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James M Mayer - One of the best experts on this subject based on the ideXlab platform.
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c h oxidation in fluorenyl Benzoates does not proceed through a stepwise pathway revisiting asynchronous proton coupled electron transfer
Chemical Science, 2021Co-Authors: Scott Coste, Anna C Brezny, Brian Koronkiewicz, James M MayerAbstract:2-Fluorenyl Benzoates were recently shown to undergo C–H bond oxidation through intramolecular proton transfer coupled with electron transfer to an external oxidant. Kinetic analysis revealed unusual rate-driving force relationships. Our analysis indicated a mechanism of multi-site concerted proton–electron transfer (MS-CPET) for all of these reactions. More recently, an alternative interpretation of the kinetic data was proposed to explain the unusual rate-driving force relationships, invoking a crossover from CPET to a stepwise mechanism with an initial intramolecular proton transfer (PT) (Costentin, Saveant, Chem. Sci., 2020, 11, 1006). Here, we show that this proposed alternative pathway is untenable based on prior and new experimental assessments of the intramolecular PT equilibrium constant and rates. Measurement of the fluorenyl 9-C–H pKa, H/D exchange experiments, and kinetic modelling with COPASI eliminate the possibility of a stepwise mechanism for C–H oxidation in the fluorenyl benzoate series. Implications for asynchronous (imbalanced) MS-CPET mechanisms are discussed with respect to classical Marcus theory and the quantum-mechanical treatment of concerted proton–electron transfer.
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c h oxidation in fluorenyl Benzoates does not proceed through a stepwise pathway revisiting asynchronous proton coupled electron transfer
ChemRxiv, 2021Co-Authors: Scott Coste, Anna C Brezny, Brian Koronkiewicz, James M MayerAbstract:2-fluorenyl Benzoates were recently shown to undergo C–H bond oxidation through intramolecular proton transfer coupled with electron transfer to an external oxidant. Kinetic analysis revealed unusual rate-driving force relationships and indicated a mechanism of multi-site concerted proton-electron transfer (MS-CPET) for all reactions. More recently, an alternative interpretation of the data was proposed to explain the rate-driving force relationships, invoking a crossover from CPET to a stepwise mechanism with an initial intramolecular proton transfer (PT) (Costentin, Saveant, Chem. Sci., 2020, 11, 1006). Here, we show that this proposed alternative pathway is untenable based on new experimental assessments of the intramolecular PT equilibrium constant and rates. Measurement of the fluorenyl 9-C–H pKa, H/D exchange experiments, and kinetic modelling eliminate the possibility of a stepwise mechanism for C–H oxidation in the fluorenyl benzoate series. Implications for asynchronous MS-CPET mechanisms are discussed with respect to classical Marcus theory and the quantum-mechanical treatment of CPET.
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transition state asymmetry in c h bond cleavage by proton coupled electron transfer
Journal of the American Chemical Society, 2019Co-Authors: Julia W Darcy, Scott S Kolmar, James M MayerAbstract:The selective transformation of C-H bonds is a longstanding challenge in modern chemistry. A recent report details C-H oxidation via multiple-site concerted proton-electron transfer (MS-CPET), where the proton and electron in the C-H bond are transferred to separate sites. Reactivity at a specific C-H bond was achieved by appropriate positioning of an internal benzoate base. Here, we extend that report to reactions of a series of molecules with differently substituted fluorenyl-Benzoates and varying outer-sphere oxidants. These results probe the fundamental rate versus driving force relationships in this MS-CPET reaction at carbon by separately modulating the driving force for the proton and electron transfer components. The rate constants depend strongly on the pKa of the internal base, but depend much less on the nature of the outer-sphere oxidant. These observations suggest that the transition states for these reactions are imbalanced. Density functional theory (DFT) was used to generate an internal reaction coordinate, which qualitatively reproduced the experimental observation of a transition state imbalance. Thus, in this system, homolytic C-H bond cleavage involves concerted but asynchronous transfer of the H+ and e-. The nature of this transfer has implications for synthetic methodology and biological systems.
Junichi Hasegawa - One of the best experts on this subject based on the ideXlab platform.
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inhibitory effects of cucurbitane glycosides and other triterpenoids from the fruit of momordica grosvenori on epstein barr virus early antigen induced by tumor promoter 12 o tetradecanoylphorbol 13 acetate
Journal of Agricultural and Food Chemistry, 2002Co-Authors: Motohiko Ukiya, Teruo Mukainaka, Toshihiro Akihisa, Yumiko Kimura, Masakazu Toriumi, Norihiro Banno, Junichi HasegawaAbstract:Two new triterpene Benzoates, 5-dehydrokarounidiol dibenzoate (1) and karounidiol dibenzoate (2), and two new triterpene glycosides, 5α,6α-epoxymogroside IE1 (8) and 11-oxomogroside A1 (9), along with 15 known triterpenoids (one triterpene benzoate, 3; three triterpene mono-ols, 4−6; one triterpene aglycon, 7; and 10 triterpene glycosides, 10−19), were isolated from the ethanol extract of the fruit of Momordica grosvenori. The structures of 1, 2, 8, and 9 were determined on the basis of spectroscopic and chemical methods. Among the known triterpene glycosides, mogroside I E1 (12) was a new naturally occurring compound. Eighteen triterpenoids (2−19) and 11-oxomogrol (20), a hydrolysis product of 9, were evaluated with respect to their inhibitory effects on the induction of Epstein−Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on...
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inhibitory effects of cucurbitane glycosides and other triterpenoids from the fruit of momordica grosvenori on epstein barr virus early antigen induced by tumor promoter 12 o tetradecanoylphorbol 13 acetate
Journal of Agricultural and Food Chemistry, 2002Co-Authors: Motohiko Ukiya, Teruo Mukainaka, Toshihiro Akihisa, Yumiko Kimura, Masakazu Toriumi, Norihiro Banno, Junichi HasegawaAbstract:Two new triterpene Benzoates, 5-dehydrokarounidiol dibenzoate (1) and karounidiol dibenzoate (2), and two new triterpene glycosides, 5alpha,6alpha-epoxymogroside IE(1) (8) and 11-oxomogroside A(1) (9), along with 15 known triterpenoids (one triterpene benzoate, 3; three triterpene mono-ols, 4-6; one triterpene aglycon, 7; and 10 triterpene glycosides, 10-19), were isolated from the ethanol extract of the fruit of Momordica grosvenori. The structures of 1, 2, 8, and 9 were determined on the basis of spectroscopic and chemical methods. Among the known triterpene glycosides, mogroside I E(1) (12) was a new naturally occurring compound. Eighteen triterpenoids (2-19) and 11-oxomogrol (20), a hydrolysis product of 9, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on EBV-EA induction (70-100% inhibition at 1 x 10(3) mol ratio/TPA).
Rich G Carter - One of the best experts on this subject based on the ideXlab platform.
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stereoselective ag catalyzed cyclizations to access polysubstituted pyran ring systems synthesis of c1 c12 subunit of madeirolide a
Organic Letters, 2016Co-Authors: Kazuhiro Watanabe, Nagarathanam Veerasamy, Ankan Ghosh, Jinming Li, Rich G CarterAbstract:The exploration into the scope of a silver-catalyzed cyclization (AgCC) of propargyl Benzoates for accessing pyran ring systems has been reported. The impact of the degree of substitution, nature of the substitution on the carbon backbone/benzoate moiety, and stereochemistry has been evaluated. The application of this methodology to the synthesis of the C1-C12 southern fragment of madeirolide A is disclosed.
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Stereoselective, Ag-Catalyzed Cyclizations To Access Polysubstituted Pyran Ring Systems: Synthesis of C1–C12 Subunit of Madeirolide A
2016Co-Authors: Kazuhiro Watanabe, Nagarathanam Veerasamy, Ankan Ghosh, Rich G CarterAbstract:The exploration into the scope of a silver-catalyzed cyclization (AgCC) of propargyl Benzoates for accessing pyran ring systems has been reported. The impact of the degree of substitution, nature of the substitution on the carbon backbone/benzoate moiety, and stereochemistry has been evaluated. The application of this methodology to the synthesis of the C1–C12 southern fragment of madeirolide A is disclosed
Motohiko Ukiya - One of the best experts on this subject based on the ideXlab platform.
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inhibitory effects of cucurbitane glycosides and other triterpenoids from the fruit of momordica grosvenori on epstein barr virus early antigen induced by tumor promoter 12 o tetradecanoylphorbol 13 acetate
Journal of Agricultural and Food Chemistry, 2002Co-Authors: Motohiko Ukiya, Teruo Mukainaka, Toshihiro Akihisa, Yumiko Kimura, Masakazu Toriumi, Norihiro Banno, Junichi HasegawaAbstract:Two new triterpene Benzoates, 5-dehydrokarounidiol dibenzoate (1) and karounidiol dibenzoate (2), and two new triterpene glycosides, 5α,6α-epoxymogroside IE1 (8) and 11-oxomogroside A1 (9), along with 15 known triterpenoids (one triterpene benzoate, 3; three triterpene mono-ols, 4−6; one triterpene aglycon, 7; and 10 triterpene glycosides, 10−19), were isolated from the ethanol extract of the fruit of Momordica grosvenori. The structures of 1, 2, 8, and 9 were determined on the basis of spectroscopic and chemical methods. Among the known triterpene glycosides, mogroside I E1 (12) was a new naturally occurring compound. Eighteen triterpenoids (2−19) and 11-oxomogrol (20), a hydrolysis product of 9, were evaluated with respect to their inhibitory effects on the induction of Epstein−Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on...
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inhibitory effects of cucurbitane glycosides and other triterpenoids from the fruit of momordica grosvenori on epstein barr virus early antigen induced by tumor promoter 12 o tetradecanoylphorbol 13 acetate
Journal of Agricultural and Food Chemistry, 2002Co-Authors: Motohiko Ukiya, Teruo Mukainaka, Toshihiro Akihisa, Yumiko Kimura, Masakazu Toriumi, Norihiro Banno, Junichi HasegawaAbstract:Two new triterpene Benzoates, 5-dehydrokarounidiol dibenzoate (1) and karounidiol dibenzoate (2), and two new triterpene glycosides, 5alpha,6alpha-epoxymogroside IE(1) (8) and 11-oxomogroside A(1) (9), along with 15 known triterpenoids (one triterpene benzoate, 3; three triterpene mono-ols, 4-6; one triterpene aglycon, 7; and 10 triterpene glycosides, 10-19), were isolated from the ethanol extract of the fruit of Momordica grosvenori. The structures of 1, 2, 8, and 9 were determined on the basis of spectroscopic and chemical methods. Among the known triterpene glycosides, mogroside I E(1) (12) was a new naturally occurring compound. Eighteen triterpenoids (2-19) and 11-oxomogrol (20), a hydrolysis product of 9, were evaluated with respect to their inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, which is known to be a primary screening test for antitumor promoters. All of the compounds tested showed potent inhibitory effects on EBV-EA induction (70-100% inhibition at 1 x 10(3) mol ratio/TPA).
Lindsay D Eltis - One of the best experts on this subject based on the ideXlab platform.
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characterization of hybrid toluate and benzoate dioxygenases
Journal of Bacteriology, 2003Co-Authors: Lindsay D EltisAbstract:Bacterial ring-hydroxylating dioxygenases are involved in the aerobic catabolism of a wide variety of aromatic compounds and thus play a critical role in the global carbon cycle. These multicomponent enzymes catalyze the NAD(P)H-dependent dihydroxylation of the aromatic ring, incorporating both atoms of dioxygen into the product (14, 21). Ring-hydroxylating dioxygenases have applications in the biodegradation of pollutants, many of which are aromatic compounds (49). In addition, due to their regio- and enantiospecificity, these enzymes are of burgeoning importance in generating synthons for the pharmaceutical and chemical industries (7, 22). Ring-hydroxylating dioxygenases typically consist of a hexameric oxygenase (ISP) of (αβ)3 configuration, a reductase (RED), and sometimes a ferredoxin. The α subunit of the ISP contains a Rieske-type Fe2S2 center and an active-site mononuclear iron. RED and the ferredoxin, if present, transfer reducing equivalents from NAD(P)H to the ISP. Due to their importance and potential applications, considerable effort has been focused on identifying the specificity determinants of these enzymes. Structural studies of naphthalene dioxygenase (NDO) (9) and biphenyl dioxygenase (BPDO) (12) indicate that the substrate-binding pocket is contained entirely within the C terminus of the ISP α subunit. To functionally evaluate specificity determinants, hybrid ISPs consisting of the α subunit of one enzyme and the β subunit of a related enzyme have been studied. Such experiments with NDO, BPDO, and related enzymes indicate that the α subunit is responsible for substrate preference (2, 5, 31, 40, 41). Directed mutagenesis and gene-shuffling approaches have further indicated that the α subunit harbors the principal determinants of substrate preference (3, 32, 36, 42, 43, 48). In each of these studies, enzyme function was evaluated solely in terms of substrate preference, in part due to the limited solubility of the substrates. Moreover, this preference was evaluated by using whole-cell biotransformation. Interestingly, some studies using purified hybrid ISPs indicate that the β subunit can influence the substrate preference (28, 33). This is consistent with structural data indicating that the β subunit interacts with the α subunit close to the active site of the enzyme (9, 12). Toluate dioxygenase of Pseudomonas putida mt-2 (TADOmt2) (EC 1.14.12.-) (27) and benzoate dioxygenase of Acinetobacter calcoaceticus ADP1 (BADOADP1) (EC 1.14.12.10) are group II dioxygenases (37) (class IB according to the system of Batie et al. [4]) that catalyze the dihydroxylation of Benzoates (Fig. (Fig.1).1). The α and β subunits of TADOmt2 are encoded by xylXY, respectively, and those of BADOADP1 are encoded by benAB, respectively (39). The RED components of TADOmt2 and BADOADP1 are encoded by xylZ and benC, respectively (25, 38). The ISP components of TADOmt2 (ISPTADO or αTβT) and BADOADP1 (ISPBADO or αBβB) share approximately 62% sequence identity yet transform different ranges of substituted Benzoates. Thus, TADOmt2 transforms a wide range of substituted Benzoates (54) and shows highest specificity for 3-methylbenazoate (20). In contrast, BADO transforms a much narrower range of substrates (53). The different specificities of these related enzymes and the solubility of their substrates allow kinetics studies to be performed with a wider range of substrate concentrations, thereby facilitating a more thorough investigation of the structural determinants of function in this important class of enzymes. FIG. 1. The reaction catalyzed by TADOmt2 and BADOADP1. These ring-hydroxylating dioxygenases initiate the catabolism of substituted Benzoates, catalyzing their transformation to the corresponding cis-1,2-dihydroxycyclohexadienes. Each enzyme consists of two ... In the present study, BADOADP1 was overexpressed and purified by using approaches similar to those developed for TADOmt2. Hybrids ISPs consisting of the α subunit of one enzyme and the β subunit of the other were expressed and purified, and their respective specificities for a range of substituted Benzoates were compared to those of the parent enzymes. The coupling of substrate utilization in the hybrid enzymes was also investigated. The contributions of the different subunits to the activities of these enzymes are discussed.
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reactivity of toluate dioxygenase with substituted Benzoates and dioxygen
Journal of Bacteriology, 2002Co-Authors: Frederic H Vaillancourt, Nathalie Y R Agar, Lindsay D EltisAbstract:Toluate dioxygenase (TADO) of Pseudomonas putida mt-2 catalyzes the dihydroxylation of a broad range of substituted Benzoates. The two components of this enzyme were hyperexpressed and anaerobically purified. Reconstituted TADO had a specific activity of 3.8 U/mg with m-toluate, and each component had a full complement of their respective Fe(2)S(2) centers. Steady-state kinetics data obtained by using an oxygraph assay and by varying the toluate and dioxygen concentrations were analyzed by a compulsory order ternary complex mechanism. TADO had greatest specificity for m-toluate, displaying apparent parameters of KmA = 9 +/- 1 microM, k(cat) = 3.9 +/- 0.2 s(-1), and K(m)O(2) = 16 +/- 2 microM (100 mM sodium phosphate, pH 7.0; 25 degrees C), where K(m)O(2) represents the K(m) for O(2) and KmA represents the K(m) for the aromatic substrate. The enzyme utilized Benzoates in the following order of specificity: m-toluate > benzoate approximately 3-chlorobenzoate > p-toluate approximately 4-chlorobenzoate >> o-toluate approximately 2-chlorobenzoate. The transformation of each of the first five compounds was well coupled to O(2) utilization and yielded the corresponding 1,2-cis-dihydrodiol. In contrast, the transformation of ortho-substituted Benzoates was poorly coupled to O(2) utilization, with >10 times more O(2) being consumed than benzoate. However, the apparent K(m) of TADO for these Benzoates was >100 microM, indicating that they do not effectively inhibit the turnover of good substrates.