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The gas phase conformational and nonlinear optical properties of cis-N-phenylbenzohydroxamic acid (cis-NPBHA) keto and enol forms were studied applying traditional hybrid and long-range-corrected Density Functional Theory (DFT) and time-dependent density functional (TD-DFT) methods. The calculated geometrical parameters for the two isomers agreed satisfactorily with literature ones. The keto form was predicted to be more stable than the enol counterpart by 10.70–12.60 kcal/mol, and the Gibb’s free energies for the conversion: enol⇌keto were found to be 11.14 kcal/mol (B3LYP/6-311+G**), 12.53 kcal/mol (CAM-B3LYP/6-311+G**) and 13.28 kcal/mol (ωB97XD/6-311+G**). All the selected functionals have computed larger total hyperpolarizabilities for the enol tautomer compared to those of the keto rival. The traditional hybrid functional yielded higher total hyperpolarizabilities than those of the long-range-corrected ones. The total hyperpolarizabilities were nicely correlated with HOMO–LUMO energy gaps and absorption maxima. The support of these molecular properties by natural bond orbital (NBO) calculations was evaluated and discussed.

The present study addresses the conformational preferences and the mechanism of decarboxylation of levodopa (LD). LD is used to increase dopamine concentrations in the treatment of Parkinson's disease. LD crosses the protective blood-brain barrier, where it is converted into dopamine by the process of decarboxylation. Molecular dynamics simulation has been carried out at the DFT/6-31++G level of theory to identify the global minimum structure of LD. Conformational preferences of the amino acid side chain of LD has been investigated at the B3LYP/6-311++G** level of theory. Fourier transform analysis has been performed to identify the origin of the rotational barriers. Electrostatic dipole moment and bond interactions underlie the observed potential energy barriers for rotation of the amino acid side chain of LD. The vital biological process of decarboxylation of LD has been examined in the gas phase and in aqueous solution. Without the presence of water, there is only one possible route for the decarboxylation of LD. In this concerted mechanism, a proton transfer and breakage of the C10C18 bond, take place simultaneously (E# = 73.2 kcal/mol). In solution, however, two possible decarboxylation routes are available for LD. The first involve the formation of a zwitterionic intermediate (E# = 72.4 kcal/mol). The zwitterionic form of LD have been localized using explicitly bound water molecules to model short-range solvent effects and self-consistent reaction field polarized continuum model to estimate long-range solvent interactions. The second route involve the formation of a cyclic structure in which a water molecule acts as a bridge linking the anticarboxylic hydrogen and -position carbon atom (E# = 59.8 kcal/mol). Natural bond orbital (NBO) analysis reveals that the conformational and overall stability of the amino acid side chain is facilitated by the antiperiplanar interactions between the phenyl moiety CH and CC bonds and CX bonds of the amino acid side chain. However, much of the major donor-acceptor interactions is of the lone pair type and is localized within the amino acid side chain itself. Results of the present work reveal that NBO data reflect nicely and identify clearly reaction coordinates at the transition species.

The transition structures and the activation energies for the possible thermal elimination of H2O, HF and HCl from ethane-1,2-diol, 2-fluoroethanol and 2-chloroethanol respectively, were investigated. The relative stabilities and associated barrier heights of syn and anti vinyl alcohol isomers and their acetaldehyde tautomer were estimated. HF, DFT/B3LYP and MP2 methods at 3-21G, 6-31+G(d), 6-311++G(d,p) and aug-cc-pvdz basis sets were applied to identify the stationary points of the studied systems. The optimized geometries and electronic energies of reactants, transition states and products were analyzed. The dependence of these properties upon the theoretical level was discussed. A concerted proton release and a hydroxide or halide ion expulsion mechanism was proposed to account for the thermal rearrangement of reactants to products. A thorough understanding of syn vinyl alcohol preference is provided by performing natural bond orbital (NBO) analysis. The oxygen atom lone pair (LP) and periplanar hyper...

8-Hydroxyquinoline (8HyQ) and its derivatives are the important constituents in a variety of pharmaceutical compounds. The effect of protonation and deprotonation of 8HyQ on its electronic structure and fluorescence was investigated using B3LYP/6-311G** level of theory. We also investigated the interaction of chemosensor, 8HyQ, with different transition metals (Zn2+, Fe2+, Ni2+ and Co2+) at the same level. Our results revealed that 8HyQ displays an unusual fluorescence intensity–proton transfer relationship with diminished emission in a protonated form but enhanced emission in a deprotonated form. The Zn2+, Fe2+, Ni2+ and Co2+ complexes of 8HyQ, which were investigated at the same level of theory, showed that the order of binding energies was 8HyQ-Ni2+>8HyQ-Zn2+>8HyQ-Co2+>8HyQ-Fe2+. Time-dependent density functional theory calculations indicated that Zn ion enhances the fluorescence of 8HyQ as a consequence of the inhibition of the proton transfer. The results are in good agreement between the predicted p...

The gas-phase decomposition mechanism of the photochemical and thermal reaction of cyclopropenone leading to carbon monoxide and acetylene has been investigated theoretically. We employed the B3LYP, MP2, and CASSCF methods with the 6-311 + G** basis set to determine the pathways and the potential energy surface (PES) of this reaction. PES minima were characterized by the absence of any imaginary frequencies and compared with the transition states that contained single imaginary frequencies. The intrinsic reaction coordinate (IRC) method was used to find the minimum energy paths in which reactants and products were connected to the transition states. Activation barrier, thermodynamic, and IRC analyses were performed using the above three methods. Our computations indicated that the decomposition of cyclopropenone proceeds through a stepwise mechanism containing two transition states (TS1 and TS2) and an intermediate. The results show that TS1, the critical transition state, determines the rate of the cyclo...

Quantitative structure–activity relationships (QSARs) have been established for two sets of antitumour drugs 2-(4-aminophenyl)benzothiazoles (APBT). Constitutional, geometrical, topological, electronic descriptors (computed at the B3LYP/6-31G** level) and some empirical descriptors related to the hypophilicity were computed and analysed. Multiple regression analysis led to a set of equations that reflected the weight of each of the studied descriptors. The most relevant of these descriptors were grouped, and a new multiple regressions analysis was carried out and we arrived at the final QSAR models. A validation set of 11 APBT were selected, and their activities were computed using the proposed QSAR model. The correlation between the predicted and observed activities was excellent. The resulting best models exhibited good q 2 and r 2 values up to 0.867 and 0.954.

The tautomerisation reaction of 1,2,3-triazole and some of its derivatives has been studied and the transition states were located. The analysis of results indicates that 2H-triazole is more stable than the 1H-tautomer in all studied compounds in gas phase and in solution. The proton detachment energies and the geometries of the compounds studied were analysed using density functional theory (DFT) and Hartree–Fock (HF) methods in gas phase and solution. Deprotonation takes place in all cases studied by the detachment of N–H proton. The solvent effect on the stability the tautomeric and anion forms of studied compounds has been examined using B3LYP/6-31G* level of theory by applying the polarisable continuum model.

A density functional theory study of the behavior of hemispherands toward alkali metal ions (Li+, Na+, and K+) is performed. The effect of the replacement of the rigid anisyl group(s) by the mobile ether group(s) on the binding energy of hemispherands with alkali metal ions is investigated. The results indicated that the binding energies are inversely proportional to the ionic radius of the cations. Moreover, increasing the flexibility of the ligand results in decreasing the binding toward small ions. The structures of the hosts and the guests are correlated to the binding energies, and the correlations are interpreted in terms of the principle of preorganization. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

N-Bromosuccinimide (NBS) is a brominating and oxidizing agent that is used as a source of bromine. The proton affinities, the tautomeric forms and N Br bond dissociation of NBS have been computed using the B3LYP functional as implemented in the density functional approach. The electronic structures of all possible tautomeric forms of NBS have been thoroughly investigated. The keto form of NBS has been shown to be more stable than any other tautomeric forms. The geometries and relative energies for various stationary structures were determined. The results indicate clearly that O-site protonation is strongly favored over N-site protonation for the studied compound in case of mono- and di-protonation. The bond dissociation energies (BDEs), involving the formation of the bromine radical, cation, and anion, of the N Br bond have been investigated. The N Br BDE of the Br radical formation is lower than that of the Br anion or cation. These conclusions are in good agreement with the experimental results.

Spherands are highly preorganized hosts composed of methoxy 1, fluoro 2, and cyano 3 benzene units attached to one another at their 2,6-positions. Density functional theory calculations were used to investigate the complexation between these spherands and alkali metal ions (Li ! , Na ! , and K ! ) to understand the intrinsic factors affecting cation complexation. A comparison of binding energies for these spherands shows that, this order O-Me " " F " " CN. Although anisyl units are basically poor ligands for metal ions, the rigid placements of their oxygen during synthesis rather than during complexation are undoubtedly responsible for the enhanced binding and selectivity of the spherand. The ion-dipolar moiety interactions are found to be the main factors affecting the preference of external binding in the CN-spherands. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem 109: 1515-1521, 2009

Cyanospherands (CN-spherands) are highly preorganized hosts which bind cations. Density functional theory calculations were used to investigate the complexation between cyanospherands and alkali metal ions (Li ,N a, and K). CN8- spherand undergoes significant shape change upon complexation, i.e., the oval free host becomes spherical when complexed with cations. All cationic guests prefer external binding to encapsulation in spite of spherically well organized charged moieties and the spacious cavity of hosts. The ion-dipolar moiety interaction has been found to be a decisive factor for the preference for external binding. This demonstrates the importance of ion-dipolar moiety orientations as well as the host-guest size complementarity, to design novel ionophores.

The optimized geometries and energies of the four cyclic structures of the orotic acid–water complex are computed using density functional theory (B3LYP) combined with the 6-31++G(d,p) basis set. In the three most stable cyclic structures, the water molecule accepts the NH proton and donates a proton to the carbonyl oxygen atoms. Less stable cyclic complexes involving the C5H bond also formed. The proton affinity of the oxygen atoms and the deprotonation enthalpy of the NH bonds of orotic acid are computed at the same level and compared with reported data on uracil and thymine. The most stable cyclic complex is formed at the oxygen lone pair characterized by the lowest basicity and at the NH bond characterized by the highest acidity. Although intrinsic acidities are lower in orotic acid than in uracil and thymine, the binding energies with one water molecule do not differ markedly for uracil and orotic acid. Substituent of carboxylic group at the 6-position, however do not seem to have much effect on the proton affinities and the deprotonation enthalpy of uracil.

Fluorospherands (F-spherands) are highly preorganized hosts composed of fluorobenzene or 4-methylfluorobenzene units attached to one another at their 2,6-positions. To understand the intrinsic factors affecting cation complexation, we investigated the complexation behavior between F-spherands and cations using density functional theory (DFT) at the level of B3LYP/6-31G**. The F6-spherand (C6H3F)6, (1) has a highly preorganized spherical cavity, which can encapsulate Li and Na . Its cavity is not big enough for K and NH4 , which prefer external binding. Plausible conformations were studied for F8-spherand (C6H3F)8. Conformer of D2d symmetry (2b) is more stable than that of D4d (2a), in agreement with NMR experiments. The cavity size of F8-spherand is big enough to encapsulate all cations studied. However, the cavity size of 2b is smaller than that of 2a, which resulted in the guest selectivity. Upon complexation, 2b conformation is more stable for Li and Na , while 2a conformation is preferred for larger cations such as K and NH4 . Thus, the ab initio calculations over these highly preorganized fluorospherands give important insights into their host–guest chemistry. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem 107: 930–936, 2007

Ab initio molecular orbital computation has been performed to study the electronic structure, substituent and solvent effects on the singlet–triplet gaps of a series of nitrenium ions. DFT calculations at the B3LYP/6-311++G** level of theory predict that, the nitrenium ions derived from the metabolism of the antitumor 2-(4-aminophenyl)benzothiazoles exist in the ground singlet state. The preferential stabilization of the singlet state relative to the triplet is due to the transfer of charge density from the phenyl ring to formally electron deficient nitrogen atom. Calculations in solution were carried out using the PCM model. Solvent–solute interaction energies were estimated and reflect a considerable net stabilization of the triplet species at the PCM model. Fourier transform analysis of the internal rotation potential energy function, around the exocyclic bond (C 4 –N), has been performed for niternium ions studied. The magnitudes and origin of the potential energy barriers have been discussed.

The proton affinity on each of the possible sites in the antitumor 2-(4-aminophenyl)benzazoles has been calculated at the B3LYP/6-311G** level of theory in the gas phase and in solution. The N3-site of protonation is found to be strongly favored over the NH2-site for the studied compounds both in gas phase and in solution. The stability of N3-protonated species is explained by the resonance interaction of the NH2-group with the heterocyclic ring. The potential energy surface (PES) for the protonation process was studied at the density functional theory (DFT)/B3LYP/6-311++G** level of theory. Solvent effects on the PES were also examined using two models: Onsager self-consistent field and polarizable continuum model (PCM). © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005

The ground-state equilibrium geometries of benzothiazole, benzoxazole, and benzimidazole were optimized at the density functional theory (DFT)/6-31G** level of theory. Proton affinities on each of the possible sites in the studied series of compounds have been calculated at the DFT/6-31G**/6-311G** level. The results indicate clearly that N-site protonation is strongly favored over X-site protonation (X NH, O, S) for the series studied. Correlation of the computed proton affinities to the energy (EHOMO) of the highest occupied MO in the gas phase and in solution has been explored and discussed. A comprehensive investigation of the effect of solvent on the process of protonation of the studied compounds has been performed. Different dielectric continuum models (i.e., Onsager, PCM, and IPCM) have been tested; their performance and range of applicability are reported and discussed. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem 103: 332-343, 2005

The molecular geometry of orotic acid was fully optimized using the gradient minimization technique. The computed geometrical parameters at the B3LYP/6-311G** level correspond well to those determined experimentally by X-ray diffraction. The relative stability of both the syn and anti conformations was investigated at the B3LYP/6-311G** level, where the syn-form was shown to be slightly more stable by 1.58 kcal/mol. The barrier to internal rotation about the C6–C12 bond was computed and this low barrier (7.655 kcal/mol) was shown to be associated with the θ=90° conformation. The results of the present work indicate that orotic acid behaves as a free rotor in the C6–C12 bond region and both the syn- and anti conformations were equally probable. Fourier analysis of the internal rotation function was carried out. The results indicate that the stability of the syn- over the anti-form was not due to increased or tight conjugative interaction, but rather due to decreased dipole–dipole repulsion and bond moment's interactions that is of electrostatic nature. The electronic structures of all possible tautomeric forms of orotic acid and that of its zwitterion have been thoroughly investigated. Equilibrium geometries were determined and compared to that of orotic acid. Solvent effects were taken in consideration. The self-consistent reaction field model (SCRF) was adopted to estimate gross solvent effects. The keto-form of orotic acid has been shown to be more stable than any other tautomeric forms.