Stereoselective Polymerization Methods for the Synthesis of Degradable Biomaterials

项目概要/摘要 Leibfarth小组的研究目标是开发平台合成方法，以增强 聚合物的热机械，粘合和降解性能，同时也揭示了机理的见解 这为合成方法的发展提供了广泛的信息。这一目标为我们两个互补的研究领域提供了信息 其寻求1）利用化学和区域选择性C-H官能化来增强商品的性质， 聚合物和2）开发立体选择性聚合方法， 简单的化学构件我们已经确定了一个令人信服的机会， 生物医学的挑战-发现可降解的生物材料，同时控制 热机械性能，降解概况和代谢命运-通过利用我们的专业知识， 不对称催化、C-H官能化和高分子化学界面。在这五年中， MIRA赠款，我们建议开发新的催化方法来控制可降解的立体化学 聚合物和建立一个域选择性的方法来调整聚合物的材料性能后生产。 这些方法将提供迄今未知的半结晶生物材料，其中关键参数 例如化学组成、聚合物摩尔质量和结晶度百分比可以系统地变化。 作为这项工作的结果，获得了新的聚合物结构，并对其进行了综合评价。 降级机制将能够识别用于开发新类表面的设计规则 侵蚀生物材料更具体地说，我们的目标是开发新的催化方法， 通过互补动力学拆分和对映会聚合成的环状单体的聚合 接近。我们设想，以前前所未有的立体定向聚合物的发现可以 通过全面了解结构-反应性关系来完成， 单体向反应性聚合物链端的立体选择性加成。进一步阐述这种立体选择性 聚合原理将使得能够追求用于立体选择性自由基聚合的方法， 通过手性刘易斯酸催化，以可控的方式，从而提供了一种策略， 由广泛可得的乙烯基单体制备的立体定向聚合物。对立体选择性 聚合，我们已经确定了后期官能化作为一种未充分利用的方法，以多样化的 与生物医学相关的现有聚合物的性质，而不求助于从头合成。这种哲学 可用于医疗器械中的现有材料，并进一步扩展新的立体定向材料的实用性。 我们在研究项目中发现的聚合物。通过开发方法来进行域- 选择性C-H官能化反应，我们建议系统地调整水的运输到 半结晶聚合物的非晶相，并因此影响其降解机制。

Project Summary / Abstract The goal of research in the Leibfarth group is to develop platform synthetic methods that enhance the thermomechanical, adhesion, and degradation properties of polymers while also uncovering mechanistic insights that broadly inform synthetic method development. This goal informs our two complementary research areas that seek to 1) leverage chemo- and regioselective C–H functionalization to enhance the properties of commodity polymers and 2) develop stereoselective polymerization methods that uncover emergent polymer properties from simple chemical building blocks. We have identified a compelling opportunity to make progress on a grand challenge in biomedicine – the discovery of degradable biomaterials with concomitant control of thermomechanical properties, degradation profile, and metabolic fate – by leveraging our expertise at the interface of asymmetric catalysis, C–H functionalization, and polymer chemistry. In the five-year period of this MIRA grant, we propose to develop new catalytic approaches to control the stereochemistry of degradable polymers and establish a domain-selective approach to tune the material properties of polymers post-production. These methods will provide access to heretofore unknown semicrystalline biomaterials where critical parameters such as the chemical composition, polymer molar mass, and percent crystallinity can be systematically varied. The novel polymer structures accessed as a result of this work and the comprehensive evaluation of their degradation mechanism will enable the identification of design rules for the development of new classes surface eroding biomaterials. More specifically, we aim to develop new catalytic methods for the stereoselective polymerization of cyclic monomers through complementary kinetic resolution and enantioconvergent synthetic approaches. We envision that the discovery of previously unprecedented stereodefined polymers can be accomplished by developing a comprehensive understanding of structure–reactivity relationships that determine stereoselective addition of monomers to a reactive polymer chain-end. Further elaboration of this stereoselective polymerization philosophy will enable the pursuit of methods for stereoselective radical polymerization in a controlled manner through chiral Lewis acid catalysis, thus providing a strategy to create highly functional and stereodefined polymers from widely-available vinyl monomers. Complementary to the pursuit of stereoselective polymerization, we have identified late-stage functionalization as an underutilized approach to diversify the properties of existing polymers relevant to biomedicine without resorting to de novo synthesis. This philosophy can be used on current materials in medical devices as well as further expand the utility of the new, stereodefined polymers we discover in the course of our research program. By developing methods to conduct domain- selective C–H functionalization reactions, we propose to systematically tune the water transport into the amorphous phase of semicrystalline polymers and, therefore, influence their degradation mechanism.