Stereoselective Polymerization Methods for the Synthesis of Degradable Biomaterials

合成可降解生物材料的立体选择性聚合方法

• 批准号: 10417221
• 负责人: Frank Albert Leibfarth
• 金额: $ 34.53万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10417221
• 关键词: Acids; Adhesions; Area; Biocompatible Materials; Catalysis; Chemicals; Development; Evaluation; Goals; Grant; Kinetics; Medical Device; Metabolic; Methods; Periodicity; Pharmaceutical Chemistry; Phase; Philosophy; Polymer Chemistry; Polymers; Production; Property; Protocols documentation; Reaction; Research; Resolution; Resort; Structure; Surface; Water; Work; biodegradable polymer; crystallinity; design; insight; method development; monomer; next generation; novel; polymerization; programs; stereochemistry; tool

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.

项目摘要 /摘要 Leibfarth小组研究的目的是开发平台合成方法，以增强 聚合物的热机械，粘合剂和降解特性，同时还发现机械洞察力 这广泛地为综合方法开发提供了信息。这个目标为我们的两个完整的研究领域提供了信息 寻求1）利用化学和调节性的C – H功能化来增强商品的特性 聚合物和2）开发了立体选择性聚合方法，从而发现了新兴的聚合物特性 简单的化学构建块。我们已经确定了一个令人信服的机会来取得巨大的进步 生物医学的挑战 - 发现可降解的生物材料以及同时控制的生物材料 热机械特性，降解概况和代谢命运 - 利用我们的专业知识 不对称催化，C – H功能化和聚合物化学的界面。在这五年 Mira Grant，我们建议开发新的催化方法来控制可降解的立体化学 聚合物并建立一种域选择方法，以调整聚合物后生产的材料特性。 这些方法将提供迄今未知的半晶体生物材料的访问权限 例如化学成分，聚合物摩尔质量和结晶度百分比可以系统地变化。 由于这项工作而获得的新型聚合物结构以及对其的全面评估 降解机制将使设计规则确定新阶层的设计规则 侵蚀生物材料。更具体地说，我们旨在为立体选择性开发新的催化方法 通过完整的动力学分辨率和对映体合成的聚合循环单体聚合 方法。我们设想发现以前前所未有的立体定盘聚合物的发现可能是 通过对确定结构与反应关系的全面理解来完成 立体选择性添加单体在反应性聚合物链端中。进一步阐述此立体选择性 聚合哲学将使人们能够追求一种立体选择性激进聚合的方法 通过手性路易斯酸催化的控制方式，从而提供了一种策略来创建高度功能和 来自广泛可用的乙烯基单体的定型聚合物。互补地追求立体选择性 聚合，我们已经确定了晚期功能化是一种未充分利用的方法，可以多样化 与生物医学相关的现有聚合物的性质，而无需从头合成。这个哲学 可以在医疗设备中的当前材料上使用，并进一步扩大新的，旋转的构造的实用性 我们在研究计划过程中发现的聚合物。通过开发进行域的方法 选择性C – H官能化反应，我们建议系统地调整水中的水 半晶聚合物的无定形相，因此影响其降解机制。