In this paper, the intermolecular structural study asserted by the vibrational analysis in the stretch frequencies of hydrogen bonds (π···H) and dihydrogen bonds (H(-δ)···H(+δ)) have definitively been revisited by means of calculations carried out by Density Functional Theory (DFT) and topological parameters derived from the classic treatise of the Quantum Theory of Atoms in Molecules (QTAIM). As a matter of fact the π···H hydrogen bond is formed between the hydrofluoric acid and the C≡C bond of the acetylene, but the QTAIM calculations revealed a distortion in this interaction due to the formation of the ternary complex C(2)H(2)···2(HF). Although the π bonds of ethylene (C(2)H(4)), propylene (C(2)H(3)(CH(3))), and t-butylene (C(2)H(2)(CH(3))(2)) are considered proton acceptors, two hydrogen-bond types--π···H and C···H--can be observed. Over and above the analysis of the π hydrogen bonds, theoretical arguments also were used to discuss the red-shifts in the stretch frequencies of the binary dihydrogen complexes formed by BeH(2)···HX with X = F, Cl, CN, and CCH. Although a vibrational blue-shift in the stretch frequency of the H-C bond of HCF(3) due to the formation of the BeH(2)···HCF(3) dihydrogen complex was obtained, unmistakable red-shifts were detected in LiH···HCF(3), MgH(2)···HCF(3), and NaH···HCF(3). Moreover, the alkali-halogen bonds were identified in relation to the formation of the trimolecular systems NaH···2(HCF(3)) and NaH···2(HCCl(3)). At last, theoretical calculations and QTAIM molecular integrations were used to study a novel class of dihydrogen-bonded complexes (mC(2)H(5)(+)···nMgH(2) with m = 1 or 2 and n = 1 or 2) based in the insight that MgH(2) can bind with the non-localized hydrogen H(+δ) of the ethyl cation (C(2)H(5)(+)). In an overview, QTAIM calculations were applied to evaluate the molecular topography, charge density, as well as to interpret the shifted frequencies either to red or blue caused by the formation of the hydrogen bonds and dihydrogen bonds.

In this theoretical work, the characterization of multiple proton donors in three isomers of BeH 2 ÁÁÁ2HCl trimolecular dihydrogen-bonded complex was developed through the analysis of structural parameters, electronic criteria, and analysis of vibrational harmonic spectrum, where all these data were obtained from the B3LYP/6-311++G(3d,3p) calculations. As dihydrogen bonds are formed by the interaction between two hydrogen atoms, proton donors and hydride hydrogen, the isomers of BeH 2 ÁÁÁ2HCl trimolecular dihydrogen-bonded complexes are stabilized by two, three, and four centers of proton donors. By analyzing the charge density integrations calculated by the theory of Atoms in Molecules, these multiple centers of proton donors were identified by quantification of the intermolecular electronic density, Laplacian operators, and charge transfers.

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Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target, since inhibitors of this protease affect the pathology appropriately. By exploring the N-acylhydrazones (NAH) as privileged structures usually present in antiparasitic agents, we investigated a library of 16 NAH bearing the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold (NAH 3a-h, 4a-h). The in vitro bioactivity against epimastigote and trypomastigote forms of T. cruzi was evaluated, and some NAH under study exhibited antitrypanosomal activity at concentrations that are not toxic to mammalian cells. The series of compounds based on the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold revealed the remarkable importance of each substituent at the phenyl's 4-position for the inhibitory activity. Non-nitrated compounds 3a and 4e were found to be as potent as the reference drug, Benznidazole. In addition, the molecular origin of the antitrypanosomal properties for these series was investigated using docking studies of the TCC structure.

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Recebido em 26/6/09; aceito em 10/1/10; publicado na web em 23/4/10 THE QTAIM MOLECULAR TOPOLOGY AND THE QUANTUM-MECHANICAL DESCRIPTION OF HYDROGEN BONDS AND DIHYDROGEN BONDS. Hydrogen bonds formed through the interaction between a high electronic density center (lone electron pairs, π or pseudo-π bonds) and proton donors cause important electronic and vibrational phenomena in many systems. However, it was demonstrated that proton donors interact with hydrides, such as alkali and alkaline earth metals (BeH 2 , MgH 2 , LiH and NaH), what yields a new type of interaction so-called dihydrogen bonds. The characterization of these interactions has been performed at light of the Quantum Theory of Atoms in Molecules (QTAIM), by which the electronic densities r are quantified and the intermolecular regions are characterized as closed-shell interactions through the analysis of the Laplacian field ∇ 2 r.Keywords: QTAIM; hydrogen bonds; dihydrogen bonds. 21,22 por Hohenberg, Kohn e Sham, 23,24 a densidade eletrônica é também considerada um parâmetro físico-químico bastante polêmico devido à inexistência de uma expressão analítica clara que a descreva e que possa ser usada na interpretação da concentração de carga em sítios moleculares específicos. Trabalhando neste sentido, alguns cientistas têm apresentado algumas propostas como, por exemplo, a baseada nos conceitos de Hirshfeld 25,26 descrita pela Equação 1. INTRODUÇÃO(1) Nesta expressão, I define uma quantidade de carga eletrônica perdida na sobreposição atômica, ou seja, uma diferença entre as densidades eletrônicas dos átomos A e B livres (rA°( r) e rB°( r) ) e quando formam a ligação química A-B (rA (r) e rB (r) ). Na abordagem da QTAIM, a densidade eletrônica é usada como observável mecânico-quântico para execução de integrações numéricas, onde o vetor gradiente ∇r é a condição básica para se determinar a topologia molecular.27 Considerando os átomos como sistemas de camada aberta (Ω) e restringindo condições de contorno na superfície molecular S (Ω,r) , Bader utilizou destes argumentos para mostrar que o fluxo de densidade de carga é nulo em qualquer ponto desta superfície. 28 Como consequência, o gradiente ∇r é perpendicular a um vetor unitário n (r) normal à superfície definida em S (Ω,r) , 29 conforme demonstrado pela Equação 2:A partir de uma sequência de vetores gradientes ∇r é que são obtidas todas as trajetórias ou linhas de contorno da densidade eletrônica, as quais podem ser ascendentes ou em declive. Na prática, as trajetórias de ∇r são bem definidas por um ponto específico no espaço, denominado de atrator. 30 Como o gradiente da densidade eletrônica é função de seus atratores, estes são propriamente os núcleos do sistema molecular. Considerando todos os atratores nucleares, o conjunto de

A theoretical study of the molecular properties of AH⅐⅐⅐HCF 3 and TH 2 ⅐⅐⅐HCF 3 (A ϭ Li or Na and T ϭ Be or Mg) model systems has been carried out at the B3LYP/6-311ϩϩG(3df,3pd) level of theory. Once the interactions between the proton donor (H ϩ␦ ) of HCF 3 and protonic hydrides (H Ϫ␦ ) have been produced, these systems appear, at first sight, to be dihydrogen-bonded complexes. Although a blue-shift was observed on the HC bond of HCF 3 upon the formation of the BeH 2 ⅐⅐⅐HCF 3 dihydrogen complex, in the case of LiH⅐⅐⅐HCF 3 , MgH 2 ⅐⅐⅐HCF 3 , and NaH⅐⅐⅐HCF 3 , however, a red-shift was detected on their HCF 3 species. As far as B3LYP/6-311ϩϩG(3df,3pd) calculations are concerned, we have used the quantum theory of atoms in molecules to evaluate the molecular topography and charge density, according to which higher levels of charge transfer were computed on the red-shifted complexes. Finally, computation of ⌬E C dihydrogen bond energies revealed that vibrational red-shifts are observed in more strongly bonded complexes (values for ⌬E C ranging from 6.67 kJ mol Ϫ1 to 19.66 kJ mol Ϫ1 ), whereas blue-shifts are found in weakly bonded ones (higher value for ⌬E C is 2.31 kJ mol Ϫ1 ). FIGURE 4. Electronic density contour lines (thin), molecular pathways (bold), and BCPs (little squares) of the BeH 2 ⅐⅐⅐HCF 3 (I) dihydrogen-bonded complex obtained from QTAIM numeric integration.