Besides intensive studies into the synthesis of the complex trans-Hlnd[RuCl4(ind)2] (Ind = indazole)
1, which differs remarkably from the usual method for the complexes of the HL[RuCl4L2] - type,
competitive products and hydrolysis of this species are described. Stability and pseudo-first-order
rate constant under physiological conditions of complex 1 in comparison with the analogous imidazole
complex trans-Hlm[RuCl4(im)2] (Im = imidaZole) ICR were examined by means of HPLC, UV
and conductivity measurements (Kobs.(1) = 1.55 × 10-4s-1; Kobs.(ICR) = 9.10 × 10-4s-1). An attempt
was made to elucidate the bonding conditions in 1 by studying the reactions of Ru(lll) and the two
N-methyl isomers of indazole. It can be expected that bonding in the unsubstituted ligand should
occur via the N2 nitrogen. The molecular structures of the complex trans-H(1-Melnd)[RuCl4(1-Melnd)2] × 1H2O (1-Melnd = 1-methylindazole) 6 and its hydrolysis product in aqueous solution
[RuCl3(H2O)(1-Melnd)2]7 were determined crystallographically. After anisotropic refinement of F
values by least squares, R is 0.053 for 6 and 0.059 for 7. Both complexes crystallize with four molecules in a unit cell of monoclinic symmetry. The space group is P2.1/n for 6 with cell dimensions
a = 10.511Å, b = 13.87Å, c = 19.93Å, and β = 98.17° and C2/c for 7 with a = 19.90Å, b = 10.94Å, c = 8.490Å and β = 96.74° The fact that the aqua species 7 could be isolated after dissolving
6 in a water/acetone solution confirmed the theory of many Ru(lll) complexes being initially
transformed, under physiological conditions, into aqua complexes in a first and often rate-determining
hydrolysis step. Compounds 1 and ICR are potent antitumor agents which exhibit activity
against a variety of tumor cells and experimental tumor models in animals, including autochthonous
colorectal tumors. Clinical studies with 1 are in preparation.
