Polymerisations of hydroxyacids performed by Candida rugosa lipase

Abstract

This thesis is describes the polymerisation of hydroxyacids catalysed by the Candida rugosa lipase (CRL). Chapter 1 involves a background introduction to enzymes in general and specifically lipases. Several commercial applications of lipases are discussed, followed by the use of lipases in the synthesis of polymeric materials. Chapter 2 covers the experimental work carried out on our system to determine the optimal conditions for the enzymatic reaction to take place. For CRL these are using hexane at 55 C. Several ω-hydroxyacids are investigated for the relative rates of reaction, using (^1)H NMR and GPC analytical techniques. The use of molecular sieves is evaluated, as is reprecipitation from hexane, to establish the optimal method for obtaining high molecular weight polymers. Chapter 3 includes a comparison of the six co-hydroxyacids which were used, and expresses the observation that CRL has a preference for the hydroxyacids with 8 and 9 carbons. There is an investigation into the sequence of the assembly of the polymer using deuterium labelled monomers, and several functionalised monomers are also polymerised. A comparison is made between the enzymatic and a chemically (Ti(0Bu)(_4)) catalysed process. Chapter 4 introduces molecular modelling studies, and docks 9-hydroxy- nonanoic acid into the cavity beyond the enzyme active site. Various potential affinity labels are designed to covalently modify the active site cavity, and are thus synthesised to determine if the polymerisation process can be inhibited. Finally in this Chapter an investigation into the stereospecificity of CRL is undertaken, using 10-hydroxy- undecanoic acid, and a binding mechanism between the enzyme and the substrate is proposed. Chapter 5 outlines the synthetic pathways to all of the materials which are synthesised in this thesis, and Chapter 6 describes the experimental routes to each of these materials.