Reactive Thiol Frameworks Enabled by Peptide Assembly

Thiols are potent nucleophiles, redox-active, and capable of undergoing a variety of reversible reactions, making their incorporation into porous materials such as metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) highly desirable. However, their high reactivity and sensitivity have posed significant challenges for direct incorporation into these frameworks, relying on postsynthetic modifications to graft thiol units randomly or incompletely throughout the materials. The less-defined nature of MOFs and COFs has prevented thorough structural characterization, especially by single-crystal X-ray diffraction (SC-XRD) impeding the rational engineering of their function. We address this challenge by employing a noncovalent peptide-π-stack assembly strategy which uses shape-specific, weak interactions including van der Waals, H-bonding, and π−π interactions encoded by a peptide sequence to control the framework synthesis. Hence, our approach tolerates the presence of reactive thiol groups during the assembly process to provide a novel and convenient route toward well-defined thiol-containing materials. Chapter 1 outlines the importance of noncovalent interactions, specifically π-stacking, in affecting the self-assembly process of peptide-based materials. Their significance in determining the structural and functional properties of the resulting nanostructures through strong, directional, and predictable interactions is highlighted. The chapter further explores how the specific site of attachment of these π-stacking units to the peptide backbone influences the type of nanostructures formed —including spheres, fibers, and tubes— each with distinct physical properties and potential applications. The relationship between molecular design and self-assembled nanomaterial further highlights the versatility and precision of aromatic units within a peptide-based self-assembly system. Chapter 2 focuses on the exceptional versatility of thiol groups. Leveraging the mild conditions of our noncovalent peptide assembly, we readily synthesized and characterized a number of frameworks with thiols displayed at many unique positions and in several permutations via SC-XRD. Furthermore, the thiol-containing frameworks undergo diverse single-crystal-to-single-crystal reactions, including toxic metal ion coordination (e.g., Cd2+, Pb2+, and Hg2+), selective uptake of Hg2+ ions, and redox transformations. Chapter 3 explores the formation of dichalcogenide bonds, specifically sulfenic acid, persulfide, thioselenide, and thiotelluride bonds. Enhancements to my former noncovalent framework through the addition of a β-sheet and extending the α-helix length increased stability and pore sizes. Through iodine pre-functionalization and subsequent reaction with hydrochalcogen sodium salts, the formation of RSOH, RSS¯̄, RSSe¯̄, and RSTe¯̄ bonds was confirmed via SC-XRD. Additionally, reactivity studies were performed through reactions with 5,5-Dimethyl-1-Pyrroline-N-Oxide serving as evidence of thiyl radical formation. In conclusion, this thesis overcomes the long-standing challenge of incorporating thiols into porous crystalline materials through rational design. It highlights the versatility of thiols in stabilized environments, demonstrating applications as molecular sieves for toxic heavy metals and precursors to functional groups such as sulfonic acids and nitroso thiols. Additionally, we elucidate the formation of labile dichalcogenide bonds and thiyl radicals, underscoring the potential of thiol-functionalized frameworks for advanced applications.