Table of Contents
Metal-Based Drugs
Volume 7, Issue 6, Pages 325-334
http://dx.doi.org/10.1155/MBD.2000.325

Reaction of cis- and trans-Dichlorotetra(Dimethylsulfoxide)Ruthenium(II) With the Antiviral Drug Acyclovir

1NCSR Demokritos, Institute of Physical Chemistry, Paraskevi Attikis GR-153 10 Ag, Greece
2Dipartimento Farmaco-Chimico, via E. Orabona 4, Bari I-70125, Italy

Received 11 January 2001; Accepted 21 January 2001

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

NMR was used to investigate the reaction of cis- and trans-[RuCl2(DMSO)4] with the antiviral drug acyclovir, a guanine derivative containing the acyclic (2-hydroxo) ethoxymethyl pendant linked to N(9). Studies were performed in aqueous solutions at ambient temperature and at 37 °C, and at various molar ratios. Both isomers yielded two compounds, a monoadduct and a bisadduct, the relative yields being dependent upon the metal to ligand concentration ratios. The products derived from the two Ru isomers displayed identical NMR spectra, suggesting that they have the same coordination environment, however the rate of formation of the monoadduct was higher in the case of the trans isomer than in the case of the cis isomer, while the rate of conversion of the monoadduct into the bisadduct appeared to be similar in both cases. As a consequence in the case of the trans isomer there is accumulation of monoadduct in the early stage of the reaction, whose concentration afterwards decreases with the progress of the reaction. As for platinum, also for ruthenium the preferred binding site is N(7) of the purine base, however, in the case of ruthenium a discrete amount of bisadduct is formed even in the presence of an excess of metallic substrate with respect to the acyclovir ligand; under similar conditions a platinum substrate would have given, nearly exclusively, the monoadduct.