目的:利用计算机辅助新药设计(Computer Aided Drug Design,CADD)技术中的受体图像法,对不同类型降血脂药物的化学结构及甘草次酸类的降血脂药效结构进行模型化研究,并初步探讨甘草次酸类的降血脂药理作用机制。方法:利用计算机程序EMO...目的:利用计算机辅助新药设计(Computer Aided Drug Design,CADD)技术中的受体图像法,对不同类型降血脂药物的化学结构及甘草次酸类的降血脂药效结构进行模型化研究,并初步探讨甘草次酸类的降血脂药理作用机制。方法:利用计算机程序EMO(分子力学程序)和GEOMOS(量子力学)以及Semi-empirical PM3方法,对4种不同类型的32个具有降血脂活性的分子进行分析。通过分子能量的降低和空间结构的优化处理,测定和计算这些分子的有关几何性、电性和能量参数。然后对优化后分子进行类型内重叠和有关参数的类型间对比观察,预测各类分子的共同药效结构和功能基刚。分了重叠的可行性用参数RMS(Root Meam Square)进行判断。结果:分别获得32个降血脂活性分子的4种不同特征的药效基本结构图像,并发现甘草酸类(如18β-甘草次酸)与苯氧乙酸类(fibrates)分子的优化空间构型中,存在类似的特定结构片段,相应原子和原子团的电荷密度分布(netchrges)、3个电荷中心分布及其相间距离具有可观的相似性。说明在甘草酸类的优化空间结构上可能具有与笨氧乙酸类药物类似的药效结构片段存在,甘草次酸及18-脱氢甘草次酸的铵盐降低71％的甘油三酯和51％胆固醇浓度。结论:甘草次酸类可能具有与苯氧乙酸类类似的降血脂作用机理。展开更多
The catalytic activity of trimethyl phosphite modified HZSM-5 zeolite and un-modified HZSM-5zeolite treated with 100% steam at 673,773,873,973 and 1073K, respectively, were investigated using heptanecracking as a prob...The catalytic activity of trimethyl phosphite modified HZSM-5 zeolite and un-modified HZSM-5zeolite treated with 100% steam at 673,773,873,973 and 1073K, respectively, were investigated using heptanecracking as a probe reaction. The results showed that the heptane conversion of both trimethyl phosphitetreated samples and un-phosphated samples decreased with an increase in treating temperature, but trimethylphosphite modified samples showed higher activity in comparison with the un-modified samples, which weresteam-treated at a higher temperature. The results were firstly elucidated by the model cluster method andcomputational quantum chemistry method. Full optimization and frequency analysis of all cluster model havebeen carried out using the Gaussian 94 software-package with the PM 3 semi-empirical method performed onsmall cluster models. The computational results showed that the dealumination of trimethyl phosphite modi-fied zeolite model cluster was more difficult than that of un-modified zeolite model cluster when they weretreated with steam while investigating the heat of reaction.展开更多
基金Project supported by National Natural Science Fundation of China(20807563)The project Foundation of Education Department of Liaoning Province(2004-c022)The project Foundation of Technology Bureau of Shenyang(2007GX-32)
文摘The catalytic activity of trimethyl phosphite modified HZSM-5 zeolite and un-modified HZSM-5zeolite treated with 100% steam at 673,773,873,973 and 1073K, respectively, were investigated using heptanecracking as a probe reaction. The results showed that the heptane conversion of both trimethyl phosphitetreated samples and un-phosphated samples decreased with an increase in treating temperature, but trimethylphosphite modified samples showed higher activity in comparison with the un-modified samples, which weresteam-treated at a higher temperature. The results were firstly elucidated by the model cluster method andcomputational quantum chemistry method. Full optimization and frequency analysis of all cluster model havebeen carried out using the Gaussian 94 software-package with the PM 3 semi-empirical method performed onsmall cluster models. The computational results showed that the dealumination of trimethyl phosphite modi-fied zeolite model cluster was more difficult than that of un-modified zeolite model cluster when they weretreated with steam while investigating the heat of reaction.
