Trapped Ion Mobility Mass Spectrometry is able to resolve minor size differences in supramolecular structures

Significance of the topic

Ion mobility mass spectrometry (IM-MS) has emerged as a powerful analytical tool for characterizing supramolecular assemblies by measuring their gas-phase collisional cross sections (CCS). This capability provides detailed insights into the size, shape, and conformational dynamics of complex nanoscale architectures, which are increasingly important in areas such as host–guest chemistry, catalysis, molecular machines, and materials science.

Objectives and overview of the study

The study aimed to demonstrate the high-resolution separation of a ten‐component library of coordination cages, including two isomeric species with nearly identical masses, using trapped ion mobility spectrometry (TIMS) coupled with time‐of‐flight mass spectrometry (timsTOF). By correlating experimental CCS values with theoretical predictions from molecular modeling, the work sought to validate TIMS as a routine method for resolving subtle structural differences in supramolecular chemistry.

Methodology and instrumental setup

The cages were generated by electrospray ionization of a mixture of four shape‐complementary bis‐monodentate ligands and PdII cations. The resulting ions were introduced into a Bruker timsTOF instrument featuring:

• A trapped ion mobility spectrometry cell with nitrogen as the drift gas (305 K, optimized entrance/exit pressures)
• Stepwise release of ions by reducing the electric field, achieving mobility resolution up to 160
• A TOF analyzer for high‐resolution mass detection

Experimental parameters included a capillary voltage of +3600 V, dry gas flow of 3.0 L/min at 200 °C, and accumulation times of 5 ms.

Used instrumentation

• ESI source (DMSO/MeCN solvent, 0.7 mmol analyte concentration)
• Bruker timsTOF mass spectrometer (TIMS cell + TOF analyzer)
• Syringe pump KDScientific KDS900 (flow rate 180 µL/min)
• Calibration with Agilent ESI tune mix for both MS and IMS

Main results and discussion

The approach successfully separated all ten coordination cages by their CCS and m/z values. Even the cis‐ and trans‐isomers of [Pd2LCLFLPLP' + BF4]3+ (m/z 656.15) were distinguished by a CCS difference of only 4.3 Å2 (0.8%). Analysis revealed that variations in appended substituent size on the ligand backbone led to measurable mobility shifts, confirming the technique’s sensitivity to minor dimensional changes. Combining TIMS data with CCS values computed via GFN-xTB geometry optimization and MOBCAL/IMoS calculations enabled unambiguous assignment of isomeric species.

Benefits and practical applications

• High‐throughput differentiation of supramolecular assemblies in complex mixtures without the need for extensive chromatographic separation
• Quantitative access to molecular size and shape information in the gas phase
• Complementary validation of computational models for structural prediction
• Applications in quality control, host–guest screening, and mechanistic studies of self‐assembled systems

Future trends and potential applications

Advances in TIMS resolution and integration with other spectroscopic techniques will enable:

• Real‐time monitoring of dynamic assembly/disassembly processes and photo‐switchable systems
• Mapping of guest‐induced conformational changes in helicene‐ or cage‐based architectures
• Extension to larger biomolecular complexes and nano‐materials
• Improved computational workflows for rapid CCS prediction and structural annotation

Conclusion

Trapped ion mobility mass spectrometry on the timsTOF platform provides a robust, high-resolution method for resolving subtle size differences among supramolecular coordination cages. The synergy between experimental CCS measurements and molecular modeling delivers a comprehensive analytical framework for structural characterization in supramolecular chemistry.

References

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