Ashok L. Cholli

Synthesis, Characterization and In Vitro Anti-invasive Activity Screening of Polyphenolic and Heterocyclic Compounds

Invasion is the hallmark of malignant tumors, and is responsible for the bad prognosis of the untreated cancer patients. The search for anti-invasive treatments led us to screen compounds of different classes for their effect in an assay for invasion. Thirty-nine new compounds synthesized in the present study along with 56 already reported compounds belonging mainly to the classes of lactones, pyrazoles, isoxazoles, coumarins, desoxybenzoins, aromatic ketones, chalcones, chromans, isoflavanones have been tested against organotypic confronting cultures of invasive human MCF-7/6 mammary carcinoma cells with embryonic chick heart fragments in vitro. Three of them (a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin) inhibited invasion at concentrations as low as 1 microM; instead of occupying and replacing the heart tissue within 8 days, the MCF-7/6 cells grew around the heart fragments and left it intact, when treated with these compounds. At the anti-invasive concentration of 1 microM, the three compounds did not affect the growth of the MCF-7/6 cells, as shown in the sulforhodamine B assay. Aggregate formation on agar was not stimulated by any of the three anti-invasive compounds, making an effect on the E-cadherin/catenin complex improbable. This is an invasion suppressor that can be activated in MCF-7/6 cells by a number of other molecules. Our data indicate that some polyphenolic and heterocyclic compounds are anti-invasive without being cytotoxic for the cancer cells.

Nanoreactors for the enzymatic synthesis of conducting polyaniline

The mechanistic role of template in the enzymatic synthesis of conducting polyaniline has been investigated using micelles and DNA as ionic templates. These studies show the existence and importance of a molecular local environment where the pH and charge density near the template molecule is different form that of the bulk solution. This local environment serves as a type of nanoreactor that ultimately controls the type of polyaniline that is produced enzymatically. When DNA is used as the template, an electro-responsive polyaniline/DNA complex is formed where the conformation of the DNA may be controlled through the electronic state of the polyaniline.

Synthesis and Properties of a Soluble Polythiophene Derivative with a Urethane Side Chain

Abstract A solution processible thiophene polymer with a hydrogen-bond-forming urethane group in the side chain, viz., poly[2-(3-thienyl)ethanol n-butoxycarbonylmethylurethane] (PURET), has been synthesized. The polymer is soluble in a wide variety of solvents such as chloroform, dimethylsulfoxide, N-methylpyrrolidone, and trifluoroacetic acid among others. Optical quality thick films are obtained by solution casting. The presence of extensive hydrogen bonding is established with the help of temperature-dependent infrared spectroscopy. NMR spectroscopic study indicates the presence of about 33% regio-isomeric defects in the polymer. The polymer forms yellow-colored solutions (λmax = 430 nm) in most of the organic solvents, while in trifluoroacetic acid the polymer is oxidized and exhibits an additional band with an absorption maximum at around 780 nm. The conductivity of the polymer is in the order of 1 S/cm.

PHOTOINDUCED SURFACE RELIEF GRATINGS ON AZOCELLULOSE FILMS

Surface relief gratings (SRG) on films of azobenzene–modified cellulose (azocellulose) with ultrahigh molecular weight were holographically recorded in a single step. Surface modulation depth of the SRGs increased with the degree of substitution (DS) of the azobenzene chromophores in the cellulose as well as with the grating spacing. Large surface modulations over 500 nm on all samples were obtained with a grating spacing of 4 μm. A linear increase of photoinduced birefringence with the azobenzene chromophore concentration in these photodynamic polymers was also observed. The maximum birefringence of 0.11 was achieved for an azocellulose polymer with a DS of 0.99. †Deceased.

Synthetic and novel biocatalytic resolution studies on (±)-5/6/7-acetoxy-4-aryl-3,4-dihydrocoumarins

Eleven (+/-)-5/6/7-acetoxy-4-aryl-3,4-dihydrocoumarins have been synthesised in two steps starting from the coupling of cinnamic acid/substituted cinnamic acid with appropriate phenols, followed by acetylation in 50-83% overall yields. All hydroxy- and acetoxycoumarins were unambiguously identified on the basis of their spectral data. Candida antarctica lipase-catalysed deacetylation of these racemic acetoxydihydrocoumarins in dioxane occurred with moderate enantioselectivity. This is one of the rare examples of resolution using phenolic ester moiety as a remote handle for chiral recognition by a lipase.

VARIATION IN THE STRUCTURE OF CONDUCTING POLYANILINE WITH AND WITHOUT THE PRESENCE OF TEMPLATE DURING ENZYMATIC POLYMERIZATION: A SOLID-STATE NMR STUDY

ABSTRACT Polyanilines (PANI) were synthesized from peroxidase-catalyzed polymerization of aniline with and without the presence of a template in the aqueous buffer solution of pH 4.3. The template used was poly(vinylphosphonic acid) (PVP). Solid-state 13C and 15N CP/MAS NMR techniques were applied to characterize the structure of polyaniline in its self-doped conducting, dedoped base, and redoped conducting form of PANI. The charge distribution along the polymer backbone in the protonated form of the polyaniline is also discussed. The structural features exhibited by a template assisted enzymatically synthesized PANI is the result of linear 1,4-coupling of aniline moiety while the PANI synthesized in the absence of template contains both 1,2- and 1,4-coupled products. Solid-state NMR studies on the enzymatically-synthesized polyaniline with the aid of template (PANI-PVP) confirmed the formation of a linear polymer chain containing alternate benzenoid-quinoid repeat units. The dedoped form is in the emeraldine base state of the polyaniline. The structural features in the spectra of the PANI synthesized without a template are quite different. Solid-state NMR data suggest that the PANI synthesized without aid of the template contains structures having C-C and C-N-C coupled products indicating the presence of branching in the polymer chain.

Biocatalytic approaches for synthesis of conducting polyaniline nanoparticles

A biocatalytic approach has been developed to synthesize conducting polyaniline (PANI) nanoparticles. The method involves the formation of nanocomposites of PANI and poly(acrylic acid) (PAA) by polymerizing aniline (AN)-camphorsulfonic acid (CSA) macromonomer (AN/CSA) using a biocatalyst in the presence of template PAA. The second step involves the separation of PANI polymers from PAA and CSA in the nanocomposites. The formation of PANI nanoparticles by this two-step approach is studied by transmission electron microscopy (TEM). High-resolution solution 13C NMR and UV/visible spectroscopic techniques have been used to characterize the formation of conducting PANI chains by the enzymatic method.

Highly efficient diastereoselective biocatalytic acylation of a diastereotopic furanose diol and synthesis of key intermediates for amino derivatized bicyclonucleosides

The selectivity of Candida antarctica lipase has been demonstrated and employed in the manipulation of a diastereotopic furanose diol as the key step in the synthesis of a novel bicyclo 3-amino-3-deoxy furanose derivative, which is an important intermediate for the synthesis of bicyclic analogs of AZT. The asymmetrization of the diol has been achieved with preferred formation of a monoacylated product with 100% diastereoselectivity. An efficient synthesis of an intermediate in the synthesis of amino derivatized bicyclonucleosides is also described, two such novel compounds containing cycloamino residues have been prepared.

Fast detection of anionic components in sugar and wine samples using a novel device based on capillary zone electrophoresis

Abstract The quality of sugar and wine are dependent on the processing steps that are involved to remove extraneous components of starting materials, sugar canes, sugar beets and grapes. Many of the residual components present in the final product such as organic acids (malate, oxalate, formate, acetate, pyroglutamate, etc.) and inorganic ions (nitrate, nitrite, chloride, sulfate, sodium, potassium, calcium, etc.) may influence on the quality. There is a need for the development of new devices that can detect these multiple species in near-real time so that each of the processing steps can be monitored effectively. Preliminary data are presented here on the applicability of such a near real-time detection device that is based on the principles of capillary zone electrophoresis to monitor organic acid and anionic impurities in white sugar and wine samples at concentration levels that are required to meet national and international standards. Applicability of this device to monitor water pollutants is also discussed.

Enzyme-catalyzed polymerization of 8-hydroxyquinoline-5-sulfonate by in situ nuclear magnetic resonance spectroscopy

In this report, we describe the use of in situ NMR spectroscopy to elucidate the mechanism of horseradish peroxidase-catalyzed oxidative free-radical coupling of phenols. We demonstrate the potential of the technique for the polymerization of 8-hydroxyquinoline-5-sulfonate (HQS). Based on the structural changes, we establish the involvement of ortho- and para-position protons (to the hydroxyl group) in the oxidative free-radical coupling polymerization with their relative preferences. For example, in HQS, we establish that the positions 2, 4, and 7 are involved in the chemical bonding with the order of preference being 7 ≥ 2 > 4. Analyses of 13 C-NMR data suggest the formation of C-C- and C-O-C-type coupling bonds during enzymatic polymerization.