摘要
研究取代基对核苷分子构成的氢键复合物稳定性的影响,对于推动新型抗病毒药物的研发工作有着重要的意义.在M06-2X/6-31+G(d,p)水平上对9种不同的屈氟尿苷或其取代类似物与腺嘌呤核苷构成的氢键复合物的结构进行了预测,并在M06-2X/aug-cc-pVTZ水平上对复合物相对稳定性进行了探讨.研究发现,该类氢键复合物中N—H…N氢键作用最强,N—H…O=C次之,C—H…O=C最弱.基于模拟结果,嘧啶环C5上的吸电子取代基使嘧啶环作为氢键质子供体的能力增强,从而加强了它与腺嘌呤核苷间氢键作用,供电子取代基使嘧啶环作为氢键质子供体的能力减弱,从而削弱了它与腺嘌呤核苷间氢键作用.推测F、CN、Cl和SO_3H取代的脱氧核苷类化合物很可能成为新的抗病毒药物而引起广泛关注.
The knowledge about the effect of substituents on the binding energy of nucleoside hydrogen-bonded complexes can provide guidance to design new antiviral medicine.In this work,the optimized structures of nine derivatives of deoxythymidine and deoxyadenosine hydrogen-bonded complexes were located by using the M06-2 X/6-31＋G（d,p）method,and the binding energies were evaluated by using the M06-2 X/aug-cc-pVTZ method.The effect of substituents on the binding energies was therefore explored.The results show that the N—H…N type hygrogen bonds play a key role in stabilizing these complexes,while the N—H…O=C and C—H…O=C type hydrogen bonds play smaller roles.According to our simulation results,the electron withdrawing group on the deoxythymidine molecule could strengthen the binding,while the electron donating group on the deoxythymidine molecule could weaken the binding.Above all,the new antiviral nucleoside prodrugs F,CN,Cl,or SO3 H substituted deoxythymidine,may draw considerable attention in the foreseeable future.
出处
《辽宁师范大学学报（自然科学版）》
CAS
2017年第4期502-507,共6页
Journal of Liaoning Normal University:Natural Science Edition
基金
辽宁省教育厅科学研究一般项目(L201683671)
辽宁省自然科学基金资助项目(20170540580)
