青霉素侧链结构对其聚合反应的影响探讨

Discussion on the effects of side chains of penicillins on their polymerization reaction

目的 青霉素是临床中应用最广泛的抗生素之一。控制青霉素中的聚合物含量对保证药品安全具有重要的意义,但目前对青霉素类抗生素聚合反应的认知尚不全面,因此需对其相关机制进行分析。方法 本文选择苯唑西林钠和磺苄西林钠,分别作为侧链为苯甲异恶唑类青霉素和侧链具有较强的吸电子基团青霉素的代表,采用理论计算进一步验证前期文献提出的基于青霉素母核的聚合反应途径,并探讨侧链结构对其聚合反应的影响。结果 聚合反应Ⅰ(青霉素母核的羧基与另一分子β-内酰胺环的反应)是优势聚合反应途径,但侧链具有较强吸电子基团的青霉素如磺苄西林不易发生聚合反应,提示青霉素侧链结构对聚合反应具有明显影响。结论 理论分析聚合反应途径结合强制聚合反应验证是聚合物分析的理想方案;采用LC-MS方法,根据聚合物的质谱裂解途径,结合聚合反应机理,可以较好地推断聚合物的结构。

Objective Penicillins are one of the most widely used antibiotics in clinic. Controlling the polymers in penicillins is of great significance to ensure drug safety, but the understanding of the polymerization reaction of penicillins is not comprehensive. It is necessary to explore the mechanism of the polymerization reaction of penicillins.Methods In this paper, oxacillin sodium and sulbacillin sodium were selected as the respective representative of benzoisoxazole penicillins and penicillins with strong electron absorbing group in the side chain. The polymerization reaction pathway based on penicillin mother nucleus proposed in previous literature was further verified, and the influence of the side chain on polymerization reaction was discussed. Results Polymerization reaction □(the reaction of carboxyl group of penicillin mother nucleus and lactam ring of another molecule) is the dominant polymerization pathway, but penicillins with strong electron absorbing groups in the side chain, such as sulbacillin, are not easy to polymerize, suggesting that side chain of penicillins has a significant effect on the polymerization. Conclusion The results show that theoretical analysis of polymerization pathway combined with forced polymerization is an ideal scheme for polymer analysis. The structure of polymer can be inferred by LC-MS method according to the fragmentation pathway and polymerization mechanism.