Odon Farkas - Academia.edu (original) (raw)

Papers by Odon Farkas

Journal of the Chemical Society, Dalton Transactions, 2002

Several aspects of the mechanism of the Friedel–Crafts acetylation of benzene were studied by in ... more Several aspects of the mechanism of the Friedel–Crafts acetylation of benzene were studied by in situ spectroscopic methods in ionic liquids, prepared from MCl3 (M = Al or Fe) and 1-butyl-3-methylimidazolium chloride ([bmim]Cl). Mossbauer measurements have revealed that the addition of FeCl3 to [bmim]Cl leads to an equilibrium mixture that contains solid FeCl3, [bmim][Fe2Cl7], and Fe2Cl6 and/or [bmim][FeCl4], depending on the molar ratio of FeCl3 and [bmim]Cl. The formation of [(CH3CO)2CHCO]+[MCl4]−, a potential side product in the Friedel–Crafts acetylation of benzene, was shown to require the presence of both the acetylium ion [CH3CO]+[MCl4]− and free acetyl chloride. We have confirmed that [(CH3CO)2CHCO]+[MCl4]− does not involve in the Friedel–Crafts acetylation of benzene. Experimental data and theoretical calculations indicate that the acetylium ion [CH3CO]+[MCl4]− is the key intermediate in the Friedel–Crafts acetylation of benzene and the reaction proceeds through an ionic mechanism.

Computational and Theoretical Chemistry, Jun 1, 2022

ChemBioChem, Oct 21, 2015

Journal of Molecular Structure-theochem, Dec 1, 1998

The optimized geometries and relative energies obtained by four force field and two semi-empirica... more The optimized geometries and relative energies obtained by four force field and two semi-empirical methods were compared with ab initio results computed for formyl-l-alaninamide. Not all methods yielded the same number of minimum energy conformers. Furthermore, while the optimized geometries of the conformers found were comparable, the computed relative energies varied substantially. Also, the force field calculations produced Ramachandran maps that did not even have the appearance of the ab initio Ramachandran map. Correlating the ab initio relative energies (DE) or free energy (DG) with the log of relative populations, ln(p x ap g L), led to linear relationships from which four conformers deviated; two of them (a L and L) were overly destabilized and two of them (g L and g D) were over-stabilized. It is suggested that, after such deviations are corrected, a primary standard may be obtained that might be useful in further investigations related to force-field parametrization as well as protein folding.

Journal of Chemical Physics, Nov 1, 1998

The most recent methods in quantum chemical geometry optimization use the computed energy and its... more The most recent methods in quantum chemical geometry optimization use the computed energy and its first derivatives with an approximate second derivative matrix. The performance of the optimization process depends highly on the choice of the coordinate system. In most cases the optimization is carried out in a complete internal coordinate system using the derivatives computed with respect to Cartesian coordinates. The computational bottlenecks for this process are the transformation of the derivatives into the internal coordinate system, the transformation of the resulting step back to Cartesian coordinates, and the evaluation of the Newton-Raphson or rational function optimization ͑RFO͒ step. The corresponding systems of linear equations occur as sequences of the form y i ϭM i x i , where M i can be regarded as a perturbation of the previous symmetric matrix M iϪ1. They are normally solved via diagonalization of symmetric real matrices requiring O(N 3) operations. The current study is focused on a special approach to solving these sequential systems of linear equations using a method based on the update of the inverse of the symmetric matrix M i. For convergence, this algorithm requires a number of O(N 2) operations with an O(N 3) factor for only the first calculation. The method is generalized to include redundant ͑singular͒ systems. The application of the algorithm to coordinate transformations in large molecular geometry optimization is discussed.

Journal of Chemical Physics, Dec 22, 1999

Journal of Molecular Structure, 1995

Journal of Molecular Structure-theochem, Dec 1, 2007

ABSTRACT Most of the drug molecules exhibit their biological activity through binding to the targ... more ABSTRACT Most of the drug molecules exhibit their biological activity through binding to the target protein. When the D structure of the binding site is unknown, pure ligand-based approaches are often used to perceive the 3D pharmacophore. However, dealing with conformational flexibility of ligands in such methods is still in the frontline of the current research. The special thermodynamic properties of the binding of flexible molecules, as derived here, show that the probability of the bioactive conformations in solution can determine the likelihood of binding. The binding activities can be obtained experimentally, while the probability of conformations in solution can be computed. Our present paper discusses the thermodynamic basis of performing 3D QSAR studies on molecules, with considerable conformational flexibility. In addition, we supply an algorithm to locate the bioactive conformations. The work is initiated to find the binding conformation of the therapeutically promising mucin epitope pentapeptides.

Chemical Physics Letters, Mar 1, 2013

Journal of Molecular Structure-theochem, Jul 1, 2001

The Ramachandran or backbone potential energy surface (PES) of N-acetyl-l-isoleucine-N-methylamid... more The Ramachandran or backbone potential energy surface (PES) of N-acetyl-l-isoleucine-N-methylamide has been explored using the a,a side-chain conformation. The side-chain conformational PES were generated with ®xed backbone conformations: g l and b l. The b l side-chain PES of the isoleucine derivative was compared to that of the nor-isoleucine derivative.

Journal of Medicinal Chemistry, Feb 20, 2008

Here we report on the synthesis, antibody binding, and QSAR studies of a series of linear and cyc... more Here we report on the synthesis, antibody binding, and QSAR studies of a series of linear and cyclic peptides containing a-amyloid plaque-specific epitope (A (4-10); FRHDSGY). In these constructs, two or three R-L-Ala, R-D-Ala, or-Ala residues were introduced at both N-and C-termini of the epitope as non-native flanking sequences. Cyclization of the linear A (4-10) epitope peptide resulted in reduced antibody binding. However, the antibody binding could be fully compensated by insertion of alanine flanks into the corresponding cyclic peptides. These results indicate that the modification of a-amyloid plaque-specific epitope by combination of cyclization and flanking sequences could generate highly antigenic peptides compared to the native sequence. A novel 3D QSAR method, which explicitly handles conformational flexibility, was developed for the case of such molecular libraries. This method led to the prediction of the binding conformation for the common FRHDSGY sequence.

International Journal of Quantum Chemistry, 2000

The results of a geometry optimization on the 1226 atom Kringle 1 of plasminogen are presented. T... more The results of a geometry optimization on the 1226 atom Kringle 1 of plasminogen are presented. The energy and gradients were calculated using a linearscaling PM3 semiempirical method with a conjugate gradient density matrix search replacing the diagonalization step. The geometry was optimized with the rational function optimization technique combined with a modified version of the direct inversion in the iterative subspace procedure. The optimization required 362 geometry update steps to reach a local minimum. An analysis is given of the optimization and timing results using a single processor on the SGI Origin2000.

Journal of Molecular Structure-theochem, Jul 1, 2002

... Azar Mehdizadeh a , Corresponding Author Contact Information , E-mail The Corresponding Autho... more ... Azar Mehdizadeh a , Corresponding Author Contact Information , E-mail The Corresponding Author , Gregory A. Chass a , b , E-mail The Corresponding Author , Ödön Farkas c , András Perczel c , Ladislaus L. Torday d , András Varro d and Julius Gy. Papp d , e. ...

Journal of Molecular Structure-theochem, Jun 12, 2000

ABSTRACT

Journal of Physical Organic Chemistry, Dec 4, 2007

A DFT study of transition structures and reactivity in solvolyses of tert-butyl chloride, cumyl c... more A DFT study of transition structures and reactivity in solvolyses of tert-butyl chloride, cumyl chlorides, and benzyl chlorides Ferenc Ruff a * and Ö dö n Farkas a DFT computations were performed on the S N 1 and S N 2 solvolyses of substituted cumyl chlorides and benzyl chlorides in ethanol and water, by increasing stepwise the C-Cl distance and by optimization. The total energy increases with the increase in the Cl-C distance in S N 1 reactions, while free energy of activation pass through maximum. To validate the results, the calculated free energies of activation were compared with data obtained by kinetic measurements. The structural parameters of the transition states were correlated with the Hammett substituent constants and compared with the data of hydrolyses of tert-butyl chloride and methyl chloride, which proceed with known mechanisms. Conclusions on the mechanisms of the reactions were driven from the effect of substituents on free energies of activation. Cumyl chlorides substituted with electron-donating (e-d) groups solvolyze with S N 1 mechanism, while the reactions of substrates that bear electron-withdrawing groups proceed with weak nucleophilic assistance of the solvent. Benzyl chlorides hydrolyze through an S N 2 pathway except those derivatives that have strongly e-d groups, where the reaction has S N 1 character, but a weak nucleophilic assistance of the water should also be taken into consideration.

Journal of Physical Organic Chemistry, Nov 1, 2008

biá n a , Ferenc Ruff a * and Ö dö n Farkas a * DFT computations have been performed on nucleophi... more biá n a , Ferenc Ruff a * and Ö dö n Farkas a * DFT computations have been performed on nucleophilic substitutions of phenacyl bromides with pyridines to investigate the mechanism of the reaction. In contrast with earlier suppositions, tetrahedral intermediate is not formed by the addition of pyridine on the CO group of phenacyl bromide, because the total energy of the reacting species increases continuously, when the distance between the N and C(-O) atoms of reactants is shorter than 2.7 Å. At a greater distance, however, a bridged complex of the reactants is observed, in which the N atom of pyridine is slightly closer to the C atom of the CO , than to the C atom of the CH 2 Br group of phenacyl bromide, the distances are 2.87 and 3.05 Å , respectively. The attractive forces between the oppositely polarized N and C(-O) atoms in the complex decrease the free energy of activation of the S N 2 attack of pyridine at the CH 2 Br group. The calculated structural parameters of the S N 2 transition states (TS) indicate, that earlier TSs are formed when the pyridine nucleophile bears electron-donating (e-d) groups, while electron-withdrawing (e-w) groups on phenacyl bromide substrate increase the tightness of the TS. Free energies of activation computed for the S N 2 substitution agree well with the data calculated from the results of kinetic experiments and correlate with the s Py substituent constants, derived for pyridines, and with the Hammett s constants, when the substituents (4-MeO-4-NO 2) are varied on the pyridine or on the phenacyl bromide reactants.

European Journal of Organic Chemistry, May 1, 2009

DFT computations have been performed at different levels of theory to identify the mechanism for ... more DFT computations have been performed at different levels of theory to identify the mechanism for the oxidation of sulfides and sulfoxides with periodates. The periodate ion (IO4–), periodic acid (HIO4) and their hydrated derivatives all oxidize sulfides to sulfoxides in one‐step oxygen‐transfer reactions and the relative reactivities are HIO4 >> H5IO6 > IO4– > H4IO6– >> H3IO62–. The hydration and dissociation equilibria of the periodates are shifted towards IO4– in neutral and moderately acidic solutions, and sulfides are oxidized mainly with IO4– under normal experimental conditions. The oxygen atoms of the periodates attack the sulfides perpendicularly to the plane of the C–S–C atoms and the S···O···I atoms are in a linear arrangement in the very early transition state (TS). The sulfides are the electron donors and periodates are the electron acceptors in the reactions; the geometries of the TSs are determined by the overlap of the HOMO and the LUMO of the reactants. Other mechanisms can be ruled out because the attack of the sulfur atom of the substrate on the iodine atom of the reactants increases the energy of the system continuously very steeply as the S···I distance decreases. Experimentally derived ΔG‡ values are in good agreement with the ΔG‡ data computed for the oxygen‐transfer mechanism. Sulfoxides are also oxidized to sulfones with IO4– in a one‐step oxygen‐transfer reaction, and the structures of the TSs and the ΔG‡ data are similar to those obtained for the reactions of sulfides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)