Margarita M. Vallejos

Topological analysis of aromatic halogen/hydrogen bonds by electron charge density and electrostatic potentials.

AbstractIn this work, the intermolecular distribution of the electronic charge density in the aromatic hydrogen/halogen bonds is studied within the framework of the atoms in molecules (AIM) theory and the molecular electrostatic potentials (MEP) analysis. The study is carried out in nine complexes formed between benzene and simple lineal molecules, where hydrogen, fluorine and chlorine atoms act as bridge atoms. All the results are obtained at MP2 level theory using cc-pVTZ basis set. Attention is focused on topological features observed at the intermolecular region such as bond, ring and cage critical points of the electron density, as well as the bond path, the gradient of the density maps, molecular graphs and interatomic surfaces. The strength of the interaction increases in the following order: F⋅⋅⋅π < Cl⋅⋅⋅π < H⋅⋅⋅π. Our results show that the fluorine atom has the capability to interact with the π−cloud to form an aromatic halogen bond, as long as the donor group is highly electron withdrawing. The Laplacian topology allows us to state that the halogen atoms can act as nucleophiles as well as electrophiles, showing clearly their dual character. FigureA study by electron charge density and electrostatic potentials about aromatic halogen/hydrogen bonds.

Bifunctional hydrogen bonds in monohydrated cycloether complexes.

In this work, the cooperative effects implicated in bifunctional hydrogen bonds (H-bonds) were studied (in monohydrated six-membered cycloether) within the framework of the atoms in molecules (AIM) theory and of the natural bond orbitals (NBO) analysis. The study was carried out in complexes formed by six-membered cycloether compounds (tetrahydropyrane, 1,4-dioxane, and 1,3-dioxane) and a water molecule. These compounds were used as model systems instead of more complicated molecules of biological importance. All the results were obtained at the second-order Møller-Plesset (MP2) level theory using a 6-311++G(d,p) basis set. Attention was focused on the indicators of the cooperative effects that arise when a water molecule interacts simultaneously with a polar and a nonpolar portion of a six-membered cycloether (via bifunctional hydrogen bonds) and compared with conventional H-bonds where the water molecule only interacts with the polar portion of the cycloether. Different indicators of H-bonds strength, such as structural and spectroscopic data, electron charge density, population analysis, hyperconjugation energy and charge transference, consistently showed significant cooperative effects in bifunctional H-bonds. From the AIM, as well as from the NBO analysis, the obtained results allowed us to state that in the monohydrated six-membered cycloether, where the water molecule plays a dual role, as proton acceptor and proton donor, a mutual reinforcement of the two interactions occurs. Because of this feature, the complexes engaged by bifunctional hydrogen bonds are more stabilized than the complexes linked by conventional hydrogen bonds.

Preferential formation of the different hydrogen bonds and their effects in tetrahydrofuran and tetrahydropyran microhydrated complexes.

The role of cycloether-water (c-w) and water-water (w-w) hydrogen bonds (H-bonds) on the stability of the tetrahydrofuran THF/(H(2)O)(n) and the tetrahydropyran THP/(H(2)O)(n) complexes with n = 1-4 was investigated herein using the density functional and ab initio methods and the atoms in molecules theory. Geometry optimizations for these complexes were carried out with various possible initial guess structures. It was revealed that the major contributions of the mono and dihydrated complexes came from c-w H-bonds. A competition between c-w and w-w H-bonds contribution was observed for trihydrated complexes. For most of tetrahydrated complexes, the inter-water H-bonds provided the greatest contribution, whereas the c-w contributions were small but not negligible. It was confirmed that to produce a hydrophobic hydration of cycloethers, the C-H···O(w) H-bond should be associated with a network of H-bonds that connects both portions of the solute, through the formation of a bifunctional H-bond. A linear correlation is obtained for the sum of electron density at the bond critical points (ρ(b)) with the interaction energy (ΔE) and with the solute-solvent interaction energy (ΔE(s-w)) of the microhydrated complexes. In addition, a new way to estimate the energetic contribution as well as the preferential formation of the different H-bonds based completely on ρ(b) was found. Even more, it allows to differentiate the contribution from c-w interactions in both hydrophilic and hydrophobic contributions, it is therefore a useful tool for studying the hydration of large biomolecules. The analysis of the modifications in the atomic and group properties brought about by successive addition of H(2)O molecules allowed to pinpoint the atoms or molecular groups that undergo the greatest changes in electron population and energetic stabilization. It was identified that the remarkable stabilization of the water oxygen atoms is crucial for the stabilization of the complexes.

Competing mechanisms for the reaction of dichloropropynylborane with 2-tert-butylbutadiene. Diels–Alder reaction versus alkynylboration

Density functional theory and the quantum theory of atoms in molecules approach were used to study two competing process: the Diels–Alder reaction (DA) and the 1,4-alkynylboration (AB) between dichloropropynylborane (1) and 2-tert-butylbutadiene (2) in dichloromethane. We analyzed several reaction pathways related with such reactions for both orientations (meta and para). The stepwise mechanisms for the two competitive reactions share the first step that leads to an intermediate zwitterionic structure. The second step is more favorable for the reaction occurring via TSC-m that leads to the meta enyne product 5, which is the kinetic product. The formation of the meta DA product cannot be explained through a direct cycloaddition, due to the higher activation free energy of the associated transition structure (TSB-m). An alternative transition structure with [4 + 3] character (TSD-m) that connects the meta enyne 5 with the meta cycloadduct 3 was found. We propose that at longer reaction times, 5 rearranges to the thermodynamic product 3 via TSD-m passing by a six-membered ring structure and a seven-membered ring structure. The topological analysis of the charge density along the selected reaction coordinates provided some understanding on the intriguing competitive reactions.

Reactivity and selectivity of boron-substituted alkenes in the Diels-Alder reaction with cyclopentadiene. A study of the electron charge density and its Laplacian.

The effect of the nature of the boron moiety upon the reactivity and the selectivity of a variety of vinylboron dienophiles (1-12) in the Diels-Alder (DA) reaction was investigated using density functional theory and the quantum theory of atoms in molecules. The calculated reactivity of the dienophiles decreases in the order vinylborane (1) > dihalovinylboranes (2-4) > dialkylvinylboranes (5-7) ≈ vinyl boronic acid (8) > vinylboronates (9, 10) > vinyl MIDA boronate (11) ≈ vinyltrifluoroborate (12). The DA reactions of 1-7 were slightly endo-selective due to the stronger C6-B secondary orbital interaction in the endo transition structures (TSs) evaluated by the C6|B delocalization index. In the TSs of 5 and 7, a combination of electronic and steric factors reduce the endo selectivity. The moderate exo selectivity calculated for the DA reactions of boronates 8-11 was attributed mainly to the hydrogen bond between the oxygen atom of boronate moieties and one of the acidic hydrogens of the methylene of cyclopentadiene in the exo TSs, which also reduces the ability of the oxygen lone pairs to donate electron density into the vacant boron orbital. Interestingly, the cooperative effect between the two hydrogen bonds in the exo TS of the DA reaction of vinyltrifluoroborate (12) determines the almost exclusive exo selectivity predicted for this DA reaction. We propose that the relative reactivities of the dienophiles can be estimated by the charge density (ρr) and its Laplacian (∇(2)ρr) at the (3,+1) critical point in the topology of ∇(2)ρr, evaluated at the reactant molecules in the ground state. The profiles of the several topological parameters along the reaction are affected by the nature of the substituents attached to the boron atom and by the mode of addition (endo and exo) in the DA reactions.

Theoretical Study of the BF3-Promoted Rearrangement of Oxiranyl N-Methyliminodiacetic Acid Boronates

The mechanism of the rearrangement of oxiranyl N-methyliminodiacetyl (MIDA) boronates in dicholoromethane has been extensively investigated with density functional theory. Several reaction pathways were examined. Our results revealed that the most-favorable mechanisms for the BF3-promoted rearrangement of 2-phenyl oxiranyl MIDA boronate (1) and 1-phenyl oxiranyl MIDA boronate (24) comprise two steps: ring opening of the epoxide to a carbocation intermediate followed by migration of a MIDA-boryl group (for the reaction of 1) and hydrogen (for the reaction of 24), to give the same BF3-coordinated α-boryl aldehyde in both cases. The first step of the ring opening of the epoxide is the rate-determining step of these reactions. In the rearrangement step for the reaction of 1, the MIDA-boryl group migrates easily, probably because of its electron-rich sp3-hybridized boron center. For 24, the most-favorable pathway involves a rare boryl-substituted carbocation. The course of these reactions is mainly controlled by electronic effects, although steric effects are also significant. The higher energy barrier calculated for the unsubstituted oxiranyl MIDA boronate (31) explains the lack of reactivity in the studied BF3-promoted rearrangement.

Effect of beryllium bonds on the keto–enol tautomerism of formamide derivatives: a subtle basicity–acidity balance

The effects of the association of BeH2 to formamide derivatives have been investigated through the use of G4 high-level ab initio calculations. The association takes place preferentially at the carbonyl group of the amide in the keto tautomer and to the imino group in the enol form. In both cases, the complexes formed are stabilized through the formation of beryllium and dihydrogen bonds. The relative stability of these complexes is the result of a subtle balance between the changes induced by the formation of the beryllium bond on the intrinsic basicity and acidity of the amide. One of the main consequences of this balance is the significant stabilization of the enol tautomer due to the concomitant increase in the basicity of the imino group with respect to the carbonyl group and the significant acidity enhancement of the OH group, which leads to the formation of very strong BeH···HO dihydrogen bonds in the enol complexes. For the Cl-, Br- and NO2-formamide derivatives, this dihydrogen bond is so strong that a spontaneous formation of hydrogen molecule takes place. The formation of the beryllium bond not only stabilizes the enol forms, but also leads to a significant decrease in the activation barriers involved in the enolization process.