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

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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.