Syntheses,toxicity and biodistribution of CO‐releasing molecules containing M(CO)5 (M = Mo,W and Cr)

A series of CO‐releasing molecules M(CO)₅ L (M = Mo, W and Cr), ( 1 , 2 , 3 , L = glycine methyl ester; 4 , 5 , 6 , N‐methylimidazole; 7 , 8 , 9 , 2‐aminopyridine; 10 , 11 , 12 , 3‐aminopyridine; 13 , 14 , 15 , 4‐aminopyridine), were synthesized. All complexes have been characterized by NMR, IR and electrospray ionization mass spectroscopy; the octahedral structures of 14 and 15 were also established by X‐ray crystallography. Furthermore, all complexes were evaluated for toxicity, pharmacokinetics and metabolic processes. Cytotoxic effects on the proliferation of fibroblast cell line were assayed by MTT. Among the complexes, Mo complex 1 showed the lowest cytotoxicity (IC₅₀ = 597 µmol l^?1) and W complex 2 showed a remarkable toxic effect, with IC₅₀ = 52 µmol l^?1. With the same ligand, the toxic effects of the complexes increase in the order of metal element W < Cr < Mo. For the same central metal element, the complexes containing imidazole showed lower toxic effects than those containing amino acid ester or aminopyridine. In accordance with the results from cytotoxicity, the complexes also showed corresponding toxic effects in animal models. The biodistributions of the complexes were established by inductively coupled plasma–atomic emission spectroscopy, measuring metal in tissues and organs. The results show that the complexes were gradually absorbed and unevenly distributed in vivo. The complexes containing imidazole entered tissues and organs faster than those containing amino acid ester. The complexes containing W atom were absorbed and distributed more slowly than those containing Mo or Cr atoms. Copyright © 2014 John Wiley & Sons, Ltd.