Benchmark Experimental Gas-Phase Intermolecular Dissociation Energies by the SEP-R2PI Method.

The gas-phase ground-state dissociation energy D0(S0) of an isolated and cold bimolecular complex is a fundamental measure of the intermolecular interaction strength between its constituents. Accurate D0 values are important for the understanding of intermolecular bonding, for benchmarking high-level theoretical calculations, and for the parameterization of dispersion-corrected density functionals or force-field models that are used in fields ranging from crystallography to biochemistry. We review experimental measurements of the gas-phase D0(S0) and D0(S1) values of 55 different M⋅S complexes, where M is a (hetero)aromatic molecule and S is a closed-shell solvent atom or molecule. The experiments employ the triply resonant SEP-R2PI laser method, which involves M-centered (S0 → S1) electronic excitation, followed by S1 → S0 stimulated emission spanning a range of S0 state vibrational levels. At sufficiently high vibrational energy, vibrational predissociation of the M⋅S complex occurs. A total of 49 dissociation energies were bracketed to within ≤1.0 kJ/mol, providing a large experimental database of accurate noncovalent interactions.

Resolution of Isomeric Mixtures in Ion Mobility Using a Combined Demultiplexing and Peak Deconvolution Technique.

A combined data acquisition and data processing strategy for improving the sensitivity and resolution of ion mobility measurements is described. This strategy is implemented on a commercially available drift tube ion mobility-mass spectrometry (IM-MS) instrument and utilizes both an existing ion multiplexing strategy to achieve up to an 8-fold gain in ion signal and a new postacquisition data reconstruction technique, termed "high resolution demultiplexing" (HRdm), to improve resolution in the ion mobility dimension. A series of isomeric mixtures were qualitatively investigated with HRdm, including biologically relevant lipids and carbohydrates, which were successfully resolved by HRdm, including two monosaccharide regioisomers which differed in drift time by only 0.8%. For a complex trisaccharide isomer mixture, HRdm was able to resolve 5 out of 6 components. An analysis of two-peak resolution (Rpp) and peak-to-peak separation (ΔP) indicated that HRdm performs with an effective resolving power (Rp) of between 180 to 250 for the highest deconvolution settings. Overall analysis times and drift time measurement precision were found to be unaffected between standard and HRdm processed data sets, which allowed statistically identical collision cross section values to be directly determined from all ion mobility spectra.

Intermolecular dissociation energies of 1-naphthol complexes with large dispersion-energy donors: Decalins and adamantane.

The ground-state intermolecular dissociation energies D0(S0) of supersonic-jet cooled intermolecular complexes of 1-naphthol (1NpOH) with the bi- and tricycloalkanes trans-decalin, cis-decalin, and adamantane were measured using the stimulated-emission-pumping/resonant two-photon ionization (SEP-R2PI) method. Using UV/UV holeburning, we identified two isomers (A and B) of the adamantane and trans-decalin complexes and four isomers (A-D) of the cis-decalin complex. For 1NpOH·adamantane A and B, the D0(S0) values are 21.6 ± 0.15 kJ/mol and 21.2 ± 0.32 kJ/mol, those of 1NpOH·trans-decalin A and B are 28.7 ± 0.3 kJ/mol and 28.1 ± 0.9 kJ/mol, and those of 1NpOH·cis-decalin A and B are 28.9 ± 0.15 kJ/mol and 28.7 ± 0.3 kJ/mol. Upon S0 → S1 electronic excitation of the 1NpOH moiety, the dissociation energies of adamantane, trans-decalin, and the cis-decalin isomer C change by <1% and those of cis-decalin isomers A, B, and D increase only slightly (1%-3%). This implies that the hydrocarbons are dispersively adsorbed to a naphthalene "face." Calculations using the dispersion-corrected density functional theory methods B97-D3 and B3LYP-D3 indeed predict that the stable structures have face geometries. The B97-D3 calculated D0(S0) values are within 1 kJ/mol of the experiment, while B3LYP-D3 predicts D0 values that are 1.4-3.3 kJ/mol larger. Although adamantane has been recommended as a "dispersion-energy donor," the binding energies of the trans- and cis-decalin adducts to 1NpOH are 30% larger than that of adamantane. In fact, the D0 value of 1NpOH·adamantane is close to that of 1NpOH·cyclohexane, reflecting the nearly identical contact layer between the two molecules.

Face, Notch, or Edge? Intermolecular dissociation energies of 1-naphthol complexes with linear molecules.

The stimulated-emission-pumping/resonant 2-photon ionization (SEP-R2PI) method was used to determine the intermolecular dissociation energies D0 of jet-cooled 1-naphthol(1NpOH)·S complexes, where S is a linear molecule (N2, CO, CO2, OCS, N2O, and ethyne) or symmetric-top molecule (2-butyne) that contains double or triple bonds. The dissociation energies D0(S0) are bracketed as follows: 6.68 ± 0.08 kJ/mol for S=N2, 7.7 ± 0.8 kJ/mol for CO, 12.07 ± 0.10 kJ/mol for CO2, 13.03 ± 0.01 kJ/mol for N2O, 14.34 ± 0.08 kJ/mol for ethyne, 15.0 ± 1.35 kJ/mol for OCS, and 29.6 ± 2.4 kJ/mol for 2-butyne. The minimum-energy structures, vibrational wavenumbers, and zero-point vibrational energies were calculated using the dispersion-corrected density functional theory methods such as B97-D3 and B3LYP-D3 with the def2-QZVPP basis set. These predict that N2 and CO are dispersively bound Face complexes (S bound to a naphthalene Face), while CO2, N2O, and OCS adsorb into the "Notch" between the naphthyl and OH groups; these are denoted as Notch complexes. Ethyne and 2-butyne form Edge complexes involving H-bonds from the -OH group of 1NpOH to the center of the molecule. The presence of a double or triple bond or an aromatic C=C bond within S does not lead to a specific calculated geometry (Face, Notch or Edge). However, a correlation exists between the structure and the sign of the quadrupole moment component Θzz of S: negative Θzz correlates with Face or Notch, while positive Θzz correlates with Edge geometries.

Intermolecular dissociation energies of dispersively bound complexes of aromatics with noble gases and nitrogen.

We measured accurate intermolecular dissociation energies D0 of the supersonic jet-cooled complexes of 1-naphthol (1NpOH) with the noble gases Ne, Ar, Kr, and Xe and with N2, using the stimulated-emission pumping resonant two-photon ionization method. The ground-state values D0(S0) for the 1NpOH⋅S complexes with S= Ar, Kr, Xe, and N2 were bracketed to be within ±3.5%; they are 5.67 ± 0.05 kJ/mol for S = Ar, 7.34 ± 0.07 kJ/mol for S = Kr, 10.8 ± 0.28 kJ/mol for S = Xe, 6.67 ± 0.08 kJ/mol for isomer 1 of the 1NpOH⋅N2 complex, and 6.62 ± 0.22 kJ/mol for the corresponding isomer 2. For S = Ne, the upper limit is D0 < 3.36 kJ/mol. The dissociation energies increase by 1%-5% upon S0 → S1 excitation of the complexes. Three dispersion-corrected density functional theory (DFT-D) methods (B97-D3, B3LYP-D3, and ωB97X-D) predict that the most stable form of these complexes involves dispersive binding to the naphthalene "face." A more weakly bound edge isomer is predicted in which the S moiety is H-bonded to the OH group of 1NpOH; however, no edge isomers were observed experimentally. The B97-D3 calculated dissociation energies D0(S0) of the face complexes with Ar, Kr, and N2 agree with the experimental values within <5%, but the D0(S0) for Xe is 12% too low. The B3LYP-D3 and ωB97X-D calculated D0(S0) values exhibit larger deviations to both larger and smaller dissociation energies. For comparison to 1-naphthol, we calculated the D0(S0) of the carbazole complexes with S = Ne, Ar, Kr, Xe, and N2 using the same DFT-D methods. The respective experimental values have been previously determined to be within <2%. Again, the B97-D3 results are in the best overall agreement with experiment.

Intermolecular dissociation energies of hydrogen-bonded 1-naphthol complexes.

We have measured the intermolecular dissociation energies D 0 of supersonically cooled 1-naphthol (1NpOH) complexes with solvents S = furan, thiophene, 2,5-dimethylfuran, and tetrahydrofuran. The naphthol OH forms non-classical H-bonds with the aromatic π-electrons of furan, thiophene, and 2,5-dimethylfuran and a classical H-bond with the tetrahydrofuran O atom. Using the stimulated-emission pumping resonant two-photon ionization method, the ground-state D 0(S 0) values were bracketed as 21.8 ± 0.3 kJ/mol for furan, 26.6 ± 0.6 kJ/mol for thiophene, 36.5 ± 2.3 kJ/mol for 2,5-dimethylfuran, and 37.6 ± 1.3 kJ/mol for tetrahydrofuran. The dispersion-corrected density functional theory methods B97-D3, B3LYP-D3 (using the def2-TZVPP basis set), and ωB97X-D [using the 6-311++G(d,p) basis set] predict that the H-bonded (edge) isomers are more stable than the face isomers bound by dispersion; experimentally, we only observe edge isomers. We compare the calculated and experimental D 0 values and extend the comparison to the previously measured 1NpOH complexes with cyclopropane, benzene, water, alcohols, and cyclic ethers. The dissociation energies of the nonclassically H-bonded complexes increase roughly linearly with the average polarizability of the solvent, α ¯ (S). By contrast, the D 0 values of the classically H-bonded complexes are larger, increase more rapidly at low α ¯ (S), but saturate for large α ¯ (S). The calculated D 0(S 0) values for the cyclopropane, benzene, furan, and tetrahydrofuran complexes agree with experiment to within 1 kJ/mol and those of thiophene and 2,5-dimethylfuran are ∼3 kJ/mol smaller than experiment. The B3LYP-D3 calculated D 0 values exhibit the lowest mean absolute deviation (MAD) relative to experiment (MAD = 1.7 kJ/mol), and the B97-D3 and ωB97X-D MADs are 2.2 and 2.6 kJ/mol, respectively.

Intermolecular dissociation energies of 1-naphthol·n-alkane complexes.

Using the stimulated-emission-pumping/resonant 2-photon ionization (SEP-R2PI) method, we have determined accurate intermolecular dissociation energies D0 of supersonic jet-cooled intermolecular complexes of 1-naphthol (1NpOH) with alkanes, 1NpOH·S, with S = methane, ethane, propane, and n-butane. Experimentally, the smaller alkanes form a single minimum-energy structure, while 1-naphthol·n-butane forms three different isomers. The ground-state dissociation energies D0(S0) for the complexes with propane and n-butane (isomers A and B) were bracketed within ±0.5%, being 16.71 ± 0.08 kJ/mol for S = propane and 20.5 ± 0.1 kJ/mol for isomer A and 20.2 ± 0.1 kJ/mol for isomer B of n-butane. All 1NpOH·S complexes measured previously exhibit a clear dissociation threshold in their hot-band detected SEP-R2PI spectra, but weak SEP-R2PI bands are observed above the putative dissociation onset for the methane and ethane complexes. We attribute these bands to long-lived complexes that retain energy in rotation-type intermolecular vibrations, which couple only weakly to the dissociation coordinates. Accounting for this, we find dissociation energies of D0(S0) = 7.98 ± 0.55 kJ/mol (±7%) for S = methane and 14.5 ± 0.28 kJ/mol (±2%) for S = ethane. The D0 values increase by only 1% upon S0 → S1 excitation of 1-naphthol. The dispersion-corrected density functional theory methods B97-D3, B3LYP-D3, and ωB97X-D predict that the n-alkanes bind dispersively to the naphthalene "Face." The assignment of the complexes to Face structures is supported by the small spectral shifts of the S0 → S1 electronic origins, which range from +0.5 to -15 cm-1. Agreement with the calculated dissociation energies D0(S0) is quite uneven, the B97-D3 values agree within 5% for propane and n-butane, but differ by up to 20% for methane and ethane. The ωB97X-D method shows good agreement for methane and ethane but overestimates the D0(S0) values for the larger n-alkanes by up to 20%. The agreement of the B3LYP-D3 D0 values is intermediate between the other two methods.

Comment on "Non-linear photoelectron effect contributes to the formation of negative matrix ions in UV-MALDI".

Alonso and Zenobi (AZ) recently claimed "a comprehensive theoretical description of negative ion formation in UV-MALDI" (Phys. Chem. Chem. Phys., 2016, 18, 19574). Emphasizing photoelectrons, it is found to be unphysical in several respects, including violation of charge and mass conservation, and in the treatment of ablation, expansion and electron capture. It is not internally consistent, and ions created by the photoelectron mechanism are given artificial preference. Although AZ claimed the "first proposal for a comprehensive theoretical description of negative ion formation in UV-MALDI", the Coupled Physical and Chemical Dynamics model has successfully reproduced a number of phenomena relevant to negative ion production over many years.

Oxysterols direct immune cell migration via EBI2.

Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3ß,7α,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7α,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7α,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7α,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response.

Measuring Intermolecular Binding Energies by Laser Spectroscopy.

The ground-state dissociation energy, D0(S0), of isolated intermolecular complexes in the gas phase is a fundamental measure of the interaction strength between the molecules. We have developed a three-laser, triply resonant pump-dump-probe technique to measure dissociation energies of jet-cooled M•S complexes, where M is an aromatic chromophore and S is a closed-shell 'solvent' molecule. Stimulated emission pumping (SEP) via the S0→S1 electronic transition is used to precisely 'warm' the complex by populating high vibrational levels v" of the S0 state. If the deposited energy E(v") is less than D0(S0), the complex remains intact, and is then mass- and isomer-selectively detected by resonant two-photon ionization (R2PI) with a third (probe) laser. If the pumped level is above D0(S0), the hot complex dissociates and the probe signal disappears. Combining the fluorescence or SEP spectrum of the cold complex with the SEP breakoff of the hot complex brackets D0(S0). The UV chromophores 1-naphthol and carbazole were employed; these bind either dispersively via the aromatic rings, or form a hydrogen bond via the -OH or -NH group. Dissociation energies have been measured for dispersively bound complexes with noble gases (Ne, Kr, Ar, Xe), diatomics (N2, CO), alkanes (methane to n-butane), cycloalkanes (cyclopropane to cycloheptane), and unsaturated compounds (ethene, benzene). Hydrogen-bond dissociation energies have been measured for H2O, D2O, methanol, ethanol, ethers (oxirane, oxetane), NH3 and ND3.

Intermolecular dissociation energies of dispersively bound 1-naphthol⋠cycloalkane complexes.

Intermolecular dissociation energies D0(S0) of the supersonic jet-cooled complexes of 1-naphthol (1NpOH) with cyclopentane, cyclohexane, and cycloheptane were determined to within <0.5% using the stimulated-emission pumping resonant two-photon ionization method. The ground state D0(S0) values are bracketed as 20.23±0.07 kJ/mol for 1NpOH⋅cyclopentane, 20.34±0.04 kJ/mol for 1NpOH⋅cyclohexane, and 22.07±0.10 kJ/mol for two isomers of 1NpOH⋅cycloheptane. Upon S0→S1 excitation of the 1-naphthol chromophore, the dissociation energies of the 1NpOH⋅cycloalkane complexes increase from 0.1% to 3%. Three dispersion-corrected density functional theory (DFT) methods predict that the cycloalkane moieties are dispersively bound to the naphthol face via London-type interactions, similar to the "face" isomer of the 1-naphthol⋅cyclopropane complex [S. Maity et al., J. Chem. Phys. 145, 164304 (2016)]. The experimental and calculated D0(S0) values of the cyclohexane and cyclopentane complexes are practically identical, although the polarizability of cyclohexane is ∼20% larger than that of cyclopentane. Investigation of the calculated pairwise atomic contributions to the D2 dispersion energy reveals that this is due to subtle details of the binding geometries of the cycloalkanes relative to the 1-naphthol ring. The B97-D3 DFT method predicts dissociation energies within about ±1% of experiment, including the cyclopropane face complex. The B3LYP-D3 and ωB97X-D calculated dissociation energies are 7-9 and 13-20% higher than the experimental D0(S0) values. Without dispersion correction, all the complexes are calculated to be unbound.

Accurate dissociation energies of two isomers of the 1-naphthol⋠cyclopropane complex.

The 1-naphthol⋅cyclopropane intermolecular complex is formed in a supersonic jet and investigated by resonant two-photon ionization (R2PI) spectroscopy, UV holeburning, and stimulated emission pumping (SEP)-R2PI spectroscopy. Two very different structure types are inferred from the vibronic spectra and calculations. In the "edge" isomer, the OH group of 1-naphthol is directed towards a C-C bond of cyclopropane, the two ring planes are perpendicular. In the "face" isomer, the cyclopropane is adsorbed on one of the π-aromatic faces of the 1-naphthol moiety, the ring planes are nearly parallel. Accurate ground-state intermolecular dissociation energies D0 were measured with the SEP-R2PI technique. The D0(S0) of the edge isomer is bracketed as 15.35 ± 0.03 kJ/mol, while that of the face isomer is 16.96 ± 0.12 kJ/mol. The corresponding excited-state dissociation energies D0(S1) were evaluated using the respective electronic spectral shifts. Despite the D0(S0) difference of 1.6 kJ/mol, both isomers are observed in the jet in similar concentrations, so they must be separated by substantial potential energy barriers. Intermolecular binding energies, De, and dissociation energies, D0, calculated with correlated wave function methods and two dispersion-corrected density-functional methods are evaluated in the context of these results. The density functional calculations suggest that the face isomer is bound solely by dispersion interactions. Binding of the edge isomer is also dominated by dispersion, which makes up two thirds of the total binding energy.

DOSY NMR, X-ray Structural and Ion-Mobility Mass Spectrometric Studies on Electron-Deficient and Electron-Rich M6L4 Coordination Cages.

A novel modular approach to electron-deficient and electron-rich M6L4 cages is presented. From the same starting compound, via a minor modulation of the synthesis route, two C3-symmetric ligands L1 and L2 with different electronic properties are obtained in good yield. The trifluoro-triethynylbenzene-based ligand L1 is more electron-deficient than the well-known 2,4,6-tri(4-pyridyl)-1,3,5-triazine, while the trimethoxy-triethynylbenzene-based ligand L2 is more electron-rich than the corresponding benzene analogue. Complexation of the ligands with cis-protected square-planar [(dppp)Pt(OTf)2] or [(dppp)Pd(OTf)2] corner-complexes yields two electron-deficient (1a and 1b) and two electron-rich (2a and 2b) M6L4 cages. The single crystal X-ray diffraction study of 1a and 2a confirms the expected octahedral shape with a ca. 2000 Å(3) cavity and ca. 11 Å wide apertures. The crystallographically determined diameters of 1a and 2a are 3.7 and 3.6 nm, respectively. The hydrodynamic diameters obtained from the DOSY NMR in CDCl3:CD3OD (4:1), and diameters calculated from collision cross sections (CCS) acquired by ion-mobility mass spectrometry (IM-MS) were for all four cages similar. In solution, the cage structures have diameters between 3.3 to 3.6 nm, while in the gas phase the corresponding diameters varied between 3.4 to 3.6 nm. In addition to the structural information the relative stabilities of the Pt6L4 and Pd6L4 cages were studied in the gas phase by collision-induced dissociation (CID) experiments, and the photophysical properties of the ligands L1 and L2 and cages 1a, 1b, 2a, and 2b were studied by UV-vis and fluorescence spectroscopy.

Superchiral Pd3 L6 Coordination Complex and Its Reversible Structural Conversion into Pd3 L3 Cl6 Metallocycles.

Large, non-symmetrical, inherently chiral bispyridyl ligand L derived from natural ursodeoxycholic bile acid was used for square-planar coordination of tetravalent Pd(II) , yielding the cationic single enantiomer of superchiral coordination complex 1 Pd3 L6 containing 60 well-defined chiral centers in its flower-like structure. Complex 1 can readily be transformed by addition of chloride into a smaller enantiomerically pure cyclic trimer 2 Pd3 L3 Cl6 containing 30 chiral centers. This transformation is reversible and can be restored by the addition of silver cations. Furthermore, a mixture of two constitutional isomers of trimer, 2 and 2', and dimer, 3 and 3', can be obtained directly from L by its coordination to trans- or cis-N-pyridyl-coordinating Pd(II) . These intriguing, water-resistant, stable supramolecular assemblies have been thoroughly described by (1) H DOSY NMR, mass spectrometry, circular dichroism, molecular modelling, and drift tube ion-mobility mass spectrometry.

Evaluation of Hadamard transform atmospheric pressure ion mobility time-of-flight mass spectrometry for complex mixture analysis.

Ion mobility mass spectrometry (IMMS) has gained popularity in the analysis of complex mixtures such as those encountered in metabolomics and proteomics. However, the challenge that exists in conventional pulsed IMMS is its inherent low duty cycle. The first application of Hadamard transform (HT)-type signal coupled with atmospheric pressure IMMS to complex mixtures is presented. Performance of the prototype was assessed by the analysis of metabolite standard mixture. With 200 times increased IMS duty cycle in HT mode compared with conventional pulsed mode, the limit of detection (LOD) was decreased by ∼10 times. Evaluation for application to complex mixtures was achieved using the NIST Standard Reference Material 1950 Metabolites in Human Plasma. Approximately 180 metabolite ions were detected within 1 min with an IMS resolving power (Rp) of ∼100. Rapid chromatographic separation prior to IMMS analysis was also demonstrated for improving the response of metabolite ions in rat brain tissue extract.

Excited state dynamics in the matrix-assisted laser desorption/ionization matrix 2,4,6-trihydroxyacetophenone: evidence for triplet pooling charge separation reactions.

RATIONALE: Excited state pooling reactions are a central part of some models of ultraviolet matrix-assisted laser desorption/ionization (MALDI) mechanisms. Evidence has been found for pooling in several matrix materials, but a recent report of pure exponential fluorescence decay at MALDI-relevant laser fluences suggested that 2,4,6-trihydroxy-acetophenone (THAP) may be an example of a matrix in which pooling does not occur (Lin et al., Rapid Commun. Mass Spectrom. 2014, 28, 77). However, those data were instrumentally limited in dynamic range and signal/noise ratio, and the conclusion does not take into account several aspects of THAP excited state dynamics. METHODS: Using time-correlated single photon counting, and absorption and emission spectroscopies, the excited state dynamics of THAP are reexamined. RESULTS: Like many other aromatic ketones and acetophenone, isolated THAP molecules undergo very efficient intersystem crossing. No fluorescence is observed in dilute solution. In the solid state, efficient fluorescence reappears, but is non-exponential even at very low excitation intensity. The solvent used for sample preparation was found to have a large effect on the spectra and decay curves. Needle-like crystals seem to be correlated with reduced intersystem crossing. CONCLUSIONS: THAP solid state fluorescence is entirely due to intermolecular interactions. Activation of fluorescence, instead of quenching, is a clear indicator of delocalized excited state phenomena in THAP. Contrary to the conclusions of Lin et al., the greatly increased singlet lifetime in the solid state substantially increases the probability that pooling-type reactions are indeed involved in ionization processes. The sensitivity of fluorescence and phosphorescence on sample morphology appears to reflect changes in intermolecular interactions due to crystal packing. Pooling charge separation pathways based on known triplet-triplet ionization reactions of aromatic ketones are proposed.

MALDI mechanisms: wavelength and matrix dependence of the coupled photophysical and chemical dynamics model.

The ultraviolet wavelength and fluence dependence of MALDI ion yields using several matrices has recently been reported (Soltwisch et al., Anal. Chem., 2012, 84, 6567). These extensive data provide a test of the coupled photophysical and chemical dynamics (CPCD) model, and are used to extend the model to new matrices. The experimental phenomena are generally well reproduced by the model, particularly when transient photochemical products or exciplexes are included. While the CPCD is consistent with the data, thermal models appear to be largely incompatible with it.

Comparison of UHPLC-ESI-MS and Hadamard transform atmospheric pressure ion mobility-ESI-MS for rapid profiling of isomeric flavonoids.

Hadamard transform atmospheric pressure ion mobility-MS and rapid UHPLC-MS methods were investigated for analysis of closely related isomeric flavonoids and their glycosides using a test set of seven standards. On a time scale of a few minutes, the flavonoid aglycones were all separated by ion mobility, but not by UHPLC. The glycosides were better resolved by IMS but not completely separated by both methods. The results suggest that IMS provides sufficient resolution for separation of isomeric polyphenols such as flavonoids in high-throughput metabolomics studies.

Coupling laser ablation/desorption electrospray ionization to atmospheric pressure drift tube ion mobility spectrometry for the screening of antimalarial drug quality.

Significant developments in the field of ambient desorption/ionization mass spectrometry (MS) have led to high-throughput direct analysis and imaging capabilities. However, advances in coupling ambient ionization techniques with standalone drift tube ion mobility spectrometry (DTIMS) have been comparatively slower, despite the attractive ruggedness and simplicity of IMS. In this study, we have developed and characterized a laser ablation/desorption electrospray ionization (LADESI) DTIMS platform, and applied it to the detection of active pharmaceutical ingredients (APIs) in antimalarial tablets collected in developing countries. The overarching goal of this work was to perform an initial evaluation of LADESI DTIMS as a technique with the potential for constituting the core of a portable drug quality-testing platform. The set-up consisted of an IR laser for desorption and an electrospray ionizer for capturing the ablated plume coupled to a high-resolution monolithic resistive glass drift tube ion mobility spectrometer. For more confident API identification, tablet extracts were also investigated via electrospray IM MS to correlate LADESI DTIMS reduced mobility (K(0)) values to m/z values. Overall, it was found that the IR LADESI DTIMS platform provided distinct ion mobility spectral fingerprints that could be used to detect the presence of the expected APIs, helping to distinguish counterfeit drugs from their genuine counterparts.

What determines MALDI ion yields? A molecular dynamics study of ion loss mechanisms.

Ion recombination in matrix-assisted laser desorption/ionization (MALDI) is as important as any ion formation process in determining the quantity of ions observed but has received comparatively little attention. Molecular dynamics simulations are used here to investigate some models for recombination, including a Langevin-type model, a soft threshold model and a tunneling model. The latter was found to be superior due to its foundations in a widespread physical phenomenon, and its lack of excessive sensitivity to parameter choice. Tunneling recombination in the Marcus inverted region may be a major reason why MALDI is a viable analytical method, by allowing ion formation to exceed ion loss on the time scale of the plume expansion. Ion velocities, photoacoustic transients and pump-probe measurements might be used to investigate the role of recombination in different MALDI matrices, and to select new matrices.