THEORETICAL STUDY OF BETA-LACTAM ANTIBIOTICS

β-内酰胺类抗生素的理论研究

• 批准号: 3896423
• 负责人: R J LONCHARICH
• 金额: --
• 依托单位: CENTER FOR INFORMATION TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3896423
• 关键词: beta lactam antibiotic; chemical models; chemical reaction; computer program /software; computer simulation; electron transport; quantum chemistry

The GAUSSIAN 86 series of programs has been used to carry out ab initio quantum mechanical calculations to model nucleophilic additions to beta-lactam antibiotics. So far we have studied the attack of the beta-lactam by water. There are two transitions states to the formation of product. In the first water attacks the carbonyl with transfer of one hydrogen to the carbonyl oxygen. The second occurs after ring opening and is a direct transfer of a hydrogen atom to the nitrogen. At the moment the mechanistic results appear to be basis set dependent, however this project is still in progress and the prediction of a mechanistic pathway remains unanswered. Further aspects of the electronic nature of nucleophilic addition to the beta-lactam will be studied by substituting an amine (donating) group or a formyl (withdrawing) group as the carbon atom adjacent to the carbonyl. Placing substitutents on the lactam ring will give an indication of the polarization changes that occur as nucleophilic addition proceeds. It will also be of interest to study the binding of beta-lactam using molecular dynamics approach for simulating chemical reactions.

用GAUSSIAN 86系列程序进行了从头算 量子力学计算模拟亲核加成， β-内酰胺类抗生素到目前为止，我们已经研究了 β-内酰胺通过水。有两个过渡状态的形成， 产品在第一个水攻击羰基转移一个 将氢转化为羰基氧。第二次发生在开环之后， 是氢原子直接转移到氮原子上。的瞬间 机械的结果似乎是基础设置依赖，但该项目 仍在进行中，对机械路径的预测仍然存在 无人回答。亲核的电子性质的其他方面 将研究通过用胺取代β-内酰胺的加成反应， （给）基或甲酰基（吸）基作为碳原子 与羰基相邻。在内酰胺环上放置取代基将 给出了当亲核时发生的极化变化的指示 添加收益。研究《公约》的约束力也是有意义的。 β-内酰胺的分子动力学模拟 反应.