Extending fragment-based free energy calculations with library Monte Carlo simulation: Annealing in interaction space

Pre-calculated libraries of molecular fragment configurations have previously been used as a basis for both equilibrium sampling (via "library-based Monte Carlo") and for obtaining absolute free energies using a polymer-growth formalism. Here, we combine the two approaches to extend the size of systems for which free energies can be calculated. We study a series of all-atom poly-alanine systems in a simple dielectric "solvent" and find that precise free energies can be obtained rapidly. For instance, for 12 residues, less than an hour of single-processor is required. The combined approach is formally equivalent to the "annealed importance sampling" algorithm; instead of annealing by decreasing temperature, however, interactions among fragments are gradually added as the molecule is "grown." We discuss implications for future binding affinity calculations in which a ligand is grown into a binding site

Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation

Nitric oxide NO. has been shown to act as a mediator of cytokines in bone tissue. We have previously demonstrated that vanadium compounds are insulin- and growth factor-mimetic compounds in osteoblasts in culture, although high doses are toxic to these cells. In this study, we measured NO production in two osteoblast-like cells UMR106 and MC3T3E1. incubated with different concentrations 2.5–100 mM. of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 mM. The NO donor, sodium nitroprusside, mimicked the vanadate effect: it inhibited cell growth and alkaline phosphatase activity in a dose-dependent manner. Vanadate enhanced the NO synthases, the endothelial and inducible eNOS and iNOS. isoforms, in a dose-dependent manner. Experiments performed with the ionophore A23187 and EGTA suggested that vanadate-induced NO production involves Ca2q-dependent and -independent mechanisms. Altogether, our results suggest that NO may play a critical role in the bioactivity of vanadium in osteoblast-like cells. q2000 Elsevier Science B.V. All rights reserved

Vanadate-induced nitric oxide production: role in osteoblast growth and differentiation

Nitric oxide NO. has been shown to act as a mediator of cytokines in bone tissue. We have previously demonstrated that vanadium compounds are insulin- and growth factor-mimetic compounds in osteoblasts in culture, although high doses are toxic to these cells. In this study, we measured NO production in two osteoblast-like cells UMR106 and MC3T3E1. incubated with different concentrations 2.5–100 mM. of vanadate. Vanadate induced NO release in a biphasic manner, with levels being significantly increased at concentrations over 50 mM. The NO donor, sodium nitroprusside, mimicked the vanadate effect: it inhibited cell growth and alkaline phosphatase activity in a dose-dependent manner. Vanadate enhanced the NO synthases, the endothelial and inducible eNOS and iNOS. isoforms, in a dose-dependent manner. Experiments performed with the ionophore A23187 and EGTA suggested that vanadate-induced NO production involves Ca2q-dependent and -independent mechanisms. Altogether, our results suggest that NO may play a critical role in the bioactivity of vanadium in osteoblast-like cells.Facultad de Ciencias Exacta

Multicomponent Synthesis of Benzothiophen-2-acetic Esters by a Palladium Iodide Catalyzed S-cyclization – Alkoxycarbonylation Sequence

A catalytic carbonylative approach to the multicomponent synthesis of benzothiophene derivatives from simple building blocks [1-(2-(methylthio)phenyl)prop-2-yn-1-ols, carbon monoxide, and an alcohol)] is presented. It is based on an S-cyclization-demethylation-alkoxycarbonylation-reduction sequence promoted by the PdI2/KI catalytic system, occurring under relatively mild conditions (40 atm, 80 °C, 15 h). Benzothiophene-2-acetic esters are obtained in moderate to good yields (35–70%) starting from variously substituted substrates in combination with different alcohols as external nucleophiles (17 examples). (Figure presented.)

On quantitative analysis of interband recombination dynamics: Theory and application to bulk ZnO

The issue of the quantitative analysis of time-resolved photoluminescence experiments is addressed by developing and describing two approaches for determination of unimolecular lifetime, bimolecular recombination coefficient, and equilibrium free-carrier concentration, based on a quite general second-order expression of the electron-hole recombination rate. Application to the case of band-edge emission of ZnO single crystals is reported, evidencing the signature of sub-nanosecond second-order recombination dynamics for optical transitions close to the interband excitation edge. The resulting findings are in good agreement with the model prediction and further confirm the presence, formerly evidenced in literature by non-optical methods, of near-surface conductive layers in ZnO crystals with sheet charge densities of about 3{\div}5*10^13 cm^-2Comment: 4 pages, 5 figure