Complexation of the anti-Trypanosoma cruzi drug benznidazole improves solubility and efficacy.

The ruthenium complex, trans-[Ru(Bz)(NH 3) 4SO 2](CF 3SO 3) 2 1, Bz = benznidazole ( N-benzyl-2-(2-nitro-1 H-imidazol-1-yl)acetamide), is more hydrosoluble and more active (IC 50try/1 h = 79 +/- 3 microM) than free benznidazole 2 (IC 50try/1 h > 1 mM). 1 also exhibits low acute toxicity in vitro (IC 50macrophages > 1 mM) and in vivo (400 micromol/kg < LD 50 < 600 micromol/kg) and the formation of hydroxylamine is more favorable in 1 than in 2 by 9.6 kcal/mol.