Synthesis and Preliminary Biological Study of Bisindolylmethanes Accessed by an Acid-Catalyzed Hydroarylation of Vinylindoles

An acid-catalyzed hydroarylation reaction of vinyl indoles is reported, which tolerates a wide range of heterocycles as the exogenous nucleophile such as indoles, pyrroles, and indolizines. The method rapidly accesses the biologically relevant bisindolylmethane scaffold in good to excellent yields. Evaluation of the biological activity of several synthesized analogues reveals cytotoxic activity against and selectivity for the MCF-7 breast cancer cell line.     

Aminosilane-based functionalization of two-photon polymerized 3D SU-8 microstructures

There is an increasing interest in functionalized complex 3D microstructures with sub-micrometer features for micro- and nanotechnology applications in biology. Depending primarily on the material of the structures various methods exist to create functional layers of simple chemical groups, biological macromolecules or metal nanoparticles. Here an effective coating method is demonstrated and evaluated on SU-8 based 3D microstructures made by two-photon polymerization. Protein streptavidin and gold nanoparticles (NP) were bound to the microstructures utilizing acid treatment-mediated silane chemistry. The protein surface density, quantified with single molecule fluorescence microscopy revealed that the protein forms a third of a monolayer on the two-photon polymerized structures. The surface coverage of the gold NPs on the microstructures was simply controlled with a single parameter. The possible degrading effect of the acid treatment on the sub-micrometer features of the TPP microstructures was analyzed. Our results show that the silane chemistry-based method, used earlier for the functionalization of large-area surfaces can effectively be adapted to coat two-photon polymerized SU-8 microstructures with sub-micrometer features.     

Thermal Degradation of Adsorbed Bottle-Brush Macromolecules: When Do Strong Covalent Bonds Break Easily?

The scission kinetics of bottle-brush molecules in solution and on an adhesive substrate is modeled by means of Molecular Dynamics simulation with Langevin thermostat. Our macromolecules comprise a long flexible polymer backbone with L segments, consisting of breakable bonds, along with two side chains of length N, tethered to segments of the backbone with grafting density σ_g. In agreement with recent experiments and theoretical predictions, we find that bond cleavage is significantly enhanced on a strongly attractive substrate even though the chemical nature of the bonds remains thereby unchanged. Our simulation results indicate that the mean life time of covalent bonds decreases by more than an order of magnitude upon adsorption even for brush molecules with comparatively short side chains . The distribution of scission probability along the bonds of the backbone is found to change significantly when the length and/or the grafting density of the side chains are varied. The tension, experienced by the covalent bonds is found to grow steadily with increasing σ_g. The mean life time declines with growing contour length L as , and also with growing side chain length N. The probability distribution of fragment lengths at different times is compatible with experimental observations and reveals a two-stage (initially fast, then slow) process with different rates. The variation of the mean length L(t) of the fragments with elapsed time characterizes the thermal degradation process as a first order reaction.     

On the transferability of folding and threading potentials and sequence-independent filters for protein folding simulations

Significant progress has recently been made in de novo protein structure prediction. The Rosetta method by Baker and colleagues, which is based on the idea of assembling putative models from a library of k-mer fragments derived from known three-dimensional protein structures, proved to be particularly successful. Critical components of the Rosetta approach are various sequence-dependent as well as sequence-independent measures that are used to rank alternative models and to enhance sampling of native-like conformations. In the present work we revisit several sequence-independent filters that have been used to enhance the discrimination of native and native-like structures from misfolded structures, such as the overall compactness of the structure and its contact order. We also propose a novel sequence-independent filter, based on the shape of the mean inter-residue radial distribution function. Using the Rosetta, Park–Levitt and CASP4 sets of decoys it is shown that sequence-independent filters are in fact more successful in distinguishing native structures in Rosetta and CASP4 tests than commonly used knowledge-based pairwise potentials. The latter are typically designed to distinguish native structures in a population of well-folded alternatives, and they fail to discriminate between native-like and non-physically packed misfolded structures from Rosetta simulations. Moreover, a rigorous attempt to optimize pairwise potentials for recognition of homologous structures in threading by using a linear programming approach leads to further deterioration of performance in terms of recognition of native structures from the Rosetta set. These findings shed light onto the success of tailored scoring functions used in the Rosetta protocol and provide support for explicit inclusion of both sequence dependent and sequence independent measures in the design of scoring functions. A Web server that enables ranking of decoy structures according to sequence independent filters considered here is available at http://sift.chmcc.org.     

Simultaneous Anodic Stripping Voltammetric Determination of Pb and Cd,Using a Vibrating Gold Microwire Electrode,Assisted by Chemometric Techniques

Simultaneous anodic stripping voltammetric determination of Pb and Cd is restricted on gold electrodes as a result of the overlapping of these two peaks. This work describes the quantitative determination of a binary mixture system of Pb and Cd, at low concentration levels (up to 15.0 and 10.0 µg L^?1 for Pb and Cd, respectively) by differential pulse anodic stripping voltammetry (DPASV; deposition time of 30 s), using a green electrode (vibrating gold microwire electrode) without purging in a chloride medium (0.5 M NaCl) under moderate acidic conditions (HCl 1.0 mM), assisted by chemometric tools. The application of multivariate curve resolution alternating least squares (MCR‐ALS) for the resolution and quantification of both metals is shown. The optimized MCR‐ALS models showed good prediction ability with concentration prediction errors of 12.4 and 11.4 % for Pb and Cd, respectively. The quantitative results obtained by MCR‐ALS were compared to those obtained with partial least squares (PLS) and classical least squares (CLS) regression methods. For both metals, PLS and MCR‐ALS results are comparable and superior to CLS. For Cd, as a result of the peak shift problem, the application of CLS was unsuitable. MCR‐ALS provides additional advantage compared to PLS since it estimates the pure response of the analytes signal. Finally, the built up multivariate calibration models, based either in MCR‐ALS or PLS regression, allowed to quantify concentrations of Pb and Cd in surface river water samples, with satisfactory results.     

On the value distribution of the Matsumoto zeta-function

The Matsumoto zeta-function is defined by a polynomial Euler product and is a generalization of classical zeta-functions. In the paper a discrete limit theorem in the sense of the weak convergence of probability measures on the complex plane for the Matsumoto zeta-function is proved.     

The comparison of geometric and electronic properties of molecular surfaces by neural networks: Application to the analysis of corticosteroid-binding globulin activity of steroids

Summary It is shown how a self-organizing neural network such as the one introduced by Kohonen can be used to analyze features of molecular surfaces, such as shape and the molecular electrostatic potential. On the one hand, two-dimensional maps of molecular surface properties can be generated and used for the comparison of a set of molecules. On the other hand, the surface geometry of one molecule can be stored in a network and this network can be used as a template for the analysis of the shape of various other molecules. The application of these techniques to a series of steroids exhibiting a range of binding activities to the corticosteroid-binding globulin receptor allows one to pinpoint the essential features necessary for biological activity.     

Reduced-size polarized basis sets for calculations of molecular electric properties. II. Simulation of the Raman spectra

The accuracies of the calculated vibrational frequencies and Raman intensities given by two new, highly compact Pol-type basis sets, Z2PolX and Z3PolX, have been determined and compared to the 6-31G(d), PolX, and aug-cc-pVTZ basis sets. Calculation of accurate Raman intensities has previously required large basis sets, but the ZmPolX basis sets are smaller even than PolX, which are the most compact basis sets able to calculate accurate Raman intensities. For the largest compound studied, C5H10O2, Z3PolX required more than an order of magnitude less CPU time than PolX, which has been shown to be 10 times faster than aug-cc-pVTZ. Two sets of test molecules were studied: one was a series of small molecules for which experimental values for absolute Raman activities were available; the second was a series of medium-sized molecules (mainly common organic solvents) where only relative Raman band intensities were available. The accuracies of the Raman intensities given by both of the ZmPolX basis sets were good compared to those of the PolX and aug-cc-pVTZ sets, and much better than the 6-31G(d) values. The errors in even unscaled frequency values <2000 cm(-1) were also acceptable and were slightly lower for Z3PolX than Z2PolX (30 cm(-1) vs. 48 cm(-1)). The combination of good intensity and frequency data meant that for the medium-sized organic molecules there was a close correspondence between the simulated Raman spectra and experimental data, and that the observed bands could easily be assigned on the basis of these calculations. Achieving this level of accuracy in the simulations at modest computational cost should now allow computational methods to be combined with experimental Raman studies much more widely than is currently the case.