Recent advances with electro-optic polymers

Abstract

In recent years the electro-optic polymers emerged as an important branch of material science. This growth and interest is fundamentally motivated by practical application of these materials in second-order nonlinear optics and in waveguiding configuration. Indeed, these materials marry excellent optical quality of amorphous σ bonded polymers with enhanced first hyperpolarizability of imbedded organic nonlinear optical molecules. Although a big progress was achieved with them, concerning particularly the science, understanding and applications, some problems remain still incompletely solved, particularly the stability of induced polar order by the application of external electric field and the molecule aggregation. In this review paper we recall techniques of thin film fabrication, poling, characterization of NLO properties and discuss more precisely problems of molecule aggregation as well as the temporal decay of polar order. A novel 3D second-order NLO chromophores, namely the [2] paracyclophanes, which may help to limit the aggregation, are proposed. We show, in particular, that this molecule can be poled in doped PMMA thin films. Practical applications of electro-optic polymers are also reviewed and discussed.     

Rapid and accurate prediction of binding free energies for saquinavir-bound HIV-1 proteases

To explain drug resistance by computer simulations at the molecular level, we first have to assess the accuracy of theoretical predictions. Herein we report an application of the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) technique to the ranking of binding affinities of the inhibitor saquinavir with the wild type (WT) and three resistant mutants of HIV-1 protease: L90M, G48V, and G48V/L90M. For each ligand-protein complex we report 10 ns of fully unrestrained molecular dynamics (MD) simulations with explicit solvent. We investigate convergence, internal consistency, and model dependency of MM/PBSA ligand binding energies. Converged enthalpy and entropy estimates produce ligand binding affinities within 1.5 kcal/mol of experimental values, with a remarkable level of correlation to the experimentally observed ranking of resistance levels. A detailed analysis of the enthalpic/entropic balance of drug-protease interactions explains resistance in L90M in terms of a higher vibrational entropy than in the WT complex, while G48V disrupts critical hydrogen bonds at the inhibitor's binding site and produces an altered, more unfavorable balance of Coulomb and polar desolvation energies.     

H2‐Fueled ATP Synthesis on an Electrode: Mimicking Cellular Respiration

ATP, the molecule used by living organisms to supply energy to many different metabolic processes, is synthesized mostly by the ATPase synthase using a proton or sodium gradient generated across a lipid membrane. We present evidence that a modified electrode surface integrating a NiFeSe hydrogenase and a F₁F₀‐ATPase in a lipid membrane can couple the electrochemical oxidation of H₂ to the synthesis of ATP. This electrode‐assisted conversion of H₂ gas into ATP could serve to generate this biochemical fuel locally when required in biomedical devices or enzymatic synthesis of valuable products.     

Improved protein identification efficiency by mass spectrometry using N-terminal chemical derivatization of peptides from Angiostrongylus costaricensis, a nematode with unknown genome

Matrix-assisted laser desorption ionization (MALDI), Peptide Mass Fingerprinting (PMF) and MALDI-MS/MS ion search (using MASCOT) have become the preferred methods for high-throughput identification of proteins. Unfortunately, PMF can be ambiguous, mainly when the genome of the organism under investigation is unknown and the quality of spectra generated is poor and does not allow confident identification. The post-source decay (PSD) fragmentation of singly charged tryptic peptide ions generated by MALDI-TOF/TOF typically results in low fragmentation efficiency and/or complex spectra, including backbone fragmentation ions (series b and y), internal fragmentation etc. Interpreting these data either manually and/or using de novo sequencing software can frequently be a challenge. To overcome this limitation when studying the proteome of adult Angiostrongylus costaricensis, a nematode with unknown genome, we have used chemical N-terminal derivatization of the tryptic peptides with 4-sulfophenyl isothiocyanate (SPITC) prior to MALDI-TOF/TOF MS. This methodology has recently been reported to enhance the quality of MALDI-TOF/TOF-PSD data, allowing the obtainment of complete sequence of most of the peptides and thus facilitating de novo peptide sequencing. Our approach, consisting of SPITC derivatization along with manual spectra interpretation and Blast analysis, was able to positively identify 76% of analyzed samples, whereas MASCOT analysis of derivatized samples, MASCOT analysis of nonderivatized samples and PMF of nonderivatized samples yielded only 35, 41 and 12% positive identifications, respectively. Moreover, de novo sequencing of SPITC modified peptides resulted in protein sequences not available in NCBInr database paving the way to the discovery of new protein molecules.     

Saari's conjecture is true for generic vector fields

The simplest non-collision solutions of the -body problem are the ``relative equilibria', in which each body follows a circular orbit around the centre of mass and the shape formed by the bodies is constant. It is easy to see that the moment of inertia of such a solution is constant. In 1970, D. Saari conjectured that the converse is also true for the planar Newtonian -body problem: relative equilibria are the only constant-inertia solutions. A computer-assisted proof for the 3-body case was recently given by R. Moeckel, Trans. Amer. Math. Soc. (2005). We present a different kind of answer: proofs that several generalisations of Saari's conjecture are generically true. Our main tool is jet transversality, including a new version suitable for the study of generic potential functions.

     

Computational analysis and in vivo validation of a microRNA encoded by the IBTK gene,a regulator of B-lymphocytes differentiation and survival

MicroRNAs (miRNAs) are small single-stranded RNA molecules that play an essential role in the regulation of gene expression and cell physiology. Gene rearrangements occurring in the miRNA sequence are associated with cancer. The IBTK genetic locus is located in the genomic sequence 6q14.1 that undergoes chromosomal aberration in lymphoproliferative disorders. The IBTK gene encodes the proteins IBtk-α, β and γ that regulate the B cell receptor signalling through Bruton's tyrosine kinase, which promotes B cell survival and differentiation. Pro-MirII-based analysis predicted four precursors of microRNAs (pre-miR) encoded by introns 17, 21, 26 and the 3′ un-translated region of the IBTK gene. Pre-miR-IBTK3, which was encoded by intron 26, was the effective substrate of RNase III Dicer in vitro as well as the precursor of an IBtk miRNA generated in vivo. By CLUSTALW-based analysis, pre-miR-IBTK3 homologues were found in Pan troglodytes, Pongo pygmaeus and Macaca mulatta, suggesting an evolutionary conserved function in primates.     

Electrochemical evidence of self-substrate inhibition as functions regulation for cellobiose dehydrogenase from Phanerochaete chrysosporium

The reaction mechanism of cellobiose dehydrogenase (CDH) from Phanerochaete chrysosporium, adsorbed on graphite electrodes, was investigated by following its catalytic reaction with cellobiose registered in both direct and mediated electron transfer modes between the enzyme and the electrode. A wall-jet flow through amperometric cell housing the CDH-modified graphite electrode was connected to a single line flow injection system. In the present study, it is proven that cellobiose, at concentrations higher than 200 μM, competes for the reduced state of the FAD cofactor and it slows down the transfer of electrons to any 2e⁻/H⁺ acceptors or further to the heme cofactor, via the internal electron transfer pathway. Based on and proven by electrochemical results, a kinetic model of substrate inhibition is proposed and supported by the agreement between simulation of plots and experimental data. The implications of this kinetic model, called pseudo-ping-pong mechanism, on the possible functions CDH are also discussed. The enzyme exhibits catalytic activity also for lactose, but in contrast to cellobiose, this sugar does not inhibit the enzyme. This suggests that even if some other substrates are coincidentally oxidized by CDH, however, they do not trigger all the possible natural functions of the enzyme. In this respect, cellobiose is regarded as the natural substrate of CDH.