Non-Uniform Chiralization of Metal-Organic Frameworks Using Imine Chemistry

Homochiral metal-organic frameworks (MOFs) are exceptional media for heterogenous enantiodifferentation processes. Modifying available achiral structure-bearing MOF scaffolds is a preferred method to extend this class of materials. However, reported post-synthetic covalent chiralizations generally lead to uniform, site-specific modifications. The use of chemically versatile modifying agents, like aldehydes, may instead result in the statistical formation of non-uniform anchored products. Such molecular non-uniformity and grain structure formation greatly increase the system’s complexity. The use of such modifying agents, therefore, necessitates a broader, holistic characterization. The present work explores the adaptation of imine chemistry for post-synthetic chiralization. A chiral aldehyde and a chiral ketone have been probed on two amine-functionalized MOF substrates - MIL-125 NH2, and UiO-66 NH2. The UiO-66 NH2 modified with the natural product-derived (R)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde ((R)-1 aldehyde) was found to have the best performance and a comprehensive toolbox of characterization methods was demonstrated to robustly assess the obtained material’s complexity. This includes high-resolution accurate mass electrospray ionization mass spectrometry (HRAM-ESI-MS) to reveal the competing reactions that yield a statistical set of oligomer-rich structures. In silico modeling correctly predicted the localization of the modification. The modification was covalent and chiral and mainly proceeded through imine formation, resulting in a surface enantioselector display formation. Restricted diffusion lengths in the solid phase infer good retention of resolving power in ascending van Deemter régimes in chromatography. This makes the yielding material a promising stationary phase candidate for performant chromatographic enantioseparations.