CO Releasing Properties and Cytoprotective Effect of cis-trans- [ReII(CO)2Br2L2]n Complexes

The carbon monoxide (CO) releasing properties of a series of rhenium(II)-based complexes of general formula cis-trans-[Re-II(CO)(2)Br2L2](n) and cis-trans-[Re-II(CO)(2)Br2N boolean AND N] (where L = monodentate and N boolean AND N = bidentate ligand) are reported. Complexes evaluated in this study were obtained from direct ligand substitution reactions of the cis-[Re-II(CO)(2)Br-4](2-) synthon (2) recently described.(1) All molecules have been fully characterized. The solid-state structures of the cis-trans-[Re-II(CO)(2)Br2L2] (with L = N-methylimidazole (3), benzimidazole (4) and 4-picoline (5)) and the cis-trans-[ReII(CO)(2)Br2N boolean AND N] (with N boolean AND N = 4,4'-dimedthyl-2,2'-bipyridine (8) and 2,2'-dipyridylamine (11)) adducts are presented. The release of CO from the cis-trans-[Re-II(CO)(2)Br2L2](n) complexes was assessed spectrophotometrically by measuring the conversion of deoxymyoglobin (Mb) to carbonmonoxy myoglobin (MbCO). Only compounds bearing monodentate ligands were found to liberate CO. The rate of CO release was found to be pH dependent with half-lives (t(1/2)) under physiological conditions (25 degrees C, 0.1 M phosphate buffer, and pH 7.4) varying from ca. 6-43 min. At lower pH values, the time required to fully saturate Mb with CO liberated from the metal complexes gradually decreased. Complex 2 and the cis-trans-[Re-II(CO)(2)Br-2(lm)(2)] adduct (with lm = imidazole (6)) show a protective action against ischemia-reperfusion stress of neonatal rat ventricular cardiomyocytes in culture.