Synthesis and reactivity of the aquation product of the antitumor complex trans-[RuIIICl4(indazole)2]-

d Aquation of the investigational anticancer drug trans-[(RuCl4)-Cl-III(Hind)(2)](-) (1, KP1019) results in the formation of mer,trans-[(RuCl3)-Cl-III(Hind)(2)(H2O)] (2), which was isolated in high yield (85%) and characterized. by spectroscopic methods and X-ray crystallography. Dissolution of 2 in acetone, led to its dimerization into [Ru-2(III)(mu-Cl)(2)Cl-4(Hind)(4)]center dot 2(Me)(2)CO (3) in 79% yield, with release of two water molecules. Complex 2 reacts readily with nucleophilic organic molecules, viz., methanol or dimethyl sulfide, at room temperature by replacement of the aqua ligand to give mer,trans[(RuCl3)-Cl-III(Hind)(2)(MeOH)] (4) and mer,trans-[(RuCl3)-Cl-III(Hind)(2)(Me2S)] (5) in 58 and 64% yield, respectively. By reaction of 2 with DMSO at room temperature or dimethyl sulfide at elevated temperatures trans,trans,trans[(RuCl2)-Cl-III(Hind)(2)(Me2S)(2)] (6) and trans,trans,trans-[(RuCl2)-Cl-II(Hind)(2)(S-DMSO)(2)] (7) were prepared in 64 and 75% yield, respectively, Dissolution of 2 in acetonitrile or benzonitrile gave rise to mer,trans-[(RuCl3)-Cl-III(Hind)(HN=C(Me)ind)] (8a), mer,trans-[(RuCl3)-Cl-III(Hind)(HN=C(Ph)ind)] (8b), and trans,trans-[(RuCl2)-Cl-III(HN=C(Me)ind)(2)]Cl (9) in 67, 50, and 23% yield, respectively, upon metal-assisted iminoacylation of indazole, which is unprecedented for ruthenium(III). Furthermore, complex 2 reacts with the DNA-model bases 9-methyladenine (9-meade) and N6,N6-dimethyladenine (6-me(2)ade) to yield mer,trans-[(RuCl3)-Cl-III(Hind)(2)(9-meade)] (10) and mer,trans-[(RuCl3)-Cl-III(Hind)(2)(6-me(2)ade)] (11) with the purine bases bound to the Ru(III) center via N7 and N3, respectively. Complex 11 represents the first ruthenium complex in which the coordination of the purine ligand N6,N6-dimethyladenine occurs via N3. In addition, the polymer [Na(EtOAc)(2)Ru-III(mu-Cl)(4)(Hind)(2)](n) (12) was crystallized from ethyl acetate/diethyl ether solutions of Na[trans-(RuCl4)-Cl-III(Hind)(2)]center dot 1.5H(2)O (1a). The reported complexes were characterized by elemental analysis, IR and UV-vis spectroscopy, ESI mass spectrometry, cyclic voltarnmetry, and X-ray crystallography. Electrochemical investigations give insight into the mechanistic details of the solvolytic behavior of complex 2. The lability of the aqua ligand in 2 suggests that this complex is a potential active species responsible for the high antitumor activity of trans-[(RuCl4)-Cl-III(Hind)(2)](-).