Abstract
Peroxynitrite, as a member of short-lived reactive oxygen species, plays an important role in biological systems. Its balance is related to the origin and development of diseases. Meanwhile, fluorescence detection is a low-cost and easy-operated method and exhibits good sensing performance in biological systems and great potential for the development of theranostic systems. So, it is meaningful to design fluorescent probes and use fluorescence spectra to detect and track peroxynitrite in order to further explore its nature and function in biological cycles and pathology.A brief introduction of fluorescence and its mechanism are covered in the first chapter. In the same chapter, the design principles of typical turn-on probes and related mechanisms are also explained. As the main target analyte in this thesis, peroxynitrite and the common receptors for targeting this species are also introduced. Besides, as the main fluorophore used in the probes designed in this thesis, the naphthalimide fluorophores are also exemplified.
In Chapter 2, at first, a coumarin-based probe and a naphthalimide-based probe respectively with a boronate ester group were obtained. Based on their excellent sensing performances, a FRET platform was constructed. However, the FRET process did not work. So, the remaining section in this chapter discusses the potential reasons for the failure of this FRET platform.
Chapter 3 focuses on a successful developed ICT-based probe consisting of a naphthalimide fluorophore and isatin receptor system. Here, the main drawback of naphthalimide-based fluorescent probes is addressed. The ACQ effect of the probe lowers the sensing performance of the probe resulting in reduced fluorescence responses. Finally, PEG encapsulation was used to improve solubility and optimize the probe. Due to this modification, the fluorescence of the probe was improved, and it could be used to image exogenous and endogenous peroxynitrite in live cells.
The design a peptide modified naphthalimide-isatin system instead of PEG modification was discussed in Chapter 4. Several synthesis routes were designed and attempted, however, due to the difficulties encountered for the synthesis and purification, the final peptide-modified probe was not obtained.
Based on the work of Chapter 4, carbon dots were used to modify the naphthalimide-isatin system to construct a FRET platform successfully in Chapter 5. Solution bases analysis of this self-assembled probe indicated that the system exhibited excellent fluorescence properties. In addition, the cell imaging experiments indicated the excellent ability of the probe to image exogenous and endogenous ONOO- in live cells, which indicates the potential application in detecting ONOO- in liver injury models.
In brief, this thesis describes the synthesis and evaluation of highly selective naphthalimide-based fluorescent probes to detect peroxynitrite. Using molecular modification and nanoparticle modification to overcome the solubility problem associated with naphthalimide fluorophores resulted in probes with excellent sensing performance suitable for cell imaging.
| Date of Award | 11 Oct 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Tony James (Supervisor) & Steven Bull (Supervisor) |