Conformational Energy Differences Research Articles

Computational reexamination of the eclipsed conformation in cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3-dioxane

The conformational free energy differences, ΔG° values, for the methyl sulfide, methyl sulfoxide, methyl sulfone, tert-butyl sulfide, tert-butyl sulfoxide, and tert-butyl sulfone groups at C(5) in the 1,3-dioxane ring have been calculated at two different levels, B3LYP/6-31G(d) and B3LYP/6-311++G(d,p). There is good agreement between experimental and calculated values, particularly in the case of data obtained at the lower level of theory, B3LYP/6-31G(d). In order to get information that could help understand the nature of the effects present in the molecules of interest, the charge distribution in representative compounds was analyzed by means of the natural bond orbital (NBO) analysis. NBO calculations indicate the existence of substantial negative charges at oxygen and significant positive charge at sulfur. This observation seems to support the argument the existence of electrostatic, attractive interactions between the endocyclic oxygens and the axial sulfonyl group. From the second order perturbation theory analysis of Fock matrix, two σ C–C → σ*S–O delocalizing interactions are observed in the methyl-inside conformer of cis-2-tert-butyl-5-(methylsulfonyl)-1,3-dioxane derivative cis-7. These results are in line with anti-periplanar σ C–C → σ*S–O hyperconjugative interactions that help stabilize the methyl-inside conformation of cis-7, as previously found by 1H NMR analysis. By contrast, NBO analysis does not provide evidence for the existence of σ C–C → σ*S–O hyperconjugative interactions that might help stabilize the eclipsed tert-butyl—outside conformation previously found in the solid-state crystallographic structure of analog cis-1. Because of the threshold value of the NBO calculations, if present such syn-periplanar stereoelectronic interaction should be less than 0.5 kcal mol−1. This observation suggests that an anti-periplanar orientation of the interacting orbitals is more effective relatively to the corresponding syn-periplanar orientation.

Structural conformations and density functional study on the intramolecular charge transfer based on vibrational spectra of 2,4-dihydroxy-N′-(4-methoxybenzylidene)benzohydrazide

The NIR-FT Raman and FT-IR spectra of 2,4-dihydroxy-N′-(methoxybenzylidene) benzohydrazide (DMBBH) molecule have been recorded and analyzed. Density functional theory (DFT) calculations at the B3LYP/6-31G(d) level has been used to compute energies of different conformers of DMBBH to find out their stability, the optimized geometry of the most stable conformer and its vibrational spectrum. Information about the size, shape, charge density distribution and site of chemical reactivity of the molecules has been obtained by mapping electron density isosurface with electrostatic potential surfaces (ESP). A complete vibrational analysis has been attempted on the basis of experimental infrared and Raman spectra and calculated vibrational modes and potential energy distribution over the internal coordinates. The vibrational analysis confirm the charge transfer interaction between the phenyl rings through CNN skeleton. The broadening of the band at 1631cm−1 and the appearance of the band at 1556cm−1 strongly suggests the existence of proton equilibrium.

Conformational stability, vibrational spectra, molecular structure, NBO and HOMO–LUMO analysis of 5-nitro-2-furaldehyde oxime based on DFT calculations

The FTIR and FT-Raman spectra of 5-nitro-2-furaldehyde oxime (NFAO) have been recorded in the regions 4000–400cm−1 and 3500–50cm−1, respectively. The total energies of different conformations have been obtained from DFT (B3LYP) with 6-311++G(d,p) basis set calculations. The computational results identify the most stable conformer of NFAO as the C1 form. Utilizing the observed FTIR and FT-Raman data, a complete vibrational assignment and analysis of the fundamental modes of the compound were carried out. The optimum molecular geometry, harmonic vibrational frequencies, infrared intensities and Raman scattering activities, were calculated by density functional theory (DFT/B3LYP) method with 6-31+G(d,p) and 6-311++G(d,p) basis sets. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. A detailed interpretation of the infrared and Raman spectra of NFAO is also reported based on total energy distribution (TED). Stability of the molecule arising from hyperconjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. Besides, molecular electrostatic potential (MEP), HOMO and LUMO analysis, and several thermodynamic properties were performed by the DFT method. Mulliken’s net charges have been calculated and compared with the natural atomic charges. Ultraviolet–visible spectrum of the title molecule has also been calculated using TD-DFT method.

Assessment of density functionals on intramolecular dispersion interaction in large normal alkanes

The performance of a number of density functionals in describing intramolecular dispersion interaction has been assessed by studying the conformational energy differences between the all-gauche and all-trans conformers of large normal alkanes. The generalized energy-based fragmentation approach is applied to perform CCSD(T) or MP2 calculations for these large alkanes. The M06-2X functional is demonstrated to provide satisfactory descriptions. With an empirical dispersion correction, some functionals like wB97X and LC-wPBE can also show comparable performance as the M06-2X functional, while other functionals like PBE, TPSS and B3LYP are still not accurate enough for quantitative descriptions.

Vibrational spectra, conformations, quantum chemical calculations and spectral assignments of 1-chloro-1-silacyclohexane

The infrared spectra of 1-chloro-1-silacyclohexane have been studied as a vapour and liquid at ambient temperature and as amorphous and annealed crystalline solids at 78K. Various infrared bands present in the vapour and liquid states vanished in the crystalline state upon cooling. Raman spectra of the liquid were recorded at 293K and polarization data obtained. Additional Raman spectra were recorded at various temperatures between 293 and 163K, and intensity changes with temperature of certain Raman bands were detected. A crystalline phase was observed around 140K, leading to spectral shifts and a number of vanishing bands.The compound exists in two conformers, equatorial (e) and axial (a) in the fluid phases, but only the a-conformer was present in the crystal. The experimental results suggest that the a-conformer has 2.8kJmol−1 lower enthalpy than e in the liquid, leading to 69% of the a conformer at 293K.B3LYP calculations with various basis sets and the G3 model chemistry gave conformational energy difference ΔE (e−a) in the range 0.4–1.4kJmol−1. Infrared and Raman intensities, polarization ratios and vibrational frequencies for the e and a conformers were calculated. The fundamental wavenumbers were also derived in the anharmonic approximation in B3LYP/cc-pVTZ calculations, a relative deviation of less than 2% between the observed and calculated wave numbers for the 48 modes of the e- and a-conformers was obtained.

PDB ligand conformational energies calculated quantum-mechanically.

We present here a greatly updated version of an earlier study on the conformational energies of protein-ligand complexes in the Protein Data Bank (PDB) [Nicklaus et al. Bioorg. Med. Chem. 1995, 3, 411-428], with the goal of improving on all possible aspects such as number and selection of ligand instances, energy calculations performed, and additional analyses conducted. Starting from about 357,000 ligand instances deposited in the 2008 version of the Ligand Expo database of the experimental 3D coordinates of all small-molecule instances in the PDB, we created a "high-quality" subset of ligand instances by various filtering steps including application of crystallographic quality criteria and structural unambiguousness. Submission of 640 Gaussian 03 jobs yielded a set of about 415 successfully concluded runs. We used a stepwise optimization of internal degrees of freedom at the DFT level of theory with the B3LYP/6-31G(d) basis set and a single-point energy calculation at B3LYP/6-311++G(3df,2p) after each round of (partial) optimization to separate energy changes due to bond length stretches vs bond angle changes vs torsion changes. Even for the most "conservative" choice of all the possible conformational energies-the energy difference between the conformation in which all internal degrees of freedom except torsions have been optimized and the fully optimized conformer-significant energy values were found. The range of 0 to ~25 kcal/mol was populated quite evenly and independently of the crystallographic resolution. A smaller number of "outliers" of yet higher energies were seen only at resolutions above 1.3 Å. The energies showed some correlation with molecular size and flexibility but not with crystallographic quality metrics such as the Cruickshank diffraction-component precision index (DPI) and R(free)-R, or with the ligand instance-specific metrics such as occupancy-weighted B-factor (OWAB), real-space R factor (RSR), and real-space correlation coefficient (RSCC). We repeated these calculations with the solvent model IEFPCM, which yielded energy differences that were generally somewhat lower than the corresponding vacuum results but did not produce a qualitatively different picture. Torsional sampling around the crystal conformation at the molecular mechanics level using the MMFF94s force field typically led to an increase in energy.

Hindered rotation in a novel 1,2,4-triazinyl phenanthroline (t-phen) ligand leading to improved separation of Am3+ and Eu3+vis-à-vis 1,2,4-triazinyl bipyridine (t-bipy): a computational validation of the experimental results

A novel nitrogen donor ligand having a more pre-organized structure, 1,2,4-triazinyl phenanthroline (t-phen), is synthesized and evaluated for lanthanide–actinide separation in the present work. The extraction and selectivity for Am3+ over Eu3+ was found to be improved with t-phen as compared to the analogous 1,2,4-triazinyl bipyridine (t-bipy), which was explained by analyzing their conformational energies and energy differences between the frontier orbitals (highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO)) with the help of density functional theoretical calculations. Higher covalence in Am3+ complexes as compared to the Eu3+ complexes was indicated by more shared electrons between Am3+ and bonded ‘N’ atoms, shorter ‘Am–N’ bonds and higher overlap between the orbitals of Am3+ and ligands in the frontier orbitals of the complexes in the case of both the ligands. Natural bond order analysis also supports these observations.

GIAO/DFT calculations of relative conformer energies and 1H NMR shifts of unsaturated alcohols in benzene

Density functional theory calculations were performed on alkenols and alkynols at the PBE1PBE/6‐311 + G(d,p) level with the inclusion of solvent (benzene) effects by the integral‐equation‐formalism polarizable continuum model (IEFPCM). For the smaller molecules, conformers in which the OH group is in the vicinity of the double or triple bond are preferred, but this preference falls as the alkyl chain is lengthened. The solvent effect on the relative Gibbs energies of different conformers is irregular, and in only two cases, 3‐buten‐1‐ol and 3‐butyn‐1‐ol, is there marked levelling. Gauge‐including atomic orbital calculations, based on the PBE1PBE/6‐311 + G(d,p) geometries but using a larger basis set, cc‐pVTZ, give nuclear magnetic resonance shifts for all the protons in each conformer. Overall shifts are calculated by weighing these according to the conformer population. Calculated values are well correlated with experimental data from high‐dilution spectra in the same solvent, ranging from about 0.4 to 5.8 ppm, with a slope of 1.09 ± 0.01. Calculations on some alcohols with hetero‐atom substituents confirm that these also prefer gauche (synclinal) conformers in the gas phase, with a less marked preference in benzene. The nuclear magnetic resonance shifts, however, are calculated to be on average over 0.8 ppm higher than observed. Copyright © 2011 John Wiley & Sons, Ltd.

On the Use of Enveloping Distribution Sampling (EDS) to Compute Free Enthalpy Differences between Different Conformational States of Molecules: Application to 310-, α-, and π-Helices.

Enveloping distribution sampling (EDS) is a powerful method to compute relative free energies from simulation. So far, the EDS method has only been applied to alchemical free energy differences, i.e., between different Hamiltonians defining different systems, and not yet to obtain free energy differences between different conformations or conformational states of a system. In this article, we extend the EDS formalism such that it can be applied to compute free energy differences of different conformations and apply it to compute the relative free enthalpy ΔG of 310-, α-, and π-helices of an alanine deca-peptide in explicit water solvent. The resulting ΔG values are compared to those obtained by standard thermodynamic integration (TI) and from so-called end-state simulations. A TI simulation requires the definition of a λ-dependent pathway which in the present case is based on hydrogen bonds of the different helical conformations. The values of ⟨(∂VTI)/(∂λ)⟩λ show a sharp change for a particular range of λ values, which is indicative of an energy barrier along the pathway, which lowers the accuracy of the resulting ΔG value. In contrast, in a two-state EDS simulation, an unphysical reference-state Hamiltonian which connects the parts of conformational space that are relevant to the different end states is constructed automatically; that is, no pathway needs to be defined. In the simulation using this reference state, both helices were sampled, and many transitions between them occurred, thus ensuring the accuracy of the resulting free enthalpy difference. According to the EDS simulations, the free enthalpy differences of the π-helix and the 310-helix versus the α-helix are 5 kJ mol(-1) and 47 kJ mol(-1), respectively, for an alanine deca-peptide in explicit SPC water solvent using the GROMOS 53A6 force field. The EDS method, which is a particular form of umbrella sampling, is thus applicable to compute free energy differences between conformational states as well as between systems and has definite advantages over the traditional TI and umbrella sampling methods to compute relative free energies.

Role of conserved active site tryptophan-101 in functional activity and stability of phosphoserine aminotransferase from an enteric human parasite

Site-directed mutagenesis study was performed to elucidate the role of conserved tryptophan-101 present at the active site of phosphoserine aminotransferase from an enteric human parasite Entamoeba histolytica. Fluorescence resonance energy transfer and molecular dynamic simulation show that the indole ring of Trp101 stacks with the cofactor PLP. Loss of enzymatic activity and PLP polarization values suggest that Trp101 plays a major role in maintaining a defined PLP microenvironment essentially required for optimal enzymatic activity. Studies on W101F, W101H and W101A mutants show that only the indole ring of the conserved Trp101 forms most favorable stacking interaction with the pyridine ring of the cofactor PLP. Protein stability was compromised on substitution of Trp101 with Phe/His/Ala amino acids. A difference in conformational free energy of 1.65kcalmol(-1) was observed between WT-protein and W101A mutant.

Discovery of novel checkpoint kinase 1 inhibitors by virtual screening based on multiple crystal structures.

Incorporating receptor flexibility is considered crucial for improvement of docking-based virtual screening. With an abundance of crystallographic structures freely available, docking with multiple crystal structures is believed to be a practical approach to cope with protein flexibility. Here we describe a successful application of the docking of multiple structures to discover novel and potent Chk1 inhibitors. Forty-six Chk1 structures were first compared in single structure docking by predicting the binding mode and recovering known ligands. Combinations of different protein structures were then compared by recovery of known ligands and an optimal ensemble of Chk1 structures were selected. The chosen structures were used in the virtual screening of over 60 000 diverse compounds for Chk1 inhibitors. Six novel compounds ranked at the top of the hits list were tested experimentally, and two of these compounds inhibited Chk1 activity-the best with an IC(50) value of 9.6 μM. Further study indicated that achieving a better enrichment and identifying more diverse compounds was more likely using multiple structures than using only a single structure even when protein structures were randomly selected. Taking into account conformational energy difference did not help to improve enrichment in the top ranked list.

Conformational state‐specific free energy differences by one‐step perturbation: Protein secondary structure preferences of the GROMOS 43A1 and 53A6 force fields

The one-step free energy perturbation approach can be applied to obtain conformational state-specific free energy differences (FEDs) associated with changes in force field parameters, and thus offers the possibility to consider conformational equilibria during force field parameterization. In this work, using the alanine decapeptide in explicit water solution as a model, the α-helical and β-hairpin state-specific FEDs associated with force field changes between two widely used parameter sets of the GROMOS force field, namely, 43A1 and 53A6, were determined using one-step perturbation. The results mostly deviated by only 1 kJ mol(−1) in absolute or a few percent in relative values from thermodynamic integration results, suggesting that the convergence ranges of one-step perturbation were large enough to cover the substantial changes in nonbonded parameters between the two parameter sets. It was also found that one-step perturbation may give larger errors when the changes from the reference state include a large decrease in van der Waals radius, as indicated by the result for the β-hairpin state-specific free energy change going from 53A6 to 43A1. According to the free energy results, the α-helical state of the alanine decapeptide is destabilized by 15 kJ mol(−1), i.e., 1.5 kJ mol(−1) per residue, relative to the β-hairpin state when going from 43A1 to 53A6, in agreement with previous direct simulations in which native α-helices were often found to be unstable in simulations using 53A6, despite that the 53A6 parameters better reproduce a range of thermodynamic properties of small molecular systems. By applying one-step perturbation to analyze the effects of perturbing individual parameters, the differential stabilization of the two secondary structure states can be traced to the changes in van der Waals parameters, especially a van der Waals parameter involved in third-neighbor interactions. This study provides an example of the efficiency of one-step perturbation in force field development, reducing the computational cost by orders of magnitude.

Structures and conformations of heteroatom‐bridged calixarenes

AbstractThe structures and conformational energies of twelve MeN‐, O‐, S‐, MeP‐, CO‐bridged homocalix[4]arenes and two kinds of O‐bridged alternate hybrid‐calix[4]arenes have been calculated at the B3LYP/6‐31G* level of theory. The 1,3‐alternate or twisted‐1,3‐alternate conformations are found to be the lowest energy structures in all cases except for MeP‐bridged calix[4]pyridine and calix[4]benzene, for which the twist‐pinched cone and partial cone are the most stable conformations, respectively. The conformational energy differences calculated between the lowest energy and the next conformation are on the order of 2.0–3.0 kcal/mol, but smaller for the S‐ and MeP‐bridged compounds. Analysis of the structures and relative energies shows that the phenyl hydrogens have electrostatic attractions with the lone pairs of the heteroatoms and steric repulsions with the methyl groups on bridgehead groups. Conversely, the lone electron pair in the pyridyl compounds engage in a repulsive electrostatic interaction. The interactions of 1,3‐aromatic rings play a minor but important role in the relative stability sequence. This detailed understanding of the factors governing the conformational space of hetero calixarences can be used to design conformationally biased analogs of these interesting compounds. Copyright © 2011 John Wiley & Sons, Ltd.

Analyzing the robustness of the MM/PBSA free energy calculation method: Application to DNA conformational transitions

The ability to predict and characterize free energy differences associated with conformational equilibria or the binding of biomolecules is vital to understanding the molecular basis of many important biological functions. As biological studies focus on larger molecular complexes and properties of the genome, proteome, and interactome, the development and characterization of efficient methods for calculating free energy becomes increasingly essential. The aim of this study is to examine the robustness of the end-point free energy method termed the molecular mechanics Poisson-Boltzmann solvent accessible surface area (MM/PBSA) method. Specifically, applications of MM/PBSA to the conformational equilibria of nucleic acid (NA) systems are explored. This is achieved by comparing A to B form DNA conformational free energy differences calculated using MM/PBSA with corresponding free energy differences determined with a more rigorous and time-consuming umbrella sampling algorithm. In addition, the robustness of NA MM/PBSA calculations is also evaluated in terms of the sensitivity towards the choice of force field and the choice of solvent model used during conformational sampling. MM/PBSA calculations of the free energy difference between A-form and B-form DNA are shown to be in very close agreement with the PMF result determined using an umbrella sampling approach. Further, it is found that the MM/PBSA conformational free energy differences were also in agreement using either the CHARMM or AMBER force field. The influence of ionic strength on conformational stability was particularly insensitive to the choice of force field. Finally, it is also shown that the use of a generalized Born implicit solvent during conformational sampling results in free energy estimates that deviate slightly from those obtained using explicitly solvated MD simulations in these NA systems.

A 1H NMR and theoretical investigation of the conformations of some monosubstituted cyclobutanes

The complete analysis of the complex (1)H NMR spectra of some monosubstituted cyclobutanes was achieved to give all the (1)H chemical shifts and (n)J(HH) (n = 2, 3 and 4) coupling constants in these molecules. The substituent chemical shifts of the substituents in the cyclobutane ring differ significantly from those in acyclic systems. For example, the OH and the NH(2) groups in cyclobutanol and cyclobutylamine produce a large shielding of the hydrogens of the opposite CH(2) group of the ring compared with little effect on the comparable methylene protons of butane. These effects and the other (1)H shifts in the cyclobutanes were modelled successfully in the CHARGE program. The RMS error (calculated vs observed shifts) for the 34 (1)H shifts recorded was 0.053 ppm. The conformational equilibrium in these compounds between the axial and the equatorial conformers was obtained by comparing the observed and the calculated (4)J(HH) couplings. These couplings in cyclobutanes, in contrast to the corresponding (3)J(HH) couplings, show a pronounced orientation dependence; (4)J(eq-eq) is ca 5 Hz and (4)J(ax-ax) ca 0 Hz. The couplings in the individual conformers were calculated at the B3LYP/EPR-III level. The conformer energy differences ΔG(ax-eq) vary from 1.1 kcal mol(-1) for OH to 0.2 kcal mol(-1) for the CH(2)OH substituent. The values of the conformer energy differences are compared with the previous IR data and the corresponding theoretical values from molecular mechanics (MM) and DFT theory. Generally, good agreement is observed although both the MM and the DFT calculations deviate significantly from the observed values for some substituents.

Computing free energies of protein conformations from explicit solvent simulations

We report a fully general technique addressing a long standing challenge of calculating conformational free energy differences between various states of a polymer chain from simulations using explicit solvent force fields. The main feature of our method is a special mapping variable, a path coordinate, which continuously connects two conformations. The path variable has been designed to preserve locality in the phase space near the path endpoints. We avoid the problem of sampling the unfolded states by creating an artificial confinement “tube” in the phase space that prevents the molecule from unfolding without affecting the calculation of the desired free energy difference. We applied our technique to compute the free energy difference between two native-like conformations of the small protein Trp-cage using the CHARMM force field with explicit solvent. We verified this result by comparing it with an independent, significantly more expensive calculation. Overall, the present study suggests that the new method of computing free energy differences between polymer chain conformations is accurate and highly computationally efficient.

A Low Affinity Ground State Conformation for the Dynein Microtubule Binding Domain

Dynein interacts with microtubules through a dedicated binding domain that is dynamically controlled to achieve high or low affinity, depending on the state of nucleotide bound in a distant catalytic pocket. The active sites for microtubule binding and ATP hydrolysis communicate via conformational changes transduced through a approximately 10-nm length antiparallel coiled-coil stalk, which connects the binding domain to the roughly 300-kDa motor core. Recently, an x-ray structure of the murine cytoplasmic dynein microtubule binding domain (MTBD) in a weak affinity conformation was published, containing a covalently constrained beta(+) registry for the coiled-coil stalk segment (Carter, A. P., Garbarino, J. E., Wilson-Kubalek, E. M., Shipley, W. E., Cho, C., Milligan, R. A., Vale, R. D., and Gibbons, I. R. (2008) Science 322, 1691-1695). We here present an NMR analysis of the isolated MTBD from Dictyostelium discoideum that demonstrates the coiled-coil beta(+) registry corresponds to the low energy conformation for this functional region of dynein. Addition of sequence encoding roughly half of the coiled-coil stalk proximal to the binding tip results in a decreased affinity of the MTBD for microtubules. In contrast, addition of the complete coiled-coil sequence drives the MTBD to the conformationally unstable, high affinity binding state. These results suggest a thermodynamic coupling between conformational free energy differences in the alpha and beta(+) registries of the coiled-coil stalk that acts as a switch between high and low affinity conformations of the MTBD. A balancing of opposing conformations in the stalk and MTBD enables potentially modest long-range interactions arising from ATP binding in the motor core to induce a relaxation of the MTBD into the stable low affinity state.

Structure and conformational dynamics of oxiranecarboxaldehyde in the ground and excited electronic states

Geometrical parameters, fundamental frequencies, conformer energy differences and barriers to inversion and internal rotation of the oxiranecarboxaldehyde molecule (OXCA) in the ground S 0 and lowest excited triplet (T 1) and singlet (S 1) electronic states were obtained by means of various ab initio methods. The OXCA molecule displayed two stable conformations in the S 0 state. The electronic excitation of OXCA caused pyramidalization of the carbonyl fragment and rotation of the oxirane fragment relative to the carbonyl group. The number of stable OXCA conformations in the T 1 and S 1 states strongly depended on the basis and method of calculation and varied from three to six. One- and two-dimensional PES sections, corresponding to the rotation of the oxirane ring and (or) inversion of the carbonyl fragment, were calculated to study the conformational dynamics of OXCA in the S 0, T 1 and S 1 states. Vibrational energy levels and wave functions were obtained variationally from the PES. We found a strong coupling of the large-amplitude motions in some regions on the PES.

Quantum Chemical Study of Conformational Fingerprints in the Photoelectron Spectra and (e, 2e) Electron Momentum Distributions ofn-Hexane

The main purpose of the present work is to simulate from many-body quantum mechanical calculations the results of experimental studies of the valence electronic structure of n-hexane employing photoelectron spectroscopy (PES) and electron momentum spectroscopy (EMS). This study is based on calculations of the valence ionization spectra and spherically averaged (e, 2e) electron momentum distributions for each known conformer by means of one-particle Green's function [1p-GF] theory along with the third-order algebraic diagrammatic construction [ADC(3)] scheme and using Kohn-Sham orbitals derived from DFT calculations employing the Becke 3-parameters Lee-Yang-Parr (B3LYP) functional as approximations to Dyson orbitals. A first thermostatistical analysis of these spectra and momentum distributions employs recent estimations at the W1h level of conformational energy differences, by Gruzman et al. [J. Phys. Chem. A 2009, 113, 11974], and of correspondingly obtained conformer weights using MP2 geometrical, vibrational, and rotational data in thermostatistical calculations of partition functions beyond the level of the rigid rotor-harmonic oscillator approximation. Comparison is made with the results of a focal point analysis of these energy differences using this time B3LYP geometries and the corresponding vibrational and rotational partition functions in the thermostatistical analysis. Large differences are observed between these two thermochemical models, especially because of strong variations in the contributions of hindered rotations to relative entropies. In contrast, the individual ionization spectra or momentum profiles are almost insensitive to the employed geometry. This study confirms the great sensitivity of valence ionization bands and (e, 2e) momentum distributions on the molecular conformation and sheds further light on spectral fingerprints of through-space methylenic hyperconjugation, in both PES and EMS experiments.

A DFT-Based Theoretical Study on the Photophysics of 4-Hydroxyacridine: Single-Water-Mediated Excited State Proton Transfer

Study of intra- and intermolecular hydrogen-bonding interaction and excited state proton transfer reaction has been carried out in 4-hydroxyacridine (4-HA) and its hydrated clusters theoretically. Density functional theory [B3LYP/6-311++G(d,p)] has been exploited to calculate structural parameters and relative energies of different conformers of 4-HA and its hydrates. The substantial impact of solvent reaction field on hydrogen-bond energies, conformational equilibrium, and tautomerization reaction in aqueous medium have been realized by employing Onsager and PCM reaction field methods, and the stability of the conformers of 4-HA is found to be profusely modulated by the electrostatic influence of the solvent. A deeper insight into the nature of H-bonding in 4-HA and its hydrated clusters has been achieved under the provision of natural bond orbital and atoms in molecule analysis. Elucidation of potential energy curves for proton transfer reaction reveals that an intrinsic and two-water-molecule-assisted proton transfer (PT) reaction in 4-HA is hindered by high energy barrier in the S(1) surface, whereas single-water-assisted PT reaction is practically rendered barrierless. At the same time, the appreciably high barrier height of the ground state potential energy curve in all the cases unambiguously rules out the possibility of ground state proton transfer reaction.