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: 10610417
• 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/10610417
• 关键词: Acids; Adhesions; Area; Biocompatible Materials; Catalysis; Chemicals; Development; Evaluation; Goals; Grant; Kinetics; Mechanics; 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; invention; mechanical properties; 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 莱布法斯集团的研究目标是开发平台合成方法，以增强 聚合物的热机械、粘合和降解特性，同时揭示机理洞察 这为合成方法的发展提供了广泛的信息。这一目标告诉我们两个互补的研究领域 寻求1)利用化学和区域选择性的C-H官能化来提高商品的性质 聚合物和2)开发立体选择性聚合方法，该方法从 简单的化学积木。我们发现了一个令人信服的机会，可以在一项重大的 生物医学中的挑战-可降解生物材料的发现伴随着对 热机械特性、降解特性和代谢命运--通过利用我们在 不对称催化、C-H官能化和聚合物化学的界面。在这五年期间 米拉·格兰特，我们建议开发新的催化方法来控制可降解的立体化学 并建立一种领域选择性的方法来调整聚合物的后期材料性能。 这些方法将提供对迄今未知的半晶体生物材料的访问，其中关键参数 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改变。 作为这项工作的结果而获得的新型聚合物结构及其综合评价 退化机制将使得能够确定开发新类表面的设计规则 侵蚀生物材料。更具体地说，我们的目标是开发立体选择性的新催化方法。 环状单体的互补动力学拆分聚合和对映体收敛合成 接近了。我们设想，以前史无前例的立体定义聚合物的发现可以 通过发展对结构-反应性关系的全面理解来实现这一点 单体与反应性聚合物链端的立体选择性加成。对这一立体选择的进一步阐述 聚合哲学将使人们能够追求立体选择性自由基聚合的方法 通过手性路易斯酸催化的受控方式，从而提供了一种创建高功能性和 由广泛可用的乙烯基单体制成的立体定义聚合物。与追求立体选择相辅相成 聚合，我们已经确定后期功能化是一种未得到充分利用的方法，可以使 与生物医学相关的现有聚合物的性质，而无需求助于从头合成。这一哲学 可以在现有材料上用于医疗器械以及进一步扩大新的、立体定义的用途 我们在研究过程中发现的聚合物。通过开发方法来进行领域- 选择性C-H官能化反应，我们建议系统地将水的传输调节到 半结晶聚合物的非晶态相，从而影响其降解机理。

项目成果

A dual initiator approach for oxygen tolerant RAFT polymerization.

• DOI: 10.1039/d2py00603k
• 发表时间: 2022-09
• 期刊: Polymer chemistry
• 影响因子: 4.6
• 作者: N. G. Taylor;Marcus H. Reis;Travis P Varner;Johann L. Rapp;Alexis Sarabia;Frank A. Leibfarth

Circular Upcycling of Bottlebrush Thermosets.

洗瓶刷热固性材料的循环升级。

• DOI: 10.1002/anie.202217941
• 发表时间: 2023
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Zhang,Daixuan;Vashahi,Foad;Dashtimoghadam,Erfan;Hu,Xiaobo;Wang,ClaireJ;Garcia,Jessica;Bystrova,AleksandraV;Vatankhah-Varnoosfaderani,Mohammad;Leibfarth,FrankA;Sheiko,SergeiS
• 通讯作者: Sheiko,SergeiS

Stereoselective Helix-Sense-Selective Cationic Polymerization of N-Vinylcarbazole Using Chiral Lewis Acid Catalysis.

• DOI: 10.1021/jacs.2c02738
• 发表时间: 2022-05
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Cole C Sorensen;Frank A. Leibfarth