Isodensity Polarized Continuum Model Research Articles

Theoretical study of solvent effects on the conformational preference in CH 2FWH (W=O, S) using PCM and IPCM methods

The solvent effect on conformational stability and physical properties, such as dipole moment, chemical potential and chemical hardness in CH 2FWH (W=S, O) has been examined using HF, MP2 and B3LYP methods with the 6-311 + G(d,p) basis set by applying the polarizable continuum model (PCM) and the isodensity polarizable continuum model (IPCM). All the conformers are stabilized in going from the gas phase to solution one. Gauche conformer, the most stable conformer in the gas phase, is still the most stable conformer in the solution phase. The electrostatic contribution to the salvation energy is mainly responsible for the changes of relative energies. The results obtained with these methods reveal that the anomeric effect decreases as the dielectric constant of medium increases. The energetic preference of gauche over anti in polar solvents ( ε > 5) is greater in CH 2FSH than in CH 2FOH. Similar to the gas phase, natural bond orbital (NBO) analysis shows that the effect of electrostatic and steric contributions involved in the Lewis term on stability of gauche conformers is still less important than the charge delocalization. Furthermore, the preference of delocalization effect over electrostatic and steric effects in the solution phase is greater than the gas phase.

Ground and excited states calculations of 7-phenylamino-substituted coumarins

A theoretical calculation of the ground and first excited states of two 7-phenylamino-substituted coumarin compounds are performed. In order to study the effect of phenyl substituted in amino group and fluorine atoms substituted in methyl group, 7-amino-4-methyl coumarin (C120) and 7-amino-4-(trifluoromethyl) coumarin (C151) were also studied. The geometries of the ground state and the first ground state were optimized using density function theory and configuration interaction singles levels of theory. Molecular orbitals (MO) of the ground and first excited states of the four coumarin compounds were obtained to explain the change of the structures. ZINDO and TD-DFT methods with different basis sets were applied to predict the UV absorption spectra. The solvent effect had also been taken into account using self-consistent isodensity polarized continuum model. The predicted spectra are in agreement with the experimental data.

UV–visible, 1H and 13C NMR spectroscopic studies on the interaction between protons or alkaline earth metal ions and the benzoate ion in acetonitrile

The interaction between protons (H +) or alkaline earth metal ions (Mg 2+, Ba 2+) and the benzoate ion has been examined in acetonitrile by means of UV–visible, 1H and 13C NMR spectroscopy. The assignments of 13C NMR spectra for the benzoate ion (L −), benzoic acid (HL), and the protonated benzoic acid (H 2L +) in acetonitrile were properly performed by means of theoretical calculations, including the influence of the acetonitrile solvent by using the self-consistent isodensity polarized continuum model and the polarized continuum model. It is demonstrated that “strong” interactions of alkaline earth metal ions (M 2+ = Mg 2+, Ba 2+) with the benzoate ion (L −) lead to the formation of mono-charged species, ML +, as well as non-charged species, ML 2, in acetonitrile solution: the strong ability in coordination for alkaline earth metal ions is verified.

TDDFT Study of the Electronic Structure, Absorption and Emission Spectra of the Light Emitters of the Amazing Firefly Bioluminescence and Solvation Effects on the Spectra

AbstractThe ground and excited state properties of luciferin (LH2) and oxyluciferin (OxyLH2), the bioluminescent chemicals in the firefly, have been characterized using density functional theory (DFT) and time dependent DFT (TDDFT) methods. The effects of solvation on the electronic absorption and emission spectra of luciferin and oxyluciferin were predicted with a self‐consistent isodensity polarized continuum model of the solvent using TDDFT. The S0→S1 vertical excitation energies in the gas phase and in water were obtained. Optimizations of the excited state geometries permitted the first predictions of the fluorescence spectra for these biologically important molecules. Shifts in both of the absorption and emission spectra on proceeding from the gas phase to aqueous solution were also predicted.

Conformational Preferences of N-Acetyl-l-leucine-N‘-methylamide. Gas-Phase and Solution Calculations on the Model Dipeptide

A DFT study of N-acetyl-l-leucine-N'-methylamide conformers in the gas phase and in solution was carried out. The theoretical computational analysis revealed 43 different conformations at the B3LYP/6-31G(d) level of theory in the gas phase. In addition, the effects of three solvents (water, acetonitrile, and chloroform) were included in the calculations using the isodensity polarizable continuum model (IPCM) and the Poisson-Boltzmann self-consistent reaction field (PB-SCRF) method. The stability order of the different conformers in solution has been analyzed. The theoretical results were compared with some experimental data (X-ray, IR, and NMR).

The effects of conformation and solvation on optical rotation: Substituted epoxides

The vapor-phase optical rotation (or circular birefringence) of (S)-1,2-epoxybutane, (S)-epichlorohydrin, and (S)-epifluorohydrin has been measured at the nonresonant excitation wavelengths of 355 nm and 633 nm by means of Cavity Ring-Down Polarimetry (CRDP). Complementary solution-phase studies were performed in a wide variety of dilute solvent media to highlight the pronounced influence of solute-solvent interactions. Density functional theory calculations of optical activity have been enlisted to unravel the structural and electronic provenance of experimental observations. Three stable, low-lying conformers have been identified and characterized for each of the targeted chiral species, with thermal (relative population weighted) averaging of their antagonistic chiroptical properties allowing specific rotation values to be predicted under both isolated and solvated conditions. For (S)-epichlorohydrin and (S)-epifluorohydrin, a self-consistent isodensity polarizable continuum model (SCI-PCM) has been exploited to gain further insight into the underlying nature of solvation effects.

Medium Effect on the Rotational Barrier of Carbamates and Its Sulfur Congeners

The solvent effect on rotation about the conjugated C-N bond has been studied for methyl N,N-dimethylcarbamate (1), S-methyl N,N-dimethylthiocarbamate (2), O-methyl N,N-dimethylthiocarbamate (3), and methyl N,N-dimethyldithiocarbamate (4). The present investigation included experimental determination of activation parameters (DeltaH, DeltaS, and DeltaG) combined with theoretical calculations via both quantum and classical approaches. Rotational barriers were measured through dynamic NMR experiments in solvents of varied polarity and proton donor ability. In the less polar solvents, the values were 15.3+/-0.5 (CS2), 14.0+/-1.1 (CS2), 17.5+/-0.4 (CCl4), and 14.6+/-0.5 kcal/mol (CCl4) for 1, 2, 3, and 4, respectively. Upon changing to an aqueous solution, the greatest variations occurred for 2 and 4, whereas for 1 and 3, there was no observable effect. Quantum chemical calculations at the HF/6-311+G(2d,p) and B3LYP/6-311+G(2d,p) levels, with the inclusion of solvation effects via the isodensity polarizable continuum model (IPCM), correctly reproduced the experimentally observed trends but failed to account for some of the measured rotational barrier's magnitudes. Hydrogen-bonding effects were included by performing molecular dynamic simulations. For these latter calculations, it was necessary to parametrize the force field against energies of water-solute complexes calculated at B3LYP/6-31+G(d,p). Through the results of radial distribution functions, solution rotational barriers could be calculated, presenting good agreement with experimental determinations and revealing the role of hydrogen bonding. Interestingly, only for 2, the rotational barrier is predicted to increase as a result of complexation with water. For the remaining compounds, hydrogen bonding causes the barrier to decrease, contrasting with most of the molecular systems studied up to now.

Importance of the Single Amino Acid Potential in Water for Secondary and Tertiary Structures of Proteins

The structure of a protein molecule is considered to be primarily determined by the inter-amino-acid nonbonded interactions, such as hydrogen bonds. However, the conformational space of the polypeptide chain should be simultaneously restricted by the intrinsic conformational preferences of the individual amino acids. We present here precise single amino acid potential (SAAP) surfaces for glycine (For-Gly-NH(2)) and alanine (For-Ala-NH(2)) in water (epsilon = 78.39) and ether (epsilon = 4.335), which were calculated at the HF/6-31+G(d,p) level applying the self-consistent isodensity polarizable continuum model (SCIPCM) reaction field with geometry optimization in the corresponding solvents. The obtained Ramachandran potential surfaces in water showed distinct potential wells in the alpha- and beta-regions. The profiles were in almost perfect agreement with the Ramachandran plots of glycine and alanine residues in folded proteins, suggesting the Boltzmann distributions on the SAAP surfaces. Molecular simulations of polyalanines (For-Ala(n)-NH(2); n = 3-5) by using the SAAP force field equipped with the SCIPCM potentials revealed that the polyalanines readily form 3(10)-helical structures in water but not in vacuo. In ether (hydrophobic environments), the helical structures were relatively stable, but the most stable structure was assigned to a different one. These results indicated that the intrinsic conformational preferences of the individual amino acids (i.e., the SAAPs) in water are of significant importance not only for describing conformations of a polypeptide chain in the random coil state but also for understanding the folding to the secondary and tertiary structures.

The water exchange process of tetraaquaplatinum(II): Density-functional theory and ab initio computational study

The water exchange process of square planar tetraaquaplatinum(II) was computationally investigated at the Hartree-Fock, density-functional theory (B3LYP, PW91PW91, and mPW1PW91) and the second-order Moller-Plesset perturbation theory of levels of calculation. The stationary points on the gas phase and on the reaction field potential-energy surface were fully optimized and characterized. The self-consistent reaction field (SCRF) methods were also applied on the same system. The structures and energetic processes of all the species involved were investigated. The kinetic and thermodynamic properties for the gas phase and SCRF model data were compared with the available experimental data. The rate constants in MP2 level of theory and B3LYP isodensity polarized continuum model reaction field are in good agreement with the experimental data.

Conformational and electronic study ofN‐acetyl‐L‐isoleucine‐N‐methylamide using DFT and IPCM calculations

AbstractA conformational and electronic study onN‐acetyl‐L‐isoleucine‐N‐methylamide was carried out. All side‐chain as well as backbone conformations were explored for this compound. Multidimensional conformational analysis predicts 81 structures in the case ofN‐acetyl‐L‐isoleucine‐N‐methylamide, 53 relaxed structures were determined at the DFT (B3LYP/6‐31G(d)) level of theory. An exhaustive electronic study employing the atoms‐in‐molecules (AIM) method was carried out. In addition, the effects of three solvents (water, acetonitrile, and chloroform) were included in the calculations using the isodensity polarizable continuum model (IPCM) method. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006

Predictions of the electronic absorption and emission spectra of luciferin and oxyluciferins including solvation effects

The ground and excited state properties of luciferin (LH 2) and oxyluciferin (OxyLH 2), the bioluminescent chemical in the firefly, have been characterized using the configuration interaction singles (CIS) and time dependent density functional (TDDFT) methods. The effects of solvation on the electronic absorption and emission spectra of luciferin and oxyluciferin are predicted with a self-consistent isodensity polarized continuum model of the solvent using both the configuration interaction singles model and time dependent density functional theory. The S 0 → S 1 vertical excitation energies in the gas phase and in water are obtained with both methods. Optimizations of the excited state geometries permit the first predictions of the fluorescence spectra for these biologically important molecules. Shifts in both the absorption and emission spectra on proceeding from the gas phase to aqueous solution also are predicted.

Acidities of azoles in the gas phase and in DMSO: an ab initio and DFT study§

Acidity of azoles, a very important family of biological molecules with useful pharmacological applications, is examined in the gas phase and in DMSO. The gas phase proton affinities of the corresponding conjugate bases are calculated by the G3 computational scheme and used as a measure of acidity. A good accordance with available experimental data is obtained. It is confirmed that acidity increases with the number of nitrogen atoms in the five-membered ring. The calculated deprotonation energies are interpreted by the triadic formula. It turns out that acidity of azoles is a result of the final state effect and the relaxation energy contribution. It is shown, by using NICS(1) values, that azoles are aromatic compounds and that their aromatic character increases with the number of N atoms. It is also found that aromaticity slightly increases upon deprotonation. Acidity of azoles in DMSO is considered using the isodensity polarized continuum model (IPCM) at the DFT-B3LYP level. A good agreement with accessible experimental results is obtained again. In other cases pKa values are theoretically predicted and it was found that pentaazole is the most acidic compound with pKa = 2. A very good linear relation between theoretical pKa values and calculated proton affinities of conjugate bases is obtained implying that the trend of changes in the gas phase and in the DMSO solutions is the same.

Thermochemistry and structures of solvated S N2 complexes and transition states in the gas phase: experiment and theory

The standard enthalpy and entropy changes (Δ H° and Δ S°) for the formation of solvated S N2 complexes (S)X −(RY) (X, Y = Cl, Br; R = (CH 3) 2CH; S = CH 3OH, CH 3CN, (CH 3) 2CO, CH 3CF 2H) have been determined by pulsed-ionization high pressure mass spectrometry. Not surprisingly, solvent effects are evident even at this mono-salvation level. Structures of solvated S N2 complexes and transition states for the Cl −(S) + CH 3Cl S N2 reaction (S = H 2O, H 2S, NH 3, PH 3, SO 2) have also been determined at the MP2/6-31+G(d) level of theory. A large variety of solvent dependent structures have been obtained, showing solvent reorganization upon going from the complex to the transition state. Standard binding and activation enthalpies ( Δ H 298 ∘ and Δ H 298 ‡ ) were determined at the MP2/6-311+G(3df,2p)//MP2/6-31+G(d,p) level of theory. For the Cl −(H 2O) + CH 3Br and Br −(H 2O) + CH 3Cl reactions, structures and enthalpies were calculated at the MP2/[6-31+G(d)/LanL2DZ(spd)] and MP2/[6-311+G(3df,2p)/LanL2DZ(spdf)]//MP2/[6-31+G(d)/LanL2DZ(spd)] level of theory. For the Cl − + CH 3Br and Cl −(H 2O) + CH 3Br reactions potential energy surface scans were performed at the MP2/[6-31+G(d)/LanL2DZ(spd)] level of theory. Formation of the two possible sets of solvated products, Br −(H 2O) + CH 3Cl and Br − + (CH 3Cl)(H 2O) proceeds through two different surfaces. Water transfer to the leaving group can be facilitated by rotation of the Br −(CH 3Cl) part in the exit channel Br −(CH 3Cl)(H 2O) complex. Finally, for the Cl − + CH 3Cl reactions in the condensed phase, complexation and activation energies (Δ E( ɛ) and Δ E ‡( ɛ)) were determined for a variety of solvents at the MP2/6-31+G(d) level of theory using the isodensity polarized continuum model. A linear correlation between −Δ E( ɛ) and Δ E ‡( ɛ) was obtained, and a similar correlation exists for the mono-solvated gas phase S N2 reaction, indicating that mono-solvation already exhibits some features of the condensed phase reaction.

Excited state tautomerization of azaindole

Fluorescent tryptophan analogs, like azatryptophan, offer an advantage for exploring protein and peptide structure and dynamics. The chromophoric moieties, azaindole, of the azatryptophan analogs are investigated for their potential as fluorescent probes. The photophysical properties of 4-azaindole (4AI) and 5-azaindole (5AI) and their tautomers are characterized through computational and experimental methods. Both 4AI and 5AI undergo excited state tautomerization in the presence of 1 M NaOH. The protonated forms of 4AI and 5AI have a fluorescence emission of 415 and 410 nm, respectively, while the tautomers of 4AI and 5AI have a fluorescent emission of 480 and 450 nm, respectively. Gas phase computations (B3LYP/6-31+G**) show that the N1H azaindole tautomer is lower in energy in the ground state by as much as 12.5 kcal mol(-1), while the N(n)H azaindole tautomer is lower in energy in the excited state by as much as 18.1 kcal mol(-1). Solvent effects on the tautomer energy differences were computed using the isodensity polarized continuum model (IPCM). The polarity of the solvent helps to reduce the energy difference between the tautomers in the ground state by as much as 5.8 kcal mol(-1), but not enough to reverse the ground state tautomer preference.

The Acidity of Brønsted CH Acids in DMSO − The Extreme Acidity of Nonacyanocyclononatetraene

AbstractThe gas‐phase (GP) acidity of a large variety of CH organic acids is studied by a carefully selected B3LYP/6‐311+G(2d,p)//B3LYP/6‐31G(d) theoretical model. Acidities are mirrored by the proton affinities of the corresponding conjugate bases. A very good agreement with available experimental data is achieved. It is concluded that the model applied has a high predictive value and that theoretical PA(anion)GP values can be used instead of measured data in cases where experiments are not feasible or not performed. It is shown, employing the isodensity polarized continuum model (IPCM), that there is a good linear relationship between the enthalpies of the proton‐transfer reactions in DMSO and the observed pKa(DMSO) values. This relation can be used in predicting the acidity of strong, neutral organic superacids. As an illustrative case, the acidity of cyclononatetraene‐1,2,3,4,5,6,7,8,9‐nonacarbonitrile (“nonacyanocyclononatetraene”) is considered. It is conclusively shown that this compound should be a very potent superacid, as evidenced by its PA(anion)GP (260.0 kcal·mol−1) and pKa (−14.8). The origin of high acidity is identified as a very strong anionic resonance effect in the resulting conjugate base. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Density functional study of the lithiation of cyclic vinyl ethers in solution

Lithiation of three cyclic vinyl ethers—2,3-dihydrofuran, 3,4-dihydro-2 H-pyran, and 2,3-dihydrooxepin in ethereal solution are investigated at the density functional theory level of B3LYP/6-31++G(d,p). Several solvation models were used, including the microsolvation model, the continuum models such as the Onsager model, the polarized continuum models, and the isodensity polarized continuum model, and the mixed discrete-continuum model. Both the microsolvation and the mixed discrete-continuum model gave results consistent with experiments. Theoretical calculations also indicate that lithiation of 2,3-dihydrooxepin undergoes allylic lithiation concomitant with ring opening.

Ab initio study of the SN1Ar and SN2Ar reactions of benzenediazonium ion with water. On the conception of "unimolecular dediazoniation" in solvolysis reactions.

The nucleophilic substitution of N2 in benzenediazonium ion 1 by one H2O molecule to form protonated phenol 2 has been studied with ab initio (RHF, MP2, QCISD(T)//MP2) and hybrid density functional (B3LYP) methods. Three mechanisms were considered: (a) the unimolecular process SN1Ar with steps 1 --> Ph+ + N2 and Ph+ + H2O --> 2, (b) the bimolecular process SN2Ar with precoordination 1 + H2O --> 1 x H2O, SN reaction 1 x H2O --> [TS]++ --> 2 x N2 and dissociation of the postcoordination complex 2 x N2 --> 2 + N2, and (c) the direct bimolecular process SN2Ar that bypasses precoordination and involves just the SN reaction 1 + H2O --> [TS]++ --> 2 + N2. The SN2Ar reactions proceed by way of a Cs symmetric SN2Ar transition state structure that is rather loose, contains essentially a phenyl cation weakly bound to N2 and OH2, and is analogous to the transition state structures of front-side nucleophilic replacement at saturated centers. In solvolysis reactions, all of these processes follow first-order kinetics, and the electronic relaxation is essentially the same. It is argued that "unimolecular dediazoniations" have to proceed by way of SN2Ar transition state structures because strict SN1Ar reactions cannot be realized in solvolyses, despite the fact that the Gibbs free energy profile favors the strict SN1Ar process over the SN2Ar reaction by 6.7 kcal/mol. It is further argued that the direct SN2Ar process is the best model for the solvolysis reaction for dynamic reasons, and its Gibbs free energy of activation is 19.3 kcal/mol and remains higher than the SN1Ar value. Even though the SN1Ar and SN2Ar models provide activation enthalpies and SKIE values that closely match the experimental data, the analysis leads us to the unavoidable conclusion that this agreement is fortuitous. While the experiments do show that the solvent effect on the activation energy is about the same for all solvents, they do not show the absence of a solvent effect. The ab initio results presented here suggest that the solvent effect on the direct SN2Ar dediazoniation is approximately 12 kcal/mol, and computation of solvent effects with the isodensity polarized continuum model (IPCM) support this conclusion.

5-Cyanoimino-4-oxomethylene-4,5-dihydroimidazole and Nitrosative Guanine Deamination. A Theoretical Study of Geometries, Electronic Structures, and N-Protonation

The 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole 1 (R = H), its N1-derivatives 2 (R = Me) and 3 (R = MOM) and their cyano-N (4, 6, 8) and imino-N protonated (5, 7, 9) derivatives were studied with RHF, B3LYP, and MP2 theory. Solvation effects were estimated with the isodensity polarized continuum model (IPCM) at the MP2 level using the dielectric constant of water. Carbodiimide 10, cyanamide 12, N-cyanomethyleneimine 13, and its protonated derivatives 14 and 15 were considered for comparison as well. Adequate theoretical treatment requires the inclusion of dispersion because of the presence of intramolecular van der Waals, charge-dipole, and dipole-dipole (including H-bonding) interactions. All conformers were considered for the MOM-substituted systems, and direct consequences on the preferred site of protonation were found. The vicinal push (oxomethylene)-pull (cyanoimino) pattern of the 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazoles results in the electronic structure of aromatic imidazoles with 4-acylium and 5-cyanoamido groups. The gas-phase proton affinities of 1-3 are over 30 kcal/mol higher than that for N-cyanomethyleneimine 13, and this result provides compelling evidence in support of the zwitterionic character of 1-3. Protonation enhances the push-pull interaction; the OC charge is increased from about one-half in 1-3 to about two-thirds in the protonated systems. In the gas phase, cyano-N protonation is generally preferred but imino-N protonation can compete if the R-group contains a suitable heteroatom (hydrogen-bond acceptor, Lewis base). In polar solution, however, imino-N protonation is generally preferred. Solvation has a marked consequence on the propensity for protonation. Whereas protonation is fast and exergonic in the gas phase, it is endergonic in the polar condensed phase. It is an immediate consequence of this result that the direct observation of the cations 8 and 9 should be possible in the gas phase only.

Computational study of conformational preferences of thioamide-containing azaglycine peptides.

The effect of thioamide substitution on the conformational stability of an azaglycine-containing peptide, For-AzaGly-NH2 (1), was investigated for the sake of finding possible applications by using ab initio and DFT methods. As model compounds, For-[psiCSNH]-AzaGly-NH2 (2), For-AzaGly-[psiCSNH]-NH2 (3), and For-[psiCSNH]-AzaGly-[psiCSNH]-NH2 (4) were used. Two-dimensional phi-psi potential energy surfaces (PESs) for 2-4 were calculated at the B3LYP/6-31G*//HF/6-31G* level in gas (epsilon = 1.0) and in water (epsilon = 78.4) by applying the isodensity polarizable continuum model (IPCM) method. On the basis of these PESs, the minimum energy conformations for 2-4 were characterized at the B3LYP level with 6-31G*, 6-311G**, and 6-31+G** basis sets. The remarkable structural effect of thioamide substitution for 2-4 is that beta-strand structure is observed as a global or local minimum. The minima of 2-4 are also compared with those for glycine and thioamide-containing glycine peptides. Our theoretical results demonstrate that compounds 2-4 would be used to design controllable secondary structures.

Conformational preference of azaglycine-containing dipeptides studied by PCM and IPCM methods

The minimum energy conformations for azaglycine-containing dipeptides, Ac-Ala-azaGly-NH2 (I) and AcPhe-azaGly-NH2 (II) were calculated at the HF/6-31G* level of theory by applying the polarizable continuum model (PCM) and the isodensity polarizable continuum model (IPCM) to investigate solvent effect on conformational stability. The most stable conformers calculated by two solvation methods were confirmed experimentally to evaluate which of solvation models is more reliable. A wide range of conformers was searched in the HF/6-31G* structures for azapeptide I. The conformers less than 5 kcal/mol in relative energy were selected as minima of I, and minima of azapeptide II were generated at the HF/6-31G* level based on the backbone geometries for minima of I. The relative energies of stable conformers and the global minima for I and II in DMSO solvent depend significantly on solvation methods. To characterize these inconsistencies in solvation models, the solution conformations of II were examined with NMR spectroscopy and the restricted molecular dynamics in conjunction with the ab initio method. The solution conformation of II by NMR spectroscopy is determined to adopt a bII-turn(major) or bI-turn(minor) structures as predicted by IPCM method. These theoretical and experimental results indicate that IPCM is more reliable than PCM in prediction of the conformational preference for azapeptide in DMSO solution structures. 2003 Elsevier B.V. All rights reserved.