The Library
Electron paramagnetic resonance techniques for pharmaceutical characterization and drug design
Tools
Vallotto, Claudio (2017) Electron paramagnetic resonance techniques for pharmaceutical characterization and drug design. PhD thesis, University of Warwick.
|
PDF
WRAP_Theses_Vallotto_2017.pdf - Submitted Version - Requires a PDF viewer. Download (7Mb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b3184138~S15
Abstract
This thesis aims to explore the applicability of Electron Paramagnetic Resonance (EPR) spectroscopy in the pharmaceutical field. EPR is a powerful biophysical tool that allows the detection and characterisation of paramagnetic species, such as free organic radicals and metal complexes. EPR is widely used across all disciplines but to date has been much underutilised in the pharmaceutical industry.
In the first part of this work, EPR techniques were applied to characterise the degradation products originating from irradiation sterilization of two common excipients, L-histidine and D-mannitol. Radicalic degradants can form as a result of several degradation pathways and industrial processes, including γ-radiation sterilization. A quantification of the radical species formed upon γ-irradiation was performed, indicating a much higher radical concentration for D-mannitol compared to L-histidine at pharmaceutically relevant irradiation doses. Cold irradiation analysis allowed the study of the low temperature stable species and their evolution into the r.t. stable ones. Three low temperature persistent radical species of D-mannitol were identified for the first time. The reactivity of the radicals in solution was also investigated. Spin trapping experiments allowed trapping of radicals from both L-histidine and D-mannitol. An unusual, and potentially hazardous, radical regeneration mechanism was observed for L-histidine, which was suggested to be due to the sterile metal needles used for transferring the sample solution in the EPR tubes.
The second part of this work was concerned with the investigation of the radicalic mechanism of action of a promising photo-activable platinum(IV) anticancer complex. It has been previously suggested that the cytotoxicity of the said compound is associated to the photo-release of azidyl radicals, which can be quenched in the presence of the amino acid L-tryptophan. By the use of the spin trapping methodology, an intermediate indole radical was isolated and identified from photo-activation of the anticancer complex in the presence of both L-tryptophan and melatonin. The same photo-protective effect was observed also in the presence of a tryptophan-containing peptide. Thus, this work contributed to the overall understanding on photo-irradiated platinum anticancer complexes and their generated photo-products.
Item Type: | Thesis (PhD) | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Electron paramagnetic resonance, Electron paramagnetic resonance spectroscopy, Drugs -- Design, Drugs -- Analysis -- Technique, Radiation sterilization | ||||
Official Date: | August 2017 | ||||
Dates: |
|
||||
Institution: | University of Warwick | ||||
Theses Department: | Department of Chemistry | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Newton, Mark E. ; Wedge, Christopher | ||||
Format of File: | |||||
Extent: | xxiii, 193 leaves : illustrations, charts | ||||
Language: | eng |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year