Intrinsic structure of pentapeptide Leu-enkephalin: geometry optimization and validation by comparison of VSCF-PT2 calculations with cold ion spectroscopy.

The intrinsic structure of an opioid peptide [Ala2, Leu5]-leucine enkephalin (ALE) has been investigated using first-principles based vibrational self-consistent field (VSCF) theory and cold ion spectroscopy. IR-UV double resonance spectroscopy revealed the presence of only one highly abundant conformer of the singly protonated ALE, isolated and cryogenically cooled in the gas phase. High-level quantum mechanical calculations of electronic structures in conjunction with a systematic conformational search allowed for finding a few low-energy candidate structures. In order to identify the observed structure, we computed vibrational spectra of the candidate structures and employed the theory at the semi-empirically scaled harmonic level and at the first-principles based anharmonic VSCF levels. The best match between the calculated "anharmonic" and the measured spectra appeared, indeed, for the most stable candidate. An average of two spectra calculated with different quantum mechanical potentials is proposed for the best match with experiment. The match thus validates the calculated intrinsic structure of ALE and demonstrates the predictive power of first-principles theory for solving structures of such large molecules.

Infrared Spectrum of Toluene: Comparison of Anharmonic Isolated-Molecule Calculations and Experiments in Liquid Phase and in a Ne Matrix.

First-principles anharmonic calculations are carried out for the CH stretching vibrations of isolated toluene and compared with the experimental infrared spectra of isotopologues of toluene in a Ne matrix at 3 K and of liquid toluene at room temperature. The calculations use the vibrational self-consistent field method and the B3LYP potential surface. In general, good agreement is found between the calculations and experiments. However, the spectrum of toluene in a Ne matrix is more complicated than that predicted theoretically. This distinction is discussed in terms of matrix-site and resonance effects. Interestingly, the strongest peak in the CH stretching spectrum has similar widths in the liquid phase and in a Ne matrix, despite the very different temperatures. Implications of this observation to the broadening mechanism are discussed. Finally, our results show that the B3LYP potential offers a good description of the anharmonic CH stretching band in toluene, but a proper description of matrix-site and resonance effects remains a challenge.

Hybrid MP2/MP4 potential surfaces in VSCF calculations of IR spectra: applications for organic molecules.

This study introduces an improved hybrid MP2/MP4 ab initio potential for vibrational spectroscopy calculations which is very accurate, yet without high computational demands. The method uses harmonic vibrational calculations with the MP4(SDQ) potential to construct an improved MP2 potential by coordinate scaling. This improved MP2 potential is used for the anharmonic VSCF calculation. The method was tested spectroscopically for four molecules: butane, acetone, ethylene and glycine. Very good agreement with experiment was found. For most of the systems, the more accurate harmonic treatment considerably improved the MP2 anharmonic results.

Spectroscopy of the C-H stretching vibrational band in selected organic molecules.

The vibrational spectroscopy of C-H stretches in organic molecules is of considerable importance for the characterization of these systems and for exploration of their properties. These stretches are strongly anharmonic, and thus methods including anharmonicity have to be used. The vibrational self-consistent field (VSCF) is applied to the following organic compounds: acetone, dimethylacetylene, neopentane, toluene, ethylene, and cyclopropane. The computed spectra are compared to new experimental data, including Raman measurements of all molecules except cyclopropane and IR of acetone, neopentane, and ethylene. A high level of agreement is found for all of the molecules. The characteristic features of CH3 and CH2 groups are studied and analyzed in detail. A reliable, unambiguous assignment of vibrational modes to spectral peaks is provided. Several characteristic features of CH3 and CH2 vibrations in polyatomic molecules are clarified, providing easier assignments for different types of organic molecules.

Raman spectra of long chain hydrocarbons: anharmonic calculations, experiment and implications for imaging of biomembranes.

First-principles anharmonic vibrational calculations are carried out for the Raman spectrum of the C-H stretching bands in dodecane, and for the C-D bands in the deuterated molecule. The calculations use the Vibrational Self-Consistent Field (VSCF) algorithm. The results are compared with liquid-state experiments, after smoothing the isolated-molecule sharp-line computed spectra. Very good agreement between the computed and experimental results is found for the two systems. The combined theoretical and experimental results provide insights into the spectrum, elucidating the roles of symmetric and asymmetric CH(3) and CH(2) hydrogenic stretches. This is expected to be very useful for the interpretation of spectra of long-chain hydrocarbons. The results show that anharmonic effects on the spectrum are large. On the other hand, vibrational degeneracy effects seem to be rather modest at the resolution of the experiments. The degeneracy effects may have more pronounced manifestations in higher-resolution experiments. The results show that first-principles anharmonic vibrational calculations for hydrocarbons are feasible, in good agreement with experiment, opening the way for applications to many similar systems. The results may be useful for the analysis of CARS imaging of lipids, for which dodecane is a representative molecule. It is suggested that first-principles vibrational calculations may be useful also for CARS imaging of other systems.

L-alanyl-L-alanine conformational changes induced by pH as monitored by the Raman optical activity spectra.

Fine effects of the hydration, charge, and conformational structural changes in L-alanyl-L-alanine (Ala-Ala) dipeptide were studied with the aid of Raman and Raman optical activity (ROA) spectra. The spectra were recorded experimentally and analyzed by means of density functional computations. A (15)N and (13)C isotopically labeled analogue was synthesized and used to verify the vibrational mode assignment. Calculated shifts in vibrational frequencies for isotopically labeled molecule agreed well with the experiment. The assignment made it possible to scale computed vibrational frequencies and extract better structural information from the intensities. Solvent modeling with clusters obtained from molecular dynamics led to a qualitatively correct inhomogeneous broadening of Raman spectral lines but did not bring a convincing improvement of ROA signal when compared to a standard dielectric solvent correction. In comparison with the zwitterionic form, charged anionic and cationic dipeptides provided spectral variations that indicated different conformational behavior. Only minor backbone conformational change occurs in the cation, whereas the results indicate the presence of more anion conformers differing in the rotation of the NH(2) group and the backbone psi-angle. These findings are in agreement with previous electronic circular dichroism (ECD) and NMR studies. The results confirm the large potential of the ROA technique for the determination of final details in molecular structure and conformation.

Molecular dynamics with restrictions derived from optical spectra.

The information about molecular structure coded in the optical spectra must often be deciphered by complicated computational procedures. A combination of spectral modeling with the molecular dynamic simulations makes the process simpler, by implicit accounting for the inhomogeneous band broadening and Boltzmann averaging of many conformations. Ideally, geometries of studied systems can be deduced by a direct confrontation of such modeling with the experiment. In this work, the comparison is enhanced by restrictions to molecular dynamics propagations based on the Raman and Raman optical activity spectra. The methodology is introduced and tested on model systems comprising idealized H(2)O(2), H(2)O(3) molecules, and the alanine zwitterion. An additional gradient term based on the spectral overlap smoothed by Fourier transformation is constructed and added to the molecular energy during the molecular dynamics run. For systems with one prevalent conformation the method did allow to enrich the Boltzmann ensemble by a spectroscopically favored structure. For systems with multiconformational equilibria families preferential conformations can be selected. An alternative algorithm based on the comparison of the averaged spectra with the reference enabling iterative updates of the conformer probabilities provided even more distinct distributions in shorter times. It also accounts for multiconformer equilibria and provided realistic spectra and conformer distribution for the alanine.

Ab initio modeling of the electronic circular dichroism induced in porphyrin chromophores.

The optical activity in porphyrins can easily be induced by a chiral environment, but it is difficult to determine the underlying mechanisms purely on an experimental basis. Therefore, in this study, magnitudes of the perturbational, dipolar, and direct covalent contributions to the electronic circular dichroism (CD) are evaluated with the aid of quantum chemical computations. Electronic properties of model porphyrin chromophores are analyzed. Time-dependent density functional theory (TD DFT), particularly with the hybrid B3LYP functional, appeared suitable for estimation of the electronic excitation energies and spectral intensities. The transition dipole coupling (TDC) between chirally stacked porphyrins was determined as the most important mechanism contributing to their optical activity. This is in agreement with previous experimental observations, where chiral matrices often induce the stacking and large CD signals. About a 10 times smaller signal could be achieved by a chiral orientation of the phenyl or similar residues covalently attached to the porphyrin core. Also, this prediction is in agreement with known experiments. Perturbation models realized by a chirally arranged porphyrin and a point charge, or by a porphyrin and the methane molecule, provided the smallest CD signals. The electrically neutral methane induced similar CD magnitudes as those of the charge, but spectral shapes were different. For a complex of porphyrin and the alanine cation, a significant influence of the solvent on the resultant CD spectral shape was observed, while for the charge and methane perturbations, a negligible solvent effect was found. Detailed dependence of the induced optical activity on variations of geometrical parameters is discussed. The simulations of the induced porphyrin activity can thus bring important information about the structure and intermolecular interactions in chiral complexes.

Interpretation of synchrotron radiation circular dichroism spectra of anionic, cationic, and zwitterionic dialanine forms.

Electronic absorption and synchrotron radiation circular dichroism (SRCD) spectra of the anionic, cationic, and zwitterionic forms of L-alanyl-L-alanine (AA) in aqueous solutions were measured and interpreted by molecular dynamics (MD) and ab initio computations. Time-dependent density functional theory (TD DFT) was applied to predict the electronic excited states. The modeling enabled the assessment of the role of molecular conformation, charge, and interaction with the polar environment in the formation of the spectral shapes. Particularly, inclusion of explicit solvent molecules in the computations appeared to be imperative because of the participation of water orbitals in the amide electronic structure. Implicit dielectric continuum solvent models gave inferior results for clusters, especially at low-energy transitions. Because of the dispersion of transition energies, tens of water/AA clusters had to be averaged in order to obtain reasonable spectral shapes with a more realistic inhomogeneous broadening. The modeling explained most of the observed differences, as the anionic and zwitterionic SRCD spectra were similar and significantly different from the cationic spectrum. The greatest deviation between the experimental and theoretical curves observed for the lowest-energy negative anion signal can be explained by the limited precision of the TD DFT method, but also by the complex dynamics of the amine group. The results also indicate that differences in the experimental spectral shapes do not directly correlate with the peptide main-chain conformation. Future peptide and protein conformational studies based on circular dichroic spectroscopy can be reliable only if such effects of molecular dynamics, solvent structure, and polar solvent-solute interactions are taken into account.

Geometry and solvent dependence of the electronic spectra of the amide group and consequences for peptide circular dichroism.

The influence of geometry variations and solvent environment of N-methylacetamide on its energies and absorption intensities was systematically analyzed with the aid of the time-dependent density functional theory (TD DFT). Selective and often complicated reactions of individual electronic levels on the perturbations were found important for the resultant spectral profile. For example, the n-pi band position varied by tens of nanometers due to the C=O bond length oscillations, while it was rather unaffected by surrounding water. On the contrary, pi-pi type transition energies and intensities were broadly dispersed by the aqueous environment but exhibited a modest coordinate dependence. A simple electrostatic model used previously for absorption in the IR region (J. Chem. Phys. 2005, 122, 144501) explained these changes only partially. Additionally, electronic transfer between the solute and the solvent had to be considered for faithful modeling of the ultraviolet light absorption. The inclusion of the environment and dynamics in the modeling then provided more accurate positions, intensities, and realistic inhomogeneous widths of spectral lines. These factors were found important for absorption and circular dichroism spectra of larger peptides and proteins. This was demonstrated with a combined DFT/coupled oscillator model providing principal features observed in electronic circular dichroism spectra of standard peptide conformations.

Optical sensing system for ATP using porphyrin-alkaloid conjugates.

Tetrabrucin-porphyrin as a sensor for ATP was designed and tested; selectivity for ATP was proved in the presence of ADP and AMP.