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Biomedical subjects

Gregory N Tew

Publications and source records attributed to Gregory N Tew.

24 records · Page 2Linked to original sources

Rheological studies of PLLA-PEO-PLLA triblock copolymer hydrogels.

We report detailed rheological data on aqueous gels formed from triblock copolymers of L-lactide and ethylene oxide including the dependence of the viscoelastic moduli on frequency and applied stress of these systems for the first time. We are able to create strong gels with elastic moduli greater than 10,000 Pa, which is an order of magnitude higher than previously achieved with related biocompatible physically associated gels of similar chemistry. Moreover, the value of the elastic modulus strongly depends on PLLA block length, offering a mechanism to control the mechanical properties as desired for particular applications. At the gel point, we observe scaling that is characteristic of a percolated network, G' approximately G" approximately omega(Delta), but with an exponent that is lower than predicted by percolation, Delta=0.36. Our results have implications for the design of new materials for soft tissue engineering, where native tissues have moduli in the kPa range.

Biocompatible Materials↗

Theoretical study of helix formation in substituted phenylene ethynylene oligomers.

Theoretical investigations of the relative stabilities of helical vs extended forms of phenylene ethynylene oligomers established that MMFF molecular mechanics was more useful than AM1 or DFT for calculating helical structures and for estimating relative energies. At the level of MMFF, theory predicts that for o- or m-oligophenylene ethynylenes, helix formation is enthalpically favored for ester and ether-substituted oligomers. In contrast to simple electron-demand predictions, we predict that the position of substituents can make a substantial difference in the tendency to form helices.

Journal Article↗

Synthesis of alkoxy-substituted ortho-phenylene ethynylene oligomers.

[structure: see text] This Letter describes the first published synthesis and characterization of alkoxy-substituted ortho-phenylene ethynylene (o-PE) oligomers. Sonogashira coupling was used to assemble discrete chain lengths, using a key monomer with orthogonal groups. Deprotection or activation allowed stepwise coupling to produce the dimer, trimer, and tetramer, while convergent coupling of appropriately substituted trimers produced the hexamer. The placement of alkoxy side chains renders these oligomers soluble in common organic solvents permitting solution characterization. Absorption and emission spectra of the trimer, tetramer, and hexamer are provided.

Alkynes↗

New poly(phenyleneethynylene)s with cationic, facially amphiphilic structures.

Polymers based on meta substituted phenylene ethylene are prepared with patterned polar and nonpolar groups to favor an extended conformation. These polymers were characterized at the air-water interface by Langmuir techniques and found to form stable monolayers with an extended conformation based on molecular models. In addition, these polymers show phospholipid membrane activity as measured by induced leakage of calcein from large unilamellar vesicles. These polymers represent new facially amphiphilic structures which are cationic in nature and surface active.

Alkynes↗

De novo design of biomimetic antimicrobial polymers.

The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor with both fundamental and practical implications. Recently, a number of nonnatural peptides with designed sequences have been elaborated to provide biologically active structures; in particular, facially amphiphilic peptides built from beta-amino acids have been shown to mimic both the structures as well as the biological function of natural antimicrobial peptides such as magainins and cecropins. However, these natural peptides as well as their beta-peptide analogues are expensive to prepare and difficult to produce on a large scale, limiting their potential use to certain pharmaceutical applications. We therefore have designed a series of facially amphiphilic arylamide polymers that capture the physical and biological properties of this class of antimicrobial peptides, but are easy to prepare from inexpensive monomers. The design process was aided by molecular calculations with density functional theory-computed torsional potentials. This new class of amphiphilic polymers may be applied in situations where inexpensive antimicrobial agents are required.

Anti-Bacterial Agents↗

Poly(3-hydroxyalkanoate)s functionalized with carboxylic acid groups in the side chain.

Biodegradable polyesters represent an important class of materials, and one subset of these polymers are the bacterially produced poly(3-hydroxyalkanoate)s (PHA), a bacterially produced material. These polymers are very hydrophobic, and chemical methods to increase their hydrophilicity will ultimately lead to new applications. Many copolymers of PHA are known that contain simple, nonpolar functionality in the side chain, and we explored the conversion of side-chain olefins to carboxylic acids under conditions that minimize molecular weight degradation. With the use of osmium tetraoxide and oxone, the conversion proceeded to completion with little backbone degradation, which was confirmed with NMR, IR, and gel permeation chromatography (GPC). The solubility character of the polymer before and after reaction is very different, and several solvents were explored including acetone, tetrahydrofuran (THF), and water.

Acids↗