Quantitative assessment of the stereoelectronic profile of phosphine ligands

The stereoelectronic profile of a variety of phosphine ligands (PR3) have been estimated using a combined approach of quantum mechanics (QM) and molecular mechanics (MM). The quantum mechanically derived molecular electrostatic potential minimum (Vmin) of a PR3 ligand at the phosphorus lone pair region provides a direct measure of the total electronic (Eeff) and steric effects (Seff) of the ligand. The difference between the Vmin of unsubstituted PH3 (Vmin(PH3)) and the Vmin of PR3 is considered as Eeff + Seff. It is found that a two-layer QM-MM ONIOM method comprising PH3 in the inner QM layer and the R groups in the outer MM layer is useful to locate the structure of a PR3 ligand in an electronic effect free environment of the substituents. The Vmin of the ONIOM-optimized PR3 at the phosphorus lone-pair region thus provides the quantification of the steric effect as Seff = Vmin(PH3)-Vmin(ONIOM_PR3). Because Vmin(PR3) contains both Eeff and Seff, the Eeff can be easily defined as Eeff = Vmin(ONIOM_PR3)-Vmin(PR3). A modified form of the symmetric deformation coordinate (S4) is calculated for all of the fully optimized and ONIOM-optimized free phosphines to obtain their S4-based steric effect values. Good linear correlation between S4 of ONIOM-optimized phosphines and the MESP-based Seff values was obtained. Further, the determination of the stereoelectronic profile of PR3 ligands has been achieved, leading to a general classification of the ligands into four categories, namely, ligands with (i) (+Eeff, +Seff), (ii) (+Eeff, -Seff), (iii) (-Eeff, +Seff), and (iv) (-Eeff, -Seff), where plus and minus signs indicate electron donation and electron withdrawal properties, respectively.     

Improving the performance of self-organizing maps via growing representations

Self-organizing maps (SOMs) are a type of artificial neural network that through training can produce simplified representations of large, high dimensional data sets. These representations are typically used for visualization, classification, and clustering and have been successfully applied to a variety of problems in the pharmaceutical and bioinformatics domains. SOMs in these domains have generally been restricted to static sets of nodes connected in either a grid or hexagonal connectivity and planar or toroidal topologies. We investigate the impact of connectivity and topology on SOM performance, and experiments were performed on fixed and growing SOMs. Three synthetic and two relevant data sets from the chemistry domain were used for evaluation, and performance was assessed on the basis of topological and quantization errors after equivalent training periods. Although we found that all SOMs were roughly comparable at quantizing a data space, there was wide variation in the ability to capture its underlying structure, and growing SOMs consistently outperformed their static counterparts in regards to topological errors. Additionally, one growing SOM, the Neural Gas, was found to be far more capable of capturing details of a target data space, finding lower dimensional relationships hidden within higher dimensional representations.     

A rapid spectrophotometric assay of some organophosphorus pesticide residues in vegetable samples

A rapid and sensitive spectrophotometric method for the determination of some organophosphorus insecticides, i.e. malathion, dimethoate and phorate is described. It is based on the oxidation of organophosphorus pesticide with slight excess of N-bromosuccinimide (NBS) and the unconsumed NBS is determined with rhodamine B (lambda max: 550 nm). Beer's law is obeyed in the concentration range 0.108-1.08, 0.056-0.56 and 0.028-0.28 microg mL(-1) for malathion, phorate and dimethoate, respectively. The method has been successfully applied for the determination of organophosphorus pesticide residues in various vegetable samples.     

Imaging intracellular pH in live cells with a genetically encoded red fluorescent protein sensor

Intracellular pH affects protein structure and function, and proton gradients underlie the function of organelles such as lysosomes and mitochondria. We engineered a genetically encoded pH sensor by mutagenesis of the red fluorescent protein mKeima, providing a new tool to image intracellular pH in live cells. This sensor, named pHRed, is the first ratiometric, single-protein red fluorescent sensor of pH. Fluorescence emission of pHRed peaks at 610 nm while exhibiting dual excitation peaks at 440 and 585 nm that can be used for ratiometric imaging. The intensity ratio responds with an apparent pK(a) of 6.6 and a >10-fold dynamic range. Furthermore, pHRed has a pH-responsive fluorescence lifetime that changes by ~0.4 ns over physiological pH values and can be monitored with single-wavelength two-photon excitation. After characterizing the sensor, we tested pHRed's ability to monitor intracellular pH by imaging energy-dependent changes in cytosolic and mitochondrial pH.     

Biotin-, fluorescein- and 'clickable' conjugates of phospha-oseltamivir as probes for the influenza virus which utilize selective binding to the neuraminidase

The synthesis of conjugates of phospha-oseltamivir to the well established reporter groups fluorescein and biotin and an approach to multimeric inhibitors is described. We report powerful inhibition of the influenza neuraminidase by these probes and quantify fluorescence quenching during binding of the fluorescein conjugate through titration with the neuraminidase. Thus, we show that they could be useful tools to efficiently inhibit, detect and quantify the virus and the neuraminidase in biological systems.     

Fast and flexible synthesis of pantothenic acid and CJ-15,801

The fast and efficient syntheses of pantothenic acid and the antiparasitic agent CJ-15,801 have been achieved starting from a common imide unit through the selective manipulation of enamide intermediates.     

Boxicity of line graphs

The boxicity of a graph H, denoted by , is the minimum integer k such that H is an intersection graph of axis-parallel k-dimensional boxes in R^k. In this paper we show that for a line graph G of a multigraph, , where Δ(G) denotes the maximum degree of G. Since G is a line graph, Δ(G)≤2(χ(G)−1), where χ(G) denotes the chromatic number of G, and therefore, . For the d-dimensional hypercube Q_d, we prove that . The question of finding a nontrivial lower bound for was left open by Chandran and Sivadasan in [L. Sunil Chandran, Naveen Sivadasan, The cubicity of Hypercube Graphs. Discrete Mathematics 308 (23) (2008) 5795–5800].The above results are consequences of bounds that we obtain for the boxicity of a fully subdivided graph (a graph that can be obtained by subdividing every edge of a graph exactly once).     

A modular phase transfer and ligand exchange protocol for quantum dots

In this paper, we describe a quantum dot (qdot) phase transfer protocol using ligand exchange and the amino acid histidine. The phase transfer from nonpolar solvents to aqueous buffers is homogeneous, and no appreciable precipitation occurs. The molecule histidine was chosen in order to first displace the organic encapsulation and second to provide a weakly chemisorbing intermediate at the qdot ionic interface. This allows the histidine to act as an intermediate shell upon which further direct ligand exchange can occur. Since this intermediate encapsulation is easily displaced by an assortment of different molecules while in aqueous buffers, we refer to this approach as modular. Characterization via FTIR and NMR revealed the extent of ligand exchange, and provides insights into the interfacial binding mechanism. The colloidal stability and photostability of the qdots was probed via UV-vis and steady state fluorescence, which revealed promising quantum yield stability of greater than 1 year. The qdots have hydrodynamic diameters of <12 nm and surface charges dependent upon ligand type and coverage. The modularity of this approach is shown by tailoring the qdot surface charge via sequential ligand exchange using mixed monolayers of carboxylic acid and poly(ethylene glycol)-terminated thiols.