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

在这个由化学系高分子、超分子和纳米化学计划资助的项目中，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过程中溶液产生的纳米颗粒的稳定性。动力学-共价相互作用指的是化学反应中可逆的化学键的形成/断裂。它提供了目标化学结构的“纠错”，因为反应物的选择方式使反应过程中形成的化学键以可预测、精确和可控制的方式形成。这种合成策略允许从离散的分子构建块制备非常复杂的分子。这种化学在生物技术和医学的许多领域都有应用。特别令人感兴趣的是人工聚合物的设计，用于在人体内靶向递送药物。在本研究中，制备了具有复杂结构的具有亲水和憎水链段的大分子。这些聚合物还含有在溶液中自组装过程中触发动态共价化学的化学元素硼。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课程以及对研究生和本科生进行培训。通过指导西班牙裔学院和大学协会的学生成员，努力留住本科生任职人数不足的少数群体。外展活动的重点是通过科罗拉多州-怀俄明州少数民族参与联盟(Co-WY AMP)为本科生提供招聘活动和暑期研究机会。这项研究围绕动态-共价相互作用的研究，以提高由两亲性瓶刷的溶液自组装产生的动力学阻挡纳米颗粒的稳定性。该项目的第一个目标是建立一个嵌段状瓶刷共聚物库，展示对动态共价(DC)相互作用敏感的功能部分。受自然界中硼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层。还制备了互补型大分子交联剂。在第二个目标中，研究了块状瓶刷自组装的动力学特征，以深入了解其组装机理、工艺条件对纳米颗粒性能的影响以及特征聚集时间。此外，还研究了由块状瓶刷介导的一族溶质的封装，以了解该过程和所产生的结构与基于相似化学组成的线性两亲性的体系的根本差异。最后，系统地评价了嵌段状瓶刷与小分子或大分子交联剂之间通过形成硼酸酯形成的壳层交联剂对纳米粒子的稳定性。利用这些相互作用的可逆性，可以在特定的环境触发因素下，包括低pH值、氧化环境和竞争顺式二醇的存在下，允许受控的空间/时间释放。总体目标是更好地了解大分子结构对动态阻止自组装的影响，以及基于BottleBrush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瓶刷动态自组装和稳定化策略的基本和技术见解，该策略基于热力学驱动的硼酸和含顺二醇化合物之间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优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.