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Luminescent europium(III) probes for time-resolved detection of peroxynitrite and bioactive anions
thesisposted on 28.07.2021, 15:02 by Colum Breen
A series of novel europium(III) complexes have been designed and synthesised for the purpose of: 1) the selective detection of peroxynitrite; and 2) the reversible binding of monophosphate anions. In Chapters 2 and 3, the development of a luminescent probe, Eu.BOH2, for selectively detecting peroxynitrite (ONOO⁻) in biological media and living cells is presented. This probe is based on a luminescent Eu(III) complex bearing an 8-alkoxyquinoline group functionalised with a phenylboronic acid. Upon rapid and selective oxidation of the phenylboronic acid residue by peroxynitrite, the resulting 8-hydroxyquinoline unit is unable to sensitise Eu(III) emission, resulting in a dramatic decrease in luminescence. The long-lived emission of the probe allowed for time-resolved measurements, significantly increasing signal-to-noise by completely removing short-lived autofluorescence from biomolecules. The probe was applied to the detection of ONOO⁻ in cellulo, during non-thermal atmospheric plasma treatment using the clinical device, kINPen. Furthermore, Eu.BOH2 was utilised to measure ONOO⁻ concentrations and lifetimes in human blood and human serum, following treatment with the microsecond DBD plasma device.
Using the structural insights gained in the work described in Chapters 2 and 3, Chapter 4 presents the synthesis and photophysical characterisation of three novel boronic acid bearing europium(III) complexes, [Eu.pBOH2]+, [Eu.mBOH2]+, and [Eu.oBOH2]+. These complexes were used to bind reversibly to monophosphate anions (e.g. AMP) and signal their presence by an increase in emission intensity and lifetime. Chapter 5 focuses on an investigation of the affinities of these complexes towards different monophosphate anions and explores the potential application of two of these anion receptors in monitoring specific enzyme reaction in real-time. it was demonstrated that two of the receptors, [Eu.pBOH2]+ and [Eu.mBOH2]+ could be utilised to monitor the activity of phosphodiesterase and sulfotransferase enzymes in real-time, by reporting the production of AMP and PAP anions, respectively. Such receptors have high potential in high throughput assays for monitoring these enzymes and screening of potential inhibitors.
Loughborough University funded Mini-CDT