From Chemotherapy to Phototherapy – Changing the Therapeutic Action of a Metallo-Intercalating RuII-ReI Luminescent System by Switching its Sub-Cellular Location

Journal article

Saeed, H.K.,, Jarman, P.J., Sreedharan, S., Mowll, R., Auty, A.J., Chauvet, A.A., Smythe, C.G., de la Serna, J.B. and Thomas, J.A. 2023. From Chemotherapy to Phototherapy – Changing the Therapeutic Action of a Metallo-Intercalating RuII-ReI Luminescent System by Switching its Sub-Cellular Location. Chemistry: A European Journal . 29 (34), pp. 1-6. https://doi.org/10.1002/chem.202300617
AuthorsSaeed, H.K.,, Jarman, P.J., Sreedharan, S., Mowll, R., Auty, A.J., Chauvet, A.A., Smythe, C.G., de la Serna, J.B. and Thomas, J.A.
Abstract

The synthesis of a new heterodinuclear ReIRuII metallointercalator containing RuII(dppz) and ReI(dppn) moieties is reported. Cell-free studies reveal that the complex has similar photophysical properties to its homoleptic M(dppz) analogue and it also binds to DNA with a similar affinity. However, the newly reported complex has very different in-cell properties to its parent. In complete contrast to the homoleptic system, the RuII(dppz)/ReI(dppn) complex is not intrinsically cytotoxic but displays appreciable phototoxic, despite both complexes displaying very similar quantum yields for singlet oxygen sensitization. Optical microscopy suggests that the reason for these contrasting biological effects is that whereas the homoleptic complex localises in the nuclei of cells, the RuII(dppz)/ReI(dppn) complex preferentially accumulates in mitochondria. These observations illustrate how even small structural changes in metal based therapeutic leads can modulate their mechanism of action.

KeywordsChemotherapy ; Phototherapy ; DNA
Year2023
JournalChemistry: A European Journal
Journal citation29 (34), pp. 1-6
PublisherWiley
ISSN 1521-3765
Digital Object Identifier (DOI)https://doi.org/10.1002/chem.202300617
Web address (URL)https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202300617
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Output statusPublished
Publication dates
Online04 Apr 2023
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Deposited12 Jul 2024
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