Quantum-Chemical Descriptors in QSAR/QSPR Studies
Quantum-Chemical Descriptors in QSAR/QSPR Studies
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DOI：
10.1002/chin.199635327
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发表时间：
1996-08
期刊：
影响因子：
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通讯作者：
M. Karelson;V. Lobanov;A. Katritzky
中科院分区：
文献类型：
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作者：
M. Karelson;V. Lobanov;A. Katritzky
定量构效关系（QSAR/QSPR）研究无疑在现代化学和生物化学中具有重要意义。QSAR/QSPR的概念是利用化学直觉和经验将对具有期望性质的化合物的搜索转化为数学量化和计算机化的形式。一旦发现结构与活性/性质之间的相关性，任何数量的化合物，包括尚未合成的化合物，都可以很容易地在计算机上筛选，以便选择具有所需性质的结构。然后可以选择最有希望的化合物进行合成并在实验室进行测试。因此，QSAR/QSPR方法节省了资源，加速了新分子的开发过程，可用于药物、材料、添加剂或任何其他目的。虽然找到成功的结构活性/性质相关性并不容易，但最近处理QSAR/QSPR研究的论文数量呈指数增长，清楚地表明该领域的快速进展。为了获得显著的相关性，使用合适的描述符是至关重要的，无论是理论的，经验的，还是从现成的结构实验特征中得出的。许多描述符反映了简单的分子性质，因此可以深入了解所考虑的活性/性质的物理化学性质。计算硬件的最新进展和高效算法的发展有助于分子量子力学计算的常规发展。新的半经验方法在相对较短的计算时间内提供了真实的量子化学分子量。因此，量子化学计算是新分子描述符的一个有吸引力的来源，它原则上可以表达分子的所有电子和几何性质及其相互作用。事实上，最近的许多QSAR/QSPR研究都单独使用量子化学描述符或与传统描述符结合使用。量子化学提供了比经验方法更准确和详细的电子效应描述。量子化学方法可以通过从分子波函数直接推导电子描述符来应用于定量的构效关系。在许多情况下，已经确定，由于量子化学方法的近似性质和忽略溶剂化效应而引起的误差在很大程度上可在结构相关系列中转移；因此，计算出的描述符的相对值可能是有意义的，即使它们的绝对值不能直接应用。2此外，由分子波函数衍生的电子描述符也可以在原子或基团的基础上进行划分，从而可以分别描述各个分子区域。大多数使用量子化学描述符的工作都是在QSAR领域进行的，而不是在QSPR领域，即描述符与生物活性相关，如酶抑制活性，致幻活性等。3-6部分原因是，从历史上看，寻找与化学结构的定量关系始于理论药物设计方法的发展。据报道，量子化学描述符也与有机化合物的反应性、辛醇/水分配系数、色谱保留指数和分子的各种物理性质有关。7-11本文综述了量子化学描述符在处理化学、物理、物理等问题的QSAR/QSPR开发中的应用。
Quantitative structure-activity and structureproperty relationship (QSAR/QSPR) studies are unquestionably of great importance in modern chemistry and biochemistry. The concept of QSAR/QSPR is to transform searches for compounds with desired properties using chemical intuition and experience into a mathematically quantified and computerized form. Once a correlation between structure and activity/property is found, any number of compounds, including those not yet synthesized, can be readily screened on the computer in order to select structures with the properties desired. It is then possible to select the most promising compounds to synthesize and test in the laboratory. Thus, the QSAR/QSPR approach conserves resources and accelerates the process of development of new molecules for use as drugs, materials, additives, or for any other purpose. While it is not easy to find successful structureactivity/property correlations, the recent exponential growth in the number of papers dealing with QSAR/QSPR studies clearly demonstrates the rapid progress in this area. To obtain a significant correlation, it is crucial that appropriate descriptors be employed, whether they are theoretical, empirical, or derived from readily available experimental characteristics of the structures. Many descriptors reflect simple molecular properties and thus can provide insight into the physicochemical nature of the activity/property under consideration.Recent progress in computational hardware and the development of efficient algorithms has assisted the routine development of molecular quantummechanical calculations. New semiempirical methods supply realistic quantum-chemical molecular quantities in a relatively short computational time frame. Quantum chemical calculations are thus an attractive source of new molecular descriptors, which can, in principle, express all of the electronic and geometric properties of molecules and their interactions. Indeed, many recent QSAR/QSPR studies have employed quantum chemical descriptors alone or in combination with conventional descriptors. Quantum chemistry provides a more accurate and detailed description of electronic effects than empirical methods. 1 Quantum chemical methods can be applied to quantitative structure-activity relationships by direct derivation of electronic descriptors from the molecular wave function. In many cases it has been established that errors due to the approximate nature of quantum-chemical methods and the neglect of the solvation effects are largely transferable within structurally related series; thus, relative values of calculated descriptors can be meaningful even though their absolute values are not directly applicable. 2 Moreover, electronic descriptors derived from the molecular wave function can be also partitioned on the basis of atoms or groups, allowing the description of various molecular regions separately. Most work employing quantum chemical descriptors has been carried out in the field of QSAR rather than QSPR, ie the descriptors have been correlated with biological activities such as enzyme inhibition activity, hallucinogenic activity, etc. 3-6 In part this has been because, historically, the search for quantitative relationships with chemical structure started with the development of theoretical drug design methods. Quantum-chemical descriptors have also been reported to correlate the reactivity of organic compounds, octanol/water partition coefficients, chromatographic retention indices, and various physical properties of molecules. 7-11 The present article reviews applications of quantum chemical descriptors in the development of QSAR/QSPR dealing with the chemical, physical …