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Proton Abstraction (proton + abstraction)
Selected AbstractsThe Superbase-Mediated Pairwise Substitution of the 2,2,- and 6,6,-Positions in a Biphenyl DerivativeEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 5 2004Manfred Schlosser Abstract The superbasic mixture of butyllithium and potassium tert -butoxide is powerful enough to enable the double proton abstraction from one ortho and one ortho, position of 4,4,-di- tert -butylbiphenyl. In this way, a series of functionalized derivatives becomes readily accessible, among them 4,4,-di- tert -butylbiphenyldiyl-2,2,-dicarboxylic acid (2a) and 4,4,-di- tert -butylbiphenyl-2,2,-diol (2d). The latter compound can be subjected again to a superbase-promoted double metalation, thus giving rise to 2,2,,6,6,-tetrasubstituted biphenyl derivatives. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Importance of tyrosine residues of Bacillus stearothermophilus serine hydroxymethyltransferase in cofactor binding and l - allo -Thr cleavageFEBS JOURNAL, Issue 18 2008Crystal structure, biochemical studies Serine hydroxymethyltransferase (SHMT) from Bacillus stearothermophilus (bsSHMT) is a pyridoxal 5,-phosphate-dependent enzyme that catalyses the conversion of l -serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. In addition, the enzyme catalyses the tetrahydrofolate-independent cleavage of 3-hydroxy amino acids and transamination. In this article, we have examined the mechanism of the tetrahydrofolate-independent cleavage of 3-hydroxy amino acids by SHMT. The three-dimensional structure and biochemical properties of Y51F and Y61A bsSHMTs and their complexes with substrates, especially l - allo -Thr, show that the cleavage of 3-hydroxy amino acids could proceed via C, proton abstraction rather than hydroxyl proton removal. Both mutations result in a complete loss of tetrahydrofolate-dependent and tetrahydrofolate-independent activities. The mutation of Y51 to F strongly affects the binding of pyridoxal 5,-phosphate, possibly as a consequence of a change in the orientation of the phenyl ring in Y51F bsSHMT. The mutant enzyme could be completely reconstituted with pyridoxal 5,-phosphate. However, there was an alteration in the ,max value of the internal aldimine (396 nm), a decrease in the rate of reduction with NaCNBH3 and a loss of the intermediate in the interaction with methoxyamine (MA). The mutation of Y61 to A results in the loss of interaction with C, and C, of the substrates. X-Ray structure and visible CD studies show that the mutant is capable of forming an external aldimine. However, the formation of the quinonoid intermediate is hindered. It is suggested that Y61 is involved in the abstraction of the C, proton from 3-hydroxy amino acids. A new mechanism for the cleavage of 3-hydroxy amino acids via C, proton abstraction by SHMT is proposed. [source] Characterization of the glycosidic linkage of underivatized disaccharides by interaction with Pb2+ ionsJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 8 2007Ahlam El Firdoussi Abstract Electrospray ionization in combination with tandem mass spectrometry and lead cationization is used to characterize the linkage position of underivatized disaccharides. Lead(II) ions react mainly with disaccharides by proton abstraction to generate [Pb(disaccharide)m, H]+ ions (m = 1,2). At low cone voltages, an intense series of doubly charged ions of general formula [Pb(disaccharide)n]2+ are also observed. Our study shows that MS/MS experiments have to be performed to differentiate Pb2+ -coordinated disaccharides. Upon collision, [Pb(disaccharide) , H]+ species mainly dissociate according to glycosidic bond cleavage and cross-ring cleavages, leading to the elimination of CnH2nOn neutrals (n = 2,4). The various fragmentation processes allow the position of the glycosidic bond to be unambiguously located. Distinction between glc-glc and glc-fru disaccharides also appears straightforward. Furthermore, for homodimers of D -glucose our data demonstrate that the anomericity of the glycosidic bond can be characterized for the 1 , n linkages (n = 2, 4, 6). Consequently, Pb2+ cationization combined with tandem mass spectrometry appears particularly useful to identify underivatized disaccharides. Copyright © 2007 John Wiley & Sons, Ltd. [source] Structural characterization of hexoses and pentoses using lead cationization.JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 4 2002An electrospray ionization, tandem mass spectrometric study Abstract The analytical potential of the complexation of isomeric underivatized hexoses (D -glucose, D -galactose, D -mannose, D -talose, D -fructose), methylglycosides (1- O -methyl-,- D -glucose and 1- O -methyl-,- D -glucose) and pentoses (D -ribose, D -xylose, D -arabinose and D -lyxose) by Pb2+ ions, was investigated by electrospray ionization and tandem mass spectrometry (MS/MS). Pb2+ ions react mainly with monosaccharides by proton abstraction to generate [Pb(monosaccharide)m , H]+ ions (m = 1,3). At low cone voltage, a less abundant series of doubly charged ions of general formula [Pb(monosaccharide)n]2+ is also observed. The maximum number n of monosaccharides surrounding a single Pb2+ ion depends on the metal : monosaccharide ratio. Our study shows that MS/MS experiments have to be performed to differentiate Pb2+ -coordinated monosaccharides. Upon collision, [Pb(monosaccharide) , H]+ species mainly dissociate according to cross-ring cleavages, leading to the elimination of CnH2nOn neutrals. The various fragmentation processes observed allow the C(1), C(2) and C(4) stereocenters of aldohexoses to be characterized, and also a clear distinction aldoses and fructose. Furthermore, careful analysis of tandem mass spectra also leads to successful aldopentose distinction. Lead cationization combined with MS/MS therefore appears particularly useful to identify underivatized monosaccharides. Copyright © 2002 John Wiley & Sons, Ltd. [source] Deactivation reactions in the modeled 2,2,6,6-tetramethyl-1-piperidinyloxy-mediated free-radical polymerization of styrene: A comparative study with the 2,2,6,6-tetramethyl-1-piperidinyloxy/acrylonitrile systemJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 2 2007Andrzej Kaim Abstract The competitiveness of the combination and disproportionation reactions between a 1-phenylpropyl radical, standing for a growing polystyryl macroradical, and a 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radical in the nitroxide-mediated free-radical polymerization of styrene was quantitatively evaluated by the study of the transition geometry and the potential energy profiles for the competing reactions with the use of quantum-mechanical calculations at the density functional theory (DFT) UB3-LYP/6-311+G(3df, 2p)//(unrestricted) Austin Model 1 level of theory. The search for transition geometries resulted in six and two transition structures for the radical combination and disproportionation reactions, respectively. The former transition structures, mainly differing in the out-of-plane angle of the NO bond in the transition structure TEMPO molecule, were correlated with the activation energy, which was determined to be in the range of 8.4,19.4 kcal mol,1 from a single-point calculation at the DFT UB3-LYP/6-311+G(3df, 2p)//unrestricted Austin Model 1 level. The calculated activation energy for the disproportionation reaction was less favorable by a value of more than 30 kcal mol,1 in comparison with that for the combination reaction. The approximate barrier difference for the TEMPO addition and disproportionation reaction was slightly smaller for the styrene polymerization system than for the acrylonitrile polymerization system, thus indicating that a ,-proton abstraction through a TEMPO radical from the polymer backbone could diminish control over the radical polymerization of styrene with the nitroxide even more than in the latter system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 232,241, 2007 [source] Determination of enzyme mechanisms by molecular dynamics: Studies on quinoproteins, methanol dehydrogenase, and soluble glucose dehydrogenasePROTEIN SCIENCE, Issue 8 2004Swarnalatha Y. Reddy Abstract Molecular dynamics (MD) simulations have been carried out to study the enzymatic mechanisms of quinoproteins, methanol dehydrogenase (MDH), and soluble glucose dehydrogenase (sGDH). The mechanisms of reduction of the orthoquinone cofactor (PQQ) of MDH and sGDH involve concerted base-catalyzed proton abstraction from the hydroxyl moiety of methanol or from the 1-hydroxyl of glucose, and hydride equivalent transfer from the substrate to the quinone carbonyl carbon C5 of PQQ. The products of methanol and glucose oxidation are formaldehyde and glucolactone, respectively. The immediate product of PQQ reduction, PQQH, [,HC5(O,) ,C4( = O) ,] and PQQH [,HC5(OH) ,C4( = O) ,] converts to the hydroquinone PQQH2 [,C5(OH) = C4(OH) ,]. The main focus is on MD structures of MDH , PQQ , methanol, MDH , PQQH,, MDH , PQQH, sGDH , PQQ , glucose, sGDH , PQQH, (glucolactone, and sGDH , PQQH. The reaction PQQ , PQQH, occurs with Glu 171,CO2, and His 144,Im as the base species in MDH and sGDH, respectively. The general-base-catalyzed hydroxyl proton abstraction from substrate concerted with hydride transfer to the C5 of PQQ is assisted by hydrogen-bonding to the C5 = O by Wat1 and Arg 324 in MDH and by Wat89 and Arg 228 in sGDH. Asp 297,COOH would act as a proton donor for the reaction PQQH, , PQQH, if formed by transfer of the proton from Glu 171,COOH to Asp 297,CO2, in MDH. For PQQH , PQQH2, migration of H5 to the C4 oxygen may be assisted by a weak base like water (either by crystal water Wat97 or bulk solvent, hydrogen-bonded to Glu 171,CO2, in MDH and by Wat89 in sGDH). [source] Structural characterization of tartrate dehydrogenase: a versatile enzyme catalyzing multiple reactionsACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2010Radhika Malik The first structure of an NAD-dependent tartrate dehydrogenase (TDH) has been solved to 2,Å resolution by single anomalous diffraction (SAD) phasing as a complex with the intermediate analog oxalate, Mg2+ and NADH. This TDH structure from Pseudomonas putida has a similar overall fold and domain organization to other structurally characterized members of the hydroxy-acid dehydrogenase family. However, there are considerable differences between TDH and these functionally related enzymes in the regions connecting the core secondary structure and in the relative positioning of important loops and helices. The active site in these complexes is highly ordered, allowing the identification of the substrate-binding and cofactor-binding groups and the ligands to the metal ions. Residues from the adjacent subunit are involved in both the substrate and divalent metal ion binding sites, establishing a dimer as the functional unit and providing structural support for an alternating-site reaction mechanism. The divalent metal ion plays a prominent role in substrate binding and orientation, together with several active-site arginines. Functional groups from both subunits form the cofactor-binding site and the ammonium ion aids in the orientation of the nicotinamide ring of the cofactor. A lysyl amino group (Lys192) is the base responsible for the water-mediated proton abstraction from the C2 hydroxyl group of the substrate that begins the catalytic reaction, followed by hydride transfer to NAD. A tyrosyl hydroxyl group (Tyr141) functions as a general acid to protonate the enolate intermediate. Each substrate undergoes the initial hydride transfer, but differences in substrate orientation are proposed to account for the different reactions catalyzed by TDH. [source] Synthesis and Reactivity of Rare Earth Metal Alkyl Complexes Stabilized by Anilido Phosphinimine and Amino Phosphine LigandsCHEMISTRY - A EUROPEAN JOURNAL, Issue 3 2007Bo Liu Abstract Anilido phosphinimino ancillary ligand H2L1 reacted with one equivalent of rare earth metal trialkyl [Ln{CH2Si(CH3)3}3(thf)2] (Ln=Y, Lu) to afford rare earth metal monoalkyl complexes [L1LnCH2Si(CH3)3(THF)] (1,a: Ln=Y; 1,b: Ln=Lu). In this process, deprotonation of H2L1 by one metal alkyl species was followed by intramolecular CH activation of the phenyl group of the phosphine moiety to generate dianionic species L1 with release of two equivalnts of tetramethylsilane. Ligand L1 coordinates to Ln3+ ions in a rare C,N,N tridentate mode. Complex l,a reacted readily with two equivalents of 2,6-diisopropylaniline to give the corresponding bis-amido complex [(HL1)LnY(NHC6H3iPr2 -2,6)2] (2) selectively, that is, the CH activation of the phenyl group is reversible. When 1,a was exposed to moisture, the hydrolyzed dimeric complex [{(HL1)Y(OH)}2](OH)2 (3) was isolated. Treatment of [Ln{CH2Si(CH3)3}3(thf)2] with amino phosphine ligands HL2-R gave stable rare earth metal bis-alkyl complexes [(L2-R)Ln{CH2Si(CH3)3}2(thf)] (4,a: Ln=Y, R=Me; 4,b: Ln=Lu, R=Me; 4,c: Ln=Y, R=iPr; 4,d: Ln=Y, R=iPr) in high yields. No proton abstraction from the ligand was observed. Amination of 4,a and 4,c with 2,6-diisopropylaniline afforded the bis-amido counterparts [(L2-R)Y(NHC6H3iPr2 -2,6)2(thf)] (5,a: R=Me; 5,b: R=iPr). Complexes 1,a,b and 4,a,d initiated the ring-opening polymerization of d,l -lactide with high activity to give atactic polylactides. [source] Understanding the Key Factors that Control the Inhibition of Type,II Dehydroquinase by (2R)-2-Benzyl-3-dehydroquinic AcidsCHEMMEDCHEM, Issue 10 2010Antonio Peón Abstract The binding mode of several substrate analogues, (2R)-2-benzyl-3-dehydroquinic acids 4, which are potent reversible competitive inhibitors of type,II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway, has been investigated by structural and computational studies. The crystal structures of Mycobacterium tuberculosis and Helicobacter pylori DHQ2 in complex with one of the most potent inhibitor, p -methoxybenzyl derivative 4,a, have been solved at 2.40,Å and 2.75,Å, respectively. This has allowed the resolution of the M.,tuberculosis DHQ2 loop containing residues 20,25 for the first time. These structures show the key interactions of the aromatic ring in the active site of both enzymes and additionally reveal an important change in the conformation and flexibility of the loop that closes over substrate binding. The loop conformation and the binding mode of compounds 4,b,d has been also studied by molecular dynamics simulations, which suggest that the benzyl group of inhibitors 4 prevent appropriate orientation of the catalytic tyrosine of the loop for proton abstraction and disrupts its basicity. [source] | ||||||||||