title: Self-immolative entities for the enhanced disclosure of electrophilic species
Creators: name: Gavriel, Alexander
Publisher: name: University of Reading
Year: 2022

description: 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.