Dynamic-covalent Interactions for Enhanced Stabilization of Kinetically-arrested Nanoparticles

动态共价相互作用增强动力学捕获纳米颗粒的稳定性

• 批准号: 2003789
• 负责人: Margarita Herrera-Alonso
• 金额: $ 45万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003789&HistoricalAwards=false
• 关键词: Dynamic; covalent; Interactions; Enhanced; Stabilization

In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Professor Margarita Herrera-Alonso at Colorado State University is using dynamic-covalent interactions to enhance the stability of nanoparticles generated from solution in the self-assembly of polymers. Dynamic-covalent interactions refer to reversible chemical bond forming/breaking during a chemical reaction. It offers “error-correction” of the targeted chemical structures because the reactants are chosen in such a way that chemical bonds during the reaction form in a predictable, precise and controlled manner. This synthetic strategy allows for the preparation of very complex molecules from discrete molecular building blocks. Applications of this chemistry are found in numerous areas of biotechnology and medicine. Of particular interest is the design of artificial polymers for targeted delivery of drugs in a human body. In this research, large molecules with complex architectures are prepared that have water-loving and water-hating segments. These polymers also contain the chemical element boron that triggers dynamic-covalent chemistry during self-assembly in solution. Educational impacts of this work are focused on the incorporation of research results into graduate and undergraduate courses and training of students at graduate and undergraduate levels. Efforts to retain undergraduate underrepresented minorities are undertaken through mentoring of student members of the Hispanic Association of Colleges and Universities. Outreach activities center on recruiting activities and summer research opportunities for undergraduates through The Colorado-Wyoming Alliance for Minority Participation (CO-WY AMP). This research centers around the study of dynamic-covalent interactions to enhance the stability of kinetically-arrested nanoparticles generated by the solution self-assembly of amphiphilic bottlebrushes. The first objective of the project focuses on generating a library of block-like bottlebrush copolymers exhibiting functional moieties susceptible to dynamic-covalent (DC) interactions. Inspired by the role of boron as a stabilizer in nature, the chemistry utilizes boronic acid-diol interactions for shell stabilization. Complementary macromolecular crosslinkers are also prepared. In the second objective, the kinetic features of self-assembly from block-like bottlebrushes are examined in order to obtain insight regarding their assembly mechanism, effect of processing conditions on nanoparticle properties, and characteristic aggregation times. The encapsulation of a family of solutes mediated by block-like bottlebrushes to understand fundamental differences of the process and the resulting constructs with respect to systems based on linear amphiphiles of similar chemical composition is additionally investigated. Lastly, nanoparticle stabilization through shell-crosslinking via boronate ester formation between block-like bottlebrushes and either small-molecule or macromolecular crosslinkers is systematically evaluated. The reversible nature of these interactions is harnessed to allow for controlled spatio/temporal release under specific environmental triggers, including low pH, oxidative environments and in the presence of competing cis-diols. The overall goal is to achieve a better understanding of the effects of macromolecular architecture on kinetically-arrested self-assemblies, and the uniqueness of bottlebrush-based constructs with respect to their linear analogs. This research could provide fundamental and technological insights regarding the dynamics of bottlebrush self-assembly and stabilization strategies based on a thermodynamically-driven dynamic-covalent interaction between boronic acids and cis-diol containing compounds.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在这个由化学系高分子、超分子和纳米化学项目资助的项目中，科罗拉多州立大学的 Margarita Herrera-Alonso 教授正在利用动态共价相互作用来增强聚合物自组装溶液中产生的纳米颗粒的稳定性。动态共价相互作用是指化学反应过程中可逆化学键的形成/断裂。它可以对目标化学结构进行“纠错”，因为反应物的选择方式使得反应过程中的化学键以可预测、精确和受控的方式形成。这种合成策略允许从离散的分子构建单元制备非常复杂的分子。这种化学的应用广泛应用于生物技术和医学的许多领域。特别令人感兴趣的是用于在人体内靶向递送药物的人造聚合物的设计。在这项研究中，制备了具有复杂结构的大分子，这些分子具有喜水和憎水的片段。这些聚合物还含有化学元素硼，在溶液中自组装过程中会引发动态共价化学。 这项工作的教育影响集中在将研究成果纳入研究生和本科生课程以及对研究生和本科生的培训。通过对西班牙裔学院和大学协会的学生成员进行指导，努力留住本科生中代表性不足的少数群体。外展活动的重点是通过科罗拉多州-怀俄明州少数族裔参与联盟 (CO-WY AMP) 为本科生招募活动和暑期研究机会。这项研究的重点是动态共价相互作用的研究，以增强两亲性洗瓶刷溶液自组装产生的动力学捕获纳米颗粒的稳定性。该项目的第一个目标侧重于生成一个具有易受动态共价 (DC) 相互作用影响的功能部分的块状洗瓶刷共聚物库。受硼在自然界中作为稳定剂作用的启发，该化学利用硼酸-二醇相互作用来稳定壳层。还制备了互补的大分子交联剂。在第二个目标中，研究了块状洗瓶刷自组装的动力学特征，以便深入了解其组装机制、加工条件对纳米粒子特性的影响以及特征聚集时间。另外还研究了由块状瓶刷介导的一系列溶质的封装，以了解该过程的基本差异以及所得构建体相对于基于具有相似化学成分的线性两亲物的系统的基本差异。最后，系统地评估了通过块状瓶刷与小分子或大分子交联剂之间形成硼酸酯形成壳交联而实现的纳米颗粒稳定性。利用这些相互作用的可逆性质，可以在特定环境触发条件下（包括低 pH 值、氧化环境和存在竞争性顺式二醇的情况下）实现受控的时空释放。总体目标是更好地理解大分子结构对动力学阻滞自组装的影响，以及基于洗瓶刷的结构相对于其线性类似物的独特性。这项研究可以提供有关基于硼酸和含顺式二醇化合物之间热力学驱动的动态共价相互作用的洗瓶刷自组装动力学和稳定策略的基础和技术见解。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。