Hydrolysis of [Pt(dien)H 2 O] 2+ and [Pd(dien)H 2 O] 2+ complexes in water Z Ï ivadin D. BugarcÏicÂ*, Biljana V. Petrovic and Ratomir Jelic Department of Chemistry, Faculty of Science, University of Kragujevac, P.O. Box 60, YU-34000 Kragujevac, Yugoslavia Received 02 October 2000; accepted 22 November 2000 Abstract The hydrolysis of the [Pt(dien)H 2 O] 2+ and [Pd(dien)H 2 O] 2+ complexes has been investigated by potentiometry at 298 K, in 0.1 mol dm )3 aqueous NaClO 4 . Least-squares treatment of the data obtained indicates the formation of mononuclear and l-hydroxo-bridged dinuclear complexes with stability constants: log b 11 = )6.94 for [Pt(dien)OH] + , log b 11 = )7.16 for [Pd(dien)OH] + , and also log b 22 = )9.37 for [Pt 2 (dien) 2 (OH) 2 ] 2+ and log b 22 = )10.56 for [Pd 2 (dien) 2 (OH) 2 ] 2+ . At pH values >5.5, formation of the dimer becomes signi®cant for the Pt II complex, and at pH > 6.5 for the Pd II complex. These results have been analyzed in relation to the antitumor activity of Pt II complexes. Introduction The aqueous solution chemistry of platinum(II) com- plexes has been extensively studied during recent decades, owing to the anticancer activity of cisplatin, cis-diamminedichloroplatinum(II), cis-[PtCl 2 (NH 3 ) 2 ] and related compounds [1]. Extensive mechanistic investigations of the interaction of the anticancer drug, cisplatin, with DNA and with simpler nucleotides and nucleosides have emphasized the importance of aqua species derived from the chloro species by hydrolysis in a medium of low chloride concentration [2, 3]. The acidic aqua species is readily deprotonated by bases to yield the corresponding mono- and dihydroxo species [3]. However, at higher pH values, near the pK a , l-hydroxo- bridged complexes [4±6] are formed which reduce the reactivity of the platinum(II) complexes. When Pt antitumor drugs are injected into the blood, it is important for them to reach their ®nal destination, the DNA in the cell, without reacting with other nucleophiles within the cytoplasma. Human blood plasma has a chloride concentration of ca. 104 mM, so that hydrolysis of cis-[PtCl 2 (NH 3 ) 2 ] is less likely to occur than within the cell where the chloride concentration is as low as 4 mM [7]. The high chloride concentration allows the neutral complex, cis-[PtCl 2 (NH 3 ) 2 ], to travel nearly unchanged through the blood. It then diuses through the cell membrane and is then hydrolyzed to give the more reactive aquated species. Due to the lower chloride concentration the aquated complexes then can react with DNA. On the other hand, under certain conditions (neutral pH and high concentration) l-hydroxo-bridged dinuclear and trinuclear species can be formed from cis-[Pt(NH 3 ) 2 (H 2 O)(OH)] + [5]. The non-antitumor active monofunctional [PtCl- (dien)] + complex (dien = diethylenetriamine) is stable and has been often studied as a model for the ®rst binding step of cisplatin. Previous kinetic analyses of reactions of [PtCl(dien)] + with nucleotides [8±10] are consistent with hydrolysis as the initial step, although the aqua complex has not been directly detected during the reaction [10]. Dimerization of [Pt(dien)H 2 O] 2+ to form the l-hydroxo-bridged species has been investi- gated by pH-varied methods [11]. Recently the reversible hydrolysis of [PtCl(dien)] + and [PtCl(NH 3 ) 3 ] + in aqueous acid has been studied [12]. It appears that the relatively fast anation, which limits the extent of hydrolysis, prevents hydrolysis [12]. In this paper, we have studied the hydrolysis of [Pt(dien)H 2 O] 2+ complexes in an eort to understand the substitution and biological behaviour of cis- [PtCl 2 (NH 3 ) 2 ]. For comparison, we have also studied the hydrolysis of the analogous [Pd(dien)H 2 O] 2+ com- plex. For kinetic and mechanistic investigations of the mechanism of action of platinum(II) anticancer drugs, their palladium(II) analogues are suitable model com- pounds since they exhibit ca. 10 4 ±10 5 times higher reactivity, whereas their structural and equilibrium behaviour are similar [13]. Experimental Chemicals and solutions The [PtCl(dien)]Cl and [PdCl(dien)]Cl complexes were synthesized according to the published procedure [14, 15]. Chemical analyses and u.v.±vis. spectral data * Author for correspondence Transition Metal Chemistry 26: 668±671, 2001. 668 Ó 2001 Kluwer Academic Publishers. Printed in the Netherlands.