Physico-chemical investigation of nucleoside-containing Pt(II) triamines

Abstract

The discovery of the antitumor activity of cisPt(NH 3) 2Cl 2 has aroused considerable interest in the study of Pt(II) complexes with nucleosides [1]. Most of the compounds investigated contain two nucleoside molecules and are of the nonelectrolyte or cation type [2–5]. We have synthesized and investigated isomeric Pt(II) triamines of composition [Pt(NH 3) 2LCl]Cl, where L = adenosine(ado), inosine(Ino), and cis[Pt(NH 3) 2L′Cl]Cl, where L = cytidine(Cyd). The coordination formulae have been proved by the measurement of molecular conduction (Λ in aqueous solution = 100–110 (ohm −1 cm 2 mol −1) and by long-wave IR spectroscopy (ν PtCl lies in the range 330–337 cm −1). The hydrolysis constant K h of the above triamines and [Pt(NH 3) 3Cl]Cl has been determined potentiometrically with the use of Ag/AgCl and chloroselective electrodes. ▪ K h × 10 4: [Pt(NH 3) 3Cl]Cl trans-[Pt(NH 3) 2InoCl]Cl 2.3 7.0 trans-[Pt(NH 3) 2Clado]Cl cis-[Pt(NH 3) 2CydCl]Cl 9.0 20.6 cis-[Pt(NH 3) 2adoCl]Cl 19.0 The substitution of NH 3 by a purine or pyrimidine molecule leads to an increase in K h which is likely to be due to steric factors. The hydrolysis constant K h is slightly affected by the nature of the nucleoside. The geometric structure of the complexes affects K h: cis-isomers are approximately 2–3 times less stable than trans-isomers. The lower stability of the PtCl bond in the cis-triamine [Pt(NH 3) 2·adoCl]Cl also follows from the comparison of ν PtCl in isomers: cis, 330 cm −1; trans, 337 cm −1. The acidic properties of isomers [Pt(NH 3) 2InoCl]Cl have been investigated by the method of potentionmetric titration with an alkali in the presence of 0.3 N KCl (Fig. 1). Coordination leads to the enhancement of the acidic properties of inosine: pK a of the ▪ cis-isomer = 7.9, trans-isomer = 7.2, whereas for free inosine it is 9.0. The difference in acidity of isomers and in the stability of the PtCl bond may be accounted for by the higher trans-effect of NH 3 compared with inosine. Solution of isomeric aquo complexes [Pt(NH 3) 2InoH 2O] 2+ have been obtained by the action of AgNO 3 on isomeric triamines. The curves of potentiometric titration with an alkali of isomeric aquoions practically coincide and correspond to titration of the mixture of a strong acid (the first portion of the curve) and coordinated water (the second portion).The titration curve of the synthesized complex [Pt(NH 3) 2Ino](NO 3) 2 obtained in solid state by the action of inosine on the solution of cis-[Pt(NH 3) 2(H 2O) 2](NO 3) 2 is of the same type. Since the acidic properties of isomeric aquocomplexes and [Pt(NH 3) 2Ino](NO 3) 2 are similar it may be concluded that in the aqueous solutions of these compounds there are no complexes with inosine bidentate coordinated through N(7), O(6) atoms. At the first portion of the curve the strong acid is titrated, it being formed in solution due to partial polymerization of complexes according to the type: ▪