Development of a Neutral Diketopyrrolopyrrole Phosphine Oxide for the Selective Bioimaging of Mitochondria at the Nanomolar Level

Abelha, Thais F.; Morris, Graeme; Lima, Sandro M.; Andrade, Luis H. C.; McLean, Andrew J.; Alexander, Cameron; Calvo-Castro, Jesus; McHugh, Callum J.

Abstract

© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Development of novel bioimaging materials that exhibit organelle specific accumulation continues to be at the forefront of research interests and efforts. Among the various subcellular organelles, mitochondria, which are found in the cytoplasm of eukaryotic cells, are of particular interest in relation to their vital function. To date, most molecular probes that target mitochondria utilise delocalised lipophilic cations such as triphenylphosphonium and pyridinium. However, the use of such charged motifs is known to be detrimental to the working function of the mitochondrial transmembrane potential and there remains a strong case for development of neutral mitochondrial fluorescent probes. Herein, we demonstrate for the first time the exploitation of diketopyrrolopyrrole-based chemistries for the realisation of a neutral fluorescent probe that exhibits organelle specific accumulation within the mitochondria at the nanomolar level. The synthesised probe, which bears a neutral triphenylphosphine oxide moiety, exhibits a large Stokes shift and high fluorescence quantum yield in water, both highly sought-after properties in the development of bioimaging agents. In vitro studies reveal no interference with cell metabolism when tested for the human MCF7 breast cancer cell and nanomolar subcellular organelle colocalisation with commercially available mitochondrial staining agent Mitotracker Red. In light of its novelty, neutral structure and the preferential accumulation at nanomolar concentrations we anticipate this work to be of significant interest for the increasingly larger community devoted to the realisation of neutral mitochondrial selective systems and more widely to those engaged in the rational development of superior organic architectures in the biological field.

Citation

Abelha, T. F., Morris, G., Lima, S. M., Andrade, L. H. C., McLean, A. J., Alexander, C., …McHugh, C. J. (2020). Development of a Neutral Diketopyrrolopyrrole Phosphine Oxide for the Selective Bioimaging of Mitochondria at the Nanomolar Level. Chemistry - A European Journal, 26(14), 3173-3180. https://doi.org/10.1002/chem.201905634

• Journal Article Type: Article
• Acceptance Date: Jan 8, 2020
• Online Publication Date: Feb 21, 2020
• Publication Date: Mar 9, 2020
• Deposit Date: Feb 22, 2020
• Publicly Available Date: Feb 22, 2021
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 14
• Pages: 3173-3180
• DOI: https://doi.org/10.1002/chem.201905634
• Public URL: https://nottingham-repository.worktribe.com/output/4007052
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1002/chem.201905634
• Additional Information: This is the peer reviewed version of the following article: Abelha, T.F., Morris, G., Lima, S.M., Andrade, L.H.C., McLean, A.J., Alexander, C., Calvo?Castro, J. and McHugh, C.J. (2020), Development of a Neutral Diketopyrrolopyrrole Phosphine Oxide for the Selective Bioimaging of Mitochondria at the Nanomolar Level. Chem. Eur. J.. , which has been published in final form at https://doi.org/10.1002/chem.201905634. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.