Tuning Chemical and Physical Properties of Phosphorus Corroles for Advanced Applications

Although the affinity of metallocorroles to axial ligands is quite low, this is not the case when the chelated element is phosphorus. This work is hence focused on the mechanism of ligand exchange of six-coordinate phosphorus corroles as a tool for affecting their chemical and physical properties. These fundamental investigations allowed for the development of facile methodologies for the synthesis of a large series of complexes and the establishment of several new structure/activity profiles that may be used to understand and predict spectroscopic features and for tailor-made modification of photophysical and electrochemical properties. This is exemplified by the facile access to complexes with terminal groups that are of large potential for practical applications based on click chemistry, optical imaging, and surface science.     

Spectral,Optical and Mechanical studies on pure and thiourea doped ammonium di-hydrogen phosphate NLO single crystals

Pure and thiourea substituted single crystals of ammonium di-hydrogen phosphate have been grown from aqueous solution by isothermal solvent evaporation technique. Doped crystal exhibits prominent changes in physical and chemical properties. Single crystal XRD analyses of the samples are carried out and the results are compared. FTIR and UV–vis–NIR spectral analyses have been employed to identify the presence of various functional groups and the UV cut-off range in the grown crystals. Density measurements have been made and Photoconductivity studies revealed the negative photo conducting nature. Hardness measurement shows that the mechanical strength of the doped crystal is high when compared to pure ammonium di-hydrogen phosphate. The dielectric response of the samples has been studied in the frequency range 100 Hz–5 MHz at room temperature and the results are discussed.     

An Efficient Process for the Synthesis of Renin Inhibitor,ABT-517

An efficient process for the preparation of renin inhibitor, ABT-517 is described. The process avoids solvent extractions or chromatographic purifications and is used on multi-kilogram scale.     

On the Strategy of NMR Spectral Analysis. The 1H-NMR Spectrum of Amphetamine

The successive steps of the computer analysis of a NMR spectrum are examined. Better results can be obtained by direct simulation of tentative model spectra. As an example the ¹H-NMR spectrum of amphetamine is analysed.     

Oxidation of Ascorbate by Ni(III) Complexes with Tetraaza-macrocyclic Ligands in Neutral Aqueous Solutions. A Pulse-Radiolysis Study

Abstract

The mechanisms and kinetics of oxidation of ascorbate, AH^?, by Ni(III)Lⁱ _aq and by LⁱNi(III) (HPO₄)₂ ^? complexes (L¹ = meso-(5,12)-7,7,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane; L² = 1,8-dimethyl-1,3,6,8,10,13-hexaazacyclotetradecane) in neutral aqueous solutions have been investigated.

The oxidation of ascorbate by the LⁱNi(III) (HPO₄)₂ ^? and Ni(III)L¹ _aq proceeds via two consecutive reactions well separated in time. The products of the first reaction are the A^.? radical anion and the corresponding Ni(II) complex. The oxidations by the LⁱNi(III)(HPO₄)₂ ^? complexes proceed via the outer sphere mechanism, whereas the detailed mechanism of reaction of Ni(III)L¹ _aq cannot be determined. The rate of reaction decreases with the increase in the concentration of phosphate, thus indicating that LⁱNi(III)(HPO₄)(H₂O)⁺ and LⁱNi(III)OH²⁺ are stronger oxidizing agents than LⁱNi(III)(HPO₄)^? ₂.

The oxidation of ascorbate by Ni(III)L² _aq proceeds via three consecutive reactions which are well separated in time. Thus the results clearly point out that this process occurs via the inner sphere mechanism. The first transient observed is tentatively identified as L²(H₂O)Ni(II)(A^.?)²⁺, i.e., an unexpected complex of the ascorbate anion radical. Also in this process the last transient observed is the A^.? anion radical. The stabilization of the ascorbyl radical in a transient complex might be of biological significance.     

A novel homogeneous immunoassay for anthrax detection based on the AlphaLISA method: detection of B. anthracis spores and protective antigen (PA) in complex samples

Amplified Luminescent Proximity Homogeneous Assay (AlphaLISA) technology is an energy-transfer-based assay, utilizing singlet oxygen as an energy donor to a fluorescent acceptor. The long singlet oxygen migration distance allows the energy transfer mechanism to go up to ～200 nm, facilitating flexible and sensitive homogeneous immunoassays. While soluble protein detection using AlphaLISA was previously described, the detection of particles such as bacteria and viruses was not reported. In this work, we show for the first time the implementation of the AlphaLISA technology for the detection of a particulate antigen, i.e., Bacillus anthracis spores. Here, we show that an efficient particle immunoassay requires a high acceptor-to-donor ratio (>4:1). The results suggested that the high acceptor/donor ratio is required to avoid donor aggregation (“islands”) on the spore surface, hence facilitating donor/acceptor interaction. The developed assay enabled the detection of 10⁶ spores/mL spiked in PBS. We also demonstrate the development of a highly sensitive AlphaLISA assay for the detection of the main toxin component of anthrax, protective antigen (PA). The assay enabled the detection of 10 and 100 pg/mL PA in buffer and spiked naïve rabbit sera, respectively, and was successfully implemented in sera of anthrax-infected rabbits. To summarize, this study demonstrates that AlphaLISA enables detection of anthrax spores and toxin, utilizing short homogeneous assays. Moreover, it is shown for the first time that this technology facilitates the detection of particulate entities and might be suitable for the detection of other bacteria or viruses.     

VinaMPI: Facilitating multiple receptor high‐throughput virtual docking on high‐performance computers

The program VinaMPI has been developed to enable massively large virtual drug screens on leadership‐class computing resources, using a large number of cores to decrease the time‐to‐completion of the screen. VinaMPI is a massively parallel Message Passing Interface (MPI) program based on the multithreaded virtual docking program AutodockVina, and is used to distribute tasks while multithreading is used to speed‐up individual docking tasks. VinaMPI uses a distribution scheme in which tasks are evenly distributed to the workers based on the complexity of each task, as defined by the number of rotatable bonds in each chemical compound investigated. VinaMPI efficiently handles multiple proteins in a ligand screen, allowing for high‐throughput inverse docking that presents new opportunities for improving the efficiency of the drug discovery pipeline. VinaMPI successfully ran on 84,672 cores with a continual decrease in job completion time with increasing core count. The ratio of the number of tasks in a screening to the number of workers should be at least around 100 in order to have a good load balance and an optimal job completion time. The code is freely available and downloadable. Instructions for downloading and using the code are provided in the Supporting Information. © 2013 Wiley Periodicals, Inc.