了解trimethoprim分子离子共晶中的synthon偏好 - 一项实验和计算研究
Lamis Alaa Eldin Refat1,2, Andrea Erxleben1,2
1School of Biological and Chemical Sciences, University of Galway, Galway H91TK33, Ireland.
ACS omega
|May 19, 2025
概括
设计分子离子共晶体 (ICC) 是一个挑战. 这项研究探讨了基于三甲的ICCs,揭示了质子转移削弱了键,使这些复杂材料的合理合成策略复杂化.
科学领域:
- 晶体学 晶体学是指结晶学.
- 材料科学 材料科学 材料科学
- 药用化学 医学化学
背景情况:
- 分子离子共晶体 (ICCs) 涉及离子 (A-) 和质基 (BH+) 之间的电荷辅助键.
- 对于三元共晶的合理设计原则已经确立,但对于分子ICCs则不那么确立.
- 抗生素三甲 (tmp) 很容易与碳素酸形成盐,并有可能产生二次相互作用.
研究的目的:
- 使用trimethoprim (tmp) 调查三元分子ICCs的合成.
- 在质子三甲 (Htmp+) 中探索二次结合部位的结合倾向.
- 了解开发复杂分子ICC的合理设计策略所面临的挑战.
主要方法:
- 溶液结晶实验,以获得单晶结构.
- 单晶X射线衍射分析.
- 计算方法包括希尔什菲尔德表面分析,分子静电潜力和现场相互作用能量计算.
主要成果:
- 成功合成并确定了Htmp+dif-·H2fum的单晶结构 (dif- = diflunisal离子;H2fum = 烟酸).
- 从辅助器 (HX) 到tmp的N1的质子转移显著降低了N3位点的键受体强度.
- 计算分析证实了N3位点在质子化后降低的静电电位.
结论:
- 三甲烯的N1位点的质子化减少了N3位点的结能力,这对设计三元ICC构成了挑战.
- 在复杂的分子ICCs的合理合成中,很难应用synthon层次和偏好.
- 需要进一步的研究来克服这些挑战,并为分子ICC合成开发可预测的策略.
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