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ISSN print edition: 0366-6352
ISSN electronic edition: 1336-9075
Registr. No.: MK SR 9/7
Published monthly
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Abinitio and PCILO investigations of the antiarrhythmic tocainide, its cation and hydrochloride
M. Remko
Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
Comenius University, CS-832 32 Bratislava
Abstract: The quantum-chemical PCILO and ab initio SCF methods (STO-3G
basis) were applied to the conformational analysis of antiarrhythmic tocainide (2-amino-2',6'-propionoxilidine) (B) and its cation (BH+). For В the
conformation with N—H...N hydrogen bond, corresponding to the mutual
cis arrangement of both nitrogen atoms of—N—CO—CH—N— fragment,
has been found to be most stable. On the other hand, for BH+ the most
stable conformation is stabilized by the bifurcated intramolecular hydrogen bond of the N+— H...0 = C type formed by two protons of—NH3+
group of drug and carbonyl oxygen. The proton affinity was determined by
means of ab initio SCF (STO-3G and MINI-1 bases, respectively) and
PCILO methods. The STO-3G calculated energy of intermolecular hydrogen bond N+—H...Cl- in the tocainide hydrochloride is very high
(507.8 kJ mol-1). The gross atomic charges resulting from the STO-3G ab
initio calculations for B, BH+, and BHCl were compared.
Full paper in Portable Document Format: 432a267.pdf
Chemical Papers 43 (2) 267–278 (1989)
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