Design And Synthesis Of Organometallic Ruthenium And Iridium Compounds And Their Interaction With Proteins

Malignant tumors are great threats to human health,the clinic treatments of which are mainly based on surgery,radiotherapy,and chemical therapy nowadays.However,due to the side-effects and resistance of present anticancer drugs,more and more efforts have been endeavored into the development of novel ones with high-efficiency and low toxicity.For example,recently non-platinum metal-based anticancer drugs have achieved great success.Ruthenium and iridium anticancer complexes have attracted wide interest due to good water solubility and low toxicity,which has become a major target in the development anticancer drugs in recent years.During the development of a new drug,in vitro anticancer activity screening is a key step and research on molecular mechanisms greatly facilitates the design of anticancer complexes with higher performance.Herein,we designed and synthesized a series of organometallic ruthenium and iridium anticancer drugs by applying molecular structures based drug design strategies and their structures were characterized.Furthermore,we investigated their hydrolysis,interaction with proteins and tumor cell proliferation inhibiting activities.The results include the following three parts.?1?We chose ruthenium?II?or iridium?III?complex with half-sandwich configuration as a structural unit,and designed and synthesized a series of organometallic complexes for further screening of drug activity.The structures of synthesized complexes were confirmed by using ¹H NMR,¹³C NMR,and FT-ICR-MS analytical methods.?2?We selected six complexes and investigated their hydrolysis in aqueous solution by UV-Vis spectroscopy and liquid chromatography-mass spectrometry?LC-MS?techniques.The results revealed that organometallic ruthenium and iridium complexes with chlorine ligands quickly hydrolyzed in water.By comparison,those with iodine ligands were very stable in water which were observed to be barely hydrolyzed.?3?Then,we applied super high-resolution Fourier-transform ion cyclotron resonance-mass spectrometry?FT-ICR-MS?technique to study the interaction of two representative complexes with a protein,cytochrome C,and the results suggested those two complexes did not bind to the protein by amide condensation reaction.?4?Moreover,we carried out in vitro screening of proliferation inhibiting activity for seven complexes against MCF-7 and A549 tumor cells using MTT colorimetric assay.The results suggested that Ru organometallic complex SCF7 possessed good anti-proliferation activity on MCF7 cells.