【摘要】 青霉素类抗生素化学稳定性问题一直是理论研究和医药生产的热点和难点。选取青霉素、阿莫西林两种代表性药物,采用精确的杂化密度泛函理论(B3LYP)方法,从分子几何构型、键能、价键轨道、静电势和化学硬度等方面分析了化学结构对于化学稳定性的影响。结果表明:稠环张力是导致该类化合物不稳定的主要原因,取代基影响分子的电子排布和分子间的相互作用。该理论研究为青霉素类抗生素新药设计、构效关系和化学反应规律的研究,以及医药生产中产品质量的控制提供了理论参考。更多还原

【Abstract】 Chemical stability of penicillin antibiotics has been challenge to theoretical studies and pharmaceutical production.This paper introduces the selection two kinds of representative drugs,namely penicillin,amoxicillin and the application of the hybrid density functional theory methods to an analysis of the effect on chemical stability by chemical structure in everything from molecular geometry,bond dissociation energy,natural bond orbital,and electrostatic potential to the hydrogen bonds between molecules,and chemical hardness.The results show that the ring tension occurs as the main cause of the instability,and substituents have great influence on the electron distribution and intermolecular interactions.The study provides theoretical references for design of the penicillin antibiotics,investigation into the structure-activity relationships and the laws of chemical reactions,and control of product quality in pharmaceutical production.更多还原