Some Iron Carbonyl Compounds And Their CO-releasing Studies

Carbon monoxide(CO)is a gaseous signaling molecule that plays an important role in regulating cellular functions.Clinically,it reduces the muscular injury caused by ischemia reperfusion in surgical operations,particularly,in organ transplantations.To efficiently make use of the medical values of CO,it is necessary to develop molecules which can controllably deliver CO,that is,CO-releasing Molecules(CORMs)under certain conditions.Most CORMs are transition metal carbonyl compounds.Because iron is a necessary element in human body,CORMs based on iron carbonyl compounds have the greatest potential for clinical applications.In this dissertation,a series of iron carbonyl compounds were synthesized,characterized.Their CO releasing behaviors and cytotoxicity were studied.The entire dissertation is composed of three parts.In the first part,the synthesis and characterization of five iron carbonyl compounds,[Fe2(?-SR)3(CO)5X](R = CH2CH3:1I,3Br;R = CH2CH2CH3:2I,4Br)were reported.Their CO-releasing behaviors in various solvents were investigated.Based on their different CO-releasing processes in the solvents,two CO-releasing pathways were observed.In strongly polar solvents,such as DMSO and DMF,the compounds decomposed spontaneously to release CO with no influence from any auxiliary ligands.However,in solvents with relatively weak polarity,such as dichloromethane(DCM),methanol(MeOH)and acetonitrile(MeCN),their decomposition underwent such a process that an intermediate was isolatable,[Fe3(?-SCH2CH3)6(CO)6]+,which decomposed further.For compounds 1I and 3Br,the intermediates,5 and 6,differed in their counter ions,[I3]-and[FeBr4]-,respectively.Compound 3Br is not photo-sensitive whereas compound 6 undergoes obviously photoinduced degradation to release CO.The decomposing behaviors of these compounds conforms to first-order kinetic model.In cytotoxicity assessments,these five carbonyl compounds showed decent biocompatibility.In the second part,the synthesis and characterization of five[Fe(CO)3I3]-ammonium salts(cation = NMe4+(1-NMe4),NEt4+(2-NEt4),NBu4+(3-NBu4),Ch+(4-Ch),ACh+(5-ACh))were reported,where Ch+ and ACh+ are choline,acetylcholine,respectively.Their CO-releasing behaviors in DMSO were investigated.The CO-releasing kinetics of all these compounds fit first-order kinetic model and their CO-releasing rates are affected by the cations.The CO-release from compounds 4-Ch and 5-ACh can be accelerated by the induction of red-light.Preliminary studies have shown that these compounds have significant cytotoxicity,which may be contributed by their organic ammonium cations(vide infra).The third part dealt with the synthesis and preliminary characterization of three simple cationic iron carbonyl compounds,[Fe(CO)3I3]-,cation = NH4+(6-NH4);Na+(7-Na);K+,(8-K).These salts are extremely water-soluble and decompose rapidly to release CO in aqueous solution.Their decomposing behavior in physiological saline also conformed to first-order kinetic model.Their CO-releasing rate depended on their anions.Among the compounds,compound 8-K possessed the shortest half-life time.In cytotoxicity assessments,these carbonyl compounds showed good biocompatibility and the residues after CO-release showed no any detrimental effect at all to the tested cells.Therefore,they are a promising type of compounds of great potentials as CORMs.