Cu-Catalyzed Azide-Alkyne Reactions for Novel Dental Composite Materials

描述（由申请人提供）：每年进行的超过1亿次牙科修复中，超过60%涉及使用光聚合聚合物复合材料。尽管这些复合材料在现代牙科中无处不在，但它们的适用性和实用性仍然受到严重问题的限制。基于近50年前开发和实施的树脂化学，这些材料的问题包括与固化后可提取的未反应单体的存在，单体和复合材料的降解，聚合收缩和收缩引起的应力，聚合的长时间框架，树脂材料缺乏韧性和其他机械行为，样品在聚合后的热量和水分吸收有关的问题。由于平均使用寿命不到8年，这些问题的结果通常是复合修复体的过早失效，这可能是由于继发性龋蚀，也可能是由于整体或界面内的机械故障。我们建议基于经典的“咔嗒”反应，即铜催化叠氮-炔（CuAAC）反应，开发和评价一种复合修复体系。它的特点包括实现高转化率而无副反应，坚固耐用，易于在环境中进行，并且形成不易被酸，水或酶降解的产物。此外，该反应的产物是一个三唑环结构，该结构能够进行二级分子相互作用（即非共价键的形成），从而增强交联聚合物材料的韧性、玻璃化转变和模量。因此，本研究将通过以下方式解决甲基丙烯酸酯复合体系的关键缺陷：(i)开发一种全新的方法来实现这些复合材料的树脂部分，这种方法实现了CuAAC反应，从而实现了接近定量的官能团转换，限制了可提取的单体，消除了水解和酶降解的可能性，通过二级分子相互作用提高了机械性能；并显著减少收缩和应力；（ii）将这种新型的基于cuaac的树脂相与适当的功能化填料相结合，以达到所需的机械性能，提高断裂韧性，延长这些修复体的使用寿命，并增强复合材料的尺寸稳定性；（三）分析这些树脂和复合材料的附着力、降解、萃取和其他长期性能指标。光诱导的CuAAC聚合系统非常适合下一代牙科修复体，我们的目标是开发一种与当前牙科实践和粘合剂兼容的复合系统，同时使这些修复体的使用寿命至少增加两倍。

DESCRIPTION (provided by applicant): More than 60% of the more than one hundred million dental restorations performed each year involve the use of photopolymerizable polymeric composites. Despite their ubiquitous presence in modern dentistry, these composites suffer from significant problems that limit their applicability and utility. Based on resin chemistry developed and implemented nearly 50 years ago, the problems with these materials include issues associated with the presence of extractable, unreacted monomer following cure, degradation of the monomers and composite, polymerization shrinkage and shrinkage induced stresses, the long timeframe for polymerization, lack of toughness and other mechanical behavior of the resin material, thermal and moisture uptake by the sample following polymerization. With less than an 8 year average service life, the result of these problems is often the premature failure of composite restorations, resulting either from secondary caries or from mechanical failure within the bulk or at the interface. We propose to develop and evaluate a composite restorative system based on the now-classic "click" reaction, that is the copper catalyzed azide-alkyne (CuAAC) reaction. Its characteristics include achieving high conversion without side reactions, being robust and readily performed at ambient, and forming a product that is not readily degradable by acids, water, or enzymes. Moreover, the product of the reaction is a triazole ring structure that is capable of secondary molecular interactions (i.e., non-covalen bond formation) that enhance toughness, glass transition, and modulus of the crosslinked polymer material. Thus, this research will address the critical shortcomings of methacrylate composite systems by (i) developing a completely new approach to the resin portion of these composites that implements the CuAAC reaction in a manner that will lead to achievement of near-quantitative functional group conversions, limit extractable monomers, eliminate the potential for hydrolytic and enzymatic degradation, improve the mechanical properties through secondary molecular interactions, and dramatically reduce shrinkage and stress; (ii) combining this novel CuAAC-based resin phase with appropriately functionalized fillers to achieve the desired mechanical performance, improve fracture toughness, extend the lifetime of these restorations, and achieve enhanced dimensional stability of the composite; and (iii) analyzing the adhesion, degradation, extraction, and other long-term performance metrics for these resins and composites. The photo-induced CuAAC polymerization system is ideally suited for the next generation of dental restoratives and our goal is the development of a composite system that is compatible with current dental practices and adhesives and yet yields at least a two fold increase in the service life of these restoratives.