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New materials for biological applications prepared by olefin metathesis reactions

Citation

Maynard, Heather Dawn (2001) New materials for biological applications prepared by olefin metathesis reactions. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:03202014-141427716

Abstract

With the advent of well-defined ruthenium olefin metathesis catalysts that are highly active and stable to a variety of functional groups, the synthesis of complex organic molecules and polymers is now possible; this is reviewed in Chapter 1. The majority of the rest of this thesis describes the application of these catalysts towards the synthesis of novel polymers that may be useful in biological applications and investigations into their efficacy.

A method was developed to produce polyethers by metathesis, and this is described in Chapters 2 and 3. An unsaturated 12-crown-4 analog was made by template- directed ring-closing metathesis (RCM) and utilized as a monomer for the synthesis of unsaturated polyethers by ring-opening metathesis polymerization (ROMP). The yields were high and a range of molecular weights was accessible. In a similar manner, substituted polyethers with various backbones were synthesized: polymers with benzo groups along the backbone and various concentrations of amino acids were prepared. The results from in vitro toxicity tests of the unsubstituted polyethers are considered.

The conditions necessary to synthesize polynorbornenes with pendent bioactive peptides were explored as illustrated in Chapter 4. First, the polymerization of various norbornenyl monomers substituted with glycine, alanine or penta(ethylene glycol) is described. Then, the syntheses of polymers substituted with peptides GRGD and SRN, components of a cell binding domain of fibronectin, using newly developed ruthenium initiators are discussed.

In Chapter 5, the syntheses of homopolymers and a copolymer containing GRGDS and PHSRN, the more active forms of the peptides, are described. The ability of the polymers to inhibit human dermal fibroblast cell adhesion to fibronectin was assayed using an in vitro competitive inhibition assay, and the results are discussed. It was discovered that the copoymer substituted with both GRGDS and PHSR peptides was more active than both the GRGDS-containing homopolymer and the GRGDS free peptide.

Historically, one of the drawbacks to using metathesis is the removal of the residual ruthenium at the completion of the reaction. Chapter 6 describes a method where the water soluble tris(hydroxymethyl)phosphine is utilized to facilitate the removal of residual ruthenium from RCM reaction products.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Chemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Grubbs, Robert H.
Thesis Committee:
  • Bercaw, John E.
  • Tirrell, David A.
  • Gray, Harry B.
  • Imperiali, Barbara
  • Hubbell, Jeffrey A.
Defense Date:5 July 2000
Record Number:CaltechTHESIS:03202014-141427716
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:03202014-141427716
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8153
Collection:CaltechTHESIS
Deposited By: John Wade
Deposited On:20 Mar 2014 22:30
Last Modified:20 Mar 2014 22:30

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