Study On Synthesis,CO-releasing Behaviors And Cytotoxicity Of Novel Monoiron(?) Carbonyl Complexes

Carbon monoxide?CO?is a gaseous signaling molecule,and a suitable dose of CO can bring with various physiological functions,such as anti-inflammatory,anti-oxidation,and cell protection.Therefore,how to control the concentration of CO in the body becomes the pivotal to explore its medicinal multi-value.CO-releasing molecules?CORMs?are a type of complexes that can liberate their carbonyl ligands to free CO under certain conditions.Most CORMs are transition metal carbonyl compounds.Among them,iron-based CORMs have raised an increasing attention due to that iron is the most abundant trace element in human body.CO-releasing behaviors of iron carbonyl compounds is closely related to the strength of Fe-CO bonds.CO is a typical?acceptor or?acid ligand.Accordingly,the less the amount of CO coordinated by iron,the more feedback electrons are given to each CO by the iron?II?center.The stronger the Fe-CO bond,the slower the CO release rate.In principle,CO-release rate of iron-based CORMs can be tuned by the number of carbonyl ligands and the electron-donating ability of auxiliary ligands.Therefore,in the present dissertation,a series of novel monoiron?II?carbonyl compounds were synthesized and their CO-releasing behavior and kinetics as well as cytotoxicity were investigated.The work can be mainly divided into three parts:In the first part,six fac-[Fe?CO?₃I₂L]compounds 1-6 with the iron coordinated by amine-derived nitrogen were synthesized by the reaction of cis-[Fe?CO?₄I₂]and amines within 5 min.The complexes were characterized by various techniques such as X-ray diffraction analysis,NMR,IR and elemental analysis.CO-release behaviors of compound 1-6 in DMSO solvent were monitored by infrared spectroscopy.the results revealed that a short half-life 7 min for compound 1 while compound 2-6within 3 min.Such a fast CO-liberating may be attributed to the weak electron-donating ability of amine ligand.The cytotoxicity of these compounds was initially evaluated by MTT method using Compound 1.Cytotoxicity result indicated a high death of RT112 cells at a low dose(IC₅₀¹5?M).In the second part,ionic fac-Y[Fe?CO?3I3]complexes 7-12 were prepared by following a similar procedure as described in the first part except extending the reaction time to 1-2 h.A moderate yield?⁶0%?was obtained.These iron carbonyl complexes were also structurally determined by means of single crystal X-ray diffraction,NMR,IR and elemental analysis.These ionic fac-Y[Fe?CO?3I3]compounds exhibited a slower decomposition with CO release than fac-[Fe?CO?₃I₂L]complexes in DMSO.By linearly fitting the natural logarithm of the absorbance of iron carbonyl complexes?ln A?against the reaction time?t?,kinetics of CO release procedure for these complexes are consistent with a first-order kinetic model.In addition,rates of CO release of complex 7-12 increase with the elongation of the alkyl chain in the cation.This evidence may be related to the strength of the electric field applied by the cations to the surrounding solvent.Since these ionic complexes have water solubility,their CO release behaviors in D₂O were also explored.The results indicated that the release of the aqueous solution may involve into a two-stages procedure.Cytotoxicity of these ionic complexes was evaluated by a standard MTT assay,which exhibited a high activity in killing of PC-3 cells and RT112 cells at a low IC₅₀ approximately 12?mol/L.The high performance of them may be contributed to some reactive oxygen species?ROS?which were determined during the decomposition of them with CO release.In the third part,monoiron?II?dicarbonyl compounds 13,14 were synthesized by the reaction of NH_3-n?CH₂CH₂OH?n and cis-[Fe?CO?₄I₂].The structures of these compounds were characterized by NMR,IR,et al.Due to the presence of hydroxyl group,these two complexes have also an excellent water solubility.Owning to the decrease of the numbers of carbonyl ligand from 3 to 2,complexes 13 and 14exhibited an enhanced stability with a lower CO release rate than that of fac-[Fe?CO?₃I₂L]and fac-[Fe?CO?₃I₃].Kinetic analysis revealed that the CO-releasing process was consistent with the first-order reaction kinetics model.Particularly,cytotoxicity results indicated that these complexes have an excellent biocompability(IC₅₀>1000?M).