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Synthesis, Characterization And Vitro Activity Of Ruthenium N-heterocyclic Anticancer Drugs

Posted on:2009-08-08Degree:MasterType:Thesis
Country:ChinaCandidate:X H ChaiFull Text:PDF
GTID:2121360242988659Subject:Applied Chemistry
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Cancer is one of the most important human health hazards diseases.In chapter 1, several methods of cancer treatment including surgical therapy, radiation therapy, photodynamic therapy and the most common chemotherapy are first described. Then the classification, hydrolysis, interaction with protein and DNA of ruthenium complexes are described followed. At the same time, the used methods of the interaction between anticancer drugs and DNA are also summarized. With these described above as basis, the purposes of this article are suggested.In chapter 2, the synthesis, characterization and vitro activity of ruthenium mononuclear complexes were described.Seven ruthenium mononuclear complexes [H(DMSO)2][trans-RuCl4(DMSO)2](1), Na[trans-RuCl4(DMSO)2](2), (HIm)[trans-RuCl4(Im)2](ICR,3), (HIm)[trans-RuCl4(DMSO) (Im)](NAMI-A,4), (HIm)2[trans-RuCl5(Im)}(5), [H(2-MeIm)][trans-RuCl4(2-MeIm)2] (6),[H(2, 2'-bipy)][RuCl4(2, 2'-bipy)]·HCl(7) were synthesized with ruthenium trichloride,imidazole, 2-methylimidazole, 2, 2'-bipyridine as materials, ethanol, acetone, dimethyl-sulfoxide of a little polarity as solvents. Their structures have been confirmed by element analysis, IR and UV.Studying hydrolysis of (3) and (4) in different solvents as water, dimethylsulfoxide (DMSO) aqueous solution and phosphate buffer solution (PBS) by UV spectra. We found that the hydrolysis of (3) is lower than (4) in water, and their pH reduced after hydrolysis, this showed that the generated hydrates were hydroxylation by losing a proton. In DMSO solution, the character absorption of (3) at 350nm, (4) at 390nm showed obvious hypochromic and blue shift as a result of salvation and the absorption of both two at about 250nm showed hyperchromic and blue shift with a reverse. The interaction of (3) and (4) with calf thymus DNA (ct-DNA) in PBS by UV was also described.In chapter 3, the synthesis, characterization and vitro activity of ruthenium binuclear complexes were described. Two ruthenium binuclear complexes Na2[{trans-RuCl4 (DMSO)}2(μ-pyz)](8) and Na2[{trans-Rua4(DMSO)}2(μ-4, 4'-bipy)](9) were synthesized with ruthenium trichloride, pyrazine, 4, 4'-bipyridine as materials and ethanol as solvent. Their structures have been confirmed by element analysis, IR and UV.Studying the hydrolysis of (8) and (9) in PBS by UV. We found that the hydrolysis of (8) is lower than (9) in water. The interaction of (8) and (9) with calf DNA in PBS by UV was also described.In chapter 4, hydrolysis, interaction with DNA of (3), (4), (8) and (9) were summarized. In PBS, (3), (4), (8) and (9) have a large turn point at about 75min, the absorption caused by LMCT(charge transfer transition between ligand Cl and metal Ru) of (4) at 390nm, (9) at 394nm had obvious blue shift because of hydrolysis of Cl-, and the absorption enhanced gradually after blue shift at about 350nm.When studying their binding with DNA in PBS by UV spectra, we found that when the concentration of DNA remained unchanged, as increasing of their concentration, their absorption weakened compared with without DNA (as 9), this showed that DNA had a interaction with complexes, but the absorption position didn't change, this showed that the combination degree of DNA and complexes unchanged. When their concentration remained unchanged, as increasing of DNA, their absorption had red shift and hypochromic (as 4). When the concentration of complexes and DNA both remained unchanged, there would be obvious hypochromic and red shift, this indicated that DNA had interaction with complexes, and the nitrogenous heterocyclic ligands embedded in DNA (as 4 and 8).
Keywords/Search Tags:Ruthenium, Nitrogenous heterocycles, Anticancer drugs, Hydrolysis, Anticancer mechanism, Vitro activity
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