Susana Zacchino

Exploratory molecular orbital calculations on the keto and enol forms of selected antifungals and those of side-chain substituted acetophenone model compounds

Abstract Conformational potential energy surfaces were generated using the semiempirical AM1 method for selected α -substituted arylpropanoids. The global minima were subjected to full AM1 geometry optimizations. Keto–enol tautomerization energies were also computed at the AM1 level. The results obtained were compared to those of Simple Huckel Molecular Orbital calculations. Antifungal activities of the compounds studied were reported as minimal inhibitory concentration values. These values were correlated with computed molecular parameters. A set of α -substituted acetophenones (using Me, F and Cl as substituents) were also studied, as model compounds for the antifungals, at the AM1 and the RHF/STO-3G levels of theory. The enolization energies were calculated at both levels of theory.

Conformational potential energy curves of acetophenone and α-substituted acetophenones

Abstract Acetophenone, α -fluoroacetophenone and propiophenone have been subjected to ab initio conformational analysis at the RHF/3-21G and RHF/6-31G(d,p) levels of theory. The two substituents (F and Me) modified the molecular system in different ways. This difference in substituent effect was manifested dramatically in the torsional potentials, and stabilization energies, but only modestly in molecular geometries and molecular charge distribution.

Dynamic chirality in selected diaryl methane containing drugs. An exploratory ab initio conformational study

Abstract Diaryl methane molecules (Ar–CH 2 –Ar) represent double rotor conformational problems. The simplest diaryl methane, diphenyl methane (Ph–CH 2 –Ph), governs certain symmetric conformational potential energy surface (PES) topology. With the replacement of one of the phenyl groups by a heterocyclic moiety, the PES topology may change dramatically. The induction of point-chirality, in the prochiral CH 2 group, by axis-chirality or plane-chirality is explored within the framework of ‘dynamic chirality’.

Aromatization within the putative bio-medical action mechanism of berberine and related cationic alkaloids with double iso-quinolinoid skeleton. A theoretical study

In the putative mechanism of action for berberin, to prevent DNA replication the first step is aromatization. The aromatization process, via dehydrogenation has been studied for a series of compounds related to berberine. In contrast to the covalent dehydrogenation, which is endothermic, the aromatization under ionic conditions was found to be exothermic. The availability of the hydride for ionic aromatization was indicated by the effective HOMO of berberine and related compounds. The results indicate that in the aromatization process the ease of hydride ion removal parallels the stabilizations energy of the aromatic compounds to be formed. Comparing the nucleophilic additions to the π-system, the LUMO energy values suggested a greater accessibility of the N(+) heterocycles in comparison to the polycycle aromatic hydrocarbons.