Abstract: 

Metal-organic frameworks (MOFs) present a diverse platform for designing high-performance materials with applications spanning drug delivery, catalysis, sensing, and separation.  MOF polymorphism has been widely studied from the perspective of which synthetic factors, such as ligand-to-metal ratio, solvent, and temperature, can be used to control the final polymorph formation. However, limited studies on the nucleation mechanism of multi-polymorph MOFs have been performed. This dissertation aims to highlight the study and understanding of metal-organic framework polymorphs and how to observe and control polymorph formation. Advanced microscopy, scattering and spectroscopy techniques such as cryogenic transmission electron microscopy (cryoTEM), scanning electron microscopy (SEM), powder x-ray diffraction (PXRD), and electrospray ionization mass spectrometry (ESI-MS) are employed to conduct these studies. Here we study the formation of a model zeolitic imidazole framework-8 (ZIF-8) and the mechanism that drives the formation of the two most observed polymorphs, sodalite (SOD) and diamondoid (dia). To understand the mechanism and factors that affect polymorph formation, the prenucleation clusters were studied mainly through in-situ WAXS and ESI-MS, uncovering the role of prenucleation cluster size on the polymorph formation.  In a follow up study, we investigate the effect of confinement through reaction vessel size on the nucleation and growth of ZIF-8.  This study is of importance for studies involving analytical techniques where the experimental reaction volume varies from the bulk reaction. In addition, we study the encapsulation of bovine serum albumin (BSA) in ZIF-8 frameworks and the effect of supramolecular modification with cyclodextrin on the encapsulation efficiency. To further the studies with cyclodextrin, cyclodextrin-based MOFs are studied to understand their encapsulation efficiency and structure.  In summary, this work provides insights into the field of MOF nucleation and growth through a lens of polymorph control and lays the foundation for the development of new MOFs.