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

Acylation of acetylcholine (ACh) catalyzed by acetylcholinesterase (AChE) 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.     

Internal dynamics of the LaI3 molecule. II. Thermal average structure of the molecule and mean square vibration amplitudes

The structural parameters of the effective r _g configuration of the LaI₃ molecule were calculated using the DFT/B3LYP method. The difference between the calculated values of r _e (La-I) and r _g (La-I) is mostly due to the anharmonicity of the ν₁ and ν₂ vibrations and does not exceed the error in determining the distance r _g (La-I) in the electron diffraction experiment. Inclusion of the anharmonicity of the ν₂ and ν₄ deformation vibrations in calculations leads to decreased amplitudes l(I…I) and shrinking effect δ(I…I) compared to the respective values obtained in the harmonic approximation. The LaI₃ molecule proved to be more rigid than predicted by B3LYP calculations.     

Reaction sites of <Emphasis Type="Italic">N,N′</Emphasis>-substituted <Emphasis Type="Italic">p</Emphasis>-phenylenediamine antioxidants

The geometries of N,N′-diphenylbenzene-1,4-diamine (DPPD), N-phenyl-N′-(1-phenylethyl)benzene-1,4-diamine (SPPD), N-(4-methylpentan-2-yl)-N′-phenylbenzene-1,4-diamine (6PPD), N-propan-2-yl-N′-phenylbenzene-1,4-diamine (IPPD), N-(2-methoxybenzyl)-N′-phenylbenzene-1,4-diamine (MBPPD), and N-phenyl-N′-(2-phenylpropan-2-yl)benzene-1,4-diamine (CPPD) as well as of their dehydrogenation products were optimized by the semiempirical AM1 method. The results support the idea of stable N_B=C_X structures formation during the consecutive dehydrogenation of SPPD, 6PPD, IPPD, and MBPPD antioxidants. The biradicals formed during the second step of dehydrogenation of substituted phenylenediamines might be important for their antioxidant effectiveness. Dedicated to Professor Vladimír Kvasnička, DrSc., in honour of his 65th birthday     

Photophysics of eumelanin: ab initio studies on the electronic spectroscopy and photochemistry of 5,6-dihydroxyindole.

Excited-state reaction paths and energy profiles of 5,6-dihydroxyindole (DHI), one of the elementary building blocks of eumelanin, have been determined with the approximated singles-and-doubles coupled-cluster (CC2) method. 6-Hydroxy-4-dihydro-indol-5-one (HHI) is identified as a photochromic species, which is formed via nonadiabatic hydrogen migration from the dangling OH group of DHI to the neighboring carbon atom of the six-membered ring. It is shown that HHI is a typical excited-state hydrogen-transfer (ESIHT) system. HHI absorbs strongly in the visible range of the spectrum. A barrierless hydrogen transfer in the (1)pipi* excited state, followed by barrierless torsion of the hydroxyl group, lead to a low-lying S(1)-S(0) conical intersection and thus to ultrafast internal conversion. This very efficient mechanism of excited-state deactivation provides HHI with a high degree of intrinsic photostability. It is suggested that the metastable photochemical product HHI plays an essential role for the photoprotective biological function of eumelanin.     

Chemo- and periselectivity in the addition of [OsO2(CH2)2] to ethylene: a theoretical study

Quantum chemical calculations by using density functional theory at the B3LYP level have been carried out to elucidate the reaction course for the addition of ethylene to [OsO2(CH2)2] (1). The calculations predict that the kinetically most favorable reaction proceeds with an activation barrier of 8.1 kcal mol(-1) via [3+2] addition across the O=Os=CH2 moiety. This reaction is -42.4 kcal mol(-1) exothermic. Alternatively, the [3+2] addition to the H2C=Os=CH2 fragment of 1 leads to the most stable addition product 4 (-72.7 kcal mol(-1)), yet this process has a higher activation barrier (13.0 kcal mol(-1)). The [3+2] addition to the O=Os=O fragment yielding 2 is kinetically (27.5 kcal mol(-1)) and thermodynamically (-7.0 kcal mol(-1)) the least favorable [3+2] reaction. The formal [2+2] addition to the Os=O and Os=CH2 double bonds proceeds by initial rearrangement of 1 to the metallaoxirane 1 a. The rearrangement 1-->1 a and the following [2+2] additions have significantly higher activation barriers (>30 kcal mol(-1)) than the [3+2] reactions. Another isomer of 1 is the dioxoosmacyclopropane 1 b, which is 56.2 kcal mol(-1) lower in energy than 1. The activation barrier for the 1-->1 b isomerization is 15.7 kcal mol(-1). The calculations predict that there are no energetically favorable addition reactions of ethylene with 1 b. The isomeric form 1 c containing a peroxo group is too high in energy to be relevant for the reaction course. The accuracy of the B3LYP results is corroborated by high level post-HF CCSD(T) calculations for a subset of species.     

Infrared spectra of two sexithiophenes in neutral and doped states: a theoretical and spectroscopic study

The FT-infrared spectra of two sexithiophenes having their end ,′-positions substituted by n-hexyl or -thiohexyl groups, in neutral and doped states, are studied with the main aim of deriving information about the π-electrons delocalization and about the electronic structure of the charged defects created upon doping with iodine. The analysis of the experimental data is aided by Density Functional Theory calculations. The modifications in the electronic structure of the sexithiophene backbone induced by the n-thiohexyl encapsulation are discussed from the point of view of single molecule interactions in thiol-terminated π-conjugated oligomers bound to metallic or cluster electrodes.     

Fractal Characterization of Silica Sol Prepared by the Sol-Gel Method: From the Sol Formation to the Flocculation Process

The fractal characterization of silica particles prepared by the sol-gel method was obtained; from the beginning of the sol-gel synthesis to the aggregation process of these particles by adding metal ions in solution, the fractal dimension was determined. At the beginning of the sol-gel process, unstable structures were formed due, essentially, to the auto-catalytic nature of the sol-gel condensation reactions; these particles are fractal structures with a fractal exponent corresponding to a reaction limited aggregation regime. As the time proceeds, the reactants are consumed approaching the system to equilibrium, stabilizing the size of the silica particles. The silica sol can be flocculated by adding metal ions in solution. The fractal exponent for the aggregation process was determined, obtaining a value corresponding to a diffusion limited aggregation regime.     

The hydration of the uranyl dication: Incorporation of solvent effects in parallel density functional calculations with the program PARAGAUSS

The parallel density functional program PARA GAUSS has been extended by a tool for computing solvent effects based on the conductor‐like screening model (COSMO). The molecular cavity in the solvent is constructed as a set of overlapping spheres according to the GEPOL algorithm. The cavity tessellation scheme and the resulting set of point charges on the cavity surface comply with the point group symmetry of the solute. Symmetry is exploited to reduce the computational effort of the solvent model. To allow an automatic geometry optimization including solvent effects, care has been taken to avoid discontinuities due to the discretization (weights of tesserae, number of spheres created by GEPOL). In this context, an alternative definition for the grid points representing the tesserae is introduced. In addition to the COSMO model, short‐range solvent effects are taken into account via a force field. We apply the solvent module to all‐electron scalar‐relativistic density functional calculations on uranyl, UO₂²⁺, and its aquo complexes in aqueous solution. Solvent effects on the geometry are very small. Based on the model [UO₂(H₂O)₅]²⁺, the solvation energy of uranyl is estimated to be about ?400 kcal/mol, in agreement with the range of experimental data. The major part of the solvation energy, about ?250 kcal/mol, is due to a donor–acceptor interaction associated with a coordination shell of five water ligands. One can interpret this large solvation energy also as a compounded effect of an effective reduction of the uranyl moiety plus a solvent polarization. The energetic effect of the structure relaxation in the solution is only about 8 kcal/mol. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001     

Molecular dynamics and quantum chemical approaches in the study of the hydration of protonated cyclohexyldiamines

Explicit hydration of the neutral and charged cyclohexylamine and of the cyclohexyldiamine isomers in their mono- or diprotonated forms is investigated through classical molecular dynamics (MD) simulations in aqueous solutions combined with DFT calculations in amine–water complexes. The MD studies performed in the monoamines reveal that the structure of the hydration shell around the neutral amino group (NH₂) is quite distinct from that around the charged one (NH₃⁺). On average, the number of water molecules surrounding the two groups is calculated to be ～2 and 3–4, respectively. The variation of the hydration structure prompted by the groups’ proximity is discussed based on the data found for the mono- and diprotonated diamines. To have a more detailed picture of the water molecules’ arrangement around the amino groups and of the amine–water hydrogen bonds, geometry optimisations in hydrates with up to six water molecules are carried out at the B3LYP/aug-cc-pVDZ level. Complexation energies are also computed. The main findings emerging from these calculations are found to be very helpful to rationalise the mutual influence of the amino groups and therefore to better elucidate the MD findings. The complementary nature of the two research methods is emphasised as an excellent tool in order to closely examine the hydration of polyamines, as exemplified for the cyclohexyldiamines.