Traditional and ion-pair halogen-bonded complexes between chlorine and bromine derivatives and a nitrogen-heterocyclic carbene.

A theoretical study of the halogen-bonded complexes (A-X···C) formed between halogenated derivatives (A-X; A = F, Cl, Br, CN, CCH, CF3, CH3, H; and X = Cl, Br) and a nitrogen heterocyclic carbene, 1,3-dimethylimidazole-2-ylidene (MeIC) has been performed using MP2/aug'-cc-pVDZ level of theory. Two types of A-X:MeIC complexes, called here type-I and -II, were found and characterized. The first group is described by long C-X distances and small binding energies (8-54 kJ·mol(-1)). In general, these complexes show the traditional behavior of systems containing halogen-bonding interactions. The second type is characterized by short C-X distances and large binding energies (148-200 kJ·mol(-1)), and on the basis of the topological analysis of the electron density, they correspond to ion-pair halogen-bonded complexes. These complexes can be seen as the interaction between two charged fragments: A(-) and (+)[X-CIMe] with a high electrostatic contribution in the binding energy. The charge transfer between lone pair A(LP) to the σ* orbital of C-X bond is also identified as a significant stabilizing interaction in type-II complexes.

The reaction force constant as an indicator of synchronicity/nonsynchronicity in [4+2] cycloaddition processes.

A variety of experimental and computational analyses support the concept that a chemical reaction has a transition region, in which the system changes from distorted states of the reactants to distorted states of the products. The boundaries of this region along the intrinsic reaction coordinate ξ, which includes the traditional transition state, are defined unambiguously by the minimum and maximum of the reaction force F(ξ), which is the negative gradient of the potential energy V(ξ). The transition region is characterized by the reaction force constant κ(ξ), the second derivative of V(ξ), being negative throughout. It has recently been demonstrated that the profile of κ(ξ) in the transition region is a sensitive indicator of the degree of synchronicity of a concerted reaction: a single κ(ξ) minimum is associated with full or nearly full synchronicity, while a κ(ξ) maximum (negative) between two minima is a sign of considerable nonsynchronicity, i.e. a two-stage concerted process. We have now applied reaction force analysis to the Diels-Alder cycloadditions of the various cyanoethylenes to cyclopentadiene. We examine the relative energy requirements of the structurally- and electronically-intensive phases of the activation processes. We demonstrate that the variation of κ(ξ) in the transition region is again indicative of the level of synchronicity. The fully synchronous cycloadditions are those in which the cyanoethylenes are symmetrically substituted. Unsymmetrical substitution leads to minor nonsynchronicity for monocyanoethylene but much more - i.e. two stages - for 1,1-dicyano- and 1,1,2-tricyanoethylene. We also show that the κ(ξ) tend to become less negative as the activation energies decrease.

Theoretical analysis based on X-H bonding strength and electronic properties in red- and blue-shifting hydrogen-bonded X-H···π complexes.

A theoretical study based on the X-H bond strength of the proton donor fragment and its concomitant classical red-shifting or improper blue-shifting of the pure stretching frequency, in weakly hydrogen-bonded X-H···π complexes, is presented. In this sense, the dissociation energy differences, defined as, ΔD(e) = D(e)(X-H)[complex] - D(e)(X-H) [isolated], showed to be linearly connected with the change in stretching frequencies, Δν = ν(X-H)[complex] - ν(X-H)[isolated], of red- and blue-shifting H-bonds. This relationship allows us to define a threshold for the type of the stretching shift of the X-H bond: ΔD(e)(X-H) > 50.3 kcal mol(-1) leads to blue-shifting whereas ΔD(e)(X-H) < 50.3 kcal mol(-1) leads to red-shifting behavior. Complementarily, natural bond orbital analysis along the X-H stretching coordinate and electric dipole polarizability was performed to investigate the factors involved in red- or blue-shifting hydrogen-bonded complexes. It has been found that a high tendency to deplete the electronic population on the H atom upon X-H stretching is exhibited in blue-shifting H-bonded complexes. On the other hand, these types of complexes present a compact electronic redistribution in agreement with polarizability values. This study has been carried out taking as models the following systems: chloroform-benzene (Cl(3)C-H···C(6)H(6)), fluoroform-benzene (F(3)C-H···C(6)H(6)), chloroform-fluorobenzene, as blue-shifting hydrogen-bonded complexes and cyanide acid-benzene (NC-H···C(6)H(6)), bromide and chloride acids-benzene ((Br)Cl-H···C(6)H(6)) and acetylene-benzene (C(2)H(2)···C(6)H(6)) as red-shifting complexes.

Structural antitumoral activity relationships of synthetic chalcones.

Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2'-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2'-hydroxychalcones, showed the mayor structure-activity pattern along the series.

Five bicyclo[3.3.0]octa-2,6-dienes.

A series of five compounds containing the bicyclo[3.3.0]octa-2,6-diene skeleton are described, namely tetramethyl cis,cis-3,7-dihydroxybicyclo[3.3.0]octa-2,6-diene-2,4-exo,6,8-exo-tetracarboxylate, C(16)H(18)O(10), (I), tetramethyl cis,cis-3,7-dihydroxy-1,5-dimethylbicyclo[3.3.0]octa-2,6-diene-2,4-exo,6,8-exo-tetracarboxylate, C(18)H(22)O(10), (II), tetramethyl cis,cis-3,7-dimethoxybicyclo[3.3.0]octa-2,6-diene-2,4-exo,6,8-exo-tetracarboxylate, C(18)H(22)O(10), (III), tetramethyl cis,cis-3,7-dimethoxy-1,5-dimethylbicyclo[3.3.0]octa-2,6-diene-2,4-exo,6,8-exo-tetracarboxylate, C(20)H(26)O(10), (IV), and tetramethyl cis,cis-3,7-diacetoxybicyclo[3.3.0]octa-2,6-diene-2,4-exo,6,8-exo-tetracarboxylate, C(20)H(22)O(12), (V). The bicyclic core is substituted in all cases at positions 2, 4, 6 and 8 with methoxycarbonyl groups and additionally at positions 3 and 7 with hydroxy [in (I) and (II)], methoxy [in (III) and (IV)] or acetoxy [in (V)] groups. The conformations of the methoxycarbonyl groups at positions 2 and 4 are exo for all five compounds. Each C(5) ring of the bicyclic skeleton is almost planar, but the rings are not coplanar, with dihedral angles of 54.93 (7), 69.85 (5), 64.07 (4), 80.74 (5) and 66.91 (7) degrees for (I)-(V), respectively, and the bicyclooctadiene system adopts a butterfly-like conformation. Strong intramolecular hydrogen bonds exist between the -OH and C=O groups in (I) and (II), with O...O distances of 2.660 (2) and 2.672 (2) A in (I), and 2.653 (2) and 2.635 (2) A in (II). The molecular packing is stabilized by weaker C-H...O(=C) interactions, leading to dimers in (I)-(III) and to a chain structure in (V). The structure series presented in this article shows how the geometry of the cycloocta-2,6-diene skeleton changes upon substitution in different positions and, consequently, how the packing is modified, although the intermolecular interactions are basically the same across the series.

4-(2-Hydroxyphenyl)-2-phenyl-2,3-dihydro-1H-1,5-benzodiazepine and the 2-(2,3-dimethoxyphenyl)-, 2-(3,4-dimethoxyphenyl)- and 2-(2,5-dimethoxyphenyl)-substituted derivatives.

The 1,5-benzodiazepine ring system exhibits a puckered boat-like conformation for all four title compounds [4-(2-hydroxyphenyl)-2-phenyl-2,3-dihydro-1H-1,5-benzodiazepine, C(21)H(18)N(2)O, (I), 2-(2,3-dimethoxyphenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepine, C(23)H(22)N(2)O(3), (II), 2-(3,4-dimethoxyphenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepine, C(23)H(22)N(2)O(3), (III), and 2-(2,5-dimethoxyphenyl)-4-(2-hydroxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepine, C(23)H(22)N(2)O(3), (IV)]. The stereochemical correlation of the two C(6) aromatic groups with respect to the benzodiazepine ring system is pseudo-equatorial-equatorial for compounds (I) (the phenyl group), (II) (the 2,3-dimethoxyphenyl group) and (III) (the 3,4-dimethoxyphenyl group), while for (IV) (the 2,5-dimethoxyphenyl group) the system is pseudo-axial-equatorial. An intramolecular hydrogen bond between the hydroxyl OH group and a benzodiazepine N atom is present for all four compounds and defines a six-membered ring, whose geometry is constant across the series. Although the molecular structures are similar, the supramolecular packing is different; compounds (I) and (IV) form chains, while (II) forms dimeric units and (III) displays a layered structure. The packing seems to depend on at least two factors: (i) the nature of the atoms defining the hydrogen bond and (ii) the number of intermolecular interactions of the types O-H...O, N-H...O, N-H...pi(arene) or C-H...pi(arene).

(2S,RS)-6-Phenyl-1-(p-tolylsulfinyl)hexa-3(E),5(E)-dien-2-ol.

The molecule of the title compound, C19H20O2S, corresponds to a chiral sulfinyldienol with two stereogenic centres, viz. the C atom susbtituted by the hydroxy group and the sulfinyl S atom. The molecule displays a V-shape in the solid state. The dihedral angle defined by the least-squares planes of the aromatic rings is 72.9 (1) degrees. The packing pattern exhibits the following intermolecular hydrogen bonds: one O-H...O [H...O = 1.98 A, O...O = 2.785 (4) A and O-H...O = 166 degrees] and two C-H...O [H...O = 2.58 and 2.60 A, C...O = 3.527 (5) and 3.347 (5) A, and C-H...O = 164 and 134 degrees]. These define a chain along b.