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.

在这个由化学系大分子、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教授正在使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在化学反应期间可逆的化学键形成/断裂。它提供了目标化学结构的“纠错”，因为反应物的选择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结构单元制备非常复杂的分子。这种化学的应用在生物技术和医学的许多领域都有发现。特别感兴趣的是用于在人体中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，这些分子具有亲水和憎水部分。这些聚合物还含有化学元素硼，其在溶液中自组装期间触发动态共价化学。 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培训研究生和本科生。通过对西班牙裔学院和大学协会的学生成员进行辅导，努力留住本科生中代表性不足的少数民族。外展活动中心通过科罗拉多州怀俄明州少数民族参与联盟（CO-WY AMP）为本科生提供招聘活动和夏季研究机会。本研究围绕动态共价相互作用的研究，以提高稳定性的动力学逮捕的纳米粒子产生的溶液自组装的两亲性bottlebrush。该项目的第一个目标的重点是产生一个图书馆的块状瓶刷共聚物表现出功能部分易受动态共价（DC）相互作用。受硼在自然界中作为稳定剂的作用的启发，该化学利用硼酸-二醇相互作用来稳定壳。还制备了互补的大分子交联剂。在第二个目标中，从块状瓶刷的自组装的动力学特征进行检查，以获得关于其组装机制，加工条件对纳米颗粒性能的影响，和特征聚集时间的洞察力。此外，还研究了由块状瓶刷介导的溶质家族的封装，以了解该过程的根本差异和所得到的构建体相对于基于类似化学组成的线性两亲物的系统。最后，纳米粒子的稳定通过壳交联通过硼酸酯之间形成块状瓶刷和小分子或大分子交联剂进行了系统的评估。这些相互作用的可逆性质被利用，以允许在特定的环境触发下，包括低pH值，氧化环境和竞争性顺式二醇的存在下，控制时空释放。总体目标是更好地理解大分子结构对动力学停滞自组装的影响，以及基于瓶刷的构建体相对于其线性类似物的独特性。这项研究可以提供关于瓶刷自组装和稳定策略的动力学的基础和技术见解，该策略基于硼酸和顺式二醇化合物之间的化学驱动的动态共价相互作用。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。