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We investigate the relationships between electron-density and electronic-energy errors produced by modern exchange-correlation density-functional approximations belonging to all of the rungs of Perdew's ladder. To this aim, a panel of relevant (semi)local properties evaluated at critical points of the electron-density field (as defined within the framework of Bader's atoms-in-molecules theory) are computed on a large selection of molecular systems involved in thermodynamic, kinetic, and noncovalent interaction chemical databases using density functionals developed in a nonempirical and minimally and highly parametrized fashion. The comparison of their density- and energy-based performance, also discussed in terms of density-driven errors, casts light on the strengths and weaknesses of the most recent and efficient density-functional approximations.

We assess the ability of various atomic and molecular electrophilicity descriptors to predict the strength of halogen bonds. To this aim, several physicochemical quantities rooted within the framework of conceptual density functional theory were derived using second and third order Taylor expansions of the electronic energy, and their correlation to binding energies were compared with those obtained for more usual electronic descriptors. This benchmark was performed for a large and representative database of noncovalent complexes involving fluorine, chlorine, and bromine atoms, and showed that some of these new quantities, in particular the atomic cubic electrophilicity index, exhibited more transferability and broadness of application than did more common descriptors such as the molecular electrostatic potential.

In this publication, we propose a new set of reactivity/selectivity descriptors, derived within a Rayleigh-Schrödinger perturbation theory framework, for chemical systems undergoing an electrostatic (point-charge) perturbation. From the electron density polarization at first order, qualitative insight on reactivity is retrieved, while more quantitative information (noteworthy selectivity) can be obtained from either the second-order energy response or the number of shifted electrons under perturbation. Noteworthily, only a small number of excitations contribute significantly to the overall responses to perturbation, suggesting chemical reactivity could be foreseen by a careful scrutiny of the electron density reorganization upon excitation.

We discuss two main approaches to decompose the Møller-Plesset perturbation theory molecular energies into atomic contributions within the interacting quantum atoms (IQA) formalism, as implemented in the programs Morphy and AIMAll. For this purpose, the so-called intraatomic energies (also known as self-energies) of a representative set of 55 small molecules are compared with each other. The origin of the possible discrepancies between both approaches is analyzed, and linear models linking the two approaches are proposed for each atom type.

A palladium-catalyzed C-H bond functionalization of acrylamides was developed to build up stereoselectively trifluoromethylated 1,3-butadienes. Using a tertiary amide as a directing group, olefins were selectively functionalized with 2-bromo-3,3,3-trifluoropropene to access these important fluorinated compounds. The methodology was extended to the construction of pentafluoroethyl-substituted 1,3-dienes. Mechanistic studies supported by density functional theory calculations suggested a redox neutral mechanism for this transformation.

In this article, we conduct a comprehensive molecular relaxation study of amorphous Quinidine above and below the glass-transition temperature (Tg) through broadband dielectric relaxation spectroscopy (BDS) experiments and theoretical density functional theory (DFT) calculations, as one major issue with the amorphous state of pharmaceuticals is life expectancy. These techniques enabled us to determine what kind of molecular motions are responsible, or not, for the devitrification of Quinidine. Parameters describing the complex molecular dynamics of amorphous Quinidine, such as Tg, the width of the α relaxation (βKWW), the temperature dependence of α-relaxation times (τα), the fragility index (m), and the apparent activation energy of secondary γ relaxation (Ea-γ), were characterized. Above Tg (> 60 °C), a medium degree of nonexponentiality (βKWW = 0.5) was evidenced. An intermediate value of the fragility index (m = 86) enabled us to consider Quinidine as a glass former of medium fragility. Below Tg (< 60 °C), one well-defined secondary γ relaxation, with an apparent activation energy of Ea-γ = 53.8 kJ/mol, was reported. From theoretical DFT calculations, we identified the most reactive part of Quinidine moieties through exploration of the potential energy surface. We evidenced that the clearly visible γ process has an intramolecular origin coming from the rotation of the CH(OH)C9H14N end group. An excess wing observed in amorphous Quinidine was found to be an unresolved Johari-Goldstein relaxation. These studies were supplemented by sub-Tg experimental evaluations of the life expectancy of amorphous Quinidine by X-ray powder diffraction and differential scanning calorimetry. We show that the difference between Tg and the onset temperature for crystallization, Tc, which is 30 K, is sufficiently large to avoid recrystallization of amorphous Quinidine during 16 months of storage under ambient conditions.

A complete experimental and theoretical study of the thermally controlled metal-free decarboxylative hetero-Diels–Alder (HDA) reaction of 5-alkoxyoxazoles with acrylic acid is reported. This strategy offers a new entry to valuable 2,6-difunctionalized 3-hydroxypyridines from readily available 2- and 4-disubstituted 5-alkoxyoxazoles. The reaction conditions proved compatible with, among others, ketone, amide, ester, ether, and nitrile groups. The broad functional group tolerance of the protocol allows a rapid and versatile access to both hydroxyindolizidine and hydroxyquinolizidine derivatives via a pyridine dearomatization strategy.

Through-space charge transfers upon photon absorption in aminated epicocconone analogues, which serve as promising proteins markers, are investigated within time-dependent density functional theory using total densities differences and various point-charge models (with a special emphasis on Bader's atoms-in-molecules theory). In particular, the distances and the amounts of charge transfer, as well as the transition dipole moments, are discussed from a methodological point of view, and their values are subsequently linked with the chemical structures of these efficient fluorophores. Finally, on the basis of these theoretical findings, several hints for the future improvement of the photochemical properties of these analogues are advanced.

In this article, we report a detailed study on halogen bonds in complexes of CHCBr, CHCCl, CH2CHBr, FBr, FCl, and ClBr with a set of Lewis bases (NH3, OH2, SH2, OCH2, OH(-), Br(-)). To obtain insight into the physical nature of these bonds, we extensively used Bader's Quantum Theory of Atoms-in-Molecules (QTAIM). With this aim, in addition to the examination of the bond critical points properties, we apply Pendás' Interacting Quantum Atoms (IQA) scheme, which enables rigorous and physical study of each interaction at work in the formation of the halogen-bonded complexes. In particular, the influence of primary and secondary interactions on the stability of the complexes is analyzed, and the roles of electrostatics and exchange are notably discussed and compared. Finally, relationships between QTAIM descriptors and binding energies are inspected.

A modified Kondrat'eva cycloaddition involving an unprecedented thermally controlled metal-free decarboxylative aromatization affords an expedient access to natural 3-hydroxypyridine/piperidine systems.

In this work we present a combined theoretical and experimental study of UV/vis absorption spectra of novel organic chromophores derived from epicocconone. A computational protocol, consistent with experimental findings, is proposed in the framework of time-dependent density functional theory. More precisely, the influence of density functional, basis set, and solvation effects is assessed through theory-experiment matching. On the one hand, it is shown that global hybrid functionals fail to describe excitation spectra for the whole training set. On the other hand, range-separated hybrids allow a description of the complete set of epicocconone derivatives on equal footing, while the double-ζ basis set is shown to be sufficiently accurate for the screening of the spectroscopic properties in epicocconone analogues. The inclusion of solvent effects within a polarizable continuum model appears to be compulsory to decrease the residual dispersion. State specific solvation, on the contrary, does not provide a significant consistency/accuracy improvement. Besides, conformational transformations in investigated compounds and their influence on electronic absorption spectra are pointed out. A systematic choice of the same conformation for each compound from the training set enhances consistency and accuracy of our theoretical model. Lastly, a TDDFT-based calibration is proposed for prediction of absorption wavelengths in epicocconone analogues.

In this paper, we extend the work of Popelier and Logothetis [J. Organomet. Chem. 1998, 555, 101] on the characterization of agosticity by considerably enlarging the set of the studied organometallic molecules. To this aim, 23 representative complexes have been considered, including all first line transition metals at various oxidation states and exhibiting four types of agosticity (α, β, γ, and δ). From these examples, the concepts of agostic atom, agostic bond, and agostic interaction are defined and discussed, notably by advocating Bader's analysis of the electron density. The nature and the local properties of the bond critical points are then investigated, and the relationships with the main geometric parameters of the complexes are particularly examined. Moreover, new local descriptors based on kinetic energy densities are developed in order to provide new tools for bond characterization.

In this article, we assess the ability of various density functionals to predict accurate values for some basic properties of the bond critical points of about 50 small molecules, including the recently proposed reduced gradient variation rates and involving typical ionic and covalent bonds, agostic interactions, and van der Waals complexes. The relation between the computed deviations and the geometric variations are discussed, as well as the topology variations. The possible correlation of these descriptors to atomization energies is considered, and the relevance of an accurate QTAIM analysis for correct descriptions of potential energy surfaces is addressed. Finally, we provide typical margins of error for the evaluation of these quantities and discuss their consequences for computational applications., (© 2011 American Chemical Society)

Infrared spectra of 0.5 mol·L(-1) uranium(VI) nitrate monoamide complexes in toluene have been recorded and compared with infrared spectra calculated by DFT. The investigated monoamides were N,N-dimethylformamide (DMF), N,N-dibutylformamide (DBF), and N,N-dicyclohexylformamide (DcHF). The validity of DFT calculations for describing uranium nitrate monoamide complexes has been confirmed as a fair agreement between experimental and calculated spectra was obtained. Furthermore, a topological analysis of the electron density has been carried out to characterize monoamide-uranium interactions. From this work, it appears that the increase of stability of uranylmonoamide complexes may be directly linked to the degree of polarization of the ligands in interaction with uranylnitrate. Among the investigated monoamides, the most stable complex is UO(2)(NO(3))(2)·2DcHF. This complex is characterized by a high positive charge delocalization in the outer part of the ligand molecule, which leads to a more concentrated positive charge close to the uranyl cation (UO(2)(2+)), thus strengthening the electrostatic interaction between the metal and the ligand.

The pathways corresponding to the most energetically favorable decomposition reactions that can be envisaged for o-nitrotoluene (and 20 of its derivatives) have been studied, using density functional theory, in order to evaluate the influence of substituents' nature (nitro, methyl, amino, carboxylic acid, and hydroxyl) and position. The first mechanism consists of the direct dissociation (homolysis) of the carbon nitrogen bond (CH(3)C(6)H(4)NO(2) = CH(3)C(6)H(4) + NO(2)) whereas the second one is a more complex process initiated by C-H alpha attack and leading to the formation of anthranil and water (C(6)H(4)C(H)ON + H(2)O). For each compound, the initial step of this last channel is the rate limiting one, the Gibbs activation energy of all systems being very close, that is all in the 40-44 kcal/mol range. More important variations have been observed for the C-NO(2) homolysis Gibbs activation energies (46-60 kcal/mol). These variations have been related to electron donor-acceptor properties of substituents by considering significant correlations (R(2) > 0.9) with the Hammett parameters (sigma). Nevertheless, though the influence of substituents on the direct breaking of the C-NO(2) bond was important, the C-H alpha attack remained finally the major decomposition channel for the studied compounds. Our study underlines the complexity of the decomposition process in nitroaromatic compounds and casts some doubts on the characterization of the energetic properties of such molecules only on the basis of C-NO(2) homolysis.

A detailed analysis concerning the effect of the exchange-correlation functional on a prototypical agostic niobium complex has been carried out, with particular attention to a fundamental property of the functional, namely, the recovering of the uniform electron gas limit. The obtained results allow for revisiting the role of this limit for a proper description of the beta-H agostic interaction. Starting from these results, a new criterion for the bond analysis based on the electron density behavior is proposed. Indeed, the density homogeneity between the metal and the involved hydrogen has been evaluated at the bond critical point, as defined in the framework of Bader's atoms in molecules theory, by calculating the average variation rates of the (reduced) density gradients. Such descriptors not only provide useful insights on the nature of such an interaction but also could be used as a starting point for a deep (and new) analysis of the chemical bond.

A theoretical study on the complexation of uranyl cation (UO2(2+)) by three different functional groups of a calix[6]arene cage, that is, two hydroxamic and a carboxylic acid function, has been carried out using density functional theory calculations. In particular, interaction energies between the uranyl and the functional groups have been used to determine their affinity toward uranyl, whereas pKa calculations give some information on the availability of the functional groups in the extraction conditions. On the one hand, calculations of the interaction energies have pointed out clearly a better affinity with the hydroxamic groups. The stabilization of this complex was rationalized in terms of a stronger electrostatic interaction between the uranyl cation and the hydroxamic groups. The presence of a water molecule in the first coordination sphere of uranyl does not destabilize the complex, and the most stable complex is obtained with two functional groups and two water molecules, leading to a coordination number of 8 for the central uranium atom. On the other hand, pKa theoretical evaluation shows that both hydroxamic (deprotonated on the oxygen site) and carboxylic groups are potential extractants in aqueous medium with a preference for carboxylic functions at low pH. Moreover, these data allowed to unambiguously identify the oxygen of the alcohol function as the favored deprotonation site on the hydroxamic function.

The influence of substituent nature and position on the unimolecular decomposition of nitroaromatic compounds was investigated using the density functional theory at a PBE0/6-31+G(d,p) level. As the starting point, the two main reaction paths for the decomposition of nitrobenzene were analyzed: the direct carbon nitrogen dissociation (C6H5 + NO2) and a two step mechanism leading to the formation of phenoxyl and nitro radicals (C6H5O + NO). The dissociation energy of the former reaction was calculated to be 7.5 kcal/mol lower than the activation energy of the second reaction. Then the Gibbs free energies were computed for 15 nitrobenzene derivatives characterized by different substituents (nitro, methyl, amino, carboxylic acid, and hydroxyl) in the ortho, meta, and para positions. In meta position, no significant changes appeared in the reaction energy profiles whereas ortho and para substitutions led to significant deviations in energies on the decomposition mechanisms due to the resonance effect of the nitro group without changing the competition between these mechanisms. In the case of para and meta substitutions, the carbon-nitro bond dissociation energy has been directly related to the Hammett constant as an indicator of the electron donor-acceptor effect of substituents.

Ab initio molecular-dynamic simulations, using density functional theory (DFT) and the recent atom-centered density-matrix propagation method (ADMP), were used to study the bond formation process in a prototypical SN2 reaction, namely the Walden inversion. Using the real space partition schemes of both electronic density and electron localization function gradient fields, we analyzed different quantum chemical topology (QCT) properties along the ADMP trajectory. In particular, atomic charges derived from the Bader's atoms-in-molecules (AIM) theory were used to analyze intra- and intermolecular charge transfers between atoms, while the electronic population of the forming bonding basin obtained from the electron localization function (ELF) gradient field was employed to describe the bond formation process. These results were compared to the corresponding QCT properties issuing from a static approach based on the intrinsic reaction path (IRP). Although similar features are found for both static and dynamic approaches, the dynamic QCT analysis provides some explanation of the differences observed during the formation of the ion-molecule complex. In particular, it suggests a stronger electron exchange leading to an effective maximization of both covalent and noncovalent interactions.

An experimental and theoretical study on the conformational behavior of the 1,3,5-OMe-2,4,6-OCH(2)CONHOH-p-tert-butylcalix[6]arene has been carried out. In particular, semiempirical (AM1) and density functional theory (DFT) calculations have been performed in order to identify the possible conformers. The obtained results show that the cone structure is the most stable conformer at any level of theory, even if significant differences have been obtained for the other species. The inclusion of solvent effect, through a continuum model, also points out the relevant role played by the solvent in the stabilization of the cone structure in solution. These latter results have been confirmed by NMR experiments, which clearly show the presence of only the cone conformer in a polar solvent, such as DMSO. Finally, (1)H and (13)C NMR spectra on model systems, i.e., two successive phenol rings (Ar(1)-CH(2)-Ar(2)), have been computed at the DFT level and compared with the experimental spectra of the complete molecule. The results show an overall good agreement with the experimental data, thus leading to an unambiguous assignment of the experimental spectra.

Several molecular descriptors, based on topological approaches as well as on a more traditional orbital-based decomposition, have been used to asses relations with hydrogen bond strengths in a series of formic acid dimers and its sulfur derivatives. Particular attention has been devoted to the analysis of the core-valence bifurcation topological index and to the bond order index. Their values are seen to be linearly related to bond energies estimated through a bond-energy-bond-order relationship; also, the mean value of the topological index appears to be related to the complexation energy computed by methods based on density functional theory. The dependence of the index upon the donor-acceptor couple in relation to its applicability is discussed.

While usual atomic population methods give a consistent view of trivalent lanthanide or a uranium-ligand bond, the description of the bonding of americium(III), which is a key element for nuclear fuel processes, is a challenge. Neither experimental data nor theoretical calculations have been able so far to evidence covalency effects in the americium-ligand bond. We show herein that the use of more sophisticated methods based on a topological approach (AIM and ELF) gives a consistent view of such an interaction for the first time, showing a weak covalent back-bonding interaction with the CO ligand.

A systematic analysis of the electrostatic interaction between 27 natural DNA base pairs was carried out, based on ab initio correlated wave functions and the topology of the electron density. Using high rank multipole moments we show that the atomic partitioning of the interaction energy contains many substantial contributions between distant atoms. Profiles of cumulative energy versus internuclear distance show large fluctuations and provide an electrostatic fingerprint of the partitioning of interaction energy in a complex. A quantified comparison between each pair of energy profiles, one for each base pair, makes clear that there is no correlation between the total base pair interaction energy and the shape of the profile. In other words, base pairs with similar interaction energy are not stable for the same reasons in terms of atomic partitioning. In summary, simple rules to rationalize the pattern of energetic stability of naturally occurring base pairs in terms of subsets of atoms are elusive. Our work cautions against inappropriate use of Jorgensen's secondary interaction hypothesis.