Modification of 1-substituents in the 2-azabicyclo[2.1.1]hexane ring system; approaches to potential nicotinic acetylcholine receptor ligands from 2,4-methanoproline derivatives

Successful nucleophilic substitution at a methylene attached to the bridgehead (1-) position of the 2-azabicyclo[2.1.1]hexane ring system opens the way to construction of novel derivatives having a wider range of functional groups attached to the 1-position via a methylene "spacer" (including the beta-amino acid homologue of 2,4-methanoproline) and provides access to epibatidine analogues containing heterocyclic substituents and also to further homologation at the 1-position. Displacements with loss of a nucleofuge (e.g., loss of mesylate anion from the 1-mesyloxymethyl derivative) require thermal activation but proceed without the rearrangement initially anticipated in such a strained bicyclic ring system. A novel tricyclic carbamate intermediate 17 has been isolated; nucleophilic attack on 17 leads directly to the isolation of N-deprotected substitution products (with concomitant decarboxylation).     

Detection and determination of free and plasma protein-bound astemizole by thin-layer chromatography: a useful technique for bioavailability studies

A thin-layer chromatographic (TLC) procedure has been developed for the determination of astemizole in plasma as the free and as protein-bound substance. The detection and quantification were performed without using internal standards. In earlier described methods for the estimation of astemizole by high-performance liquid chromatography and radioimmunoassay, only free levels in plasma were quantified, at 3.3% of the total astemizole, with the remaining 96.7% bound to plasma protein and tissue. Our method employs proteolysis of plasma proteins by incubating plasma for 2 h in pepsin. After proteolysis the astemizole is extracted, and a known amount of the extract is spotted on precoated silica gel F 254 plates. Astemizole was quantified using a Shimadzu CS-930 dual-wavelength TLC scanner. The method provides a direct estimate of total astemizole present in the plasma.     

Iron wheels on silicon: wetting behavior and electronic structure of adsorbed organostannoxane clusters

Atomic force microscopy and synchrotron radiation (SR) spectroscopy have been used to study the wetting behavior and electronic structure of thin films of a novel organometallic cluster--[BuSn(O)OC(O)Fc]6 ("Fc" = ferrocenyl)--on silicon substrates. This cluster comprises six ferrocene units connected to a stannoxane central core--"an iron wheel on a tin drum" (V. Chandrasekhar; et al. Angew. Chem., Int. Ed. 2000, 39, 1833). Thin films spin-cast onto native oxide-terminated silicon readily dewet the substrate. We have utilized advanced image analysis techniques based on Minkowski functionals to provide a detailed quantitative analysis of the morphology of the stannoxane overlayers. This analysis shows that the dewetting patterns are rather far removed from those expected to arise from a simple Poisson distribution of centers, and we discuss the implications of this finding in terms of nucleated and spinodal dewetting. Variations in both the surface roughness and the in-plane correlation length have been followed as a function of annealing time to probe the surface dewetting dynamics. SR valence band photoemission illustrates that the highest occupied molecular orbital (HOMO) of the cluster is found 2 eV below the Fermi level. Fe 2p --> 3d and Sn 3d --> 5p resonant photoemission spectroscopy have been used to enhance the cross sections of the partial density of states associated with the Fe and Sn atoms. Sn atoms make a large contribution to the HOMO of the cluster, whereas the Fe atoms are associated with an electronic environment seemingly very similar to that in the "parent" ferrocene molecule.     

Extractive Determination of Vanadium in Fungi Samples

A new reagent system has been reported for the extractive separation and simultaneous spectrophotometric de termination of vanadium (V). The method is based on the formation of a water in soluble blue‐violet V(V) complex with N‐hydroxy‐N‐m‐tolyl‐N′‐phenylbenzamidine (HTPBA), and neutral surfactant Triton X‐100 into chloroform over an acidity range of 1.0–10.0 M acetic acid. The complex shows a broad absorption maximum at 570 nm, when measured against a chloroform blank. The λ_max (570 nm) of the complex and that of re agent (313 nm) are well separated, hence the excess of the reagent does not interfere in the spectrophotometric de termination of the metal. The molar absorptivity (?) of the complex is (4.74) × 10³ 1 mol^?1 cm^?1. The linearity of the calibration curve is followed between 0.5–12.0 μg mL^?1 with slope, intercept and correlation coefficient of 9.16× 10^?2, 4.5 × 10^?3 and 0.999, respectively. The detection limit of the method is 45 μgl^?1. The proposed re agent system provides significantly higher tolerance limit for iron (500 μg mL^?1) and also various metalions commonly associated with vanadium did not interfere. The method was applied for the deter mi nation of vanadium content of three samples i.e. Spirogyra, Puccinia and Riccia.     

TRYPTOPHAN PROTECTION OF PHAGE FROM ULTRAVIOLET IRRADIATION

Abstract— Bacteriophage SP02c12 and its isolated DNA were irradiated at 254 nm in tryptophan solutions. At a concentration of 10 m M , the amino acid exerted a protective effect on intact virus. The magnitude of this effect depended upon the length of time elapsed between mixing and irradiation. No protection was observed for solutions irradiated immediately after mixing. Tryptophan did not have a significant effect on UV sensitivity of the isolated viral DNA. No covalent crosslinking of tryptophan to DNA was observed.     

Solvent extraction and spectrophotometric including graphite furnace atomic absorption determination of molybdenum in the environment

A selective and sensitive method for the extraction and microgram determination of molybdenum (VI) with hydroxamic acid as yellow molybdenum-hydroxamate complex from acidic medium is described. The molybdenum-PCPPSAHA complex has _max 388 nm, molar absorptivity 5.0 × 10³l mol^–1 cm^–1. The system obeys Beer's law in the range of 1–28 g/ml of molybdenum(VI). Sandell's sensitivity is 0.0192 g cm² and stoichiometry of the complex is 12, molybdenum: PCPPSAHA while mixed complex molybdenum-PCPPSAHA-morin has _max 400 nm and molar absorptivity 5.9 × 10³lmo1^–1 cm^–1 and stoichiometry of the complex is 121.The molybdenum is determined by graphite furnace atomic absorption spectrophotometry after directly pipetted the extract into the furnace which increases the sensitivity 20 fold.     

N-Mannich bases of benzimidazole as a potent antitubercular and antiprotozoal agents: Their synthesis and computational studies

Abstract

This article dealing with the microwave assisted synthesis of N-Mannich bases of pyridine clubbed with two different benzimidazole cores with their micromolar biological potency. All the synthesized compounds were evaluated for their in-vitro antibacterial, antimycobacterial and antiprotozoal potency. One of the final compound was found to be most active against M. tuberculosis (MIC = 3.125?µM) in the primary screening. N-Mannich bases of benzimidazole with pyridine-3-amine and 5-methyl-pyridine-2-amine showed potency against L. mexicana and T. cruzi respectively with IC₅₀ value 0.25 and 1.02?µg/mL. Compound 4a showed good binding energy in the active pocket of receptor (PDB: 4cod) with ?11.013 docking score. The stability of docked complex was validated by performing Molecular dynamics (MD) up to 20?ns simulation time. In silico ADME parameters and toxicity predicted that the active compounds belong to the Class IV GHS with LD₅₀ value 1360?mg/kg and hence found to be mildly toxic.     

Patenting computer-designed peptides

The problem of designing new peptides that possess specific properties, such as bactericidal activity, is of wide interest. Recently, attention has focused on the use of Computer-Aided Molecular Design techniques in parallel with more traditional 'synthesise and test' methods. These techniques may typically use Genetic Algorithms to optimise molecules based on Neural Network models that predict activity. In this paper we describe a successful application of this Molecular Design methodology that has resulted in novel bactericidal peptides of real value. A key issue for commercial utilisation of such results is the ability to protect the intellectual property rights associated with the discovery of new molecules. Typically peptide patents use structural templates of amino acid hydrophobicity-hydrophilicity that define highly regular peptide patent spaces. In an extension of established patenting practice we describe a patent application that uses a Neural Net predictive model to define the regions of peptide space that we claim within the patent. This formalism makes no a priori assumptions about the regularity of the patent space. A preliminary comparative investigation of the shape and size of this and other bactericidal peptide patent spaces is conducted.