Metal-ion-mediated tuning of duplex DNA binding by bis(2-(2-pyridyl)-1H-benzimidazole)

Studies of double-stranded-DNA binding have been performed with three isomeric bis)2-(n-pyridyl)-1H-benzimidazole)s (n = 2, 3, 4). Like the well-known Hoechst 33258, which is a bisbenzimidazole compound, these three isomers bind to the minor groove of duplex DNA. DNA binding by the three isomers was investigated in the presence of the divalent metal ions Mg2+, Co2+, Ni2+, Cu2+, and Zn2+. Ligand-DNA interactions were probed with fluorscence and circular dichroism spectroscopy. These studies revealed that the binding of the 2-pyridyl derivative to DNA is dramatically reduced in the presence of Co2+, Ni2+, and Cu2+ ions and is abolished completely at a ligand/metal-cation ratio of 1:1. Control experiments done with the isomeric 3- and 4-pyridyl derivatives showed that their binding to DNA is unaffected by the aforementioned transition-metal ions. The ability of 2-(2-pyridyl)benzimidazole changes of the ligand associated with ion chelation probably ledto such unusual binding results for the ortho isomer. The addition of ethylenediaminetetraacetic acid (EDTA) reversed the effects completely.

Characterization of the interactions of a polycationic, amphiphilic, terminally branched oligopeptide with lipid A and lipopolysaccharide from the deep rough mutant of Salmonella minnesota

The lipid A and lipopolysaccharide (LPS) binding and neutralizing activities of a synthetic, polycationic, amphiphilic peptide were studied. The branched peptide, designed as a functional analog of polymyxin B, has a six residue hydrophobic sequence, bearing at its N-terminus a penultimate lysine residue whose alpha- and epsilon-amino groups are coupled to two terminal lysine residues. In fluorescence spectroscopic studies designed to examine relative affinities of binding to the toxin, neutralization of surface charge and fluidization of the acyl domains, the peptide was active, closely resembling the effects of polymyxin B and its nonapeptide derivative; however, the synthetic peptide does not induce phase transitions in LPS aggregates as do polymyxin B and polymyxin B nonapeptide. The peptide was also comparable with polymyxin B in its ability to inhibit LPS-mediated IL-l and IL-6 release from human peripheral blood mononuclear cells. The synthetic compound is devoid of antibacterial activities and did not induce conductance fluxes in LPS-containing asymmetric planar membranes. These results strengthen the premise that basicity and amphiphilicity are necessary and sufficient physical properties that ascribe endotoxin binding and neutralizing activities, and further suggest that antibacterial/membrane perturbant and LPS neutralizing activities are dissociable, which may be of value in designing LPS-sequestering agents of low toxicity.

On the performance analysis of a class of neuron circuits

A new performance metric, Peak-Error Ratio (PER) has been presented to benchmark the performance of a class of neuron circuits to realize neuron activation function (NAF) and its derivative (DNAF). Neuron circuits, biased in subthreshold region, based on the asymmetric cross-coupled differential pair configuration and conventional configuration of applying small external offset voltage at the input have been compared on the basis of PER. It is shown that the technique of using transistor asymmetry in a cross-coupled differential pair performs on-par with that of applying external offset voltage. The neuron circuits have been experimentally prototyped and characterized as a proof of concept on the 1.5 mu m AMI technology.

Photoswitchable multivalent sugar ligands: Synthesis, isomerization, and lectin binding studies of azobenzene-glycopyranoside derivatives

Coating of azobenzene chromophore with multivalent sugar ligands has been accomplished. Such sugar coating allows the study of the isomerization properties of this chromophore in aqueous solutions. The predominantly cis-isomer-containing photostationary state (PS) mixture of these azobenzene derivatives is found to be stable for hours. The rate constants for their isomerization, as well as the Arrhenius activation energies, are determined experimentally. An assessment of the lectin binding properties of the lactoside bearing isomeric azobenzene derivatives, by isothermal calorimetric methods, reveals the existence of an unusual cooperativity in their binding to lectin peanut agglutinin. Thermodynamic parameters evaluated for the trans and the PS mixture are discussed, in detail, for the lactoside bearing bivalent azobenzene derivative.

On the performance analysis of a class of neuron circuits

A new performance metric, Peak-Error Ratio (PER) has been presented to benchmark the performance of a class of neuron circuits to realize neuron activation function (NAF) and its derivative (DNAF). Neuron circuits, biased in subthreshold region, based on the asymmetric cross-coupled differential pair configuration and conventional configuration of applying small external offset voltage at the input have been compared on the basis of PER. It is shown that the technique of using transistor asymmetry in a cross-coupled differential pair performs on-par with that of applying external offset voltage. The neuron circuits have been experimentally prototyped and characterized as a proof of concept on the 1.5 mu m AMI technology.

Stabilisation and characterisation of N,N′-dibenzylidene-o-phenylenediamine as a copper(I) perchlorate complex

QUITE OFTEN, metal ions profoundly affect the condensation of carbonyl compounds with primary amines to form Schiff bases as well as their subsequent reactions[I-4]. Condensation of benzaldehyde with o-phenylenediamine (opd) in glacial acetic acid[5] or in absolute alcohol[6] gives benzimidazole derivative, 1-benzyl-2-phenylbenzimidazole (bpbi). In this reaction, the Schiff base N,N'-dibenzylidene-o-phenylenedianfme (dbpd) has been postulated as an intermediate, which cyclises to give bpbi. It was found that the reaction of opd in presence of copperO1) perchlorate with benzaldehyde gave dbpd complex of copper(l) perchlorate instead of bpbi.

Synthetic investigations in the sesamin group - Part I. Synthesis of samin, a degradation product of sesamolin

Ethylα-bromovinylacetate (VII) was condensed with the sodio derivative of ethyl piperonoylacetate (VIII) to give diethylα-vinyl-α′-piperonoylsuccinate (IX). The latter on reduction with lithium aluminium hydride furnished the triol (X), which underwent smooth cyclisation with 1% ethanolic hydrogen chloride to 2-(3′, -methylenedioxyphenyl)-hydroxymethyl-4-vinyltetrahydrofuran (XIa). The structure of XIa was established by Oppenauer oxidation to an aldehyde. Ozonolysis of XIa afforded samin (I).

Boundary layer on a flat plate with suction

In this paper we have discussed the boundary layer on a plate with suction. The problem is solved near the leading edge as well as far downstream. A linear suction law is assumed near the leading edge for simplicity, whereas no restriction is placed on the suction law in the region downstream. An explict expression for boundary layer thickness in terms of suction speed and distance from leading edge is derived. It is found that the thickness of the boundary layer depends on the derivative of the suction speed. The skin friction also has been evaluated. Though near the leading edge a linear law of suction is assumed, the method used in the paper can be easily generalised for any other power law, for example, we may use a power series expansion for the function defining the suction velocity.

Click chemistry inspired synthesis of ferrocene amino acids and other derivatives

This work reports the synthesis of a wide range of ferrocenyl-amino acids and other derivatives in excellent yield. Diverse amino acid containing azides were synthesized and ligated to ferrocene employing click reaction to access ferrocenyl amino acids. Chiral alcohols, esters, diols, amines containing azido group were tagged to ferrocene via click reaction to generate ferrocene derived chiral derivatives. A novel strategy for direct incorporation of ferrocene into a peptide and a new route to 1, 1′disubstituted ferrocene amino acid derivative are reported.

(Z)-2-(2-Isopropyl-5-methylphenoxy)-N`-(2-oxoindolin-3-ylidene)acetohydrazide

In the title Mannich base, C20H21N3O3, an isatin derivative of thymol the O-CH2-C(=O)-N(H)-N fragment connecting the aromatic and fused-ring systems is approximately planar, with the N-N single bond in a Zmconfiguration. The amino H atom of this N-N fragment is intramolecularly hydrogen bonded to the carbonyl O atom of the indolinone fused ring as well as to the phenoxy O atom of the aromat ring. The amino H atom of the indoline fused ring forms a hydrogen bond with the double-bond O atom of an adjacent molecule, this hydrogen bond giving rise to a linear chain motif.

Four-dimensional current algebra from Chern-Simons theory

We study an abelian Chern-Simons theory on a five-dimensional manifold with boundary. We find it to be equivalent to a higher-derivative generalization of the abelian Wess-Zumino-Witten model on the boundary. It contains a U(1) current algebra with an operational extension.

Synthesis based on cyclohexadienes. Part 34. A tandem cationic rearrangement-ene cyclisation route to 2-pupukeanone

A new strategy for the construction of the isotwistane skeleton is reported from easily available cyclohexadienes, which involves a one-pot cationic skeletal rearrangement and ene cyclisation of a bicyclo[2.2.2]octenone derivative and a cationic rearrangement of a tricyclo[5.3.0.0(4,8)]decane to a [4.3.1.0(3,7)]decane skeleton as the key steps in the synthesis of 2-pupukeanone.

Role of the environment in the interaction of nonintercalators with Z-DNA

Interaction of the DNA binding nonintercalators Netropsin, Distamycin and the mPD derivative with Z-DNA has been studied. It has been found that environmental factors like the solvent and added cations significantly modulate the interaction of these ligands with Z-DNA. However no definite Z to B transition in presence of these ligands was found in any case, in contrast to previously reported results (Ch. Zimmer, C. Marck and W. Guschlbauer, FEBS Lett. 154, 156-160 (1983)).

Plasticity in the primary binding site of galactose/N-acetylgalactosamine-specific lectins - Implication of the C-H center dot center dot center dot O hydrogen bond at the specificity-determining C-4 locus of the saccharide in 4-methoxygalactose recognition by jacalin and winged bean (basic) agglutinin I

It is currently believed that an unsubstituted axial hydroxyl at the specificity-determining C-4 locus of galactose is indispensable for recognition by galactose/N-acetylgalactosamine-specific lectins. Titration calorimetry demonstrates that 4-methoxygalactose retains binding allegiance to the Moraceae lectin jacalin and the Leguminosae lectin, winged bean (basic) agglutinin (WBA I). The binding reactions were driven by dominant favorable enthalpic contributions and exhibited significant enthalpy-entropy compensation. Proton NMR titration of C-methoxygalactose with jacalin and WBA I resulted in broadening of the sugar resonances without any change in chemical shift. The alpha-and beta-anomers of 4-methoxygalactose were found to be in slow exchange with free and lectin-bound states. Both the anomers experience magnetically equivalent environments at the respective binding sites. The binding constants derived from the dependence of NMR line widths on 4-methoxygalactose concentration agreed well with those obtained from titration calorimetry. The results unequivocally demonstrate that the loci corresponding to the axially oriented C-4 hydroxyl group of galactose within the primary binding site of these lectins exhibit plasticity. These analyses suggest, for the first time, the existence of C-H ... O-type hydrogen-bond(s) in protein-carbohydrate interactions in general and between the C-4 locus of galactose derivative and the lectins jacalin and WBA I in particular.

A formal synthesis of the perhydrogephyrotoxin

A short but uneventful formal synthesis of perhydrogephyrotoxin 3 from readily available tricyclo[5.2.1.0(2,6)]decane derivative 8 via the intermediacy of the cis-hydroindanone 13 is reported. This work constitutes further demonstration of the carbocycle-heterocycle equivalency theme in the synthesis of alkaloids.