Selective host-guest chemistry, self-assembly and conformational preferences of m-xylene macrocycles probed by ion-mobility spectrometry mass spectrometry

We demonstrated ion-mobility spectrometry mass spectrometry (IMS-MS) as a powerful tool for interrogating and preserving selective chemistry including non-covalent and host-guest complexes of m-xylene macrocycles formed in solution. The technique readily revealed the unique favorability of a thiourea-containing macrocycle MXT to Zn2+ to form a dimer complex with the cation in an off-axis sandwich structure having the Zn-S bonds in a tetrahedral coordination environment. Replacing thiourea with urea generates MXU which formed high-order oligomerization with weak binding interactions to neutral DMSO guests detected at every oligomer size. The self-assembly pathway observed for this macrocycle is consistent with the crystalline assembly. Further transformation of urea into squaramide produces MXS, a rare receptor for probing sulfate in solution. Tight complexes were observed for both monomeric and dimeric of MXS in which HSO4- bound stronger than SO42- to the host. The position of HSO4- at the binding cavity is a 180 degrees inversion of the reported crystallographic SO42-. The MXS dimer formed a prism-like shape with HSO4- exhibiting strong contacts with the 8 amine protons of two MXS macrocycles. By eliminating intermolecular interferences, we detected the low energy structures of MXS with collisional cross section (CCS) matching cis-trans and cis-cis squaramides-amines, both were not observed in crystallization trials. The experiments collectively unravel multiple facets of macrocycle chemistry including conformational flexibility, self-assembly and ligand binding; all in one analysis. Our findings illustrate an inexpensive and widely applicable approach to investigate weak but important interactions that define the shape and binding of macrocycles.