Calculation Of Collision Cross Sections Research Articles

Trapped and drift-tube ion-mobility spectrometry for the analysis of environmental contaminants: Comparability of collision cross-section values and resolving power.

Ion-mobility (IM)-derived collision cross-section (CCS) values can serve as a valuable additional identification parameter within suspect and non-target screening studies of environmental contaminants. However, these applications require to assess the reproducibility of CCS calculations between different IM set-ups. Especially for the comparison of trapped and drift-tube IM (TIMS/DTIM) derived CCS values, data for environmental applications is lacking. The presented study assessed the bias of TIMS derived CCSN2 (TIMSCCSN2) values of 48 environmental contaminants from three classes in comparison to a previously established DTIM database. Based on two sets of isomeric bisphenols, the resolving power of both systems was compared, addressing the instrumental settings which influence the resolution of TIMS measurements. For 91% of the datapoints, bias between TIMSCCSN2 and DTCCSN2 values (latter set as reference) were < 2%, indicating a good inter-platform reproducibility. TIMS resolving power was dependent on the selected mobility window and ramping times whereby a resolution of up to 116 was achieved. Similar resolving power was observed for multiplexed DTIMS data if a high-resolution post-processing step was implemented. These results provide valuable insights in CCSN2 reproducibility facilitating database transfer in future TIMS based studies. Knowledge on the influence of acquisition settings on robustness of TIMSCCSN2 calculations and resolving power can ease method development supporting efficient development and reliable identifications of emerging environmental contaminants.

Using ion mobility spectrometry to understand signal dilution during tandem mass spectrometry sequencing of digital polymers: Experimental evidence of intramolecular cyclization.

Optimizing the structure of digital polymers is an efficient strategy to ensure their tandem mass spectrometry (MS/MS) readability. In block-truncated poly(phosphodiester)s, homolysis of C-ON bonds in long chains permits the release of smaller blocks amenable to sequencing. Yet the dissociation behavior of diradical blocks was observed to strongly depend on their charge state. Polymers were ionized in negative mode electrospray and activated in-source so that blocks released as primary fragments can be investigated using ion mobility spectrometry (IMS) or sequenced in the post-IMS collision cell. Collision cross sections (CCS) were derived from arrival times using a calibration procedure developed for polyanions using the IMSCal software. A multistep protocol based on quantum methods and classical molecular dynamics was implemented for molecular modeling and calculation of theoretical CCS. Unlike their triply charged homologues, dissociation of diradical blocks at the 2- charge state produces additional fragments, with +1m/z shift for those holding the nitroxide α-termination and -1m/z for those containing the carbon-centered radical ω-end. These results suggest cyclization of these diradical species, followed by H• transfer on activated reopening of this cycle. This assumption was validated using IMS resolution of the cyclic/linear isomers and supported by molecular modeling. Combining IMS with molecular modeling provided new insights into how the charge state of digital blocks influences their dissociation. These results permit to define new guidelines to improve either ionization conditions or the structural design of these digital polymers for best MS/MS readability.

Utilization of bis-MPA Dendrimers for the Calibration of Ion Mobility Collision Cross Section Calculations.

Ion mobility-mass spectrometry (IM-MS) has become increasingly popular with the rapid expansion of available techniques and instrumentation. To enable accuracy, standardization, and repeatability of IM-MS measurements, the community requires reliable and well-defined reference materials for calibration and tuning of the equipment. To address this need, synthetic dendrimers of high chemical and structural purity were tested on three ion mobility platforms as potential calibrants. First, synthesized dendrimers were characterized by drift tube ion mobility (DTIMS), using an Agilent 6560 IM-qTOF-MS to assess their drift tube collision cross section (DTCCS) values. Then, assessment of obtained CCS values on trapped ion mobility (TIMS) and traveling wave ion mobility (TWIMS) ion mobility platforms were compared to those found by DTIMS. Across all three systems, dendrimers were found to have high potential for m/z and ion mobility calibration in the CCS range of 160-1700 Å2. To further validate their use as calibrants, drift tube calculated CCS values for dendrimers were utilized to calibrate calculations of CCS for known standards including Agilent Tuning mix, the CCS Major mix from Waters, and SPLASH LIPIDOMIX. Additionally, structures of sodiated dendrimers were computated along with theoretical CCS values which showed good agreement with the experimental CCS values. On the basis of the results presented, we recommend the use of dendrimers as alternatives and/or complementary compounds to commonly used calibrants for ion mobility platforms.

Ion-molecule collision cross-section calculations using trajectory parallelization in distributed systems

Ion Mobility coupled with Mass Spectrometry (IM-MS) stands as a strong analytical method for structurally characterizing complex molecules. In IM-MS, the sample under investigation is ionized and propelled by an electric field into a drift tube, which collides against a buffer gas. The separation of the ion gas phase is then measured through the differences in their rotationally averaged Collision Cross-Section (CCS) values. The effectiveness of the measured Collision Cross-Section (CCS) for structural characterization critically depends on the validation against theoretical calculations. This validation process relies on intensive molecular mechanics simulations, which can be computationally demanding, especially for large systems such as molecular assemblies and viruses. Therefore, reliable and fast CCS calculations are needed to help interpret IM-MS experimental data. This work presents the MassCCS software, which considerably increases the CCS simulation performance by implementing a linked-cell-based algorithm, incorporating High-Performance Computing (HPC) techniques. We performed extensive tests regarding the system size, shape, and number of CPU cores. Experimental results reveal speedups up to 3 orders of magnitude faster than Collision Simulator for Ion Mobility Spectrometry (CoSIMS) and High-Performance Collision Cross Section (HPCCS), optimized solutions for CCS simulations, for a single node execution. In addition, we extended MassCCS at the inter-node level by employing OpenMP Cluster (OMPC). OMPC is an innovative programming model designed for the development of HPC applications. It streamlines the development process and simplifies software maintenance using only OpenMP directives. Notably, OMPC delivers a performance level comparable to a pure MPI implementation. This enhancement enabled expensive CCS calculations using nitrogen buffer gas for large systems such as human adenovirus with ∼11 million atoms in just ∼4 min, making MassCCS the most performant software nowadays, to the best of our knowledge. MassCCS is available as free software for Academic use at https://github.com/cces-cepid/massccs.

Nitrile Imines as Peptide and Oligonucleotide Photo-Cross-Linkers in Gas-Phase Ions.

Nitrile imines produced by photodissociation of 2,5-diaryltetrazoles undergo cross-linking reactions with amide groups in peptide-tetrazole (tet-peptide) conjugates and a tet-peptide-dinucleotide complex. Tetrazole photodissociation in gas-phase ions is efficient, achieving ca. 50% conversion with 2 laser pulses at 250 nm. The formation of cross-links was detected by CID-MS3 that showed structure-significant dissociations by loss of side-chain groups and internal peptide segments. The structure and composition of cross-linking products were established by a combination of UV-vis action spectroscopy and cyclic ion mobility mass spectrometry (c-IMS). The experimental absorption bands were found to match the bands calculated for vibronic absorption spectra of nitrile imines and cross-linked hydrazone isomers. The calculated collision cross sections (CCSth) for these ions were related to the matching experimental CCSexp from multipass c-IMS measurements. Loss of N2 from tet-peptide conjugates was calculated to be a mildly endothermic reaction with ΔH0 = 80 kJ mol-1 in the gas phase. The excess energy in the photolytically formed nitrile imine is thought to drive endothermic proton transfer, followed by exothermic cyclization to a sterically accessible peptide amide group. The exothermic nitrile imine reaction with peptide amides is promoted by proton transfer and may involve an initial [3 + 2] cycloaddition followed by cleavage of the oxadiazole intermediate. Nucleophilic groups, such as cysteine thiol, did not compete with the amide cyclization. Nitrile imine cross-linking to 2'-deoxycytidylguanosine was found to be >80% efficient and highly specific in targeting guanine. The further potential for exploring nitrile-imine cross-linking for biomolecular structure analysis is discussed.

Multi-Scale Simulations of Gas-Phase Particles Generated in Plasma Enhanced Atomic Layer Deposition Processes

Recently, Plasma Enhanced Atomic Layer Deposition (PEALD) has been investigated as an advanced semiconductor deposition method to expand the number and variety of materials other than those available in thermal ALD. The high reactivity of the plasma species at the deposition surface during PEALD has the advantage of increasing the degree of freedom of processing conditions and enabling a wider range of material properties. PEALD consists of four steps in the order of feed, 1st purge, reaction, and 2nd purge. In this reaction step, the secondary gas-phase reaction is important because the properties of the thin film vary greatly depending on the particles that arrive on the growing surface. Therefore, the particle distribution in the gas phase before arrival on the surface should be accurately predicted to estimate the film quality. Generally, the DSMC (Direct Simulation Monte Carlo) method is a commonly used method for analyzing particle distribution in the gas phase. The DSMC method requires reaction and scattering models that simulate the behavior between molecules. Variable Hard Sphere and Variable Soft Sphere are often used as the model in DSMC. These models are about molecular transport, such as molecular diffusion, and cannot deal with molecular reactions. The total collision energy model is determined for molecular reactions, but it may not accurately describe molecular reactions in non-equilibrium flow. The purpose of the study is to develop a new reaction-scattering model in non-equilibrium flow in the DSMC method for determining the particle distribution in the gas phase in the PEALD processes. Here, we focus on ammonia plasma used in the reaction step of boron nitride nanomaterial films, which are used in various applications, such as semiconductors and fine ceramics with two-dimensional and three-dimensional structures. This study focused on neutral and ionic molecules, NH3 and NH4 +, which can be the main collisional species in secondary gas-phase reactions.A molecular dynamics simulation with a reactive force field (ReaxFF) was performed. The left figure shows the simulation system of NH3 and NH4 + collisions. The periodic boundary conditions were applied to the simulation box for all directions in the size of 100 Å × 100 Å × 100 Å. Randomly oriented NH3 and NH4 + were placed in a line at an initial distance of 15 Å. NH4 + was given an electric charge of –0.22892 on N and 0.30723 on H. The initial translational energy of NH4 + was set at 5-60 eV, and the difference in the vertical coordinate at 0.1-5.0 Å. The collisions were sampled 2000 times.The right figure shows the calculated collision cross section, which determines whether a collision occurs or not. The collision coefficient bcoll represents the difference in the maximum vertical coordinate at which the absolute value of the scattering angle is greater than 1 degree. The collision cross section decreases as the translational energy increases because the negligible attraction-force act on NH3 and NH4 + at a long distance. When the translational energy exceeds 40 eV, the collisional cross-section no longer decreases and becomes asymptotic. The reason can be considered as follows. As the cross-section approaches 40 Å2, the collision cross section asymptotically approaches 40 Å2, regardless of the translational energy, because the attractive and repulsive forces are balanced. We compared our results with a reference model in grey color. In the reference model, Etr, 0 represents the minimum translational energy, σT,0 is the collision cross section at the minimum, Etr is the translational energy, and ω is a fitting parameter. Here, ω was set at –3.1. The reference model shows a good agreement with our results. However, the collision cross section is asymptotic above 40 eV, which may affect the results when the DSMC simulations are performed. We will apply the reaction scattering model to the DSMC method and analyze the gas-phase reaction of PEALD, including a comparison of the results of existing models. Figure 1

Axisymmetric inertialess model for the capture of airborne microparticles using an electrospray

We theoretically analyze the effectiveness of an electrospray of ultrafine droplets to filter out micron sized particles from a gas stream. To that end, we introduce an axisymmetric configuration where the airborne particles merge with the electrospray. The droplets attach to the particles, charging them, and both droplets and charged particles are eventually driven towards a collector by means of an electric field. The attachment process is described through a set of reaction constants based on calculated collision cross-sections, yielding particles with different charge levels. The problem involves computation of the concentrations of each type of particle, the gas flow, and the electric field due to the applied voltages and the space charge. Preliminary numerical simulations show a filtration efficiency that is above 95% for particles larger than about 2μm and rapidly declines for smaller particles, though this drop of the efficiency can be postponed to smaller particle sizes by decreasing the ratio of particle to electrospray fluxes or the ratio of the inlet velocity of the particle carrying gas to the velocity induced by electric forces inside the device. Pending an exhaustive numerical exploration of the parameter space of the system, these results also show that the gas flow structure, which is strongly affected by the charged particles, is key for high filtration efficiency.

MassCCS: A High-Performance Collision Cross-Section Software for Large Macromolecular Assemblies.

Ion mobility mass spectrometry (IM-MS) techniques have become highly valued as a tool for structural characterization of biomolecular systems since they yield accurate measurements of the rotationally averaged collision cross-section (CCS) against a buffer gas. Despite its enormous potential, IM-MS data interpretation is often challenging due to the conformational isomerism of metabolites, lipids, proteins, and other biomolecules in the gas phase. Therefore, reliable and fast CCS calculations are needed to help interpret IM-MS data. In this work, we present MassCCS, a parallelized open-source code for computing CCS of molecules ranging from small organic compounds to massive protein assemblies at the trajectory method level of description using atomic and molecular buffer gas particles. The performance of the code is comparable to other available software for small molecules and proteins but is significantly faster for larger macromolecular assemblies. We performed extensive tests regarding accuracy, performance, and scalability with system size and number of CPU cores. MassCCS has proven highly accurate and efficient, with execution times under a few minutes, even for large (84.87 MDa) virus capsid assemblies with very modest computational resources. MassCCS is freely available at https://github.com/cces-cepid/massccs.

Collisional excitation of N+(3P) in interstellar clouds

ABSTRACT The detection of the N+ ion in ionized interstellar regions, as well as its use as a tracer for atomic nitrogen (N) in interstellar media, makes it an interesting ion from the astrophysical point of view. Accurate determination of the N+ abundance in the interstellar clouds requires detailed modelling of its excitation conditions. Hence, collisional excitation induced by the dominant interstellar species has to be studied. In this paper, we study the collisional excitation of N+ by He and H2. We provide new potential energy surfaces describing the interactions between N+ and He and between N+ and H2 considered as a structureless collider. Quantum calculations of the excitation cross-sections for collisions of N+ with He and H2 are provided, as well as the first excitation rate coefficients for N+ induced by these two species. The results are compared to collisional data for the excitation induced by electrons. It is shown that the excitation of N+ by a neutral collider can play a significant role in weakly ionized regions as well as in warm molecular clouds.

Rate coefficients for rotational state-to-state transitions in H2O + H2O collisions for cometary and planetary applications, as predicted by mixed quantum-classical theory

Aims. We present new calculations of collision cross sections for state-to-state transitions between the rotational states in an H2O + H2O system, which are used to generate a new database of collisional rate coefficients for cometary and planetary applications. Methods. Calculations were carried out using a mixed quantum-classical theory approach that is implemented in the code MQCT. The large basis set of rotational states used in these calculations permits us to predict thermally averaged cross sections for 441 transitions in para- and ortho-H2O in a broad range of temperatures. Results. It is found that all state-to-state transitions in the H2O + H2O system split into two well-defined groups, one with higher cross-section values and lower energy transfer, which corresponds to the dipole-dipole driven processes. The other group has smaller cross sections and higher energy transfer, driven by higher-order interaction terms. We present a detailed analysis of the theoretical error bars, and we symmetrized the state-to-state transition matrixes to ensure that excitation and quenching processes for each transition satisfy the principle of microscopic reversibility. We also compare our results with other data available from the literature for H2O + H2O collisions.

Energy-Resolved Ion Mobility Spectrometry: Composite Breakdown Curves for Distinguishing Isomeric Product Ions.

Identification of lipopeptides (LpAA) synthesized from bacteria involves the study of structural characterization. Twenty LpAA have been characterized using commercial tandem high-resolution mass spectrometers in negative electrospray, employing nonresonant excitation in "RF only" collision cells and generally behave identically. However, [LpAA-H]- (AA = Asp or Glu) shows surprising fragmentation pathways, yielding a complementary fatty acid carboxylate and dehydrated amino acid fragment anions. In this study, the dissociation mechanisms of [C12Glu-H]- were determinate using energy-resolved mass spectrometry (ERMS). Product ion breakdown profiles are, generally, unimodal with full width at half-maximum (fwhm) increasing as product ion m/z ratios decrease, except for the two product ions of interest (fatty acid carboxylate and dehydrated glutamate) characterized by broad and composite profiles. Such behavior was already shown for other ions using a custom-built guided ion beam mass spectrometer. In this study, we investigate the meaning of these particular profiles from an ERMS breakdown, using fragmentation mechanisms depending on the collision energy. ERMS on line with ion mobility spectrometry (IMS), here called ER-IMS, provides a way to probe such questions. Broad or composite profiles imply that the corresponding product ions may be generated by two (or more) pathways, resulting in common or isomeric product ion structures. ER-IMS analysis indicates that the fatty acid carboxylate product ion is produced with a common structure through different pathways, while dehydrated glutamate has two isomeric forms depending on the mechanism involved. Drift time values correlate with the calculated collision cross section that confirms the product ion structures and fragmentation mechanisms.

Prediction of Structures of Compounds Encountered in Complex Organic Matter with Highly Flexible Alkyl Chains Using Ion Mobility-Mass Spectrometry.

The chemical structure of an organic molecule has a direct influence on its three-dimensional conformation. One way to obtain information on this conformation is to use ion mobility spectrometry. This technique allows the separation of different isomers according to their collision cross section (CCS) with an inert gas. Smaller or more compact molecules will have lower collision cross section values than larger molecules. The CCS is an intrinsic ion parameter for a specific gas and is thus predictable. Today, calculations of rigid molecules are commonly performed to obtain additional structural information on an ion. However, calculations are more complex with very flexible molecules. In particular, molecules presenting long alkyl chains can yield a high number of conformers. Each conformer is then associated with a CCS value that is specific to it. We report, here, a methodology to predict CCS of flexible molecules. The used approach is based on automatic conformers research followed by geometry optimization and CCS calculations. Determination of theoretical and experimental CCS values for a rigid polycyclic aromatic hydrocarbons (PAHs) standard was used to calibrate the Mobcal software. Then, 13 standard molecules ranging from 4 to 19 carbon alkyl chains, including three long alkyl chain isomers of C22H38, were analyzed on a TWIMS-ToF and calculated using our methodology. CCS deviations between experimental and theoretical values were found to be less than 1.5% over the whole studied CCS range. This method was finally applied for structural analysis of petroleum compounds refractory to the hydro-denitrogenation process.

Modeling approaches for atmospheric ion–dipole collisions: all-atom trajectory simulations and central field methods

Abstract. Ion–dipole collisions can facilitate the formation of atmospheric aerosol particles and play an important role in their detection in chemical ionization mass spectrometers. Conventionally, analytical models, or simple parametrizations, have been used to calculate the rate coefficients of ion–dipole collisions in the gas phase. Such models, however, neglect the atomistic structure and charge distribution of the collision partners. To determine the accuracy and applicability of these approaches under atmospheric conditions, we calculated collision cross sections and rate coefficients from all-atom molecular dynamics collision trajectories, sampling the relevant range of impact parameters and relative velocities, and from a central field model using an effective attractive interaction fitted to the long-range potential of mean force between the collision partners. We considered collisions between various atmospherically relevant molecular ions and dipoles and charged and neutral dipolar clusters. Based on the good agreement between collision cross sections and rate coefficients obtained from molecular dynamics trajectories and a generalized central field model, we conclude that the effective interactions between the collision partners are isotropic to a high degree, and the model is able to capture the relevant physicochemical properties of the systems. In addition, when the potential of mean force is recalculated at the respective temperatures, the central field model exhibits the correct temperature dependence of the collision process. The classical parametrization by Su and Chesnavich (1982), which combines a central field model with simplified trajectory simulations, is able to predict the collision rate coefficients and their temperature dependence quite well for molecular systems, but the agreement worsens for systems containing clusters. Based on our results, we propose the combination of potential of mean force calculation and a central field model as a viable and elegant alternative to the brute force sampling of individual collision trajectories over a large range of impact parameters and relative velocities.

Ion Mobility and Fourier Transform Ion Cyclotron Resonance Collision Cross Section Techniques Yield Long-Range and Hard-Sphere Results, Respectively.

We determined collision cross section (CCS) values for singly and doubly charged cucurbit[n]uril (n = 5-7), decamethylcucurbit[5]uril, and cyclohexanocucurbit[5]uril complexes of alkali metal cations (Li+-Cs+). These hosts are relatively rigid. CCS values calculated using the projection approximation (PA) for computationally modeled structures of a given host are nearly identical for +1 and +2 complexes, with weak metal ion dependence, whereas trajectory method (TM) calculations of CCS for the same structures consistently yield values 7-10% larger for the +2 complexes than for the corresponding +1 complexes and little metal ion dependence. Experimentally, we measured relative CCS values in SF6 for pairs of +1 and +2 complexes of the cucurbituril hosts using the cross-sectional areas by Fourier transform ion cyclotron resonance ("CRAFTI") method. At center-of-mass collision energies <∼30 eV, CRAFTI CCS values are sensitive to the relative binding energies in the +1 and +2 complexes, but at collision energies >∼40 eV (sufficient that ion decoherence occurs on essentially every collision) that dependence is not evident. Consistent with the PA calculations, these experiments found that the +2 complex ions have CCS values ranging between 94 and 105% of those of their +1 counterparts (increasing with metal ion size). In contrast, but consistent with the TM CCS calculations, ion mobility measurements of the same complexes at close to thermal energies in much less polarizable N2 find the CCS of +2 complexes to be in all cases 9-12% larger than those of the corresponding +1 complexes, with little metal ion dependence.

In Silico Collision Cross Section Calculations to Aid Metabolite Annotation

The interpretation of ion mobility coupled to mass spectrometry (IM-MS) data to predict unknown structures is challenging and depends on accurate theoretical estimates of the molecular ion collision cross section (CCS) against a buffer gas in a low or atmospheric pressure drift chamber. The sensitivity and reliability of computational prediction of CCS values depend on accurately modeling the molecular state over accessible conformations. In this work, we developed an efficient CCS computational workflow using a machine learning model in conjunction with standard DFT methods and CCS calculations. Furthermore, we have performed Traveling Wave IM-MS (TWIMS) experiments to validate the extant experimental values and assess uncertainties in experimentally measured CCS values. The developed workflow yielded accurate structural predictions and provides unique insights into the likely preferred conformation analyzed using IM-MS experiments. The complete workflow makes the computation of CCS values tractable for a large number of conformationally flexible metabolites with complex molecular structures.

Simultaneous spatial, conformational, and mass analysis of intact proteins and protein assemblies by nano-DESI travelling wave ion mobility mass spectrometry imaging

We have previously demonstrated native nano-desorption electrospray ionization (nano-DESI) mass spectrometry imaging of proteins and protein complexes in thin tissue section of rat kidney. Here, we demonstrate the integration of travelling wave ion mobility spectrometry (TWIMS) into the native nano-DESI MSI workflow. The benefits of TWIMS are twofold: Firstly, arrival time filtering allows subtraction of chemical noise and the resulting ion images show improved specificity. Secondly, the incorporation of TWIMS enables the calculation of collision cross sections, and thus a measure of protein structure, directly from the imaging dataset. Our results show good agreement between the collision cross sections determined from nano-DESI, which requires the use of a heated inlet, and those determined experimentally from liquid extraction surface analysis (LESA) with an ambient temperature inlet, and those available in the literature. Ion images and collision cross sections are presented for a range of proteins and protein assemblies with molecular weights of up to 42.6 kDa.

Action spectroscopy of isomer-selected luciferin anions

Luciferin molecules are common luminophores found throughout the biological kingdoms. Here, electrospray ionization and tandem ion mobility spectrometry coupled with laser spectroscopy are used to demonstrate that D-luciferin and oxyluciferin deprotonated anions can be produced in two isomeric forms, which can be separated by virtue of their different collision cross sections with a buffer gas. The two isomers possess distinguishable but partially overlapping photodepletion action spectra over the visible range, implying distinct intrinsic absorption profiles. The site of deprotonation and tautomeric forms of the electrosprayed isomers are assigned through comparisons between experimental and calculated collision cross sections and electronic excitation energies. The study clearly shows that electrospray ionization of biochromophore molecules can generate multiple isomeric forms with distinct electronic spectra.

Assessing collision cross section calculations using MobCal-MPI with a variety of commonly used computational methods

Structural studies with ion mobility require an accurate methodology to bridge theoretical modelling of chemical structure with experimental determination of an ion’s collision cross section (CCS). The parallelized MobCal-MPI package enables rapid and accurate evaluation of CCSs that are applicable to several chemical classes, but was only assessed for accuracy using a single model chemistry: B3LYP-D3/6-31++G(d,p). In this work, the performance of MobCal-MPI was validated across 25 different model chemistries, which encompassed PM7, Hartree-Fock, and three common DFT functionals (B3LYP-D3, ωB97X-D, and M06-2X-D3) using six different basis sets (6-31 G, 6-31 G(d,p), 6-31++G(d,p), def2-SVP, def2-TZVP, and def2-TZVPP). Performance assessment was accomplished using geometries generated from a set of 50 structurally diverse molecules at each level of theory. MobCal-MPI calculates CCSs that correlate well with experimental values for all model chemistries explored (< 2.5% RMSD) with the exception of PM7 (3.0 % RMSD) and methods that employ basis sets lacking polarization functions (e.g., 6-31G; < 4% RMSD). While any of the 25 model chemistries can be used with MobCal-MPI with reasonable accuracy, caution should be exercised when coupling CCS calculations with PM7 or basis sets that lack polarization functions. Following benchmarking, MobCal-MPI was used to calculate the CCS of a macromolecular construct consisting of atropine and β-cyclodextrin. The CCSs calculated for the β-cyclodextrin complex using either the PM7 or B3LYP-D3 model chemistries agree with experimental values within the expected error of the method (< 2.5 %).

Validating Experimental Results of Cardiac Glycosides and Monoterpene Indole Alkaloids using Cheminformatics

Predictive classification of metabolites from natural products holds immense promise for developing new therapeutics to treat diseases that involve cell-surface proteins. Cardiac glycosides and monoterpene indole alkaloids are metabolite compounds that can be extracted from plants and have therapeutic applicability in the treatment of irregular heartbeats and pain sensitivity through their interactions with ion pumps and neurotransmitter receptors. We seek to combine the results of analytical experiments involving ion mobility mass spectrometry (IM-MS) with computational studies involving open-source cheminformatics software. Our goal for this project is to predict the collision cross section (CCS) values of modeled structures and match with our IM-MS experimental results. Using a standard off-the-shelf cheminformatics software (RDKit), we can rapidly generate molecular ensembles based on simple SMILES strings and calculate different geometric properties that allow us to cluster these ensembles and obtain the most representative conformers to match with experiment. Using an open-source quantum chemistry software (Psi4), we can generate Mulliken charges of the representative conformers to conduct CCS calculations and compare with IM-MS experiments. We are currently applying this method to a suite of cardiac glycosides and monoterpene indole alkaloids to create a library of ion mobility data for rapid classification and identification of mixtures of plant-based toxin molecules. This combined experimental and computational approach will allow scientists to rapidly analyze and identify toxins in unknown mixtures based on their mobilities and CCS values.

Linear Size Contraction of Ligand Protected Ag29 Clusters by Substituting Ag with Cu

There are only a few examples of atomically precise, ligand protected, bimetallic coinage metal clusters in which molecular structure remains essentially unchanged over a wide composition range starting from the corresponding homometallic species. Such model systems are particularly useful to study the dynamics of alloy formation on the nanoscale. Here we demonstrate the unusual reactivity of solvated metalloid-superatom Ag29(BDT)12(PPh3)4 (BDT = 1,3 benzenedithiol) clusters toward semiconducting Cu12S6(DPPPT)4 (DPPPT = bis(diphenylphosphino)pentane) clusters as an efficient way to exchange multiple copper atoms into the atomically precise silver clusters without changing overall the structure type. Concentration-dependent UV-vis absorption and online mass spectrometry shows that 14 Cu atoms can be exchanged into the silver cluster. Beyond the 14 Cu atom exchange, the cluster degrades to smaller thiolates. Information on cluster structures is obtained from high-resolution ion mobility mass spectrometry, which shows a linear decrease in collision cross section (CCS) with each Ag/Cu exchanged. Several isomeric structures are calculated by density functional theory (DFT), and their calculated collision cross sections are used to identify the most stable isomers for each Ag/Cu exchange product. Ag/Cu exchange is essentially limited to the cluster surface/shell. The core appears not to be involved.