The effect of specific modifications of the amine ligands on the solubility, stability, CO release to myoglobin and whole blood, cell toxicity and haemolytic index of [Mo(CO)4(NR3)2] complexes

A series of cis-[Mo(CO)4(amine)2] complexes (NR3 = morpholine 1; 4-Me–piperazine, 2; H2NCH2CH2NH2, 3; H2NCH2CH2–morpholine (4) R2NCH2CH2–piperazine–4-Me (R = H, 5); R = Me, 6); Me2NCH2CH2NMe2, 7) was prepared in good yields, in a one-step microwave-assisted synthesis. The X-ray diffraction structures of the complexes 4, 5 and 6 are reported. The stability of the complexes 1–7 in aqueous, aerobic media was studied by UV–Vis spectrophotometry, RP-HPLC and gas chromatography at several pH values. Stability beyond 1 h requires bidentate ligands with at least one tertiary amine ligand and increases in the order 4 < 5 < 6. Stability is approximately the same at pH 7.5 and pH 3.9 for 5 and 6 in solutions acidified with HCl. Acidification with CF3COOH induces decomposition. The order of CO transfer rate to deoxy-Mb and haemoglobin in whole blood is 1 > 2 > 3 > 4 > 5 > 6 >> 7, but it is much faster to whole blood. The haemolytic index of some compounds increases in a similar order: 1 < 2 < 5 < 6; with the exception of 1, the complexes are not toxic to RAW264.7 cells up to a concentration of 100 μM.