Heterogeneous-phase reaction of glycidyl methacrylate and chondroitin sulfate: Mechanism of ring-opening-transesterification competition
Heterogeneous-phase reaction of glycidyl methacrylate and chondroitin sulfate: Mechanism of ring-opening-transesterification competition
复制标题
DOI：
10.1021/ma021190w
复制
发表时间：
2003-04-08
期刊：
影响因子：
5.5
通讯作者：
Elisseeff, JH
中科院分区：
文献类型：
--
作者：
Li, Q;Wang, DA;Elisseeff, JH
硫酸软骨素（CS）与甲基丙烯酸缩水甘油酯（GMA）的甲基丙烯酸酯结合是一种新型的制备光交联多糖的方法，通过原位注射和光诱导聚合可制备可生物降解的水凝胶。由于CS是天然软骨的主要成分之一，负责组织的抗压强度，也能够吸收大量的水，1，2我们假设CS水凝胶可能适用于许多生物医学应用。Hennink等人研究并报道了葡聚糖与GMA在非水相体系（DMSO）中的“类似”反应。3，4意外的酯交换而不是环氧化物开环主导了反应。然而，在我们关于水溶性CS和水不溶性GMA的不同溶解度/可溶解性的研究中，设计了CS与GMA的缓慢非均相反应，并在水介质中进行，而不管GMA与水的潜在副反应。通过用NMR监测甲基丙烯酸酯缀合，发现了不同的反应机理。两个反应，包括快速可逆的酯交换和缓慢不可逆的开环共轭，同时发生。随着反应的进行，酯交换产物的量有所下降，而开环产物的浓度随着时间的推移逐渐增加。这些反应在方案1中说明。
The methacrylate-conjugation of chondroitin sulfate (CS) with glycidyl methacrylate (GMA) is a novel strategy for producing photo-cross-linkable polysaccharides that can generate biodegradable hydrogels by in situ injection and light-induced polymerization. Since CS is one of the major components of native cartilage, responsible for the tissue’s compressive strength and also capable of absorbing a large volume of water, 1, 2 we hypothesize that CS-based hydrogels may be useful for a number of biomedical applications. A “similar” reaction of dextran with GMA in a homogeneous-phase system (DMSO) was studied and reported by Hennink et al. 3, 4 An unexpected transesterification, instead of epoxide ring-opening, dominated the reaction. However, in our study concerning the different solubility/miscibility of the water-soluble CS and the water-insoluble GMA, a slow heterogeneous-phase reaction of CS with GMA was designed and performed in aqueous medium regardless of GMAs potential side-reaction with water. By monitoring the methacrylate-conjugation with NMR, a different reaction mechanism was discovered. Two reactions, including a rapid reversible transesterification and a slow irreversible ring-opening conjugation, took place simultaneously. As the reaction proceeds, there is a decline in the amount of transesterification products, while the concentration of ring-opening products gradually increased with time. These reactions are illustrated in Scheme 1.