Design, Synthesis And Antibacterial Activity Of Water - Soluble Fischer Carbene Compounds

CO releasing molecules (CO-RMs) of transition metal carbonyl complexes is emerging as a new interdisciplinary advance of inorganic chemistry, biological medicine and materials chemistry. In this dissertation, we devised new anionic Fischer carbene carbonyls bearing Cr, Mo, W as metallic centre in order to tune CO releasing and improve the water solubility of transition metal carbonyls. Fifteen anionic Fischer carbene complexes have been synthesized and fully characterized. Horse heart myoglobin assays show that these anionic carbonyls release carbon monoxide in well-controlled fashion under physiological conditions, and their CO release kinetic is dependent on pH of the Mb assay. The Structure-Releasing correlation reveals that the metallic centre of anionic carbene complexes is the key factor governing their carbon monoxide release behaviors, and also consistent to their antimicrobial activities. This dissertation is composed of following four parts:Firstly, starting from M(CO)6(M=Cr,Mo,W), and CH3Li were used nucleophile for preparing anionic carbene precursors. Quaternary ammoniums are employed to stabilize Fischer carbonyl anions, and tune the water-solubility. All compounds have been characterised by FT-IR,1H,13C NMR and ESI-MS.Secondly, fifteen anionic-type complexes are assessed using myoglobin assay under in vitro physiological condition. The results showed these complexes have a excellent releasing kinetics in water. The correlation of infrared data and release kinetics confirm that among the fifteen complexes, Cr (la-le) had the fastest release rate, Mo(2a-2e) slower and W(3a-3e) sluggish.The antimicrobial activity and minimum inhibiting concentration (MIC) of these complexes were evaluated in vitro and in vivo. CO-RM Cr(2b) was most sensitive to the gram-negatives E.coli, with MIC of30μM. The comparison of antibacterial activity of CORM and iCORM found that CO release rate is directly related to the bactericidal effects.Finally, we investigated the degradation of CO-RM (2e) in aqueous solution in order to elucidate the CO release pathway of anionic carbene compounds. The degradation of2e was monitored by1H NMR and IR.. The experimentations identified several degradation intermediates, which formed via the ligands dissociation and the sequential CO liberation. In a postulated degradation pathway, the protonation of anionic carbene is the key step of CO releasing, and the carbene moiety might degrade as acetate.