Probing the specific interactions and structures of gas-phase vancomycin antibiotics with cell-wall precursor through IRMPD spectroscopy.

Biomolecular recognition of vancomycin antibiotics with its cell-wall precursor analogue Ac(2)(L)K(D)A(D)A has been investigated in the gas phase through a combined laser spectroscopy/mass spectrometry approach. The mid-IR spectra (1100-1800 cm(-1)) of these mass-selected anionic species have been recorded by means of resonant infrared multiphoton dissociation (IRMPD) spectroscopy performed with the free-electron laser CLIO. Structural assignment has been achieved through comparisons with the low-energy conformers obtained from replica-exchange molecular dynamics simulations, for which IR spectra were calculated using a hybrid quantum mechanics/semi-empirical (QM/SE) method at the DFT/B3LYP/6-31+G*/AM1 level. Comparison between deprotonated vancomycin and its non-covalently bound V + Ac(2)(L)K(D)A(D)A complex shows significant spectral shifts of the carboxylate stretches and the Amide I and Amide II modes that are satisfactorily reproduced in the structures known from the condensed phase. Both theoretical and experimental findings provide strong evidence that the native structure of the deprotonated V + Ac(2)(L)K(D)A(D)A complex is preserved in the gas phase.

Intrinsic neutral and anionic structures of glutathione.

Gas-phase intrinsic structures of intact neutral and anionic glutathione (GSH) have been determined by means of a combination of negative ion photo-electron spectroscopy and quantum chemistry calculations. The inferred structures of the neutral parents of those peptide anions are canonical (non-zwitterionic). These intrinsic structures are compared to those already known in aqueous solution or determined by crystallography in binding sites of enzymes.

Evaluation of MP2, DFT, and DFT-D methods for the prediction of infrared spectra of peptides.

The prediction accuracy of second-order Moller-Plesset theory MP2 and density functional theory DFT-(D) with and without empirical dispersion correction within the resolution of identity approximation (ri) have been investigated for the assignment of infrared spectra of gas-phase peptides. A training set of 17 conformers of phenylalanine containing capped peptides have been used to establish mode-specific local scaling factors. Inclusion of dispersion terms at the DFT level turns to significantly improve the accuracy of predicted IR spectra. At the DFT-D level, the nonhybrid generalized gradient approximation functional B97-D (TZVP basis set) provides even better results than the popular hybrid functional B3LYP (6-31+G* basis set) while reducing the computational cost by almost 1 order of magnitude. Besides, MP2 (SVP basis set) outperforms all other tested methods in terms of reliability and transferability to larger molecular systems with typical prediction errors of about 5 cm(-1).

The parent anion of the RGD tripeptide: Photoelectron spectroscopy and quantum chemistry calculations.

The gas-phase conformation of the intact (parent) unprotected RGD(-) peptide anion has been investigated using a combination of anion photoelectron spectroscopy and quantum chemistry calculations of its low-energy stable structures. The experimentally observed RGD(-) species correspond to a conformation in which the guanidinium group is protonated, the C-terminus is neutral, the aspartic acid carboxyl is deprotonated, and the anion's excess electron orbital is localized on the protonated guanidinium. This structure is reminiscent of the RGD loop, which is the peptide motif recognized by trans-membrane integrins. The parent RGD(-) radical anion was generated using a unique infrared desorption-photoemission-helium jet ion source, whose ability to produce radical anions of peptides may also have analytical mass spectrometric implications.

Experimental observation of the transition between gas-phase and aqueous solution structures for acetylcholine, nicotine, and muscarine ions.

Structural information on acetylcholine and its two agonists, nicotine, and muscarine has been obtained from the interpretation of infrared spectra recorded in the gas-phase or in low pH aqueous solutions. Simulated IR spectra have been obtained using explicit water molecules or a polarization continuum model. The conformational space of the very flexible acetylcholine ions is modified by the presence of the solvent. Distances between its pharmacophoric groups cover a lower range in hydrated species than in isolated species. A clear signature of the shift of protonation site in nicotine ions is provided by the striking change of their infrared spectrum induced by hydration. On the contrary, structures of muscarine ions are only slightly influenced by the presence of water.

Gas-phase structure of amyloid-ß (12-28) peptide investigated by infrared spectroscopy, electron capture dissociation and ion mobility mass spectrometry.

The gas-phase structures of doubly and triply protonated Amyloid-ß12-28 peptides have been investigated through the combination of ion mobility (IM), electron capture dissociation (ECD) mass spectrometry, and infrared multi-photon dissociation (IRMPD) spectroscopy together with theoretical modeling. Replica-exchange molecular dynamics simulations were conducted to explore the conformational space of these protonated peptides, from which several classes of structures were found. Among the low-lying conformers, those with predicted diffusion cross-sections consistent with the ion mobility experiment were further selected and their IR spectra simulated using a hybrid quantum mechanical/semiempirical method at the ONIOM DFT/B3LYP/6-31 g(d)/AM1 level. In ECD mass spectrometry, the c/z product ion abundance (PIA) has been analyzed for the two charge states and revealed drastic differences. For the doubly protonated species, N - Cα bond cleavage occurs only on the N and C terminal parts, while a periodic distribution of PIA is clearly observed for the triply charged peptides. These PIA distributions have been rationalized by comparison with the inverse of the distances from the protonated sites to the carbonyl oxygens for the conformations suggested from IR and IM experiments. Structural assignment for the amyloid peptide is then made possible by the combination of these three experimental techniques that provide complementary information on the possible secondary structure adopted by peptides. Although globular conformations are favored for the doubly protonated peptide, incrementing the charge state leads to a conformational transition towards extended structures with 310- and α-helix motifs.

Structural dependence of electron transfer to non-covalent polar complexes.

Electron attachment to polar molecules and their non-covalent complexes can lead to different kinds of anions which differ from their excess electron localization. Spectroscopic methods for studying anion structures are reviewed. In many cases, the neutral and anion structures are identical and can be deduced from the electron attachment properties. Examples are given for complexes containing polar solvents or building blocks of biomolecules (nucleobases, amino acid residues...).