Kier L B, Hall L H
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond 23298-0581.
Pharm Res. 1990 Aug;7(8):801-7. doi: 10.1023/a:1015952613760.
A new method for molecular structure description is presented in which both electronic and topological characteristics are combined. The method makes use of the hydrogen-suppressed graph to represent the structure. The focus of the method is on the individual atoms and hydride groups of the molecular skeleton. An intrinsic atom value is assigned to each atom as I = (delta v + 1)/delta, in which delta v and delta are the counts of valence and sigma electrons of atoms associated with the molecular skeleton. The electrotopological-state value, Si, for skeletal atom i is defined as Si = Ii + delta Ii, for second row atoms, where the influence of atom j on atom i, delta Ii, is given as sigma(Ii-Ij)/rij2; rij is the graph separation between atom i and atom j, counted as the number of atoms. The characteristics of the electrotopological state values are indicated by examples of various types of organic structures, including chain lengthening, branching, heteroatoms, and unsaturation. The relation of the E-state value to NMR chemical shift is investigated for a series of alkyl ethers. The E-state oxygen value gives an excellent correlation with the 17O NMR: r = 0.993 for 10 ethers. A biological application of the E-state values in QSAR analysis is given for the binding of barbiturates to beta-cyclodextrin.
本文提出了一种结合电子和拓扑特征的分子结构描述新方法。该方法利用氢抑制图来表示结构。其重点在于分子骨架的各个原子和氢化物基团。为每个原子赋予一个固有原子值(I = (\delta v + 1)/\delta)，其中(\delta v)和(\delta)分别是与分子骨架相关的原子的价电子数和(\sigma)电子数。对于第二周期原子，骨架原子(i)的电拓扑状态值(Si)定义为(Si = Ii + \delta Ii)，其中原子(j)对原子(i)的影响(\delta Ii)为(\sigma(Ii - Ij)/rij^2)；(rij)是原子(i)和原子(j)之间的图距离，以原子数计。通过各种类型有机结构的例子，包括链延长、分支、杂原子和不饱和结构，展示了电拓扑状态值的特征。研究了一系列烷基醚的(E)态值与核磁共振化学位移的关系。(E)态氧值与(^{17}O)核磁共振有极好的相关性：对于(10)种醚，(r = 0.993)。给出了(E)态值在巴比妥类药物与β - 环糊精结合的定量构效关系分析中的生物学应用。
