Rational Design of Multifunctional Complex Molecular Architectures via Dynamic Covalent Chemistry

Dynamic covalent chemistry offers a transformative platform for the rational design and synthesis of structurally intricate materials with broad applications in drug discovery, biotechnology, molecular separation, and storage technology. By applying this powerful approach, this dissertation investigates the underutilized potential of the nitroaldol (Henry) reaction and the versatility of imine (Schiff base) formation to build complex molecular architectures. Traditionally limited to small molecule synthesis, we have reimagined the century-old nitroaldol reaction as an enabling tool for macromolecular assembly. By exploring reaction conditions, monomer selection, and thermodynamic equilibria, this research provides more insights into the design principles governing nitroaldol-mediated polymerization and macrocyclization. Concurrently, we explored a modulation-controlled strategy for Schiff base chemistry, taking advantage of its reversibility to construct advanced frameworks. Through parameter optimization, we gained precise control over the material structure and functionality to create adaptive materials tailored for specific applications. By tapping into these complementary dynamic covalent reactions, we have synthesized a diverse range of multifunctional architectures that include macrocycles, linear and network dynamic covalent polymers (dynamers), and reticulated frameworks. Consequently, this work offers a comprehensive approach for the development of dynamic covalent systems with complex architectures while simultaneously expanding the library and diversity of synthetic methods for multifunctional materials. 

Chapter 1 lays the foundation of the dissertation by introducing the concept of dynamic covalent chemistry, nitroaldol, and imine formation reactions. The chapter also provides an overview of reticular chemistry and various classes of CMAs, including macrocycles, dynamers, organogels, covalent organic frameworks (COFs), and porous aromatic frameworks (PAFs). Chapter 2 explores the formation of self-sorting macrocycles through nitroaldol chemistry as it discusses how tetra-β-nitroalcohol macrocycles are formed from the spontaneous depolymerization of linear dynamers. Chapter 3 focuses on the development of network dynamers in the form of self-healing nitroalcohol-based organogels, which exhibit excellent regenerable, recyclable, and stimuli-responsive properties. In Chapter 4, we describe an intriguing odd-even effect in the nitroaldol-based alternating formation of macrocycles and linear dynamers. Chapter 5 highlights our transition to the imine chemistry domain, showing how we developed a novel class of pyridine-based, two-dimensional COFs through a systematic, modulation-enhanced approach. These frameworks exhibit high crystallinity and possess exceptional properties that make them suitable for diverse applications. Finally, Chapter 6 expands the synthetic utility of the nitroaldol reaction as we present preliminary results on the formation of oxygen-rich macrocycles, dynamers, and reticulated frameworks, thereby establishing new versatile pathways for the synthesis of complex molecular architectures.