Organic Polymerization Catalysis: Precision Macromolecules for Recognition in Biological Systems

有机聚合催化：生物系统中识别的精密大分子

• 批准号: 9322538
• 负责人: Garret Morgan Miyake
• 金额: $ 8.74万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2017-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9322538
• 关键词: Address; Architecture; Bacteria; Biochemistry; Biological; Catalysis; Cells; Characteristics; Chemicals; Chemistry; Colorado; Development; Drug Delivery Systems; Drug Targeting; Engineering; Foundations; Goals; Growth; Knowledge; Length; Mammalian Cell; Mechanics; Mediating; Metals; Methodology; Methods; Mission; Molecular; Molecular Conformation; National Institute of General Medical Sciences; Pattern; Polymers; Printing; Property; Public Health; Reaction; Research; Research Proposals; Route; Structure; Structure of parenchyma of lung; System; Technology; Tissue Engineering; Universities; Work; Writing; antimicrobial; antimicrobial drug; biological systems; biomaterial compatibility; catalyst; copolymer; design; engineering design; innovation; macromolecule; materials science; monomer; photopolymerization; polymerization; programs; restoration; scaffold; solid state; tissue support frame

There is a fundamental lack of understanding in how the structure and architecture of a synthetic polymer influences recognition in biological systems. Furthermore, there is a disconnection between the properties of polymers in solution and the solid state with their relationships with biological systems. Understanding how the conformational dynamics of a synthetic polymer can enhance biological recognition will advance fields including targeted drug delivery, antimicrobial agents, and tissue engineering. However, gaining the knowledge required to address this fundamental gap first necessitates the capability to synthesize precision macromolecules and scaffolds through a biocompatible approach. The long-term goal of this project is to establish a modular polymerization technology, using organic photocatalysts, for 3D printing of scaffolds with precisely defined molecular, chemical, mechanical, and geometric properties targeting lung tissue restoration. The central hypothesis of this research program is that the ability to use our biocompatible photo- mediated polymerization technology for 3D printing of scaffolds with defined components over several different length scales will enable tuning the scaffold for nurturing tissue growth. The overall objective of this application is to advance our polymerization technology using organic photocatalysts to mediate a metal free atom transfer radical polymerization en route to realizing a stereospecfic radical polymerization through flow chemistry reaction engineering design. With the capability to synthesize functionally diverse stereoregular polymers, we will determine the effects of polymer tacticity on their antimicrobial activity and selectivity for bacteria and compatibility with mammalian cells. Through catalyst development and expansion of monomer scope, we will establish a photographic photolithography approach to write distinct 2 and 3D polymer patterns in chemical composition through monomer selection. Furthermore, our approach to connect polymers in solution to those in the solid state will investigate molecular brush copolymers as intermediate macromolecules that possess characteristics similar to both forms. We will introduce these molecular brush copolymers into biological systems to explore the differences between them and the discrete polymer chains from our concurrent cell studies. These findings will help resolve the essential structural features of polymers to yield efficient solid state scaffolds for tissue engineering. The innovation of this research is within the methodology built upon our group’s foundational and ongoing work of developing an organocatalyzed atom transfer radical polymerization, which promises to yield new materials for introduction in biomedical applications. The rationale for this research is that it brings forth new materials that are only accessible through the development of our polymerization technology, which will allow the design and synthesis of polymers that more efficiently mimic natural systems for enhanced biological recognition.

人们根本不了解合成物的结构和体系结构是如何 聚合物影响生物系统中的识别。此外，两者之间存在着脱节。 聚合物在溶液和固态中的性质及其与生物系统的关系。 了解合成聚合物的构象动力学如何增强生物识别将 先进领域，包括靶向药物输送、抗菌剂和组织工程。然而，获得了 解决这一根本差距所需的知识首先需要有综合能力 通过生物兼容的方法获得精确的大分子和支架。这个项目的长期目标是 是建立一种使用有机光催化剂的模块化聚合技术，用于支架的3D打印 具有精确定义的以肺组织为靶点的分子、化学、机械和几何特性 修复。这项研究计划的中心假设是，使用我们的生物兼容照片的能力- 介体聚合技术在几种不同类型支架上的3D打印 长度刻度将使支架能够进行调节，以促进组织生长。本应用程序的总体目标是 是提高我们的聚合技术，使用有机光催化剂来中介金属自由原子转移 自由基聚合--通过流动化学实现立体定向自由基聚合 反应工程设计。有能力合成不同功能的立体规则聚合物，我们 将确定聚合物的规整度对其抗菌活性和对细菌的选择性的影响 与哺乳动物细胞的兼容性。通过催化剂的开发和单体范围的扩大，我们将 建立一种照相光刻方法以在化学物质中写入不同的2和3维聚合物图案 通过单体选择合成。此外，我们在溶液中连接聚合物的方法 在固态中将研究分子刷共聚物作为中间大分子拥有 这两种形式都有相似的特点。我们将把这些分子刷共聚物引入生物 系统来探索它们与我们同时存在的细胞中的离散高分子链之间的差异 学习。这些发现将有助于解决聚合物的基本结构特征，以产生高效固体 用于组织工程的国家支架。这项研究的创新之处在于建立在我们的 集团开发有机催化原子转移自由基聚合的基础和正在进行的工作， 它有望为生物医学应用提供新的材料。这样做的理由是 研究是，它带来了新的材料，只有通过我们的发展才能获得 聚合技术，这将允许设计和合成更有效地模仿 增强生物识别的自然系统。