Studies On The Molecular Design And Antitumor Activity Of A Series Of Chiral Ruthenium(Ⅱ) Complexes

In recent years, most of studies report that the ruthenium complexes generally have the features of low toxicity, easy absorption and rapid excretion; at the same time, these ruthenium complexes were also absorbed readily by tumor tissue, therefore the ruthenium complexes are likely to be a class of new antitumor drugs, which have high anticancer activity and different biological activity and toxicity compar to platinum compounds, it will be one of the most promising anticancer drugs.In this paper, we apply designing, synthesizing different ligands and changing the auxiliary ligands to synthesized a series of chiral bipyridine and phenanthroline ruthenium complexes by the method of resolution. The acute toxicity and pathological section studies of chiral ruthenium complexesΛ-[Ru(bpy)2 (o-tFPIP)](Cl)2. Studied DNA binding properties ofΛandΔisomers of ruthenium complexes. The experim ental results show that:1. We designed and Synthesized 20 chiral ruthenium complexes, which were characterized by, ES-MS, elemental analysis and 1HNMR. It was confirmed that the experimental results and theoretical values with the product, these products were the target complexes through the above experiments.2. The acute toxicity experiment showed that: when these mouses were injected byΛ-[Ru(bpy)2(o-tFPIP)](Cl)2, they all showed symptoms of poisoning.Some one died immediately on the spot, the other appeared normal diet, behavior and physiclal status in the two weeks, the majority of mice was also to appear the phenomenon of weight gain.3. The pathological section experiment showed that: when the mouse were injected byΛ-[Ru(bpy)2(o-tFPIP)](Cl)2, the mouse organs (heart, liver, lung and kidney) are appeared in varying degrees symptoms of poisoning (except for the mouse died after two weeks, their hearts did not appear strange phenomena), these organs had pathological changes, which indicated that the chiral ruthenium complexes have taken place toxicity in the mouse organs.4. The interaction of chiral ruthenium complexesΛ-[Ru(bpy)2(o-tFPIP)](PF6)2 andΔ-[Ru(bpy)2(o-tFPIP)](Cl)2 with calf thymus DNA(CT-DNA) have been investigated by electronic absorption spectra,fluorescent spectra,viscosity measurements. The experimental results show that: two chiral ruthenium complexes can bind to DNA in an intercalative mode and the DNA-binding affinity ofΔ-isomer is greater than thatΛ-isomer.