Gas-phase Potential Energy Surface Research Articles

How Solvation Alters the Thermodynamics of Asymmetric Bond-Breaking: Quantum Simulation of NaK+ in Liquid Tetrahydrofuran.

Gas-phase potential energy surfaces (PESs) are often used to provide an intuitive understanding of molecular chemical reactivity. Most chemical reactions, however, take place in solution, and it is unclear whether gas-phase PESs accurately represent chemical processes in solvent environments. In this work we use quantum simulations to investigate the dissociation energetics of NaK+ in liquid tetrahydrofuran (THF) to understand the degree to which solvent interactions alter the gas-phase picture. Using umbrella sampling and thermodynamic integration techniques, we construct condensed-phase free energy surfaces of NaK+ on THF in both the ground and electronic excited states. We find that solvation by THF completely alters the nature of the NaK+ bond by reordering the thermodynamic dissociation products. Reaching the thermodynamic dissociation limit in THF also requires a long-range charge transfer process that has no counterpart in the gas phase. Gas-phase PESs, even with perturbations, cannot adequately describe the reactivity of simple asymmetric molecules in solution.

Hemicellulose pyrolysis: mechanism and kinetics of functionalized xylopyranose.

This work analyzes the thermochemical kinetic influence of the most prominent functionalizations of the β-D-xylopyranose motif, specifically 4-methoxy, 5-carboxyl, and 2-O-acetyl, regarding the pyrolytic depolymerization mechanism. The gas-phase potential energy surface of the initial unimolecular decomposition reactions is computed with M06-2X/6-311++G(d,p), following which energies are refined using the G4 and CBS-QB3 composite methods. Rate constants are computed using the transition state theory. The energies are integrated within the atomization method to assess for the first time the standard enthalpy of formation of β-D-xylopyranose, 4-methoxy-5-carboxy-β-D-xylopyranose, and 2-O-acetyl-β-D-xylopyranose: -218.2, -263.1, and -300.0 kcal mol-1, respectively. For all isomers, the activation enthalpies of ring-opening are considerably lower, 43.8-47.5 kcal mol-1, than the ring-contraction and elimination processes, which show higher values ranging from 61.0-81.1 kcal mol-1. The functional groups exert a notable influence, lowering the barrier of discrete elementary reactions by 1.9-8.3 kcal mol-1, increasing thus the reaction rate constant by 0-4 orders of magnitude relative to unsubstituted species. Regardless of the functionalization, the ring-opening process appears to be the most kinetically favored, characterized by a rate constant on the order 101 s-1, exceeding significantly the values associated with ring-contraction and elimination, which fall in the range 10-4-10-10 s-1. This analysis shows the decomposition kinetics are contingent on the functionalization specificities and the relative orientation of reacting centers. A relatively simple chemical reactivity and bonding analysis partially support the elaborated thermokinetic approach. These insights hold significance as they imply that many alternative decomposition routes can be quickly, yet accurately, informed in forthcoming explorations of potential energy surfaces of diverse hemicellulose motifs under pyrolysis conditions.

The potential energy profile of the decomposition of 1,1-diamino-2,2-dinitroethylene (FOX-7) in the gas phase.

1,1-Diamino-2,2-dinitroethene (FOX-7) is an energetic material with low sensitivity and high detonation performance, thus it has been considered as a potential replacement for traditional nitro-based energetic materials. In a recent publication (J. Phys. Chem. A, 2022, 126, 4747), the initial decomposition steps of FOX-7 were studied using reflectron time-of-flight mass spectrometry and infrared spectroscopy. The experimental study was complemented with quantum chemistry calculations, which demonstrated the gas phase potential energy surface to be indicative of the reaction process in the condensed phase. The computation in J. Phys. Chem. A, 2022, 126, 4747 focuses on the primary decomposition - but in this manuscript, the full decomposition pathway on the singlet surface, consisting of 54 intermediates and 37 transition states, is characterized at an unprecedented detail. The calculations show that the nitro group, instead of the amine group, is primarily responsible for the sensitivity and endothermicity of FOX-7 decomposition. This result sheds light on how to critically optimize the performance of FOX-7 and design the next generation of nitro-based energetic materials. A comprehensive roadmap, initiated from FOX-7, covers the chemical space of the entire decomposition thus providing a holistic demonstration of various key decomposition pathways leading to various small, gas phase products such as NO, NO2, NH2, CO2, and CO.

Structure and Bonding in [Sb@In8 Sb12 ]3- and [Sb@In8 Sb12 ]5.

We report the characterization of the compound [K([2.2.2]crypt)]4 [In8 Sb13 ], which proves to contain a 1:1 mixture of [Sb@In8 Sb12 ]3- and [Sb@In8 Sb12 ]5- . The tri-anion displays perfect Th symmetry, the first completely inorganic molecule to do so, and contains eight equivalent In3+ centers in a cube. The gas-phase potential energy surface of the penta-anion has eight equivalent minima where the extra pair of electrons is localized on one In+ center, and these minima are linked by low-lying transition states where the electron pair is delocalized over two adjacent centers. The best fit to the electron density is obtained from a model where the structure of the 5- cluster lies close to the gas-phase transition state.

Highly accurate computation of free energies in complex systems through horsetail QM/MM molecular dynamics combined with free-energy perturbation theory

We report a method to calculate very accurate free-energy values in complex systems using hybrid QM/MM approaches. The method combines the recently developed horsetail sampling technique in molecular dynamics and the dual-level technique derived from free-energy perturbation theory. The former is a particular type of multiple molecular dynamics that has been specifically designed for an efficient parallelization of QM/MM simulations. The latter allows estimating free-energy corrections at a high QM/MM level from a reference sampling obtained at a lower QM/MM level. The methodology is illustrated through the study of hydrogen peroxide at the vapor–liquid water interface, a system of considerable atmospheric and environmental relevance. We focus on the calculation of the free-energy profile for the torsional motion of the solute at the CCSD(T)/aug-cc-pVTZ level of theory. It is shown that the equilibrium angle is 87.7°, and that the free-energy barriers for cisoid and transoid transition states are 4.3 and 1.4 kcal/mol, respectively. These values are significantly different from the gas phase potential energy surface at the equivalent computational level (112.8°, 7.3 and 1.1 kcal/mol, respectively) suggesting that adsorption of hydrogen peroxide on water droplets could have major implications on its atmospheric chemistry.

Solvent effect on proton transfer in the complexes of N,N-dimethylformamide with sulfuric and phosphoric acid: A DFT investigation

Ab initio quantum-chemical calculations of structure and energies of the complexes of N,N-dimethylformamide (DMF) with sulfuric (H2SO4) and phosphoric (H3PO4) acids have been carried out. It has been found that the hydrogen bond between H2SO4 and DMF molecules is a little shorter and stronger than that between H3PO4 and DMF. The H-bond strength is different both in acid–acid and (acid)n–DMF complexes for n = 1, 2. The polar solvent effect is taken into account by using the CPCM approach. The differences of geometric parameters of the H-bonds in the gas phase and DMF are analyzed. The potential energy surface (PES) of the proton transfer reaction in acid–DMF and (acid)2–DMF complexes was calculated. The calculations have shown that the gas phase PES has a single distinct minimum (with the exception of the (H2SO4)2–DMF). In DMF, the proton transfer reaction takes place in all complexes, if OACID … ODMF distance is constrained. The solvent effect favors a proton transfer from sulfuric acid to oxygen atom of DMF molecule and formation of stable ionic pairs.

Gas Phase Conformations of Selenocysteine and Related Ions: A Comprehensive Theoretical Study

Extensive ab initio molecular calculations have been first performed to thoroughly characterize the gas-phase potential energy surfaces (PES) of the 21th amino acid selenocysteine and related ions (neutral, protonated and deprotonated). A wide range of trial structures generated by considering the combinations of all internal single-bond rotamers was surveyed at the BHandHLYP/6-31G(d) level, and then refined at the BHandHLYP/6-311++G(d,p) level. A total of 76, 23, 38, and 3 unique stable conformers respectively for neutral, protonated, deprotonated, and doubly deprotonated selenocysteine is identified, and neutral zwitterionic forms are found to be as local minima on the gas-phase PES. The properties of the low energy conformers, such as relative energies, dipole moments, rotational constants, and intramolecular hydrogen bonds, were determined and analyzed. The thermochemical properties of proton affinity (PA), gas-phase basicity (GB), proton dissociation energy (PDE), gas-phase acidity (GA), and the vertical ionization energies (VIEs) were computed by the theoretical approaches of BHandHLYP, B3LYP, MP2, and CCSD(T). Moreover, the conformational equilibrium effect (CEE) on thermochemical properties was analyzed. The statistical simulation predicts that the CEE generally yields a physical correction on about a 1 kBT scale in GA/GB calculations for multi-conformer systems.

Specific Reaction Path Hamiltonian for Proton Transfer in Water: Reparameterized Semiempirical Models.

The semiempirical MNDO-based AM1 and PM3 methods and the orthogonalization-corrected OM1, OM2, and OM3 models were reparameterized to improve their description of bulk water and of proton transfer in water. Reference data included the gas-phase geometries and energies of the water molecule, small water clusters, the hydronium ion, and small hydronium ion-water clusters, as well as the gas-phase potential energy surface for proton transfer between the two water molecules in a Zundel ion, all calculated at the MP2/aug-cc-pVTZ level of theory. Combined QM/MM molecular dynamics simulations were carried out for bulk water and for a proton solvated in water using large cluster models. Both the authentic and reparameterized semiempirical models were employed in the simulations. The reparameterization led to significantly better results in all cases. The new set of OM3 parameters gave the best overall results for the structural and dynamic properties of water and the hydrated proton, with a small but finite barrier of 0.1-0.2 kcal/mol in the potential of mean force for proton transfer, in agreement with ab initio path-integral molecular dynamics simulations. The reparameterized OM3 model is expected to be useful for efficient modeling of proton transfer in aqueous solution.

Molecular structure of antihypertensive drug perindopril, its active metabolite perindoprilat and impurity F

The molecular structure of the antihypertensive drug perindopril (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2 carboxylic acid), its active metabolite perindoprilat ((2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid), and impurity F (ethyl (2S)-2-((3S,5aS,9aS,10aS)-3-methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl) pentanoate) has been investigated using B3LYP/6-31g(d) and B3LYP/6-311+g(d,p) model chemistry. It has been found that solid state conformations of perindoprilat occur close to, but not actually at minima on the computed gas-phase potential energy surfaces. Both, neutral and zwitterionic structures of perindopril and perindoprilat have been investigated. Relative stability of individual ionized species of this drug has been determined. Water has a remarkable effect on the geometry of the perindopril species studied.

Characterization of the stacking interactions between DNA or RNA nucleobases and the aromatic amino acids

MP2/6-31G ∗(0.25) gas-phase potential energy surfaces of stacked dimers between the four aromatic amino acids and the natural (DNA or RNA) nucleobases were considered as a function of three variables (vertical separation, angle of rotation, and horizontal displacement). The maximum stacking interaction was found to increase with the amino acid according to PHE < HIS ≈ TYR < TRP, while the stacking energy is generally largest for the purines compared to the pyrimidines. Most notably, the interaction energies are up to −43 kJ mol −1. Comparison of the magnitude of these interactions with, for example, hydrogen-bonding and stacking interactions that stabilize DNA duplexes suggests that π–π stacking between nucleobases and amino acids likely plays a large role in many fundamental biological processes.

Ab initio study of the structural properties of ascorbic acid (vitamin C)

AbstractGeometries of the neutral and ionic tautomeric species of ascorbic acid were optimized at the density functional theory (DFT) level using the B3LYP functional. The radical species were evaluated using the unrestricted B3LYP method. Single‐point energy calculations were also performed using the Møller–Plesset (MP2) and unrestricted MP2 (UMP2) methods for the closed‐shell and open‐shell systems, respectively. The effects of aqueous solution were evaluated using the conducting polarized continuum model (CPCM) and polarized continuum model (PCM). The geometries of most stable radicals in the respective groups were also optimized in the water solution using the CPCM model at the UB3LYP level. All calculation were performed using the 6‐311++G(d,p) basis set. The nature of stationary points on the gas phase potential energy surfaces (PESs) was evaluated using vibrational frequency calculations; all geometries characterize local minima. The species obtained by the deprotonation of the O3 site is the most stable monoanion of ascorbic acid. For the radical species, the structure obtained by the dehydrogenation of the O3 site is the most stable monoradical. Among the radical anions, the species obtained by the deprotonation of the O3 site and subsequent dehydrogenation of the O2 site is the most stable in the gas phase and in an aqueous medium. The computed isotropic hyperfine coupling constants of this species were found to be in good agreement with the experimental data. Our investigation also supports the earlier findings that the oxidized species of ascorbic acid in water solution by the OH• radical is radical anion of the AAOO form. The spin densities and molecular electrostatic potentials are also discussed. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

DFT and MP2 investigation of the [formula omitted] anion potential energy surface

The B 2 H 3 - gas phase potential energy surface is studied at DFT(B3LYP/6-311+g(3df,2p)), MP2/6-311+g(3df,2p) and CCSD(T)//DFT and MP2 levels of theory. Many structures (isomers and transition states), which are not reported before, have been detected at these levels. Structural connectivities between these energetic extrema are brought to the fore and some H–H exchanges mechanisms are proposed. This leads to, on one hand H b–H t and on another hand B 1–B 2 possible spectral equivalences. Our results are briefly compared to Schaefer III’s ones on isoelectronic C 2H 3 radical and Si 2H 3.

High-Level Computational Studies of Nonidentity Proton Transfer Reactions: Variations in Their Gas Phase Potential Energy Surfaces

High-level calculations (G2+) have been used to characterize the gas phase potential energy surfaces of the nonidentity proton transfer reactions of a series of simple anions (H-, CH3-, NH2-, OH-, F-, SiH3-, PH2-, SH-, Cl-, HCC-, and NC-) with their conjugate acids. Only the combinations that give reactions that are exothermic by less than 20 kcal/mol were considered. The surfaces for the nonidentity reactions appear to be hybridizations of those of the corresponding identity reactions, and a simple averaging approach provides a reasonable representation of the nonidentity surface. Measures based on the geometry or electron density indicate that the position of the transition state (“early” or “late”) is better correlated with the properties of the proton donor/acceptor than the exothermicity of the proton transfer process in these systems.

The hydrolysis process of the cis-dichloro(ethylenediamine)platinum(II): A theoretical study

The hydrolysis process of the cisplatin analog cis-dichloro(ethylenediamine)platinum(II) (cis-DEP) was theoretically investigated at the Hartree–Fock, density functional theory and the second order Møller–Plesset perturbation theory levels of calculation. The stationary points on the gas phase potential energy surface for the first and second hydrolysis steps were fully optimized and characterized. For the first aquation process the gas phase results are in satisfactory agreement with the experimental data. However in order to reproduce the observed rate constant for the second hydrolysis step it is essential to include the solvent effect. The structures and energetic properties are similar to the values found for the parent compound cisplatin, showing that the cis-DEP analog should be considered as a potential drug concerning its hydrolysis process.

DIFFERENT PROTONATION STATES OF THE BACILLUS CEREUS BINUCLEAR ZINC METALLO-β-LACTAMASE ACTIVE SITE STUDIED BY COMBINED QUANTUM MECHANICAL AND MOLECULAR MECHANICAL SIMULATIONS

Three different protonation states of the active site of the Bacillus cereus zinc-β-lactamase in its binuclear form are studied using combined quantum mechanics/molecular mechanics molecular dynamics simulations. The reliability of the quantum mechanical model, the self-consistent-charge density-functional-based tight binding method, in describing the zinc centers are tested through comparisons with ab initio quantum mechanical results. We found that this model gave relatively accurate results for structures and performed much better than the MNDO type semi-empirical method for the particular systems. The enzyme simulations suggested that when the overall charge of the active site is +1, i.e., both Asp90 and Wat1 (a water molecule coordinated with the first zinc ion) deprotonated, the second zinc ion is coordinated with Asp90 and Wat1, and a second water molecule cannot coordinate with the second zinc ion. When the overall charge is +2, i.e., either Asp90 or Wat1 protonated, Asp90 and Wat1 form a stable hydrogen bond. Depending on the proton being on Asp90 or on Wat1, the active site structure produced by the simulations is either similar to molecule A or to molecule B, both contained in the same crystal structure that has two enzyme molecules in a single asymmetric unit. The simulations of the +2 charge states also reproduced the experimentally observed "loose" coordination around the second zinc for the Bacillus Cereus enzyme. Based on the simulations and a gas phase potential energy surface scanning using ab initio model, we argue that the penta-coordination around the second zinc ion is not a stable arrangement. Mechanistic implications of these results are discussed.

Three conformational polymorphs of di-mu-chlorotetrakis(1-methylboratabenzene)diyttrium: synthesis, x-ray structures, quantum chemical calculations, and lattice energy minimizations.

The reaction of yttrium trichloride with lithium 1-methylboratabenzene (1/2) in toluene (110 degrees C, 3 days) afforded the donor-free dinuclear sandwich complex [(C(5)H(5)BMe)(2)Y(mu-Cl)](2) (1) in 85% yield as pale-yellow crystals. By means of single crystal and powder diffraction methods, three conformational polymorphs, alpha-1 [P2(1)/n (No. 14), monoclinic, a = 6.6124(8) A, b = 14.352(9) A, c = 14.120(1) A, beta = 95.57(1) degrees, V = 1333.7(9) A(3), Z = 2], beta-1 [P2(1)/a (No. 14), monoclinic, a = 8.542(2) A, b = 13.712(6) A, c = 11.76(1) A, beta = 102.60(4) degrees, V = 1344.5(13) A(3), Z = 2], and gamma-1 [Pbca (No. 61), orthorhombic, a = 20.091(5) A, b = 13.527(3) A, c = 9.976(2) A, V = 2711.2(11) A(3), Z = 4], were characterized in the solid state of 1. The molecules in the three phases vary remarkably in the rotational position of boratabenzene ligands with differences of 91.1, 133.1, and 24.9 degrees between each pair. DFT calculations at the B3LYP/LanL2DZ level reveal that the three molecular structures observed in the solid state correspond closely to three minima on the gas-phase potential energy surface. The beta conformation is 2.8 and 7.2 kJ/mol more stable than the alpha and gamma conformations, respectively. Lattice energy minimizations predict that the alpha-1 phase is about 5.5 and 18.7 kJ mol(-)(1) more stable than the beta-1 and gamma-1 modifications, in agreement with the packing coefficients and the molecular volumes of the three crystal structures. While the alpha-1 and beta-1 modifications have comparable total energies, the gamma-1 form is less stable. The total energy differences among the polymorphs are greater than generally expected.

The local minima method (LMM) of pharmacophore determination: a protocol for predicting the bioactive conformation of small, conformationally flexible molecules.

Software has been developed for potential energy surface analysis and the local minima method of pharmacophore determination. LMM is rigorous and systematic and employs multiple conformations which are the local minima from the potential energy surface of each compound in the data set. It produces a series of possible pharmacophores from a postulated set of pharmacophore elements. The best pharmacophore is then determined by performing a comparative molecular field analysis (CoMFA) on each one. The pharmacophore which produces the most self-consistent model is deemed the best. Local minima on the gas-phase potential energy surface are shown to be a reasonably close approximation to protein bound conformations, and these conformations can be found through systematic conformational searches followed by minimization of the local minima. LMM was used to develop a 3D-QSAR model for dopamine beta-hydroxylase (DBH) inhibitors which was highly predictive (predictive R2 = 0.71 and standard error of predictions = 0.41). The model predicted that the phenyl and thienyl series of inhibitors were acting as bioisosteres. Examination of compounds overlayed in the model indicated a possible hydrogen bond acceptor in the DBH active site. Three tyrosine residues previously labeled by mechanism based inhibitors may be acting as the acceptor and therefore represent excellent candidates for site-directed mutagenesis studies.

Theoretical Studies of the Potential Energy Surfaces and Compositions of the d-Aldo- and d-Ketohexoses

The potential energy surfaces of all eight d-aldohexoses and four d-ketohexoses have been extensively studied, employing quantum mechanical and molecular mechanical calculations. Anomeric preferences for the axial OH positions were observed for all of the hexoses studied. Several stability factors determining the potential energy surface were examined, and we found that the Hassel−Ottar effect, the delta-two effect and the cis−trans effect are not discernible on the gas-phase potential energy surfaces of the cyclic hexoses. Instead, the anomeric effect and intramolecular hydrogen bonding effects dominate. The most important finding in this study is that in the gas phase, furanose forms are more stable than pyranose forms for all of the hexoses except galactose, idose, psicose, and sorbose, in contrast to the generally greater stability of pyranose forms observed in solution. The decrease of intramolecular hydrogen bonding stabilization in solution was found to be primarily responsible for the composition differences between the gas and solution phases.

Molecular Dynamics with a Quantum‐Chemical Potential: Solvent Effects on an SN2 Reaction at Nitrogen

AbstractSolvent effects on an SN2 reaction at nitrogen (Cl− + NH2Cl → ClNH2 + Cl−) in dimethyl ether solution were studied by means of molecular dynamics simulation with a combined quantum‐chemical and molecular‐mechanical potential. The energetics and geometrical parameters of the reaction in the gas phase, calculated by means of the semiempirical model PM3(the quantum chemical part of the combined potential), were compared with ab initio calculations up to the 6‐311 + G* */MP2 and 6‐311 + G(2 d,p)/MP2 levels of theory. Compared with the gas phase potential energy surface, the free energy profile of the reaction in dimethyl ether solution shows that the solvent makes the ion‐dipole complex well shallower by approximately 6.4 kcal mol−1 and raises the height of the effective barrier from the complex to the transition state by about 2.2 kcal mol−1. The overall transition barrier between the separated reactants and the products is raised from 6.4 kcal mol−1 to 15.0 kcal mol−1 upon solvation. The radial distribution functions between solvent‐solute atom pairs at different stages of the reaction course were compared. Results show that better solvation of the charge‐localised separated reactants is responsible for the increase in the barrier height. Polarisation of the solute by its surroundings is also discussed.

A molecular dynamics simulation study with a combined quantum mechanical and molecular mechanical potential energy function: Solvation effects on the conformational equilibrium of dimethoxyethane

Solvent effects on the conformational equilibria of dimethoxyethane (DME, CH3–O–CH2–CH2–O–CH3) have been studied using molecular dynamics simulation with a combined molecular mechanical and semiempirical quantum mechanical potential energy function. The potential of mean force around the central O–C–C–O dihedral angle of DME in water was determined using umbrella sampling, with the DME molecule treated by the modified intermediate neglect of diatomic differential overlap (MNDO) method and water molecules described using the extended simple point charge model. This potential of mean force shows the same bias as the gas phase potential energy surface calculated by MNDO: the heights of the barriers are underestimated and the stability of the gauche conformation with respect to the trans conformation is overestimated. However, the calculated stabilization of the gauche state by solvation is in good agreement with experimental results, suggesting a quite reasonable description of this system by the combined potential energy function. The solute–water atom pair distributions and the averaged percentage of solute–water hydrogen bonding does not change much when the central dihedral angle changes, but in the gauche conformation one water hydrogen can be hydrogen bonded with the two solute oxygen atoms simultaneously. The interactions between DME and its explicit water environment favor the gauche over the trans conformation much more than predicted by the reaction field model, although the overall relative stabilities predicted by the latter model are not so biased due to compensation of errors. The trans conformation of the outer C–O–C–C dihedral angles is most favored during the simulations, which is qualitatively different from the reaction field prediction that the trans–gauche+–gauche− would be the most stable conformer in solution.