UC Irvine

This dissertation demonstrates the utility of high-resolution microscopy methods to visualize the biomimetic crystallization mechanisms that dictate protein localization and spatial distribution pattern outcomes. Biomineralization is the intricate biochemical process through which living organisms create hierarchically structured organic-inorganic composites that offer crucial biological functionalities like catalysis, storage, and protection. Biomineralization processes have inspired the biomimetic crystallization of protein-based metal-organic framework biocomposites (p@MOFs) to form biohybrid materials for potential applications in biomedicine and biocatalysis. A critical knowledge gap in our understanding of p@MOF structure-function relationships is how the precise spatial localization and distribution patterns of the proteins embedded within the MOF crystals affect their overall properties. Furthermore, the spatiotemporal tracking of protein molecules during the biomimetic crystallization process has yet to be fully elucidated, which is essential for designing synthetic procedures to target specific structures and functions.

Chapter 1 outlines fundamental concepts of classical and non-classical crystallization, focusing on techniques used to decipher the key parameters governing crystal nucleation and growth in biomolecule-directed and biomimetic systems. In Chapter 2, the naturally occurring iron oxide mineral core of the protein horse spleen ferritin (Fn) is leveraged as a contrast agent to directly observe individual proteins during the crystallization pathways and outcomes of p@MOFs using transmission electron microscopy (TEM) methods. Chapter 2 illustrates how the 3D mapping of proteins in the crystallization of p@MOFs using advanced TEM techniques can be utilized to analyze protein spatial distribution and aggregation outcomes quantitatively. In Chapter 3, different electron microscopy modalities such as cryogenic TEM (cryo-TEM), cryo-electron tomography (cryo-ET), and liquid phase TEM (LP-TEM) are explored to understand further how proteins influence both classical and nonclassical crystallization pathways. The collective work in Chapters 2 and 3 demonstrates that adjusting the MOF precursor ratios and protein concentrations alters how proteins are arranged, localized, and aggregated within MOF crystals. Furthermore, this localization is intimately tied to the underlying crystal formation mechanism. This work gives essential insights into the influence proteins have on the crystallization pathways of MOFs, serving as a potential roadmap for designing highly controlled advanced materials capable of improving protein immobilization, performance, and delivery.

Finally, Chapters 4 and 5 describe the effects of incorporating proximal Lewis acids and electric fields in CO2 activation. Chapter 4 outlines how oriented electric fields have been used to investigate their impact on catalytic activity in synthetic and biological systems. Chapter 5 illustrates heterobimetallic complexes with incorporated alkali cations close to a redox-active transition metal center for CO2 activation and reduction. This work examines how positioned proximal cations can be used in synthetic systems to enhance catalytic performance.