Polarizable Continuum Method Research Articles

A mechanism for production of singlet oxygen by acidification of hypochlorite

A mechanism for the production of singlet oxygen by acidification of hypochlorite in aqueous solution is proposed based on electron structure calculations. The mechanism involves two transition states and a peroxyhypochlorous acid intermediate. The calculations include six explicit water molecules to give some allowance for solvation of the produced electrolyte. The theoretical level is the density functional theory and the isodensity polarized continuum method.

Theoretical studies on tautomerism of tetrazole derivatives by polarisable continuum method (PCM)

Computational calculations at B3LYP/6-31++G(d,p) level were employed in the study of the predominant tautomeric forms of 1-H and 2-H tetrazole derivatives (5-NO 2, 5-CF 3, 5-F, 5-H, 5-NH 2, 5-OH, 5-CH 3) in the gas phase and solution using PCM model. For electron withdrawing derivatives in the gas phase and solution 2-H forms are more stable and dominant form. For electron releasing groups in the gas phase and solution with low dielectric constants the 2-H form is more stable but in solvents with high dielectric constants 1-H isomer is dominant form. In addition variation of dipole moments and charges on atoms in the solvents are studied.

Tautomeric Forms of 2-Thiobarbituric Acid As Studied in the Solid, in Polar Solutions, and on Gold Nanoparticles

2-Thiobarbituric acid (TBA) coated gold nanoparticles (average diameter = 5.90 nm) were produced and studied by several experimental and theoretical methods. As part of this study, the molecular structure of TBA tautomers in the solid, in polar solutions, and adsorbed onto gold nanoparticles was studied. The resolution of this complicated system (10 possible isomers) was accomplished with the aid of experimental (IR, UV−vis, and NMR) and theoretical (DFT and MP2) methods. The general conclusion is that there are two preeminent isomers, N1 and N10, with different stabilities in different media. N1, the keto−thione tautomer, is the most stable in gas phase (ΔGo298 ≈ 8−9 kcal/mol lower than the second-most stable isomer, depending on the method of calculation used). However, experimental spectroscopic data supported by the theoretical calculations strongly suggest an equilibrium between the tautomers N1 and N10 in methanol solution, where enolization of one keto group is produced by proton transfer from the methylene group, which is more acidic than the NH groups. With the use of the polarizable continuum method for simulating solvents, N10 is predicted to be even more stable than N1 by ΔGo298 ≈ 1 kcal/mol in methanol. On the other hand, the IR spectrum of the solid can be best explained by assuming that only N10 is present, a fact also supported by the observation that the IR spectrum of TBA absorbed onto gold nanoparticles can be explained by a larger ratio of [N10]/[N1] than that present in methanolic solution. Isomerization of N1⇋ N10 can be explained by intervention of the solvent, proceeding faster in methanol solutions than in DMSO, where it is nevertheless observed after a time, according to the 13C NMR spectra. Our experiments support absorption of TBA onto gold nanoparticles through S−Au and N−Au interactions, with the preeminence of a N10-like enol structure. The experiments also demonstrate that the synthesized TBA-coated gold nanoparticles can autoassociate by hydrogen bonding to form larger structures. This same H-bonding capacity also assures that these coated nanoparticles act as thistles toward proteins in solution, binding them strongly, presumably not by chemical reaction but by a network of hydrogen bonds.

Calculation of the relative acidities and oxidation potentials of para-substituted phenols. A model for α-tocopherol in solution

Relative acidities (Delta pK(a)) of phenols and oxidation potentials (Delta E(ox)) of the phenoxide anions have been calculated for nine para-substituted phenols using density functional theory. Solvent effects were incorporated using the conductor-like polarisable continuum method. Using the calculated Delta pK(a) and Delta E(ox) values in a thermodynamic cycle, the DeltaBDE (bond dissociation enthalpy) of the phenols were also determined with all values calculated to within 1.5 kcal mol(-1) of experiment. The Delta pK(a) and Delta E(ox) values were calculated for 6-hydroxy-2,2,5,7,8-pentamethylchroman (HPMC), a model for alpha-tocopherol for which there are no known experimental values. The acidity of this compound is raised by 2.4 pK(a) units and lowered by -0.79 V relative to phenol with a calculated Delta BDE of -14.9 kcal mol(-1). There is a negative correlation (r(2) = 0.86) between the Delta pK(a) and the Delta BDE values. A stronger and positive correlation is found between the Delta E(ox) (r(2) = 0.98) and the Delta BDE values. Using these correlations it is uncovered that hydrogen abstraction of phenols, as measured by the Delta BDE, is driven by electron transfer rather than by proton transfer.

Role of Solvation in the Energy Stabilization Inside the Hydrophobic Core of the Protein Rubredoxin

There are many forces that contribute to the stability of a protein; among these are dispersion interactions, hydrogen bonding, and solvation effects. In a recent work, Vondrasek et al. estimated the in vacuo stabilization energy of the hydrophobic core of the protein rubredoxin using high level ab initio methods (Vondrasek, J.; et al. J. Am. Chem. Soc. 2005, 127, 2615). In this work, we evaluate the effects of solvation on the stability of the hydrophobic core of this protein. Solvation calculations are made using the polarizable continuum method at the MP2/aug-cc-pVDZ level of theory. It is found that, in a protein-like environment (mimicked by a continuum solvent with a dielectric constant of approximately 4), the stability of rubredoxin's hydrophobic core is decreased by 40-50%. We also observed that the stabilization energy of the hydrophobic core is only slightly lower in a protein-like medium than in an aqueous one (DeltaGether-DeltaGwater approximately 1.0-3.5 kcal/mol).

Reaction paths for production of singlet oxygen from hydrogen peroxide and hypochlorite

The mechanism for production of singlet oxygen from hydrogen peroxide and hypochlorite in aqueous solution is studied computationally. Geometries of various complexes and transition states are found by quantum mechanical geometry optimizations of the species in gas phase. The activation energies pertaining to the mechanism in aqueous solution are estimated using the isodensity polarized continuum method at various levels of theory up to CCSD//B3LYP/6-311+G(d,p). Three reaction paths have been identified: two with a single transition state and one involving two transition states and a H 2O 3 intermediate. The latter path has the smallest activation energy.

Density functional theory investigations on acid-catalysed epoxide oxidative ring-opening by DMSO. Competition between oxidation processes

DFT investigations of the acid-catalysed oxidation of linear and cyclic epoxides by DMSO revealed that a first step of nucleophilic ring-opening is followed by two different reaction pathways: on one hand α-hydroxycarbonyl derivatives are formed, via oxidative ring-opening, and on the other hand two aldehyde moieties are obtained, via oxidative cleavage. Calculations with the polarized continuum method (PCM) taking into account the DMSO solvation effect did not significantly change the energy barriers.

Quantum Chemical Study of Solvent and Substituent Effects on the 1,5-Hydride Shift in 2,6-Dimethyl-2-heptyl Cations

The mechanism of the degenerate 1,5-hydride shift in 2,6-dimethyl-2-heptyl cations has been investigated using ab initio MP2 and density functional theory (DFT) hybrid (B3LYP) calculations. The potential-energy profile for the 1,5-hydride shift consists of three minima corresponding to two equivalent acyclic carbocations and one symmetrically mu-hydrido-bridged carbocation, while two equivalent unsymmetrically hydrido-bridged carbocations were located as transition-state structures. The calculated relative energy differences between acyclic carbocations and symmetrically mu-hydrido-bridged structure are significantly affected by introduction of alkyl and (CH2)n-substituents at the C4 position of the 2,6-dimethyl-2-heptyl cation structure. DFT self-consistent isodensity polarizable continuum method (SCI-PCM) and MP2 PCM continuum methods have been used to calculate the effect of solvation on geometries and relative energies of the species involved in the 1,5-hydride shift. It is found that relative energies of acyclic and mu-hydrido-bridged carbocation structures as well as the energy barriers for 1,5-hydride shifts are in accord with experimental data if solvation effects are taken into account.

Activation barriers for DNA alkylation by carcinogenic methane diazonium ions

Methylation reactions of the DNA bases with the methane diazonium ion, which is the reactive intermediate formed from several carcinogenic methylating agents, were examined. The SN2 transition states of the methylation reactions at N7, N3, and O6 of guanine; N7, N3, and N1 of adenine; N3 and O2 of cytosine; and O2 and O4 of thymine were calculated using the B3LYP density functional method. Solvation effects were examined using the conductor-like polarizable continuum method and the combined discrete/SCRF method. The transition states for reactions at guanine N3, adenine N7, and adenine N1 are influenced by steric interactions between the methane diazonium ion and exocyclic amino groups. Both in the gas phase and in aqueous solution, the methylation reactions at N atoms have transition states that are looser, and generally occur earlier along the reaction pathways than reactions at O atoms. The forming bonds in the transition states in water are 0.03 to 0.13 A shorter than those observed in the gas phase, and the activation energies are 13 to 35 kcal/mol higher. The combined discrete/SCRF solvation energy calculations using base-water complexes with three water molecules yield base solvation energies that are larger than those obtained from the CPCM continuum method, especially for cytosine. Reactivities calculated using barriers obtained with the discrete/SCRF method are consistent with the experimentally observed high reactivity at N7 of guanine.

Excited State Properties of 7-Hydroxy-4-methylcoumarin in the Gas Phase and in Solution. A Theoretical Study

TDDFT/B3LYP and RI-CC2 calculations with different basis sets have been performed for vertical and adiabatic excitations and emission properties of the lowest singlet states for the neutral (enol and keto), protonated and deprotonated forms of 7-hydroxy-4-methylcoumarin (7H4MC) in the gas phase and in solution. The effect of 7H4MC-solvent (water) interactions on the lowest excited and fluorescence states were computed using the Polarizable Continuum Method (PCM), 7H4MC-water clusters and a combination of both approaches. The calculations revealed that in aqueous solution the pi pi* energy is the lowest one for excitation and fluorescence transitions of all forms of 7H4MC studied. The calculated excitation and fluorescence energies in aqueous solution are in good agreement with experiment. It was found that, depending on the polarity of the medium, the solvent shifts vary, leading to a change in the character of the lowest excitation and fluorescence transition. The dipole-moment and electron-density changes of the excited states relative to the ground state correlate with the solvation effect on the singlet excited states and on transition energies, respectively. The calculations show that, in contrast to the ground state, the keto form has a lower energy in the pi pi* state as compared to enol, demonstrating from this point of view the energetic possibility of proton transfer from the enol to the keto form in the excited state.

Boric acid, “carbonic” acid, and N-containing oxyacids in aqueous solution: Ab initio studies of structure, p Ka, NMR shifts, and isotopic fractionations

B(OH) 3 and CO 2 are acidic species of considerable geochemical importance, yet the microscopic nature of the acid dissociation reactions for these B and C species is not well understood. Quantum mechanical methods have recently been applied to the direct ab initio calculation of p K a values for many organic and inorganic weak acids, but the B and C acids have not yet been considered in detail. In the present study, p K a values are calculated quantum mechanically for the oxyacids B(OH) 3, H 2CO 3 and HNO 3, which have experimental first p K a values of 9.2, 6.4 and −1.3, respectively. We calculate the gas-phase reaction free energies at the highly accurate CBS-QB3 ab initio quantum mechanical level and reaction free energies of hydration using a polarizable continuum method. Using a thermodynamic cycle corresponding to the simple dissociation process HA A − + H +, in aqueous solution, we calculate p K a values of 21.6, 3.8 to 2.2 and −0.8 for the three oxyacids mentioned above, closely matching experiment only for HNO 3. The discrepancies with experiment arise from the more complex nature of the acid dissociation process for B(OH) 3, which involves the addition of H 2O to B(OH) 3 and formation of the B(OH) 4 − anion, and from the instability of hypothetical H 2CO 3 compared to the proper hydrated reactant complex CO 2. . . H 2O. When the proper microscopic description of the reactants and products is used the calculated p K a values for the three acids become 11.1, 7.2 and −0.8, in considerably better agreement with experiment for B(OH) 3 and CO 2. . . H 2O. Thus p K a calculations using this approach are accurate enough to give information on the actual acid species present in solution and the details of their acid dissociation processes at the microscopic level. 11B and 13C-NMR chemical shifts are also calculated for the various species and compared to experiment. By comparison of our calculations with experiment it is apparent that the 13C-NMR chemical shift has never been measured for an actual H 2CO 3 molecule in solution, consistent with its thermodynamic and kinetic instability with respect to CO 2 + H 2O. By contrast, the good agreement of calculated and experimental NMR shifts for the species B(OH) 3 and B(OH) 4 − support their existence in solution. Calculations of the IR spectra of H 2CO 3 and its H-bonded dimer support the idea that spectra previously assigned to condensed phase or surface H 2CO 3 are better interpreted as arising from some type of H-bonded H 2CO 3 oligomer, rather than the monomer. Calculations of the relative free energy for different isotopomers of the B and C oxyacids establish that the partitioning of 13C and 12C between CO 2(aq) and HCO 3 − is considerably different from the fractionation between hypothetical H 2CO 3 and HCO 3 −. We find a much better match to the experimental CO 2(g) vs. HCO 3 −(aq) 13,12C fractionation if the bicarbonate cluster model includes a counter ion, such as Na +. The 11,10B fractionation between B(OH) 3 and the van der Waals complex B(OH) 3. . . H 2O is quite small, while that between gas-phase B(OH) 3 and B(OH) 4 − is on the order of 30‰, in qualitative agreement with more rigorous values recently obtained from supermolecule or “water-droplet” calculations.

Computational Evidence for a Variable First Shell Coordination of the Cadmium(II) Ion in Aqueous Solution

In this paper, we present a state-of-the-art 100 ns molecular dynamics simulation of a cadmium(II) aqueous solution that highlights a very flexible ion first coordination shell which transits between hexa- and heptahydrated complexes. From this investigation, a dynamical picture of the water exchange process emerges that takes place through an associative mechanism for the solvent substitution reaction. Our procedure starts from the generation of an effective two-body potential from quantum mechanical ab initio calculations in which the many-body ion-water terms are accounted for by the polarizable continuum method (PCM). This approach is computationally very efficient and has allowed us to carry out extremely long molecular dynamics simulations, indispensable to reproduce the dynamic properties of the cadmium(II) aqueous solution. Quantum mechanical ab initio calculations of the hexa- and heptahydrated complexes extracted from MD configurations have revealed stable minima for both clusters with the water molecules arranged in T(h)() and C(2) symmetries in the hexa- and heptahydrated complexes, respectively, with a slight energetic preference for the heptahydrated one. Finally, a comparison of the calculated hexa- and heptahydrated cluster IR and Raman spectra with the experimental data in the literature, has demonstrated that the IR spectroscopy is not able to distinguish between the two species, whereas the Raman spectrum of the Cd(2+)-(H(2)O)(7) cluster provides a better agreement with the experimental data.

Theoretical Studies on the Mechanism of Acid-Promoted Hydrolysis of N-Formylaziridine in Comparison with Formamide

[reaction: see text] We present an ab initio study of the acid-promoted hydrolysis reaction mechanism of N-formylaziridine in comparison with formamide. Since the rate of amide hydrolysis reactions depends on the formation of the tetrahedral intermediate, we focused our attention mainly on the reactant complex, the tetrahedral intermediate, and the transition state connecting these two stationary points. Geometries were optimized using the density functional theory, and the energetics were refined using ab initio theory including electron correlation. Solvent effects were investigated by using polarizable continuum method calculations. The proton-transfer reaction between the O-protonated and N-protonated amides was investigated. In acidic media, despite that the N-protonated species is more stable than the O-protonated one, it is predicted that both N-protonated and O-protonated pathways compete in the hydrolysis reaction of N-formylaziridine.

A multilayered approach to approximating solute polarization

A hybrid multilayered "ONIOM"-type approach to solvation is presented in which the basic free energy of hydration is taken from the Poisson Boltzmann method and the contribution to the solute polarization is taken from a quantum mechanical implementation of the Born method. The method has been tested on the 52 neutral molecules used in the AM1-SM2 parameterization, and the polarized continuum method is taken as the standard by which the results are assessed. Regression analysis shows that the method gives a small improvement over the standard Poisson Boltzmann method or a dramatic improvement over the Born method. The system presented here represents one of the more straightforward applications of the multilayered approach to solvation, but other more sophisticated approaches are discussed.

A theoretical study of tetrabutylammonium [bis(1,3-dithiole-2-thione-4,5-dithiolato)bismuthate], [NBu4][Bi(dmit)2]: infrared spectrum in the solid state and solvation effects on the molecular geometry

A theoretical study of tetrabutylammonium [bis(1,3-dithiole-2-thione-4,5-dithiolato)bismuthate], [NBu4][Bi(dmit)2] is reported. The vibrational spectrum and the molecular orbitals were calculated at the Hartree–Fock level of theory with the pseudo-potential SBKJC for Bi and a basis set of 6-31G or 6-31G(d,p) for the other atoms. The molecular geometry of the anion, [Bi(dmit)2]−, was optimised with the same level of theory and basis sets, but utilising the polarisable continuum method, for simulation of acetone and benzene media. Molecular geometries of solvated and solid-state species are compared: solvation effects are discussed in terms of anisotropy or isotropy of the media. Analysis of the molecular orbitals allowed a qualitative description of the anion–anion intermolecular interactions.

Observed and calculated 1H- and 13C-NMR chemical shifts of substituted 5H-pyrido[3,2-a]- and 5H-pyrido[2,3-a]phenoxazin-5-ones and of some 3H-phenoxazin-3-one derivatives.

Carbon and proton NMR spectra of several substituted 5H-pyrido[3,2-a]-, 5H-pyrido[2,3-a]phenoxazin-5-ones and 3H-phenoxazin-3-one derivatives have been assigned, and the experimental chemical shifts have been compared with the results of density functional calculations employing large basis sets. Solvent effects were explored by means of the polarizable continuum method (PCM), while the (limited) side-chain flexibility of the compounds has been addressed by Boltzmann averaging of the computed spectral parameters over different conformational minima. Overall, the calculated shifts reproduce well the experiment results; thus, the computational procedure represents a feasible and useful complement to multidimensional NMR experiments in the assignment process.

Quantum Mechanical Study of theSynandAntiConformations of Solvated Cyclic GMP

Self-consistent Reaction Field (SCRF) computational methods have been applied to guanosine 3′:5′-cyclic monophosphate (cGMP) to determine the geometries and energetics of the syn and anti conformations of this cyclic nucleotide in aqueous solution. The syn conformation of cGMP has been predicted to be more stable in the gas phase due to an internal hydrogen bond. The syn conformation is observed in the crystal structure of the sodium tetrahydrate salt, although a bridging water molecule is present in lieu of the internal hydrogen bond. In the gas phase, we find from Hartree–Fock/6-31+G(d) optimizations that the syn conformation is more stable than the anti by about 4 kcal/mol. However, we report here that the anti conformation is more stable in aqueous solution, according to estimates based upon results from both the Onsager model and the Isodensity Polarized Continuum Method (IPCM). Our best estimate from single-point IPCM B3LYP/6-31+G(d) calculations has the anti conformation 19 kcal/mol lower in energy. For comparison purposes, we also present SCRF results for syn and anti adenosine 3′:5′-cyclic monophosphate (cAMP). For cAMP, we estimate the anti conformation to be more stable than the syn by about 6 kcal/mol. We suggest that the relative stability of the anti conformation of cGMP be considered in studies, such as, enzyme docking.

Calculation of the energetics for the oxidation of Sb(III) sulfides by elemental S and polysulfides in aqueous solution

Recent experimental studies have reported the existence of two new Sb sulfide species, Sb 2S 5 2− and Sb 2S 6 2−, in alkaline sulfidic solutions in equilibrium with stibnite, Sb 2S 3, and orthorhombic S. These species contain Sb(V), which has also recently been identified in similar solutions using EXAFS by other researchers. This represents a significant change from the consensus a decade ago that sulfidic solutions of Sb contained only Sb(III) species. I have calculated from first principles of quantum mechanics the energetics for the oxidation of the Sb(III) sulfide dimer Sb 2S 4 2− to the mixed Sb(III,V) dimer Sb 2S 5 2− and then to the all Sb(V) dimer, Sb 2S 6 2−. Gas-phase reaction energies have been evaluated using polarized valence double zeta effective core potential basis sets and Moller-Plesset second order treatments of electron correlation. All translational, rotational and vibrational contributions to the gas-phase reaction free energy have been calculated. Hydration energies have been obtained using the COSMO version of the self-consistent reaction field polarizable continuum method. Negative free energy changes are calculated for the oxidation of the dianion of the III,III dimer to the III,V dimer by both small polysulfides, like S 4H −, and elemental S, modeled as S 8. For the further oxidation of the III,V dimer to the V,V dimer the reaction free energies are calculated to be close to zero. The partially protonated Sb III,III dimer monoanion HSb 2S 4 − can also be oxidized, but the reaction is not so favorable as for the dianion. Comparison of the calculated aqueous deprotonation energies of H 2Sb 2S 4, H 2Sb 2S 5 and H 2Sb 2S 6 and their dianions with values calculated for various oxyacids indicates that the III,V and V,V dimers will have p K a2 values <5, so that their dianions will be the dominant species in alkaline solutions. These results are thus consistent with the recent identification of Sb 2S 5 2− and Sb 2S 6 2− species. I have also calculated the Raman spectra of Sb 2S 5 2− and Sb 2S 6 2− to assist in their identification. The calculated vibrational frequencies of the III,V and V,V dimers are characteristically higher than those of the III,III dimer I previously studied. The III,V dimer may contribute shoulders to the Raman spectrum.

Theoretical Conformational Analysis for Codeinone-6-oximes in Gas Phase and in Solution

The Z/E isomer ratios for codeinone-6-oxime and 7,8-dihydro-codeinone-6-oxime in chloroform and in a water:acetonitrile 85:15 (volume ratio) mixture have been theoretically calculated using the polarizable continuum method at the B3LYP/6-31G* level. Gas phase optimized geometries and thermal corrections were used for obtaining total relative free energies in solution. For validating the B3LYP/6-31G* calculations, optimized geometries and relative energies for the gas phase formaldoxime have been compared with values from B3LYP/6-311++G** calculations. B3LYP/6-31G* optimized geometric parameters are almost constant for formaldoxime, the C-ring model compound, (methoxy-methyl)vinyl-ketone oxime, and codeinone oximes in the absence of special structural features. Transition states, one for each, have been identified for the syn−anti and anti−anti transformations of formaldoxime. The energy and free energy of the barrier for the syn to anti rotation are 9.4 and 8.5 kcal/mol, respectively; the corresponding ba...

Vibrational analysis of small species in the liquid phase by a combined density functional theory and polarizable continuum method

The vibrational frequencies of small organic molecules and inorganic ions were predicted both in vacuum and in the liquid phase at the B3LYP/6-311G++(d,p) level of theory, within the harmonic approximation. The solvent effect was introduced as an electrostatic influence of the bulk by means of the integral equation formalism of the polarizable continuum model. The results show that the application of this continuum solvation model can reduce the overall error in the theoretical predictions. In order to improve the quality of the results, two different scaling procedures were applied. The frequencies obtained for the continuum, when compared with vacuum calculations, show a better linear correlation with experimental data, which increases the efficiency of the scaling procedures. A further reduction of the errors is obtained by partitioning the overall set of frequencies according to the nature of the normal modes and the charge of the solutes. The quality of the theoretical predictions, especially for the stretching modes of vibration of nonionic chemical species, is here noteworthy.