Electronegativity and resonance parameters from the geometry of monosubstituted benzene rings

Reference values of the structural substituent parameters, S _E and S _R, measuring the electronegativity and resonance effects, respectively, of functional groups (Campanelli et al. J Phys Chem A 107:6429–6440, 2003) have been determined from the benzene ring geometries of 100 Ph–X species, including different conformations of the same molecule. Geometries have been obtained by quantum chemical calculations at the HF/6-31G*, HF/6-311++G**, and B3LYP/6-311++G** levels of theory. The substituent parameters from HF/6-311++G** calculations are in close agreement with those determined at the HF/6-31G* level. Using the B3LYP density functional yields S _E and S _R values which—in general—correlate well with the corresponding HF values. Exceptions occur with some charged groups, and, in the case of S _E, with a few dipolar groups having very high or low electronegativities. S _R values from B3LYP calculations are about 22% smaller than the corresponding HF values. The variations of the benzene ring geometry caused by electronegativity, resonance, and steric effects are illustrated in some detail.     

Kinetic, DFT and TD-DFT studies on the mechanism of stabilization of pyramidal H3PO3 at the [Mo3M'S4(H2O)10]4+ clusters (M' = Pd, Ni)

The kinetics of reaction between the [Mo(3)M'S(4)(H(2)O)(10)](4+) clusters (M' = Pd, Ni) and H(3)PO(3) has been studied in 4.0 M Hpts/Lipts (pts(-) = p-toluenesulfonate). For both complexes there is an initial kinetic step with small absorbance changes that corresponds to substitution of the water coordinated to Pd by a molecule of tetrahedral H(3)PO(3). For the Pd complex, tautomerization of H(3)PO(3) occurs in a slower kinetic step with much larger absorbance changes; it leads to formation of [Mo(3)Pd(pyr-H(3)PO(3))S(4)(H(2)O)(9)](4+) in which H(3)PO(3) adopts a pyramidal structure, but the process is not as favored as for H(3)PO(2). The kinetics of this second step is independent of the concentration of H(3)PO(3) but dependent on the concentration of Hpts on the supporting electrolyte. For the Ni complex, the second step is severely hindered and its kinetics could not be studied. DFT calculations indicate that tautomerization of H(3)PO(3) is expected to be less favoured than that of H(3)PO(2), both processes being less favored at the Ni cluster than at its Pd analogue. With regard to the tautomerization mechanism, the calculations indicate that the mechanism previously proposed for H(3)PO(2) can be the same for H(3)PO(3), although the initial H-shift can also occur through a protonation-deprotonation sequence with participation of external protons instead of a second molecule of the phosphorus acid. TD-DFT studies have been also carried out to understand the similarity between the spectra of the starting complex and the reaction intermediate formed in the first kinetic step as well as the large spectral changes associated to the tautomerization process. Although it contains contributions from several transitions, the intense band observed for clusters containing coordinated pyr-H(3)PO(3) involves essentially ligand-to-metal charge-transfer (LMCT) transitions.     

New ammonium surfactant-stabilized rhodium(0) colloidal suspensions: influence of novel counter-anions on physico-chemical and catalytic properties

Novel anionic species, such as hydrogen carbonate (HCO(3)(?)), fluoride (F(?)), triflate (CF(3)SO(3)(?)), tetrafluoroborate (BF(4)(?)) and chloride (Cl(?)) were investigated as new partners of water soluble N,N-dimethyl-N-cetyl-N-(2-hydroxyethyl) ammonium salts, used as a protective agent of rhodium colloids. The effect of the surfactant polar head on the micellar behavior, size and morphology of the nanospecies was studied by adapted physico-chemical experiments (surface tension measurements, dynamic light scattering, thermogravimetric and TEM analyses) and discussed in terms of strong or weak stabilization of the growing nanoparticles surface. Finally, the influence of the nanoenvironment generated by the surfactant with various counter-anions was evaluated via the hydrogenation of aromatics.     

Structure and cytotoxicity of phidianidines A and B: first finding of 1,2,4-oxadiazole system in a marine natural product

Two indole alkaloids, phidianidines A (1) and B (2), exhibiting an uncommon 1,2,4-oxadiazole ring linked to the indole system, have been isolated from the marine opisthobranch mollusk Phidiana militaris. The structures of the two metabolites have been elucidated by spectroscopic techniques. Phidianidines exhibit high cytotoxicity against tumor and nontumor mammalian cell lines in in vitro assays.     

Characterizing the dynamics and ligand-specific interactions in the human leukocyte elastase through molecular dynamics simulations

The human leukocyte elastase (HLE), a neutrophil serine protease of the chymotrypsin superfamily, is a major therapeutic target for a number of inflammatory diseases, such as chronic obstructive pulmonary disease (COPD). In this work, we present a comparative explicit water molecular dynamics (MD) study on the free and inhibitor-bound HLE. Knowledge of the flexibility and conformational changes induced by this irreversible inhibitor, whether in a prebound stage or covalently bound at the enzyme binding site, encases fundamental biological interest and is particularly relevant to ongoing structure-based drug design studies. Our results suggest that HLE operates by an induced-fit mechanism with direct intervention of a surface loop which is open toward the solvent in the free enzyme and closed while in the presence of the ligand. MM-PBSA free energy calculations furthermore elucidate the energetic contributions to the distinct conformations adopted by this loop. Additionally, a survey of the major contributions to the inhibitor binding free energies was attained. Our findings enforce the need to account for HLE flexibility, whether through the use of MD-generated ensembles of HLE conformations as targets for molecular docking or via sophisticated flexible-docking algorithms. We anticipate that inclusion of the observed HLE dynamic behavior into future drug design methodologies will have a relevant impact in the development of novel, more efficient, inhibitors.     

Direct experimental evidence for an enamine radical cation in SOMO catalysis

SOMO catalysis has lately obtained large interest as a new and powerful version of enantioselective organocatalysis which includes radical steps initiated by a one-electron oxidation. The intermediate enamine radical cation has been postulated, but has not been observed directly so far. This communication now reports the direct detection of this key intermediate.     

Quercetin-PVP K25 solid dispersions

Quercetin is a flavonoid very well studied and has already entered clinical trials emerging as prospective anticancer drug candidate. In addition, quercetin has being reported to its free-radical scavenging activity and suggests potential uses for the prevention and treatment of pathologies as atherosclerosis, chronic inflammation, and others. However, quercetin is sparingly soluble in water, which may be responsible for its limited absorption upon oral administration. The solid dispersion of quercetin with polyvinylpyrrolidone Kollidon^® 25 (PVP K25) suggests an interesting way to increase quercetin solubility, antioxidant activity, and consequently bioavailability. Then, the purpose of this study was to prepare solid dispersions of quercetin with PVP K25 and evaluate their thermal characterization, antioxidant activity and quercetin improvement solubility. For this purpose, quercetin-PVP K25 solutions were dried and quercetin-PVP K25 solids were obtained. The formation of quercetin-PVP K25 solid dispersion was evaluated by solubility studies, powder X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetry (TG), and antioxidant activity. It was observed that PVP K25 was able to provide quercetin clear aqueous solutions and that quercetin solubility was increased in a PVP K25 concentration dependent manner, improving solubility even 436-fold the pure quercetin. The results obtained with XRD, FT-IR, DSC, and TG demonstrated possible quercetin-PVP K25 solid dispersion formation. Besides, the antioxidant activity of the quercetin-PVP K25 solid dispersions dissolved in aqueous solution and pure quercetin dissolved in methanol showed IC₅₀ value of 0.61 ± 0.03 and 1.00 ± 0.02 μg/mL, respectively, demonstrating that the solid dispersions presented a significant increase in antioxidant activity (P < 0.05). Putting results together, it was possible to conclude there was the formation of quercetin-PVP K25 solid dispersion.     

Antimicrobial activities of indole alkaloids from Tabernaemontana catharinensis

Tabernaemontana catharinensis root bark ethanol extract, EB2 fraction and the MMV alkaloid (12-methoxy-4-methylvoachalotine) were evaluated for their antimicrobial activities. T. catharinensis ethanol extract was effective against both strains of the dermatophyte Trichophyton rubrum at concentrations of 2.5 mg/mL (wild strain) and 1.25 mg/mL (mutant strain), while the EB2 fraction and MMV alkaloid showed a strong antifungal activity against wild and mutant strains with MIC values of <0.02 and 0.16 mg/mL, respectively. The EB2 fraction showed a strong antibacterial activity against ATCC strains of S. aureus, S. epidermidis, E. coli and P. aeruginosa with MICs from <0.02 to 0.04 mg/mL, as well as against resistant clinical isolates species of Enterococcus sp, Klebsiella oxytoca, Citrobacter, K. pneumoniae, P. mirabilis, S. aureus, S. epidermidis, E. coli and P. aeruginosa with MIC values ranging from 0.04 to 0.08 mg/mL. The MMV alkaloid presented a MIC of 0.16 mg/mL against the strains of S. aureus and E. coli ATCC. For the resistant clinical isolates Enterococcus sp, Citrobacter, S. aureus, S. epidermidis, E. coli and P. aeruginosa the MIC of MMV ranged from 0.08 to 0.31 mg/mL. The chromatography analysis of the EB2 fraction revealed the presence of indole alkaloids, including MMV, possibly responsible for the observed antimicrobial activity.     

The convex hull of two core capacitated network design problems

The network loading problem (NLP) is a specialized capacitated network design problem in which prescribed point-to-point demand between various pairs of nodes of a network must be met by installing (loading) a capacitated facility. We can load any number of units of the facility on each of the arcs at a specified arc dependent cost. The problem is to determine the number of facilities to be loaded on the arcs that will satisfy the given demand at minimum cost.This paper studies two core subproblems of the NLP. The first problem, motivated by a Lagrangian relaxation approach for solving the problem, considers a multiple commodity, single arc capacitated network design problem. The second problem is a three node network; this specialized network arises in larger networks if we aggregate nodes. In both cases, we develop families of facets and completely characterize the convex hull of feasible solutions to the integer programming formulation of the problems. These results in turn strengthen the formulation of the NLP.Research of this author was supported in part by a Faculty Grant from the Katz Graduate School of Business, University of Pittsburgh.     

The effect of second neighbour repulsion on fcc binary alloy phase diagrams: A Monte Carlo study

We report the results of the Monte Carlo simulation of the phase diagram of fcc binary alloys using a 3-D Ising model with nearest and next-nearest neighbour repulsive interactions. Calculations are carried out for a ratio of second- to first-neighbour interaction energies of 0.4. The resulting phase diagram contains three superstructures A₂B₂, A₂B and A₅B, each separated by a disordered fcc phase. There was no evidence for the formation of an A₃B phase. These results are in qualitative agreement with CVM results.