Chemistry and biology of manganese carbon-releasing molecules containing thiosemicarbazone ligands

Abstract A series of manganese complexes bearing 6-nitropiperonal thiosemicarbazone ligands have been synthesized and characterized. The ligands differ by the alkyl substituent on the amine nitrogen. These complexes, formulated as Mn(CO) 3 (TSC)Br, where TSC represents the thiosemicarbazone ligand, show very rapid release of carbon monoxide upon exposure to light, establishing them as photoCORMs (light activated carbon monoxide-releasing molecules). The photo-reactivity profile of the complexes have been studied in detail using the myoglobin assay as a detection system for carbon monoxide. Three different wavelengths of light were used: 365 nm (UV), 405 nm (purple) and 435 nm (blue). It was observed that the half-life for the CO release was dependent on the wavelength of light. These half-lives were on the order of 10 to 100 seconds which is very fast for this type of complex. Typically, the half-lives increased with a decrease in the energy of the incident radiation. For the compound bearing the phenyl-substituted amine group, t½ (in seconds) was 44.54, 59.59 and 65.90 for the UV, purple and blue light respectively. The amount of CO released was also wavelength dependent, with higher energy wavelength generally releasing more CO. UV light caused 2 equivalents of CO to be released while roughly 1.5 and 1.0 equivalents were released for the purple and blue light respectively. The biological profile of the complexes were also studied using antibacterial and anticancer assays. Against both Gram-negative and Gram-positive bacteria, the complexes showed good growth inhibitory effects with minimum inhibitory concentration (MIC) values no higher than 50 μM and as low as 3.13 μM. More importantly, these estimated MIC values were noticeably reduced when the bacteria, incubated with the complexes, were irradiated. All four compounds displayed intrinsic cytotoxicity against HEK293T (kidney) and A549 (lung carcinoma) cell lines, as indicated by relatively efficient cell killing for CORMs without irradiation. Irradiation of treated cultures with short wavelength visible spectrum light augmented these cytotoxic effects.