Validation of Field-Dependent Ion-Solvent Cluster Modeling via Direct Measurement of Cluster Size Distributions

Ion mobility spectrometry is widely used in analytical chemistry, either as a stand-alone technique or coupled to mass spectrometry. Ions in the gas phase tend to form loosely bound clusters with surrounding solvent vapors, artificially increasing the collisional cross section and the mass of the ion. This, in turn, affects ion mobility and influences separation. Further, ion-solvent clusters play an important role in most ionization mechanisms occurring in the gas phase. Consequently, a deeper understanding of ion-solvent cluster association and dissociation processes is desirable to guide experimental design and interpretation. A few computational models exist, which aim to describe the amount of clustering as a function of the reduced electric field strength, bath gas pressure and temperature, and the chemical species probed. It is especially challenging to model ion mobility under high reduced electrical field strengths due to the nonthermal conditions created by the field. In this work, we aim to validate a recently proposed first-principles model by comparing its predictions with direct measurements of cluster size distributions over a range of 20-120 Td as observed using a High Kinetic Energy Ion Mobility Spectrometer coupled to a mass spectrometer (HiKE-IMS-MS). By studying H⁺(H₂O), [MeOH + H + n(H₂O)]⁺, [ACE + H + n(H₂O)]⁺, and [PhNH₂ + H + n(H₂O)]⁺ as test systems, we find very good agreement between model and experiment, supporting the validity of the computational workflow. Further, the detailed information gained from the modeling yields important insights into the cluster dynamics within the HiKE-IMS, allowing for better interpretation of the measured ion mobility spectra.