Synthesis and reactions of platinum(IV) complexes with sodium ascorbate Malcolm J. Arendse a , Gordon K. Anderson b, *, Raquel N. Majola a , Nigam P. Rath b a Department of Chemistry, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa b Department of Chemistry, University of Missouri  /St. Louis, 8001 Natural Bridge Road, St. Louis, MO 63121, USA Received 7 January 2002; accepted 3 May 2002 Abstract The platinum(IV) complexes [PtCl 2 (OH) 2 (N S N )] (N S N /en, N ,N -dmen, N ,N ?-dmen) were prepared by oxidation of [PtCl 2 (N S N )] with hydrogen peroxide. The complexes were characterized by multinuclear NMR and infrared spectroscopy, as well as microanalysis. The reactions of these compounds with sodium ascorbate were monitored spectroscopically. Reduction of the platinum(IV) complexes by sodium ascorbate occurred only slowly. An oxalatoplatinum(IV) complex [Pt(C 2 O 4 )Cl(OH)(N ,N - dmen)] × /H 2 O was isolated from the reaction of [PtCl 2 (OH) 2 (N ,N -dmen)] and sodium ascorbate and characterized by an X-ray diffraction study. # 2002 Elsevier Science B.V. All rights reserved. Keywords: Platinum complexes; Antitumor activity; Ascorbic acid; Oxalate; Oxidation 1. Introduction Platinum(IV) complexes, such as iproplatin, [PtCl 2 (OH) 2 (NH 2 Pr i ) 2 ], are currently used as antitumor drugs in chemotherapy, where their higher water solubility makes oral administration possible. These platinum(IV) compounds have less severe side effects than cisplatin, cis -[PtCl 2 (NH 3 ) 2 ], and they are active against certain tumor cells that are resistant to cisplatin [1  /4]. Platinum(IV) complexes generally undergo ligand substitution more slowly than their platinum(II) ana- logues [5] and, since platinum(II) species are known to bind to DNA, it is believed that platinum(IV) complexes serve as prodrugs for platinum(II) derivatives. Thus, they must be reduced in vivo before DNA binding occurs. A number of cellular reductants could achieve this, including cysteine, the sulfhydryl protein, glu- tathione and ascorbic acid. A recent study focused on the reduction of platinu- m(IV) complexes by ascorbic acid. Choi and coworkers found that the rate of reduction of [PtX 2 Cl 2 L 2 ] (X / OH, Cl, OCOCH 3 , OCOCF 3 ;L 2 /en, dach or L / NH 2 Pr i ) was dependent on the nature of the axial ligands and the amine ligands [6]. For the ethylenedia- mine complexes, the reduction rates and reduction potentials were found to increase in the order OH B/ OCOCH 3 B/Cl B/OCOCF 3 , which follows the order of increasing electron-withdrawing abilities of the ligands. Reduction of the ethylenediamine complexes was slower than the corresponding reactions of the diaminocyclo- hexane or isopropylamine complexes. Hambley and coworkers earlier investigated the electrochemical re- duction of platinum(IV) complexes [Pt(en)Cl 2 Y 2 ] (Y / Cl, OH, RCOO) and found that the tetrachloro com- plexes were reduced more readily than the complexes with hydroxo or carboxylato axial ligands [7]. We have investigated the effect of N-methyl substituents on the rate of ascorbic acid reduction of ethylenediamineplati- num(IV) complexes, and the results of this study are presented here. 2. Experimental K 2 PtCl 4 , deuterium oxide, N ,N -dmen and N ,N ?- dmen were purchased from Sigma Aldrich. [PtI 2 (N ,N - * Corresponding author. Tel.:  /1-314-516-5311; fax:  /1-314-516- 5342 E-mail address: ganderson@umsl.edu (G.K. Anderson). Inorganica Chimica Acta 340 (2002) 65  /69 www.elsevier.com/locate/ica 0020-1693/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved. PII:S0020-1693(02)01058-7