+) ion and a stepwise mechanism. In contrast, the observed (18)k(nuc) for phosphodiester reactions were normal: 1.027 +/- 0.013 and 1.030 +/- 0.012 for the Mg(2+)- and ribozyme-catalyzed reactions, respectively. Such normal effects indicate that nucleophilic attack occurs in the rate-limiting step for these reactions, consistent with concerted mechanisms. However, these magnitudes are significantly less than the (18)k(nuc) observed for nucleophilic attack by hydroxide (1.068 +/- 0.007), indicating a "stiffer" bonding environment for the nucleophile in the transition state. Kinetic analysis of the Mg(2+)-catalyzed reaction indicates that a Mg(2+)-hydroxide complex is the catalytic species; thus, the lower (18)k(nuc), in large part, reflects direct metal ion coordination of the nucleophilic oxygen. A similar value for the RNase P

  4. Palladium-Catalyzed Cross Coupling of Secondary and Tertiary Alkyl Bromides with a Nitrogen Nucleophile

    PubMed Central

    2016-01-01

    We report a new class of catalytic reaction: the thermal substitution of a secondary and or tertiary alkyl halide with a nitrogen nucleophile. The alkylation of a nitrogen nucleophile with an alkyl halide is a classical method for the construction of C–N bonds, but traditional substitution reactions are challenging to achieve with a secondary and or tertiary alkyl electrophile due to competing elimination reactions. A catalytic process could address this limitation, but thermal, catalytic coupling of alkyl halides with a nitrogen nucleophile and any type of catalytic coupling of an unactivated tertiary alkyl halide with a nitrogen nucleophile are unknown. We report the coupling of unactivated secondary and tertiary alkyl bromides with benzophenone imines to produce protected primary amines in the presence of palladium ligated by the hindered trialkylphosphine Cy2t-BuP. Mechanistic studies indicate that this amination of alkyl halides occurs by a reversible reaction to form a free alkyl radical. PMID:27725963

  5. Dehalogenation of arenes via SN2 reactions at bromine: competition with nucleophilic aromatic substitution.

    PubMed

    Gronert, Scott; Garver, John M; Nichols, Charles M; Worker, Benjamin B; Bierbaum, Veronica M

    2014-11-21

    The gas-phase reactions of carbon- and nitrogen-centered nucleophiles with polyfluorobromobenzenes were examined in a selected-ion flow tube (SIFT) and modeled computationally at the MP2/6-31+G(d,p)//MP2/6-31+G(d) level. In the gas-phase experiments, rate constants and branching ratios were determined. The carbon nucleophiles produce expected nucleophilic aromatic substitution (SNAr) and proton transfer products along with unexpected products that result from SN2 reactions at the bromine center (polyfluorophenide leaving group). With nitrogen nucleophiles, the SN2 at bromine channel is suppressed. In the SNAr channels, the "element effect" is observed, and fluoride loss competes with bromide loss. The computational modeling indicates that all the substitution barriers are well below the entrance channel and that entropy and dynamics effects control the product distributions.

  6. 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

  7. Mechanistic Studies of Wacker-Type Intramolecular Aerobic Oxidative Amination of Alkenes Catalyzed by Pd(OAc)2/Pyridine

    PubMed Central

    Ye, Xuan; Liu, Guosheng; Popp, Brian V.; Stahl, Shannon S.

    2011-01-01

    Wacker-type oxidative cyclization reactions have been the subject of extensive research for several decades, but few systematic mechanistic studies of these reactions have been reported. The present study features experimental and DFT computational studies of Pd(OAc)2/pyridine-catalyzed intramolecular aerobic oxidative amination of alkenes. The data support a stepwise catalytic mechanism that consists of (1) steady-state formation of a PdII-amidate-alkene chelate with release of one equivalent of pyridine and AcOH from the catalyst center, (2) alkene insertion into a Pd–N bond, (3) reversible β-hydride elimination, (4) irreversible reductive elimination of AcOH, and (5) aerobic oxidation of palladium(0) to regenerate the active trans-Pd(OAc)2(py)2 catalyst. Evidence is obtained for two energetically viable pathways for the key C–N bond-forming step, featuring a pyridine-ligated and a pyridine-dissociated PdII species. Analysis of natural charges and bond lengths of the alkene-insertion transition state suggest that this reaction is best described as an intramolecular nucleophilic attack of the amidate ligand on the coordinated alkene. PMID:21250706

  8. 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.

  9. Iodine-catalyzed oxidative coupling reactions utilizing C - H and X - H as nucleophiles.

    PubMed

    Liu, Dong; Lei, Aiwen

    2015-04-01

    In recent decades, iodine-catalyzed oxidative coupling reactions utilizing C - H and X - H as nucleophiles have received considerable attention because they represent more efficient, greener, more atom-economical, and milder bond-formation strategies over transition-metal-catalyzed oxidative coupling reactions. This Focus Review gives a brief summary of recent development on iodine-catalyzed oxidative coupling reactions utilizing C - H and X - H as nucleophiles.

  10. Comparison of alternative nucleophiles for Sortase A-mediated bioconjugation and application in neuronal cell labelling.

    PubMed

    Baer, Samuel; Nigro, Julie; Madej, Mariusz P; Nisbet, Rebecca M; Suryadinata, Randy; Coia, Gregory; Hong, Lisa P T; Adams, Timothy E; Williams, Charlotte C; Nuttall, Stewart D

    2014-05-01

    The Sortase A (SrtA) enzyme from Staphylococcus aureus catalyses covalent attachment of protein substrates to pentaglycine cross-bridges in the Gram positive bacterial cell wall. In vitro SrtA-mediated protein ligation is now an important protein engineering tool for conjugation of substrates containing the LPXTGX peptide recognition sequence to oligo-glycine nucleophiles. In order to explore the use of alternative nucleophiles in this system, five different rhodamine-labelled compounds, with N-terminal nucleophilic amino acids, triglycine, glycine, and lysine, or N-terminal non-amino acid nucleophiles ethylenediamine and cadaverine, were synthesized. These compounds were tested for their relative abilities to function as nucleophiles in SrtA-mediated bioconjugation reactions. N-Terminal triglycine, glycine and ethylenediamine were all efficient in labelling a range of LPETGG containing recombinant antibody and scaffold proteins and peptides, while reduced activity was observed for the other nucleophiles across the range of proteins and peptides studied. Expansion of the range of available nucleophiles which can be utilised in SrtA-mediated bioconjugation expands the range of potential applications for this technology. As a demonstration of the utility of this system, SrtA coupling was used to conjugate the triglycine rhodamine-labelled nucleophile to the C-terminus of an Im7 scaffold protein displaying Aβ, a neurologically important peptide implicated in Alzheimer's disease. Purified, labelled protein showed Aβ-specific targeting to mammalian neuronal cells. Demonstration of targeting neuronal cells with a chimeric protein illustrates the power of this system, and suggests that SrtA-mediated direct cell-surface labelling and visualisation is an achievable goal. PMID:24643508

  11. 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.

  12. 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.

  13. 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

  14. Intramolecular excited-state interactions of surfactant-active osmium(II) photosensitizers

    SciTech Connect

    Sasksteder, L.; Demas, J.N. ); DeGraff, B.A. )

    1989-05-17

    A new class of luminescent surfactant-active complexes, cis-OsL{sub 2}(CO)NC(CH{sub 2}){sub n}CH{sub 3}{sup 2+} (n = 0-19; L = 2,2{prime}-bipyridine and 1,10-phenanthroline), were synthesized and characterized. They represent another example of an intramolecular perturbation of excited-state properties by what would normally be considered an electronically passive alkyl ligand. The effect is smaller in the Os(II) case and has a different n dependence than was observed in the fac-ReL(CO){sub 3}NC(CH{sub 2}){sub n}CH{sub 3}{sup +} system. The differences arise from varied geometric constraints on the foldback and the orbital parentage of the emitting state. Foldback must be directly to ligands involved in the emission process in order to perturb the emission. The osmium(II) center highly activates the bound nitrile to thermal nucleophilic attack, and luminescent adducts are formed with alcohols and aliphatic and aromatic amines. Such activation has not been previously observed in complexes with {alpha}-diimine ligands. The complexes also photodecompose by labilization of the nitrile. 37 refs., 5 figs.

  15. 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.

  16. Intramolecular interactions in the polar headgroup of sphingosine: serinol.

    PubMed

    Loru, Donatella; Peña, Isabel; Alonso, José L; Sanz, M Eugenia

    2016-03-01

    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.

  17. Thermal induced intramolecular [2 + 2] cycloaddition of allene-ACPs.

    PubMed

    Chen, Kai; Sun, Run; Xu, Qin; Wei, Yin; Shi, Min

    2013-06-28

    A facile synthetic method for preparation of bicyclo[4.2.0] nitrogen heterocycles has been developed via a thermal induced intramolecular [2 + 2] cycloaddition reaction of allene-ACPs. The DFT calculations indicate that this intramolecular cycloaddition proceeds in a concerted manner and a strained small ring is essential.

  18. Catalytic enantioselective intramolecular aza-diels-alder reactions.

    PubMed

    Min, Chang; Lin, Chih-Tsung; Seidel, Daniel

    2015-05-26

    A readily available chiral Brønsted acid was identified as an efficient catalyst for intramolecular Povarov reactions. Polycyclic amines containing three contiguous stereogenic centers were obtained with excellent stereocontrol in a single step from secondary anilines and aldehydes possessing a pendent dienophile. These transformations constitute the first examples of catalytic enantioselective intramolecular aza-Diels-Alder reactions.

  19. High 1,3-trans stereoselectivity in nucleophilic substitution at the anomeric position and β-fragmentation of the primary alkoxyl radical in 3-amino-3-deoxy-ribofuranose derivatives: application to the synthesis of 2-epi-(-)-jaspine B.

    PubMed

    Sánchez-Eleuterio, Alma; Quintero, Leticia; Sartillo-Piscil, Fernando

    2011-07-01

    The high inverse stereoselectivity in the nucleophilic substitution at the anomeric position of 3-amino-3-deoxy-ribofuranose derivatives is reported. This unprecedented stereoselectivity is explained in terms of preferential nucleophilic attack on the "inside face" of the respective five-membered ring oxocarbenium ion that orients pseudoequatorially to the benzylamine group placed at the C-3 position. In addition, an unusual β-fragmentation of a primary alkoxyl radical generated from its corresponding N-phthalimide derivative was achieved, and thus taking advantages of both reactions, the total synthesis of 2-epi-(-)-jaspine B was completed.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  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. Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence

    PubMed Central

    Du, Eun Jo; Ahn, Tae Jung; Wen, Xianlan; Seo, Dae-Won; Na, Duk L; Kwon, Jae Young; Choi, Myunghwan; Kim, Hyung-Wook; Cho, Hana; Kang, KyeongJin

    2016-01-01

    Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. We discover that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.18425.001 PMID:27656903

  6. Kinetics and mechanism of propachlor reductive transformation through nucleophilic substitution by dithionite.

    PubMed

    Liu, C S; Shih, K; Wei, L; Wang, F; Li, F B

    2011-11-01

    Chloroacetanilide herbicides are extensively used in the control of weeds and have widely resulted in nonpoint contamination of groundwater and soil resources. In the attempt to achieve better remediation for herbicide-contaminated resources, we investigated the reductive transformation of propachlor through nucleophilic substitution by dithionite (S(2)O(4)(2-)). Results showed that propachlor underwent rapid dechlorination in the presence of dithionite. The reaction was of second-order kinetics and strongly influenced by pH and temperature. At pH 7.0 and temperature 308K, the rate constant of propachlor dechlorination was estimated at 123.4±0.7M(-1)h(-1). Within the pH range tested (3.0-9.5), higher pH promoted the ionization of dithionite, resulting in a more active nucleophilic reagent of S(2)O(4)(2-) to enhance the propachlor transformation rate. Similarly, higher reaction temperature overcame the activation barrier of steric hindrance in propachlor structure and accelerated the excitation of dithionite, in which higher rate constants of propachlor reductive dechlorination were obtained. Dechlorination was found to be the first and necessary step of propachlor nucleophilic substitution by dithionite. Sulfur nucleophile substituted compounds, including propachlor dithionite, propachlor ethanesulfonic acid (ESA), and hydroxyl propachlor, were identified as the dechlorination products of propachlor, indicating bimolecular nucleophilic substitution (S(N)2) as the mechanism for propachlor transformation initiated by dithionite.

  7. Copper-catalysed intramolecular O-arylation: a simple and efficient method for benzoxazole synthesis.

    PubMed

    Wu, Fengtian; Zhang, Jie; Wei, Qianbing; Liu, Ping; Xie, Jianwei; Jiang, Haojie; Dai, Bin

    2014-12-21

    A wide range of 2-substituted benzoxazoles can be efficiently synthesized from N-(2-iodo-/bromo-phenyl)benzamides, and even the less reactive N-(2-chlorophenyl)benzamides, via Cu-catalysed intramolecular coupling cyclization reactions using methyl 2-methoxybenzoate as the ligand under mild reaction conditions. In addition, the benzoxazoles can be easily prepared from the primary amides coupling with o-dihalobenzenes in a single step.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

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

    DOE PAGES

    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

  16. Direct Observation and Control of Ultrafast Photoinduced Twisted Intramolecular Charge Transfer (TICT) in Triphenyl-Methane Dyes

    PubMed Central

    Li, Guifeng; Magana, Donny; Dyer, R. Brian

    2012-01-01

    Femtosecond time-resolved infrared spectroscopy was employed to study intramolecular charge transfer in triphenylmethane dyes, including malachite green (MG), malachite green carbinol base (MGCB), and leucomalachite green (LMG). A local excited state (LE) and a twisted intramolecular charge-transfer (TICT) state have been observed directly in MG. Furthermore, solvent-controlled TICT measurements in a series of linear alcohols indicate that the transition time (4–11 ps) from LE to TICT is strongly dependent on alcohol viscosity, which is due to rotational hindrance of dimethylaniline in high-viscosity solvents. For LMG, no TICT is observed due to steric hindrance caused by the sp3-hybridized central carbon atom. However, for MGCB, TICT is rescued by the addition of the electron-donating hydroxyl group to the bridge. These results for MG and its analogues provide new insight regarding the dynamics and mechanism of twisted intramolecular charge transfer (TICT) in triphenylmethane dyes. PMID:23009668

  17. 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

  18. Biphenyl-derived phosphepines as chiral nucleophilic catalysts: enantioselective [4+1] annulations to form functionalized cyclopentenes.

    PubMed

    Ziegler, Daniel T; Riesgo, Lorena; Ikeda, Takuya; Fujiwara, Yuji; Fu, Gregory C

    2014-11-24

    Because of the frequent occurrence of cyclopentane subunits in bioactive compounds, the development of efficient catalytic asymmetric methods for their synthesis is an important objective. Introduced herein is a new family of chiral nucleophilic catalysts, biphenyl-derived phosphepines, and we apply them to an enantioselective variant of a useful [4+1] annulation. A range of one-carbon coupling partners can be employed, thereby generating cyclopentenes which 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.

  19. 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.

  20. 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.

  1. 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.

  2. Total synthesis of debromoflustramines B and E based on the intramolecular carbamoylketene-alkene [2 + 2] cycloaddition.

    PubMed

    Ozawa, Tsukasa; Kanematsu, Makoto; Yokoe, Hiromasa; Yoshida, Masahiro; Shishido, Kozo

    2012-10-19

    Total synthesis of debromoflustramines B and E has been accomplished by using a platinum-catalyzed addition reaction of o-aminophenylboronic acid with the allene and an intramolecular carbamoylketene-alkene [2 + 2] cycloaddition for the construction of the basic carbon framework of the target alkaloids as the key steps.

  3. 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

  4. Exciton Correlations in Intramolecular Singlet Fission

    DOE PAGES

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

    2016-05-16

    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,more » 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.« less

  5. Substituent Effects on the Formation and Nucleophile Selectivity of Ring-Substituted Phenonium Ions in Aqueous Solution.

    PubMed

    Tsuji, Yutaka; Ogawa, Shin; Richard, John P

    2013-12-01

    The reaction of 2-(4-methyphenyl)ethyl tosylate (Me-1-OTs) in 50/50 (v/v) trifluoroethanol/water at 25 °C is first-order in the concentration of azide anion nucleophile. A carbon-13 NMR analysis of the products of the reactions of Me-1-[α-(13)C]OTs in 50/50 (v/v) trifluoroethanol/water at 25 °C shows the formation of Me-1-[β-(13)C]OH, Me-1-[β-(13)C]OCH2CF3 and Me-1-[β-(13)C]N3 from the trapping of a symmetrical 4-methylphenonium ion reaction intermediate Me-2 (+). The formation of Me-1-[α-(13)C]N3 by concerted bimolecular displacement of azide ion at Me-1-[α-(13)C]OTs (k N = 3.8 × 10(-6) M(-1) s(-1)) and of Me-1-[α-(13)C]OH and Me-1-[α-(13)C]OCH2CF3 by concerted bimolecular displacement of solvent (k solv = 1.8 × 10(-8) s(-1)) is also observed. An analysis of the rate and product data provides a value of k az/k s = 32 M(-1) for partitioning of Me-2 (+) between addition of azide ion and solvent that is nearly 3-fold smaller than k az/k s = 83 M(-1) reported in an earlier study on the partitioning of MeO-2 (+) [J. Org. Chem. 2011, 76, 9568]. This change is attributed to a decrease in nucleophile selectivity with increasing electrophile reactivity for the activation-limited addition of solvent and azide anion to X-2 (+). These data set a limit of 1/k s ≥ 10(-7) s for the lifetime of Me-2 (+) in aqueous solution.

  6. 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.

  7. 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

  8. 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…

  9. 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 ...

  10. Reactivity of the actinoid-carbon bond: alkyluranium compounds as selective nucleophilic reagents in organic synthesis

    SciTech Connect

    Dormond, A.; Aaliti, A.; Moiese, C.

    1988-03-04

    Stable tris(bis(trimethylsilyl)amido)methyluranium is a very highly selective nucleophilic Grignard-like reagent in chemo- and stereoselective alkylation reactions of carbonyl compounds. Related tris(bis(trimethylsilyl)amido)-trichloro-, and cyclopenadienyldichloroalkyluranium complexes are less selective reagents. 16 references, 7 tables.

  11. Hydroxyalkoxy radicals: importance of intramolecular hydrogen bonding on chain branching reactions in the combustion and atmospheric decomposition of hydrocarbons.

    PubMed

    Davis, Alexander C; Francisco, Joseph S

    2014-11-20

    During both the atmospheric oxidation and combustion of volatile organic compounds, sequential addition of oxygen can lead to compounds that contain multiple hydrogen-bonding sites. The presence of two or more of these sites on a hydrocarbon introduces the possibility of intramolecular H-bonding, which can have a stabilizing effect on the reactants, products, and transition states of subsequent reactions. The present work compares the absolute energies of two sets of conformations, those that contain intramolecular H-bonds and those that lack intramolecular H-bonds, for each reactant, product, and transition state species in the 1,2 through 1,7 H-migrations and Cα-Cβ, Cα-H, and Cα-OH-bond scission reactions in the n-hydroxyeth-1-oxy through n-hydroxyhex-1-oxy radicals, for n ranging from 1 to 6. The difference in energy between the two conformations represents the balance between the stabilizing effects of H-bonds and the steric cost of bringing the two H-bonding sites together. The effect of intramolecular H-bonding and the OH group is assessed by comparing the net intramolecular H-bond stabilization energies, the reaction enthalpies, and barrier heights of the n-hydroxyalkoxy radical reactions with the corresponding alkoxy radicals values. The results suggest that there is a complex dependence on the location of the two H-bonding groups, the location of the abstraction or bond scission, and the shape of the transition state that dictates the extent to which intramolecular H-bonding effects the relative importance of H-migration and bond scission reactions for each n-hydroxyalkoxy radical. These findings have important implications for future studies on hydrocarbons with multiple H-bonding sites.

  12. 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.

  13. Extremely slow intramolecular diffusion in unfolded protein L.

    PubMed

    Waldauer, Steven A; Bakajin, Olgica; Lapidus, Lisa J

    2010-08-01

    A crucial parameter in many theories of protein folding is the rate of diffusion over the energy landscape. Using a microfluidic mixer we have observed the rate of intramolecular diffusion within the unfolded B1 domain of protein L before it folds. The diffusion-limited rate of intramolecular contact is about 20 times slower than the rate in 6 M GdnHCl, and because in these conditions the protein is also more compact, the intramolecular diffusion coefficient decreases 100-500 times. The dramatic slowdown in diffusion occurs within the 250 micros mixing time of the mixer, and there appears to be no further evolution of this rate before reaching the transition state of folding. We show that observed folding rates are well predicted by a Kramers model with a denaturant-dependent diffusion coefficient and speculate that this diffusion coefficient is a significant contribution to the observed rate of folding.

  14. Anionic polymerization of oxadiazole-containing 2-vinylpyridine by precisely tuning nucleophilicity and the polyelectrolyte characteristics of the resulting polymers

    DOE PAGES

    Goodwin, Andrew; Goodwin, Kimberly M.; Wang, Weiyu; Yu, Yong -Guen; Lee, Jae -Suk; Mahurin, Shannon M.; Dai, Sheng; Mays, Jimmy W.; Kang, Nam -Goo

    2016-09-01

    Anionic polymerization is one of the most powerful techniques for preparation of well-defined polymers. However, this well-known and widely employed polymerization technique encounters major limitations for the polymerization of functional monomers containing heteroatoms. This work presents the anionic polymerization of 2-phenyl-5-(6-vinylpyridin-3-yl)-1,3,4-oxadiazole (VPyOzP), a heteroatom monomer that contains both oxadiazole and pyridine substituents within the same pendant group, using various initiating systems based on diphenylmethyl potassium (DPM-K) and triphenylmethyl potassium (TPM-K). Remarkably, well-defined poly(2-phenyl-5-(6-vinylpyridin-3-yl)-1,3,4-oxadiazole) (PVPyOzP) polymers having predicted molecular weights (MW) ranging from 2200 to 21 100 g/mol and polydispersity indices (PDI) ranging from 1.11 to 1.15 were prepared with TPM-K,more » without any additional additives, at –78 °C. The effect of temperature on the polymerization of PVPyOzP was also studied at –78, –45, 0, and 25 °C, and it was observed that increasing the polymerization temperature produced materials with unpredictable MW’s and broader molecular weight distributions. Furthermore, the nucleophilicity of PVPyOzP was investigated through copolymerization with methyl methacrylate and acrylonitrile, where only living poly(methyl methacrylate) (PMMA) prepared by DPM-K/VPPy and in the absence of additives such as lithium chloride (LiCl) and diethyl zinc (ZnEt2) could be used to produce the well-defined block copolymer of PMMA-b-PVPyOzP. It was also demonstrated by sequential monomer addition that the nucleophilicity of living PVPyOzP is located between that of living PMMA and polyacrylonitrile (PAN). Here, the pyridine moiety of the pendant group also allowed for quaternization and produced PQVPyOzP homopolymer using methyl iodide (CH3I) and bis(trifluoromethylsulfonyl)amide [Tf2N–]. The resulting charged polymer and counterion complexes were manipulated and investigated

  15. Catalytic conjugate additions of geminal bis(sulfone)s: expanding the chemistry of sulfones as simple alkyl anion equivalents.

    PubMed

    Landa, Aitor; Puente, Angel; Santos, J Ignacio; Vera, Silvia; Oiarbide, Mikel; Palomo, Claudio

    2009-11-01

    The value of cyclic gem-bis(sulfone) 4 as a simple alkyl nucleophile equivalent in catalytic C-C bond-forming reactions is demonstrated. The 1,4-type nucleophilic additions of bis(sulfone) 4 to alpha,beta-unsaturated ketones take place by assistance of catalytic guanidine base. On the other hand, pyrrolidines are able to catalyze the conjugate addition of 4 to both enones and enals, likely by means of iminium ion activation. Upon exploration of the best chiral pyrrolidine catalyst, it has been found that the addition of 4 to enals catalyzed by diphenylprolinol silyl ether 10 proceeds with very high enantioselectivity (beta-aryl-substituted enals >95% ee; beta-alkyl substituted enals up to 94% ee; ee = enantiomeric excess). Further reductive desulfonation of adducts gives rise to the corresponding beta-methyl aldehydes, as well as the derived alcohols, acetals, and methyl esters after simple (Mg, MeOH) well-established protocols. Application of the procedure to the synthesis of biologically relevant phenethyl building blocks is shown. Most interestingly, alpha-alkylation of initially obtained bis(sulfone) adducts can be done even with less reactive alkylating reagents, such as long linear-chain or branched-chain alkyl halides. Accordingly, upon the desulfonation process, a general, experimentally simple and highly enantioselective access to beta-branched aldehydes, alcohols, or esters is possible. Further exploration of the method includes the use of chiral alpha,beta-unsaturated aldehydes derived from citronellal as the Michael acceptor partners. In these instances, the sense of the conjugate addition of 4 is controlled by the chirality of the pyrrolidine catalyst, thus allowing for a stereochemically predictable access to 1,3-dimethyl arrays, such as those present in deoxygenated polyketide-type natural products. The intramolecular variation of this technology by using doubly unsaturated aldehyde-ester 22 illustrated the site selectivity of the procedure and its

  16. 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.

  17. Chemically modified electrodes by nucleophilic substitution of chlorosilylated platinum oxide surfaces

    NASA Astrophysics Data System (ADS)

    Chen, Chun-Hsien; Hutchison, James H.; Postlethwaite, Timothy A.; Richardson, John N.; Murray, R. W.

    1994-07-01

    Chlorosilylated platinum oxide electrode surfaces can be generated by reaction of SiCl4 vapor with an electrochemically prepared monolayer of platinum oxide. A variety of nucleophilic agents (such as alcohols, amines, thiols, and Grignard reagents) can be used to displace chloride and thereby functionalize the metal surface. Electroactive surfaces prepared with ferrocene methanol as the nucleophile show that derivatization by small molecules can achieve coverages on the order of a full monolayer. Surfaces modified with long-chain alkyl groups efficiently block electrode reactions of redox probes dissolved in the contacting solution, but other electrochemical (double layer capacitance and surface coverage) and contact angle measurements suggest that these molecule films are not highly ordered, self-assembled monolayers.

  18. 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.

  19. Interrupting Nazarov Reaction with Different Trapping Modality: Utilizing Potassium Alkynyltrifluoroborate as a σ-Nucleophile.

    PubMed

    William, Ronny; Wang, Siming; Mallick, Asadulla; Liu, Xue-Wei

    2016-09-16

    The putative oxyallyl cation intermediate generated following Nazarov cyclization of dienone has been successfully intercepted with potassium alkynyltrifluoroborates which act as σ-nucleophiles in the presence of BF3·Et2O. This new trapping modality allowed unprecedented introduction of an alkynyl moiety to the cyclopentanone framework by means of an interrupted Nazarov reaction. The α-alkynyl cyclopentanone product can be further transformed into an array of densely functionalized cyclic compounds. PMID:27603230

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Reactivity of Aziridinomitosene Derivatives Related to FK317 in the Presence of Protic Nucleophiles

    PubMed Central

    Wiedner, Susan D.; Vedejs, Edwin

    2012-01-01

    The syntheses and reactivity of N-TBDPS and N-trityl protected derivatives of an aziridinomitosene corresponding to FK317 are described. New reactivity patterns were observed for these highly sensitive and functionally dense heterocycles under mild nucleophilic conditions approaching the threshold for degradation. Thus, the silyl or trityl protected aziridinomitosene reacted with Cs2CO3/CD3OD to give isomeric products where substitution occurred at C(10) and C(9a) (mitomycin numbering) providing a CD3 ether and a CD3 hemiaminal respectively. These findings show that heterolysis at C(10) is faster than at aziridine C(1), in contrast to the behavior of typical aziridinomitosenes in the mitomycin series. The labile N-TBDPS hemiaminal and the more stable N-trityl hemiaminal resemble the mitomycin K substitution pattern. A reagent consisting of CsF in CF3CH2OH/CH3CN desilylated a simple N-TBDPS aziridine, but caused nucleophilic cleavage at C(1) as well as C(10) without cleavage of the N-TBPDS group in the fully functionalized penultimate aziridinomitosene. The high reactivity of the C(10) carbamate with nucleophiles precludes the use of deprotection methodology that requires N-protonation for fully functionalized aziridinomitosenes in the FK317 series. PMID:22208619

  6. 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

  7. Syntheses of arabinose-derived pyrrolidine catalysts and their applications in intramolecular Diels-Alder reactions.

    PubMed

    Shing, Tony K M; Wu, Kwun W; Wu, Ho T; Xiao, Qicai

    2015-02-14

    Six chiral hydroxylated pyrrolidine catalysts were synthesized from commercially available D-arabinose in seven steps. Various aromatic substituents α to the amine can be introduced readily by a Grignard reaction, which enables facile optimization of the catalyst performance. The stereoselectivities of these catalysts have been assessed by comparing with those of MacMillan's imidazolidinone in a known intramolecular Diels-Alder (IMDA) reaction of a triene. Two additional IMDA reactions of symmetrical dienals with concomitant desymmetrisation further established the potential use of these novel amine catalysts. These pyrrolidines are valuable catalysts for other synthetic transformations. PMID:25503272

  8. Copper-Catalyzed Intramolecular Benzylic C-H Amination for the Synthesis of Isoindolinones.

    PubMed

    Yamamoto, Chiaki; Takamatsu, Kazutaka; Hirano, Koji; Miura, Masahiro

    2016-09-01

    A copper-catalyzed intramolecular amination occurs at the benzylic C-H of 2-methylbenzamides to deliver the corresponding isoindolinones of great interest in medicinal chemistry. The mild and abundant MnO2 works well as a terminal oxidant, and the reaction proceeds smoothly under potentially explosive organic peroxide-free conditions. Additionally, the directing-group-dependent divergent mechanisms are proposed: 8-aminoquinoline-containing benzamides include a Cu-mediated organometallic pathway whereas an aminyl radical-promoted Hofmann-Loffler-Freytag (HLF)-type mechanism can be operative in the case of N-naphthyl-substituted substrates. PMID:27504671

  9. C-Terminally modified peptides via cleavage of the HMBA linker by O-, N- or S-nucleophiles.

    PubMed

    Hansen, J; Diness, F; Meldal, M

    2016-03-28

    A large variety of C-terminally modified peptides was obtained by nucleophilic cleavage of the ester bond in solid phase linked peptide esters of 4-hydroxymethyl benzamide (HMBA). The developed methods provided peptides, C-terminally functionalized as esters, amides and thioesters, with high purity directly from the resin in a single reaction step. A comprehensive screening of the reaction conditions and scope for nucleophilic cleavage of peptides from the HMBA linker was performed. PMID:26924021

  10. Synthesis of 3,3-disubstituted oxindoles by one-pot integrated Brønsted base-catalyzed trichloroacetimidation of 3-hydroxyoxindoles and Brønsted acid-catalyzed nucleophilic substitution reaction.

    PubMed

    Piemontesi, Cyril; Wang, Qian; Zhu, Jieping

    2013-03-01

    Treatment of 3-hydroxyoxindoles with trichloroacetonitrile (1.3 equiv.) and a catalytic amount of DBU (0.1 equiv.) followed by addition of nucleophiles (1.5 equiv.) and diphenylphosphoric acid (0.2 equiv.) afforded the 3,3-disubstituted oxindoles in good to excellent yields. DFT computations supported the notion that the reaction went through the 1-alkyl-2-oxo-2H-indol-1-ium intermediate.

  11. Regioselective intramolecular [3+2] annulation of allene-nitrones.

    PubMed

    Inagaki, Fuyuhiko; Kobayashi, Harumi; Mukai, Chisato

    2012-01-01

    The regioselective intramolecular 1,3-dipolar cycloaddition of the phenylsulfonylallene-nitrone derivatives has been developed. This reaction showed that the distal double bond of the allene exclusively reacted with the nitrone group to produce the bicyclic isoxazolidine derivatives regardless of the substitution pattern on the allenyl moiety.

  12. 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.

  13. Intramolecular radical rearrangement reactions of 2-methyleneaziridines: application to the synthesis of substituted piperidines, decahydroquinolines, and octahydroindolizines.

    PubMed

    Prévost, N; Shipman, M

    2001-07-26

    [reaction: see text] Intramolecular 5-exo cyclization of 3-(2-methyleneaziridin-1-yl)propyl radicals leads to the generation of a highly strained, bicyclic aziridinylcarbinyl radical that undergoes C-N bond fission to the ring-expanded aminyl radical. This methodology provides access to substituted 3-methylenepiperidines and, by combining it with an additional 5-exo-trig cyclization reaction, the octahydroindolizidine skeleton.

  14. Role of Intramolecular Aromatic π-π Interactions in the Self-Assembly of Di-l-Phenylalanine Dipeptide Driven by Intermolecular Interactions: Effect of Alanine Substitution.

    PubMed

    Reddy, Samala Murali Mohan; Shanmugam, Ganesh

    2016-09-19

    Although the role of intermolecular aromatic π-π interactions in the self-assembly of di-l-phenylalanine (l-Phe-l-Phe, FF), a peptide that is known for hierarchical structure, is well established, the influence of intramolecular π-π interactions on the morphology of the self-assembled structure of FF has not been studied. Herein, the role of intramolecular aromatic π-π interactions is investigated for FF and analogous alanine (Ala)-containing dipeptides, namely, l-Phe-l-Ala (FA) and l-Ala-l-Phe (AF). The results reveal that these dipeptides not only form self-assemblies, but also exhibit remarkable differences in structural morphology. The morphological differences between FF and the analogues indicate the importance of intramolecular π-π interactions, and the structural difference between FA and AF demonstrates the crucial role of the nature of intramolecular side-chain interactions (aromatic-aliphatic or aliphatic-aromatic), in addition to intermolecular interactions, in deciding the final morphology of the self-assembled structure. The current results emphasise that intramolecular aromatic π-π interaction may not be essential to induce self-assembly in smaller peptides, and π (aromatic)-alkyl or alkyl-π (aromatic) interactions may be sufficient. This work also illustrates the versatility of aromatic and a combination of aromatic and aliphatic residues in dipeptides in the formation of structurally diverse self-assembled structures.

  15. Effect of α- and β-cyclodextrins on the intramolecular charge transfer and intramolecular proton transfer fluorescence of methyl o-hydroxy p-dimethylaminobenzoate

    NASA Astrophysics Data System (ADS)

    Józefowicz, Marek

    The influence of α- and β-cyclodextrins on the spectral characteristics of methyl o-hydroxy p-dimethylaminobenzoate has been studied using steady-state and time-resolved spectroscopic technique. The stoichiometries and equilibrium constants of the solute molecule-cyclodextrin inclusion complexes have been determined by the steady-state fluorescence measurements. Nonlinear least-squares regression analysis indicates that both 1:1 and 1:2 inclusion complexes were formed between studied compound and α- and β-cyclodextrins. The contribution of the fluorophore in free, 1:1, and 1:2 complexes was calculated for a particular concentration of α- and β-CD. Additionally, the location of the fluorophore inside the cavity was reported, with regard to the intra- and intermolecular proton transfer and intramolecular charge transfer processes.

  16. 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.

  17. 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.

  18. 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.

  19. Palladium(II)-catalyzed intramolecular carboxypalladation-olefin insertion cascade: direct access to indeno[1,2-b]furan-2-ones.

    PubMed

    Vinoth, Perumal; Vivekanand, Thavaraj; Suryavanshi, Padmakar A; Menéndez, J Carlos; Sasai, Hiroaki; Sridharan, Vellaisamy

    2015-05-14

    A catalytic, atom-economical, domino 5-endo-dig cyclization-intramolecular olefin insertion sequence was developed under mild conditions. Aryl alkynoic acids bearing a tethered enone partner afforded the indeno[1,2-b]furan-2-ones, the core skeleton present in a number of biologically significant molecules including the natural product solanacol, under ligand-free, palladium-catalyzed reaction conditions in high yields. The competitive β-hydride elimination in the final step leading to the conjugated analogs was avoided by the addition of lithium bromide. A plausible mechanism for this domino sequence is proposed involving intramolecular carboxypalladation and olefin insertion steps.

  20. 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

  1. Stereoselective nucleophilic fluoromethylation of aryl ketones: dynamic kinetic resolution of chiral α-fluoro carbanions.

    PubMed

    Shen, Xiao; Miao, Wenjun; Ni, Chuanfa; Hu, Jinbo

    2014-01-13

    Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to-handle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state. Excellent stereoselective control at the fluorinated carbon chiral center was found, an effect believed to be facilitated by the dynamic kinetic resolution of the chiral α-fluoro carbanions.

  2. 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

  3. Palladium-Catalyzed Alkene Carboamination Reactions of Electron-Poor Nitrogen Nucleophiles

    PubMed Central

    Peterson, Luke J.

    2015-01-01

    Modified reaction conditions that facilitate Pd-catalyzed alkene carboamination reactions of electron-deficient nitrogen nucleophiles are reported. Pent-4-enylamine derivatives bearing N-tosyl or N-trifluoroacetyl groups are coupled with aryl triflates to afford substituted pyrrolidines in good yield. These reactions proceed via a mechanism involving anti-aminopalladation of the alkene, which differs from previously reported analogous reactions of N-aryl and N-boc pentenylamines. The application of these conditions to a formal synthesis of (±)-aphanorphine is also described. PMID:26622222

  4. Unconventional Bifunctional Lewis-Brønsted Acid Activation Mode in Bicyclic Guanidine-Catalyzed Conjugate Addition Reactions.

    PubMed

    Cho, Bokun; Wong, Ming Wah

    2015-08-18

    DFT calculations have demonstrated that the unconventional bifunctional Brønsted-Lewis acid activation mode is generally applicable to a range of nucleophilic conjugate additions catalyzed by bicyclic guanidine catalysts. It competes readily with the conventional bifunctional Brønsted acid mode of activation. The optimal pro-nucleophiles for this unconventional bifunctional activation are acidic substrates with low pKa, while the best electrophiles are flexible 1,4-diamide and 1,4-diester conjugated systems.

  5. 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

  6. 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.

  7. 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.

  8. Dendrimer light-harvesting: intramolecular electrodynamics and mechanisms.

    PubMed

    Andrews, David L; Bradshaw, David S; Jenkins, Robert D; Rodríguez, Justo

    2009-12-01

    In the development of highly efficient materials for harvesting solar energy, there is an increasing focus on purpose-built dendrimers and allied multi-chromophore systems. A proliferation of antenna chromophores is not the only factor determining the sought light-harvesting efficiency; the internal geometry and photophysics of these molecules are also crucially important. In particular, the mechanisms by means of which radiant energy is ultimately trapped depends on an intricate interplay of electronic, structural, energetic and symmetry properties. To better understand these processes a sound theoretical representation of the intramolecular electrodynamics is required. A suitable formalism, based on quantum electrodynamics, readily delivers physical insights into the necessary excitation channelling processes, and it affords a rigorous basis for modelling the intramolecular flow of energy.

  9. 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.

  10. Synthesis of Normorphans through an Efficient Intramolecular Carbamoylation of Ketones.

    PubMed

    Diaba, Faïza; Montiel, Juan A; Serban, Georgeta; Bonjoch, Josep

    2015-08-01

    An unexpected C-C bond cleavage was observed in trichloroacetamide-tethered ketones under amine treatment and exploited to develop a new synthesis of normophans from 4-amidocyclohexanones. The reaction involves an unprecedented intramolecular haloform-type reaction of trichloroacetamides promoted by enamines (generated in situ from ketones) as counter-reagents. The methodology was applied to the synthesis of compounds embodying the 6-azabicyclo[3.2.1]octane framework.

  11. Influence of receptor flexibility on intramolecular H-bonding interactions.

    PubMed

    Sun, Hongmei; Guo, Kai; Gan, Haifeng; Li, Xin; Hunter, Christopher A

    2015-08-01

    Atropisomers of a series of zinc tetraphenyl porphyrins were synthesized and used as supramolecular receptors. Rotation around the porphyrin-meso phenyl bonds is restricted by installing ortho-chlorine substituents on the phenyl groups. The chlorine substituents allowed chromatographic separation of atropisomers, which did not interconvert at room temperature. The porphyrin meso phenyl groups were also equipped with phenol groups, which led to the formation of intramolecular H-bonds when the zinc porphyrins were bound to pyridine ligands equipped with ester or amide side arms. Binding of the pyridine ligands with the conformationally locked chloroporphyrins was compared with the corresponding unsubstituted porphyrins, which are more flexible. The association constants of 150 zinc porphyrin-pyridine complexes were measured in two different solvents, toluene and 1,1,2,2-tetrachloroethane (TCE). These association constants were then used to construct 120 chemical double mutant cycles to quantify the influence of chlorine substitution on the free energy of intramolecular H-bonds formed between the phenol side arms of the porphyrins and the ester or amide side arms of the pyridine ligands. Conformational restriction leads to increases in the stability of some complexes and decreases in the stability of others with variations in the free energy contribution due to intramolecular H-bonding of -5 to +6 kJ mol(-1).

  12. Stereocontrolled intramolecular iron-mediated diene/olefin cyclocoupling

    NASA Astrophysics Data System (ADS)

    Dorange, Ismet B.

    A methodology for stereocontrol during the intramolecular coupling between cyclohexadiene-Fe(CO)3 complexes and pendant alkenes is presented. Introduction of a methoxy group at the C(3) position of the diene moiety controls pre- and post-cyclization rearrangements of the diene Fe(CO)3 unit, allowing the preparation of spirolactams with defined relative stereochemistry and with a cyclohexenone framework, thus making this reaction a potentially valuable tool for the construction of quaternary carbon centers.* A new methodology for the formation of tricarbonyl(cyclohexadienyl)ketone iron complexes was also developed. This method involves the coupling of a Grignard reagent with an acyl mesylate iron complex, giving rise to ketone derivatives in excellent yields. The possibility of intramolecular coupling between diene-Fe(CO)3 complexes and homoallylic olefin was demonstrated. The stereospecific formation of spiroketones occurred in excellent yields under thermal conditions, but appeared to be limited to the simpler, less substituted pendant alkenes. The control of the stereochemical outcome of these spirocyclization was achieved using the "C(3) substitution method" previously described. The same trends were observed in these series. Also illustrated in these studies is the extension of this spirocoupling to the formation of a spiro[5.5]undecane framework. It is the first time that this framework has been accessed using this intramolecular coupling.* *Please refer to dissertation for diagram.

  13. Intramolecular pnicogen interactions in PHF-(CH2)(n)-PHF (n=2-6) systems.

    PubMed

    Sánchez-Sanz, Goar; Alkorta, Ibon; Trujillo, Cristina; Elguero, José

    2013-06-01

    A computational study of the intramolecular pnicogen bond in PHF-(CH2)n-PHF (n=2-6) systems was carried out. For each compound, two different conformations, (R,R) and (R,S), were considered on the basis of the chirality of the phosphine groups. The characteristics of the closed conformers, in which the pnicogen interaction occurs, were compared with those of the extended conformer. In several cases, the closed conformations are more stable than the extended conformations. The calculated interaction energies of the pnicogen contact, by means of isodesmic reactions, provide values between -3.4 and -26.0 kJ mol(-1). Atoms in molecules and electron localization function analysis of the electron density showed that the systems in the closed conformations with short P···P distances have a partial covalent character in this interaction. The calculated absolute chemical shieldings of the P atoms showed an exponential relationship with the P···P distance. In addition, a search in the Cambridge crystallographic database was carried out to detect those compounds with a potential intramolecular pnicogen bond in the solid phase.

  14. Stabilization of intermediate density states in globular proteins by homogeneous intramolecular attractive interactions.

    PubMed Central

    Bahar, I; Jernigan, R L

    1994-01-01

    On-lattice simulations of two-dimensional self-avoiding chains subject to homogeneous intramolecular attractive interactions were performed as a model for studying various density regimes in globular proteins. For short chains of less than 15 units, all conformations were generated and classified by density. The range of intramolecular interactions was found to increase uniformly with density, and the average number of topological contacts is directly proportional to density. The uniform interaction energy increases the probability of high density states but does not necessarily lead to dominance of the highest density state. Typically, several large peaks appear in the probability distribution of packing densities, their location and amplitude being determined by the balance between entropic effects enhancing more expanded conformations and attractive interactions favoring compact forms. Also, the homogeneous interaction energy affects the distribution of most probable interacting points in favor of the longer range interactions over the short range ones, but in addition it introduces some more detailed preferences even among short range interactions. There are some implications about the characteristics of the intermediate density states and also for the likelihood that the native state does not correspond completely to the lowest energy conformation. Images FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 PMID:8161699

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Enantioselective Desymmetrization of Prochiral Cyclohexanones by Organocatalytic Intramolecular Michael Additions to α,β-Unsaturated Esters**

    PubMed Central

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

    2015-01-01

    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

  2. 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

  3. 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

  4. About the stereoelectronics of the intramolecular addition of allylsilanes to aldehydes.

    PubMed

    Schlosser, M; Franzini, L; Bauer, C; Leroux, F

    2001-05-01

    (Z)-omega-Trimethylsilyl-(omega-2)-alken-1-ols are readily accessible by consecutive superbase metalation and silylation of (omega-1)-alken-1-ols. These versatile intermediates may be oxidized to give the corresponding (Z)-omega-trimethylsilyl-(omega-2)-alkenals which, in the presence of trifluoroacetic acid, can be converted into 2-vinylcycloalkanols such as 2-vinylcyclohexanol (2), isopulegol (4), and bis(2-vinylcyclobutyl) ether (8). The stereochemical outcome of these cyclization reactions suggests the interference of a novel electrodynamic effect. PMID:11405469

  5. 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

  6. Pyrrolidine and piperidine formation via copper(II) carboxylate-promoted intramolecular carboamination of unactivated olefins: diastereoselectivity and mechanism.

    PubMed

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

    2007-05-11

    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 gamma- and delta-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.

  7. Application to processing system using intra-molecular BRET

    NASA Astrophysics Data System (ADS)

    Otsuji, Tomomi; Okuda-Ashitaka, Emiko; Kojima, Satoshi; Akiyama, Hidehumi; Ito, Seiji; Ohmiya, Yoshihiro

    2003-07-01

    Luciferases are used as the reporter gene for promoter activity, whereas a green fluorescent protein (GFP) is used as marker for cellular function and localization. Recently, bioluminescence resonance energy transfer (BRET) between luciferase and YFP is used for analysis of inter-molecular reaction such as ligand-receptor in the living cells. The neuropeptides nocistatin (NST) and nociceptin/orphanin FQ (Noc/OFQ) are derived from the same precursor protein, while NST exhibits antagonism against Noc/OFQ-actions. In this study, we attempt an intra-molecular BRET system for monitoring dynamic biological process of the production of NST and Noc/OFQ in the living cells. At first, we constructed a fusion protein (Rluc-GFP) covalently linking luciferase (Renilla luciferase; Rluc) to Aequorea GFP as an intra-molecular BRET partner. Furthermore, we inserted constructs of mouse NST and Noc/OFQ (Rluc-m-GFP) or bovine NST and Noc/OFQ (Rluc-b-GFP) containing a proteolytic cleavage motif (Lys-Arg) within Rluc-GFP. When these constructions were transfected into Cos7 cells, all fusion proteins had luciferase activity and specific fluorescence. Luminescence spectra of Rluc-GFP, Rluc-m-GFP and Rluc-b-GFP fusion proteins with DeepBlueC as a substrate showed two peaks centered at 400 nm and 510 nm, whereas Rluc showed one peak centered at 400 nm. These results indicate that the proteolytic cleavage motif inserted fusion proteins between luciferase and GFP are available for intra-molecular BRET systems at first step.

  8. Intramolecular and dissociation dynamics of the CF2Br radical

    NASA Astrophysics Data System (ADS)

    Bintz, Karen L.; Thompson, Donald L.; Gosnell, T. R.; Hay, P. Jeffrey

    1992-11-01

    Classical trajectory methods were used to investigate the nature of the intramolecular dynamics (quasiperiodic vs chaotic) of the CF2Br radical. The potential energy surface is based on empirical and ab initio results. Power spectra show that the Br-C-F bend exhibits quasiperiodic dynamics while the other modes are chaotic. Despite the presence of quasiperiodic dynamics, the dissociation rates for mode-specific excitations of the normal modes are essentially the same as those for equipartitioning of the excitation energy among all the normal modes.

  9. Recording Intramolecular Mechanics during the Manipulation of a Large Molecule

    NASA Astrophysics Data System (ADS)

    Moresco, Francesca; Meyer, Gerhard; Rieder, Karl-Heinz; Tang, Hao; Gourdon, André; Joachim, Christian

    2001-08-01

    The technique of single atom manipulation by means of the scanning tunneling microscope (STM) applies to the controlled displacement of large molecules. By a combined experimental and theoretical work, we show that in a constant height mode of manipulation the STM current intensity carries detailed information on the internal mechanics of the molecule when guided by the STM tip. Controlling and time following the intramolecular behavior of a large molecule on a surface is the first step towards the design of molecular tunnel-wired nanorobots.

  10. Recording intramolecular mechanics during the manipulation of a large molecule.

    PubMed

    Moresco, F; Meyer, G; Rieder, K H; Tang, H; Gourdon, A; Joachim, C

    2001-08-20

    The technique of single atom manipulation by means of the scanning tunneling microscope (STM) applies to the controlled displacement of large molecules. By a combined experimental and theoretical work, we show that in a constant height mode of manipulation the STM current intensity carries detailed information on the internal mechanics of the molecule when guided by the STM tip. Controlling and time following the intramolecular behavior of a large molecule on a surface is the first step towards the design of molecular tunnel-wired nanorobots.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Identification of glutamic acid 78 as the active site nucleophile in Bacillus subtilis xylanase using electrospray tandem mass spectrometry.

    PubMed

    Miao, S; Ziser, L; Aebersold, R; Withers, S G

    1994-06-14

    A new mechanism-based inactivator of beta-1,4-xylanases, 2',4'-dinitrophenyl 2-deoxy-2-fluoro-beta-xylobioside, has been synthesized and used to trap the covalent intermediate formed during catalysis by Bacillus subtilis xylanase. Electrospray mass spectrometry confirmed the 1:1 stoichiometry of the incorporation of inactivator into the enzyme. Inactivation of xylanase followed the expected pseudo-first-order kinetic behavior, and kinetic parameters were determined. The intermediate trapped was relatively stable toward hydrolytic turnover (t1/2 = 350 min). However, turnover could be facilitated by transglycosylation following the addition of the acceptor benzyl thio-beta-xylobioside, thus demonstrating the catalytic competence of the trapped intermediate. Reactivation kinetic parameters for this process of kre = 0.03 min-1 and Kre = 46 mM were determined. The nucleophilic amino acid was identified as Glu78 by a tandem mass spectrometric technique which does not require the use of radiolabels. The peptic digest of the labeled enzyme was separated by high-performance liquid chromatography and the eluent fed into a tandem mass spectrometer via an electrospray ionization device. The labeled peptide was identified as one of m/z = 826 (doubly charged) which fragmented in the collision chamber between the mass analyzers with loss of the mass of a 2-fluoroxylobiosyl unit. Confirmation of the peptide identity was obtained both by tandem mass spectrometric sequencing and by Edman degradation of the purified peptide. Glu78 is completely conserved in all members of this xylanase family and indeed is shown to be located in the active site in the recently determined X-ray crystal structure.

  1. 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

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

    PubMed

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

    2015-01-01

    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.

  3. 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.

  4. Organic Chemistry Students' Fragmented Ideas about the Structure and Function of Nucleophiles and Electrophiles: A Concept Map Analysis

    ERIC Educational Resources Information Center

    Anzovino, Mary E.; Bretz, Stacey Lowery

    2016-01-01

    Organic chemistry students struggle with multiple aspects of reaction mechanisms and the curved arrow notation used by organic chemists. Many faculty believe that an understanding of nucleophiles and electrophiles, among other concepts, is required before students can develop fluency with the electronpushing formalism (EPF). An expert concept map…

  5. 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

  6. 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

  7. From α-nucleophiles to functionalized aggregates: exploring the reactivity of hydroxamate ion towards esterolytic reactions in micelles.

    PubMed

    Singh, Namrata; Karpichev, Yevgen; Sharma, Rahul; Gupta, Bhanushree; Sahu, Arvind K; Satnami, Manmohan L; Ghosh, Kallol K

    2015-03-14

    Owing to the rising threats of neurotoxic organophosphosphorus compounds, facile and efficient decontamination systems are required. Since the last few decades, the search for promising α-nucleophiles for straightforward and eco-friendly decontamination reactions using α-nucleophiles has been considerably boosted up. Among these, hydroxamic acids have been widely studied due to their potential α-nucleophilicity towards carbon and phosphorus based esters. This account summarizes our research on α-nucleophilicity of hydroxamate ions in water and micelles towards esterolytic reactions. Efforts of our group in the last few years have been collectively judged and compared with the crucial findings of researchers in the relevant field. The present article sheds light on the rich chemistry of the hydroxamate ion as a perfect candidate to degrade organophosphorus esters (i.e. nerve agents, pesticides and their simulants) in water, in micelles of conventional surfactants, and in functionalized micelles. The current report also provides an insight into the possible nature and mechanisms of these reactions. A brief account of the biological activities of hydroxamic acids that have recently spurred research in medicine against some fatal diseases has been included.

  8. Direct sp(3)C-H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis.

    PubMed

    Feng, Zhu-Jia; Xuan, Jun; Xia, Xu-Dong; Ding, Wei; Guo, Wei; Chen, Jia-Rong; Zou, You-Quan; Lu, Liang-Qiu; Xiao, Wen-Jing

    2014-04-01

    Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp(3) C-H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50-91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).

  9. 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.

  10. Intramolecular carbon isotope distribution of acetic acid in vinegar.

    PubMed

    Hattori, Ryota; Yamada, Keita; Kikuchi, Makiko; Hirano, Satoshi; Yoshida, Naohiro

    2011-09-14

    Compound-specific carbon isotope analysis of acetic acid is useful for origin discrimination and quality control of vinegar. Intramolecular carbon isotope distributions, which are each carbon isotope ratios of the methyl and carboxyl carbons in the acetic acid molecule, may be required to obtain more detailed information to discriminate such origin. In this study, improved gas chromatography-pyrolysis-gas chromatography-combustion-isotope ratio mass spectrometry (GC-Py-GC-C-IRMS) combined with headspace solid-phase microextraction (HS-SPME) was used to measure the intramolecular carbon isotope distributions of acetic acid in 14 Japanese vinegars. The results demonstrated that the methyl carbons of acetic acid molecules in vinegars produced from plants were mostly isotopically depleted in (13)C relative to the carboxyl carbon. Moreover, isotopic differences (δ(13)C(carboxyl) - δ(13)C(methyl)) had a wide range from -0.3 to 18.2‰, and these values differed among botanical origins, C3, C4, and CAM plants.

  11. Intramolecular motion in DIET: Desorption and dissociation of chemisorbed ammonia

    NASA Astrophysics Data System (ADS)

    Burns, A. R.; Stechel, E. B.; Jennison, D. R.

    1995-06-01

    We show that quantum-specific detection of DIET processes of polyatomic adsorbates reveals the multidimensional dynamics of intramolecular motion. Specifically, we present an analysis of the 6-350 eV electron-induced desorption and dissociation of chemisorbed NH 3 and ND 3 on Pt(1 1 1). State-selective detection of the neutral DIET products is accomplished by 2 + 1 resonance-enhanced multiphoton ionization (REMPI). Desorption and dissociation occur as a result of distinct electronic excitations that result in different, uncoupled, modes of intramolecular motion. We find that desorption results from 3a 1-1-induced inversion motion. Trajectories on a two-dimensional potential energy surface reveal that the excited molecule fully inverts; upon deexcitation, the inverted molecule is sufficiently high on the hard wall of the substrate interaction to have enough energy to desorb. Given the short excitation lifetime, the time scale in which the (H) D atoms reach the inversion geometry directly affects the desorption yield and results in an appreciable enhancement of NH 3 desorption over that of ND 3. In general, multidimensional molecule-surface potential energy surfaces should be considered in DIET processes involving molecular adsorbates.

  12. Modulating intramolecular P···N pnictogen interactions.

    PubMed

    Sánchez-Sanz, Goar; Trujillo, Cristina; Alkorta, Ibon; Elguero, José

    2016-04-01

    A computational study of the intramolecular pnictogen bond in 8-phosphinonaphthalen-1-amine derivatives (1-NX2, 8-PX2 with X = H, F, Cl, Br, CH3, CN and NC), proton sponge analogues, has been carried out to determine their structural and geometric parameters, interaction energies and electronic properties such as the electron density of the intramolecular interaction. Our results show that substitution of H atoms in the PH2 group by electron withdrawing groups on the Lewis acid moiety strengthens the P···N pnictogen bond, evidenced by the increasing electron density values at the bond critical point and by shorter distances. However, substitutions on the Lewis base moiety (NX2) show weaker P···N interactions than when the substitution is done on the Lewis acid counterpart (PX2). Nevertheless, in all cases, pnictogen bonds are enhanced upon substitution with respect to the parent 1-NH2, 8-PH2 system. Second-order orbital interaction energies, electron density maps, electron delocalization functions and charge transfer corroborate the evolution of the P···N strength upon substitution. PMID:26972057

  13. 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.

  14. 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.

  15. CMPO-calix[4]arenes with spacer containing intramolecular hydrogen bonding: effect of local rigidification on solvent extraction toward f-block elements.

    PubMed

    Chu, Hongzhu; He, Lutao; Jiang, Qian; Fang, Yuyu; Jia, Yiming; Yuan, Xiangyang; Zou, Shuliang; Li, Xianghui; Feng, Wen; Yang, Yuanyou; Liu, Ning; Luo, Shunzhong; Yang, Yanqiu; Yang, Liang; Yuan, Lihua

    2014-01-15

    To understand intramolecular hydrogen bonding in effecting liquid-liquid extraction behavior of CMPO-calixarenes, three CMPO-modified calix[4]arenes (CMPO-CA) 5a-5c with hydrogen-bonded spacer were designed and synthesized. The impact of spacer rotation that is hindered by introduction of intramolecular hydrogen bonding upon extraction of La(3+), Eu(3+), Yb(3+), Th(4+), and UO2(2+) has been examined. The results show that 5b and 5c containing only one hydrogen bond with a less hindered rotation spacer extract La(3+) more efficiently than 5a containing two hydrogen bonds with a more hindered rotation spacer, demonstrating the importance of local rigidification of spacer in the design of extractants in influencing the coordination environment. The large difference in extractability between La(3+) and Yb(3+) (or Eu(3+)) by 5b (or 5c), and the small difference by 5a, suggests intramolecular hydrogen bonding do exert pronounced influence upon selective extraction of light and heavy lanthanides. Log-log plot analysis indicates a 1:1, 2:1 and 1:1 stoichiometry (ligand/metal) for the extracted complex formed between 5b and La(3+), Th(4+), UO2(2+), respectively. Additionally, their corresponding acyclic analogs 7a-7c exhibit negligible extraction toward these metal ions. These results reveal the possibility of selective extraction via tuning local chelating surroundings of CMPO-CA by aid of intramolecular hydrogen bonding.

  16. Excited-state intramolecular hydrogen bonding of compounds based on 2-(2-hydroxyphenyl)-1,3-benzoxazole in solution: a TDDFT study.

    PubMed

    Li, Hui; Liu, Yufang; Yang, Yonggang; Yang, Dapeng; Sun, Jinfeng

    2014-12-10

    The excited-state properties of intramolecular hydrogen bonding in the compounds based on 2-(2-hydroxyphenyl)-1,3-benzoxazole (6 and its tautomers 6a and 6b) have been investigated using theoretical methods. According to the geometric optimization and IR spectra in the ground and excited states calculated by density functional theory (DFT) and time-dependent DFT (TD-DFT) methods respectively, the type of intramolecular hydrogen bonding N⋯HO in 6 and 6a is demonstrated to be significantly strengthened, while NH⋯O in the tautomers 6a and 6b are proved to be sharply weakened upon excitation to excited state S1. The calculated absorption peaks of 6 are in good accordance with the experimental results. Moreover, other compounds based on 6 that R1 and R2 are both substituted as well as that only R1 is substituted are investigated to understand the effect of substituent on intramolecular hydrogen bonding. It is found that the hydrogen bond strength can be controlled by the inductive field effect of the substituent. In addition, the intramolecular charge transfers (ICT) of the S1 state for 6 and its tautomers 6a and 6b were theoretically investigated by analyses of molecular orbital.

  17. Laurdan solvatochromism: solvent dielectric relaxation and intramolecular excited-state reaction.

    PubMed Central

    Viard, M; Gallay, J; Vincent, M; Meyer, O; Robert, B; Paternostre, M

    1997-01-01

    Absorption, steady-state, and time-resolved fluorescence measurements have been performed on laurdan dissolved either in white viscous apolar solvents or in ethanol as a function of temperature. The heterogeneity of the absorption spectra in white oils or in ethanol is consistent with semiempirical calculations performed previously on Prodan. From steady-state and time-resolved fluorescence measurements in apolar media, an excited state reaction is evidenced. The bimodal lifetime distribution determined from the maximum entropy method (MEM) analysis is attributed to the radiative deexcitation of a "locally excited" (LE) state and of a "charge transfer" (CT) state, whereas a very short component (20 ps), the sign and the amplitude of which depend on the emission wavelength, is attributed to the kinetics of the interconvertion reaction. The observation of an isoemissive point in the temperature range from -50 degrees C to -110 degrees C in ethanol suggests an interconvertion between two average excited-state populations: unrelaxed and solvent-relaxed CT states. A further decrease in temperature (-190 degrees C), leading to frozen ethanol, induces an additional and important blue shift. This low temperature spectrum is partly attributed to the radiative deexcitation of the LE state. Time-resolved emission spectra (TRES) measurements at -80 degrees C in the ethanol liquid phase show a large spectral shift of approximately 2500 cm(-1) (stabilization energy of the excited state: 7.1 kcal x M(-1)). The time-dependent fluorescence shift (TDFS) is described for its major part by a nanosecond time constant. The initial part of the spectral shift reveals, however, a subnanosecond process that can be due to fast internal solvent reorientation and/or to intramolecular excited-state reactions. These two relaxation times are also detected in the analysis of the fluorescence decays in the middle range of emission energy. The activation energy of the longest process is

  18. Studies on Lewis acid-mediated intramolecular cyclization reactions of allene-ene systems.

    PubMed

    Hiroi, K; Watanabe, T; Tsukui, A

    2000-03-01

    The Lewis acid-mediated reactions of allene-ene compounds, derived from 3-methylcitronellal or dimethyl malonate, were carried out using various Lewis acids such as ethylaluminum dichloride, diethylaluminum chloride, titanium chloride, zinc chloride etherate, or boron trifluoride etherate, affording unexpectedly intramolecular [2+2]cycloaddition products under some particular reaction conditions without any formation of intramolecular ene reaction products.

  19. 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

  20. 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

  1. A study of intramolecular H-complexes of novel bis(heptamethine cyanine) dyes.

    PubMed

    Kim, Jun Seok; Kodagahally, Ravikumar; Strekowski, Lucjan; Patonay, Gabor

    2005-10-31

    Near-infrared (NIR) bis(heptamethine cyanine) (BHmC) dyes containing a flexible polymethylene linker between the two cyanine subunits are a novel class of compounds with versatile spectroscopic properties. The first bis-cyanine of this type is BHmC-10 (with a decamethylene bridge) that has been reported by us recently [G. Patonay, J.S. Kim, R. Kodagahally, L. Strekowski, Appl. Spectrosc., in press]. As part of this work, additional bis-cyanines BHmC-4, BHmC-6, and BHmC-8 were synthesized and their spectral properties were evaluated for the dyes free in solution and in the presence of human serum albumin (HSA). These bis-cyanines undergo H-type aggregation, mainly H-type intramolecular complexation between the two cyanine subunits, when free in aqueous solution. This H-type interaction in phosphate buffer (pH 7.2) is characterized by hypsochromic (H) absorption at 700nm, low extinction coefficient, and low fluorescence quantum yield. By contrast, an analogous monomeric cyanine exhibits strong fluorescence under similar conditions. Upon binding with HSA, the fluorescence of BHmC-6 changes negligibly, that for BHmC-8 shows a slight increase, and the fluorescence of BHmC-4 is greatly increased. It is suggested that BHmC-4 binds with HSA in the open form exclusively, while the H-type intramolecular interaction in BHmC-6 is mostly retained in the complex with HSA. Bis-cyanine BHmC-4 may be of significant bioanalytical utility due to its negligible fluorescence in aqueous solution and a strong increase in fluorescence upon binding with a protein.

  2. 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

  3. Rapid intramolecular turnover of N-linked glycans in plasma membrane glycoproteins. Extension of intramolecular turnover to the core sugars in plasma membrane glycoproteins of hepatoma.

    PubMed

    Tauber, R; Park, C S; Becker, A; Geyer, R; Reutter, W

    1989-12-01

    Plasma membrane glycoproteins of rat hepatocytes undergo a rapid terminal deglycosylation in that the terminal sugars of the oligosaccharide side chains are rapidly removed from the otherwise intact glycoproteins [Tauber, R., Park, C.S. & Reutter, W. (1983) Proc. Natl Acad. Sci. USA 80, 4026-4029]. The present paper demonstrates that this rapid intramolecular turnover of plasma membrane glycoproteins is not restricted to peripheral sugars but, in contrast to liver, in hepatoma the core sugars of the oligosaccharide chains are also involved. Intramolecular turnover was measured in Morris hepatoma 7777 in five plasma membrane glycoproteins with Mr of 85,000 (hgp85), 105,000 (hgp105), 115,000 (hgp115), 125,000 (hgp125), 175,000 (hgp175) (hgp = hepatoma glycoprotein) that were isolated and purified to homogeneity by concanavalin-A--Sepharose affinity chromatography and semipreparative SDS gel electrophoresis. Analysis of the carbohydrates of hgp85, hgp105, hgp115 and hgp125 revealed the presence of N-linked oligosaccharides containing L-fucose, D-galactose, D-mannose and N-acetyl-D-glucosamine, but only of trace amounts of N-acetyl-D-galactosamine; hgp175 additionally contained significant amounts of N-acetyl-D-galactosamine, indicating the presence of both N- and O-linked oligosaccharides. As shown by digestion with endoglucosaminidase H, the N-linked oligosaccharides of hgp105, hgp115, hgp125 and hgp175 were of the complex type, whereas hgp85 also contained oligosaccharides of the high-mannose type. Half-lives of the turnover of the oligosacharide chains and of the protein backbone of the five glycoproteins were measured in the plasma membrane in pulse-chase experiments in vivo, using L-[3H]fucose as a marker of terminal sugars, D-[3H]mannose as marker of a core sugar and L-[3H]leucine for labelling the protein backbone. Protein backbones of the five glycoproteins were degraded with individual half-lives ranging over 41-90 h with a mean of 66 h. Compared to the

  4. Intramolecular charge transfer effects on 4-hydroxy-3-methoxybenzaldehyde

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Balasubramanian, T.

    2008-03-01

    The absorption and fluorescence spectral characteristics of 4-hydroxy-3-methoxybenzaldehyde (HMB) have been studied in different solvents, pH and β-cyclodextrin (β-CD) and compared with 4-hydroxy-3,5-dimethoxybenzaldehyde (HDMB). The inclusion complex of HMB with β-CD is analysed by UV-vis, fluorimetry, FT-IR, 1H NMR, SEM and AM1 methods. In HMB, the normal emission (B band) is originates from a locally excited state and the longer emission (A band) is due to intramolecular charge transfer state (ICT). The OH group of HMB is present in the interior part of the β-CD cavity and aldehyde group present in the upper part of the β-CD cavity.

  5. 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.

  6. Intramolecular hydrophobic interactions are critical mediators of STAT5 dimerization

    PubMed Central

    Fahrenkamp, Dirk; Li, Jinyu; Ernst, Sabrina; Schmitz-Van de Leur, Hildegard; Chatain, Nicolas; Küster, Andrea; Koschmieder, Steffen; Lüscher, Bernhard; Rossetti, Giulia; Müller-Newen, Gerhard

    2016-01-01

    STAT5 is an essential transcription factor in hematopoiesis, which is activated through tyrosine phosphorylation in response to cytokine stimulation. Constitutive activation of STAT5 is a hallmark of myeloid and lymphoblastic leukemia. Using homology modeling and molecular dynamics simulations, a model of the STAT5 phosphotyrosine-SH2 domain interface was generated providing first structural information on the activated STAT5 dimer including a sequence, for which no structural information is available for any of the STAT proteins. We identified a novel intramolecular interaction mediated through F706, adjacent to the phosphotyrosine motif, and a unique hydrophobic interface on the surface of the SH2 domain. Analysis of corresponding STAT5 mutants revealed that this interaction is dispensable for Epo receptor-mediated phosphorylation of STAT5 but essential for dimer formation and subsequent nuclear accumulation. Moreover, the herein presented model clarifies molecular mechanisms of recently discovered leukemic STAT5 mutants and will help to guide future drug development. PMID:27752093

  7. Easy access to modified cyclodextrins by an intramolecular radical approach.

    PubMed

    Alvarez-Dorta, Dimitri; León, Elisa I; Kennedy, Alan R; Martín, Angeles; Pérez-Martín, Inés; Suárez, Ernesto

    2015-03-16

    A simple method to modify the primary face of cyclodextrins (CDs) is described. The 6(I)-O-yl radical of α-, β-, and γ-CDs regioselectively abstracts the H5(II), located in the adjacent D-glucose unit, by an intramolecular 1,8-hydrogen-atom-transfer reaction through a geometrically restricted nine-membered transition state to give a stable 1,3,5-trioxocane ring. The reaction has been extended to the 1,4-diols of α- and β-CD to give the corresponding bis(trioxocane)s. The C2-symmetric bis(trioxocane) corresponding to the α-CD is a stable crystalline solid whose structure was confirmed by X-ray diffraction analysis. The calculated geometric parameters confirm that the primary face is severely distorted toward a narrower elliptical shape for this rim.

  8. Intramolecular transposition by a synthetic IS50 (Tn5) derivative

    SciTech Connect

    Tomcsanyi, T.; Phadnis, S.H.; Berg, D.E. ); Berg, C.M. )

    1990-11-01

    We report the formation of deletions and inversions by intramolecular transposition of Tn5-derived mobile elements. The synthetic transposons used contained the IS50 O and I end segments and the transposase gene, a contraselectable gene encoding sucrose sensitivity (sacB), antibiotic resistance genes, and a plasmid replication origin. Both deletions and inversions were associated with loss of a 300-bp segment that is designated the vector because it is outside of the transposon. Deletions were severalfold more frequent than inversions, perhaps reflecting constraints on DNA twisting or abortive transposition. Restriction and DNA sequence analyses showed that both types of rearrangements extended from one transposon end to many different sites in target DNA. In the case of inversions, transposition generated 9-bp direct repeats of target sequences.

  9. 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.

  10. 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

  11. 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

  12. Deep evolutionary conservation of an intramolecular protein kinase activation mechanism.

    PubMed

    Han, Jingfen; Miranda-Saavedra, Diego; Luebbering, Nathan; Singh, Aman; Sibbet, Gary; Ferguson, Michael A J; Cleghon, Vaughn

    2012-01-01

    DYRK-family kinases employ an intramolecular mechanism to autophosphorylate a critical tyrosine residue in the activation loop. Once phosphorylated, DYRKs lose tyrosine kinase activity and function as serine/threonine kinases. DYRKs have been characterized in organisms from yeast to human; however, all entities belong to the Unikont supergroup, only one of five eukaryotic supergroups. To assess the evolutionary age and conservation of the DYRK intramolecular kinase-activation mechanism, we surveyed 21 genomes representing four of the five eukaryotic supergroups for the presence of DYRKs. We also analyzed the activation mechanism of the sole DYRK (class 2 DYRK) present in Trypanosoma brucei (TbDYRK2), a member of the excavate supergroup and separated from Drosophila by ∼850 million years. Bioinformatics showed the DYRKs clustering into five known subfamilies, class 1, class 2, Yaks, HIPKs and Prp4s. Only class 2 DYRKs were present in all four supergroups. These diverse class 2 DYRKs also exhibited conservation of N-terminal NAPA regions located outside of the kinase domain, and were shown to have an essential role in activation loop autophosphorylation of Drosophila DmDYRK2. Class 2 TbDYRK2 required the activation loop tyrosine conserved in other DYRKs, the NAPA regions were critical for this autophosphorylation event, and the NAPA-regions of Trypanosoma and human DYRK2 complemented autophosphorylation by the kinase domain of DmDYRK2 in trans. Finally, sequential deletion analysis was used to further define the minimal region required for trans-complementation. Our analysis provides strong evidence that class 2 DYRKs were present in the primordial or root eukaryote, and suggest this subgroup may be the oldest, founding member of the DYRK family. The conservation of activation loop autophosphorylation demonstrates that kinase self-activation mechanisms are also primitive.

  13. 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

  14. Harnessing reversible oxidative addition: application of diiodinated aromatic compounds in the carboiodination process.

    PubMed

    Petrone, David A; Lischka, Matthias; Lautens, Mark

    2013-09-27

    An I for an I: Conditions for the intramolecular carboiodination and the simultaneous convergent intramolecular carboiodination/intermolecular Heck reaction of various diiodoarenes were developed. The ability of the Pd(0)/QPhos catalyst/ligand combination to undergo reversible oxidative addition allows these reactions to proceed well, thus increasing both the appeal and utility of this class of substrates in site-selective cross-coupling reactions.

  15. 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

  16. 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

  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. Understanding the nucleophilic character and stability of the carbanions and alkoxides of 1-(9-anthryl)ethanol and derivatives.

    PubMed

    Ramírez, Ramsés E; García-Martínez, Cirilo; Méndez, Francisco

    2013-08-22

    The nucleophilic character and stability of the carbanions vs. alkoxides derived from 2,2,2-trifluoro-1-(9-anthryl)ethanol and 1-(9-anthryl)ethanol containing X electron-releasing and X electron-acceptor substituents attached to C-10, have been studied at the B3LYP/6-31+G(d,p) level of theory. Results analyzed in terms of the absolute gas-phase acidity, Fukui function, the local hard and soft acids and bases principle, and the molecular electrostatic potential, show that the central ring of the 9-anthryl group confers an ambident nucleophilic character and stabilizes the conjugated carbanion by electron-acceptor delocalization.

  19. Lipase and esterase-catalyzed acylation of hetero-substituted nitrogen nucleophiles in water and organic solvents.

    PubMed

    Hacking, M A; Akkus, H; van Rantwijk, F; Sheldon, R A

    2000-04-01

    The lipase- and esterase-catalyzed acylations of hydroxylamine and hydrazine derivatives with octanoic acid and ethyl octanoate are described. The influence of solvent and nucleophile on the initial reaction rate was investigated for a number of free and immobilized enzymes. Initial rates were highest in water, but the overall productivity was optimal in dioxane. Octanoic acid (250 g/L) was converted for 93% into the hydroxamic acid in 36 h with only 1% (w/w) Candida antarctica lipase B (Novozym 435) in dioxane at 40 degrees C. This translates to a catalyst productivity of 68.5 g. g(-1). day(-1) and a space time yield of 149 g. L(-1). day(-1), unprecedented figures in the direct reaction of an acid with a nitrogen nucleophile in an organic solvent.

  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.

  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. Intramolecular OH···FC hydrogen bonding in fluorinated carbohydrates: CHF is a better hydrogen bond acceptor than CF2.

    PubMed

    Giuffredi, Guy T; Gouverneur, Véronique; Bernet, Bruno

    2013-09-27

    An intramolecular bifurcated H-bond from the axial HO-2 group to the axial F-4 atom and to the O5 atom of α-D-hexopyranosides in apolar solvents is evidenced in (1)H NMR spectra. The H-accepting properties of the F atom are modulated by the orientation of the O-substituent at the C3 atom and by an additional F atom at the C4 atom.

  3. 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.

  4. 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

  5. Understanding the participation of quadricyclane as nucleophile in polar [2sigma + 2sigma + 2pi] cycloadditions toward electrophilic pi molecules.

    PubMed

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

    2008-11-21

    The formal [2sigma + 2sigma + 2pi] cycloaddition of quadricyclane, 1, with dimethyl azodicarboxylate, 2, in water has been studied using DFT methods at the B3LYP/6-31G** and MPWB1K/6-31G** levels. In the gas phase, the reaction of 1 with 2 has a two-stage mechanism with a large polar character and an activation barrier of 23.2 kcal/mol. Inclusion of water through a combined discrete-continuum model changes the mechanism to a two-step model where the first nucleophilic attack of 1 to 2 is the rate-limiting step with an activation barrier of 14.7 kcal/mol. Analysis of the electronic structure of the transition state structures points out the large zwitterionic character of these species. A DFT analysis of the global electrophilicity and nucleophilicity of the reagents provides a sound explanation about the participation of 1 as a nucleophile in these cycloadditions. This behavior is reinforced by a further study of the reaction of 1 with 1,1-dicyanoethylene.

  6. Solvent-controlled intramolecular [2 + 2] photocycloadditions of alpha-substituted enones.

    PubMed

    Ng, Stephanie M; Bader, Scott J; Snapper, Marc L

    2006-06-01

    The regio- and stereoselectivity of intramolecular [2 + 2] photocycloadditions of 2'-hydroxyenones are shown to be solvent-dependent. In the presence of aprotic solvents, 2'-hydroxyenones undergo photocycloadditions in a manner consistent with the presence of an intramolecular hydrogen bond between the carbonyl group and the tether's hydroxy functionality. In protic solvents, intermolecular interactions appear to disrupt the intramolecular hydrogen bond, providing products with complementary diastereoselectivity. If the facial accessibility of the alpha-tethered olefin is limited, the cycloadditions proceed to give head-to-tail or head-to-head regioisomers, depending on the nature of the solvent employed.

  7. Revising Intramolecular Photoinduced Electron Transfer (PET) from First-Principles.

    PubMed

    Escudero, Daniel

    2016-09-20

    Photoinduced electron transfer (PET) plays relevant roles in many areas of chemistry, including charge separation processes in photovoltaics, natural and artificial photosynthesis, and photoluminescence sensors and switches. As in many other photochemical scenarios, the structural and energetic factors play relevant roles in determining the rates and efficiencies of PET and its competitive photodeactivation processes. Particularly, in the field of fluorescent sensors and switches, intramolecular PET is believed (in many cases without compelling experimental proof) to be responsible of the quench of fluorescence. There is an increasing experimental interest in fluorophore's molecular design and on achieving optimal excitation/emission spectra, excitation coefficients, and fluorescence quantum yields (importantly for bioimaging purposes), but less efforts are devoted to fundamental mechanistic studies. In this Account, I revise the origins of the fluorescence quenching in some of these systems with state-of-the-art quantum chemical tools. These studies go beyond the common strategy of analyzing frontier orbital energy diagrams and performing PET thermodynamics calculations. Instead, the potential energy surfaces (PESs) of the lowest-lying excited states are explored with time-dependent density functional theory (TD-DFT) and complete active space self-consistent field (CASSCF) calculations and the radiative and nonradiative decay rates from the involved excited states are computed from first-principles using a thermal vibration correlation function formalism. With such a strategy, this work reveals the real origins of the fluorescence quenching, herein entitled as dark-state quenching. Dark states (those that do not absorb or emit light) are often elusive to experiments and thus, computational investigations can provide novel insights into the actual photodeactivation mechanisms. The success of the dark-state quenching mechanism is demonstrated for a wide variety of

  8. 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.}

  9. Revising Intramolecular Photoinduced Electron Transfer (PET) from First-Principles.

    PubMed

    Escudero, Daniel

    2016-09-20

    Photoinduced electron transfer (PET) plays relevant roles in many areas of chemistry, including charge separation processes in photovoltaics, natural and artificial photosynthesis, and photoluminescence sensors and switches. As in many other photochemical scenarios, the structural and energetic factors play relevant roles in determining the rates and efficiencies of PET and its competitive photodeactivation processes. Particularly, in the field of fluorescent sensors and switches, intramolecular PET is believed (in many cases without compelling experimental proof) to be responsible of the quench of fluorescence. There is an increasing experimental interest in fluorophore's molecular design and on achieving optimal excitation/emission spectra, excitation coefficients, and fluorescence quantum yields (importantly for bioimaging purposes), but less efforts are devoted to fundamental mechanistic studies. In this Account, I revise the origins of the fluorescence quenching in some of these systems with state-of-the-art quantum chemical tools. These studies go beyond the common strategy of analyzing frontier orbital energy diagrams and performing PET thermodynamics calculations. Instead, the potential energy surfaces (PESs) of the lowest-lying excited states are explored with time-dependent density functional theory (TD-DFT) and complete active space self-consistent field (CASSCF) calculations and the radiative and nonradiative decay rates from the involved excited states are computed from first-principles using a thermal vibration correlation function formalism. With such a strategy, this work reveals the real origins of the fluorescence quenching, herein entitled as dark-state quenching. Dark states (those that do not absorb or emit light) are often elusive to experiments and thus, computational investigations can provide novel insights into the actual photodeactivation mechanisms. The success of the dark-state quenching mechanism is demonstrated for a wide variety of

  10. Metal-ligand cooperation in catalytic intramolecular hydroamination: a computational study of iridium-pyrazolato cooperative activation of aminoalkenes.

    PubMed

    Tobisch, Sven

    2012-06-01

    The present study comprehensively explores diverse mechanistic pathways for intramolecular hydroamination of prototype 2,2-dimethyl-4-penten-1-amine by Cp*Ir chloropyrazole (1; Cp*=pentamethylcyclopentadienyl) in the presence of KOtBu base with the aid of density functional theory (DFT) calculations. The most accessible mechanistic pathway for catalytic turnover commences from Cp*Ir pyrazolato (Pz) substrate adduct 2⋅S, representing the catalytically competent compound and proceeds via initial electrophilic activation of the olefin C=C bond by the metal centre. It entails 1) facile and reversible anti nucleophilic amine attack on the iridium-olefin linkage; 2) Ir-C bond protonolysis via stepwise transfer of the ammonium N-H proton at the zwitterionic [Cp*IrPz-alkyl] intermediate onto the metal that is linked to turnover-limiting, reductive, cycloamine elimination commencing from a high-energy, metastable [Cp*IrPz-hydrido-alkyl] species; and 3) subsequent facile cycloamine liberation to regenerate the active catalyst species. The amine-iridium bound 2 a⋅S likely corresponds to the catalyst resting state and the catalytic reaction is expected to proceed with a significant primary kinetic isotope. This study unveils the vital role of a supportive hydrogen-bonded network involving suitably aligned β-basic pyrazolato and cycloamido moieties together with an external amine molecule in facilitating metal protonation and reductive elimination. Cooperative hydrogen bonding thus appears pivotal for effective catalysis. The mechanistic scenario is consonant with catalyst performance data and furthermore accounts for the variation in performance for [Cp*IrPz] compounds featuring a β- or γ-basic pyrazolato unit. As far as the route that involves amine N-H bond activation is concerned, a thus far undocumented pathway for concerted amidoalkene → cycloamine conversion through olefin protonation by the pyrazole N-H concurrent with N-C ring closure is disclosed as a

  11. 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

  12. Measurement of the intramolecular isotope effect on aliphatic hydroxylation by Chromobacterium violaceum phenylalanine hydroxylase.

    PubMed

    Panay, Aram J; Fitzpatrick, Paul F

    2010-04-28

    The non-heme iron enzyme phenylalanine hydroxylase from Chromobacterium violaceum has previously been shown to catalyze the hydroxylation of benzylic and aliphatic carbons in addition to the normal aromatic hydroxylation reaction. The intrinsic isotope effect for hydroxylation of 3-cyclochexylalanine by the enzyme was determined in order to gain insight into the reactivity of the iron center. With 3-[(2)H(11)-cyclohexyl]alanine as the substrate, the isotope effect on the k(cat) value was 1, consistent with an additional step in the overall reaction being significantly slower than hydroxylation. Consequently, the isotope effect was determined as an intramolecular effect by measuring the amount of deuterium lost in the hydroxylation of 3-[1,2,3,4,5,6-(2)H(6)-cyclohexyl]alanine. The ratio of 4-HO-cyclohexylalanine that retained deuterium to that which lost one deuterium atom was 2.8. This gave a calculated value of 12.6 for the ratio of the primary deuterium kinetic isotope effect to the secondary isotope effect. This value is consistent with hydrogen atom abstraction by an electrophilic Fe(O) center and a contribution of quantum-mechanical tunneling to the reaction.

  13. Time-dependent density functional theory (TD-DFT) study on the excited-state intramolecular proton transfer (ESIPT) in 2-hydroxybenzoyl compounds: Significance of the intramolecular hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Lan, Xin; Yang, Dapeng; Sui, Xiao; Wang, Dandan

    2013-02-01

    The excited-state properties of intramolecular hydrogen bonding (IMHB) in methyl salicylate (MS) and its effects on the excited-state intramolecular proton transfer (ESIPT) have been investigated using theoretical methods. From the geometric optimization and IR spectra in the ground and excited states calculated by density functional theory (DFT) and time-dependent DFT (TD-DFT) methods respectively, the IMHB is demonstrated to be significantly strengthened upon excitation to excited state S1. Thereby, the ESIPT is facilitated by the excited-state IMHB strengthening since ESIPT takes place through IMHB. In addition, the absorption and fluorescence peaks of the S1 state are also calculated using the TD-DFT method. It is noted that the calculated spectra are in good agreement with the experimental results, which has confirmed the ESIPT mechanism of MS first proposed by Weller. Moreover, other four 2-hydroxybenzoyl compounds forming strong IMHB are investigated to understand the effect of substituent R on the ESIPT process. We find that the hydrogen bond strength can be controlled by the inductive field effect of the substituent. Thus it is inferred that the ESIPT reaction can be facilitated by the inductive effect of electron-donating substituent.

  14. Detection of a transient intramolecular hydrogen bond using (1)JNH scalar couplings.

    PubMed

    Xiang, ShengQi; Zweckstetter, Markus

    2014-06-01

    Hydrogen bonds are essential for the structure, stability and folding of proteins. The identification of intramolecular hydrogen bonds, however, is challenging, in particular in transiently folded states. Here we studied the presence of intramolecular hydrogen bonds in the folding nucleus of the coiled-coil structure of the GCN4 leucine zipper. Using one-bond (1)JNH spin-spin coupling constants and hydrogen/deuterium exchange, we demonstrate that a transient intramolecular hydrogen bond is present in the partially helical folding nucleus of GCN(16-31). The data demonstrate that (1)JNH couplings are a sensitive tool for the detection of transient intramolecular hydrogen bonds in challenging systems where the effective/useable protein concentration is low. This includes peptides at natural abundance but also uniformly labeled biomolecules that are limited to low concentrations because of precipitation or aggregation.

  15. Intramolecular charge transfer effects on 3-aminobenzoic acid

    NASA Astrophysics Data System (ADS)

    Stalin, T.; Rajendiran, N.

    2006-03-01

    Effect of solvents, buffer solutions of different pH and β-cyclodextrin on the absorption and fluorescence spectra of 3-aminobenzoic acid (3ABA) have been investigated. The solid inclusion complex of 3ABA with β-CD is discussed by UV-Vis, fluorimetry, semiempirical quantum calculations (AM1), FT-IR, 1H NMR and Scanning Electron Microscope (SEM). The thermodynamic parameters (Δ H, Δ G and Δ S) of the inclusion process are also determined. The experimental results indicated that the inclusion processes is an exothermic and spontaneous. The large Stokes shift emission in solvents with 3ABA are correlated with different solvent polarity scales suggest that, 3ABA molecule is more polar in the S 1 state. Solvent, β-CD studies and excited state dipole moment values confirms that the presence of intramolecular charge transfer (ICT) in 3ABA. Acidity constants for different prototropic equilibria of 3ABA in the S 0 and S 1 states are calculated. β-Cyclodextrin studies shows that 3ABA forms a 1:1 inclusion complex with β-CD. β-CD studies suggest COOH group present in non-polar part and amino group present in hydrophilic part of the β-CD cavity. A mechanism is proposed to explain the inclusion process.

  16. Tryptophan synthase: a multienzyme complex with an intramolecular tunnel.

    PubMed

    Miles, E W

    2001-01-01

    Tryptophan synthase is a classic enzyme that channels a metabolic intermediate, indole. The crystal structure of the tryptophan synthase alpha2beta2 complex from Salmonella typhimurium revealed for the first time the architecture of a multienzyme complex and the presence of an intramolecular tunnel. This remarkable hydrophobic tunnel provides a likely passageway for indole from the active site of the alpha subunit, where it is produced, to the active site of the beta subunit, where it reacts with L-serine to form L-tryptophan in a pyridoxal phosphate-dependent reaction. Rapid kinetic studies of the wild type enzyme and of channel-impaired mutant enzymes provide strong evidence for the proposed channeling mechanism. Structures of a series of enzyme-substrate intermediates at the alpha and beta active sites are elucidating enzyme mechanisms and dynamics. These structural results are providing a fascinating picture of loops opening and closing, of domain movements, and of conformational changes in the indole tunnel. Solution studies provide further evidence for ligand-induced conformational changes that send signals between the alpha and beta subunits. The combined results show that the switching of the enzyme between open and closed conformations couples the catalytic reactions at the alpha and beta active sites and prevents the escape of indole.

  17. 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.

  18. Thiol dependent intramolecular locking of Orai1 channels

    PubMed Central

    Alansary, Dalia; Schmidt, Barbara; Dörr, Kathrin; Bogeski, Ivan; Rieger, Heiko; Kless, Achim; Niemeyer, Barbara A.

    2016-01-01

    Store-operated Ca2+ 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 Ca2+ 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

  19. 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

  20. Intramolecular vibrational energy relaxation in nitrous acid (HONO)

    NASA Astrophysics Data System (ADS)

    Botan, Virgiliu; Hamm, Peter

    2008-10-01

    Intramolecular vibrational energy relaxation (IVR) in nitrous acid (HONO) is studied with the help of ultrafast two-color pump-probe spectroscopy. In a previous paper [V. Botan et al., J. Chem. Phys. 124, 234511 (2006)], it has been observed that trans-HONO cools through a cascade of overtones of one specific mode after pumping the OH stretch vibration. We had suggested that this cooling mode is the ONO bend vibration. Furthermore, molecules that have initially been excited by the OH stretch vibration of cis-HONO and then underwent isomerization follow the same relaxation pathway. In the present study, we extend the investigation of IVR of cis- and trans-HONO to the N=O stretch and HON bend spectral regions, finding further evidence that the bottleneck of trans cooling is indeed the ONO bend vibration. In combination with information on the anharmonic coupling constants of different modes, the energy relaxation dynamics preceding this cooling cascade can also be followed in unprecedented detail.

  1. Synthesis of fluorescent naphthoquinolizines via intramolecular Houben-Hoesch reaction.

    PubMed

    Stasyuk, Anton J; Smoleń, Sabina; Glodkowska-Mrowka, Eliza; Brutkowski, Wojciech; Cyrański, Michał K; Tkachenko, Nikolai; Gryko, Daniel T

    2015-03-01

    The repertoire of synthetic methods leading to aza-analogues of polycyclic aromatic heterocycles has been enlarged by the discovery of the rearrangement of 10-substituted benzo[h]quinolines into compounds bearing an azonia-pyrene moiety. Acid-mediated intramolecular cyclization of derivatives bearing -CH2 CN and -CH2 CO2 Et groups led to compounds bearing a 5-substituted benzo[de]pyrido[3,2,1-ij]quinolinium core. Advanced photophysical studies including time-correlated single photon counting (TCSPC) and transient absorption spectroscopy of 5-aminobenzo[de]pyrido[3,2,1-ij]quinolin-4-ium salt and 5H-benzo[de]pyrido[3,2,1-ij]quinolin-5-one showed their promising optical properties such as high fluorescence quantum yields (37-59%), which was almost independent of the solvent, and high tenability of the absorption band position upon changing the solvent. The benzo[de]pyrido[3,2,1-ij]quinolinium salt selectively stains nucleic acids (in the nucleus and mitochondria) in eukaryotic cells. PMID:25580599

  2. Metal complexes with varying intramolecular hydrogen bonding networks

    PubMed Central

    Lacy, David C.; Mukherjee, Jhumpa; Lucas, Robie L.; Day, Victor W.; Borovik, A.S.

    2013-01-01

    Alfred Werner described the attributes of the primary and secondary coordination spheres in his development of coordination chemistry. To examine the effects of the secondary coordination sphere on coordination chemistry, a series of tripodal ligands containing differing numbers of hydrogen bond (H-bond) donors were used to examine the effects of H-bonds on Fe(II), Mn(II)–acetato, and Mn(III)–OH complexes. The ligands containing varying numbers of urea and amidate donors allowed for systematic changes in the secondary coordination spheres of the complexes. Two of the Fe(II) complexes that were isolated as their Bu4N+ salts formed dimers in the solid-state as determined by X-ray diffraction methods, which correlates with the number of H-bonds present in the complexes (i.e., dimerization is favored as the number of H-bond donors increases). Electron paramagnetic resonance (EPR) studies suggested that the dimeric structures persist in acetonitrile. The Mn(II) complexes were all isolated as their acetato adducts. Furthermore, the synthesis of a rare Mn(III)–OH complex via dioxygen activation was achieved that contains a single intramolecular H-bond; its physical properties are discussed within the context of other Mn(III)–OH complexes. PMID:24904193

  3. 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

  4. 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.

  5. 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

  6. Intramolecular indicator displacement assay for anions: supramolecular sensor for glyphosate.

    PubMed

    Minami, Tsuyoshi; Liu, Yuanli; Akdeniz, Ali; Koutnik, Petr; Esipenko, Nina A; Nishiyabu, Ryuhei; Kubo, Yuji; Anzenbacher, Pavel

    2014-08-13

    One of the well-known strategies for anion sensing is an indicator (dye) displacement assay. However, the disadvantage of the dye displacement assays is the low sensitivity due to the excess of the dye used. To overcome this setback, we have developed an "Intramolecular Indicator Displacement Assay (IIDA)". The IIDAs comprise a receptor and a spacer with an attached anionic chromophore in a single-molecule assembly. In the resting state, the environment-sensitive anionic chromophore is bound by the receptor, while the anionic substrate competes for binding into the receptor. The photophysical properties of the dye exhibit change in fluorescence when displaced by anions, which results in cross-reactive response. To illustrate the concept, we have prepared IID sensors 1 and 2. Here, the characterization of sensors and microtiter arrays comprising the IIDA are reported. The microtiter array including IID sensors 1 and 2 is capable of recognizing biological phosphates in water. The utility of the IIDA approach is demonstrated on sensing of a phosphonate herbicide glyphosate and other biologically important anions such as pyrophosphate in the presence of interferent sodium chloride.

  7. 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

  8. Normal coordinate analysis of bilirubin vibrational spectra: Effects of intramolecular hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Yang, Bijun; Taylor, Robert C.; Morris, Michael D.; Wang, Xiu-Zhen; Wu, Jin-guang; Yu, Bao-Zhu; Xu, Guang-xian; Soloway, Roger D.

    1993-11-01

    Normal coordinate analyses are presented for half-bilirubin molecules. Calculations for the AB pyrromethenone include intramolecular hydrogen bonds, while those for the CD chromophore exclude intramolecular hydrogen bonds. Valence force-field parameters have been optimized to correlate closely with the IR and Raman spectra of the target molecules. The results of the calculations are compared with the spectra of bilirubin IXa and various model compounds in the solid state and solution.

  9. 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.

  10. Susceptibility towards intramolecular disulphide-bond formation affects conformational stability and folding of human basic fibroblast growth factor.

    PubMed Central

    Estapé, D; van den Heuvel, J; Rinas, U

    1998-01-01

    The conformational stability and the folding properties of the all-beta-type protein human basic fibroblast growth factor (hFGF-2) were studied by means of fluorescence spectroscopy. The results show that the instability of the biological activity of hFGF-2 is also reflected in a low conformational stability of the molecule. The reversibility of the unfolding and refolding process was established under reducing conditions. Determination of the free-energy of unfolding in the presence of reducing agents revealed that the conformational stability of hFGF-2 (DeltaGH2Oapp congruent with21 kJ. mol-1, 25 degreesC) is low compared with other globular proteins under physiological conditions (20-60 kJ.mol-1). However, the conformational stability of hFGF-2 is particularly low under non-reducing conditions. This instability is attributed to intramolecular disulphide-bond formation, rendering the molecule more susceptible to denaturant-induced unfolding. In addition, denaturant-induced unfolding of hFGF-2 renders the protein more susceptible to irreversible oxidative denaturation. Experimental evidence is provided that the irreversibility of the unfolding and refolding process in the absence of reducing agents is linked to the formation of an intramolecular disulphide bond involving cysteines 96 and 101. PMID:9761733

  11. Molecular dynamics study of chemically engineered green fluorescent protein mutants: comparison of intramolecular fluorescence resonance energy transfer rate.

    PubMed

    Mitchell, Felicity L; Frank, Filipp; Marks, Gabriel E; Suzuki, Miho; Douglas, Kenneth T; Bryce, Richard A

    2009-04-01

    Because of its unusual spectroscopic properties, green fluorescent protein (GFP) has become a useful tool in molecular genetics, biochemistry and cell biology. Here, we computationally characterize the behavior of two GFP constructs, designed as bioprobes for enzymatic triggering using intramolecular fluorescence resonance energy transfer (FRET). These constructs differ in the location of an intramolecular FRET partner, an attached chemical chromophore (either near an N-terminal or C-terminal site). We apply the temperature replica exchange molecular dynamics method to the two flexible constructs in conjunction with a generalized Born implicit solvent model. The calculated rate of FRET was derived from the interchromophore distance, R, and orientational factor, kappa(2). In agreement with experiment, the construct with the C-terminally attached dye was predicted to have higher energy transfer rate than observed for the N-terminal construct. The molecular basis for this observation is discussed. In addition, we find that the orientational factor, kappa(2), deviates from the commonly assumed value, the implications of which are also considered.

  12. 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

  13. 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

  14. 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

  15. 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

  16. Twisted intramolecular charge transfer of methyl p-dimethylaminobenzoate in aqueous β-cyclodextrin solution

    NASA Astrophysics Data System (ADS)

    Jiang, Yun-Bao

    1995-02-01

    This paper reports the investigation of the twisted intramolecular charge transfer (TICT) of methyl p-dimethylaminobenzoate (MDMAB) in aqueous β-cyclodextrin (β-CD) solution by the TICT-typical dual fluorescence. In pure water, MDMAB emits only LE fluorescence, and the TICT fluorescence band is developed with the addition of β-CD. Both the LE and TICT fluorescence bands are continuously enhanced upon the increase of β-CD concentration. The intensity ratio of the TICT band to the LE band shows a hillshaped dependence on β-CD concentration, and a blue shift in both TICT and LE bands is observed with the increase of β-CD concentration, of which the blue shift in TICT band is more appreciable. Formation of a 1:1 MDMAB-β-CD inclusion complex, with an association constant of 580±80 l mol -1, is evaluated. The effect of β-CD on TICT of MDMAB is discussed, with consideration of the fact that aqueous β-CD solution is pseudoaquaorganic binary mixture and that TICT in aqueous solution acts differently than in organic solvents. A comparison is made between the TICT of MDMAB and of DMABN in aqueous β-CD solution.

  17. The mucin-degradation strategy of Ruminococcus gnavus: The importance of intramolecular trans-sialidases

    PubMed Central

    Crost, Emmanuelle H.; Tailford, Louise E.; Monestier, Marie; Swarbreck, David; Henrissat, Bernard; Crossman, Lisa C.; Juge, Nathalie

    2016-01-01

    ABSTRACT We previously identified and characterized an intramolecular trans-sialidase (IT-sialidase) in the gut symbiont Ruminococcus gnavus ATCC 29149, which is associated to the ability of the strain to grow on mucins. In this work we have obtained and analyzed the draft genome sequence of another R. gnavus mucin-degrader, ATCC 35913, isolated from a healthy individual. Transcriptomics analyses of both ATCC 29149 and ATCC 35913 strains confirmed that the strategy utilized by R. gnavus for mucin-degradation is focused on the utilization of terminal mucin glycans. R. gnavus ATCC 35913 also encodes a predicted IT-sialidase and harbors a Nan cluster dedicated to sialic acid utilization. We showed that the Nan cluster was upregulated when the strains were grown in presence of mucin. In addition we demonstrated that both R. gnavus strains were able to grow on 2,7-anyhydro-Neu5Ac, the IT-sialidase transglycosylation product, as a sole carbon source. Taken together these data further support the hypothesis that IT-sialidase expressing gut microbes, provide commensal bacteria such as R. gnavus with a nutritional competitive advantage, by accessing and transforming a source of nutrient to their own benefit. PMID:27223845

  18. 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

  19. 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

  20. Scalable Synthesis of the Amber Odorant 9-epi-Ambrox through a Biomimetic Cationic Cyclization/Nucleophilic Bromination Reaction.

    PubMed

    Fontaneda, Raquel; Alonso, Pedro; Fañanás, Francisco J; Rodríguez, Félix

    2016-09-16

    A novel biomimetic nucleophilic bromocyclization reaction is used in the key step of a new and straightforward synthesis of 9-epi-Ambrox, an organic compound of high interest and value in the context of fragrances. This strategic reaction allows access to 9-epi-Ambrox on a gram scale from a dienyne derivative, easily available from geraniol, following a sequence of seven steps (35% global yield) with just one purification process. Both enantiomers of the molecule were obtained by a challenging enzymatic resolution. PMID:27588550

  1. 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

  2. Facile nucleophilic fluorination reactions using tert-alcohols as a reaction medium: significantly enhanced reactivity of alkali metal fluorides and improved selectivity.

    PubMed

    Kim, Dong Wook; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Katzenellenbogen, John A; Chi, Dae Yoon

    2008-02-01

    Although protic solvents are generally not preferred for nucleophilic displacement reactions because of their partial positive charge and hydrogen-bonding capacity that solvate the nucleophile and reduce its reactivity, we recently reported a remarkably beneficial effect of using tertiary alcohols as a reaction media for nucleophilic fluorination with alkali metal fluorides, as well as fluorine-18 radiolabeling with [18F]fluoride ion for the preparation of PET radiopharmaceuticals. In this work, we investigate further the influence of the tert-alcohol reaction medium for nucleophilic fluorination with alkali metal fluorides by studying various interactions among tert-alcohols, the alkali metal fluoride (CsF), and the sulfonyloxy substrate. Factors such as hydrogen bonding between CsF and the tert-alcohol solvent, the formation of a tert-alcohol solvated fluoride, and hydrogen bonding between the sulfonate leaving group and the tert-alcohol appear to contribute to the dramatic increase in the rate of the nucleophilic fluorination reaction in the absence of any kind of catalyst. We found that fluorination of 1-(2-mesyloxyethyl)naphthalene (5) and N-5-bromopentanoyl-3,4-dimethoxyaniline (8) with Bu(4)N(+)F(-) in a tert-alcohol afforded the corresponding fluoro products in much higher yield than obtained by the conventional methods using dipolar aprotic solvents. The protic medium also suppresses formation of byproducts, such as alkenes, ethers, and cyclic adducts.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. Accounting for intra-molecular vibrational modes in open quantum system description of molecular systems.

    PubMed

    Roden, Jan; Strunz, Walter T; Whaley, K Birgitta; Eisfeld, Alexander

    2012-11-28

    Electronic-vibrational dynamics in molecular systems that interact with an environment involve a large number of degrees of freedom and are therefore often described by means of open quantum system approaches. A popular approach is to include only the electronic degrees of freedom into the system part and to couple these to a non-Markovian bath of harmonic vibrational modes that is characterized by a spectral density. Since this bath represents both intra-molecular and external vibrations, it is important to understand how to construct a spectral density that accounts for intra-molecular vibrational modes that couple further to other modes. Here, we address this problem by explicitly incorporating an intra-molecular vibrational mode together with the electronic degrees of freedom into the system part and using the Fano theory for a resonance coupled to a continuum to derive an "effective" bath spectral density, which describes the contribution of intra-molecular modes. We compare this effective model for the intra-molecular mode with the method of pseudomodes, a widely used approach in simulation of non-Markovian dynamics. We clarify the difference between these two approaches and demonstrate that the respective resulting dynamics and optical spectra can be very different.

  10. Synthesis of trifluoromethylated isoxazoles and their elaboration through inter- and intra-molecular C-H arylation.

    PubMed

    Poh, Jian-Siang; García-Ruiz, Cristina; Zúñiga, Andrea; Meroni, Francesca; Blakemore, David C; Browne, Duncan L; Ley, Steven V

    2016-07-01

    We report conditions for the preparation of a range of trifluoromethylated isoxazole building blocks through the cycloaddition reaction of trifluoromethyl nitrile oxide. It was found that controlling the rate (and therefore concentration) of the formation of the trifluoromethyl nitrile oxide was Critical for the preferential formation of the desired isoxazole products versus the furoxan dimer. Different conditions were optimised for both aryl- and alkyl-substituted alkynes. In addition, the reactivity at the isoxazole 4-position has been briefly explored for these building blocks. Conditions for intermolecular C-H arylation, lithiation and electrophile quench, and alkoxylation were all identified with brief substrate scoping that signifies useful tolerance to a range of functionalities. Finally, complementary processes for structural diversification through either intramolecular cyclisation or intermolecular cross-coupling were developed.

  11. α(δ')-Michael addition of alkyl amines to dimethyl (E)-hex-2-en-4-ynedioate: synthesis of α,β-dehydroamino acid derivatives.

    PubMed

    Chavan, Arjun S; Deng, Jie-Cheng; Chuang, Shih-Ching

    2013-02-27

    The direct nucleophilic addition of alkyl amines to the α(δ')-carbon atom of dimethyl (E)-hex-2-en-4-ynedioate to generate α,β-dehydroamino acid derivatives is reported. Herein, we have studied the reactivity of various primary and secondary alkyl amines in the α-selective nucleophilic conjugate addition to conjugated dimethyl (E)-hex-2-en-4-ynedioate. The reaction with primary alkyl amines gives only the (2E,4E)-stereoisomer, while that with secondary alkyl amines gives the (2E,4E) and (2Z,4E)-stereoisomers of dimethyl (2-alkylamino)-muconic ester.

  12. Intramolecular aggregation and optical limiting properties of triazine-linked mono-, bis- and tris-phthalocyanines.

    PubMed

    Chen, Jun; Zhang, Tao; Wang, Shuangqing; Hu, Rui; Li, Shayu; Ma, Jin Shi; Yang, Guoqiang

    2015-10-01

    A series of triazine-linked mono-, bis- and tris-phthalocyanines are synthesized, intramolecular aggregation is found in bis- and tris-phthalocyanines via π-π stacking interaction. Theoretical and experimental studies reveal the formation of the intramolecular aggregation. The spectrographic, photophysical and nonlinear optical properties of these compounds are adjusted for the formation of the intramolecular aggregation. The bis-phthalocyanine dimer presents smaller fluorescence quantum yield, lower triplet formation yield and the triplet-minus-ground state extinction coefficient, which causes poorer optical limiting performance. It is interesting that the tris-phthalocyanine is composed of a mono-phthalocyanine part and a bis-phthalocyanine part, the optical limiting property of the tris-phthalocyanine is similar to that of mono-phthalocyanine.

  13. 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.

  14. Intermolecular and intramolecular contributions to the relaxation process in sorbitol and maltitol

    NASA Astrophysics Data System (ADS)

    Sixou, B.; Faivre, A.; David, L.; Vigier, G.

    Molecular mobility in sorbitol and maltitol is studied with spectroscopic techniques and molecular dynamics simulations in order to evaluate the relative contributions of the intermolecular and intramolecular interactions involved in the relaxation processes. The results of the molecular dynamics simulations performed on the polyols in the bulk or in vacuum compares well with the results of the analysis of the relaxation diagrams in the framework of the Perez et al . model. They both imply that the difference in the relative contributions of the intermolecular and intramolecular interactions associated with the different chemical architectures of the two polyols must be taken into account. The intermolecular interactions cannot be neglected and they are stronger in sorbitol than in maltitol in relation with the linear structure of this polyol. The intramolecular barrier, higher in the maltitol molecule with a more complex structure, could be at the origin of the higher junction temperature between the αand βrelaxation processes.

  15. 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

  16. 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.

  17. Ratiometric fluorescent/colorimetric cyanide-selective sensor based on excited-state intramolecular charge transfer-excited-state intramolecular proton transfer switching.

    PubMed

    Lin, Wei-Chi; Fang, Sin-Kai; Hu, Jiun-Wei; Tsai, Hsing-Yang; Chen, Kew-Yu

    2014-05-20

    A novel salicylideneaniline-based fluorescent sensor, SB1, with a unique excited-state intramolecular charge transfer-excited-state intramolecular proton transfer (ESICT-ESIPT) coupled system was synthesized and demonstrated to fluorescently sense CN(-) with specific selectivity and high sensitivity in aqueous media based on ESICT-ESIPT switching. A large blue shift (96 nm) was also observed in the absorption spectra in response to CN(-). The bleaching of the color could be clearly observed by the naked eye. Moreover, SB1-based test strips were easily fabricated and low-cost, and could be used in practical and efficient CN(-) test kits. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations further support the cyanide-induced ESICT-ESIPT switching mechanism. The results provide the proof of concept that the colorimetric and ratiometric fluorescent cyanide-selective chemodosimeter can be created based on an ESICT-ESIPT coupled system. PMID:24809868

  18. 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

  19. 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.

  20. 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

  1. Enantioselective desymmetrization of cyclohexadienones via an intramolecular Rauhut-Currier reaction of allenoates

    NASA Astrophysics Data System (ADS)

    Yao, Weijun; Dou, Xiaowei; Wen, Shan; Wu, Ji'en; Vittal, Jagadese J.; Lu, Yixin

    2016-10-01

    The Rauhut-Currier (RC) reaction represents an efficient method for the construction of carbon-carbon bond in organic synthesis. However, the RC reactions involving allenoate substrates are very rare, and in particular, asymmetric intramolecular RC reaction of allenoates is yet to be discovered. Here, we show that the intramolecular RC reaction proceeds smoothly in the presence of 1 mol% β-ICD, and bicyclic lactones are obtained in high yields and with excellent enantiomeric excesses. With the employment of γ-substituted allenoates as racemic precursors, a novel dynamic kinetic resolution of allenes via RC reaction is observed, which allows for facile synthesis of highly enantiomerically enriched allenes.

  2. 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.

  3. Addition of methanetrisulfonyl fluoride to unsaturated bonds

    SciTech Connect

    Yagupol'skii, Yu.L.; Gerus, I.I.; Savina, T.I.

    1988-06-10

    The reactions of methanetrisulfonyl fluoride, HC(SO/sub 2/F)/sub 3/ with acrylic acid derivatives lead to addition products containing the tris(fluorosulfonyl)methyl group, while methyl vinyl ketone gives an unstable adduct. The methyl ester of propiolic acid is converted to a mixture of cis- and trans-tris(fluorosulfonyl)-crotonic acid esters. The reaction of cyclohexene with methanesulfonyl fluoride leads to dimerization of the olefin and the cyclohexyl derivative is formed in low yield. Sulfonyl fluoride acts as catalyst for the conversion of cyclohexene to dimer and only a small portion of the cyclohexyl cation reacts with the weakly nucleophilic /sup /minus//C(SO/sub 2/F)/sub 3/ anion.

  4. Phosphazene additives

    DOEpatents

    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.

  5. 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.

  6. 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.

  7. Excited state intramolecular charge transfer reaction in nonaqueous electrolyte solutions: Temperature dependence

    NASA Astrophysics Data System (ADS)

    Pradhan, Tuhin; Gazi, Harun Al Rasid; Biswas, Ranjit

    2009-08-01

    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 (LiClO4) 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 (-ΔGr) 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, LiClO4 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 (-ΔGr), the former in ethanol and ACN increases only linearly with the increase in driving force (-ΔGr). 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.

  8. 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.

  9. Thia-, aza-, and selena[3.3.1]bicyclononane dichlorides: rates vs internal nucleophile in anchimeric assistance.

    PubMed

    Accurso, Adrian A; Cho, So-Hye; Amin, Asmarah; Potapov, Vladimir A; Amosova, Svetlana V; Finn, M G

    2011-06-01

    Sulfur-, selenium-, and nitrogen-containing compounds bearing leaving groups in the β-position undergo facile substitution chemistry enabled by anchimeric assistance. Here we provide direct comparisons between such systems in the rigid bicyclo[3.3.1]nonane framework easily derived from 1,5-cyclooctadiene. For a series of dichloride electrophiles of this type, the relative reactivities were found to be Se ≫ (alkyl)N > S ≥ (propargyl)N > (phenyl)N, with the reaction rates at the two extremes differing by more than 3 orders of magnitude. For the N-alkyl case, substitution rates were largely independent of the trapping nucleophile but were strongly dependent on solvent, showing that the process is controlled by the formation of the high-energy three-membered cationic intermediate.

  10. 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

  11. 5(6)-anti-Substituted-2-azabicyclo[2.1.1]hexanes. A Nucleophilic Displacement Route

    PubMed Central

    Krow, Grant R.; Edupuganti, Ram; Gandla, Deepa; Choudhary, Amit; Lin, Guoliang; Sonnet, Philip E.; DeBrosse, Charles; Ross, Charles W.; Cannon, Kevin C.; Raines, Ronald T.

    2012-01-01

    Nucleophilic displacements of 5(6)-anti-bromo substituents in 2-azabicyclo[2.1.1]hexanes (methanopyrrolidines) have been accomplished. These displacements have produced 5-anti-X-6-anti-Y-difunctionalized-2-azabicyclo[2.1.1]hexanes containing bromo, fluoro, acetoxy, hydroxy, azido, imidazole, thiophenyl, and iodo substituents. Such displacements of anti-bromide ions require an amine nitrogen and are a function of the solvent and the choice of metal salt. Reaction rates were faster and product yields were higher in DMSO when compared to DMF and with CsOAc compared to NaOAc. Sodium or lithium salts gave products, except with NaF, where silver fluoride in nitromethane was best for substitution by fluoride. The presence of electron-withdrawing F, OAc, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position. PMID:19799411

  12. Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH.

    PubMed

    Bandyopadhyay, Anupam; Gao, Jianmin

    2015-10-12

    Bioorthogonal reactions that are fast and reversible under physiological conditions are in high demand for biological applications. Herein, it is shown that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 10(2) to 10(3) M(-1) s(-1) , comparable to the fastest bioorthogonal conjugations known to date. (11) B NMR analysis revealed the varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiological conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology.

  13. Intramolecular Interactions between the Protease and Structural Domains Are Important for the Functions of Serine Protease Autotransporters▿ †

    PubMed Central

    Tsang, Casey; Malik, Huma; Nassman, Deana; Huang, Antony; Tariq, Fayha; Oelschlaeger, Peter; Stathopoulos, Christos

    2010-01-01

    Autotransporter (AT) is a protein secretion pathway found in Gram-negative bacteria featuring a multidomain polypeptide with a signal sequence, a passenger domain, and a translocator domain. An AT subfamily named serine protease ATs of the family Enterobacteriaceae (SPATEs) is characterized by the presence of a conserved serine protease motif in the passenger domain which contributes to bacterial pathogenesis. The goal of the current study is to determine the importance of the passenger domain conserved residues in the SPATE proteolytic and adhesive functions using the temperature-sensitive hemagglutinin (Tsh) protein as our model. To begin, mutations of 21 fully conserved residues in the four passenger domain conserved motifs were constructed by PCR-based site-directed mutagenesis. Seventeen mutants exhibited a wild-type secretion level; among these mutants, eight displayed reduced proteolytic activities in Tsh-specific oligopeptide and mucin cleavage assays. These eight mutants also demonstrated lower affinities to extracellular matrix proteins, collagen IV, and fibronectin. These eight conserved residues were analyzed by molecular graphics modeling to demonstrate their intramolecular interactions with the catalytic triad and other key residues. Additional mutations were made to confirm the above interactions in order to demonstrate their significance to the SPATE functions. Altogether our data suggest that certain conserved residues in the SPATE passenger domain are important for both the proteolytic and adhesive activities of SPATE by maintaining the proper protein structure via intramolecular interactions between the protease and β-helical domains. Here, we provide new insight into the structure-function relationship of the SPATEs and the functional roles of their conserved residues. PMID:20479079

  14. 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.

  15. An efficient and practical synthesis of [2-11C]indole via superfast nucleophilic [11C]cyanation and RANEY® Nickel catalyzed reductive cyclization

    DOE PAGES

    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

  16. 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…

  17. Origin of Enhanced Reactivity of a Microsolvated Nucleophile in Ion Pair SN2 Reactions: The Cases of Sodium p-Nitrophenoxide with Halomethanes in Acetone.

    PubMed

    Li, Qiang-Gen; Xu, Ke; Ren, Yi

    2015-04-30

    In a kinetic experiment on the SN2 reaction of sodium p-nitrophenoxide with iodomethane in acetone-water mixed solvent, Humeres et al. (J. Org. Chem. 2001, 66, 1163) found that the reaction depends strongly on the medium, and the fastest rate constant was observed in pure acetone. The present work tries to explore why acetone can enhance the reactivity of the title reactions. Accordingly, we make a mechanistic study on the reactions of sodium p-nitrophenoxide with halomethanes (CH3X, X = Cl, Br, I) in acetone by using a supramolecular/continuum model at the PCM-MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p) level, in which the ion pair nucleophile is microsolvated by one to three acetone molecules. We compared the reactivity of the microsolvated ion pair nucleophiles with solvent-free ion pair and anionic ones. Our results clearly reveal that the microsolvated ion pair nucleophile is favorable for the SN2 reactions; meanwhile, the origin of the enhanced reactivity induced by microsolvation of the nucleophile is discussed in terms of the geometries of transition state (TS) structures and activation strain model, suggesting that lower deformation energies and stronger interaction energies between the deformed reactants in the TS lead to the lower overall reaction barriers for the SN2 reaction of microsolvated sodium p-nitrophenoxide toward halomethanes in acetone.

  18. Substituent controlled reactivity switch: selective synthesis of α-diazoalkylphosphonates or vinylphosphonates via nucleophilic substitution of alkyl bromides with Bestmann-Ohira reagent.

    PubMed

    Pramanik, Mukund M D; Chaturvedi, Atul Kumar; Rastogi, Namrata

    2014-11-01

    We report a substituent controlled nucleophilic displacement of alkyl bromides with Bestmann-Ohira reagent yielding either dimethyl diazoalkylphosphonates or (E)-vinylphosphonates. The dimethyl diazoalkylphosphonates could be readily converted into corresponding (E)-vinylphosphonates in the presence of Cu following nitrogen elimination in quantitative yields.

  19. Base or nucleophile? DFT finally elucidates the origin of the selectivity between the competitive reactions triggered by MeLi or LDA on propanal.

    PubMed

    Marchois, J; Fressigné, C; Lecachey, B; Maddaluno, J

    2015-06-18

    The competition between basicity and nucleophilicity of two standard organolithium reagents was studied using DFT. Comparing the reactivity of solvated (MeLi)2 and (LDA)2 toward propanal finally explains why methyllithium adds onto the carbonyl while LDA deprotonates the α-position, in accord with experiment and Ireland's deprotonation TS.

  20. Intramolecular benzyl protection delivery: a practical synthesis of DMDP and DGDP from D-fructose.

    PubMed

    García-Moreno, M Isabel; Aguilar, Matilde; Ortiz Mellet, Carmen; García Fernández, José M

    2006-01-19

    [reaction: see text] A two-step protection of 1,2-diols as the corresponding o-xylylene cyclic ethers, involving an intramolecular ring-closing O-benzylation reaction, has been developed to overcome the problems associated to regioselective benzylation reactions. The strategy has been applied to the high-yielding synthesis of the pyrrolidine glycosidase inhibitors DMDP and DGDP.

  1. 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

  2. Remarkable stereoselectivity in intramolecular Borono-Mannich reactions: synthesis of conduramines.

    PubMed

    Norsikian, Stéphanie; Soulé, Jean-François; Cannillo, Alexandre; Guillot, Régis; Dau, Marie-Elise Tran Huu; Beau, Jean-Marie

    2012-01-20

    An unprecedented intramolecular Petasis condensation provides a novel approach to biologically important conduramines. The compounds are produced with an exclusive anti stereoselectivity for the newly created β-amino alcohol motif. The stereochemical outcome of the reaction is opposite to the one usually observed in the intermolecular reaction.

  3. 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

  4. Copper(II) Carboxylate Promoted Intramolecular Carboamination of Alkenes for the Synthesis of Polycyclic Lactams

    PubMed Central

    Fuller, Peter H.; Chemler, Sherry R.

    2008-01-01

    The copper(II) carboxylate promoted intramolecular carboamination reactions of variously substituted γ-alkenyl amides have been investigated. These oxidative cyclization reactions efficiently provide polycyclic lactams, useful intermediates in nitrogen heterocycle synthesis, in good to excellent yields. The efficiency of the carboamination process is dependent upon the structure of the amide backbone as well as the nitrogen substituent. PMID:18044907

  5. A novel chiral yttrium complex with a tridentate linked amido-indenyl ligand for intramolecular hydroamination.

    PubMed

    Chai, Zhuo; Hua, Dezhi; Li, Kui; Chu, Jiang; Yang, Gaosheng

    2014-01-01

    A new chiral silicon-linked tridentate amido-indenyl ligand was developed from indene and enantiopure 1,2-cyclohexanediamine. Its yttrium complex was synthesized, characterized and applied to efficiently catalyze the intramolecular hydroamination of non-activated olefins with up to 97% ee.

  6. 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

  7. Intramolecular Schmidt reaction involving primary azidoalcohols under nonacidic conditions: synthesis of indolizidine (-)-167B.

    PubMed

    Kapat, Ajoy; Nyfeler, Erich; Giuffredi, Guy T; Renaud, Philippe

    2009-12-16

    A powerful intramolecular Schmidt reaction starting from primary azidoalcohols is reported. This approach involves a nonacidic activation of the alcohol via triflation. The synthetic potential offered by the mild reaction conditions is demonstrated by a highly selective synthesis of (-)-indolizidine 167B. PMID:19928759

  8. 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…

  9. 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…

  10. The first porphyrin-subphthalocyaninatoboron(iii)-fused hybrid with unique conformation and intramolecular charge transfer behavior.

    PubMed

    Zhang, Yuehong; Oh, Juwon; Wang, Kang; Shin, Dongju; Zhan, Xiaopeng; Zheng, Yingting; Kim, Dongho; Jiang, Jianzhuang

    2016-08-18

    Porphyrin and subphthalocyaninatoboron(iii) chromophores have been fused through a quinoxaline moiety, resulting in the first porphyrin-subphthalocyaninatoboron(iii)-fused hybrid with intramolecular charge transfer from tetrapyrrole/tripyrrole chromophores to the quinoxaline moiety. The unique plane-bowl molecular structure of this hybrid was revealed based on single crystal X-ray diffraction analysis for the first time. PMID:27492136

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Ionic S(N)i-Si Nucleophilic Substitution in N-Methylaniline-Induced Si-Si Bond Cleavages of Si2Cl6.

    PubMed

    Zhang, Jie; Xie, Ju; Lee, Myong Euy; Zhang, Lin; Zuo, Yujing; Feng, Shengyu

    2016-03-24

    N-Methylaniline-induced Si-Si bond cleavage of Si2Cl6 has been theoretically studied. All calculations were performed by using DFT at the MPWB1K/6-311++G(3df,2p)//MPWB1K/6-31+G(d,p) levels. An ionic SN i-Si nucleophilic substitution mechanism, which is a newly found nucleophilic substitution in silicon-containing compounds, is proposed in the N-methylaniline-induced Si-Si bond cleavage in Si2Cl6. Unlike general S(N)i-Si nucleophilic substitutions that go through a pentacoordinated silicon transition state, ionic nucleophilic substitution goes through a tetracoordinated silicon transition state, in which the Si-Si bond is broken and siliconium ions are formed. Special cleavage of the Si-Si bond is presumably due to the good bonding strength between Si and N atoms, which leads to polarization of the Si-Si bond and eventually to heterolytic cleavage. Calculation results show that, in excess N-methylaniline, the final products of the reaction, including (NMePh)(3-n) SiHCl(n) (n=0-2) and (NMePh)(4-n) SiCl(n) (n=2-3), are the Si-Si cleavage products of Si2Cl6 and the corresponding amination products of the former. The ionic S(N)i-Si nucleophilic substitution mechanism can also be employed to describe the amination of chlorosilane by N-methylaniline. The suggested mechanisms are consistent with experimental data.

  16. 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.

  17. Using intramolecular disulfide bonds in tau protein to deduce structural features of aggregation-resistant conformations.

    PubMed

    Walker, Sophie; Ullman, Orly; Stultz, Collin M

    2012-03-16

    Because tau aggregation likely plays a role in a number of neurodegenerative diseases, understanding the processes that affect tau aggregation is of considerable importance. One factor that has been shown to influence the aggregation propensity is the oxidation state of the protein itself. Tau protein, which contains two naturally occurring cysteine residues, can form both intermolecular disulfide bonds and intramolecular disulfide bonds. Several studies suggest that intermolecular disulfide bonds can promote tau aggregation in vitro. By contrast, although there are data to suggest that intramolecular disulfide bond formation retards tau aggregation in vitro, the precise mechanism underlying this observation remains unclear. While it has been hypothesized that a single intramolecular disulfide bond in tau leads to compact conformations that cannot form extended structure consistent with tau fibrils, there are few data to support this conjecture. In the present study we generate oxidized forms of the truncation mutant, K18, which contains all four microtubule binding repeats, and isolate the monomeric fraction, which corresponds to K18 monomers that have a single intramolecular disulfide bond. We study the aggregation propensity of the oxidized monomeric fraction and relate these data to an atomistic model of the K18 unfolded ensemble. Our results argue that the main effect of intramolecular disulfide bond formation is to preferentially stabilize conformers within the unfolded ensemble that place the aggregation-prone tau subsequences, PHF6* and PHF6, in conformations that are inconsistent with the formation of cross-β-structure. These data further our understanding of the precise structural features that retard tau aggregation.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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

  4. Stereoselective synthesis of indolines via organocatalytic thioester enolate addition reactions.

    PubMed

    Kolarovic, Andrej; Käslin, Alexander; Wennemers, Helma

    2014-08-15

    A straightforward stereoselective synthesis route to indolin-3-yl acetates has been developed using organocatalytic addition reactions of monothiomalonates to ortho-bromo nitrostyrenes as the key step. The addition products of this highly stereoselective one-pot addition-deprotection-decarboxylation sequence were easily further converted to the target indolin-3-yl acetates, via an intramolecular Buchwald-Hartwig coupling reaction. The route provided indolin-3-yl acetates bearing tertiary and exocyclic quarternary stereogenic centers in excellent stereoselectivities and overall yields of 34-83%.

  5. 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.

  6. Actin Cys374 as a nucleophilic target of alpha,beta-unsaturated aldehydes.

    PubMed

    Dalle-Donne, Isabella; Carini, Marina; Vistoli, Giulio; Gamberoni, Luca; Giustarini, Daniela; Colombo, Roberto; Maffei Facino, Roberto; Rossi, Ranieri; Milzani, Aldo; Aldini, Giancarlo

    2007-03-01

    We have recently shown that actin can be modified by the Michael addition of 4-hydroxynonenal to Cys374. Here, we have exposed purified actin at increasing acrolein concentrations and have identified the sites of acrolein addition using LC-ESI-MS/MS. Acrolein reacted with Cys374, His87, His173, and, minimally, His40. Cys374 adduction by both 4-hydroxynonenal and acrolein negligibly affected the polymerization of aldehyde-modified (carbonylated) actin, as shown by fluorescence measurements. Differently, acrolein binding at histidine residues, when Cys374 was completely saturated, inhibited polymerization in a dose-dependent manner. Molecular modeling analyses indicated that structural distortions of the ATP-binding site, induced by four acrolein-Michael adducts, could explain the changes in the polymerization process. Aldehyde binding to Cys374 does not alter significantly actin polymerization because this residue is located in a very flexible region, whose covalent modifications do not alter the protein folding. These data demonstrate that Cys374 represents the primary target site of alpha,beta-unsaturated aldehyde addition to actin in vitro. As Cys374 is a preferential target for various oxidative/nitrosative modifications, and actin is one of the main carbonylated proteins in vivo, these findings also suggest that the highly reactive Cys374 could serve as a carbonyl scavenger of reactive alpha,beta-unsaturated aldehydes and other electrophilic lipids.

  7. 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.

  8. Ion-responsive Intramolecular Charge-transfer Absorption Using a Pyridinium Benzocrown Ether Conjugate.

    PubMed

    Kuwabara, Tetsuo; Tao, Xuanyi; Guo, Haocheng; Katsumata, Masayo; Ueta, Ikuo; Takahashi, Masaki; Suzuki, Yasutada

    2015-01-01

    A pyridinium benzocrown ether conjugated compound, 1, and its analogue with a non-crown ether unit, 2, have been prepared. Both compounds showed similar absorption spectra with two absorption bands at around 260 and 330 nm in acetonitrile. The bands at the longer wavelength side are associated with intramolecular charge transfer (ICT) absorption, in which the dialkoxyphenyl unit in benzocrown ether and the pyridinium unit act as the donor and acceptor, respectively. The addition of a guest, such as Li(+) or Mg(2+), caused a blue shift in the ICT absorption band for 1, but not for 2. This is explained by the formation of a 1:1 host-guest inclusion complex of 1 with the guest. The guest-induced absorption variation of 1 can be used for alkali and alkaline metal ion sensing. Compound 1 could detect divalent cations, especially for Mg(2+), rather than univalent ones (Li(+), Na(+), K(+), Rb(+), and Cs(+)), although Li(+) was detected with high sensitivity among the alkali metal ions. Compound 3, which has a pyridyl unit at the para position on the pyridinium of 1, showed a similar trend to that of 1 with lower sensitivity than that of 1. The fact that the Mg(2+)/Li(+) sensitivity ratio of 1 and 3 was estimated to be 8.63 and 5.08, respectively, suggests a higher Mg(2+)-preference of 1 rather than 3, while the Ca(2+)/Na(+) ones were 4.98 and 4.85, respectively, when compared ions with similar ionic radii. The sensitivity values of 1 were roughly proportional to their binding constants, as shown by the binding constants with Li(+), Na(+), Mg(2+), and Ca(2+) with values of 2100, 910, 11500, and 2000 M(-1) for 1, respectively. The binding constants of 3 were estimated to be 1710, 650, 3000, and 1400 M(-1) for Li(+), Na(+), Mg(2+), and Ca(2+), respectively, but could not be obtained for alkaline metal ions. The limit concentration for the detection of 1 for Mg(2+) was estimated to be 0.0156 mM, which was the smallest value in this system.

  9. Intramolecular energy transfer and excitation coupling in metal-to-ligand charge transfer (MLCT) excited states

    NASA Astrophysics Data System (ADS)

    Riesen, Hans; Krausz, Elmars

    1995-02-01

    Several new spectroscopic studies relating to the coupling and dynamics in the spin-forbidden 3MLCT excited states of the chromophores [Ru(bpy)3]2+ and [Os(bpy)3]2+ (bpy equals 2,2'-bipyridine) in the racemic crystal lattices [Ru(bpy)3](PF6)2, [Ru(bpy)3](ClO4)2 and [Zn(bpy)3](ClO4)2 are presented. In the first of these lattices there are three closely related chromophoric sites at low temperatures, each with trigonal (C3) symmetry. In the two, isomorphic perchlorate salts there is a single chromophoric site, which has C2 symmetry. Using time resolved luminescence line narrowing, we have been able to directly measure the excitation transfer rate between two equivalent metal-ligand units in the [Ru(bpy)3]2+ chromophore doped in the [Zn(bpy)3](ClO4)2 lattice. The rate obtained (approximately equals 1 X 108 sec-1) is in excellent accord with estimates made from the observed linewidth in Stark swept transient hole-burning experiments made on the same system and confirm the single ligand, localized nature of the lowest emitting excited states and thus the very weak intramolecular coupling between metal ligand sub-units within this chromophore. The corresponding coupling in the [Os(bpy)3]2+ system is stronger and, in contrast to the ruthenium analogue, gives rise to additional features in the optical spectra in the origin region of the lowest 3MLCT excited states. The magnitude of the coupling can be probed and assessed by preparing modified chromophoric materials, in which one or two of the bpy ligands are perdeuterated (bpy-d8). This selective deuteration breaks the (near) degeneracy of excitations involving crystallographically equivalent ligands by approximately equals 30 - 40 cm-1 and this competes with or completely overrides the exciton coupling process. The exciton coupling is found to be approximately equals 2.4 cm-1 for [Os(bpy)3]2+ doped in [Ru(bpy)3](PF6)2 and can be understood within a mini-exciton description. Stronger couplings for the same chromophore in

  10. d-Orbital Effects on Stereochemical Non-Rigidity: Twisted Ti IV Intramolecular Dynamics

    SciTech Connect

    Davis, Anna V.; Firman, Timothy K.; Hay, Benjamin P.; Raymond, Kenneth N.

    2006-07-26

    The isomerization dynamics of tris-catecholate complexes have been investigated by variable temperature NMR methods, demonstrating that the intramolecular racemization of ? and ? enantiomers of d0 TiIV is facile and faster than that of d10 GaIII and GeIV analogs. Activation parameters for the racemization of K2[Ti23] (H22 = 2,3-dihydroxy-N,N?-diisopropylterephthalamide) were determined from lineshape analysis of 1H NMR spectra (methanol-d4: ?H? = 47(1) kJ/mol; ?S? = -34(4) J/molK; ?G?298 = 57(3) kJ/mol; DMF-d7: ?H? = 55(1) kJ/mol; ?S? = -16(4) J/molK; ?G?298 = 59(3) kJ/mol; D2O (pD* = 8.6, 20% MeOD): ?H? = 48(3) kJ/mol; ?S? = -28(10) J/molK; ?G?298 = 56(3) kJ/mol). The study of K2[Ti43] (H24 = 2,3-dihydroxy-N-tert-butyl-N?-benzylterephthalamide) reveals two distinct isomerization processes: faster racemization of mer-[Ti43]2- by way of a Bailar twist mechanism (D3h transition state) (Tc ? 242 K, methanol-d4), and a slower mer/fac-[Ti43]2- isomerization by way of a R?y-Dutt mechanism (C2v transition state) (Tc ? 281 K, methanol-d4). The solution behavior of the TiIV complexes mirrors that reported previously for analogous GaIII complexes, while that of analogous GeIV complexes was too inert to be detected by 1H NMR up to 400 K. These experimental findings are augmented by DFT calculations of the ML3 grounds states and Bailar and R?y-Dutt transition states, which correctly predict the relative kinetic barriers of the three metal ions, in addition to faithfully reproducing the ground state structures. Orbital calculations support the conclusion that participation of the TiIV d0 orbitals in ligand bonding contributes to the greater stabilization of the prismatic TiIV transition states. Battelle operates the Pacific Northwest National Laboratory for the U.S. Department of Energy.

  11. 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.

  12. [Analyses of biogenic related compounds based on intramolecular excimer-forming fluorescence derivatization].

    PubMed

    Yoshida, Hideyuki

    2003-08-01

    A highly selective and sensitive method based on a novel concept is introduced for the assay of biological substances. This method is based on an intramolecular excimer-forming fluorescence derivatization with a pyrene reagent, followed by reverse-phase HPLC. Polyamines, polyphenols, and dicarboxylic acids, which have two or more reactive functional groups in a molecule, were converted to the corresponding polypyrene-labeled derivatives by reaction with the appropriate pyrene reagent. The derivatives exhibited intramolecular excimer fluorescence (440-520 nm), which can clearly be discriminated from the monomer (normal) fluorescence (360-420 nm) emitted by pyrene reagents and monopyrene-labeled derivatives of monofunctional compounds. With excimer fluorescence detection, highly selective and sensitive determination of polyamines, polyphenols, and dicarboxylic acids can be achieved. Furthermore, the methods were successfully applied to the determination of various biological and environmental substances in real samples, which require only a small amount of sample and simple pretreatment.

  13. 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.

  14. Enantioselective desymmetrization of cyclohexadienones via an intramolecular Rauhut–Currier reaction of allenoates

    PubMed Central

    Yao, Weijun; Dou, Xiaowei; Wen, Shan; Wu, Ji'en; Vittal, Jagadese J.; Lu, Yixin

    2016-01-01

    The Rauhut–Currier (RC) reaction represents an efficient method for the construction of carbon–carbon bond in organic synthesis. However, the RC reactions involving allenoate substrates are very rare, and in particular, asymmetric intramolecular RC reaction of allenoates is yet to be discovered. Here, we show that the intramolecular RC reaction proceeds smoothly in the presence of 1 mol% β-ICD, and bicyclic lactones are obtained in high yields and with excellent enantiomeric excesses. With the employment of γ-substituted allenoates as racemic precursors, a novel dynamic kinetic resolution of allenes via RC reaction is observed, which allows for facile synthesis of highly enantiomerically enriched allenes. PMID:27698487

  15. Acidic C-H Bond as a Proton Donor in Excited State Intramolecular Proton Transfer Reactions.

    PubMed

    Stasyuk, Anton J; Cyrański, Michał K; Gryko, Daniel T; Solà, Miquel

    2015-03-10

    An unprecedented type of excited state intramolecular proton transfer in a series of benzo[h]quinoline (BHQ) derivatives substituted at position 10 with strong CH acid character is described using density functional theory/time-dependent density functional theory computational approaches with a hybrid functional and the 6-311++G(d,p) triple-ξ quality basis set. Our results show that for 10-malononitrile-substituted BHQ (2CNBHQ) the excited state intramolecular proton transfer C-H···N reaction is a barrierless process. Calculations also reveal that the reaction profiles of the 4-amino-substituted 2CNBHQ show a large dependence on the polarity of the environment. PMID:26579756

  16. 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

  17. Isotope effects on chemical shifts in the study of intramolecular hydrogen bonds.

    PubMed

    Hansen, Poul Erik

    2015-01-30

    The paper deals with the use of isotope effects on chemical shifts in characterizing intramolecular hydrogen bonds. Both so-called resonance-assisted (RAHB) and non-RAHB systems are treated. The importance of RAHB will be discussed. Another very important issue is the borderline between "static" and tautomeric systems. Isotope effects on chemical shifts are particularly useful in such studies. All kinds of intramolecular hydrogen bonded systems will be treated, typical hydrogen bond donors: OH, NH, SH and NH+, typical acceptors C=O, C=N, C=S C=N-. The paper will be deal with both secondary and primary isotope effects on chemical shifts. These two types of isotope effects monitor the same hydrogen bond, but from different angles.

  18. 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.

  19. Vibrational assignment, structure and intramolecular hydrogen bond of 4-methylamino-3-penten-2-one.

    PubMed

    Raissi, Heidar; Moshfeghi, Effat; Farzad, Farzaneh

    2005-12-01

    The molecular structure, intramolecular hydrogen and vibrational frequencies of 4-methylamino-3-penten-2-one were investigated by a series of density functional theoretical (DFT) calculations and ab initio calculation at the post-Hartree-Fock (MP2) level. Fourier transform infrared and Fourier transform Raman spectra of this compound and its deuterated analogue were clearly assigned. The calculated geometrical parameters show a strong intramolecular hydrogen bond with a N...O distance of 2.622-2.670 A. This bond length is about 0.02 A shorter than that in its parent, 4-amino-3- penten-2-one which is in agreement with spectroscopic results. Furthermore, the conformations of methyl groups with respect to the plane of the molecule and with respect to each other were investigated.

  20. 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

  1. 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.

  2. 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.

  3. Intramolecular Charge-Transfer Interaction of Donor-Acceptor-Donor Arrays Based on Anthracene Bisimide.

    PubMed

    Iwanaga, Tetsuo; Ogawa, Marina; Yamauchi, Tomokazu; Toyota, Shinji

    2016-05-20

    We designed anthracene bisimide (ABI) derivatives having two triphenylamine (TPA) groups as donor units at the 9,10-positions to form a novel π-conjugated donor-acceptor system. These compounds and their analogues with ethynylene linkers were synthesized by Suzuki-Miyaura and Sonogashira coupling reactions, respectively. In UV-vis spectra, the linker-free derivatives showed broad absorption bands arising from intramolecular charge-transfer interactions. Introducing ethynylene linkers resulted in a considerable red shift of the absorption bands. In fluorescence spectra, the ethynylene derivatives showed intense emission bands at 600-650 nm. Their photophysical and electrochemical properties were compared with those of the corresponding mono TPA derivatives on the basis of theoretical calculations and cyclic voltammetry to evaluate the intramolecular electronic interactions between the donor and acceptor units.

  4. [Intramolecular cyclization reaction of multiple bonds and its application].

    PubMed

    Inagaki, Fuyuhiko

    2011-01-01

    The cycloaddition and cycloisomerization of the allene with an alkyne, alkene, or an additional allene for construction of various monocyclic and bicyclic ring systems has been developed. The characteristic features of these methods using allene functionality instead of a simple alkene or alkyne include the reaction mode that originated from the double function as well as the high efficiency for the constructions of medium-sized rings. Furthermore, asymmetric formal synthesis of (+)-nakadomarin A and total synthesis of (+)-fawcettimine and (+)-lycoposerramine-B based on highly stereoselective Pauson-Khand reaction of alkene-alkynes were completed.

  5. COOH-terminal processing of nascent polypeptides by the glycosylphosphatidylinositol transamidase in the presence of hydrazine is governed by the same parameters as glycosylphosphatidylinositol addition.

    PubMed

    Ramalingam, S; Maxwell, S E; Medof, M E; Chen, R; Gerber, L D; Udenfriend, S

    1996-07-23

    Proteins anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) moiety are found in all eukaryotes. After NH2-terminal peptide cleavage of the nascent protein by the signal peptidase, a second COOH-terminal signal peptide is cleaved with the concomitant addition of the GPI unit. The proposed mechanism of the GPI transfer is a transamidation reaction that involves the formation of an activated carbonyl intermediate (enzyme-substrate complex) with the ethanolamine moiety of the preassembled GPI unit serving as a nucleophile. Other nucleophilic acceptors like hydrazine (HDZ) and hydroxylamine have been shown to be possible alternate substrates for GPI. Since GPI has yet to be purified, the use of readily available nucleophilic substitutes such as HDZ and hydroxylamine is a viable alternative to study COOH-terminal processing by the putative transamidase. As a first step in developing a soluble system to study this process, we have examined the amino acid requirements at the COOH terminus for the transamidation reaction using HDZ as the nucleophilic acceptor instead of GPI. The hydrazide-forming reaction shows identical amino acid requirement profiles to that of GPI anchor addition. Additionally, we have studied other parameters relating to the kinetics of the transamidation reaction in the context of rough microsomal membranes. The findings with HDZ provide further evidence for the transamidase nature of the enzyme and also provide a starting point for development of a soluble assay.

  6. COOH-terminal processing of nascent polypeptides by the glycosylphosphatidylinositol transamidase in the presence of hydrazine is governed by the same parameters as glycosylphosphatidylinositol addition.

    PubMed Central

    Ramalingam, S; Maxwell, S E; Medof, M E; Chen, R; Gerber, L D; Udenfriend, S

    1996-01-01

    Proteins anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) moiety are found in all eukaryotes. After NH2-terminal peptide cleavage of the nascent protein by the signal peptidase, a second COOH-terminal signal peptide is cleaved with the concomitant addition of the GPI unit. The proposed mechanism of the GPI transfer is a transamidation reaction that involves the formation of an activated carbonyl intermediate (enzyme-substrate complex) with the ethanolamine moiety of the preassembled GPI unit serving as a nucleophile. Other nucleophilic acceptors like hydrazine (HDZ) and hydroxylamine have been shown to be possible alternate substrates for GPI. Since GPI has yet to be purified, the use of readily available nucleophilic substitutes such as HDZ and hydroxylamine is a viable alternative to study COOH-terminal processing by the putative transamidase. As a first step in developing a soluble system to study this process, we have examined the amino acid requirements at the COOH terminus for the transamidation reaction using HDZ as the nucleophilic acceptor instead of GPI. The hydrazide-forming reaction shows identical amino acid requirement profiles to that of GPI anchor addition. Additionally, we have studied other parameters relating to the kinetics of the transamidation reaction in the context of rough microsomal membranes. The findings with HDZ provide further evidence for the transamidase nature of the enzyme and also provide a starting point for development of a soluble assay. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:8755508

  7. Matrix isolation infrared and DFT study of the trimethyl phosphite-hydrogen chloride interaction: hydrogen bonding versus nucleophilic substitution.

    PubMed

    Ramanathan, N; Kar, Bishnu Prasad; Sundararajan, K; Viswanathan, K S

    2012-12-13

    Trimethyl phosphite (TMPhite) and hydrogen chloride (HCl), when separately codeposited in a N(2) matrix, yielded a hydrogen bonded adduct, which was evidenced by shifts in the vibrational frequencies of the TMPhite and HCl submolecules. The structure and energy of the adducts were computed at the B3LYP level using 6-31++G** and aug-cc-pVDZ basis sets. While our computations indicated four minima for the TMPhite-HCl adducts, only one adduct was experimentally identified in the matrix at low temperatures, which interestingly was not the structure corresponding to the global minimum, but was the structure corresponding to the first higher energy local minimum. The Onsager self-consistent reaction field model was used to explain this observation. In an attempt to prepare the hydrogen bonded adduct in the gas phase and then trap it in the matrix, TMPhite and HCl were premixed prior to deposition. However, in these experiments, no hydrogen bonded adduct was observed; on the contrary, TMPhite reacted with HCl to yield CH(3)Cl, following a nucleophilic substitution, a reaction that is apparently frustrated in the matrix.

  8. 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.

  9. 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

  10. 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.

  11. Controllable defluorination of fluorinated graphene and weakening of C-F bonding under the action of nucleophilic dipolar solvent.

    PubMed

    Wang, Xu; Wang, Weimiao; Liu, Yang; Ren, Mengmeng; Xiao, Huining; Liu, Xiangyang

    2016-01-28

    The effect of solvent on the chemical structure and properties of fluorinated graphene (FG) was particularly investigated in this work. It is found that the reduction of FG and the weakening of strong covalent C-F bonding take place under the action of some dipolar solvents even at room temperature. The rate of the C-F bond rupture reaction is positively influenced by the dipole moment of solvent and fluorine coverage of FG sheets. Meanwhile, defluorination of FG is controllable through the time and temperature of solvent treatment. These solvents function as the nucleophilic catalysts, promoting chemical transformation, which leads to a series of changes in the structure and properties of FG, such as a decline of fluorine concentration of about 40% and the reduction of thermal stability and band gap from 3 to 2 eV. After the treatment with dipolar solvent N-methyl-2-pyrrolidinone, FG maintained a capacity of 255 mA h g(-1) and a power density of 2986 W kg(-1) at a high discharge rate, while the pristine FG could not be discharged at all. This is called the "solvent activation" effect on the electrochemical performance of FG. The finding may draw attention to the effect of various external factors on the chemical structure and properties of FG, which is of great importance for the realization of the FG's potential. PMID:26745282

  12. New domino transposition/intramolecular Diels-Alder reaction in monocyclic allenols: a general strategy for tricyclic compounds.

    PubMed

    Alcaide, Benito; Almendros, Pedro; Aragoncillo, Cristina; Redondo, María C

    2002-07-21

    A novel and direct synthetic strategy to prepare fused tricycles has been developed from monocyclic allenols, masked functionalized dienes, which underwent a domino allenol transposition/intramolecular Diels-Alder reaction.

  13. 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.

  14. Synthesis of Fused Polycyclic Indoles by Brønsted Acid-Catalyzed Intramolecular Alkylation of Indoles with Alcohols.

    PubMed

    Suárez, Anisley; Gohain, Mukut; Fernández-Rodríguez, Manuel A; Sanz, Roberto

    2015-10-16

    An efficient methodology for the synthesis of a series of new fused polyclyclic indoles has been developed by Brønsted acid-catalyzed intramolecular Friedel-Crafts reactions of properly designed indolyl alcohols. PMID:26418556

  15. Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition reactions of 1-ene-, 1-yne- and 1-allene-vinylcyclopropanes.

    PubMed

    Jiao, Lei; Lin, Mu; Yu, Zhi-Xiang

    2010-02-21

    New Rh(I)-catalyzed intramolecular [3 + 2] cycloaddition reactions of 1-ene-, 1-yne and 1-allene-vinylcyclopropanes have been developed, affording an efficient and versatile synthesis of cyclopentane- and cyclopentene-embedded bicyclic structures.

  16. 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

  17. Highly efficient route to functionalized tetrahydrocarbazoles using a tandem cross-metathesis/intramolecular-hydroarylation sequence.

    PubMed

    An, Xiao-Lei; Chen, Jia-Rong; Li, Chang-Feng; Zhang, Fu-Gen; Zou, You-Quan; Guo, Ying-Cen; Xiao, Wen-Jing

    2010-10-01

    The scope of the novel ruthenium-catalyzed tandem cross-metathesis/intramolecular-hydroarylation sequence is described. This methodology offers a practical and efficient synthesis of structurally diverse and complex tetrahydrocarbazoles in good to excellent yields (up to 98%). Moreover, preliminary efforts towards the development of an enantioselective version of the current process by sequential catalysis with ruthenium complex and chiral amine are presented, with high yields and enantioselectivities (up to 88% yield and 91% ee).

  18. 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

  19. Thermally-Induced Substrate Release Via Intramolecular Cyclizations of Amino Esters and Amino Carbonates

    PubMed Central

    Knipp, Ralph J.; Estrada, Rosendo; Sethu, Palaniappan; Nantz, Michael H.

    2014-01-01

    The relative cleavage of an alcohol from a panel of amino esters and amino carbonates via intramolecular cyclization was examined as a mechanism for substrate release. Thermal stability at 37 °C was observed only for the 7-membered ring progenitors. Applicability of the approach was illustrated by δ-lactam formation within a poly(dimethylsiloxane) microchannel for release of a captured fluorescent probe. PMID:25061237

  20. 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.

  1. Intramolecular vibrational relaxation in a triatomic van der Waals molecule: ArCl2

    NASA Astrophysics Data System (ADS)

    Halberstadt, Nadine; Beswick, Alberto; Roncero, Octavio; Janda, Kenneth C.

    1992-02-01

    Exact quantum mechanical calculations of the vibrational predissociation of ArCl2 are reported. The results confirm the hypothesis that Δv=-2 dissociation of the B state, v'=10 level occurs by preliminary coupling to the Δv=-1 manifold followed by coupling to the Δv=-2 continuum. The intensity borrowing due to the coupling is consistent with intramolecular vibrational relaxation (IVR) in the sparse limit, ρV≤1.

  2. 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

  3. Coupling of electrons and intramolecular vibrations in TTF-TCNQ (tetrathiafulvalene-tetracyanoquinodimethane)

    NASA Astrophysics Data System (ADS)

    Etemad, Shahab

    1981-11-01

    We report experimental evidence for electron-intramolecular vibration coupling in TTF-TCNQ (tetrathiafulvalene-tetracyanoquinodimethane). Linear coupling of totally symmetric vibrations of ag modes to the oscillation in the phase of the charge-density waves gives rise to a set of IR-(infrared-) active modes which grow in intensity with the onset of the Peierls transition. Our experimental estimates of electron-intramolecular coupling constants of the TCNQ molecule are in good agreement with previous values. Moreover, the experimentally determined total electron-intramolecular coupling constant is λ≃0.35 for TCNQ stacks in TTF-TCNQ. These results indicate that the Peierls distorted state is predominantly stabilized by coupling of the unpaired electrons to the intramolecular vibrations. With the onset of Peierls transition, the two IR-active modes of CN-stretching vibration show a splitting due to a shift in frequency of the mode with the dipole component parallel to the crystallographic b and c axes. The splitting is also seen in the selenium analog TSeF-TCNQ and is consistent with the x-ray diffuse scattering result that the Peierls distortion is due to a rigid molecular translation in the bc plane. The temperature dependence of both effects show the presence of the sizable amplitude of the fluctuating charge-density waves in the temperature range 53[Bull. Am. Phys. Soc. 23, 381 (1978)].

  4. Intramolecular [4 + 2] trapping of a hexadehydro-Diels-Alder (HDDA) benzyne by tethered arenes.

    PubMed

    Pogula, Vedamayee D; Wang, Tao; Hoye, Thomas R

    2015-02-20

    We report here the efficient, intramolecular trapping in a Diels-Alder (DA) sense of thermally generated benzynes by one of two pendant arene rings. A more electron-rich ring (p-methoxyphenyl) reacted substantially faster than a simple phenyl ring, which was, in turn, slightly more reactive vs a 4-carbomethoxyphenyl ring. Photoinduced di-π-methane rearrangement of the initial DA adducts gave rise to unusual isomeric polycyclic adducts.

  5. 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

  6. 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.

  7. 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.

  8. Nitric oxide is reduced to HNO by proton-coupled nucleophilic attack by ascorbate, tyrosine, and other alcohols. A new route to HNO in biological media?

    PubMed

    Suarez, Sebastián A; Neuman, Nicolás I; Muñoz, Martina; Álvarez, Lucía; Bikiel, Damián E; Brondino, Carlos D; Ivanović-Burmazović, Ivana; Miljkovic, Jan Lj; Filipovic, Milos R; Martí, Marcelo A; Doctorovich, Fabio

    2015-04-15

    The role of NO in biology is well established. However, an increasing body of evidence suggests that azanone (HNO), could also be involved in biological processes, some of which are attributed to NO. In this context, one of the most important and yet unanswered questions is whether and how HNO is produced in vivo. A possible route concerns the chemical or enzymatic reduction of NO. In the present work, we have taken advantage of a selective HNO sensing method, to show that NO is reduced to HNO by biologically relevant alcohols with moderate reducing capacity, such as ascorbate or tyrosine. The proposed mechanism involves a nucleophilic attack to NO by the alcohol, coupled to a proton transfer (PCNA: proton-coupled nucleophilic attack) and a subsequent decomposition of the so-produced radical to yield HNO and an alkoxyl radical.

  9. Bis(difluoromethyl)trimethylsilicate Anion: A Key Intermediate in Nucleophilic Difluoromethylation of Enolizable Ketones with Me3 SiCF2 H.

    PubMed

    Chen, Dingben; Ni, Chuanfa; Zhao, Yanchuan; Cai, Xian; Li, Xinjin; Xiao, Pan; Hu, Jinbo

    2016-10-01

    A pentacoordinate bis(difluoromethyl)silicate anion, [Me3 Si(CF2 H)2 ](-) , is observed for the first time by the activation of Me3 SiCF2 H with a nucleophilic alkali-metal salt and 18-crown-6. Further study on its reactivity by tuning the countercation effect led to the discovery and development of an efficient, catalytic nucleophilic difluoromethylation of enolizable ketones with Me3 SiCF2 H by using a combination of CsF and 18-crown-6 as the initiation system. Mechanistic investigations demonstrate that [(18-crown-6)Cs](+) [Me3 Si(CF2 H)2 ](-) is a key intermediate in this catalytic reaction. PMID:27552967

  10. 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

  11. On the Intramolecular Hydrogen Bond in Solution: Car-Parrinello and Path Integral Molecular Dynamics Perspective.

    PubMed

    Dopieralski, Przemyslaw; Perrin, Charles L; Latajka, Zdzislaw

    2011-11-01

    The issue of the symmetry of short, low-barrier hydrogen bonds in solution is addressed here with advanced ab initio simulations of a hydrogen maleate anion in different environments, starting with the isolated anion, going through two crystal structures (sodium and potassium salts), then to an aqueous solution, and finally in the presence of counterions. By Car-Parrinello and path integral molecular dynamics simulations, it is demonstrated that the position of the proton in the intramolecular hydrogen bond of an aqueous hydrogen maleate anion is entirely related to the solvation pattern around the oxygen atoms of the intramolecular hydrogen bond. In particular, this anion has an asymmetric hydrogen bond, with the proton always located on the oxygen atom that is less solvated, owing to the instantaneous solvation environment. Simulations of water solutions of hydrogen maleate ion with two different counterions, K(+) and Na(+), surprisingly show that the intramolecular hydrogen-bond potential in the case of the Na(+) salt is always asymmetric, regardless of the hydrogen bonds to water, whereas for the K(+) salt, the potential for H motion depends on the location of the K(+). It is proposed that repulsion by the larger and more hydrated K(+) is weaker than that by Na(+) and competitive with solvation by water. PMID:26598249

  12. Theoretical study on the reactive sites and intramolecular interactions in taxol and its four analogues

    NASA Astrophysics Data System (ADS)

    Zhou, Hongwei; Zhang, Zhiqiang; Cheung, Hon-Yeung

    A density-functional study of the paclitaxel (Taxol) molecule and its four analogues has been performed. The theory of Bader's atoms in molecules (AIM) was applied to examine the electronic structure of these molecules at their ground state. Topological analysis reveals that the esterification of hydroxyl group attached to the oxetane ring results in great change of conformation of the taxane ring, and thus is responsible for bioactivity of the oxetane oxygen atom. It was found that there exists some intramolecular interactions in the molecule, including normal hydrogen bonds (HBs) and double HBs. Visualization of the molecule shows that the central bodies (the four fused rings) of the molecules are wrapped by the intramolecular interactions. It is supposed that these intramolecular interactions lower the aqueous solubility and protect the flexible oxetane ring, which is regarded as the dominating bioactivity site of the drug, from being opened. Our results provide an extended and consistent set of data to gauge classical force fields in view of the atomistic investigations of the interaction of the bioactive molecules.

  13. 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.

  14. 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.

  15. Intramolecular RNA replicase: Possibly the first self-replicating molecule in the RNA world

    NASA Astrophysics Data System (ADS)

    Ma, Wentao; Yu, Chunwu

    2006-08-01

    Although there is more and more evidence suggested the existence of an RNA World during the origin of life, the scenario concerning the origin of the RNA World remains blurry. Usually it is speculated that it originated from a prebiotic nucleotide pool, during which a self-replicating RNA synthesis ribozyme may have emerged as the first ribozyme the RNA replicase. However, there is yet no ersuasive supposition for the mechanism for the self-favouring feature of the replicase, thus the speculation remains unconvincing. Here we suggest that intramolecular catalysis is a possible solution. Two RNA synthesis ribozymes may be integrated into one RNA molecule, as two functional domains which could catalyze the copy of each other. Thus the RNA molecule could self-replicate and be referred to as “intramolecular replicase“ here. Computational simulation to get insight into the dynamic mechanism of emergence of the intramolecular replicase from a nucleotide pool is valuable and would be included in a following work of our group.

  16. 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.

  17. Ladderlike oligomers; intramolecular hydrogen bonding, push-pull character, and electron affinity.

    PubMed

    Pieterse, K; Vekemans, J A; Kooijman, H; Spek, A L; Meijer, E W

    2000-12-15

    Symmetrical 2,5-bis(2-aminophenyl)pyrazines have been synthesized by application of the Stille coupling strategy. These cotrimers feature three important properties, namely strong intramolecular hydrogen bonding, push-pull character, and high electron affinity. The presence of intramolecular hydrogen bonds has been confirmed by 1H NMR, IR spectroscopy, and single-crystal X-ray diffraction. The hydrogen bond strength can be increased by substituting the amino groups with stronger electron-withdrawing functionalities. Despite the anticipated enhanced pi-conjugation through planarization, a hypsochromic shift was observed in the UV/Vis spectra, explained by a decrease in push-pull character. The electron affinity of the cotrimers was deduced from the first reduction potentials measured by cyclic voltammetry and is related to the electron-withdrawing character of the amino substituents. The results obtained have been compared with those of the corresponding 4-aminophenyl analogues and show that intramolecular hydrogen bonds can be used to design polymers with enhanced pi conjugation as well as a high electron affinity.

  18. Sulfoxide-TFAA and nucleophile combination as new reagent for aliphatic C-H functionalization at indole 2α-position.

    PubMed

    Tayu, Masanori; Higuchi, Kazuhiro; Inaba, Masato; Kawasaki, Tomomi

    2013-01-21

    Aliphatic C-H functionalization at indole 2α-position mediated by acyloxythionium species 1 generated from sulfoxide and acid anhydride has been developed. The combination of sulfoxide and TFAA with O-, N- and C-nucleophiles enabled introduction of various substituents in a one-pot procedure. Especially on utilizing DMSO, the combination provided a practical and efficient method for the synthesis of a wide range of 2α-substituted indoles.

  19. 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.

  20. 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