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Density functional theory has been used to study the biologically important coenzyme NADPH and its oxidized form NADP+ . It was found that free NADPH prefers a compact structure in gas phase and exists in more extended geometries in aqueous solution. Ultraviolet-visible absorption spectra in aqueous solution were calculated for NADPH with an explicit treatment of 100 surrounding water molecules in combination with the COSMO solvation model for bulk hydration effects. The obtained spectra using the B3LYP hybrid density functional agree quite well with experimental data. The changes of Gibbs free energies ΔG in reactions of NADPH with O2 observed experimentally in cardiovascular and in chemical systems, that is, NADPH + 2 3 O2 → NADP+ + 2 O2- + H+ and NADPH + 1 O2 + H+ → NADP+ + H2 O2 , respectively, were calculated. The NADPH oxidation reaction in the cardiovascular system cannot proceed without activation since the obtained ΔG is positive. The reaction of NADPH in the chemical system with singlet oxygen was found to proceed in two ways, each consisting of two steps, that is, NADPH firstly reacts with 1 O2 barrierlessly to form NADP+ and HO2- , from which H2 O2 is formed in a spontaneous reaction with H+ , or 1 O2 and H+ initially form 1 HO2+ , which further reacts with NADPH to yield NADP+ and H2 O2 . © 2019 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc.

A detailed TDDFT study (with all-electron STO-TZ2P basis sets and the COSMO solvation model) has been carried out on the effect of diprotonation on the UV−vis−NIR spectra of free-base tetraphenylporphyrin and tetrakis(p-aminophenyl)porphyrin. The diprotonated forms have been modeled as their bis-formate complexes, i.e., as so-called porphyrin diacids. The dramatic redshift of the Q-band of the TAPP diacid has been explained in terms of an elevated “a2u” HOMO and lowered LUMOs, both reflecting infusion of aminophenyl character into the otherwise classic Gouterman-type frontier MOs. The exercise has also yielded valuable information on the performance of different exchange− correlation functionals. Thus, the hybrid B3LYP functional was found to yield a substantially better description of key spectral features, especially the diprotonation-induced redshifts, than the pure OLYP functional. Use of the range-separated CAMY-B3LYP functional, on the other hand, did not result in improvements relative to B3LYP.

Electrostatic interaction of the solvent with the solute and fluctuations of the solvent configurations may make excitation energies of the solute different from those in the gas phase. These effects may dominate photoinduced or chemical reaction dynamics in solution systems and can be observed as shifts or broadening of peaks in absorption spectra. In this work, the nitrogen K-edge X-ray absorption spectra were measured for pyridazine in the gas phase and in aqueous solution. The ultraviolet and X-ray absorption spectra of pyridazine in aqueous solution, as well as those in the gas phase, were then calculated with models based on the algebraic-diagrammatic construction through second order [ADC(2)] with the resolution-of-identity (RI) approximation and compared with the spectra obtained in experiments. For aqueous solution, explicit local solvation structures were extracted from an ab initio molecular dynamics (AIMD) trajectory of pyridazine in bulk water, and RI-ADC(2) was combined with the conductor-like screening model (COSMO). The experimental absorption spectra of pyridazine in aqueous solution were reproduced with good accuracy by theoretical treatment of an ensemble containing the explicit local solvation structures of pyridazine with relevant water molecules combined with the COSMO solvation model of water for long-range solvation.

The various factors influencing the accuracy of 13C NMR calculations using density functional theory (DFT), including the basis set, exchange-correlation (XC) functional, and isotropic shielding calculation method, are evaluated. A wide selection of XC functionals (over 70) were considered, and it was found that long-range corrected functionals offer a significant improvement over the other classes of functionals. Based on a thorough study, it is recommended that for calculating NMR chemical shifts (δ) one should use the CSGT method, the COSMO solvation model, and the LC-TPSSTPSS exchange-correlation functional in conjunction with the cc-pVTZ basis set. A selection of problems in natural product identification are considered in light of the newly recommended level of theory.

Nanoelectrochemical experiments using detection based on tip enhanced Raman spectroscopy (TERS) show a broad distribution of single-molecule formal potentials E°′ for large π-conjugated molecules; theoretical studies are needed to understand the origins of this distribution. In this paper, we present a theoretical approach to determine E°′ for electrochemical reactions involving a single molecule interacting with an electrode represented as a metal nanocluster and apply this method to the Ag20–pyridine system. The theory is based on the semiempirical INDO electronic structure approach, together with the COSMO solvation model and an approach for tuning the Fermi energy, in which the silver atomic orbital energies are varied until the ground singlet state of Ag20–pyridine matches the lowest triplet energy, corresponding to electron transfer from the metal cluster to pyridine. Based on this theory, we find that the variation of E°′ with the structure of the Ag20–pyridine system is only weakly correlated with changes in either the ground-state interaction energy or the charge-transfer excited-state energies at zero applied potential, which shows the importance of calculations that include an applied potential in determining the variation of formal potential with geometry. Factors which determine E°′ include wavefunction overlap for geometries when pyridine is close to the surface, and electrostatics when the molecule-cluster separation is large.

Density functional calculations have been performed to study selected hydrated lanthanide(iii) motexafins (Ln-Motex2+, Ln = La, Gd, Lu) by using energy-consistent 4f-in-core lanthanide pseudopotentials to include the major relativistic effects due to the heavy metals. The maximum number (n) of water molecules bound strongly to [Ln-Motex]2+ (Ln = La, Gd, Lu) was determined to be 6 by calculating the change of the Gibbs energies for the reactions [Ln-Motex(H2O)n]2+ + H2O → [Ln-Motex(H2O)n+1]2+. The number of water molecules coordinated directly to Ln3+ was found to be 3 for La, and 2 for Gd and Lu. The explicit treatment of the tightly bound water molecules in [Ln-Motex(H2O)6]2+ in combination with the COSMO solvation model yielded calculated reduction potentials and UV-vis absorption spectra in good agreement with available experimental data.

In this article, a serie of density functional theory (DFT) calculations were carried out on Keggin heteropolyanions [ XM 12 O 40 ] n - (X = Sn(IV), Sb(V) and Te(VI); M = Mo and W; n = 2,3,4) to analyze their molecular structure, vibrational spectra and electronic structure. The energy and composition of the frontier orbitals resemble those containing internal heteroatoms of preceding periods. We found that the diameter of the encapsulated internal { XO 4 } subunit varies as X does, while { M 12 O 36 } size and distances remain almost constant along the series. Vibrational modes calculations show that exist a dependency of the frequency and the anionic charge, nature of the heteroatom X and calculation methodology. Energy decomposition analysis of the { XO 4 } – { M 12 O 36 } interaction shows a predominant ionic character due to the high charge of the { XO 4 } anionic subunit. COSMO solvation model enabled us to compare heteropolyanions with different total charges. Our results suggest the possibility that these Keggin anions should be stable, being a new challenge for synthetic inorganic chemists.

The reduction mechanism of [Pt(IV) (dach)Cl4 ] (dach=diaminocyclohexyl) in the presence of dGMP was studied. The first step is substitution of a chloro ligand by dGMP, followed by nucleophilic attack of a phosphate or sugar oxygen atom to the C8-position of guanine. Subsequent reduction forms the [Pt(II) (dach)Cl2 ] complex. The whole process is completed by a hydrolysis. Two different pathways for the substitution reaction were examined: a direct associative and a Basolo-Pearson autocatalytic mechanism. All the explored structures were optimized at the B3LYP-D3/6-31G(d) level and by using the COSMO solvation model with Klamt's radii. Single-point energetics was determined at the B3LYP-GD3BJ/6-311++G(2df,2pd)/PCM/scaled-UAKS level. Activation barriers were used for an estimation of the rate constants and these were compared with experimental values. It was found that the rate-determining step is the nucleophilic attack with a slightly faster performance in the 3'-dGMP branch than in the case of 5'-dGMP with activation barriers of 21.1 and 20.4 kcal mol(-1) (experimental: 23.8 and 23.2 kcal mol(-1) ). The reduction reaction is connected with an electron flow from guanine. The product of the reduction reaction is a chelate structure, which dissociates within the last reaction step, that is, a hydrolysis reaction. The whole redox process (substitution, reduction, and hydrolysis) is exergonic by 34 and 28 kcal mol(-1) for 5'-dGMP and 3'-dGMP, respectively.

The interacting quantum atoms (IQA) method decomposes the total energy of a molecular system in terms of one- and two-center (atomic) contributions within the context of the quantum theory of atoms in molecules. Here we incorporate electrostatic continuum solvent effects into the IQA energy decomposition. To this end, the interaction between the solute electrostatic potential and the solvent screening charges as defined within the COSMO solvation model is now included in a new version of the PROMOLDEN code, allowing thus to apply IQA in combination with COSMO-quantum chemical methods as well as to partition the electrostatic solvation energy into effective atomic and group contributions. To test the robustness of this approach, we carry out COSMO-HF/aug-cc-pVTZ calculations followed by IQA calculations on more than 400 neutral and ionic solutes extracted from the MNSol database. The computational results reveal a detailed atomic mapping of the electrostatic solvation energy that is useful to assess to what extent the solvation energy can be decomposed into atomic and group contributions of various parts of a solute molecule, as generally assumed by empirical methodologies that estimate solvation energy and/or logP values.

In order to explore the effect mechanism of solvent on the synthesis of the metal organic framework materials, the microscopic interaction between solvent and framework and the effects of N,N-dimethyl-formamide (DMF) or N-methyl- 2-pyrrolidone (NMP) on solvothermal synthesis of [Zn4O(BDC)3]8 were investigated through a combined DFT and experimental study. XRD and SEM showed that the absorbability of NMP in the pore of [Zn4O(BDC)3]8 was weaker than that of DMF. The thermal decomposition temperature of [Zn4O(BDC)3]8 synthesized in DMF was higher than that in NMP according to TG and FT-IR. In addition, the nitrogen sorption isotherms indicated that NMP improved gas sorption property of [Zn4O(BDC)3]8. The COSMO optimized calculations indicated that the total energy of Zn4O(BDC)3 in NMP was higher than that in DMF, and compared with non-solvent system, the charge of zinc atoms decreased and the charge value was the smallest in NMP. Furthermore, the interaction of DMF, NMP or DEF in [Zn4O(BDC)3]8 crystal model was calculated by DFT method. The results suggested that NMP should be easier to be removed from pore of materials than DMF from the point of view of energy state. It can be concluded that NMP was a favorable solvent to synthesize [Zn4O(BDC)3]8 and the microscopic mechanism was that the binding force between Zn4O(BDC)3 and NMP molecule was weaker than DMF.

In implicit solvation models, the electrostatic contribution to the solvation energy can be estimated by solving a system of elliptic partial differential equations modeling the reaction potential. The domain of definition of such elliptic equations is the union of the van der Waals cavities corresponding to the atoms of the solute molecule. Therefore, the computations can naturally be performed using Schwarz methods, where each atom of the molecule corresponds to a subdomain. In contrast to classical Schwarz theory, it was observed numerically that the convergence of the Schwarz method in this case does not depend on the number of subdomains, even without coarse correction. We prove this observation by analyzing the Schwarz iteration matrices in Fourier space and evaluating corresponding norms in a simplified setting. In order to obtain our contraction results, we had to choose a specific iteration formulation, and we show that other formulations of the same algorithm can generate Schwarz iteration matri...

Density functional theoretical (DFT) calculation has been used for the design and screening of ligand/solvent systems for the selective and efficient extraction of Sr 2+ ion from aqueous solution using free energy analysis. Present DFT study has shown that the metal ion selectivity cannot be predicted using intrinsic gas phase interaction energy alone. Even implicit solvation employing conductor like screening model (COSMO) approach unable to predict the correct trend of experimental selectivity. The COSMO solvation model when used explicitly by considering first solvation sphere around the metal ion it captures the correct trend of experimental selectivity. Organic solvent of high dielectric constant was found to be suitable for the extraction of the metal ion. Further, COSMO for real solvent (COSMO-RS) was successfully used to predict the solubility and partition coefficients of the ligands for screening. Presence of nitrate anion in the complexation reaction was shown to increase the gas as well as solvent phase complexion energy. The calculated theoretical extraction energy was found to be well correlated to the experimentally observed distribution constant of Sr 2+ ion in the biphasic systems. The preferential selectivity of Sr 2+ ion over other competing ions towards macrocyclic ligands was demonstrated by calculating free energy of extraction in the biphasic systems. Natural bond order (NBO) analysis was also performed to investigate the nature of bonding in Sr 2+ ion-crown ether interaction.

Accurate methods for predicting protein-ligand binding affinities are of central interest to computer-aided drug design for hit identification and lead optimization. Here, we used the mining minima (M2) method to predict cucurbit[7]uril binding affinities from the SAMPL4 blind prediction challenge. We tested two different energy models, an empirical classical force field, CHARMm with VCharge charges, and the Poisson-Boltzmann Surface Area (PBSA) solvation model; and a semiempirical quantum mechanical Hamiltonian, PM6-DH+, coupled with the COSMO solvation model and a surface area term for nonpolar solvation free energy. Binding affinities based on the classical force field correlated strongly with the experiments with a correlation coefficient (R2) of 0.74. On the other hand, binding affinities based on the quantum mechanical energy model correlated poorly with experiments (R2 = 0.24), due largely to two major outliers. As we used extensive conformational search methods, these results point to possible inaccuracies in the PM6-DH+ energy model or the COSMO solvation model. Furthermore, the different binding free energy components, solute energy, solvation free energy, and configurational entropy showed significant deviations between the classical M2 and quantum M2 calculations. Comparison of different classical M2 free energy components to experiments show that the change in the total energy, i.e. the solute energy plus the solvation free energy, is the key driving force for binding, with a reasonable correlation to experiment (R2 = 0.56); however, accounting for configurational entropy further improves the correlation.

Galactofuranose (Galf) residues are found in a number of microbial polysaccharides, and knowledge of their conformation is key for developing a molecular-level understanding of their biological roles. To this end, we studied 180 conformations of methyl α- and β-Galf in aqueous solution (COSMO solvation model) using density functional theory (DFT). We compare the calculated low energy conformations to those determined from the program PSEUROT using (1)H NMR data. The lowest energy ring conformation for methyl α-Galf is (2)E, and this conformer is also the major solution conformation obtained by NMR spectroscopy. For methyl β-Galf, (4)E is the lowest energy ring conformation; however, DFT results do not agree with the solution NMR spectroscopic results. Additionally, we developed Galf-specific Karplus-like equations from these conformations.

The prediction of protein-ligand binding affinities is of central interest in computer-aided drug discovery, but it is still difficult to achieve a high degree of accuracy. Recent studies suggesting that available force fields may be a key source of error motivate the present study, which reports the first mining minima (M2) binding affinity calculations based on a quantum mechanical energy model, rather than an empirical force field. We apply a semi-empirical quantum-mechanical energy function, PM6-DH+, coupled with the COSMO solvation model, to 29 host-guest systems with a wide range of measured binding affinities. After correction for a systematic error, which appears to derive from the treatment of polar solvation, the computed absolute binding affinities agree well with experimental measurements, with a mean error 1.6 kcal/mol and a correlation coefficient of 0.91. These calculations also delineate the contributions of various energy components, including solute energy, configurational entropy, and solvation free energy, to the binding free energies of these host-guest complexes. Comparison with our previous calculations, which used empirical force fields, point to significant differences in both the energetic and entropic components of the binding free energy. The present study demonstrates successful combination of a quantum mechanical Hamiltonian with the M2 affinity method.

Stabilization of unstable mispairs on protonation in a DNA sequence can result in a change in the sequence conformation. Such sequences are being actively used for the synthesis of pH-driven molecular switches that have applications in biological pH sensing. We have studied various conformations of different mispairs of bases and their protonated forms using density functional theory (DFT) at B3LYP/6-31+G(d) and M05-2X/6-31+G(d,p) levels. Both gas-phase and aqueous-phase calculations are reported. Solvent phase calculations were done using the PCM and the COSMO solvation model. Our results show that the criterion for the protonation of a particular base in a mispair is not just its higher proton affinity. The planarity of the structure is significantly important, and a planar structure is energetically preferred over a bent mispair. Our calculations also show that the stabilization gained through protonation for the A-C, A-G, and the C-C mispairs is substantial (~20.0 kcal/mol); therefore, these are good candidates for pH-driven molecular switches.

4-[N,N-Bisalkyl]amino-2′-chloro-4′-nitroazobenzenes were recrystallized from acetone in either triclinic or monoclinic cells with the space group P-1 or P21/c. The asymmetric unit cell of dyes having at least one N-cyanoethyl group contained two molecules that were symmetrically unequivalent. The aromatic rings in the azobenzene skeleton were essentially planar with respect to the plane of the azo group, although the C6–C1–N1–N2 torsion angle was 13.2° when the N,N-dicyanoethyl group was employed. X-ray studies were used as a basis for assessing the utility of nonlocal DFT calculations in predicting the equilibrium molecular geometry and solvatochromic properties of the compounds using MM3/ZINDO-S and the COSMO Solvation Model. Although B3LYP and PBE energy functionals were comparable in predicting bond lengths, PBE was slightly better than B3LYP in predicting torsion angles. Furthermore, the dipolarity/polarizability index (π∗) was the preferred solvent parameter for predicting the effects of solvents on λmax.

The hydrated structure of the Cu(II) ion has been a subject of ongoing debate in the literature. In this article, we use density functional theory (B3LYP) and the COSMO continuum solvent model to characterize the structure and stability of [Cu(H2O)n](2+) clusters as a function of coordination number (4, 5, and 6) and cluster size (n = 4-18). We find that the most thermodynamically favored Cu(II) complexes in the gas phase have a very open four-coordinate structure. They are formed from a stable square-planar [Cu(H2O)8](2+) core stabilized by an unpaired electron in the Cu(II) ion d(x(2)-y(2)) orbital. This is consistent with cluster geometries suggested by recent mass-spectrometric experiments. In the aqueous phase, we find that the more compact five-coordinate square-pyramidal geometry is more stable than either the four-coordinate or six-coordinate clusters in agreement with recent combined EXAFS and XANES studies of aqueous solutions of Cu(II). However, a small energetic difference (approximately 1.4 kcal/mol) between the five- and six-coordinate models with two full hydration shells around the metal ion suggests that both forms may coexist in solution.

The conformational properties of the 115–122 region of the prion protein (PrP) were investigated by means of molecular mechanics and DFT computations. From the results of the Monte Carlo Multiple Minimum conformational searches several representative groups could be distinguished. Analysis of these and other characteristic structures like the α-helix and the geometry of the 115–122 region of dissolved PrP (native) revealed the primary importance of N–H⋯O hydrogen bonding interactions in their stabilization, whereas the N–H⋯N interactions play only a marginal role. According to our PBE/TZVPP//RI-PBE/SVP DFT calculations, the isolated β-sheet and α-helical regular secondary structures and the native geometry are less stable than γ-turn, which proved to be the global minimum geometry of the isolated 115–122 PrP fragment. The different solvation energies in aqueous solution, however, change the above picture. The β-sheet structure can be considerable stabilized in water, becoming the most favoured at the PBE/TZVPP//RI-PBE/SVP level using the COSMO solvation model. These results support a possible formation of the β-sheet structure of small PrP fragments involving the 115–122 region in aqueous solution, and in this way the proposed mechanism of their inhibition of the PrP(endogenous) → PrP(pathogenic) conversion.

The influence of treatment of electron correlation, size of basis set and choice of solvation model on the predicted stabilization of zwitterionic phosphinic and phosphonic acid gamma-aminobutyric acid (GABA) analogues is investigated using ab initio molecular orbital methods and density functional theory. Density functional theory with the B3LYP functional and a composite basis set composed of the 6-31+G(2df) basis for phosphorus atoms and the 6-31+G(d,p) basis set for all other atoms is found to give an acceptable tradeoff between accuracy and computational expense. Either directly optimizing zwitterionic conformers within the conductor-like screening solvation model (COSMO) or pre-optimizing as dihydrates and then applying the COSMO solvation model give an acceptable treatment of solvation in terms of determining stable solvated structures, although directly optimizing within COSMO is simpler and less computationally expensive. With this protocol, cis-constrained phosphinic and phosphonic acid GABA analogues, which exhibit lower affinities for GABAC receptors, are found to possess only folded, intramolecularly hydrogen bonded low energy conformers. Trans-constrained analogues, on the other hand, exhibit higher affinities for GABAC receptors and are found to exist only as partially folded stable conformers. Conformationally flexible analogues can attain folded, partially folded or fully extended conformations and also have high biological activity. These results imply that the partially folded conformation is likely to be the most biologically active.

We have developed a general predictive method for vapor pressures and enthalpies of vaporization based on the calculation of the solvation free energy that consists of three components; the electrostatic, dispersion, and cavity formation contributions. The electrostatic contribution is determined using the quantum mechanical COSMO solvation model. Thermodynamic perturbation theory for hard-core molecules is used for the cavity term, and the dispersion term is modeled using a mean field term proportional to the density and molecular surface area. The proposed model uses one set of van der Waals atomic radii to describe molecular shape, two universal interaction parameters for the electrostatic interaction, one set of atom-specific dispersion coefficients, one universal parameter to scale the atomic exposed surface area, and a single universal parameter for the ratio of the hard-core to atomic radii. The model parameters have been determined using 371 pure substances of varying molecular structure, functionality, and size. The average accuracy of the model for vapor pressures and enthalpies of vaporization at the normal boiling temperature is found to be 76% and 4.81 kJ/mol, respectively, with temperature-independent parameters. The average error in the normal boiling temperature is found to be 16 K for species whose boiling points range from 191 to 610 K.

The use of the PBE0 hybrid density functional theory method in conjunction with the COSMO solvation model allowed us to reproduce, both qualitatively and quantitatively, the experimentally observed conformational compositions of 2-substituted and 2,7-disubstituted methylenecyclohexanes. An analysis revealed several different interactions that influence the overall equilibrium. It was found that the endo (general) anomeric effect plays a significant role in the equilibrium and that the "unsaturation effect" possibly comprises two effects.Key words: conformational analysis, methylenecyclohexanes, anomeric effect, unsaturation effect.

The aim of this work is to demonstrate that theoretical chemistry can be used as a complementary tool in determining geometric parameters of a number of uranyl complexes in solution, which are not observable by experimental methods. In addition, we propose plausible structures with partial geometric data from experimental results. A gradient corrected DFT methodology with relativistic effects is used employing a COSMO solvation model. The theoretical calculations show good agreement with experimental X-ray and EXAFS data for the triacetato-dioxo-uranium(VI) and tricarbonato-dioxo-uranium(VI) complexes and are used to assign possible geometries for dicalcium-tricarbonato-dioxo-uranium(VI) and malonato-dioxo-uranium(VI) complexes. The results of this exercise indicate that carbonate bonding in these complexes is mainly bidentate and that hydroxo bridging plays a critical role in the stabilization of the polynuclear uranyl complexes.

The vertical excitation energies of 3,4-dicyano-6-methoxy and 3,4-dicyano-6,7-dimethoxy carbostyril have been computed with different approximations for the time-dependent density functional theory (TD-DFT) procedure and with different implementations of the continuum solvation model COSMO. Different DFT functionals were tested in TD-DFT and Tamm-Dancoff approximations (TDA) for the excitation energies in the gas phase. TDA-B3LYP showed the best agreement with the experimental data. Then TDA-B3LYP computations were performed combined with the COSMO model of solvation comparing a linear response (LR) and a post-configuration interaction (CI) implementation of the fast solvent reorganization. The post-CI solvent model overestimates the π→π* transitions and strongly underestimates the n→π* transition. The TDA approximation in combination with the linear response implementation of the COSMO solvation model perfectly computes the experimental results. TDA-LR is the most reliable method for the computation of the vertical excitation energies in a solvent. Comparison with explicit solvent calculations shows there is only a minor effect on the energies of the electronic interaction of the solute with the solvent.

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, dipole moments and ionisation potentials for the 14 possible tautomers of 2,6-dithioxanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level, both in the gas and aqueous phases, with full geometry optimisation. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that 2,6-dithioxanthine exists as the dithiol forms, but DTX (9,10,11) with N9H of imidazolic ring is more stable than the dithiol-N7H tautomer, DTX (7,10,11) in the gas phase. The predominant tautomer in the aqueous solution exists in an dithione form with the imidazole proton on N9, that is DTX(1,3,9). The results are in good agreement with UV experimental results. The entropy effect on the Gibbs free energy of the 2,6-dithioxanthine base is very small and practically has no significance for the tautomeric equilibria of the base. The enthalpic term is dominant in the determination of the equilibrium constant.

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, relative proton affinities, dipole moments, and ionisation potentials for the fourteen possible tautomers of xanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimisation. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the two diketo tautomers X1,3,7 and X1,3,9 are the predominant species at room temperature in the gas and aqueous phase. But, the first more stable tautomer is the dioxo-7H tautomer, X1,3,7. Comparison with available experimental data provides support for quality of results derived from theoretical computations. The entropy effect on the Gibbs free energy of the xanthine is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant also in the determination of the equilibrium constant.

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, relative proton affinities, dipole moments and ionisation potentials for the fourteen possible tautomers of 6-thioguanine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level, both in the gas and aqueous phases, with full geometry optimisation. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that 6-thioguanine exists as the thiol-amino forms in the gas phase, whereas the thione-amino forms are the predominant tautomers in the aqueous solution. The N9(H) thiol is the most stable tautomer in the gas phase, while the thione-N1,7(H) tautomer is preferred in an aqueous solution. The results are in good agreement with available experimental and theoretical results. The entropy effect on the Gibbs free energy of the 6-thioguanine base is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant also in the determination of the equilibrium constant.

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, dipole moments, and ionization potentials for the eight possible tautomers of hypoxanthine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimization. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the two keto tautomers H17 and H19 are the predominant species at room temperature in the gas and aqueous phase. However, the tautomer H17 is the more dominant species in gas phase, while the H19 tautomer is the more dominant species in the aqueous phase. Comparison with available experimental data provides support for the results derived from theoretical computations. The entropy effect on the Gibbs free energy of hypoxanthine is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant in the determination of the equilibrium constant.

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, tautomeric equilibrium constants, relative proton affinities, dipole moments and ionisation potentials for the eight possible tautomers of 6-thiopurine have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level, both in the gas and aqueous phases, with full geometry optimisation. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that 6-thiopurine exists as the thiol–amino forms in the gas phase whereas the thione–amino forms are the predominant tautomers in the aqueous solution. The thione–N(7)H tautomer is more stable than the thione–N(9)H tautomers in aqueous solution. The results are in good agreement with available experimental and theoretical results. The entropy effect on the Gibbs free energy of the 6-thiopurine base is very small and there is little significance for the tautomeric equilibria of the base. The enthalpic term is dominant also in the determination of the equilibrium constant.

Heats of formation, entropies, Gibbs free energies, relative tautomerization energies, dipole moments, and ionization potentials for the tautomers of 2-thiocytosine, 2,4-dithiouracil and 2,4-dithiothymine and their 1-methyl analogues were studied by using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level both in the gas phase and in aqueous solution, with full geometry optimization. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the thiol-amino tautomer of 2-thiocytosine is the most stable in the gas phase whereas the thione-amino tautomer is the most stable in the aqueous phase. For 2,4-dithiouracil and 2,4-dithiothymine, dithione tautomers are the most stable in both phases. The results are in good agreement with available experimental and theoretical results. The entropy effect on the Gibbs free energy of the thiopyrimidine bases is very small and has practically no significance for the tautomeric equilibria of thiopyrimidine bases. The enthalpic term is dominant in the determination of the equilibrium constant. Copyright © 2001 John Wiley & Sons, Ltd.

Heats of formation, entropies, Gibbs free energies, relative tautomerisation energies, relative proton affinities, tautomeric equilibrium constants, dipole moments, and ionisation potentials for the tautomers of cytosine, uracil, thymine and their 1-methyl analogues have been studied using semiempirical AM1 and PM3 quantum-chemical calculations at the SCF level in the gas and aqueous phases, with full geometry optimisation. The COSMO solvation model was employed for aqueous solution calculations. The calculations show that the oxo-amino or dioxo tautomers are the most stable both in the gas and aqueous phase. The results are in good agreement with the available experimental and theoretical data. The entropy effect on the Gibbs free energy of the pyrimidine bases is very small and there is little significance for the tautomeric equilibria of pyrimidine bases. The enthalpic term is dominant also in the determination of the equilibrium constant.

The ionization (dissociation) constant (pK(a)) is one of the most important properties of a drug molecule. It is reported that almost 68% of ionized drugs are weak bases. To be able to predict accurately the pK(a) value(s) for a drug candidate is very important, especially in the early stages of drug discovery, as calculations are much cheaper than determining pK(a) values experimentally. In this study, we derive two linear fitting equations (pK(a) = a × ΔE + b; where a and b are constants and ΔE is the energy difference between the cationic and neutral forms, i.e., ΔE = E(neutral) -E(cationic)) for predicting pK(a) s for organic bases in aqueous solution based on a training/test set of almost 500 compounds using our previously developed protocol (OLYP/6-311+G**//3-21G(d) with the the conductor-like screening model solvation model, water as solvent; see Zhang, Baker, Pulay, J. Phys. Chem. A 2010, 114, 432). One equation is for saturated bases such as aliphatic and cyclic amines, anilines, guanidines, imines, and amidines; the other is for unsaturated bases such as heterocyclic aromatic bases and their derivatives. The mean absolute deviations for saturated and unsaturated bases were 0.45 and 0.52 pK(a) units, respectively. Over 60% and 86% of the computed pK(a) values lie within ±0.5 and ±1.0 pK(a) units, respectively, of the corresponding experimental values. The results further demonstrate that our protocol is reliable and can accurately predict pK(a) values for organic bases.

Organic radical cations form dicationic dimers in solution, observed experimentally as diamagnetic species in temperature-dependent EPR and low temperature UV/Vis spectroscopy. Dimerization of paraphenylenediamine, N,N-dimethyl-paraphenylenediamine and 2,3,5,6-tetramethyl-paraphenylenediamine radical cation in ethanol/diethylether mixture was investigated theoretically according to geometry, energetics and UV/Vis spectroscopy. Density Functional Theory including dispersion correction describes stable dimers after geometry optimization with conductor-like screening model of solvation and inclusion of the counter-ion. Energy corrections were done on double-hybrid Density Functional Theory with perturbative second-order correlation (B2PLYP-D) including basis set superposition error (BSSE), and multireference Moller-Plesset second-order perturbation theory method (MRMP2) based on complete active space method (CASSCF(2,2)) single point calculation, respectively. All three dication π-dimers exhibit long multicenter π-bonds around 2.9±0.1A with strongly interacting orbitals. Substitution with methyl groups does not influence the dimerization process substantially. Dispersion interaction and electrostatic attraction from counter-ion play an important role to stabilize the dication dimers in solution. Dispersion-corrected double hybrid functional B2PLYP-D and CASSCF(2,2) can describe the interaction energetics properly. Vertical excitations were computed with Tamm-Dancoff approximation for time-dependent Density Functional Theory (TDA-DFT) at the B3LYP level with the cc-pVTZ basis set including ethanol solvent molecules explicitly. A strong interaction of the counter-ion and the solvent ethanol with the monomeric species is observed, whereas in the dimers the strong interaction of both radical cation species is the dominating factor for the additional peak in UV/Vis spectra.

Time-dependent density functional theory (TD-DFT) method was used to study the excited-state hydrogen bonding of three esculetin complexes formed with aprotic solvents. The geometric structures, molecular orbitals (MOs), electronic spectra and the infrared (IR) spectra of the three doubly hydrogen-bonded complexes formed by esculetin and aprotic solvents dimethylsulfoxide (DMSO), tetrahyrofuran (THF) and acetonitrile (ACN) in both ground state S(0) and the first singlet excited state S(1) were calculated by the combined DFT and TD-DFT methods with the COSMO solvation model. Two intermolecular hydrogen bonds can be formed between esculetin and the aprotic solvent in each hydrogen-bonded complex. Based on the calculated bond lengths of the hydrogen bonds and the groups involved in the formation of the intermolecular hydrogen bonds in different electronic states, it is demonstrated that one of the two hydrogen bonds formed in each hydrogen-bonded complex is strengthened while the other one is weakened upon photoexcitation. Furthermore, it is found that the strength of the intermolecular hydrogen bonds formed in the three complexes becomes weaker as the solvents change from DMSO, via THF, to ACN, which is suggested to be due to the decrease of the hydrogen bond accepting (HBA) ability of the solvents. The spectral shifts of the calculated IR spectra further confirm the strengthening and weakening of the intermolecular hydrogen bonds upon the electronic excitation. The variations of the intermolecular hydrogen bond strengths in both S(0) and S(1) states are proposed to be the main reasons for the gradual spectral shifts in the absorption and fluorescence spectra both theoretically and experimentally.

Lanthanide(iii) hydration was studied by utilizing density-functional theory and second-order Møller-Plesset perturbation theory combined with scalar-relativistic 4f-in-core pseudopotentials and valence-only basis sets for the Ln(iii) ions. For [Ln(iii)(H(2)O)(h)](3+) (h = 7, 8, 9) and [Ln(iii)(H(2)O)(h-1)·H(2)O](3+) (h = 8, 9) molecular structures, binding energies, entropies and energies of hydration as well as Gibbs free energies of hydration were calculated using (8s7p6d3f2g)/[6s5p5d3f2g] basis sets for Ln(iii) and aug-cc-pV(D,T)Z basis sets for O and H in combination with the COSMO solvation model. At the generalized gradient approximation level of density-functional theory a preferred hydration number of 8 is found for La(iii)-Tm(iii) and 7 for Yb(iii)-Lu(iii), whereas hybrid density-functional theory predicts a hydration number 8 for all Ln(iii). At the SCS-MP2 level of theory the preferred hydration number is found to be 9 for La(iii)-Sm(iii) and 8 for Eu(iii)-Lu(iii) in good agreement with experimental evidence.

Donor-acceptor biphenyl derivatives are particularly interesting model compounds presenting a charge transfer absorption band because the extent of conjugation, and therefore the amount of charge transfer between the substituents, may be varied by a controllable structural feature, namely the torsion angle between the two phenyl rings. This feature has become even more interesting since chromophores of strong zwitterionic character, synthesized with a twist of nearly 90°, have been shown to exhibit unprecedented quadratic responses [1], over an order of magnitude above that of the best conventional push-pull chromophores. In this context, we have investigated both experimentally and theoretically, two biphenyl based systems with varying inter-aryl angles: a nitro-piperidinyl series [2] of conventional push-pull character and a pyridinium-phenoxide series [3] of zwitterionic character. The results agree qualitatively with semiempirical simulations based on the AM1 Hamiltonian [4] used with the COSMO solvation model [5]. For the first series, the decrease in quadratic response with increasing dihedral angle indicates that oscillator strength loss is the dominant factor. In the second series, the corresponding increase in quadratic response points to the change in dipole moment upon excitation as the leading effect. Here, we will analyze to what extent the more ab initio electronic structure calculations based on the density functional theory may provide more quantitative results in spite of the problems they face in the description of charge transfer systems.

The experimental M−A and M−B distances in several series of [MAnBm-n]-type complexes have been studied by DFT. Many of the structural features of the series, such as trans influences and sterically induced bond elongations, are not reproduced correctly in gas-phase DFT calculations. However, the correct trends are recovered by explicitly including environmental effects via the COSMO solvation model. These observations imply that the condensed-phase environment plays a critical role in determining the geometric structure of coordination complexes. Thus, any apparently satisfactory reproduction of the condensed-phase structure by an in vacuo calculation may mask an incorrect treatment of the interplay between different ligands attached to the same metal center.

We have developed a simple and quantitative explanation for the relatively low melting temperatures of ionic liquids (ILs). The basic concept was to assess the Gibbs free energy of fusion (Delta(fus)G) for the process IL(s) --IL(l), which relates to the melting point of the IL. This was done using a suitable Born-Fajans-Haber cycle that was closed by the lattice (i.e., IL(s) --IL(g)) Gibbs energy and the solvation (i.e., IL(g) --IL(l)) Gibbs energies of the constituent ions in the molten salt. As part of this project we synthesized and determined accurate melting points (by DSC) and dielectric constants (by dielectric spectroscopy) for 14 ionic liquids based on four common anions and nine common cations. Lattice free energies (Delta(latt)G) were estimated using a combination of Volume Based Thermodynamics (VBT) and quantum chemical calculations. Free energies of solvation (Delta(solv)G) of each ion in the bulk molten salt were calculated using the COSMO solvation model and the experimental dielectric constants. Under standard ambient conditions (298.15 K and 10(5) Pa) Delta(fus)G degrees was found to be negative for all the ILs studied, as expected for liquid samples. Thus, these ILs are liquid under standard ambient conditions because the liquid state is thermodynamically favorable, due to the large size and conformational flexibility of the ions involved, which leads to small lattice enthalpies and large entropy changes that favor melting. This model can be used to predict the melting temperatures and dielectric constants of ILs with good accuracy. A comparison of the predicted vs experimental melting points for nine of the ILs (excluding those where no melting transition was observed and two outliers that were not well described by the model) gave a standard error of the estimate (s(est)) of 8 degrees C. A similar comparison for dielectric constant predictions gave s(est) as 2.5 units. Thus, from very little experimental and computational data it is possible to predict fundamental properties such as melting points and dielectric constants of ionic liquids.

The most recent algorithmic enhancements of the COSMO solvation model are presented and the implementation in the TURBOMOLE program package is described. Three demonstrative applications covering homogeneous catalysis, tautomeric equilibria, and binary phase diagrams show the efficiency and general applicability of the approach. Especially when combined with the COSMO-RS extension, the method very reliably predicts thermodynamic properties of liquid mixtures.

WOS: 000085996600002, Potentially tautomeric pyrazole-3-ones were studied, in order to predict their tautomeric equilibrium constants and pK(a) values, using the semiempirical AM1 COSMO solvation model at the SCF level in aqueous solution. Syn and anti conformers of the hydroxy form were also investigated to find a more stable form. The oxo forms have been found to be more stable than the hydroxy ones. The results obtained from the tautomeric equilibria and acidity calculations are in good agreement with experimental data. (C) 2000 Elsevier Science B.V. All rights reserved.

Ab initio calculations have been carried out on both gas-phase and solvated phthalocyanines in order to determine equilibrium structures, vibrational spectra, and electronic spectra. Density functional theory (DFT) optimized geometries have the expected symmetries of D 2h for free-base phthalocyanine, D 4h for copper phthalocyanine, and C 4v for tin phthalocyanine, whereas Hartree–Fock optimized geometries, which also include lead phthalocyanine, are slightly displaced from the expected symmetries. Both sets of optimized geometries agree reasonably well with the available experimental structures. Vibrational spectra, calculated by the Hartree–Fock method, are in partial agreement with measured spectra, whereas visible absorption spectra calculated using molecular geometries obtained at three different levels of theory (DFT, HF, and PM3) showed good agreement with the measured vapor-phase spectra in the Q-band, and using the DFT optimized geometry resulted in very good agreement with measurements in the B-band. The self-consistent reaction field method for including bulk solvent effects in HF calculations had a small, nearly negligible, effect on the molecular structure of SnPc, whereas the DFT/ cosmo solvation model yielded the predictable result of increasing the Sn–N bond length by pulling the Sn atom further out of the molecular plane.

We present the design, synthesis, spectroscopy, and biological applications of PyBor, a new type of fluorescent probe for peroxynitrite detection in aqueous solution and living cells. The probe employs pyrene as the fluorophore, and is equipped with a chemically responsive unit boronate. The fluorescent probe can selectively detect peroxynitrite with fluorimetric determination and high-performance liquid chromatography analyses in aqueous solution and RAW264.7 cells intracellular free extracts. We also study our probe to time dependent peroxynitrite release from 3-morpholinylsydnonimine hydrochloride. Confocal microscopy experiments using mouse macrophage cell line RAW264.7 show that PyBor is able to detect the different intracellular peroxynitrite levels. In addition, we have performed quantum chemical calculations with TD-DFT/M06/TZVP level with COSMO solvation model basis sets using a suite of Gaussian 09 programs to provide insights into the structure optical properties of PyBor and PyOH.

First principles density functional theory (Perdew-Burke-Ernzerhof) calculations have been used to compute the hydration properties, aqueous-phase acid dissociation constants (pK(a)) and Gibbs free energies of formation of small polyphosphates in aqueous solution. The effect of the hydrated environment has been simulated through a hybrid microsolvation-continuum approach, where the phosphate species are simulated as microsolvated solutes, while the remainder of the bulk solvent is treated as a dielectric continuum using the COSMO solvation model. The solvation free energies of orthophosphates and pyrophosphates have been computed applying monomer and cluster thermodynamic cycles, and using the geometries optimised in the gas-phase as well as in the COSMO environment. The results indicate that the simple polarisable continuum or microsolvation-continuum models are unable to compute accurate free energies of solvation for charged species like phosphates. The calculation of the pK(a) shows that the computed values of acid dissociation constants are critically dependent on the number of water molecules n(H(2)O) included in the hydrated phosphate clusters. The optimal number n(H(2)O) is determined from the minimum value of the "incremental" water binding free energy associated with the process of adding a water molecule to a micro-solvated phosphate species. Analysis of the effect of n(H(2)O) on the free energies of orthophosphate condensation reactions shows that can vary by tenths of kcal mol(-1), depending on the particular choice of n(H(2)O) for the monomeric and dimeric species. We discuss a methodology for the determination of n(H(2)O); for the orthophosphates the "incremental" binding energy approach is used to determine n(H(2)O), whereas for the polyphosphates the number of explicit water molecules is simply equal to the effective charge of these anions. The application of this method to compute the free energy of formation of pyro- and tri-phosphates gives generally good agreement with the available experimental data.

Thermo-solvatochromism of two polarity probes, 2,6-diphenyl-4-(2,4,6-triphenyl- pyridinium-1-yl)phenolate, RB, and 2,6-dichloro-4-(2,4,6-triphenylpyridinium-1-yl) phenolate, WB, in aqueous acetone, Me2CO, and aqueous dimethylsulfoxide, DMSO, has been studied. The data obtained have been analyzed according to a recently introduced solvation model that explicitly considers the presence of 1:1 organic solvent-water hydrogen-bonded species, S-W, in the bulk binary mixture and its exchange equilibria with (S) and (W) in the solvation shell of the probe. Calculations require reliable values of Kdissoc, the dissociation constant of S-W. Previously, this has been calculated from the dependence of the densities of binary solvent mixtures on their composition. Using iteration, the volume of the hydrogen-bonded species, VS-W, and Kdissoc were obtained simultaneously from the same set of experimental data. This approach may be potentially suspect because Kdissoc, and VS-W are highly correlated. Therefore, we extended a recently introduced approach for the calculation of Valcohol-W to binary mixtures of water with acetone, acetonitrile, N,N-dimethylformamide, DMSO, and pyridine. This approach includes: Determination of VS-W from ab initio calculations by the COSMO solvation model; correction of these volumes for the nonideal behavior of the binary solvent mixtures at different temperatures; use of corrected VS-W as a constant (not an adjustable parameter) in the equation that is employed to calculate Kdissoc (from density versus binary solvent composition). Solvation of RB and WB by Me2CO-W showed different behavior from that of aqueous DMSO. Thus, water is able to displace Me2CO more efficiently than DMSO from the probe solvation shell. Me2CO-W and DMSO-W displace their corresponding precursor solvents; this is more efficient for the former case because the strong DMSO-W interactions attenuate the solvation capacity of this species. Temperature increase resulted in desolvation of both probes, due to concomitant decrease of the structures of the component solvents.

AM1 and PM3 SCF-MO/COSMO solvation modelling of the solvatochromic properties of the rhodamine-based colour forming dyes reproduces the known relative stabilities of these molecules and demonstrates how theoretically constructed linear-free-energy relationships could be used in the rational design of new systems.

This article describes BP86/SV(P) (DFT) calculations on a representative set of weakly coordinating anions (WCAs) of type [M(L)n]-, their parent neutral Lewis acids M(L)(n-1) and their ate complexes with fluoride, that is, [FM(L)(n)](n-1) (M=B, L=F, OTeF5, C6H5, C6F5, C6H3(CF3)2, CF3; M=P, As, Sb, L=F, OTeF5; M=Al, L=OC(CF3)3). Compounds with fluoride bridges, that is, Sb(n)F(5n) and [Sb(n)F(5n+1)]- (n=2, 3, 4), Al2(L)5F and [(L)3Al-F-Al(L)3]- (L=OC(CF3)3), (F4C6[1,2-B(L)2]2, [F4C6[1,2-B(L)2]2F]-, [F4C6[1,2-B(L)2]2OMe]- (L=C6F5) were also calculated. Based on these BP86/SV(P) and auxiliary MP2/TZVPP, G2, and CBS-Q calculations the relative stabilities and coordinating abilities of these WCAs were established with regard to the fluoride ion affinities (FIA) of the parent Lewis acids, the ligand affinity (LA) of the WCAs, the decomposition of a given WCA in the presence of a hard (H+, proton decomposition PD) and a soft electrophile (Cu+, copper decomposition CuD), the position of the HOMO, the HOMO-LUMO gap, and population analyses of the anions providing partial charges for all atoms. To obtain data that is more reliable, the assessed quantities were calculated through isodesmic reactions. If parts of the calculations could not be done isodesmically, higher levels such as MP2/TZVPP, G2, and CBS-Q were used to obtain reliable values for these reactions. Although the obtained results can not be taken as absolute, the relative ordering of the stabilities of all WCAs will undoubtedly be correct, since a single methodology was chosen for the investigation. To include media effects the decomposition reactions of a subset of 14 WCAs with the SiMe3+ and [Cp2ZrMe]+ ions were also calculated in PhCl and 1,2-F2C6H4 (COSMO solvation model). We found that in most cases gas-phase calculations and solution calculations give comparable results for the stability of the anion. Applications of the LA and FIA that allow one to decide, on thermodynamic grounds, which WCA or Lewis acid is the most suitable for a given problem are sketched.