分子光谱法研究新型抗肿瘤前药双(β-二酮)Ti(Ⅳ)与DNA相互作用

Studies on interaction of novel anti-tumor prodrug bis-(β-diketonate) Ti(Ⅳ) complex with DNA by molecular spectral methods

在生理酸度(pH=7.4)下,采用紫外及荧光等分子光谱法研究了自制的双(β-二酮)Ti(Ⅳ)新型抗肿瘤前药与DNA之间的相互作用,考察了前药和溴化乙锭与鱼精DNA结合的竞争性.研究结果表明:DNA通过静态猝灭作用机制猝灭前药的荧光,并测得其在298K和308K时的猝灭常数(Kq)分别为8.590 3×1011和7.192 2×1011 L·mol-1·s-1,结合常数(Kd)分别为5.583 9×104和4.798 1×104 L·mol-1,结合位点数(n)为1.16和0.97;DNA的存在使前药的紫外吸收光谱发生减色效应且吸收波长产生红移;前药分子可插入DNA中置换出于DNA结合的溴化乙锭.这些结果说明前药分子以嵌插方式与DNA进行结合.

The interaction between novel anti-tumor prodrug bis-（β-diketonate）Ti（Ⅳ） complex（L-Ti） and milt DNA in Tris-HC1 buffer（pH=7.4） was investigated by the application of fluo-rescence spectroscopy and ultraviolet absorption spectroscopy,the competitive binding to DNA between prodrug（L-Ti） and ethidium bromide（EB） was also studied.The results demonstrated that prodrug（L-Ti） could bind to DNA and the formed complex quenched the intrinsic fluorescence of prodrug（L-Ti） through static quenching mechanism.The quenching rate constants of biomoleeule（Kq） of the reaction of DNA with prodrug（L-Ti） were calculated to be 8.590 3×1011 and 7.192 2×1011 L·mol-1·s-1 by Stern-Volumer equation,the corresponding binding constants（Kd） were computed to be 5.583 9×104 and 4.798 1×104 L·mol-1 and the number of binding sites（n） was counted to be 1.16 and 0.97 between prodrug（L-Ti） and DNA at 298 K and 308 K,respectively.prodrug（L-Ti） could be intercalated into DNA and displaced the EB from the EB-DNA complex.It was showed that prodrug（L-Ti） could combine with DNA in the mode of intercalation.