Functional expression of a proton-coupled organic cation (H+/OC) antiporter in human brain capillary endothelial cell line hCMEC/D3, a human blood-brain barrier model.

Background: Knowledge of the molecular basis and transport function of the human blood-brain barrier (BBB) is important for not only understanding human cerebral physiology, but also development of new central nervous system (CNS)-acting drugs. However, few studies have been done using human brain capillary endothelial cells, because human brain materials are difficult to obtain. The purpose of this study is to clarify the functional expression of a proton-coupled organic cation (H+/OC) antiporter in human brain capillary endothelial cell line hCMEC/D3, which has been recently developed as an in vitro human BBB model.

Infrared study of the bacterial autoinducer N-hexanoyl-homoserine lactone (C6-HSL) in the gas-phase, water, and octanol solutions.

The N-hexanoyl-homoserine lactone (C6-HSL) molecule has been investigated by means of infrared multiphoton dissociation (IRMPD) and Fourier-transform infrared spectroscopy (FT-IR) under different conditions in an attempt to mimic biological situations encountered in communication between bacteria for quorum sensing. The protonated molecular ion was studied in the gas-phase that corresponds to a solvent-free situation somewhat analogous to that encountered in the receptor. The simulation of the IRMPD spectrum of the isolated ion was then conducted by means of quantum chemistry calculations in vacuum.

Slow photoelectron spectroscopy of δ-valerolactam and its dimer.

We studied the single-photon ionization of gas-phase δ-valerolactam (piperidin-2-one) and of its dimer using vacuum-ultraviolet (VUV) synchrotron radiation coupled to a velocity map imaging electron/ion coincidence spectrometer. The slow photoelectron spectrum (SPES) of the monomer is dominated by the vibrational transitions to the ͠X state. Moreover, several weaker and complex bands are observed, corresponding to the population of the vibrational bands (pure or combination) of the electronically excited states of the cation arising from their mutual vibronic interactions.

Proton transfer from the inactive gas-phase nicotine structure to the bioactive aqueous-phase structure.

The role of water in the structural change of nicotine from its inactive form in the gas phase to its bioactive form in aqueous solution has been investigated by two complementary theoretical approaches, i.e., geometry optimizations and molecular dynamics.

Negative ion photoelectron spectroscopy of the copper-aspartic acid anion and its hydrated complexes.

Negative ions of copper-aspartic acid Cu(Asp)(-) and its hydrated complexes have been produced in the gas phase and studied by anion photoelectron spectroscopy. The vertical detachment energies (VDE) of Cu(Asp)(-) and Cu(Asp)(-)(H(2)O)(1,2) were determined to be 1.6, 1.

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.

Photoionization of 2-pyridone and 2-hydroxypyridine.

We studied the photoionization of 2-pyridone and its tautomer, 2-hydroxypyridine by means of VUV synchrotron radiation coupled to a velocity map imaging electron/ion coincidence spectrometer. The photoionization efficiency (PIE) spectrum is composed of steps. The state energies of the [2-pyridone](+) cation in the X[combining tilde] ground and A excited electronic states, as well as of the [2-hydroxypyridine](+) cation in the electronic ground state, are determined.

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 the ONIOM method for interpretation of infrared spectra of gas-phase molecules of biological interest.

The prediction accuracy of the ONIOM method for the interpretation of infrared spectra of gas-phase molecules of biological interest has been investigated. With the use of experimental results concerning amino acids, small peptides, and sugars taken from the literature, mode-specific local scaling factors have been determined for different high-layer/low-layer couples. A significant improvement is noticed when using local scaling factors with respect to global factors.

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.

Transferable specific scaling factors for interpretation of infrared spectra of biomolecules from density functional theory.

A set of transferable local scaling factors is established for assignment of infrared spectra of molecular systems of biological interest experimentally recorded under gas-phase conditions. Each scaling factor is specific for an experimentally observable vibrational mode chosen among those bringing significant structural information. Those factors are provided for harmonic calculations at the DFT B3LYP and DFT B3PW91 levels respectively with 7 and 2 different basis sets.

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.

Resonant infrared multiphoton dissociation spectroscopy of gas-phase protonated peptides. Experiments and Car-Parrinello dynamics at 300 K.

The gas-phase structures of protonated peptides are studied by means of resonant infrared multiphoton dissociation spectroscopy (R-IRMPD) performed with a free electron laser. The peptide structures and protonation sites are obtained through comparison between experimental IR spectra and their prediction from quantum chemistry calculations. Two different analyses are conducted.

Ab initio molecular dynamics of protonated dialanine and comparison to infrared multiphoton dissociation experiments.

Finite temperature Car-Parrinello molecular dynamics simulations are performed for the protonated dialanine peptide in vacuo, in relation to infrared multiphoton dissociation experiments. The simulations emphasize the flexibility of the different torsional angles at room temperature and the dynamical exchange between different conformers which were previously identified as stable at 0 K. A proton transfer occurring spontaneously at the N-terminal side is also observed and characterized.

Control of bond-cleaving reactions of free protonated tryptophan ion by femtosecond laser pulses.

The excited-state dynamics of protonated tryptophan ions is investigated by photoinduced fragmentation in the gas phase. In contrast to the neutral molecule that decays on the nanosecond time scale, the protonated species exhibits an ultrafast decay with two time constants of about 400 fs and 15 ps. In addition, after UV excitation by a pump photon at 266 nm, specific photofragments, and in particular the NH3-loss channel, can be enhanced by the absorption of a probe photon at 800 nm.

Photoinduced processes in protonated tryptamine.

The electronic excited state dynamics of protonated tryptamine ions generated by an electrospray source have been studied by means of photoinduced dissociation technique on the femtosecond time scale. The result is that the initially excited state decays very quickly within 250 fs. The photoinduced dissociation channels observed can be sorted in two groups of fragments coming from two competing primary processes on the singlet electronic surface.

Ultrafast deactivation mechanisms of protonated aromatic amino acids following UV excitation.

Deactivation pathways of electronically excited states have been investigated in three protonated aromatic amino acids: tryptophan (Trp), tyrosine (Tyr) and phenylalanine (Phe). The protonated amino acids were generated by electrospray and excited with a 266 nm femtosecond laser, the subsequent decay of the excited states being monitored through fragmentation of the ions induced and/or enhanced by another femtosecond pulse at 800 nm. The excited state of TrpH+ decays in 380 fs and gives rise to two channels: hydrogen atom dissociation or internal conversion (IC).

Long-range electron binding to quadrupolar molecules.

An excess electron can be bound to a molecule in a very diffuse orbital as a result of the long-range contributions of the molecular electrostatic field. Following a systematic search, we report experimental evidence that quadrupole binding occurs for the trans-succinonitrile molecule (EA=20+/-2 meV), while the gauche-succinonitrile conformer supports a dipole-bound anion state (EA=108+/-10 meV). Theoretical calculations at the DFT/B3LYP level support these interpretations and give electron affinities of 20 and 138 meV, respectively.