In situ SAXS/WAXS investigation of Glyco-Zeolitic-Imidazolate Frameworks (GlycoZIFs): Monitoring the formation of nanosized GlycoZIFs crystals and study of the glyco-ZIF interactions

Glycomimetics have attracted much interest as therapeutic agents for a wide variety of diseases; however, their optimal delivery to the target site inside cells is still a major concern. The recently reported strategy to encapsulate a particular type of glycolipid mimetics (sp2-iminoglycolipids) within a zeolitic-imidazolate framework-8 (ZIF-8) nanostructure[1] is a useful approach to enhance the cellular uptake of these glycomimetics and, consequently, improve their therapeutic efficacy at low doses. This advance has opened the path for the preparation of GlycoZIFs with distinctive therapeutic potential depending on the specific glycomimetic encapsulated. However, in situ study of the formation mechanism of these GlycoZIFs and the favorable interactions between glycolipids and ZIF-8 structure have not yet been investigated, limiting the knowledge on the key structural features of these glycolipids necessary for their successful encapsulation, and thus hindering the extension of the synthetic strategy to a more diverse range of glycolipids. We aim to use in situ small-angle X-ray scattering (SAXS) and wide-angle X-ray (WAXS) to obtain real-time monitoring of the nucleation and crystallization equilibriums of GlycoZIFs in comparison to the pristine ZIF-8 nanoparticles, and to study the effect of changes in the structural formula of glycolipids (both the glycone fraction and the aglycone chain) on the mechanism and/or kinetics of the GlycoZIF formation.