Cis-dichloro(diaminosuccinate diethyl ester)palladium (II) as Pd(II)/Pt(II) model compound for dna-binding and antitumor properties: Solution equilibria of their aqua-, hydroxo-, and/or chloro-species

Abstract

Cis-Dichloro(diaminosuccinic acid)palladium(II), cis-[Pd(H 2dasa)Cl 2] (I), or cis-dichloro(diaminosuccinate diethyl ester)palladium(II), cis-[Pd(Et 2dasa)Cl 2] (II) reacts with two equivalents of AgClO 4 to give insoluble Pd(dasa) or an aqueous solution of [Pd(Et 2dasa)(H 2O) 2](ClO 4) 2, respectively. Three solutions of this salt were titrated with NaOH(I = NaClO 4 (0.15M),37°C), and 133 E(H +) data (3.5 5 pH ≤ 7) were treated by SUPERQUAD to fit log β pqr of cis-aquahydroxo( pqr = 10 − 1, −5.25(3)) and di-μ,-hydroxo-species (20 − 2, −6.55(1)). At pH > 7 the ester hydrolysis prevents the calculation of log β 10−2 for the cis-dihydroxo-complex. Another three solutions of such salt were titrated (I = 0.15M (NaClO 4), 37°C) with NaOH and NaCl simultaneously using two potentiometric systems (which measure H + or Cl −). From 147 E(H +) and E(Cl −) data pairs and the above fixed log β pqr, SUPERQUAD calculations yield log β pqr for cis-chloro-aqua (pqr = 110,3.65(1)), cis-chloro-hydroxo (11 − 1, −2.68 (4)), and cis-dichloro-species (120,5.86(3)). Simulated and experimental titrations are in good agreement. Circular dichroism spectra of native DNA and drug:DNA complexes suggest that cis-Pd(H 2dasa) and cis-Pd(Et 2dasa) chelate moieties induce an opening and rotation of the stacked bases in the double helix. This finding is explained by the abundance of each one and of the total neutral and charged species of II in the tested CD solution.