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Rapid screening of photoactivatable metallodrugs : photonic crystal fibre microflow reactor coupled to ESI mass spectrometry
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McQuitty, Ruth J., Unterkofler, Sarah, Euser, Tijmen G., Russell, Philip St. J. and Sadler, P. J. (2017) Rapid screening of photoactivatable metallodrugs : photonic crystal fibre microflow reactor coupled to ESI mass spectrometry. RSC Advances , 7 (59). pp. 37340-37348. doi:10.1039/c7ra06735f ISSN 2046-2069.
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WRAP-rapid-screening-photoactivatable-metallodrugs-ESI-Sadler-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1357Kb) | Preview |
Official URL: http://doi.org/10.1039/C7RA06735F
Abstract
We explore the efficacy of a hyphenated photonic crystal fibre microflow reactor – high-resolution mass spectrometer system as a method for screening the activity of potential new photoactivatable drugs. The use of light to activate drugs is an area of current development as it offers the possibility of reduced side effects due to improved spatial and temporal targeting and novel mechanisms of anticancer activity. The di-nuclear ruthenium complex [{(η6-indan)RuCl}2(μ-2,3-dpp)](PF6)2, previously studied by Magennis et al. (Inorg. Chem., 2007, 46, 5059) is used as a model drug to compare the system to standard irradiation techniques. The photodecomposition pathways using blue light radiation are the same for PCF and conventional cuvette methods. Reactions in the presence of small biomolecules 5′-guanosine monophosphate (5′-GMP), 5′-adenosine monophosphate (5′-AMP), L-cysteine (L-Cys) and glutathione (γ-L-glutamyl-L-cysteinyl-glycine, GSH) were studied. The complex was found to bind to nucleobases in the dark and this binding increased upon irradiation with 488 nm light, forming the adducts [(η6-indan)Ru2(μ-2,3-dpp) + 5′-GMP]2+ and [(η6-indan)Ru + (5′-AMP)]+. These findings are consistent with studies using conventional methods. The dinuclear complex also binds strongly to GSH after irradiation, a possible explanation for its lack of potency in cell line testing. The use of the PCF-MS system dramatically reduced the sample volume required and reduced the irradiation time by four orders of magnitude from 14 hours to 12 seconds. However, the reduced sample volume also results in a reduced MS signal intensity. The dead time of the combined system is 15 min, limited by the intrinsic dead volume of the HR-MS.
Item Type: | Journal Article | |||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) T Technology > TP Chemical technology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||
SWORD Depositor: | Library Publications Router | |||||||||
Library of Congress Subject Headings (LCSH): | Metallurgy., Metals in medicine, Photochemotherapy, Cancer -- Photochemotherapy., Chemical engineering. | |||||||||
Journal or Publication Title: | RSC Advances | |||||||||
Publisher: | Royal Society of Chemistry | |||||||||
ISSN: | 2046-2069 | |||||||||
Official Date: | 26 July 2017 | |||||||||
Dates: |
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Volume: | 7 | |||||||||
Number: | 59 | |||||||||
Page Range: | pp. 37340-37348 | |||||||||
DOI: | 10.1039/c7ra06735f | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Reuse Statement (publisher, data, author rights): | ** From Crossref via Jisc Publications Router. | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 11 October 2017 | |||||||||
Date of first compliant Open Access: | 11 October 2017 | |||||||||
RIOXX Funder/Project Grant: |
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