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The cyclization of a series of nonheterocyclic allenyl aryl ketones was examined using boron trifluoride etherate and indium triflate to mediate the reaction. Yields with BF3 were low in most instances due mainly to competitive destruction of the substrates. With In(OTf)3, there was less decomposition, and the yields of the cyclized product were much higher, but only for substrates with electron-donating substituents. Cyclization did not occur without those substituents. A computational study using the ωB97X-D/6-311+G(2d,p)//ωB97X-D/6-31+G(d,p) method confirmed better stability of the σ-complexed substrate by indium(III) and that meta-substituents on the phenyl ring of the substrate significantly influenced the activation barrier of the cyclization, whereas the effect of para-substituents was almost negligible. The computational results supported the idea that the cyclization is a 4π-electrocyclization and not a 5-endo-dig ring closure as had been proposed in the literature.

Cytochrome P450 enzymes were recently engineered to catalyze the C-H amination reaction of aryl sulfonyl azides with excellent regio- and stereoselectivity (Arnold and co-workers J. Am. Chem. Soc. 2014 , 136 , 15505 ). The mechanism of this reaction was studied by quantum mechanical (QM)/molecular mechanical (MM) calculations in this work. The C-H activation is found to be a stepwise process consisting of hydrogen abstraction (H-abstraction) of the reactive C-H bond by an iron nitrenoid cofactor to produce the biradical intermediate and subsequent radical rebinding to form the final product. The rate of rotation of the carbon radical center was estimated to be much faster than that of radical rebinding, which implies that the H-abstraction does not determine the stereoselectivity. For mutant A, the H-abstraction step has a barrier of 16.7 kcal/mol, which is 3.0 kcal/mol higher than that of the following radical rebinding step. The H-abstraction step determines the regioselectivity, but the radical rebinding step determines the stereoselectivity. Barriers of these two steps are 16.1 and 27.5 kcal/mol, respectively, for mutant B. It is different from mutant A in that the radical rebinding step has the higher barrier and determines both the regio- and stereoselectivity. The initial distances between the hydrogens of reactive C-H bonds and the iron nitrenoid were found to not correlate with their reactivities. The calculated barriers are qualitatively consistent with the experimentally observed regio- and stereoselectivity with the exception of the stereoselectivity of mutant B. The lower barriers of mutant A presumably come from the stabilization effect of the H-bond between G265 and the sulfone O. This H-bond does not exist in mutant B. The conformation of the protein backbone, with the exception of the active site, does not change much (RMSD0.05) along the reaction pathway.

A computational examination of the tandem Nazarov/cycloaddition process involving an allenyl vinyl ketone with a diene has been carried out using the ωB97X-D/6-311++G(d,p)//ωB97X-D/6-31+G(d,p) method with solvation modeled by SMD-PCM. The barrier for the initial Lewis acid mediated Nazarov reaction, which provided the intermediate cyclic oxylallyl cation, was higher than that for any subsequent cycloaddition. The barrier for the first step of a subsequent stepwise reaction did not vary much with the diene, and the lowest barrier was with the diene in its s-trans conformation. Stepwise formation of a (4 + 3) cycloaddition product was not energetically feasible, but (3 + 2) cycloaddition products could have been produced through low energy pathways. The barrier for a concerted (4 + 3) cycloaddition did depend upon the diene, which was always in an s-cis geometry. The barriers for the compact and the extended geometries for the transition states of (4 + 3) cycloadditions were not much different.

Predicting the correct ground-state multiplicity for iron(II) porphyrin, a high-spin quintet, remains a significant challenge for electronic-structure methods, including commonly employed density functionals. An even greater challenge for these methods is correctly predicting favorable binding of O2 to iron(II) porphyrin, due to the open-shell singlet character of the adduct. In this work, the performance of a modest set of contemporary density-functional approximations is assessed and the results interpreted using Bader delocalization indices. It is found that inclusion of greater proportions of Hartree-Fock exchange, in hybrid or range-separated hybrid functionals, has opposing effects; it improves the ability of the functional to identify the ground state but is detrimental to predicting favorable dioxygen binding. Because of the uncomplementary nature of these properties, accurate prediction of both the relative spin-state energies and the O2 binding enthalpy eludes conventional density-functional approximations.

We performed an assessment of 10 common DFT functionals to determine their suitability for calculating the reduction potentials of the ([M(S2C2H2)2](0)/[M(S2C2H2)2](1-)), ([M(Se2C2H2)2](0)/[M(Se2C2H2)2](1-)), ([M(S2C2H2)2](1-)/[M(S2C2H2)2](2-)), and ([M(Se2C2H2)2](1-)/[M(Se2C2H2)2](2-)) redox couples (M = Ni, Pd, and Pt). Overall it was found that the M06 functional leads to the best agreement with the gold standard CCSD(T) method with an average difference of only +0.07 V and a RMS of 0.07 V in calculated reduction potentials. The variability in calculated reduction potentials between the various DFT functionals arise, in part, from the multireference character of these systems, which was determined by the T1 diagnostic values. Thus, the bisdiselenolene complexes show similar multireference character as the bisdithiolene complexes, which were previously shown to have such character. In particular, for the Ni-, Pd-, and Pt-bisdiselenolene complexes the average T1 values are 0.05, 0.03, and 0.02, respectively. For the CCSD(T) calculations the similarities in the reduction potentials between analogous bisdithiolene and bisdiselenolene redox couples, which appear to be independent of the metal, is a result of the noninnocence of the dithiolene and diselenolene ligands. Thus, the reduction potential is more dependent on the ligand than the metal.

Nazarov reactions mediated by BF3-etherate of a series of carbon-substituted allenyl vinyl ketones provided intermediates in which substituents on the termini of the allenes had rotated away from the vinyl moieties, and these intermediates were trapped by (4 + 3)-cyclizations. A computational examination of the torquoselectivity of these Nazarov reactions confirmed a kinetic preference for the observed isomers and pointed to steric interactions and the degree of allene deformation as significant factors in determining the torquoselectivity. The study also suggested that the high proportion of one geometrical isomer in the Nazarov products might also be due to some preferential trapping of the major Nazarov intermediate.

The mutual interaction between beryllium bonds and halogen bonds within H2Be···FCl···Base complexes, where Base includes a wide set of N- and O-containing Lewis bases, has been studied at the M06-2X/6-31+G(d,p) level of theory. The reliability of this theoretical model was assessed by comparison with ab initio CCSD/aug-cc-pVTZ reference calculations. Cooperative effects were investigated within the framework of the atoms in molecules theory (AIM) by analyzing the topology of the electron density and the changes in the atomic energy components. The decomposition of the total stabilization energy into atomic components is found to be a very reliable tool to describe halogen bond interactions. Both the topological analysis of the electron density and the changes in the atomic energy components of the binding energy show the existence of strong cooperative effects between beryllium and halogen bonds, which are in some cases very intense. In general, there is a correlation between the intrinsic basicity of the Lewis base participating in the halogen bond and the resulting cooperativity in the sense that the stronger the base, the larger the cooperative effects.

Atomic energies are used to describe local stability in eight low-lying water hexamers: prism, cage, boat 1, boat 2, bag, chair, book 1, and book 2. The energies are evaluated using the quantum theory of atoms in molecules (QTAIM) at MP2/aug-cc-pVTZ geometries. It is found that the simple, stabilizing cooperativity observed in linear hydrogen-bonded water systems is diminished as clusters move from nearly planar to three-dimensional structures. The prism, cage, and bag clusters can have local water stabilities differing up to 5 kcal mol(-1) as a result of mixed cooperative and anticooperative interactions. At the atomic level, in many cases a water may have a largely stabilized oxygen atom but the net water stability will be diminished due to strong destabilization of the water's hydrogen atoms. Analysis of bond critical point (BCP) electron densities shows that the reduced cooperativity results in a decrease in hydrogen bond strength and an increase in covalent bond strength, most evident in the prism. The chair, with the greatest cooperativity, has the largest average electron density at the BCP per hydrogen bond, whereas the cage has the largest total value for BCP density at all hydrogen bonds. The cage also has the second largest value (after the prism) for covalent bond critical point densities and an oxygen-oxygen BCP which may factor into the experimentally observed stability of the structure.

Atomic energies are used to visualize the local stabilizing and destabilizing energy changes in water clusters. Small clusters, (H(2)O)(n), from n = 2-5, at MP2/aug-cc-pVTZ geometries are evaluated using energies defined by the quantum theory of atoms in molecules (QTAIM). The atomic energies reproduce MP2 total energies to within 0.005 kcal mol(-1). Oxygen atoms are stabilized for all systems and hydrogen atoms are destabilized. The increased stability of the water clusters due to hydrogen bond cooperativity is demonstrated at an atomic level. Variations in atomic energies within the clusters are correlated to the geometry of the waters and reveal variations in the hydrogen bond strengths. The method of visualization of the energy changes applied here is especially suited for application to large biomolecules.

The molecular structure can be defined quantum mechanically thanks to the theory of atoms in molecules. Here, we report a new molecular model that reflects quantum mechanical properties of the chemical bonds. This graphical representation of molecules is based on the topology of the electron density at the critical points. The eigenvalues of the Hessian are used for depicting the critical points three-dimensionally. The bond path linking two atoms has a thickness that is proportional to the electron density at the bond critical point. The nuclei are represented according to the experimentally determined atomic radii. The resulting molecular structures are similar to the traditional ball and stick ones, with the difference that in this model each object included in the plot provides topological information about the atoms and bonding interactions. As a result, the character and intensity of any given interatomic interaction can be identified by visual inspection, including the noncovalent ones. Because similar bonding interactions have similar plots, this tool permits the visualization of chemical bond transferability, revealing the presence of functional groups in large molecules.

Polaron formation in poly(G)-poly(C) cations is investigated with density functional theory (DFT) and molecular mechanics (MM) employing a two-layer ONIOM method. In these calculations, the high layer, composed of all complementary base pairs, is treated by a DFT method, while the low layer, which includes the sugar-phosphate backbone, counterions and water molecules, is described by the AMBER force field. The high layer is the model system in which the charge transfer takes place. According to our calculations, three or four guanines move in a paddle-like fashion when an electron is removed from the neutral model system. In the cation model system, about 80% of the charge is delocalized onto the guanine residues, and the remaining charge is delocalized onto the cytosine residues. This happens because guanine has a lower ionization potential (IP) than cytosine. The counterions and water molecules in the low layer are important in the geometry optimization. The optimized geometry of the model system is closer to the standard B-form structure when counterions and water molecules are included than when they are omitted. Comparison of the optimized neutral and cationic model systems reveals a polaron in poly(G)-poly(C) cations extending from the first to the third guanine. It is demonstrated that the position of counterions and the number of surrounding water molecules can affect polaron formation.

Enthalpies and entropies of dimerization have been determined as functions of concentration for dibutyltin dipropoxide, dibutyltin dibutoxide, and dibutyltin diisopropoxide in toluene-d8 and cyclohexane-d12 solutions from the variation in 119Sn NMR chemical shifts with temperature. The values of ΔH and ΔS obtained in toluene-d8 for dibutyltin dibutoxide were −69.5 ± 3.0 kJ mol−1 and −197 ± 10 J mol−1 K−1, respectively, and for dibutyltin diisopropoxide −67.1 ± 1.4 kJ mol−1 and −244 ± 9 J mol−1 K−1, respectively. Enthalpies and entropies of activation for this process for dibutyltin diisopropoxide have been derived by simulation of the temperature-dependent broadening of the 119Sn NMR spectra. The free energy of activation for dimerization was 33 kJ mol−1. The same thermodynamic parameters for a greater range of dibutyltin dialkoxides were derived theoretically by using MP2 single-point calculations on B3LYP-optimized geometries using the LANL2DZdp basis set with diffuse and polarization functions and its ...

The effects of introducing electron-donating (NH(2), OCH(3), CH(3)) and electron-withdrawing (NO(2), CF(3), CN, F) groups to N,N-dimethylbenzylamine-2-selenol are studied to determine the effect of the selenium electron density on the efficiency of the reduction of hydrogen peroxide. Introducing substituents in the meta and para positions decreases or increases the energy barrier of the reaction in the expected way, due to changes in the electronic environment of the reacting selenium center. Ortho substituents are found to have a greater effect on the electronic environment of the selenium center, which is mitigated by changing the steric environment. Insight into the origins of the substituent effects is obtained through quantum theory of atoms in molecules (QTAIM) and electrostatic potential analysis.

The displacement of the iron(II) atom from the porphyrin plane in iron(II) porphyrin complexes is investigated with respect to the spin state of iron(II) employing density functional theory. In this study the quantum theory of atoms in molecules (QTAIM) is used to show that the atomic volume of iron is smaller in the quintet state of imidazolium ligated iron(II) porphyrin than in the triplet state. This is consistent with what has been found for free atoms and contradicts the original interpretation of structural studies with X-rays, which assumed that the out-of-plane displacement of iron from the porphyrin ring in the quintet state is due to the increased spatial size of the high-spin iron atom. The bonding environment of the iron atom is analyzed with respect to the electron density (ρ) at the bond critical points (BCPs). It is found that in the quintet state, relative to the triplet state, there is a stronger bonding interaction between iron and the nitrogen atoms of the porphyrin despite a longer bond length. It has previously been suggested that the weakening of these bonds is the cause of the out-of-plane displacement of iron. Since this is not the case, this implies that the magnitude of the bonding interaction between the iron atom and the axial ligand has a more significant role in the domed structure of the quintet state.

The reaction mechanism for the reduction of hydrogen peroxide by N,N-dimethylbenzylamine diselenide, its selenol analogue, and the charged analogues of the diselenide and selenol are elucidated using reliable electronic structure techniques. It is found that the reaction using the diselenide has a large Gibbs energy barrier of 173.5 kJ/mol. The cationic diselenide, with both amines protonated, shows a lower barrier of 103.5 kJ/mol. Both diselenide species show significant Se-Se bond lengthening upon oxidation. An unusual two-step mechanism is found for the selenol with barriers of 136.3 and 141.9 kJ/mol, respectively, showing that it is unlikely that the selenol is the active form. The zwitterion, selenolate, and protonated amine analogues of the selenol show one-step reactions with energy barriers of 82.7, 92.7, and 102.3 kJ/mol, respectively. The zwitterion of the selenol shows the most favorable reaction energies, which is in good agreement with proposed mechanisms for this reaction.

The structures of 19 alpha-helical alanine-based peptides, 13 amino acids in length, have been fully optimized using density functional theory and analyzed by means of the quantum theory of atoms in molecules. Two types of N-H...O bonds and one type of C-H...O bond have been identified. The value of the electron density at hydrogen bond critical points corresponding to N-H...O interactions is higher than that of C-H...O interactions. The effect of amino acid substitution at the central position of the peptide on the hydrogen bond network of the alpha-helix has been assessed. The strength of the hydrogen bond network, measured as the summation of the electron density over the hydrogen bond critical points, may be used to explain experimental relative helix propensities of amino acids in cases where solvation and entropic effects cannot.

Density functional theory calculations at the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31G(d,p) level have been performed to elucidate the mechanism and reaction energetics for the reduction of hydrogen peroxide by ebselen, ebselen diselenide, ebselen selenol, and their sulfur analogues. The effects of solvation have been included with the CPCM model, and in the case of the selenol anion reaction, diffuse functions were used on heavy atoms for the geometry optimizations and thermochemical calculations. The topology of the electron density in each system was investigated using the quantum theory of atoms in molecules, and a detailed interpretation of the electronic charge and population data as well as the atomic energies is presented. Reaction free energy barriers for the oxidation of ebselen, ebselen diselenide, and ebselen selenol are 36.8, 38.4, and 32.5 kcal/mol, respectively, in good qualitative agreement with experiment. It is demonstrated that the oxidized selenium atom is significantly destabilized in all cases and that the exothermicity of the reactions is attributed to the peroxide oxygen atoms via reduction. The lower barrier to oxidation exhibited by the selenol is largely due to entropic effects in the reactant complex.

Anionic water clusters, (H2O)n(-), of various sizes, n = 1-8, have been investigated using high-level ab initio calculations and the quantum theory of atoms in molecules, which provides a topological analysis of the electron density. The results of the current study indicate that the distribution of the excess electron is dependent on the geometry of the cluster. Non-nuclear attractors (NNAs), with associated pseudo-atomic basins and populations, are observed only in the highly symmetric clusters in which several non-hydrogen-bonded (NHB) hydrogen atoms are oriented toward a central cavity. For the latter cases, the non-nuclear attractor can be considered a pseudo-atom, possessing a significant portion of the excess electron within the cavity, consistent with the cavity-bound model of the solvated electron. In some cases, the population of the NNA is more than 0.2 electrons, and it contributes in excess of 20 kJ/mol to the energy of the system. Furthermore, the less symmetric systems, which tend to orient the NHB hydrogen atoms away from the center of the cluster, tend to delocalize the excess electron to a greater extent over several atoms at the surface of the cluster, consistent with the surface-bound model of the excess electron.

Theoretical calculations have been performed on three model reactions representing the reduction of hydrogen peroxide by ebselen, ebselen selenol, and ebselen diselenide. The reaction surfaces have been investigated at the B3PW91/6-311G(2df,p) level, and single-point energies were calculated using the 6-311++G(3df,3pd) basis set. Solvent effects were included implicitly with the conductor-like polarizable continuum model and in one case with explicit inclusion of three water molecules. Mechanistic information is gained from investigating the critical points using the quantum theory of atoms in molecules. The barriers for the reduction of hydrogen peroxide with the ebselen, ebselen selenol, and ebselen diselenide models are 56.7, 53.4, and 35.3 kcal/mol, respectively, suggesting that ebselen diselenide may be the most active antioxidant in the ebselen GPx redox pathway. Results are also compared to that of the sulfur analogues of the model compounds.

A systematic comparison of the optimized geometries of five organotin compounds, Cl(n)Sn(CH(3))(4-n), n = 0-4, with the available gas-phase electron diffraction results is reported. All optimizations were carried out with the B3LYP density functional method. Comparison of 10 basis sets and three effective core potentials leads to the conclusion that the combination of the SDB-aug-cc-pVTZ basis set and the LANL2 effective core potential for tin, together with the 6-31G(d,p) basis set for the other atoms, is recommended for the prediction of the geometries of organotin compounds.

A bond path linking two saturated fluorine atoms is found to be ubiquitous in crowded difluorinated aromatic compounds. The bond path is shown to persist for a range of internuclear distances (2.3-2.8 A) and a range of relative orientations of the two C-F internuclear axes. The F. . .F bonding is shown to exhibit all the hallmarks of a closed-shell weak interaction. The presence of such a bond path can impart as much as 14 kcal/mol of local stabilization to the molecule in which it exists, a stabilization that can be offset or even overwhelmed by destabilization of other regions in the molecule. Several other weak closed-shell interactions were also found and characterized including F. . .C, F. . .O, and C. . .C interactions, hydrogen bonding, dihydrogen bonding, and hydrogen-hydrogen bonding. This study represents another example of the usefulness and richness of the bond path concept and of the theory of atoms in molecules in general.

The question of why the iron displacement out of the porphyrin plane is enhanced in quintet states of singly ligated iron-porphyrin complexes compared to lower spin states and unligated iron-porphyrin is addressed. The spatial size of the Fe2+ atom is analyzed with respect to different spin states, and it is shown that the ion size decreases with increasing spin state for the d6 electronic configuration. This contradicts the common belief that the iron out-of-plane location in the quintet state of ligated Fe(II)-porphyrins is due to an increased required space of the iron within the porphyrin ring. Therefore, the singlet, triplet, and quintet ground states of imidazole-ligated iron-porphyrin have been calculated employing density functional theory, and the relevant molecular orbitals have been analyzed. Additional comparison with the unligated iron-porphyrin molecules reveals that the enhanced doming in the quintet state is the result of a combination of the weakening of the iron-ring nitrogen bonds by oc...

The equilibrium geometries of 54 small molecules containing linear or near-linear N-H...N bonds (sample M) have been optimized at the MP2/6-31G(d,p) level and the values of p' and p" of the parameters p c at the bond-critical points (p' in the N-H, p" in the H...N bond) have been computed from the results of these optimizations. Because the N-H and the H...N part of an N-H...N bond system have different character, the trends of p' and of p" in M are described by different functions. With the p c as descriptors (the electron density ρ c , the curvatures λ c , i , the Laplacian * 2 c , the kinetic energy densities G c and K c , and the potential energy density V c ), we have searched for correlations of p' and p" (homocorrelations) in M. A high degree of correlation has been found for all the parameters. With the exception of the linear ρ',ρ" correlation the homocorrelations of the other p c are nonlinear and some of them nonmonotonic. The homocorrelations permit estimates of the p c values, p s , in symmetric N-H-N bonds, where estimates from experiment are not without problems. They also answer some of the questions concerning limiting values of the p c . With the exception of G c , correlations between unlike p c 's (heterocorrelations, p',q' and p",q") will be reported in a subsequent paper, now in preparation. The heterocorrelations involving G c are included here because of the prominence of G c in recent discussion of hydrogen bonds in the literature.

The proline-catalyzed direct aldol reaction between acetone and acetaldehyde has been investigated using density functional theory. Proline catalyzes the reaction according to the enamine mechanism characteristic of the natural class I aldolase enzymes. Although it has been postulated that the rate-limiting step in the proposed mechanism is enamine and/or C−C bond formation, the initial reaction between proline and acetone is accompanied by a very large barrier which may inhibit further progression of the reaction. However, an alternative lower energy reaction pathway is utilized when the ionizing solvent DMSO is present to assist in the formation and stabilization of separated charges. The direct aldol reaction between acetone and acetaldehyde illustrates the catalytic potential of simple organic molecules in asymmetric synthesis.

DNA-protein cross-linking is one of the many DNA lesions mediated by hydroxyl radicals, the most damaging among the reactive oxygen species in biological systems. Density functional theory methods are employed to investigate the complex reaction mechanisms of the formation of cytosine-tyrosine cross-links as observed in gamma-irradiated aqueous solutions of cytosine and tyrosine, as well as in gamma-irradiated nucleohistone. The majority of the radical addition mechanisms considered are found to have significant barriers and therefore to be thermodynamically unfavorable for the formation of the initial cross-linked product. Our calculated reaction potential energy surfaces suggest that a feasible complete mechanism consists of radical combination forming the initial cross-linked product, a hydrogen shuffle within the initial cross-linked product, and an acid-catalyzed dehydration reaction. Water and hydrogen-bonding interactions are suggested to play a key role in catalyzing the hydrogen-transfer step of the reaction.

In the present study, ab initio methods are used to study the NO3 hydrogen-abstraction reaction from a series of aldehydes: FCHO, ClCHO, HCHO, and CH3CHO. MP2 and BH&HLYP optimizations were carried out, followed by CCSD(T) single point calculations, using the 6-311G(d,p) basis set. Classical transition state theory (TST) is applied for the calculation of the rate constants, and tunneling corrections are considered assuming an unsymmetrical Eckart barrier. The experimental results (activation energy for the CH3CHO reaction and rate constants for the reaction of NO3 with HCHO and CH3CHO) are well reproduced at the CCSD(T)//BH&HLYP level of theory with some corrections. The same level was chosen to predict the remaining unknown kinetic parameters. At this level of calculation the reactions studied were assumed to be elementary.

In the present study, ab initio methods have been used to study the OH hydrogen-abstraction reaction from two substituted aldehydes: FCHO and ClCHO. A complex mechanism in which the overall rate depends on the rates of two competitive reactions, a reversible step where a reactant (or prereactive) complex is formed, followed by the irreversible hydrogen abstraction to form the products, is corroborated. This mechanism was previously shown to describe accurately the kinetics of the OH hydrogen-abstraction reaction from formaldehyde and acetaldehyde. Classical transition state theory (TST) rate constants calculated with tunneling corrections, assuming an unsymmetrical Eckart barrier, agree very well with experimental upper bound values. Activation energy barriers and enthalpies of reaction have been estimated through CCSD(T) single point calculations using MP2 geometries and frequencies and the 6-311++G(d,p) basis set.

In an attempt to discover and analyze trends in distance relationships and properties at the bond critical point (BCP) in linear or near-linear N−H···N hydrogen bonds, the geometry of such bonds in a large number of suitable simple chemical species was optimized at the RHF/6-31G** level. The results for 67 of these are reported here; the geometry of 19 of them was optimized also at the MP2/6-31G** level. Correlations between the internuclear N−H, H···N, and N···N separations as well as between the N···BCP and H···BCP distances for these data sets and for different model functions are described in detail. The special case of symmetric N−H−N bonds is discussed; comparison with available experimental evidence shows that the correlation functions derived from the ab initio data have useful predictive value for crystallographic determinations involving short N−H−N bonds. Analysis of the correlation between the d(N−H) distance and the electron density ρc at the BCP has shown that although acceptable d,ρc repres...

In this work, the OH + formaldehyde and OH + acetaldehyde reactions have been characterized using accurate ab initio methods with large basis sets. The results clearly indicate that the reaction occurs by hydrogen abstraction, and that the OH addition channel is unfavorable. Close to zero (for formaldehyde) and negative (for acetaldehyde) activation energy values are obtained, which are in excellent agreement with the experimentally observed values. The reaction rate constants, calculated using the classical transition-state theory as applied to a complex mechanism involving the formation of a prereactive complex, reproduce very well the reported experimental results. Consideration of the prereactive complex is shown to be essential for the determination of the height of the energy barrier and thus for the correct calculation of the tunneling factor.

The aminolysis of 6-chloropyrimidine and 2-amino-6-chloropyrimidine has been examined by using density functional theory. Relative to the aminolysis of 6-chloropyrimidine, the addition of an electron-donating NH(2) group to C(2) increases the barrier to aminolysis, indicating that the third hydrogen bond does not play a catalytic role but introduces additional rigidity into the system. However, the computations suggest that there is an interesting correlation between the barrier to aminolysis and the proton affinity of the species that interacts with the incoming NH(3). To extend the range of proton affinities, the aminolysis of 6-chloropyrimidine was examined by using fluoro, imine, and thioketo derivatives of the uracil-derived bases. The proton affinity of the moiety that hydrogen bonds with NH(3) is decreased by fluoro substitution, and thus the aminolysis barriers are increased. Similarly, imine substitution enhances the PA of the moiety, which is reflected in a decrease in the aminolysis barriers. The same correlation exists for the thioketo-derived bases, whose PAs are intermediate between the fluoro and imine derivatives. Thus, the aminolysis of 6-chloropryimidine and 2-amino-6-chloropyrimidine demonstrates the importance of a well-chosen proton acceptor and the catalytic possibilities associated with the formation of multiple hydrogen bonds.

The radiation products of hydroxyproline have been investigated using density functional theory. In the resulting radicals, the choice of the apical ring atom is found to be dependent on the nature and strength of the intramolecular hydrogen bonding. The observed hyperfine couplings previously assigned to two zwitterionic conformers of the hydroxyproline primary radical anion are found to be better described by its nonzwitterionic isomers and corresponding neutral protonated isomers. Similarly, the observed hyperfine couplings for radicals formed by cleavage of the Cα−N bond (deamination) are in closest agreement with those calculated for their neutral forms. Theoretical proton hyperfine couplings support the experimental assignment of the radical cation formed by decarboxylation and the radicals resulting from hydrogen abstraction from the C2 and C3 positions. The proton hyperfine couplings are sensitive to the conformations of the radicals, which, in turn, are highly dependent upon the extent of intramo...

Density functional theory was employed to investigate the radicals that have been proposed to be formed upon irradiation of glycine crystals. The present theoretical study suggests that the radicals are R1: +NH3C•HCOO-; R2: •CH2COOH; R3: NH2C•HCOOH; and R4: NH2CH2COC•HCOOH. A Cs structure for R1, obtained using the Onsager model, gives hyperfine coupling constants in agreement with experiment. Hyperfine coupling constants computed for R2 are in agreement with the unassigned experimental data of Teslenko, V. V. et al. (Mol. Phys. 1975, 30, 425). The computed hyperfine coupling constants for R4 are in good agreement with the experimental data assigned to the zwitterionic form +NH3CH2COC•HCOO-. It is shown that the structure of R3 is influenced significantly by the glycine crystal environment. Protonation of R3 gives rise to hyperfine couplings similar to the experimental values assigned to one conformer of R3.

The effects of the successive addition of alkyl substituents (methyl and reduced rings) on the excited states of naphthalene are reported. The calculated electronic states of all the reduced derivatives with two, three, and four substituents are compared with the excited states of their methylated analogues. The excited states of several reduced derivatives with seven and eight substituents are also studied. The AM1 method was used to optimize the geometry of 57 naphthalene derivatives, and excited states were calculated with the ZINDO/S (INDO/S) method. ZINDO/S calculations on naphthalene gave excited states in better agreement with experimental results than with results of other semiempirical (CNDO/S and CNDOL) and ab initio (CIS, TD-HF, and TD-DFT) methods. Successive alkyl substitutions are accompanied by bathochromic displacements of the UV-visible bands, since the occupied orbitals are raised in energy more than the unoccupied orbitals. However, not all available substituent positions in naphthalene alter its orbital energy distribution in the same way when they are occupied by alkyl substituents. Distortion from planarity of the naphthalene skeleton of some reduced derivatives is the cause of “anomalous” bathochromic displacements of the absorption bands.

Ab initio MO calculations indicate that the effect of protonation of third-row X (X = Ge, As, Se, Br) in CH3XHn, C2H5XHn, C2H3XHn, and C2HXHn is similar to that of first- and second-row X; specifically, both the CX homolytic bond dissociation energies (BDEs) and (except for As and the ethynyl compounds) the CX bond lengths (BLs) increase. Deprotonation decreases the CX BDE for saturated compounds, an electronegativity effect, but increases it for unsaturated ones (except Ge), a resonance effect; correspondingly, the CX BLs increase in saturated and decrease in unsaturated compounds (except Ge). Heterolytic CX dissociation of third-row RCXHn+1+ to RC+ and XHn+1 is often favored over the homolytic process when XHn+1 is electronegative relative to the hydrocarbon moiety (XHn+1 = AsH3, SeH2, BrH); the corresponding dissociation of RCXHn-1- to RC- and XHn-1 similarly may be favored for RC = ethynyl and Xn-1 low in electronegativity (XHn-1 = GeH2-, AsH-, Se-). The CC BDEs are also affected by protonation of X; ...

Density-functional theory is used to investigate the radiation products (radicals R1, •CH(CH3)COOH; R2, H3N+C•(CH3)COO-; and R3, H2NC•(CH3)COOH) of l-α-alanine at 295 K. Four conformers were found for R1 and R3. A planar structure of R2 in a zwitterionic form was obtained with the Onsager model. The relative energies of each of the four conformers of R1 and R3 show that structures with intramolecular hydrogen bonding are more stable. The computed hyperfine couplings are shown to be in good agreement with the accurate results obtained from the electron paramagnetic resonance (EPR), electron−nuclear double resonance (ENDOR), and EIE (ENDOR-induced EPR) experiments performed by Sagstuen et al. [Sagstuen, E.; Hole, E. O.; Haugedal, S. R.; Nelson, W. H. J. Phys. Chem. A 1997, 101, 9763]. The effects of rotation about the NC2 bond on the HFCCs of the amino protons in R2 support the previous suggestion that the amino protons are fixed by intermolecular hydrogen bonding in l-α-alanine crystals. Moreover, a good c...

The geometries, spin density distributions, and hyperfine coupling constants (HFCC) in possible radiation products of guanine are studied through the use of density functional theory. Numerous hydrogenated, dehydrogenated, and hydroxylated radicals are ex

Density functional theory is used to study the energetics, geometries, and hyperfine couplings in sugar radicals which are generated through irradiation of DNA. The C4‘−S and the C3‘−S radicals are determined to be the lowest lying species of the radicals formed through abstraction of a hydrogen or a hydroxyl group from a model of the sugar present in DNA, respectively. The C2‘ radical has the highest energy and the smallest degree of ring puckering of all possible carbon-centered radicals formed via hydrogen abstraction. In addition to the possible dehydrogenated and dehydroxylated products, various radicals which lead to substantial ring alterations, such as ring breaks or flattening of the ring, are also studied. In most cases, the calculated hyperfine coupling constants directly support the assignment of the experimentally observed couplings to the specific radicals. The effects of rotation about the C5‘C4‘ bond on the HFCCs in the C5‘ and O5‘ radicals are examined in order to compare the experimental...

Possible radical reaction products observed when subjecting monohydrate crystals of the DNA base cytosineto ionizing radiation are characterized and analyzed by means of density functional theory. Comparison ismade with data from a recently published detailed ESR and ENDOR study by Sagstuen et al. (Sagstuen, E.;Hole, E. O.; Nelson, W. H.; Close, D. M. J. Phys. Chem. 1992, 96, 8269), as well as earlier studies onmethylcytosine and cytidine monophosphates. For cytosine monohydrate it is found, when comparing computedand measured radical hyperfine coupling constants, that products other than those initially assumed are possiblybeing formed. Instead of the original model that irradiation leads to the net reaction of dehydrogenation atthe N1 position of one cytosine molecule and hydrogenation at the N3 position of a second cytosine, wepresent an alternative mechanism where water is involved in the process. This alternative mechanism leadsto the formation of N3 hydrogenation and C5 hydroxylation net products, as the main reactions. Not only dothe hyperfine couplings provide a better match for the latter but they are also energetically favored over thefirst mechanism.

Quantum-chemical studies (UMP2/6-311G*//UHF/6-311G*) on a series of phosphenium and arsenium derivatives confirm singlet ground states and reveal an unexpected model for the bonding in their lowest triplet state. Models of the novel solid-state dimer structures that are experimentally observed for some arsolanium cations reveal large positive dimerization energies (P, 3, 277 kJ/mol; As, 7, 207 kJ/mol), implying that the observed dimers are imposed by crystal-packing phenomena. The surprising contrast observed in the butadiene cycloaddition reactivities for phosphenium and arsenium cations are understood in terms of the calculated absolute energies of the observed structural arrangements for the cycloadducts in each case; the cheletropic adduct 4 is 52 kJ/mol more stable than the Diels−Alder adduct for the phospholanium cation, while in the case of the arsolanium cation the Diels−Alder adduct 9 is favored by 59 kJ/mol.

The geometries, relative energies, and hyperfine coupling constants of dehydrogenated, hydrogenated, and hydroxylated radiation products, as well as the anion and the cation, of thymine (T), 1-methylthymine (1-MeT), and uracil (U) are calculated through the use of density functional theory. The results for T and 1-MeT are subsequently compared to accurate ENDOR experiments performed by Sagstuen and co-workers (Sagstuen, E.; Hole, E. O.; Nelson, W. H.; Close, D. M. J. Phys. Chem. 1989, 93, 5974 and references therein). The theoretical coupling constants support the experimental assignment of the observed radicals. It is suggested that the hydrogen added to form the O4-hydrogenated product is located at an angle of 50° out of the molecular plane in T. Unfavorable interactions of this hydrogen with the N3 and the methyl hydrogens are shown to lead to this out-of-plane position for O4−H. For the similar radical in 1-MeT, hydrogen bonding in the crystal leads to an in-plane hydrogen position. Notable geometry ...

The interactions between polycyclic aromatic hydrocarbons (with up to four rings) and dinitrobenzene have been calculated using semiempirical methods and shown to give poor correlation with experimental stability constants. Quadrupole moments for these molecules have been calculated at the HF/6-31G(d,p) and BLYP/6-31G(d,p) levels of theory. The interaction between polycyclic aromatic hydrocarbons and nitrated benzenes is found to be dependent on the quadrupole moment. Dispersion interactions are estimated to be considerably smaller than quadrupole interactions and not a significant influence on the binding energy. The two methods used show the same trends in the calculated quadrupole moment, and it is shown that a method involving electron correlation may not be necessary for prediction of stability constants.

Ab initio MO calculations indicate that protonation of XHn to XHn+1+ increases bond dissociation energies (BDEs) for homolytic cleavage of CX bonds in CH3XHn, CH3−CH2−XHn, CH2CH−XHn, and CH⋮C−XHn compounds (X = N, O, F, P, S, and Cl). Deprotonation of XHn to XHn-1- (X = C, N, O, Si, P, and S) in saturated species generally results in small decreases in CX BDEs; in unsaturated substances, as a result of resonance, deprotonation yields large increases in the CX BDEs, X = Si being the exception. For adjacent CC bonds, protonation of XHn increases the CC BDEs because it produces larger electronegativity differences between bonded groups; deprotonation decreases the BDEs as a result of resonance effects. Two types of correlation between bond lengths and homolytic BDEs are observed, with second-row elements exhibiting bond length changes to a much lesser extent than first-row ones. Firstly, bond lengths of adjacent CC bonds increase as their BDEs decrease. Secondly, and apparently anomalously, CX bond lengths a...

The electron densities of H2, Li2, N2, O2, and F2 have been calculated by density functional theory (DFT) methods with various exchange and correlation functionals such as SVWN, BLYP, B3LYP, BP86, B3P86, and B3PW91 and compared with the results from quadratic configuration interaction calculations including all single and double substitutions (QCISD) using Dunning's correlation consistent polarized valence double- and triple-ζ basis sets augmented with the corresponding diffuse functions (aug-CC-PVDZ and aug-CC-PVTZ). The DFT methods yield electron densities and Laplacians of the densities in good agreement with the QCISD results. The gradient-corrected functionals improve upon the densities calculated by use of the local spin density approximation (SVWN) relative to the corresponding QCISD densities. All gradient-corrected functionals are generally insensitive to the grids used in the study. The basis set, however, has a significant effect on the electron density and shows a strong dependence on the choi...

The energies and structures of the 28-electron tetraatomic molecules, composed of the first row nonmetallic elements: N4 (1), CN2O (2), BFN2 (3), C2O2 (4), B2F2 (5), CBFO (6), C2FN (7), and BNO2 (8) have been studied uniformly by ab initio methods including coupled-cluster theory. New estimates of the stability of the N4 isomers, tetraazatetrahedrane and tetraazacyclobutadiene, are presented, and a new triplet NNNN open-chain isomer has been established computationally. Potential energy surfaces of the nonpolar 1 and the polar 2 are compared. Three-membered cyclic C2v fluorodiazaboririne has been found to be the most stable isomer similar to diazirinone (Chem. Phys. Lett. 1994, 227, 312). Linear triplet CO and BF dimers, OCCO, FBBF, and OCBF, are the most stable forms of 4, 5, and 6, respectively. The singlet cyanofluoromethylene, NCCF, the global energy minimum of 7, is 7 kcal/mol more stable than isomeric CNCF and 10 kcal/mol lower in energy than 3-fluoroazacycloprop-2-ylidene. The singlet and triplet ...

The solvent dependence of the tautomeric equilibria of 2-, 3- and 4-hydroxypyridines is investigated by means of self-consistent reaction field (SCRF) theory. The tautomeric equilibrium constants (KT) in cyclohexane, chloroform, and acetonitrile are predicted at both the Hartree−Fock (HF) and the second-order Moller−Plesset perturbation theory (MP2) levels. It is found that log KT is linearly dependent upon the solvent polarity as measured by the Kosower Z parameter, in agreement with earlier experimental findings. Based on this relation, log KT is predicted to be 1.72, 0.86, and 5.65 for 2-, 3-, and 4-hydroxypyridines, respectively, in aqueous solutions.

Approximate Fukui indices have been derived from the atomic volumes of molecules as calculated within the framework of Bader's atoms-in-molecules theory. Parameters of the bond critical points {∇ρ(rc)n = 0} have been explored in calculating the hardness (η) and electronegativity (χ) of a selection of typical chemical groups, widely considered as transferable entities. Resulting η and χ indices demonstrate strong dependence on the nature of neighboring atoms and on the bond system vicinal to the group; however, they are not directly related to the group charges.

The electron densities of CH3F, CO, CO2, H2CO, H2O, HCN, HF, and NH3 have been calculated by density functional theory (DFT) methods with various exchange and correlation functionals and are compared with QCISD (quadratic configuration interaction method including single and double substitutions) results. The DFT methods yield electron densities and Laplacians of the densities in good agreement with the QCISD results. As expected, the gradient-corrected functionals including B3LYP, B3P86, BP86, and BLYP improve the densities calculated by the local spin density approximation relative to the corresponding QCISD densities. Relative to his 1988 functional, Becke's three-parameter exchange functional clearly improves the results for equilibrium geometries, vibrational frequencies, dipole moments, and electron densities. For all gradient-corrected functionals, the results are generally insensitive to the numerical accuracy of the grid. The basis set, however, has a significant effect on the electron density, w...