摘要
本工作采用密度泛函B3LYP方法,在6-311+G*水平基组上对紫衫醇C13侧链(用M表示)分子离子基态进行了结构优化、频率、自然键原子轨道计算,得到其微观结构及相关性质,系统分析了体系的几何构型、原子的净电荷布局、前沿分子轨道特征,并对红外光谱特征峰进行了指认归属.结果表明:C13侧链分子离子稳定性顺序为:M-(1 A)>M(2 A)>M+(3 A),极性强弱是M+(3 A)>M-(1 A)>M(2 A),M+(3 A)的空间构型与M(2 A)相比在一些部位变化大,特别是在C1-C2位置,键长拉长很多而键角减小很多.净电荷、分子轨道特征分析一致确定Mn(n=0,1,-1)体系的酰胺、羟基、羧酸等基团是化学反应时的活性部位,能与亲核或亲电试剂反应,均是关键药效团的活性部位,这一结论与紫衫醇实验研究的构效关系结论一致.本研究成果为进一步研究紫衫醇C13侧链的修饰改造,合成更多高效低毒的紫衫醇类拟物提供可参考的理论基础和实验依据.
The structure optimization,frequency,natural bond orbital calculation of the molecular ion ground state of taxol C13side chain（with the M symbol） are carried out at the level of 6-311＋G＊ basis set by using the B3LYP density functional method,through which its microstructure and relevant properties are obtained,the geometrical structure of the system,the atomic net charge distribution,the characteristics of the frontier molecular orbit are systematically analyzed,and the infrared spectrum characteristic peaks are identified and attributed.The results show that the molecular ion stability order of the side chain of C13is M-（1A）＞M（2A）＞M＋ （3A）,the polar strength is M＋ （3A）＞M-（1A）＞M（2A）.Compared with that of M（2A）,the space configuration of M＋ （3A） has greater changes in some positions,specially in the C1-C2 position.The bond length is stretched a lot while the bond angle decreases a lot.Analysis of the net charge and the molecular orbital characteristics determine consistently that the hydroxyl,carboxylic acid and amide ground of Mn（n=0,1,-1） system are active sites of chemical reaction and can react to the nucleophilic or electrophilic reagent,and they are all active sites of key pharmacophore.This conclusion is consistent with the conclusion of paclitaxel experimental study on the structure-activity relationship.The results of this study can serve as referable theoretical basis and experimental evidence for further study of the modification and reconstruction of taxol C13 chain to synthesize more taxol analogues with good effect and low toxicity.
出处
《原子与分子物理学报》
CAS
CSCD
北大核心
2014年第2期213-217,共5页
Journal of Atomic and Molecular Physics
基金
湖北省教育厅重点项目(D20122903)
湖北省高校应用化学战略性新兴产业人才培养计划项目
