Structural studies of supramolecular complexes and assemblies by ion mobility mass spectrometry

Abstract

Recent advances in instrumentation and development of computational strategies for ion mobility mass spectrometry (IM‐MS) studies have contributed to an extensive growth in the application of this analytical technique to comprehensive structural description of supramolecular systems. Apart from the benefits of IM‐MS for interrogation of intrinsic properties of noncovalent aggregates in the experimental gas‐phase environment, its merits for the description of native structural aspects, under the premises of having maintained the noncovalent interactions innate upon the ionization process, have attracted even more attention and gained increasing interest in the scientific community. Thus, various types of supramolecular complexes and assemblies relevant for biological, medical, material, and environmental sciences have been characterized so far by IM‐MS supported by computational chemistry. This review covers the state‐of‐the‐art in this field and discusses experimental methods and accompanying computational approaches for assessing the reliable three‐dimensional structural elucidation of supramolecular complexes and assemblies by IM‐MS.

Carboxylated Pillar[5]arene Meets Medicinal Biguanides: Host–Guest Complexes with Alexidine and Phenformin in the Crystal and Solution/Gas Phase

“…The first model structure considered here was the crystal-like conformation of the CPA5−PFM complex (Figure 12B), obtained by relaxing its crystal-derived conformation in the MOPAC PM7 force field. 37 The collision cross section calculated for this crystal-like conformation is consistent with the experimental values, thus indicating the structural congruence between the solid and the solution/gas phases. In this conformation, a doubly protonated PFM molecule is trapped and symmetry positioned in the interior of the triply negatively charged CPA5 host.…”

“…Further conclusions on the structural properties of the CPA5–PFM complex were obtained by comparing its experimental collision cross section with the theoretical cross section obtained for model structures. The first model structure considered here was the crystal-like conformation of the CPA5–PFM complex (Figure B), obtained by relaxing its crystal-derived conformation in the MOPAC PM7 force field . The collision cross section calculated for this crystal-like conformation is consistent with the experimental values, thus indicating the structural congruence between the solid and the solution/gas phases.…”

“…Hence, this approach is well suited for structural analysis of supramolecular systems, providing insights into their preorganization in the mother solution, one step prior to the crystallization process. Recent advances in instrumentation and the development of computational strategies for IM-MS have enabled its use for tremendously challenging structural studies, including macrocycle–anion complexes, supramolecules with confined spaces and interlocked structures, − and self-assembled systems such as metallosupramolecular complexes …”

Ion Mobility Mass Spectrometry for Large Synthetic Molecules: Expanding the Analytical Toolbox

“…Here the macrocycle can work as an IM shift reagent, and differences in noncovalent complexation facilitate or even enable the separation with IM. 20 Isomers of bile acid, 104 enantiomers of ibuprofen and flurbiprofen, 105 and enantiomers of 19 amino acids 106 have been separated upon encapsulation in cyclodextrin macrocycles, and other IM shift reagents have also been used. 20 Since the development and manufacturing of new pharmaceutical entities relies on producing pure isomers and enantiomers, IM-MS in combination with such shift reagents has potential for applications in the screening and separation of drug candidates.…”

Cyclable Variable Path Length Multilevel Structures for Lossless Ion Manipulations (SLIM) Platform for Enhanced Ion Mobility Separations

“…Ion mobility spectrometry-mass spectrometry (IMS-MS) is a powerful technique for a variety of applications (e.g., threat detection, food, biomedical research, etc.) due to its ability to provide structural information, improve feature detection, increase throughput, and enhance selectivity. − There is, however, a need to glean more information from increasingly complex samples. One approach to address such need is adding orthogonal separations to IMS-MS such as liquid chromatography, gas chromatography, and electrophoresis .…”