Conductor-like Screening Solvation Model Research Articles

Ru‐Catalyzed Cross Dehydrogenative Coupling Leading to Si−O and Si−S Bond Formations and Also Stimulating an Alternative Scope for Hydrogenation of C=O, C=N and N=N Bonds

AbstractReaction pathways involved in catalytic Cross Dehydrogenative Coupling (CDC) reactions leading to formation of Si−O and Si−S bonds have been formulated and explored theoretically using Density Functional Theory (DFT). The advantage of the weak Si−H bond has been exploited to carry out coupling with water, alcohol and thiol, along with H2 release. Ru complex, [K(dme)2][Ru(H)(trop2dad)] when reacts with water generates a neutral complex, [Ru(trop2dad)]. This neutral complex has been employed to act as a catalyst in CDC reactions. It has also been found that the complex, [Ru(H2)(trop2dad)] formed within the catalytic cycle may also be used for hydrogenation of C=O, C=N and N=N bonds. The optimized geometries of all the complexes and transition states have been obtained using wB97xd functional in conjunction with 6‐31++G(d,p) basis set. The whole assisting phenomena in solvent medium has been investigated through the implementation of conductor‐like screening solvation model (COSMO) considering tetrahydrofuran as the bulk solvent medium. The Turnover frequency (TOF) has been calculated by Energetic Span Model. The theoretical investigation extends the role of the ruthenium catalyst to the regime of ‘element to element’ bond formation, along with H2 release, which may be significant in the field of energy storage, and also triggers an alternative possibility of hydrogenation of carbonyls, imines and diazo compounds.

Dehydrocyclization of diamine borane and amine-borane alcohol catalyzed by 1-lithio-2-alkyl-1,2-dihydropyridine and its Na & K analogues: A DFT analysis of the reaction mechanism

Reaction pathways for dehydrogenation and hence cyclization of diamine-monoborane and amine-borane alcohol have been explored theoretically using Density Functional Theory (DFT). The diamine-monoborane and amine-borane alcohol chosen for investigation in the present venture are N-(tert-butyl)(BH3)–N′-tert-butyl-ethylenediamine and α,α-Diphenyl-2-pyrrolidinemethanol-borane. Alkali metal catalysts, viz., 1-lithio-2-tert-butyl-1,2-dihydropyridine and its sodium and potassium analogues have been employed for the removal of two equivalents of H2. The optimized geometries of all the reactant complexes, intermediates, transition states and product complexes have been obtained using ωB97xd functional in conjunction with 6–31++G(d,p) basis set. The whole assisting phenomena in solvent medium has been investigated through the implementation of conductor-like screening solvation model (COSMO) primarily considering benzene as the bulk solvent medium. The investigation has further been extended to solvents tetrahydrofuran and pyridine to examine the participation of solvent molecules in bringing any change in reaction mechanism and catalytic cycle of the lithium catalyst over diamine-borane. The intramolecular and all possible intermolecular (catalytic) pathways have been studied in detail. Our study supports previous experimental studies and elucidates key role in the catalytic regime of 1,2-dihydropyridine, which is able to store and deliver Li–H on demand.

Possible reaction pathways of the lincomycin molecule according to the DFT calculation method

Human-used antibiotics are eliminated from the body with little or no transformation at all. Traces of eliminated antibiotics enter the receiving environment directly since they cannot be treated in prevalent wastewater treatment facilities. Thus, wastewaters containing traces of antibiotics have to be treated accordingly. Lincomycin is subsequently isolated from Streptomyces lincolnensis. Lincomycin and its derivatives are antibiotics exhibiting biological activity against Gram-positive bacteria, and are natural antibiotics in the environment as pollutants. This study aims to predict the degradation mechanism of lincomycin molecule in the gaseous phase and aqueous media. Probable reaction path of lincomycin molecule with OH radicals was analyzed. Optimized geometry was calculated via Gauss View 5. Subsequently, the lowest energy status was determined through geometric optimization via Gaussian 09 program. Aiming to determine the intermediates in photocatalytic degradation mechanism of lincomycin, geometric optimization of the molecule was realized through DFT method. Activation energy for the probable reaction path was calculated, and their most stable state from the thermodynamic perspective determined for the gaseous phase and aqueous media. Impact of water solvent was investigated using the conductor-like screening solvation model (COSMO). The predicted mechanism was confirmed by comparison with experimental results on simple structures reported in literature.

Use of Broken-Symmetry Density Functional Theory To Characterize the IspH Oxidized State: Implications for IspH Mechanism and Inhibition.

With current therapies becoming less efficacious due to increased drug resistance, new inhibitors of both bacterial and malarial targets are desperately needed. The recently discovered methylerythritol phosphate (MEP) pathway for isoprenoid synthesis provides novel targets for the development of such drugs. Particular attention has focused on the IspH protein, the final enzyme in the MEP pathway, which uses its [4Fe–4S] cluster to catalyze the formation of the isoprenoid precursors IPP and DMAPP from HMBPP. IspH catalysis is achieved via a 2e–/2H+ reductive dehydroxylation of HMBPP; the mechanism by which catalysis is achieved, however, is highly controversial. The work presented herein provides the first step in assessing different routes to catalysis by using computational methods. By performing broken-symmetry density functional theory (BS–DFT) calculations that employ both the conductor-like screening solvation model (DFT/COSMO) and a finite-difference Poisson–Boltzmann self-consistent reaction field methodology (DFT/SCRF), we evaluate geometries, energies, and Mössbauer signatures of the different protonation states that may exist in the oxidized state of the IspH catalytic cycle. From DFT/SCRF computations performed on the oxidized state, we find a state where the substrate, HMBPP, coordinates the apical iron in the [4Fe–4S] cluster as an alcohol group (ROH) to be one of two, isoenergetic, lowest-energy states. In this state, the HMBPP pyrophosphate moiety and an adjacent glutamate residue (E126) are both fully deprotonated, making the active site highly anionic. Our findings that this low-energy state also matches the experimental geometry of the active site and that its computed isomer shifts agree with experiment validate the use of the DFT/SCRF method to assess relative energies along the IspH reaction pathway. Additional studies of IspH catalytic intermediates are currently being pursued.

Interaction Between Group IIb Divalent Transition-Metal Cations and 3-Mercaptopropionic Acid: A Computational and Topological Perspective

Density functional theory was applied to study the interaction of group IIb transition-metal cations (Zn(2+), Cd(2+), and Hg(2+)) with one and two fully or partially deprotonated 3-mercaptopropionic acid ligands. In this investigation, we determined the geometries of all possible complexes resulting from the coordination of the metal ions with the ligands at different binding sites selected on each ligand. The relative energies of the complexes, metal-ion affinities, free energies, and entropies were also determined. The natures of the bonds were critically analyzed by natural bond orbital (NBO) analysis and clarified further using the atoms-in-molecules (AIM) approach. The substantial influence of the solvent (water) polarization on the energetics, geometries, and bonding of the molecular complexes was also investigated by the conductor-like screening solvation model (COSMO). In an attempt to simulate the complexes in an aqueous environment, water molecules were added explicitly to complete the coordination sphere of the metal cations, and the corresponding metal-ion affinities were calculated to study the effect of microhydration.

DFT calculations for intermediate and active states of the diiron center with a tryptophan or tyrosine radical in Escherichia coli ribonucleotide reductase.

Class Ia ribonucleotide reductase subunit R2 contains a diiron active site. In this paper, active-site models for the intermediate X-Trp48(•+) and X-Tyr122(•), the active Fe(III)Fe(III)-Tyr122(•), and the met Fe(III)Fe(III) states of Escherichia coli R2 are studied, using broken-symmetry density functional theory incorporated with the conductor-like screening solvation model. Different structural isomers and different protonation states have been explored. Calculated geometric, energetic, Mössbauer, hyperfine, and redox properties are compared with available experimental data. Feasible detailed structures of these intermediate and active states are proposed. Asp84 and Trp48 are most likely the main contributing residues to the result that the transient Fe(IV)Fe(IV) state is not observed in wild-type class Ia E. coli R2. Asp84 is proposed to serve as a proton-transfer conduit between the diiron cluster and Tyr122 in both the tyrosine radical activation pathway and the first steps of the catalytic proton-coupled electron-transfer pathway. Proton-coupled and simple redox potential calculations show that the kinetic control of proton transfer to Tyr122(•) plays a critical role in preventing reduction from the active Fe(III)Fe(III)-Tyr122(•) state to the met state, which is potentially the reason why Tyr122(•) in the active state can be stable over a very long period.

Continuous and smooth potential energy surface for conductorlike screening solvation model using fixed points with variable areas

Rigorously continuous and smooth potential energy surfaces, as well as exact analytic gradients, are obtained for a conductorlike screening solvation model (CPCM, a variant of the general COSMO) with Hartree-Fock (RHF, ROHF, UHF, and MCSCF) and density functional theory (R-DFT, RO-DFT, and U-DFT) methods using a new tessellation scheme, fixed points with variable areas (FIXPVA). In FIXPVA, spheres centered at atoms are used to define the molecular cavity and surface. The surface of each sphere is divided into 60, 240, or 960 tesserae, which have positions fixed relative to the sphere center and areas scaled by switching functions of their distances to neighboring spheres. Analytic derivatives of the positions and areas of the surface tesserae with respect to atomic coordinates can be obtained and used to evaluate the solvation energy gradients. Due to the accurate analytic gradients and smooth potential energy surface, geometry optimization processes using these methods are stable and convergent.

First-principles calculation of pKa for cocaine, nicotine, neurotransmitters, and anilines in aqueous solution.

The absolute pKa values of 24 representative amine compounds, including cocaine, nicotine, 10 neurotransmitters, and 12 anilines, in aqueous solution were calculated by performing first-principles electronic structure calculations that account for the solvent effects using four different solvation models, i.e., the surface and volume polarization for electrostatic interaction (SVPE) model, the standard polarizable continuum model (PCM), the integral equation formalism for the polarizable continuum model (IEFPCM), and the conductor-like screening solvation model (COSMO). Within the examined computational methods, the calculations using the SVPE model lead to the absolute pKa values with the smallest root-mean-square-deviation (rmsd) value (1.18). When the SVPE model was replaced by the PCM, IEFPCM, and COSMO, the rmsd value of the calculated absolute pKa values became 3.21, 2.72, and 3.08, respectively. All types of calculated pKa values linearly correlate with the experimental pKa values very well. With the empirical corrections using the linear correlation relationships, the theoretical pKa values are much closer to the corresponding experimental data and the rmsd values become 0.51-0.83. The smallest rmsd value (0.51) is also associated with the SVPE model. All of the results suggest that the first-principles electronic structure calculations using the SVPE model are a reliable approach to the pKa prediction for the amine compounds.

A quantitative structure–activity relationship investigation into agonist binding at GABA C receptors

The quantitative structure–activity relationship (QSAR) model constructed in this work represents the first quantitative investigation into agonist binding at GABA C receptors. This model is based upon the three-dimensional structures of (γ-aminobutyric acid (GABA) and 12 other biologically active GABA analogues. These structures are obtained by geometry optimization and conformational exploration at MP2/6-31+G* within the conductor-like screening solvation model (COSMO). The biological activity data are obtained from previous two-electrode voltage clamp electrophysiological studies on recombinant GABA C ρ1 receptors expressed in Xenopus laevis oocytes. A QSAR model to predict GABA C agonist binding is constructed from molecular superposition data, generated by least-squares superposition of the stable aqueous phase conformations of GABA and its known biologically active analogues to the bioactive conformation of TACA, the most potent GABA C receptor agonist. A significant relationship is found between the root-mean-squared deviation in atomic position for the stable conformer of each GABA analogue most closely fitting the template TACA structure and the natural log of the normalized biological activity ( R 2=0.91, p<0.0001), On the basis of molecular superposition and QSAR results, a pharmacophore model describing three-dimensional features and key interactions at the GABA C receptor binding site is proposed. As there exists no direct experimental knowledge of structure of the GABA C binding site, this approach provides a feasible and reliable alternative to gain insight into its three-dimensional structure.

Stabilization of Zwitterions in Solution: Phosphinic and Phosphonic Acid GABA Analogues

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.

Stabilization of Zwitterions in Solution: GABA Analogues

The solution-phase structures of a number of conformationally restricted gamma-aminobutyric acid (GABA) analogues are investigated at the MP2/6-31+G* level of theory, using both explicit water molecules and the conductor-like screening solvation model (COSMO) to model solvation. GABA analogues constrained in a cis conformation by either a double bond or cyclopropane ring have the potential to attain either folded, intramolecularly hydrogen-bonded, or partially folded conformations in solution. Systems constrained in a cis conformation by a cyclopentane or cyclopentene ring are more conformationally restricted and exist only in a folded, intramolecularly hydrogen-bonded form. GABA analogues constrained in a trans conformation by either a double bond or cyclopropane ring have the potential to adopt either partially folded or fully extended conformations in solution. Due to a lack of conformational flexibility, analogues that are constrained in a trans conformation by a cyclopentane or cyclopentene ring attain only partially folded conformations. Like GABA, conformationally flexible GABA analogues possess a large number of stable rotamers, and may exist in any or all of these conformations in aqueous solution. The structures of these analogues provide an essential foundation for subsequent structure-activity analysis of ligand binding at GABA receptors and transporters. This work is therefore expected to facilitate the design and development of new biologically active GABA analogues to treat GABA-related neurological disorders.

Stabilization of Zwitterions in Solution: γ-Aminobutyric Acid (GABA)

The stabilization of γ-aminobutyric acid (GABA) zwitterions in aqueous solution is investigated at the HF/6-31+G*, B3LYP/6-31+G*, and MP2/6-31+G* levels of theory using explicitly bound water molecules to model short-range solvent effects and the conductor-like screening solvation model (COSMO) to estimate long-range solvent interactions. B3LYP and MP2 yield similar structures, relative energies and overall trends whereas HF theory does not provide a realistic description of GABA. The only approaches yielding zwitterionic structures consistent with experiment are the application of COSMO to GABA·2H2O or GABA·5H2O. An accurate description of aqueous phase GABA therefore requires both explicit interaction with at least two water molecules and long-range dielectric interactions with the solvent. Both types of interaction preferentially stabilize zwitterionic over neutral structures and stabilize extended zwitterions with respect to folded conformers. No stable neutral GABA·5H2O tautomers are obtained, sugges...

Tautomerism of 6-thioxanthine in the gas and aqueous phases using AM1 and PM3 methods

Heats of formation, entropies, Gibbs free energies, relative tautomerization energies, tautomeric equilibrium constants, relative proton affinities, dipole moments, and ionization potentials for the fourteen possible tautomers of 6-thioxanthine have been studied by using semiempirical AM1 and PM3 quantum-chemical calculations at the self-consistent field level, both in the gas and aqueous phases, with full geometry optimization. The conductor-like screening solvation model was employed for aqueous solution calculations. The calculations show that the two oxothione tautomers, TX (1,3,7) and TX (1,3,9), are the predominant species at room temperature in both phases, but the oxothione-N7(H) form is more stable than the oxothione-N9(H) form. The energy difference between TX (1,3,7) and TX (1,3,9) is predicted to be significantly lowered by the polar solution. The results are in good agreement with available experimental results. The entropy effect on the Gibbs free energy of the 6-thioxanthine base is very small and has practically no significance for the tautomeric equilibrium of the base. The enthalpic term is dominant in the determination of the equilibrium constant. The protonation of 6-thioxanthine in both phases occurs at the imidazole nitrogen (N7 or N9), then pyrimidine nitrogen (N1 or N3).

Quantum Calculation of Molecular Energies and Energy Gradients in Solution by a Conductor Solvent Model

A new implementation of the conductor-like screening solvation model (COSMO) in the GAUSSIAN94 package is presented. It allows Hartree−Fock (HF), density functional (DF) and post-HF energy, and HF and DF gradient calculations: the cavities are modeled on the molecular shape, using recently optimized parameters, and both electrostatic and nonelectrostatic contributions to energies and gradients are considered. The calculated solvation energies for 19 neutral molecules in water are found in very good agreement with experimental data; the solvent-induced geometry relaxation is studied for some closed and open shell molecules, at HF and DF levels. The computational times are very satisfying: the self-consistent energy evaluation needs a time 15−30% longer than the corresponding procedure in vacuo, whereas the calculation of energy gradients is only 25% longer than in vacuo for medium size molecules.