Modeling Differential Mobility from First Principles

• Applicant: Dr. Alexander Haack
• Subject Area: Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 449651261

• Final Report Year: 2023

Final Report Abstract

Differential Mobility Spectrometry (DMS) is a technique used for the analysis of chemical samples. Whether an unknow substance needs to be identified or a sample should be tested for dangerous contaminations, it is important to have reliable and well-understood analytical tools at hand. While DMS is already used today in many fields of analytical chemistry or biochemistry, some fundamental questions about the mechanism of operation are still unanswered. Consequently, some experimental observations cannot be explained, potentially leading to inaccurate or even false conclusions. In this project, we deepened our understanding of the mechanisms of operation in DMS by developing a computational model able to simulate the most important aspects of this technique. For this we needed to consider the physics behind the principles of analysis, the chemistry occurring during the analysis, and, most importantly, how these two aspects influence each other. For example, if the analyzed substance is chemically modified through the analysis process, correct identification can only be made if this is well understood, i.e., can be modelled. By comparing our simulations with experimental observations for more and more complicated chemical systems, we were able to refine and expand our model, while also increasing the accuracy of our predictions. Although some challenges remain, this model now allows practitioners to support their experiments with simulations, increasing confidence in the interpretation of their results. This has already been demonstrated throughout this project for a number of concrete analytical problems. Further, the newly gained knowledge about the principles of operation of DMS already revealed new variations of this technique and in the future this knowledge can be used for technological advances. This expands the general field of usage of DMS in analytical chemistry.

Publications

• MobCal-MPI 2.0
  Haack, A.; Ieritano, C. & Hopkins, W.S.
  
• First-Principles Modeling Of Differential Ion Mobility – Aiming for Quantitative Prediction (Poster). ID: 306648, Nov. 5th, Proceedings of the 69th ASMS Conference on Mass Spectrometry and Allied Topics, Philadelphia, PA, Oct. 31 – Nov. 5, 2021.
  Haack, A.; Bissonnette, J.R.; Ieritano, C. & Hopkins, W.S.
  
• Higher-Order-2TT_Testset. ioChem-BD Computational Chemistry Datasets. Institute of Chemical Research of Catalonia.
  Haack, Alexander & Bissonette, Justine R.
  
• Predicting Differential Mobility from First Principles (Poster). Proceedings of the 33rd International Workshop on Tandem Mass Spectrometry, Lake Louise, Canada, Dec. 1-4, 2021.
  Haack, A. & Hopkins, W. S.
  
• UVPD spectroscopy of differential mobility-selected prototropic isomers of protonated adenine. Physical Chemistry Chemical Physics, 23(35), 19892-19900.
  Heldmaier, Fiorella Villanueva; Coughlan, Neville J. A.; Haack, Alexander; Huard, Rebecca; Guna, Mircea; Schneider, Bradley B.; Le Blanc, J. C. Yves; Campbell, J. Larry; Nooijen, Marcel & Hopkins, W. Scott
  
• First Principles Modelling of Ion-Solvent Clustering in Ion Mobility (Talk). Proceedings of the 34th International Workshop on Tandem Mass Spectrometry, Lake Louise, Canada, Nov. 30 – Dec. 3, 2022.
  Haack, A. & Hopkins, W.S.
  
• Improved First-Principles Model of Differential Mobility Using Higher Order Two-Temperature Theory. Journal of the American Society for Mass Spectrometry, 33(3), 535-547.
  Haack, Alexander; Bissonnette, Justine R.; Ieritano, Christian & Hopkins, W. Scott
  
• Kinetics in DMS: Modeling Clustering and Declustering Reactions. Journal of the American Society for Mass Spectrometry, 33(12), 2250-2262.
  Haack, Alexander & Hopkins, W. Scott
  
• Kinetics_DMS_clustering. ioChem-BD Computational Chemistry Datasets. Institute of Chemical Research of Catalonia.
  Haack, Alexander
  
• On the Conformational Changes of Tripeptides in Differential Mobility Spectrometry (Poster). ID: 309076, June 9th, Proceedings of the 70th ASMS Conference on Mass Spectrometry and Allied Topics, Minneapolis, MN, June 5-9, 2022.
  Haack, A.; Ieritano, C. & Hopkins, W.S.
  
• Protonation‐Induced Chirality Drives Separation by Differential Ion Mobility Spectrometry. Angewandte Chemie International Edition, 61(9).
  Ieritano, Christian; Yves, Le Blanc J. C.; Schneider, Bradley B.; Bissonnette, Justine R.; Haack, Alexander & Hopkins, W. Scott
  
• Bridging the Gap between Differential Mobility, Log S, and Log P Using Machine Learning and SHAP Analysis. Analytical Chemistry, 95(27), 10309-10321.
  Stienstra, Cailum M. K.; Ieritano, Christian; Haack, Alexander & Hopkins, W. Scott
  
• Chemical Transformations Can Occur during DMS Separations: Lessons Learned from Beer’s Bittering Compounds. Journal of the American Society for Mass Spectrometry, 34(7), 1315-1329.
  Ieritano, Christian; Haack, Alexander & Hopkins, W. Scott
  
• First-Principles Modeling of Preferential Solvation in Mixed-Modifier Differential Mobility Spectrometry. Journal of the American Society for Mass Spectrometry, 34(7), 1417-1427.
  Bissonnette, Justine R.; Ryan, Christopher R. M.; Ieritano, Christian; Hopkins, W. Scott & Haack, Alexander
  
• HiKE_cluster_sizes. ioChem-BD Computational Chemistry Datasets. Institute of Chemical Research of Catalonia.
  Haack, Alexander
  
• Ion Clustering and Transformation Reactions during the Transit in the HiKE-IM: Comparing Measurement and Model (Poster). ID: 313188, June 7th, Proceedings of the 71st ASMS Conference on Mass Spectrometry and Allied Topics, Houston, TX, June 4-8, 2023.
  Haack, A.; Schaefer, C.; Hopkins, W.S. & Zimmermann, S.
  
• MobCal-MPI 2.0: an accurate and parallelized package for calculating field-dependent collision cross sections and ion mobilities. The Analyst, 148(14), 3257-3273.
  Haack, Alexander; Ieritano, Christian & Hopkins, W. Scott
  
• MobCal-MPI 2023
  Ieritano, C. & Haack, A.
  
• Predicting Ion-Solvent Clustering in Differential Mobility Spectrometry using Anharmonic Thermochemistry. American Chemical Society (ACS).
  Ryan, Christopher R. M.; Haack, Alexander & Hopkins, W. Scott
  
• Preferential_Solvation_DMS. ioChem-BD Computational Chemistry Datasets. Institute of Chemical Research of Catalonia.
  Haack, Alexander; Bissonnette, Justine & Ryan, Christoph
  
• Tripeptides_MassSpec. ioChem-BD Computational Chemistry Datasets. Institute of Chemical Research of Catalonia.
  Haack, Alexander
  
• Validation of Field-Dependent Ion–Solvent Cluster Modeling via Direct Measurement of Cluster Size Distributions. Journal of the American Society for Mass Spectrometry, 34(6), 1035-1046.
  Haack, Alexander; Schaefer, Christoph; Zimmermann, Stefan & Hopkins, W. Scott