Trinuclear Magnesium Imidazolate Borohydride Complex.

A new type of hybrid compound, combining properties of MOFs and borohydrides, was synthesized solvothermally using Mg(BH4)2 and imidazole as precursors. Material in the form of acetonitrile solvate with formula [Mg3{(Im)BH2(Im)}6(ImH)6]·CH3CN crystallizes in the space group R3̅, having the unit cell parameters a = 15.1942(2) Å and c = 28.3157(3) Å as determined by single crystal X-ray diffraction. The structure was further investigated by solid-state NMR and DFT quantum chemical calculations. The main feature of the structure, reported here for the first time, is a linear trinuclear complex, where octahedrally nitrogen-coordinated Mg2+ ions are bridged with {(Im)BH2(Im)}- units, forming inside voids of 4.6 Å in diameter between the magnesium ions. Polar intermolecular interactions hold the molecules in a dense rhombohedral stacking, where a disordered acetonitrile molecule plays a cohesive role. The compound is stable in air and upon heating to about 160 °C. Using an alternative synthesis method from an imidazole melt, an imidazole solvate with the formula [Mg3{(Im)BH2(Im)}6(ImH)6]·ImH and a very similar crystal structure to acetonitrile solvate was prepared. It is stable up to 220 °C. Upon further heating, it transformed into a layered structure with the formula Mg(Im3BH)2, space group P3̅1c, and unit cell parameters a = 8.7338(9) Å and c = 17.621(2) Å determined by synchrotron powder diffraction. Besides its structural novelty, two types of potentially reactive hydrogens, bonded to boron and nitrogen in the same molecule, make the material highly interesting for future investigations in the fields of energy storage applications.

Why Monoamine Oxidase B Preferably Metabolizes N-Methylhistamine over Histamine: Evidence from the Multiscale Simulation of the Rate-Limiting Step.

Histamine levels in the human brain are controlled by rather peculiar metabolic pathways. In the first step, histamine is enzymatically methylated at its imidazole Nτ atom, and the produced N-methylhistamine undergoes an oxidative deamination catalyzed by monoamine oxidase B (MAO-B), as is common with other monoaminergic neurotransmitters and neuromodulators of the central nervous system. The fact that histamine requires such a conversion prior to oxidative deamination is intriguing since MAO-B is known to be relatively promiscuous towards monoaminergic substrates; its in-vitro oxidation of N-methylhistamine is about 10 times faster than that for histamine, yet this rather subtle difference appears to be governing the decomposition pathway. This work clarifies the MAO-B selectivity toward histamine and N-methylhistamine by multiscale simulations of the rate-limiting hydride abstraction step for both compounds in the gas phase, in aqueous solution, and in the enzyme, using the established empirical valence bond methodology, assisted by gas-phase density functional theory (DFT) calculations. The computed barriers are in very good agreement with experimental kinetic data, especially for relative trends among systems, thereby reproducing the observed MAO-B selectivity. Simulations clearly demonstrate that solvation effects govern the reactivity, both in aqueous solution as well as in the enzyme although with an opposing effect on the free energy barrier. In the aqueous solution, the transition-state structure involving histamine is better solvated than its methylated analog, leading to a lower barrier for histamine oxidation. In the enzyme, the higher hydrophobicity of N-methylhistamine results in a decreased number of water molecules at the active side, leading to decreased dielectric shielding of the preorganized catalytic electrostatic environment provided by the enzyme. This renders the catalytic environment more efficient for N-methylhistamine, giving rise to a lower barrier relative to histamine. In addition, the transition state involving N-methylhistamine appears to be stabilized by the surrounding nonpolar residues to a larger extent than with unsubstituted histamine, contributing to a lower barrier with the former.

Strong Hydrogen Bonds in Acetylenedicarboxylic Acid Dihydrate.

Acetylenedicarboxylic acid dihydrate (ADAD) represents a complex with strong hydrogen bonding between the carboxylic OH and the water molecule. An X-ray re-examination of the ADAD crystal structure confirms the O…O distance of the short hydrogen bonds, and clearly shows different bond lengths between the two oxygen atoms with respect to the carbon atom in the carboxyl group, indicating a neutral structure for the complex. The neutral structure was also confirmed by vibrational spectroscopy, as no proton transfer was observed. The diffraction studies also revealed two polymorph modifications: room temperature (α) and low temperature (ß), with a phase transition at approximately 4.9 °C. The calculated vibrational spectra are in satisfactory agreement with the experimental spectra. A comparison of the structure and the vibrational spectra between the ADAD and the oxalic acid dihydrate reveals some interesting details. The crystal structures of both crystal hydrates are almost identical; only the O…O distances of the strongest hydrogen bonds differ by 0.08 Å. Although it was expected that a larger O…O spacing in the ADAD crystal may significantly change the infrared and Raman spectra, especially for the frequency and the shape of the acidic OH stretching vibration, both the shape and frequency are almost identical, with all subpeaks topped on the broad OH stretching vibration. The O…O distance dependent are only in- and out-of-plane OH deformations modes. The presence of polarons due to the ionized defects was not observed in the vibrational spectra of ADAD. Therefore, the origin of the broad OH band shape was explained in a similar way to the acid dimers. The anharmonicity of a potential enhances the coupling of the OH stretching with the low-frequency hydrogen bond stretching, which, in addition to the Fermi resonance, structures the band shape of the OH stretching. The fine structure found as a superposition of a broad OH stretching is attributed to Davydov coupling.

An electrostatic duel: subtle differences in the catalytic performance of monoamine oxidase A and B isoenzymes elucidated at the residue level using quantum computations.

The origin of the immense catalytic power of enzymes remains one of the biggest unresolved questions in biochemistry, with electrostatics being one of the main contenders. Herein, we report results that not only confirm that electrostatics is the driving force behind enzyme catalysis, but also that it is capable of tuning subtle differences in the catalytic performance between structurally similar enzymes, as demonstrated using the example of isoenzymes, monoamine oxidases A and B. Using our own computationally efficient multiscale model [A. Prah, et al., ACS Catal., 2019, 9, 1231] we analyzed the rate-limiting step of the reaction between phenylethylamine and both isoenzymes and deduced that the electrostatic environment provided by isoenzyme B has a perceivably higher catalytic influence on all the considered parameters of the reaction (energy barrier, charge transfer, dipole moment, and HOMO-LUMO gap). This is in full agreement with the available experimental kinetic data and with our own simulations of the reaction in question. In-depth analysis of individual amino acid contributions of both isoenzymes to the barrier (based on the interaction between the electric field provided by the enzyme and the dipole moment of the reacting moiety) shows that the majority of the difference between the isoenzymes can be attributed to a small number of sizable differences between the aligned amino acid pairs, whereas in most of the pairs the difference in contribution to the barrier is vanishingly small. These results suggest that electrostatics largely controls the substrate selectivity of enzymes and validates our approach as being capable of discerning fine nuances in the selectivity of structurally related isoenzymes.

Nuclear quadrupole resonance supported by periodic quantum calculations: a sensitive tool for precise structural characterization of short hydrogen bonds.

Systems with short hydrogen bonds (H-bonds) are notoriously difficult to describe even using cutting edge experimental techniques supported by advanced computational protocols. One of the most challenging issues is the highly dislocated H-bonded proton, which is typically smeared over a large area, featuring complex dynamics governed by pronounced nuclear quantum effects. Thus, in combination with experimental results, these systems offer a rich platform for the benchmarking of various computational approaches and methods. Herein, we present a methodology combining experimental and computational assessment of H-bond observables probed by the nuclear quadrupole resonance technique. Focusing on the case of picolinic acid N-oxide featuring one of the shortest known hydrogen bonds (ROO ∼ 2.425 Å), we compare the predictions of nuclear quadrupole coupling constants (NQCCs) for a series of computational models differing in fine structural details of the H-bond. By comparing the computed 14N and 17O NQCCs with the measured ones and by analyzing the sensitivity of NQCCs to H-bond geometry variations, we demonstrate that NQCCs represent a very sensitive probe for H-bond geometry, particularly the proton location, thereby offering, in conjunction with computations, an accurate and reliable tool for the fine structural characterization of short H-bonds. Importantly, the present methodology is a good compromise between accuracy and computational cost.

Nuclear quantum effects in enzymatic reactions: simulation of the kinetic isotope effect of phenylethylamine oxidation catalyzed by monoamine oxidase A.

The kinetic isotope effect (KIE) is arguably the most established experimental observable reflecting nuclear quantum effects in enzymatic reactions. The role of nuclear quantum effects in enzymes is rather intriguing and has long been a source of profound investigations. Herein, we present a computational study of monoamine oxidase A (MAO A) enzyme and its substrate phenylethylamine, focusing on the impact of nuclear quantum effects on the reaction free energy barrier. Two distinct schemes of quantization of nuclear motion were used, one being the established Quantum Classical Path (QCP) approach, and the other our own code for quantum treatment along the selected nuclear coordinate (hydrogen transfer coordinate) which reasonably mimics the reaction coordinate. In excellent agreement with the experimental value of 8.5 ± 0.3, H/D KIE was computed to 8.66, corresponding to the D-H barrier difference of 1.28 kcal mol-1. The magnitude of KIE implies that nuclear quantum effects probably have only a minor role in the reaction, which is in accordance with the features of potentials computed along the reaction coordinate and with the pertinent energy levels and wavefunctions. The computed H/D KIE for the same reaction in aqueous solution and in the gas phase was fairly similar to the one in the enzyme, suggesting that the role of tunneling in the catalytic function of MAO A is insignificant. The agreement between the computed and observed KIE supported by analysis of nuclear quantum effects implicitly validates the assumed hydride transfer reaction mechanism.

Hydride Abstraction as the Rate-Limiting Step of the Irreversible Inhibition of Monoamine Oxidase B by Rasagiline and Selegiline: A Computational Empirical Valence Bond Study.

Monoamine oxidases (MAOs) catalyze the degradation of a very broad range of biogenic and dietary amines including many neurotransmitters in the brain, whose imbalance is extensively linked with the biochemical pathology of various neurological disorders, and are, accordingly, used as primary pharmacological targets to treat these debilitating cognitive diseases. Still, despite this practical significance, the precise molecular mechanism underlying the irreversible MAO inhibition with clinically used propargylamine inhibitors rasagiline and selegiline is still not unambiguously determined, which hinders the rational design of improved inhibitors devoid of side effects current drugs are experiencing. To address this challenge, we present empirical valence bond QM/MM simulations of the rate-limiting step of the MAO inhibition involving the hydride anion transfer from the inhibitor α-carbon onto the N5 atom of the flavin adenin dinucleotide (FAD) cofactor. The proposed mechanism is strongly supported by the obtained free energy profiles, which confirm a higher reactivity of selegiline over rasagiline, while the calculated difference in the activation Gibbs energies of ΔΔG‡ = 3.1 kcal mol-1 is found to be in very good agreement with that from the measured literature kinact values that predict a 1.7 kcal mol-1 higher selegiline reactivity. Given the similarity with the hydride transfer mechanism during the MAO catalytic activity, these results verify that both rasagiline and selegiline are mechanism-based irreversible inhibitors and offer guidelines in designing new and improved inhibitors, which are all clinically employed in treating a variety of neuropsychiatric and neurodegenerative conditions.

Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine.

Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α-CH2 group to the N5 atom of the flavin cofactor moiety. In this work, we focus on MAO A-catalyzed benzylamine decomposition in order to elucidate nuclear quantum effects through the calculation of the hydrogen/deuterium (H/D) kinetic isotope effect. The rate-limiting step of the reaction was simulated using a multiscale approach at the empirical valence bond (EVB) level. We applied path integral quantization using the quantum classical path method (QCP) for the substrate benzylamine as well as the MAO cofactor flavin adenine dinucleotide. The calculated H/D kinetic isotope effect of 6.5 ± 1.4 is in reasonable agreement with the available experimental values.

Why does the Y326I mutant of monoamine oxidase B decompose an endogenous amphetamine at a slower rate than the wild type enzyme? Reaction step elucidated by multiscale molecular simulations.

This work investigates the Y326I point mutation effect on the kinetics of oxidative deamination of phenylethylamine (PEA) catalyzed by the monoamine oxidase B (MAO B) enzyme. PEA is a neuromodulator capable of affecting the plasticity of the brain and is responsible for the mood enhancing effect caused by physical exercise. Due to a similar functionality, PEA is often regarded as an endogenous amphetamine. The rate limiting step of the deamination was simulated at the multiscale level, employing the Empirical Valence Bond approach for the quantum treatment of the involved valence states, whereas the environment (solvated protein) was represented with a classical force field. A comparison of the reaction free energy profiles delivered by simulation of the reaction in the wild type MAO B and its Y326I mutant yields an increase in the barrier by 1.06 kcal mol-1 upon mutation, corresponding to a roughly 6-fold decrease in the reaction rate. This is in excellent agreement with the experimental kinetic studies. Inspection of simulation trajectories reveals possible sources of the point mutation effect, namely vanishing favorable electrostatic interactions between PEA and a Tyr326 side chain and an increased amount of water molecules at the active site due to the replacement of tyrosine by a less spacious isoleucine residue, thereby increasing the dielectric shielding of the catalytic environment provided by the enzyme.

How fast monoamine oxidases decompose adrenaline? Kinetics of isoenzymes A and B evaluated by empirical valence bond simulation.

This work scrutinizes kinetics of decomposition of adrenaline catalyzed by monoamine oxidase (MAO) A and B enzymes, a process controlling the levels of adrenaline in the central nervous system and other tissues. Experimental kinetic data for MAO A and B catalyzed decomposition of adrenaline are reported only in the form of the maximum reaction rate. Therefore, we estimated the experimental free energy barriers form the kinetic data of closely related systems using regression method, as was done in our previous study. By using multiscale simulation on the Empirical Valence Bond (EVB) level, we studied the chemical reactivity of the MAO A catalyzed decomposition of adrenaline and we obtained a value of activation free energy of 17.3 ± 0.4 kcal/mol. The corresponding value for MAO B is 15.7 ± 0.7 kcal/mol. Both values are in good agreement with the estimated experimental barriers of 16.6 and 16.0 kcal/mol for MAO A and MAO B, respectively. The fact that we reproduced the kinetic data and preferential catalytic effect of MAO B over MAO A gives additional support to the validity of the proposed hydride transfer mechanism. Furthermore, we demonstrate that adrenaline is preferably involved in the reaction in a neutral rather than in a protonated form due to considerably higher barriers computed for the protonated adrenaline substrate. The results are discussed in the context of chemical mechanism of MAO enzymes and possible applications of multiscale simulation to rationalize the effects of MAO activity on adrenaline level.

Pressure-driven phase transition mechanisms revealed by quantum chemistry: l-serine polymorphs.

The present study delivers a computational approach for the understanding of the mechanism of phase transitions between polymorphs of small organic molecules. By using state of the art periodic DFT calculations augmented with dispersion corrections and an external stress tensor together with gas-phase cluster calculations, we thoroughly explained the reversible phase transitions of three polymorphs of the model system, namely crystalline l-serine in the pressure range up to 8 GPa. This study has shown that at the macroscopic level the main driving force of the phase transitions is the decrease in the volume of the crystal unit cell, which contributes to the enthalpy difference between the two forms, but not to the difference in their internal crystal energies. At the microscopic level we suggest that hydrogen bond overstrain leads to a martensitic-like, cooperative, displacive phase transition with substantial experimental hysteresis, while no such overstrain was found for the "normal type", atom per atom, reconstructive phase transition. The predicted pressures for the phase transitions deducted by the minimum enthalpy criterion are in reasonable agreement with the observed ones. By delivering unambiguous explanations not provided by previous studies and probably not accessible to experiment, this work demonstrates the predictive and explanatory power of quantum chemistry, confirming its indispensable role in structural studies.

Insights into enzyme point mutation effect by molecular simulation: phenylethylamine oxidation catalyzed by monoamine oxidase A.

The I335Y point mutation effect on the kinetics of phenylethylamine decomposition catalyzed by monoamine oxidase A was elucidated by means of molecular simulation. The established empirical valence bond methodology was used in conjunction with the free energy perturbation sampling technique and a classical force field representing the state of reactants and products. The methodology allows for the simulation of chemical reactions, in the present case the breaking of the α-C-H bond in a phenylethylamine substrate and the subsequent hydrogen transfer to the flavin cofactor, resulting in the formation of the N-H bond on flavin. The empirical parameters were calibrated against the experimental data for the simulated reaction in a wild type protein and then used for the calculation of the reaction free energy profile in the I335Y mutant. In very good agreement with the measured kinetic data, mutation increases the free energy barrier for the rate limiting step by slightly more than 1 kcal mol(-1) and consequently decreases the rate constant by about an order of magnitude. The magnitude of the computed effect slightly varies with simulation settings, but always remains in reasonable agreement with the experiment. Analysis of trajectories reveals a major change in the interaction between phenyl rings of the substrate and the neighboring Phe352 residue upon the I335Y mutation due to the increased local polarity, leading to an attenuated quadrupole interaction between the rings and destabilization of the transition state. Additionally, the increased local polarity in the mutant allows for a larger number of water molecules to be present near the active site, effectively shielding the catalytic effect of the enzyme and contributing to the increased barrier.

Isoenergetic Polymorphism: The Puzzle of Tolazamide as a Case Study.

In the present case study of tolazamide we illustrate how many seemingly contradictory results that have been obtained from experimental observations and theoretical calculations can finally start forming a consistent picture: a "puzzle put together". For many years, tolazamide was considered to have no polymorphs. This made this drug substance unique among the large family of sulfonylureas, which was known to be significantly more prone to polymorphism than many other organic compounds. The present work employs a broad and in-depth analysis that includes the use of optical microscopy, single-crystal and powder X-ray diffraction, IR and Raman spectroscopies, DSC, semiempirical PIXEL calculations and DFT of three polymorphs of tolazamide. This case study shows how the polymorphs of a molecular crystal can be overlooked even if discovered serendipitously on one of numerous crystallizations, and how very different molecular packings can be practically isoenergetic but still crystallize quite selectively and transform one into another irreversibly upon heating.

Nitranilic acid hexahydrate, a novel benchmark system of the Zundel cation in an intrinsically asymmetric environment: spectroscopic features and hydrogen bond dynamics characterised by experimental and theoretical methods.

Nitranilic acid (2,5-dihydroxy-3,6-dinitro-2,5-cyclohexadiene-1,4-dione) as a strong dibasic acid in acidic aqueous media creates the Zundel cation, H5O2(+). The structural unit in a crystal comprises (H5O2)2(+) (2,5-dihydroxy-3,6-dinitro-1,4-benzoquinonate)(2-) dihydrate where the Zundel cation reveals no symmetry, being an ideal case for studying proton dynamics and its stability. The Zundel cation and proton transfer dynamics are studied by variable-temperature X-ray diffraction, IR and solid-state NMR spectroscopy, and various quantum chemical methods, including periodic DFT calculations, ab initio molecular dynamics simulation, and quantization of nuclear motion along three fully coupled internal coordinates. The Zundel cation features a short H-bond with the O···O distance of 2.433(2) Å with an asymmetric placement of hydrogen. The proton potential is of a single well type and, due to the non-symmetric surroundings, of asymmetric shape. The formation of the Zundel cation is facilitated by the electronegative NO2 groups. The employed spectroscopic techniques supported by calculations confirm the presence of a short H-bond with a complex proton dynamics.

Oxidation of Flavin by Molecular Oxygen: Computational Insights into a Possible Radical Mechanism.

As a highly electrophilic moiety capable of oxidizing a variety of small organic molecules and biomolecules, flavin is an important prosthetic group in many enzymes. Upon oxidation of the substrate, flavin is converted into its reduced (dihydrogenated) form. The catalytic cycle is completed through oxidation back to the oxidized form, thus restoring the enzyme's oxidizing capability. While it has been firmly established that oxidation of the reduced form of flavin is cast by molecular oxygen, yielding oxidized flavin and hydrogen peroxide, the mechanism of this process is still poorly understood. Herein, we investigate the radical mechanism, which is one of the possible reaction mechanisms, by quantum chemical calculations. Because molecular oxygen exists as a triplet in its electronic ground state, whereas the products are singlets, the reaction is accompanied by hopping between electronic surfaces. We find that the rate-limiting factor of flavin oxidation is likely associated with the change in the spin state of the system. By considering several possible reactions involving flavin and its derivatives in the radical form and by examining the corresponding parts of the potential energy surface in various spin states, we estimate the effective barrier of the kinetically and thermodynamically preferred variant of flavin oxidation to be about 15 kcal/mol in the gas phase and about 7 kcal/mol in a polar (aqueous) environment. This is in agreement with kinetic studies of the corresponding monoamine oxidase enzymes, confirming the radical mechanism as a viable option for flavin regeneration in enzymes.

Methyl dynamics flattens barrier to proton transfer in crystalline tetraacetylethane.

We analyze the interplay between proton transfer in the hydrogen-bond bridge, O···H···O, and lattice dynamics in the model system tetraacetylethane (TAE) (CH(3)CO)(2)CH═CH(COCH(3))(2) using density functional theory. Lattice dynamics calculations and molecular dynamics simulations are validated against neutron scattering data. Hindrance to the cooperative reorientation of neighboring methyl groups at low temperatures gives a preferred O atom for the bridging proton. The amplitude of methyl torsions becomes larger with increasing temperature, so that the free-energy minimum for the proton becomes flat over 0.2 Å. For the isolated molecule, however, we show an almost temperature-independent symmetric double-well potential persists. This difference arises from the much higher barriers to methyl torsion in the crystal that make the region of torsional phase space that is most crucial for symmetrization poorly accessible. Consequently, the proton-transfer potential remains asymmetric though flat at the base, even at room temperature in the solid.

Brunner syndrome caused by point mutation explained by multiscale simulation of enzyme reaction.

Brunner syndrome is a disorder characterized by intellectual disability and impulsive, aggressive behavior associated with deficient function of the monoamine oxidase A (MAO-A) enzyme. These symptoms (along with particularly high serotonin levels) have been reported in patients with two missense variants in MAO-A (p.R45W and p.E446K). Herein, we report molecular simulations of the rate-limiting step of MAO-A-catalyzed serotonin degradation for these variants. We found that the R45W mutation causes a 6000-fold slowdown of enzymatic function, whereas the E446K mutation causes a 450-fold reduction of serotonin degradation rate, both of which are practically equivalent to a gene knockout. In addition, we thoroughly compared the influence of enzyme electrostatics on the catalytic function of both the wild type MAO-A and the p.R45W variant relative to the wild type enzyme, revealing that the mutation represents a significant electrostatic perturbation that contributes to the barrier increase. Understanding genetic disorders is closely linked to understanding the associated chemical mechanisms, and our research represents a novel attempt to bridge the gap between clinical genetics and the underlying chemical physics.

A partial proton transfer in hydrogen bond O-H···O in crystals of anhydrous potassium and rubidium complex chloranilates.

Hydrogen bonding and proton transfer in the solid state are studied on the crystals of isostructural anhydrous potassium and rubidium complex chloranilates by variable-temperature single crystal X-ray diffraction, solid state (1)H NMR and IR spectroscopies, and periodic DFT calculations of equilibrium geometries, proton potentials, and NMR chemical shifts. Their crystal structures reveal neutral molecules of chloranilic acid and its dianions connected into a chain by O-H···O hydrogen bond. A strong hydrogen bond with a large-amplitude movement of the proton with NMR shift of 13-17 ppm and a broad continuum in IR spectra between 1000 and 500 cm(-1) were observed. Periodic DFT calculations suggest that proton transfer is energetically more favorable if it occurs within a single pair of chloranilate dianion and chloranilic acid molecule but not continuously along the chains of long periodicity. The calculated chemical shifts confirm the assumption that the weak resonance signals observed at lower magnetic fields pertain to the case when the proton migrates to the acceptor side of the hydrogen bond. The detected situation can be described by a partial proton transfer.

A highly accurate, analytic potential energy surface of the hydrogendifluoride anion in the gas phase.

We calculated the full three-dimensional potential energy surface (PES) of an isolated hydrogendifluoride anion (FHF-) in the electronic ground state at a very accurate Coupled Cluster approach and large correlation-consistent valence triple-zeta basis set [CCSD(T)/aug-cc-pVTZ]. The PES was evaluated at more than 30.000 points corresponding to different geometries of the system. Analytical form of the PES was expressed in an internal coordinate set which included the F...F separation (internal coordinate R) and the longitudinal and transversal projection (internal coordinates x and y) of the proton position on the F...F line. For each constant value of x a two-dimensional fit along y and R was performed by using displaced Gaussian functions. The fitted parameters of Gaussians were then spline-interpolated along x to get the final analytical form of the three-dimensional PES. The maximum fitting error was less than 0.01 kcal/mol in the lowest 20 kcal/mol region of the PES, yielding an accurate and conveniently formulated surface which can be readily used for advanced calculations, including fully coupled anharmonic vibrational analysis and quantum dynamics simulation.

The very short hydrogen bond in the pyridine N-oxide - trichloroacetic Acid complex: an inelastic neutron scattering and computational study.

We have investigated the dynamics of the very short hydrogen bond (RO...O = 2.430 Å) of the pyridine N-oxide trichloroacetic acid complex in the solid state by combining vibrational spectroscopy using inelastic neutron scattering with extensive computational studies and analysis of the vibrational spectra. The Density Functional Theory (DFT) computational models used ranged from the isolated gas phase cluster to three approaches with periodic boundary conditions, namely CRYSTAL, CPMD and VASP, all of which, however calculate frequencies in the harmonic approximation. While all but the gas phase calculation yield structural parameters for the hydrogen bond in reasonable agreement with experiment, only the periodic VASP and CPMD approaches resulted in INS spectra (calculated with the program a-climax) that adequately reproduced some of the key features of the experimental spectrum related to the in-plane and out-of-plane bending modes of the H-bond. No clear indication was found either in experiment or computational studies for OH stretching. More sophisticated and time-consuming calculations are therefore indicated to elaborate on the hydrogen bond dynamics including molecular dynamics simulations or the use of quantum dynamics on multidimensional potential energy surfaces.