The Design and Application of Bis-Urea Derived Supramolecular Gelators

Abstract

A series of amino-acid derived bis-urea gelators were synthesised, some of which show strong gelation in a wide variety of solvents. The gels were probed at the molecular, microscopic and macroscopic levels to gain insights into the gelation behaviour observed. Mixtures of different gelators also result in gels, some of which show different fibre morphologies and X-ray powder patterns to the pure gelators. The series was extended to include fluorescent 1- and 2-pyrenylalanine derived gelators and the fluorescence behaviour of the gels in solution, the gel state, in mixed gels and with the addition of anions was investigated. Tetrabutylammonium-acetate was found to disrupt urea-hydrogen bonding leading to the break-down of the gels, a process which was followed by NMR spectroscopy, rheometry and fluorescence spectroscopy. Two gelators were used to template the formation of porous polymers which SEM and gas adsorption studies show reflect the different fibre morphologies observed in the gels.

The use of supramolecular gels as a medium for controlling the crystallisation of pharmaceutical compounds was developed. Proof of principle for the growth of a wide range of pharmaceutical compounds from a variety of different gels was demonstrated. The supramolecular nature of the gels was exploited by using anions to break down the gels in order to recover the crystals. Comparison of crystals grown from gels with those grown from solution highlighted a number of differences in crystal form, habit and stability. Gelators which mimic the chemical functionality of the drug compound being crystallised were synthesised. A study investigating the crystallisation of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) showed some differences in polymorphism when crystallised from a gel designed to mimic ROY compared to generic gels. A placement with the particle science group at GSK explored the potential of supramolecular gels for use in early stage screening of pharmaceutical compounds in an industrial setting.