Theoretical insights into the mechanism of acetylcholinesterase-catalyzed acylation of acetylcholine

Acylation of acetylcholine (ACh) catalyzed by acetylcholinesterase (ACNE) has been studied using high-level theoretical calculations on a model system that mimics the reaction center of the enzyme, and compared with uncatalyzed acylation reaction. The geometries of all the intermediates and transition states, activation energies, and solvent effects have been calculated. The calculations predict simultaneous formation of two short-strong hydrogen bonds (SSHB) in the rate-determining transition state structures [the first SSHB involves the hydrogen atom of Ser-200 (H-s) and another involves the hydrogen atom of His-440 (H-h)]. In the intermediate states, the H-bond corresponding to H-h involves SSHB, whereas the one corresponding to H-s does not. (c) 2005 Wiley Periodicals, Inc.X112527sciescopu

Theoretical studies on hydroquinone-benzene clusters

High-level ab initio calculations were carried out to evaluate the interaction between the hydroquinone and benzene molecules. The intermolecular interaction energy was calculated using the Moller-Plesset second-order perturbation theory at the complete basis set limit and also at the coupled cluster theory with single, double, and perturbatively triple excitations. The calculated binding energy is larger than the benzene dimer interaction energy. The T-shaped cluster (T-a) and the parallel conformation (P-a) are calculated to be nearly isoenergetic. Owing to the large energy gain in the attraction by electron correlation, the dispersion interaction is important for the attraction. (C) 2005 American Institute of Physics.open111214sciescopu

Ab initio studies of neutral and anionic p-benzoquinone-water clusters

Since the energy conversion reactions in most biological systems involve the interactions of various negatively charged quinones with water molecules, we have investigated the equilibrium structures, binding energies, and vibrational frequencies of the water monomer/dimer complexes of p-benzoquinones (Q) and its corresponding negatively charged anionic species (Q(-) and Q(2-)). The calculations, which include the evaluation of charges and aromaticity, indicate the existence of double hydrogen bonds in the water monomer and water dimer complexes of neutral p-benzoquinone. When two water molecules are complexing with p-benzoquinone, a conformer exhibiting an H-bond between two water molecules (W(2)Q) is energetically more favored than the conformer WQW in which there is no direct interaction between the water molecules. However, an increase in the negative charge of p-benzoquinone leads to the energetic stabilization of the WQ(2-)W conformer over the Q(2-)W(2) conformer. The charge transfer Q to water molecules is found to be significant in the case of Q(2-), up to -0.23 a.u. in the presence of two water molecules. An increase in the aromaticity of the p-benzoquinone molecule upon its interaction with the water molecules is noted from an analysis of the Nucleus Independent Chemical Shift (NICS) values. (C) 2003 American Institute of Physics.open112830sciescopu

p-benzoquinone-benzene clusters as potential nanomechanical devices: A theoretical study

The equilibrium structures and binding energies of the benzene complexes of p-benzoquinones (PBQ) and its negatively charged anionic species (PBQ(-) and PBQ(2-)) have been investigated theoretically using second-order Moller-Plesset calculations. While neutral p-benzoquinone-benzene clusters (PBQ-Bz) prefer to have a parallel displaced geometry (P-c), CH...pi interactions (T-shaped geometries) prevail in the di-anionic PBQ-benzene (PBQ(2-)-Bz) complexes (T-e(2-)). Studies on dianionic p-benzoquinone-benzene clusters showed that two nonbonded intermolecular interactions compete in the most stable conformation. One is H-bonding interaction (C-H...O type) between carbonyl oxygen of p-benzoquinone and one of the hydrogen atoms of benzene, and the other is a pi-H interaction between pi-electron cloud of PBQ(2-) and another hydrogen atom of benzene. Blueshifted H-bonds were observed in T-shaped clusters. The changes in the geometrical preference of PBQ-Bz complex upon addition of electrons would be useful in designing optimized molecular mechanical devices based on the edge-to-face and face-to-face aromatic interactions. (C) 2004 American Institute of Physics.open112627sciescopu

Theoretical studies on the mechanism of acid-promoted hydrolysis of N-formylaziridine in comparison with formamide

We present an ab initio study of the acid-promoted hydrolysis reaction mechanism of N-formylaziridine in comparison with formamide. Since the rate of amide hydrolysis reactions depends on the formation of the tetrahedral intermediate, we focused our attention mainly on the reactant complex, the tetrahedral intermediate, and the transition state connecting these two stationary points. Geometries were optimized using the density functional theory, and the energetics were refined using ab initio theory including electron correlation. Solvent effects were investigated by using polarizable continuum method calculations. The proton-transfer reaction between the O-protonated and N-protonated amides was investigated. In acidic media, despite that the N-protonated species is more stable than the O-protonated one, it is predicted that both N-protonated and O-protonated pathways compete in the hydrolysis reaction of N-formylaziridine.X111011sciescopu