Theoretical Study On The Interaction Of Antitumor Activity Of Gold(?) Complexes With Target Molecules

Square planer Au(?)compounds are similar to Pt(II)complexes for owning 4f145d8 closed shell electron configurations with cytotoxicity,which make them into noval anticancer drugs and are widely under researched.Numbers of in vitro and vivo studies have shown that,gold(?)compounds may mainly react with mitochondria,sulfur protein or DNA,therefore,this thesis wants to investigate the preferred target of Au(?)compounds in theoretical calculations.In the early time,Calamai and his co-workers synthesized and tested two gold(?)compounds,AuCl3(Hpm)and AuCl2(pm),which were similar to cisplatin's configuration.Although hydrolysis easily happen under physiological pH,these gold(?)compounds could bind with free cysteine or calf thymus DNA.Because they own typical structures: pyridine ligands(enhancement stability)and easily leaving Cl anions,so we chose them as researching objects.The first and second chapters mainly introduce the overseas and domestic status,the subject basis and theoretical methods of gold(?)compounds.The third and fourth chapters introduce the details of monofunctional and difunctional substitution reactions between AuCl3(Hpm)/AuCl2(pm)compounds,cysteine and purine bases(G/A).We also want to find the differences between B3 LYP and M06 functionals,exploring the effect of aqueous solution optimization.The third chapter shows that: on the basis of activation energies,containing solvation effects of monofunctional substitution reactions,B3 LYP and M06 functionals getting identical qualitative result,guanine is on the dynamic priority reacting with gold(?)hydrates,so DNA is prior than the protein.In aqueous solution optimization,guanine is still optimal,but Cys(O)is selected binding gold center prior to Cys(S),which is opposite to that of gas phase optimization.Diverse solvent environments in different ?(water,DNA or protein)have no effect on activation energies,and can be ignored.Hydrogen bonding interaction plays an important role in changing configurations and activation energies.The forth chapter describes that,the B3 LYP and M06 functionals receive similar qualitative conclusion in [AuCl3(Hpm)-G-H2O-Cl]2+ or [AuCl2(pm)-G-H2O]2+ difunctional substitution reactions,which are closed to monofunctional substitution reactions.What's more,guanine owns the lowest activation energy comprising solvation effect,and Cys(O)site is the weakest one.[AuCl3(Hpm)-S-H2O-Cl]2+ or [AuCl2(pm)-S-H2O]2+ chose Cys(S)than the others,but the weakest binding site of the former is adenine,Cys(O)for the latter.