Lynne A. Samuelson

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.

Biologically derived water soluble conducting polyaniline

Abstract An enzymatic, polyelectrolyte (matrix) assisted polymerization of aniline that directly leads to the formation of water soluble, electrically conducting polyaniline is reported. This new biological route is advantageous in that it offers a mild (pH 4–5), benign, one pot synthesis where the desired product requires minimal purification prior to processing. UV-visnear-IR spectroscopy, FTIR, GPC and conductivity measurements all confirm that the eluctroactive and conducting form of polyaniline, similar to that which is traditionally chemically synthesized, is formed.

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.

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.

Molecular recognition between a biotinylated polythiophene copolymer and phycoerythrin utilizing the biotin-streptavidin interaction

Abstract The interaction of photoactive proteins with an electroactive matrix is valuable in leading to potential technological applications in opto-electronic signal transduction for optical displays, color mimicking, biosensor, and protein research applications. In this study, the Langmuir-Blodgett technique is used to couple these components through the well-known biotin-streptavidin complexation. Biotinylated copolymers of 3-substituted thiophenes have been synthesized both to enhance mechanical film integrity and to provide the electroactive matrix for attachment of the antennae protein, phycoerythrin. It has been determined that biotinylation of the thiopene copolymers improves their film forming properties and results in stable monolayers. Pressure-area isotherms indicate that protein interaction with the polymer monolayer is occuring with the streptavidin and phycoerythrin proteins. Fluorescene spectroscopy of transferred films confirms the presence of phycoerythrin in the final molecular assemblies. Each stage of protein binding to the biotinylated copolymer monolayer could be monitored through fluorescence microscopy at the air-water interface. These results suggest that this copolymer system is a promising material for integrating virtually any biotinylated macromolecular system to an electroactive matrix. In addition, this copolymer system may be “fine tuned” to maximize protein integration by varying the distance between biotin functionalities and/or the length of the biotin spacer arm.

Polydiacetylenes and analogies to inorganic semiconductors and graphite

Abstract The crystallography and one-dimensional electronic structure of polydiacetylenes (PDAs) stimulate a variety of chemical and physical studies. 13 C CP-MAS n.m.r. studies of the PDAs from PTS and TCDU as well as 1, 1, 4,-4-tetraphenylbutatriene establish the en-yne bond representation for TCDU and rule out a significant contribution from a butatriene form to the ground state at room temperature. The current status of third-order non-linear optical phenomena in PDAs and the conversion of PDAs to conductive materials by ion implantation is presented. Our anisotropic chemical modification of poly-DCH is conceptually distinguished from the usual charge transfer doping of non-crystalline polymers.

Peroxidase‐Catalyzed Polymerization of 1‐Hydroxypyrene

Abstract Peroxidase‐catalyzed polymerization of a hydroxy substituted polynuclear aromatic compound, 1‐hydroxypyrene, is reported. The fluorescence spectrum of the synthesized polymer shows a dramatic red shift compared to that of the monomer. The enzymatic polymerization of 1‐hydroxypyrene demonstrates the capability of peroxidase in catalyzing the oxidation of polynuclear aromatic molecules, and offers new possibilities for the design and synthesis of polymers with interesting electrical and optical properties in an environmentally friendly way.

Biotinylated Poly(3-Hexylthiophene-co-3-Methanolthiophene): A Langmuir Monolayer-Forming Copolymer

Abstract Copolymers of 3-substituted thiophenes have been synthesized by organosynthetic routes. The chemical synthesis of the copolymer was carried out by dehydrogenation of 3-hexylthiophene and 3-methanolthiophene. Attachment of biotin to the resulting copolymer, poly(3-hexylthiophene-co-3-methanolthiophene) [PMHT], is accomplished by room temperature esterification using N,N-dicyclohexylcarbodiimide (DCC) and 4-pyrrolidinopyridine as catalyst. The resulting copolymers have well-defined chemical and electronic structures and molecular weights. The biotinylated copolymer forms a stable monolayer at the air-water interface due to the polar groups along the polymer backbone.

Photo-fabrication of electroactive polymers for photonics

Abstract Novel azo chromophore containing polymers have been synthesized both chemically and enzymatically. Surface initiated mechanism for relief structure form ation on the azo polymer films have been studied for a high molecular weight azo functionalized poly(acrylic acid) by restricting the free surface in a controlled manner. Enzyme catalyzed poly(phenol) and polyaniline containing azo functional groups have also been synthesized and for the first time the feasibility of these biologically derived electroactive polymers for surface relief grating applications are undertaken.