Tetrahedral Intermediate (tetrahedral + intermediate)

Distribution by Scientific Domains
Distribution within Chemistry


Selected Abstracts


Tetrahedral intermediates in reactions of carboxylic acid derivatives with nucleophiles,

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2005
Martin Adler
Abstract Transacylation reactions of carboxylic acids, carboxylic acid esters, carboxylic acid amides and other carboxylic acid derivatives are among the most widespread and most important reactions in chemistry and biochemistry. Already in 1887, Claisen suggested a tetrahedral intermediate in transformations of carboxylic acid derivatives with nucleophiles. A historical overview gives insight into the studies to detect possible tetrahedral intermediates in such reactions. However, only in recent years has detailed information concerning the structures of such species become available. In this review, neutral, cationic and anionic tetrahedral intermediates are described which serve as models for transacylations under neutral, acid-catalysed or basic conditions. The characteristically different structures correspond nicely with experimental experience with reactions of carboxylic acid derivatives and with quantum chemical model calculations on tetrahedral intermediates. Finally, by means of model calculations, an explanation is given for the fast reactions of Weinreb amides, RC(O)N(CH3)OCH3, with organolithium and even with Grignard reagents: the reactions are determined by comparatively stable chelate transition states. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Kinetics and mechanism of the pyridinolysis of aryl dithiobenzoates in acetonitrile

INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 8 2004
Hyuck Keun Oh
The kinetics and mechanism of the aminolysis of aryl dithiobenzoates (RC(S)SC6H4Z; R = Ph) with pyridines (XC5H4N) in acetonitrile at 60.0°C have been studied. A biphasic Brönsted plot is obtained with a change in slope from a large value (,X , 0.7,0.8) to a small value (,X , 0.2) at pKa° = 5.2, which is interpreted to indicate a change of the rate-determining step from breakdown to formation of the zwitterionic tetrahedral intermediate, T±, at pKa = 5.2 as the pyridine basicity is increased. Rates are compared with those corresponding values for aryl dithioacetates (R = Me). The faster rates for R = Me than for R = Ph, for the rate-limiting formation of T±, can be attributed to the hyperconjugative charge transfer effect of the Me group, pseudo-,Me , ,*C=S. Clear-cut change in the cross-interaction constants, ,XZ, from +1.47 to ,0.20 supports the proposed mechanistic change. The breakpoint at pKa° = 5.2 for R = Ph in the present work is in agreement with those for the pyridinolysis of R = Me and 2-furyl, and attests to the insignificant effect of acyl group, R, on the breakpoint. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 434,440, 2004 [source]


Quantum chemical study of penicillin: Reactions after acylation

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 10 2007
Rui Li
Abstract The density functional theory methods were used on the model molecules of penicillin to determine the possible reactions after their acylation on ,-lactamase, and the results were compared with sulbactam we have studied. The results show that, the acylated-enzyme tetrahedral intermediate can evolves with opening of ,-lactam ring as well as the thiazole ring; the thiazole ring-open products may be formed via ,-lactam ring-open product or from tetrahedral intermediate directly. Those products, in imine or enamine form, can tautomerize via hydrogen migration. In virtue of the water-assisted, their energy barriers are obviously reduced. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007 [source]


A theoretical study on the catalytic mechanism of Mus musculus adenosine deaminase

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 12 2010
Xian-Hui Wu
Abstract The catalytic mechanism of Mus musculus adenosine deaminase (ADA) has been studied by quantum mechanics and two-layered ONIOM calculations. Our calculations show that the previously proposed mechanism, involving His238 as the general base to activate the Zn-bound water, has a high activation barrier of about 28 kcal/mol at the proposed rate-determining nucleophilic addition step, and the corresponding calculated kinetic isotope effects are significantly different from the recent experimental observations. We propose a revised mechanism based on calculations, in which Glu217 serves as the general base to abstract the proton of the Zn-bound water, and the protonated Glu217 then activates the substrate for the subsequent nucleophilic addition. The rate-determining step is the proton transfer from Zn-OH to 6-NH2 of the tetrahedral intermediate, in which His238 serves as a proton shuttle for the proton transfer. The calculated kinetic isotope effects agree well with the experimental data, and calculated activation energy is also consistent with the experimental reaction rate. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]


Force-field parameters for the simulation of tetrahedral intermediates of serine hydrolases

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2009
Nikolaj Otte
Abstract CHARMM force-field parameters are reported for the tetrahedral intermediate of serine hydrolases. The fitting follows the standard protocol proposed for CHARMM22. The reference data include ab initio (RHF/6-31G*) interaction energies of complexes between water and the model compound 1,1-dimethoxyethoxide, torsional profiles of related model compounds from correlated ab initio (MP2/6-311+G*//B3LYP/6-31+G*) calculations, as well as molecular geometries and vibrational frequencies from density functional theory (B3LYP/6-31+G*). The optimized parameters reproduce the target data well. Their utility is demonstrated by a QM/MM study of the tetrahedral intermediate in Bacillus subtilis lipase A, and by classical molecular modeling of enantioselectivity in Pseudomonas aeruginosa lipase and its mutants. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source]


Amide and lactam hydrolysis of N -(2-hydroxyacetyl)-2-pyrrolidone: effective catalysis,

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 11 2006
Lisaedy García Borboa
Abstract When N -(2-hydroxyacetyl)-2-pyrrolidone (open form) is dissolved in water at pH,>,8, irreversible cleavage of the exocyclic and endocyclic amide CN bond occurs. The latter rupture corresponds to the lactam opening yielding N -(4-hydroxyacetyl)butanoic acid (NBA). NBA is produced from the ester hydrolysis of the ester-amide macrocycle that is in equilibrium with the cyclol form of the open form. We have previously reported this latter equilibrium for N -(2-aminoacetyl)-2-lactams. 2-pyrrolidone (lactam) and glycolic acid are produced from direct hydrolysis of the open form by means of the amide exocyclic cleavage. The [NBA]/[lactam] ratio increases at higher pH since the NBA production is second order with respect to [OH,] while the corresponding lactam formation is only first order. The obtained kobs is hence the sum of the rate constants that yield lactam and NBA, respectively. This kobs is uncatalyzed and specific base catalyzed with unusually high rate constants of 2.1,×,10,6,s,1 and 0.025,M,1,s,1, respectively. The stability of the corresponding tetrahedral intermediate formed and the intramolecular alkoxy nucleophilic attack on the lactam carbonyl group combined with an effective protonation of the lactam nitrogen that promotes the CN cleavage, contribute to increase the reaction rates and lactam opening. Rate constants for the two parallel reactions are obtained from kobs and [NBA]/[lactam] versus pH plots. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Tetrahedral intermediates in reactions of carboxylic acid derivatives with nucleophiles,

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2005
Martin Adler
Abstract Transacylation reactions of carboxylic acids, carboxylic acid esters, carboxylic acid amides and other carboxylic acid derivatives are among the most widespread and most important reactions in chemistry and biochemistry. Already in 1887, Claisen suggested a tetrahedral intermediate in transformations of carboxylic acid derivatives with nucleophiles. A historical overview gives insight into the studies to detect possible tetrahedral intermediates in such reactions. However, only in recent years has detailed information concerning the structures of such species become available. In this review, neutral, cationic and anionic tetrahedral intermediates are described which serve as models for transacylations under neutral, acid-catalysed or basic conditions. The characteristically different structures correspond nicely with experimental experience with reactions of carboxylic acid derivatives and with quantum chemical model calculations on tetrahedral intermediates. Finally, by means of model calculations, an explanation is given for the fast reactions of Weinreb amides, RC(O)N(CH3)OCH3, with organolithium and even with Grignard reagents: the reactions are determined by comparatively stable chelate transition states. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Ortho Effects in Quantitative Structure Activity Relationships for Lipase Inhibition by Aryl Carbamates

MOLECULAR INFORMATICS, Issue 8 2003
Gialih Lin
Abstract Ortho -substituted phenyl- N -butyl carbamates (1,11) are synthesized and evaluated for their inhibition effects on Pseudomonas species lipase. Carbamates 1,11 are characterized as pseudo-substrate inhibitors of the enzyme. The logarithms of dissociation constant (Ki), carbamylation constant (k2), and bimolecular inhibition constant (ki) multiply linearly correlate with Hammett substituent constant (,), Taft-Kutter-Hansch ortho steric constant (ES), and Swan-Lupton field constant (F). For ,logKi -, logk2 -, and logki -correlations, values of ,, ,, f, ,XR are 0.2, ,0.06, ,1.7, 0.8; 0.0, 0.0, 1.0, ,0.07; and ,1.8, 7, 0.6, 5; respectively. The enzyme inhibition mechanism is composed of four steps: 1) the first step which is protonation of carbamates 1,11, 2) the second step (Ki1) which involves in the proton 1,3-shift of protonated carbamates 1,11 then the pseudo- trans to cis conformational change, 3) the third step (Ki2) which is formation of a negative charged enzyme-inhibitor tetrahedral intermediate, and 4) the fourth step (k2) which is the carbamylation step. The former three steps are likely composed of the Ki step. There is little ortho steric enhancement effect in the Ki step. From cross-interaction correlations, distance between carbamate and phenyl substituents in transition state for the Ki step is relatively short due to a large ,XR value of 7. The k2 step is insensitive to ortho steric effect. The k2 step involves in departure of leaving group, substituted phenol in which is protonated from the proton 1,3-shift but not from the active site histidine of the enzyme. From cross-interaction correlations, the distance between carbamate and phenyl substituents in transition state for the k2 step is relatively long due to a small ,XR value of 0.6. [source]


Isomerization mechanism of aspartate to isoaspartate implied by structures of Ustilago sphaerogena ribonuclease U2 complexed with adenosine 3,-monophosphate

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2010
Shuji Noguchi
Aspartates in proteins are isomerized non-enzymatically to isoaspartate via succinimide in vitro and in vivo. In order to elucidate the mechanism of isoaspartate formation within the Asp45-Glu46 sequence of Ustilago sphaerogena ribonuclease U2 based on three-dimensional structure, crystal structures of ribonuclease U2 complexed with adenosine 3,-monophosphate have been solved at 0.96 and 0.99,Å resolution. The crystal structures revealed that the C, atom of Asp45 is located just beside the main-chain N atom of Glu46 and that the conformation which is suitable for succinimide formation is stabilized by a hydrogen-bond network mediated by water molecules 190, 219 and 220. These water molecules are suggested to promote the formation of isoaspartate via succinimide: in the succinimide-formation reaction water 219 receives a proton from the N atom of Glu46 as a general base and waters 190 and 220 stabilize the tetrahedral intermediate, and in the succinimide-hydrolysis reaction water 219 provides a proton for the N atom of Glu46 as a general acid. The purine-base recognition scheme of ribonuclease U2 is also discussed. [source]


Learning from Directed Evolution: Theoretical Investigations into Cooperative Mutations in Lipase Enantioselectivity

CHEMBIOCHEM, Issue 2 2004
Marco Bocola Dr.
Abstract Molecular modeling with classical force-fields has been used to study the reactant complex and the tetrahedral intermediate in lipase-catalyzed ester hydrolysis in 20 enzyme/substrate combinations. The R and S enantiomers of,-methyldecanoic acid ester served as substrates for the wild-type lipase from Pseudomonas aeruginosa and nine selected mutants. After suitable preparation of initial structures from an available wild-type crystal structure, each system was subjected to 1 ns CHARMM force-field molecular dynamics simulations. The resulting geometric and energetic changes allow interpretation of some experimentally observed effects of mutations, particularly with regard to the "hot spots" at residues 155 and 162. The replacement S155F enhances S enantiopreference through a steric relay involving Leu162. The double mutation S53P + L162G improves S enantioselectivity by creating a new binding pocket for the S enantiomer with an additional stabilizing hydrogen bond to His83. The simulations provide insight into remote and cooperative effects of mutations. [source]


Force-field parameters for the simulation of tetrahedral intermediates of serine hydrolases

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2009
Nikolaj Otte
Abstract CHARMM force-field parameters are reported for the tetrahedral intermediate of serine hydrolases. The fitting follows the standard protocol proposed for CHARMM22. The reference data include ab initio (RHF/6-31G*) interaction energies of complexes between water and the model compound 1,1-dimethoxyethoxide, torsional profiles of related model compounds from correlated ab initio (MP2/6-311+G*//B3LYP/6-31+G*) calculations, as well as molecular geometries and vibrational frequencies from density functional theory (B3LYP/6-31+G*). The optimized parameters reproduce the target data well. Their utility is demonstrated by a QM/MM study of the tetrahedral intermediate in Bacillus subtilis lipase A, and by classical molecular modeling of enantioselectivity in Pseudomonas aeruginosa lipase and its mutants. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009 [source]


Tetrahedral intermediates in reactions of carboxylic acid derivatives with nucleophiles,

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2005
Martin Adler
Abstract Transacylation reactions of carboxylic acids, carboxylic acid esters, carboxylic acid amides and other carboxylic acid derivatives are among the most widespread and most important reactions in chemistry and biochemistry. Already in 1887, Claisen suggested a tetrahedral intermediate in transformations of carboxylic acid derivatives with nucleophiles. A historical overview gives insight into the studies to detect possible tetrahedral intermediates in such reactions. However, only in recent years has detailed information concerning the structures of such species become available. In this review, neutral, cationic and anionic tetrahedral intermediates are described which serve as models for transacylations under neutral, acid-catalysed or basic conditions. The characteristically different structures correspond nicely with experimental experience with reactions of carboxylic acid derivatives and with quantum chemical model calculations on tetrahedral intermediates. Finally, by means of model calculations, an explanation is given for the fast reactions of Weinreb amides, RC(O)N(CH3)OCH3, with organolithium and even with Grignard reagents: the reactions are determined by comparatively stable chelate transition states. Copyright © 2004 John Wiley & Sons, Ltd. [source]


Altering lipase activity and enantioselectivity in organic media using organo-soluble bases: Implication for rate-limiting proton transfer in acylation step

BIOTECHNOLOGY & BIOENGINEERING, Issue 2 2006
Chun-Chi Chen
Abstract With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via a partially purified papaya lipase (PCPL) in water-saturated isooctane as the model system, the enzyme activity, and enantioselectivty is altered by adding a variety of organo-soluble bases that act as either enzyme activators (i.e., TEA, MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP). Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold increase of the initial rate for the (S)-ester is obtained when adding 120 mM of the base. By using an expanded Michaelis,Menten mechanism for the acylation step, the kinetic analysis indicates that the proton transfer for the breakdown of tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step, or more sensitive than that for the formation of tetrahedral intermediates when the enzyme activators of different pKa are added. However, no correlation for the proton transfers in the acylation step is found when adding the bases acting as enzyme deactivators. © 2006 Wiley Periodicals, Inc. [source]