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

描述(申请人提供)：在每年进行的1亿多个牙科修复中，超过60%涉及使用可光聚合聚合物复合材料。尽管它们在现代牙科中无处不在，但这些复合材料存在着严重的问题，限制了它们的适用性和实用性。基于近50年前开发和实施的树脂化学，这些材料存在的问题包括固化后存在可提取的未反应单体、单体和复合材料的降解、聚合收缩和收缩引起的应力、聚合时间较长、树脂材料缺乏韧性和其他机械行为、聚合后样品的吸热率和吸湿率。由于不到8年的平均使用寿命，这些问题的结果往往是复合修复体过早失效，要么是由于继发性龋病，要么是由于体块或界面上的机械故障。我们建议开发和评估一个基于现在经典的“点击”反应的复合修复系统，即铜催化的叠氮化物-炔烃(CuAAC)反应。它的特点包括实现无副反应的高转化率，坚固耐用，在常温下易于执行，以及形成不容易被酸、水或酶降解的产品。此外，反应的产物是三氮唑环结构，它能够进行二次分子相互作用(即非共价键的形成)，从而增强交联聚合物材料的韧性、玻璃化转变和模数。因此，本研究将通过以下方式解决甲基丙烯酸酯复合材料体系的关键缺陷：(I)开发一种全新的方法来处理这些复合材料的树脂部分，以实现近乎定量的官能团转化，限制可提取单体，消除水解和酶降解的可能性，通过二次分子相互作用改善力学性能，并显著降低收缩和应力；(Ii)将这种基于CuAAC的树脂相与适当的官能化填料相结合，以实现所需的机械性能，改善断裂韧性，延长这些修复体的寿命，并增强复合材料的尺寸稳定性；以及(Iii)分析这些树脂和复合材料的粘附性、降解性、抽出性和其他长期性能指标。光诱导CuAAC聚合体系非常适合下一代牙科修复剂，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体系，同时使这些修复剂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.