【作者】 周丛艺；

【导师】 聂长明；

【作者基本信息】 南华大学 ， 市政工程， 2007， 硕士

【摘要】 定量结构-性质相关（quantitative structure-property relationships QSPR），定量结构-活性相关（quantitative structure-activity relationships QSAR），定量结构-保留指数相关（quantitative structure-retention relationships QSRR）的研究已成为化学、环境、生命等学科研究中的一个前沿领域。近些年来发展的拓扑指数通过表征分子拓扑图某种特征而实现分子结构信息的数值化，拓扑指数法能够合理有效的对化合物分子层面进行有效的表征，已成为QSPR／QSAR／QSRR研究中的一种重要方法。本工作主要从以下方面进行：（1）为实现对有机化合物细微差异的有效合理表征，根据电负性均衡原理，通过逐级加合均分法计算分子中原子的平衡电负性。用平衡电负性对分子隐氢图着色，结合支化度，在邻接矩阵基础上增加平衡电负性和支化度参数，构建新拓扑指数AI。该指数不仅物理意义明确，而且对含多重键和杂原子的化合物具有唯一性表征。引入路径数P₂和P₃，研究烷烃的摩尔体积、摩尔折射度、临界体积、偏心因子和固定液为角鲨烷（柱温分别为3（?）、5（?）、7（?））、H-P PONA（柱温6（?））和J&W DB-5（柱温6（?））上的气相色谱保留指数，结果表明它们可用同一式子进行定量描述：P=a^*AI＋b^*P₂＋c^*P₃＋d，各样本数的相关系数均大于0.99。同时建立烷烃的标准生成焓（△_fH_m^θ）、标准熵（S_m^θ）、标准生成自由能（△_fG_m^θ）、气化焓变（△_Hv）、升华焓变（△H_s）、液态比热容（C_p^θ）和不同温度下的C_p（分别为400 K、600K、800 K和1000k）以及气体的范德华常数a和b等热力学性质；沸点（T_B）；临界温度（T_C）、临界压力（P_C）和临界体积（V_C）等临界性质的定量结构-性质关系模型，模型相关系数介于0.9916和0.9998之间。模型经检验，显示出良好稳健性和预测能力。模型物理意义明确，表明烷烃性质可用分子的大小，平衡电负性，支化度和形状等内在结构信息进行有效表征。模型经Needham公式分析，结果显示指数NI对烷烃性质影响最大。其模型有望在烷烃QSPR和QSRR研究中得到广泛的运用。（2）在传统的距离矩阵基础上，利用平衡电负性和相对化学键长对之进行修正，从而构建能够对有机化合物分子进行有效表征的新半经验拓扑指数N_t。该指数在QSPR／QSAR研究中具有良好的应用，在烷烃，烯烃，炔烃，醛酮，硫醇和氯硅烷等化合物中显示良好的应用。模型所有的相关系数均大于0.99。经留一法检验，交叉检验参数均显示模型的良好稳定性和预测能力。（3）在分子拓扑理论基础上，对分子隐氢图着色，以平衡电负性为电子描述符，结合化合物原子的几何结构特征，对距离矩阵进行扩展，构建新拓扑指数NTI。结果表明，该指数对分子结构中含有双键、叁键和杂原子的有机化合物具有优良的结构选择性，与链烷烃、环烷烃、烯烃、二烯烃、炔烃、醇、酮、醚、脂、卤代烃、卤代苯、烷基苯、卤代酚、对胺基苯甲酸脂和对羟基苯甲酸脂共15个系列化合物的正辛醇／水分配系数log K_ow拥有优良的相关性，相关系数介于0.9999和0.9900之间，可以用式子log K_ow=aNTI＋b对有机物的正辛醇／水分配系数进行定量描述，其中a，b为常数。用上述方程计算log K_ow，得出的预测值与实验值之间吻合良好。（4）提出拓扑化学行为概念，把对化合物性质最具影响力的因素归纳为拓扑生长力和拓扑阻滞力。根据该原理，利用价电子轨道能量对价电子距离矩阵进行修正。研究表明OET（轨道能量拓扑指数）对镧系元素和锕系元素的物化性质具有良好的应用，尤其是对尚未借助QSPR（定量结构性质关系）手段进行研究报道的光谱性质。LOO CV（留一法交叉检验）的结果验证了模型的良好稳定性和预测能力，采用的检验参数有：PRESS／SSY，SEP_CV，R_CV，S_PRESS和PSE，其中PRESS／SSY比值介于0.0006和0.1148。与文献进行比较，本文方法结果与之接近或更好。研究显示正是基于拓扑化学行为才有本文方法良好和较广的应用。更多还原

【Abstract】 QSPR/ QSAR/ QSRR （quantitative structure- property relationships, quantitative structure- activity relationships, quantitative structure- retention relationships） have been a cutting-edge research in chemistry, environment, life science and so on. During recent years, in QSPR/QSAR/QSRR, developing topological index has been a promising approach. Topological index is a graph theoretical descriptor obtained by transforming molecular structures into the corresponding molecular graphs on the molecular level. Topological indexes have been an important method in QSPR/QSAR/QSRR. This work mainly concentrates on the follows:（1） In order to efficiently characterize structures of organic compounds, equilibrium electronegativities were calculated, in terms of the principle of the balanced electronegativities. The novel topological index Al was proposed by extending adjacent matrix employing the degrees of branching and equilibrium electronegativities which were utilized to dye hydrogen-suppressed graph. Possessing clear physical meaning, Al can distinguish compounds containing multiple bonds and/or heteroatoms. In addition, the path number P₂ and P₃ were involVed as well. Study was performed on the properties of alkanes （e. g., molar volume, molar refraction, critical volume and eccentric factor） and retention index of gas chromatography on different stationary phases at different temperatures（e. g, on squalane at 3（?）, 5（?）, 7（?）; on H-1（?）PONA at 60; on J & W DB-5 a（?）60）. The regression results indicated that the relationship between them can be quantitatively described as the following equation: P=a*AI+b*P₂+c*P₃+d, with all the correlation coefficients being larger than 0.99. The quantitative structure-property relationships （QSPR） were conducted of the thermodynamic properties （e. g.Δ_fH_m^θ, Sm^θ,Δ_fG_m^θ,ΔH_v,ΔH_s, C_p^θ, C_p, van der Waals constants a and b）, boiling points （T_B）, critical properties （e. g. T_C, P_C and V_C） for alkanes with the correlation coefficients ranging between 0.9916 and 0.9998. The cross validation demonstrated the models to be statistically significant and reliable. The models, with explicit physical meaning, indicated that size, equilibrium electronegativity, branching degree and shape of molecules can efficiently characterize the inherent structure information of alkanes. The .analyzing results with the Needham formula showed that NI was the most influential factor. The results showed that the models have wide application to study on QSPR and QSRR of alkanes.（2） A novel semi-empirical topological descriptor Nt was proposed by revising the traditional distance matrix based on the equilibrium electronegativity and the relative. bond length. Nt can not only efficiently distinguish structures of organic compounds containing multiple bonds and/or heteroatoms, but also possess good applications of QSPR/QSAR （quantitative structure-property/activity relationships） to a large diverse set of compounds, which are alkanes, alkenes, alkynes, aldehydes, ketones, thiols and alkoxy silicon chlorides with all the correlation coefficients of the models over 0.99 The LOO CV （leave-one-out cross-validation） method was used to testify the stability and predictive ability of the models. The validation results verified the good stability and predictive ability of the models employing the cross-validation parameters: R_CV, SEP_CV and S_CV, which demonstrated the wide potential of the N_t descriptor for applications to QSPR/QSAR.（3） A novel topological index NTI was proposed in terms of the principle of the topological theory by dyeing the suppressed-hydrogen graph and expanding the distance matrix. Taken into account the atomic characteristics of geometric structure as well as electron for compounds, the new index had excellent structural selectivity for organic compounds, which comprises 15 series of organic compounds with double bonds, triple bonds and hetero atoms （e. g., chain alkanes, cycloparaffin, alkenes, alkynes, alcohols, ketones, esters, ethers, alkyl halides, alkylbenzenes, benzene halides, phenol halides, dienes, p-anthranilates and p-hydroxybenzoates）. Regression was performed between the index NTI and n-octanol/water partition coefficient of these compounds, demonstrating regression of excellence with the correlation coefficient ranging from 0.9900 to 0.9999. The relationship between log K_ow and NTI for organic, compounds can be quantitatively described as the following: log K_ow=aNTI+b （a and b are constants）, which showed that the calculated values were in good agreement with the experimented ones.（4） We introduced the chemical behavior of topology for the first time which consists of the topological growing power and the topological blocking power. On the basis of the principle, the OET （orbital-energy topological index） was proposed by revising the valence electron distance matrix with the orbital energy. The results demonstrated that OET has good application to the physicochemical properties of lanthanide and actinide, especially to the spectral properties which have not been reported by means of QSPR （quantitative structure-property relationships）. The results of LOO CV （leave-one-out cross-validation） verified the good stability and predictive ability of the models using the cross-validation parameters: PRESS/SSY, SEP_CV, R_CV, S_PRESS and PSE with the PRESS/SSY ratio ranging between 0.0006 and 0.1148. Compared with the other methods, this work provided an easier way yielding results close to or better than the others. It is on the basis of the chemical behavior of topology that leads to the good and wide application of this method.更多还原