Computational Chemical Software to Aid in the Structural Determination of Organic Molecules by Means of Nuclear Magnetic Resonance

计算化学软件有助于通过核磁共振确定有机分子的结构

• 批准号: 03554020
• 负责人: OSAWA Eiji
• 金额: $ 10.75万
• 依托单位: Toyohashi University of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03554020/
• 关键词: Solution conformation; Computational chemistry; Nuclear magnetic resonance; Conformational space search; Chemical algorithm; Molecular mechanics; Structure determination; Organic chemistry; 配列空間探索; 計算化学; ビシナル結合定数; 配座自動発生

(1) Program CONFLEX for Conformational Sparch of Flexible Molecules The program was completed within the year 1992 and has been deposited in the Japan Chemistry Program Exchange for public use. The algorithm of CONFLEX is unique in that the Program not only effects systematic rotations to the rotatable bonds, but also simulates elementary processes occurring in the thermal conformational interconversions. A remarkable aspect of this algorighm is its ability of confining the search to within the low-energy region and still capable of finding new domains in the conformational space by crossing over energy barriers. One can arbitrarily control the extent of search depending on the nature of computer resource and the purpose of search. Careful tests revealed that CONFLEX is superior in its performace than any other existing programs. Thereupon the program has been applied to a number of pending problems including the origin of regiospecific O-methylation reaction of Erythromycins, the caus … More e of failure in taxane synthesis and other problems involving macrocyclic conformation and macrocyclization reactions.(2) Program for Universal Molecular Mechanics Calculations Within the year 1992, we have been able to complete that part of molecular mechanics force field program which takes care of the careful evaluation of solvent effects on intramolecular steric interactions. The original idea of this part rests on Clark Still, Columbia University, but we have modified the original formulations to a considerable extent. Technically speaking, we use the first and second analytical derivatives of molecular volume, not the molecular surface as other investigators does, as the key variables. This part is general and can be implemented in other force field programs.(3) Program 3JHH2 for Calculation of Vicinal Coupling Constants The present version of program 3JHH2 has been critically analyzed, together with other known algorithmus for computing coupling constants, for its performance over a variety of organic molecules. As it turned out, all of the presently known methods have unexpectedly low precision in reproducing and predicting coupling constants. Unexpectedly, the greatest source of error is the experimental precision. It is concluded that a new approach is necessary in the use of Karplus equation. Based on the conclusion we will start a new project beginning from the year 1993. Less

(1)柔性分子构象研究项目CONFLEX该项目于1992年完成，并已存入日本化学项目交易所供公众使用。CONFLEX算法的独特之处在于，该程序不仅对可旋转键进行系统旋转，而且还模拟了热构象相互转换中发生的基本过程。该算法的一个值得注意的方面是它能够将搜索限制在低能区域内，并且仍然能够通过跨越能量势垒在构象空间中找到新的域。人们可以根据计算机资源的性质和搜索的目的任意控制搜索的范围。仔细的测试表明，CONFLEX在性能上优于任何其他现有程序。因此，该程序已被应用于许多悬而未决的问题，包括红霉素区域特异性o -甲基化反应的起源，紫杉烷合成失败的原因和其他涉及大环构象和大环化反应的问题。(2)通用分子力学计算程序在1992年，我们完成了分子力学力场程序的一部分，该部分负责仔细评估溶剂对分子内空间相互作用的影响。这部分最初的想法来自于哥伦比亚大学的Clark Still，但是我们对原来的配方做了相当大的修改。从技术上讲，我们使用分子体积的一阶和二阶解析导数，而不是像其他研究者那样使用分子表面作为关键变量。该部分具有通用性，可在其他力场程序中实现。当前版本的程序3JHH2已经与其他已知的计算耦合常数的算法一起进行了严格的分析，以确定其在各种有机分子上的性能。事实证明，目前所有已知的方法在再现和预测耦合常数方面的精度都很低。出乎意料的是，最大的误差来源是实验精度。结论是在Karplus方程的应用中需要一种新的方法。根据这一结论，我们将从1993年开始一个新的项目。少

项目成果

大澤 映二: "定応的コンホメーション解析入門" 広川書店, 100 (1991)

大泽英二：《固定构象分析导论》广川书店，100（1991）

H.Goto: "Further Developmint,in the Algorithm for gene-rating Cyclic Conformers" Tetrahedron Lett.33. 1343-1346 (1992)

H.Goto：“进一步开发，生成循环构象的算法”Tetrahedron Lett.33。

V.Gogonea: "Implementation of Solvent Effect in Molecular Mechanics.Part1." Supramol.Chem.1. (1993)

V.Gogonea：“分子力学中溶剂效应的实现。第 1 部分。”

H.GOTO: "An Efficient Algorithm for Searching Low-Energy Conformers of Cycl. Acycl.Molecules" J.Chem.Soc.,Perkin Trans.2. インサツチユウ (1993)

H.GOTO：“一种搜索环非环分子低能构象的有效算法”J.Chem.Soc.，Perkin Trans.2 (1993)。

S.Tsuzuki,L.Schafer,H.Goto,E.D.Jemmis,H.Hosoya,K.Tanabe,E.Osawa: "Investigation of Intramolecular Interactions in n-alkanes." J.Am.Chem.Soc.113. 4665-4671 (1991)

S.Tsuzuki、L.Schafer、H.Goto、E.D.Jemmis、H.Hosoya、K.Tanabe、E.Osawa：“正烷烃分子内相互作用的研究”。