Oligo p-Phenylenevinylene Derivatives as Electron Transfer Matrices for UV-MALDI

Phenylenevinylene oligomers (PVs) have outstanding photophysical characteristics for applications in the growing field of organic electronics. Yet, PVs are also versatile molecules, the optical and physicochemical properties of which can be tuned by manipulation of their structure. We report the synthesis, photophysical, and MS characterization of eight PV derivatives with potential value as electron transfer (ET) matrices for UV-MALDI. UV-vis analysis show the presence of strong characteristic absorption bands in the UV region and molar absorptivities at 355 nm similar or higher than those of traditional proton (CHCA) and ET (DCTB) MALDI matrices. Most of the PVs exhibit non-radiative quantum yields (φ) above 0.5, indicating favorable thermal decay. Ionization potential values (IP) for PVs, calculated by the Electron Propagator Theory (EPT), range from 6.88 to 7.96 eV, making these oligomers good candidates as matrices for ET ionization. LDI analysis of PVs shows only the presence of radical cations (M^+.) in positive ion mode and absence of clusters, adducts, or protonated species; in addition, M^+. threshold energies for PVs are lower than for DCTB. We also tested the performance of four selected PVs as ET MALDI matrices for analytes ranging from porphyrins and phthalocyanines to polyaromatic compounds. Two of the four PVs show S/N enhancement of 1961% to 304% in comparison to LDI, and laser energy thresholds from 0.17 μJ to 0.47 μJ compared to 0.58 μJ for DCTB. The use of PV matrices also results in lower LODs (low fmol range) whereas LDI LODs range from pmol to nmol.

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The first example of a recursive function which is not primitive recursive

The first example of a recursive function which is not primitive recursive is usually attributed to W. Ackermann. The authors of the present paper show that such an example can also be found in a paper by G. Sudan, published concomitantly with Ackermann's paper.     

Long-time behavior of an angiogenesis model with flux at the tumor boundary

This paper deals with a nonlinear system of partial differential equations modeling a simplified tumor-induced angiogenesis taking into account only the interplay between tumor angiogenic factors and endothelial cells. Considered model assumes a nonlinear flux at the tumor boundary and a nonlinear chemotactic response. It is proved that the choice of some key parameters influences the long-time behavior of the system. More precisely, we show the convergence of solutions to different semi-trivial stationary states for different range of parameters.     

Kinetics of N-glutaryl-L-phenylalanine p-nitroanilide hydrolysis catalyzed by alpha-chymotrypsin in aqueous solutions of alkyltrimethylammonium bromides

The rate of N-glutaryl-L-phenylalanine p-nitroanilide hydrolysis catalyzed by alpha-chymotripsin has been measured in aqueous solutions of cetyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and dodecyltrimethylammonium bromide at concentrations below and above their critical micellar concentrations (CMC). For the three surfactants considered superactivity was observed, with maximum catalytic efficiencies taking place near the corresponding CMCs. The effect of the surfactants after the CMCs is mostly due to a decreased thermodynamic activity of the substrate due to its incorporation into the micelles. After addition of the surfactants, the Michaelis constant values (corrected to take into account the free substrate concentration) tend to decrease, passing through an ill defined minimum, afterwards reaching a constant value. The catalytic rate constants show the same profiles that the catalytic efficiency, being maxima near the surfactants CMCs. This maximum is more important for the surfactant having the shorter tail. This result is explained by considering that the hydrophobicity of the surfactant influences more the CMC than its association to the enzyme.     

The first trialkylphosphane telluride complexes of Ag(I): molecular, ionic and supramolecular structural alternatives

The structures of the first phosphane telluride complexes of silver(I), obtained from i-Pr3PTe (1) with AgNMs2 [Ms = SO2CH3] and with AgSbF6, reveal the superior coordinating ability of 1, particularly as a bridging ligand, compared with related i-Pr3PS and i-Pr3PSe ligands.     

Comparative evaluation of MMPBSA and XSCORE to compute binding free energy in XIAP-peptide complexes

Evaluation of binding free energy in receptor-ligand complexes is one of the most important challenges in theoretical drug design. Free energy is directly correlated to the thermodynamic affinity constant, and, as a first step in druglikeness, a lead compound must have this constant in the range of micro- to nanomolar activity. Many efforts have been made to calculate it by rigorous computational approaches, such as free energy perturbation or linear response approximation. However, these methods are still computationally expensive. We focus our work on XIAP, an antiapoptotic protein whose inhibition can lead to new drugs against cancer disease. We report here a comparative evaluation of two completely different methodologies to estimate binding free energy, MMPBSA (a force field based function) and XSCORE (an empirical scoring function), in seven XIAP-peptide complexes using a representative set of structures generated by previous molecular dynamics simulations. Both methods are able to predict the experimental binding free energy with acceptable errors, but if one needs to identify slight differences upon binding, MMPBSA performs better, although XSCORE is not a bad choice taking into account the low computational cost of this method.     

Experimental and theoretical evidence of the first Au(i)...Bi(iii) interaction

Complex [Au(C6F5)2][Bi(C6H4CH2NMe(2)-2)2] displays the first example of an interaction between Au(I) and Bi(III), the nature of which is shown to be consistent with the presence of a high ionic contribution (79%) and a dispersion type (van der Waals) interaction (21%).     

Live-cell-permeant thiophene fluorophores and cell-mediated formation of fluorescent fibrils

In our search for thiophene fluorophores that can overcome the limits of currently available organic dyes in live-cell staining, we synthesized biocompatible dithienothiophene-S,S-dioxide derivatives (DTTOs) that were spontaneously taken up by live mouse embryonic fibroblasts and HeLa cells. Upon treatment with DTTOs, the cells secreted nanostructured fluorescent fibrils, while cell viability remained unaltered. Comparison with the behavior of other cell-permeant, newly synthesized thiophene fluorophores showed that the formation of fluorescent fibrils was peculiar to DTTO dyes. Laser scanning confocal microscopy of the fluorescent fibrils showed that most of them were characterized by helical supramolecular organization. Electrophoretic analysis and theoretical calculations suggested that the DTTOs were selectively recognized by the HyPro component of procollagen polypeptide chains and incorporated through the formation of multiple H-bondings.     

A multiscale simulation system for the prediction of drug-induced cardiotoxicity

The preclinical assessment of drug-induced ventricular arrhythmia, a major concern for regulators, is typically based on experimental or computational models focused on the potassium channel hERG (human ether-a-go-go-related gene, K(v)11.1). Even if the role of this ion channel in the ventricular repolarization is of critical importance, the complexity of the events involved make the cardiac safety assessment based only on hERG has a high risk of producing either false positive or negative results. We introduce a multiscale simulation system aiming to produce a better cardiotoxicity assessment. At the molecular scale, the proposed system uses a combination of docking simulations on two potassium channels, hERG and KCNQ1, plus three-dimensional quantitative structure-activity relationship modeling for predicting how the tested compound will block the potassium currents IK(r) and IK(s). The obtained results have been introduced in electrophysiological models of the cardiomyocytes and the ventricular tissue, allowing the direct prediction of the drug effects on electrocardiogram simulations. The usefulness of the whole method is illustrated by predicting the cardiotoxic effect of several compounds, including some examples in which classic hERG-based models produce false positive or negative results, yielding correct predictions for all of them. These results can be considered a proof of concept, suggesting that multiscale prediction systems can be suitable for being used for preliminary screening in lead discovery, before the compound is physically available, or in early preclinical development when they can be fed with experimentally obtained data.