Abstract/Summary

Novel self-immolative entities have been designed and synthesised for the disclosure of reactive electrophilic species. The disclosure systems described in this thesis were designed with the specific aims of increasing the stability of prototype self-immolative systems, amplifying the disclosure response via the degradation of dendritic frameworks and finally developing novel self-immolative solid state surfaces and liquid formulations for a disclosure spray device. The investigation into increasing the stability of a pre-existing self-immolative system was achieved by synthesising a library of low molecular weight disclosure systems whereby the electronic and steric effects of the reporter moiety were altered relative to the degradable carbamate linkage. The stability and kinetics of base-induced degradation of each self-immolative system was assessed by 1H NMR spectroscopic analysis and in addition crystalline carbamate model compounds featuring a naphthyl derivative were subjected to XRD analysis to provide detailed information on the steric effects of the reporter group upon the alignment of this unit with the carbamate bond. From this study it was apparent that the rate of 1,2- elimination appears to be more substantially affected by the nature of the reporter group. Furthermore, from the series of self-immolative disclosure systems synthesized, an ortho-methyl and a meta-nitro substituted reporter moiety was selected as the candidate for the disclosure of reactive alkylating agents, as it exhibited the optimum balance between stability and reactivity. The synthesis and degradation profiles of two novel self-immolative dendritic systems was investigated. The dendrons systems differed only in the positioning of the benzylic reporting tether, with the reporter moieties located in either the 2,4- or 2,6- position of an aniline core unit with respect to the degradable carbamate linkage. To obtain the self-immolative dendrons a different route to synthesise the trigger was employed; this involved complexation of the phosphine to borane thus decreasing the rate of unwanted oxidation. The stability and reactivity of the dendrons towards an electrophilic species was assessed by 1H NMR spectroscopic analysis and in the case of the 2,4-derivative the degradation profile was also assessed using UV-vis spectroscopy. Within this study it was also observed that with the addition of 10% D2O the rate of alkylation and elimination was significantly enhanced. With the addition of D2O a colour change observed noticeably faster in comparison to the small molecular weight self-immolative disclosure systems described in the previous section. Self-immolative materials for enhanced detection of reactive electrophilic species were also investigated. Attachment of a self-immolative system through carbene insertion was investigated insertion by irradiation of a trifluoromethyl phenyl diazirine, this approach was found unsuccessful because of multiple biproducts. Polymer end-capping of elastomeric polyurethane was also explored; however, alkylation was found unsuccessful. Physical adsorption of the self-immolative candidate described in Chapter 2 onto a polystyrene (30,000 g mol-1) film was explored successfully with visual disclosure of a reactive electrophilic species. Finally, the development of a novel formulation for use in disclosure sprays was investigated. The disclosure spray was also found to be successful visually in the disclosure of a reactive electrophilic species.