Genetic identification of a rabies virus from an insectivorous bat in an urban area of Rio Grande do Sul, Brazil.

In Latin America, hematophagous bats are the main reservoirs of rabies virus (RABV) to livestock, to other mammals and, occasionally, to human. Nonetheless, reports of exposure of human and pets to RABV upon aggression by non-hematophagous bats are increasing, possibly facilitated by the synanthropic habits of these bats. We, herein, report the detection and genetic identification of a RABV recovered from an insectivorous bat found sick in a student housing building at the Federal University of Santa Maria, Southern Brazil. Taxonomic characterization identified the captured bat as a member of the genus Nyctinomops, family Molossidae, the group of insectivorous bats. Brain fragments of the bat were positive for RABV antigens by fluorescent antibody test (FAT) and for sequences of the nucleoprotein (N) gene by RT-PCR. The N amplicon was submitted to nucleotide sequencing and analysis, showing that the consensus sequences (SV 33/19) had high identity with RABV sequences of insectivorous bats deposited in GenBank. At phylogenetic tree, the N gene sequences of SV 33/19 clustered with RABV recovered from Nyctinomops laticaudatus, Molossus molossus, and Tadarida lauticaudata bats, and a part of RABV variant 3, 4, and 6, that correspond to Desmodus rotundus, Tadarida brasiliensis, and Lasiurus cinereus, respectively. Although no direct human or domestic animal exposure has been reported, this case strengthens the need for a continuous rabies vaccination in pets in the surrounding areas, since non-hematophagous bats may serve as source of infection for these animals. These findings also call attention for continuous monitoring of populations of synanthropic bats to avoid/prevent human exposure.

Reactivity of the [Au(C

Gold complexes are promising compounds used in cancer chemotherapy. Besides their steric features, which enable biomolecule interactions, the redox instability and the high affinity of gold with cellular nucleophiles influence the biological action in these complexes. Both features were herein theoretically investigated for the [Au(C^N^C)Cl] probe complex (C^N^C = 2,6-diphenylpyridine) using H2O, CH3SH/CH3S-, CH3Se- and meim-4-H (4-methylimidazole) as biomimetic nucleophiles. Based on the results, the lowest energy reaction path followed two consecutive steps: (1) chloride-exchange ([Formula: see text] = 4.14 × 107 M-1 s-1) and (2) reduction of the resulting Au(III) metabolite to the corresponding Au(I) analog with chelate ring-opening ([Formula: see text] =+0.15 V-data based on the reaction with CH3Se-). These findings bring new insights about the mechanism of the Au(III) complex/biomolecule interaction in the cell, which is responsible for triggering biological responses.

Predicting Pt-195 NMR chemical shift using new relativistic all-electron basis set.

Predicting NMR properties is a valuable tool to assist the experimentalists in the characterization of molecular structure. For heavy metals, such as Pt-195, only a few computational protocols are available. In the present contribution, all-electron Gaussian basis sets, suitable to calculate the Pt-195 NMR chemical shift, are presented for Pt and all elements commonly found as Pt-ligands. The new basis sets identified as NMR-DKH were partially contracted as a triple-zeta doubly polarized scheme with all coefficients obtained from a Douglas-Kroll-Hess (DKH) second-order scalar relativistic calculation. The Pt-195 chemical shift was predicted through empirical models fitted to reproduce experimental data for a set of 183 Pt(II) complexes which NMR sign ranges from -1000 to -6000 ppm. Furthermore, the models were validated using a new set of 75 Pt(II) complexes, not included in the descriptive set. The models were constructed using non-relativistic Hamiltonian at density functional theory (DFT-PBEPBE) level with NMR-DKH basis set for all atoms. For the best model, the mean absolute deviation (MAD) and the mean relative deviation (MRD) were 150 ppm and 6%, respectively, for the validation set (75 Pt-complexes) and 168 ppm (MAD) and 5% (MRD) for all 258 Pt(II) complexes. These results were comparable with relativistic DFT calculation, 200 ppm (MAD) and 6% (MRD). © 2016 Wiley Periodicals, Inc.

Ligand Exchange Reaction of Au(I) R-N-Heterocyclic Carbene Complexes with Cysteine.

The chemotherapy with gold complexes has been attempted since the 90s after the clinical success of auranofin, a gold(I) coordination complex. Currently, the organometallics compounds have shown promise in cancer therapy, mainly in those complexes containing N-heterocylic carbenes (NHC) as a ligand. The present study shows a kinetic analysis of the reaction of six alkyl-substituted NHC with cysteine (Cys), which is taken as an important bionucleophile representative. The first and second ligand exchange processes were analyzed with the complete description of the mechanism and energy profiles. For the first reaction step, which is the rate-limiting step of the whole substitution reaction, the activation enthalpy follows the order 1/Me2 < 2/Me,Et < 4/n-Bu2 < 3/i-Pr2 < 6/Cy2 < 5/t-Bu2, which is fully explained by steric and electronic features. From a steric point of view, the previous reactivity order is correlated with the r(Au-S) calculated for the transition state structures where S is the sulfur ligand from the Cys entering group. This means that longer r(Au-S) leads to higher activation enthalpy and is consistent with the effectiveness of gold shielding from nucleophile attack by bulkier alkyl-substituted NHC ligand. When electronic effect was addressed we found that higher activation barrier was predicted for strongly electron-donating NHC ligand, represented by the eigenvalue of σ-HOMO orbital of the free ligands. The molecular interpretation of the electronic effects is that strong donating NHC forms strong metal-ligand bond. For the second reaction step, similar structure-reactivity relationships were obtained, however the activation energies are less sensitive to the structure.

A quasiclassical trajectory study of the OH+SO reaction: The role of rotational energy.

A full dimensional quasiclassical trajectory study of the OH+SO reaction is presented with the aim of investigating the role of the reactants rotational energy in the reactivity. Different energetic combinations with one and both reactants rotationally excited are studied. A passive method is used to correct zero-point-energy leakage in the classical calculations. The reactive cross sections, for each combination, are calculated and fitted to a capturelike model combined with a factor accounting for recrossing effects. Reactivity decreases as rotational energy is increased in any of both reactants. This fact provides a theoretical support for the experimental dependence of the rate constant on temperature.

A theoretical study of the interaction of anhydrotetracycline with Al(III).

In this article the complexation of anhydrotetracycline (AHTC), the major toxic decomposition product of the antibiotic tetracycline, with Al(III) has been investigated using the AM1 semiempirical and ab initio Hartree-Fock levels of theory. Different modes of complexation have been considered with the structure of tetra- and pentacoordinated complexes being fully optimized. In the gas phase, processes ii and iii, which lead to the complexes with stoichiometry MHL2+, are favored. Structure II ([AlLH2(OH)(H2O)]2+) has the metal coordinated to the O11 and O12 groups and the O3 group protonated and is the global minimum on the potential energy surface for the interaction. In water solution, the Al(III) is predicted to form predominantly a tetracoordinated complex at the Oam and O3 site (V) of the AHTC with the stoichiometry MH2L3+ (process i). The experimental proposal is the complexed form with the metal ion coordinated to the O11-O12 moiety (site II). The intramolecular proton transfer, which leads to the most stable Al(III)-AHTC MHL2+ complex, has not been considered by the experimentalists. The experimental structure was found to be unfavorable in our calculations in both gas phase and water solution. All the semiempirical results are in perfect agreement with the ab initio calculations. So, we suggest that the experimental assignments should be revised, taking into account the results obtained in the present study.

Conformational analysis of the anhydrotetracycline molecule: a toxic decomposition product of tetracycline.

Anhydrotetracycline (AHTC) is a toxic decomposition product of the widely used antibiotic tetracycline (TC). The side effects of AHTC have been attributed to the conformational changes in the ring system. In the present study a systematic conformational analysis has been carried out using the semiempirical quantum mechanical AM1 model. The conformational pH dependence has been analyzed through the study of all the ionized species. The results obtained showed two distinct families of conformation, referred to as A and B, with the interconversion process involving a rotation around the C4a-C12a bond. The solvent effect has been considered using the continuum model COSMO. From the population analysis in the gas phase, we conclude that form A should be dominant for the LH3+ and LH2 +/- species and B is the preferred conformer for the L2- ionized form (97.54%). For the LH- derivative, we predict that both conformations should be present in the equilibrium mixture in the gas phase, with the relative concentration found to be 68.47% (A) and 31.53% (B). The inclusion of the solvent does not change the A/B equilibrium for the LH3+ and LH2 +/- species. However, for the LH- form, the equilibrium is shifted to conformer A in water solution. The population analysis in water solution for the L2- suggest the following relative concentrations: A (34.46%) and B (65.54%). The biological activity of the TC parent compound is attributed to the zwitterionic species, which should adopt a twisted conformation. According to the results obtained in the present study, the most abundant form of the LH2 +/- zwitterionic species for the AHTC molecule is the extended one (100% in both the gas phase and water solution). Therefore, from a pharmacodynamic point of view, this conformational difference should be taken into account in order to explain the toxic effects of the anhydrous derivative. Another point related to the structure-activity relationship was analyzed through the investigation of the tautomerization process LH2(0)-->LH2 +/-. The result obtained suggests that the LH2(0) tautomer should be dominant in the gas phase (nonpolar solvent) and adopt a conformation classified as B. In water solution, the tautomer LH2 +/- is present as conformer A (96%). This result is in agreement with the conformation changes involved in the tautomerization process for the OTC active derivative.