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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.

The source function (SF) decomposes the electron density at any point into contributions from all other points in the molecule, complex, or crystal. The SF "illuminates" those regions in a molecule that most contribute to the electron density at a point of reference. When this point of reference is the bond critical point (BCP), a commonly used surrogate of chemical bonding, then the SF analysis at an atomic resolution within the framework of Bader's Quantum Theory of Atoms in Molecules returns the contribution of each atom in the system to the electron density at that BCP. The SF is used to locate the important regions that control the hydrogen bonds in both Watson-Crick (WC) DNA dimers (adenine:thymine (AT) and guanine:cytosine (GC)) which are studied in their neutral and their singly ionized (radical cationic and anionic) ground states. The atomic contributions to the electron density at the BCPs of the hydrogen bonds in the two dimers are found to be delocalized to various extents. Surprisingly, gaining or loosing an electron has similar net effects on some hydrogen bonds concealing subtle compensations traced to atomic sources contributions. Coarser levels of resolutions (groups, rings, and/or monomers-in-dimers) reveal that distant groups and rings often have non-negligible effects especially on the weaker hydrogen bonds such as the third weak CH⋅⋅⋅O hydrogen bond in AT. Interestingly, neither the purine nor the pyrimidine in the neutral or ionized forms dominate any given hydrogen bond despite that the former has more atoms that can act as source or sink for the density at its BCP. © 2018 Wiley Periodicals, Inc.

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.

Since the 1960s, dithiolene complexes have been intensely studied; however, the same cannot be said about diselenolene complexes. Thus, the chemistry associated with the reduction of several Mo- and W-tris(diselenolene) complexes was investigated. In particular, relative reduction potentials, changes in key geometrical properties, the contribution of the metal center to the redox active MO, and HOMO–LUMO energy gaps are investigated. It is noted that the results obtained for the tris(diselenolene) complexes are compared to analogous Mo- and W-tris(dithiolene) complexes to understand the effect of substituting the sulfur atoms with selenium atoms. The reduction potentials of the complexes are more dependent upon the choice of the ligand than the metal. Overall, it is found that the substitution of chalcogen atom for the tris complexes investigated herein has only a subtle effect on the calculated reduction potentials between analogous redox couples. Upon reduction of the neutral and mono-anionic complexes, it is found that changes in key bond lengths, fold angles (θ), and trigonal twist angles (ΦAvg) are very similar for the tris(diselenolene) complexes investigated. Such changes have been previously observed for several Mo- and W-tris(dithiolene) complexes. Comparing the HOMO–LUMO energy gaps of the tris(diselenolene) complexes to the tris(dithiolene) complexes, the former complexes have on average a 0.07-eV smaller energy gap and are thus expected to be slightly more reactive to reduction. Lastly, in the neutral complexes, the Mo and W atoms contribute at most 26% to the redox active MO; thus, in the case of the tris(diselenolene) complexes, it can be concluded that the redox active MO is predominantly ligand based. The contribution of the metal-based AO becomes less as the complexes are reduced. In summary, given the high interest of dithiolene complexes in the areas of alternative energy and material science, the results presented herein provide motivation to further investigate the chemistry of diselenolene complexes.

The mechanism of the iridium-catalyzed functionalization of a primary C–H bond at the γ position of an alcohol 5 is investigated by density functional theory (DFT) calculations. A new IrIII–IrV mechanism is found to be more feasible than the previously reported IrI–IrIII mechanism. 10 In the IrIII–IrV mechanism, the reaction begins with the initial formation of (Me4phen)IrIII(H)[Si(OR)Et2]2 from the catalyst precursor, [Ir(cod)OMe]2 (cod = 1,5-cyclooctadiene). The catalytic cycle includes five steps: (1) the insertion of norbornene into the Ir–H bond to produce (Me4phen)IrIII(norbornyl)[Si(OR)Et2]2 (R = –CH(C2H5)C3H7); (2) the Si–H oxidative addition of HSi(OR)Et2 to form (Me4phen)IrVH(norbornyl)[Si(OR)Et2]3; (3) the reductive elimination of norbornane to furnish (Me4phen)IrIII[Si(OR)Et2]3; (4) the intramolecular C–H activation of the primary C–H bond at the γ position; and (5) the Si–C reductive elimination to produce the final product and regenerate the catalyst. The highest barrier in the IrIII–IrV mechanism is 7.3 kcal/mol lower than that of the IrI–IrIII mechanism. In addition, the regioselectivity of the C–H activation predicted by this new IrIII–IrV mechanism is consistent with experimental observation.

We recently described the binding of 1-β-phosphonomethylene-1-deoxy-d-glucopyranose, (S)-1-β-phosphonofluoromethylene-1-deoxy-D-glucopyranose (βG1CFSP), and (R)-1-β-phosphonofluoromethylene-1-deoxy-d-glucopyranose (βG1CFRP) to the enzyme β-phosphoglucomutase as transition state analogues of phosphoryl transfer through formation of stable MgF3− and AlF4− complexes (Proc. Natl. Acad. Sci. U.S.A. 2014, 111, 12384). Herein, we describe in detail the five-fold difference in acidity (pKa2) for the (S)- and (R)-configured diastereomeric fluorophosphonates through a series of NMR spectroscopy experiments. The differences in acidity were corroborated using computational quantum mechanical calculations to determine structures of lowest energy conformers and provide insight into why the (S) isomer is substantially more acidic.

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.

Due to ligand non-innocence and reversible one-electron-transfer processes dithiolene complexes have been intensively studied both experimentally and computationally. While the substitution of the ligating sulfur atoms by selenium provides a means to delicately tune the behavior of dithiolene compounds, diselenolene complexes have not been as thoroughly examined. Yet, the search for such ligands has been ongoing since the 1970s. Thus, we have looked at several metal-bisdiselenolene complexes and have compared key properties of these complexes with their bisdithiolene analogues to determine the effect of substituting the chalcogen atom. The results herein show that substitution of the sulfur atoms by selenium within these complexes only subtly changes the thermodynamics and kinetic reactivity of bisdithiolene complexes while not significantly affecting the geometries of the complexes. The significance being that the relatively minor structural changes that occur upon redox is a key feature of dithiolene complexes. Due to ligand non-innocence and reversible one-electron-transfer processes dithiolene complexes have been intensively studied, however, diselenolene complexes have not. First-principles calculations show that substitution of the sulfur atoms by selenium within the investigated complexes does offer the ability to subtly tune the thermodynamics and kinetic reactivity of bisdithiolene complexes, while not significantly affecting the geometries of the complexes. © 2015 Wiley Periodicals, Inc.

The full catalytic mechanism for nitrile hydratase is explored, involving cysteine-sulfenic acid acting as a nucleophile, activating a water molecule to attack nitrile substrates. The iminol intermediate undergoes tautomerization to form the amide product. The computed enthalpies are closely related to experimental values, suggesting the current mechanism with two water molecules should be further investigated.

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.

To prepare for future resistance, new methods are being explored for novel treatment of malaria. The current work uses high performance docking methods to model different substrates binding into the active sites of varying Homo sapien and Plasmodium peptidyl-prolyl cis/trans isomerase enzymes and compares their subsequent docking scores. This approach has shown that the substrates ILS-920 and WYE-592 will bind less-favourably with hFKBP12 and PfFKBP35 compared to a competing substrate rapamycin; however, the binding appears to be more favourable in PvFKBP35. This could suggest a possible target for inhibition of the Plasmodium vivax parasite.

Capture of the cyclic oxyallyl cation intermediates from the BF3-mediated Nazarov reactions of three allenyl vinyl ketones with various dienes was accomplished by (3+2)- and (4+3)-cycloaddition. The relative amounts of these types of products were dependent on the substitution on the diene, and this could be linked to steric hindrance. Treatment of the (3+2)-cycloaddition products with BF3·Et2O led mainly to decomposition but also to ring-opened molecules and ring-enlarged structures. The computed Gibbs energies of the (3+2)-cycloaddition products, the products of the acid treatment and of some transition states leading to rearranged products were compared.

The local and regional stabilities in clusters of water, methanol, and formaldehyde up to the tetramers have been analyzed from an atomic energy perspective. We optimize structures at the MP2/6-311++G(d,p) level with some CCSD(T)/6-311++G(d,p) single point energies, and then decompose the electronic densities into atomic parts using the atoms in molecules (AIM) approach. We consider the changes in atomic energy in the clusters vs. the isolated monomer. This method of analysis allows us to reveal the variety of stabilities within these hydrogen-bonded clusters, including indications of cooperative, anti-cooperative, and non-cooperative interactions. Cooperatively interacting clusters have increasing stability at the atomic level as the cluster size grows. This is not observed in the anti- and non-cooperative arrangements of water and formaldehyde clusters. The cooperativity in methanol clusters is dominated by the OH regions, with negligible energy change in the methyl regions. Formaldehyde clusters, including the lowest minimum “bucket” cluster, do not show significant cooperativity. Atomic energy analysis is supported with bond critical point data as well as charge and geometric values. We represent the local stability in the clusters using a simple visual approach that allows areas of increased or decreased stability to be easily interpreted.

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.

Organotin compounds are very important in material design as well as in biomedical and biochemical applications. However, little is known about their BDEs experimentally or computationally. Thus, a variety of common quantum chemical methods in combination with several approaches to treating relativistic effects of the tin core electrons were used to calculate the BDEs of organotin compounds. Our results show that the BDEs are very sensitive to the choice of the computational method and to the treatment of relativistic effects.

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.

The reactions of XSeSX, XSeSY, and YSeSX (X, Y = CH3, NH2, OH, F) with F− and CN− nucleophiles have been investigated by means of B3PW91/6-311+G(2df,p) and G4 calculations. In systems where the two substituents are not identical (XSeSY), the more stable of the two possible isomers corresponds to those in which the most electronegative substituent is attached to Se. Nucleophilic attack takes place at Se, independent of the nature of the nucleophile, with the only exception being XSeSF (X = CH3, NH2, OH), in which case the attack occurs at S. In agreement with recent results for disulfide and diselenide linkages, the mechanisms leading to Se—S bond cleavage are not always the more favorable ones because for highly electronegative substituents the most favorable process is fission of the chalcogen-substituent bond. These dissimilarities in the observed reactivity pattern as a function of the electronegativity of the substituents are due to the fact that the σ-type Se—S antibonding orbital, which for low-electronegative substituents is the lowest unnoccupied molecular orbital (LUMO), becomes strongly destabilized when the electronegativity of the substituent increases, and is replaced by an antibonding π-type Se-X (or S-X) orbital. In contrast, however, with what has been found for disulfide and diselenide derivatives, the observed reactivity does not change with the nature of the nucleophile. The activation strain model provides interesting insight into these processes, showing that in most cases the activation barriers are the consequence of subtle differences in the strain or in the interaction energies. © 2013 Wiley Periodicals, Inc.

α-Helical peptides of the form For-AAAAAAXAAAAAA-NH 2 , where X is one of 21 amino acids, have been optimized by use of density-functional theory with the inclusion of solvent by a polarizable continuum model and analyzed by use of the quantum theory of atoms in molecules. Inclusion of solvent results in the transition from a partial 3 10 -helix geometry that was previously observed in gas-phase optimized structures to a fully α-helical geometry, resulting in a substantial loss of NH⋯O i + 3 contacts and concurrent formation of NH⋯O i + 4 contacts. An increase in the number of N⋯O i + 3 contacts was also observed. The total electron density (∑ ρ ( r c )) at the hydrogen bond critical points (HBCPs) within the peptide backbone increased by up to 160% in the solvated structure. No correlation was found between the ∑ ρ ( r c ) at HBCPs and an α-helix propensity scale, however, the ∑ ρ ( r c ) at HBCPs for the substituted amino acids yields a helix-stabilizing order for the amino acids: Thr > Asn > Ser > Glu > Trp > Arg > Asp > Leu > Cys > His + >Gln > Lys > Met > Ile > Val > Phe > His > Ala > Tyr > Pro > Gly.

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.

Analogues of the antioxidant ethoxyquin are studied to determine the effects of changing the group 16 element in the reacting center of a glutathione peroxidase mimic. The energy barrier for hydrogen peroxide reduction decreases along the group, with sulfur showing the highest, selenium intermediate, and tellurium the lowest barrier. The ethyl side chain on the chalcogen is substituted with methyl and tertiary-butyl groups to determine the degree of steric effects on the barrier. A phenyl substituent results in a higher barrier than the alkyl side chains.

The potential energy surfaces of methanol clusters, (CH3OH)n, n = 2-12, have been studied using density functional theory at the B3LYP/6-31G(d) and higher levels of theory. Cyclic clusters in which n methanol molecules are joined in a ring structure formed by n hydrogen bonds are shown to be more stable than structures of the same number of methanol molecules where one or more methanol molecules are outside the ring and are hydrogen-bonded to oxygens of methanols in rings of n - 1, n - 2, and so forth. So-called chain structures are generally even less stable. Furthermore, the hydrogen-bonding energy per methanol molecule of the n-ring clusters is shown to converge to an asymptotic value of about 27 kJ/mol at B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) after five to six methanols are included in the cluster. As expected, there are many minima on the potential energy surfaces of the methanol clusters, the number increasing rapidly with n. A cyclic cluster of five to six methanol molecules appears to be sufficient to mimic liquid behavior as far as vibrational frequencies are concerned.

We report a detailed study by means of the theory of atoms in molecules (AIM) of the resonance effect exhibited in systems where a halogen is adjacent to a carbon-carbon double bond. Moreover, we have carried out a comparable study of the respective saturated halohydrocarbons and hydrocarbons, as well as the related unsaturated hydrocarbons. The valence shell charge concentration (VSCC) of the atoms in systems that exhibit the halogen resonance effect is considerably different from that of the systems where only the electron withdrawing inductive effect is present. Our analysis of the bonded maximum charge concentration and the electronic properties at the bond critical points clearly indicate that the carbon-carbon double bond is strongly distorted as a result of the halogen resonance effect. Population analyses show that the halogen resonance effect is a donor effect, but the opposing electron-withdrawing inductive effect is stronger. Moreover, the analysis in terms of link points of the VSCCs of the carbons accounts for the observed position-dependence of electrophilic aromatic substitution in α- and β-halonaphthalenes.

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.

Inspired by the helical structure as well as the conductivity of DNA and substituted polyphenylacetylenes, a new kind of substituted polyacetylene is introduced. More specifically, polycytosineacetylene ((RC CH) n , R = cytosine) with a trans-polyacetylene backbone is investigated theoretically. The neutral and cationic geometries are optimized as single helical chains with n = 20. It is found that when an electron is removed the polymer stretches from 19.80 A to 28.41 A. The polyacetylene backbone in the optimized cationic polymer exhibits the formation of a soliton. It is predicted that a doped polycytosineacetylene would have good conductivity, and would also behave as a nanomechanical spring and as a piezoelectric material.

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.

The structures and relative stabilities of the complexes formed by uracil and its thio- and seleno-derivatives with the Sr(2+) cation, in the gas phase, have been analyzed by means of G96LYP density functional theory (DFT) calculations. The attachment of the Sr(2+) cation to the heteroatom at position 4 is preferred systematically. Although the enolic forms of uracil and its derivatives should not be observed in the gas phase, the corresponding Sr(2+) complexes are the most stable. The enhanced stability of these tautomers is two-fold, on the one hand Sr(2+) interacts with two basic sites simultaneously, and on the other hand an aromatization of the six-membered ring takes place upon Sr(2+) association. Sr(2+) attachment also has a clear catalytic effect in the tautomerization processes involving uracil and its derivatives. This catalytic effect increases when oxygen is replaced by sulfur or selenium. The Sr(2+) binding energy with uracil and its derivatives is bigger than the tautomerization barriers connecting the dioxo forms with the corresponding enolic tautomers. Consequently, when associated with Sr(2+), all tautomers are energetically accessible and should all be observed in the gas phase.

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 local value of the single-particle momentum provides a direct three-dimensional representation of bonding interactions in molecules. It is given exclusively in terms of the electron density and its gradient, and therefore is an ideal localized electrons detector (LED). The results introduced here extend to molecular systems our study of the single-particle local momentum in atomic systems (Bohorquez and Boyd in J Chem Phys 129:024110, 2008; Chem Phys Lett 480:127, 2009). LED is able to clearly identify covalent and hydrogen bonding interactions by depicting distinctive regions around the bond critical points, emerging as a complementary tool in conventional atoms in molecules studies. The local variable we introduce here is an intuitively interpretable 3D electron-pairs locator in atoms and molecules that can be computed either from theoretical or experimentally derived electron densities.

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.

We propose a general definition of the radius of an atom in terms of its ionization energy. A relationship between these two fundamental properties is derived from the radial distribution function and the exponential decay of the electron density. Strong correlations with well-known atomic radii lead us to conclude that we have found a universally valid definition of the atomic radius, defined exclusively in terms of an intrinsic property, the ionization energy of an atom, which is equally available from experiments and theoretical computations.

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 and second-order Møller–Plesset perturbation theory with effective core potentials have been used to calculate homolytic bond-dissociation enthalpies, D(Sn–X), of organotin compounds, and their performance has been assessed by comparison with available experimental bond enthalpies. The SDB-aug-cc-pVTZ basis set with its effective core potential was used to calculate the D(Sn–X) of a series of trimethyltin(IV) species, Me3Sn–X, where X = H, CH3, CH2CH3, NH2, OH, Cl, and F. This is the most comprehensive report to date of homolytic Sn–X bond-dissociation enthalpies (BDEs). Effective core potentials are then used to calculate thermodynamic parameters including donor–acceptor bond enthalpies, [Formula: see text], for a series of tin-ligand complexes, L2SnX4 (X = Br or Cl, L = py, dmf, or dmtf), which are compared with previous experimental and nonrelativistic computational results. Based on computational efficiency and accuracy, it is concluded that effective core potentials are appropriate computational methods to examine bonding in organotin systems.

When a system under consideration has some symmetry, usually its Hamiltonian space can be parallel partitioned into a set of subspaces, which is invariant under symmetry operations. The bases that span these invariant subspaces are also invariant under the symmetry operations, and they are the symmetry-invariant bases. A standard methodology is available to construct a series of generator functions (GFs) and corresponding symmetry-adapted basis (SAB) functions from these symmetry-invariant bases. Elements of the factorized Hamiltonian and overlap matrix can be expressed in terms of these SAB functions, and their simple representations can be deduced in terms of GFs. The application of this method to the Heisenberg spin Hamiltonian is demonstrated. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010

We discuss the exact Coulomb hole for the ground state of the helium atom and helium-like ions. We find that the correlated wavefunction yields a smaller probability of finding the electrons at large separations than does the Hartree–Fock wavefunction, leading to the counterintuitive conclusion that correlation brings distant electrons closer together. This effect becomes less pronounced as the nuclear charge increases.

Triply hydrogen-bonded complexes of the form AAA-DDD are shown to have the strongest interaction when the complex is substituted with electron withdrawing groups on the donor molecule (DDD) and electron donating groups on the acceptor molecule (AAA). In particular, the largest effects are observed when the withdrawing groups act through resonance. This serves to flatten the entire system resulting in more linear, and consequently stronger, hydrogen bonds. Furthermore, the present calculations show that the binding energy correlates with the electron density at the bond critical points and inversely with the hydrogen bond lengths.

Protein tyrosine phosphatase 1B (PTP1B) functions by removing the phosphoryl group from tyrosinephosphorylated proteins in insulin signaling and metabolism. The regeneration of the active site involves a sulphenylamide intermediate derived from the intrastrand cross-linking between the catalytic serine and the neighboring backbone nitrogen. Two mechanisms have been proposed for the formation of the sulphenylamide intermediate and the subsequent reactivation of the catalytic site. In the current work, the proposed mechanisms have been investigated by the use of density functional theory calculations. Our results suggest that these two mechanisms have similar overall energy barriers and that the preferred route will be determined by the availability of hydrogen peroxide or other oxidizing reagents.

The Paal–Knorr pyrrole synthesis, which involves the reaction of 1,4-dicarbonyls with amines, is among the most classical methods of heterocyclic pyrrole ring synthesis. The detailed sequence and the nature of the intermediates that occur in the Paal–Knorr reaction mechanism are not well understood. Density functional theory methods have been employed to investigate the nature of the intermediates and transition states in the Paal–Knorr pyrrole mechanism. Two mechanistic pathways for the reaction were examined: hemiaminal cyclization vs. enamine cyclization. Our calculated reaction potential energy surfaces suggest that the hemiaminal cyclization is the preferred pathway for the reaction both in gas phase and in solution. This conclusion is consistent with the experimental results which suggest that the hemiaminal intermediate undergoes cyclization in the rate-limiting step in the Paal–Knorr reaction mechanism. The preferred mechanism for the Paal–Knorr reaction consists of hemiaminal formation, hemiaminal cyclization and a dehydration step to form the pyrrole ring. Water and hydrogen-bonding interactions play a key role in catalyzing the hydrogen-transfer steps of the reaction.

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.

N,N-dimethylbenzylamine-2-selenol is a well-known, efficient glutathione peroxidase mimic. This compound reduces peroxides through a three-step catalytic mechanism, of which the first step has been well-characterized computationally. The mechanism for the reaction of N,N-dimethylbenzylamine-2-selenenic acid with a thiol, the second step in the catalytic cycle, is studied using reliable electronic structure techniques. Two different mechanisms are identified, using either a thiol or a deprotonated thiolate as the nucleophile. It is found that the lowest energy barrier mechanism incorporates two explicit solvent molecules to shuttle the thiol hydrogen to the leaving hydroxyl group, while the alternative mechanism using the thiolate has a barrier four times higher.

In this chapter, we discuss the influence of an anisotropic protein environment on the reaction mechanisms of saccharopine reductase and uroporphyrinogen decarboxylase, respectively, via the use of a quantum mechanical and molecular mechanical (QM/MM) approach. In addition, we discuss the importance of selecting a suitable DFT functional to be used in a QM/MM study of a key intermediate in the mechanism of 8R-lipoxygenase, a nonheme iron enzyme. In the case of saccharopine reductase, while the enzyme utilizes a substrate-assisted catalytic pathway, it was found that only through treating the polarizing effect of the active site, via the use of an electronic embedding formalism, was agreement with experimental kinetic data obtained. Similarly, in the case of uroporphyrinogen decarboxylase, the effect of the protein environment on the catalytic mechanism was found to be such that the calculated rate-limiting barrier is in good agreement with related experimentally determined values for the first decarboxylation of the substrate. For 8R-lipoxygenase, it was found that the geometries and energies of the multicentered open-shell intermediate complexes formed during the mechanism are quite sensitive to the choice of the density functional theory method. Thus, while density functional theory has become the method of choice in QM/MM studies, care must be taken in the selection of a particular high-level method.

Capture of the cyclic oxyallyl cation intermediates from the BF3-mediated Nazarov reactions of allenyl vinyl ketones with various dienes is accomplished by (3+2)- and (4+3)-cycloaddition.

The addition of enols and [(trimethylsilyl)oxy]alkenes, bearing methyl substituents at various positions, to a cyclic, BF3-complexed oxyallyl cation has been studied at the M06/6-311G(d)//B3LYP/6-31G(d) level of theory. The reactions with the [(trimethylsilyl)oxy]alkenes are homologous Mukaiyama reactions, which have not been examined computationally previously. In most instances a number of transition states were located, and the difference in energy between these transition states was not large, which pointed to low levels of diastereoselectivity in the reactions of the oxyallyl cation model compound. The lowest energy transition states were those with a synclinal geometry in which the alkene was positioned over the cyclic oxyallyl cation, and the relative orientation of the alkene and the oxyallyl cation was rationalized in terms of stabilizing intermolecular interactions, revealed by NBO analysis, between one or more fluorines of the complexed BF3 and hydrogens on the alkene moiety, and between the oxygen on the alkene and the π-system of the oxyallyl cation. Because, in most instances with these simple models, two or more transition states of relatively low energy were located, predictions of diastereoselectivity in more complex examples that are based on simple models cannot be recommended.