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. Reported postsynthetic 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 chemically non-uniform anchored products. In addition, use of such modifying agents gives rise to spatial non-uniformities in the radial direction, due to prohibited diffusion through the MOF bulk. The advantageous grain structure formation plus molecular non-uniformity greatly increase the complexity of such systems. 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 are 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) is found to have the best performance in terms of reactivity and MOF stability. A comprehensive toolbox of methods was demonstrated to robustly characterize the obtained material. 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 predicts the localization of the modification. The modification is found to be covalent, chiral, and mainly proceeding 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. Meeting this criterion makes the yielding material a promising potential stationary phase candidate for performant chromatographic enantioseparations.