BODIPY ligands in ruthenium-based CO probes Gregor Ekart 1 Michelle Ma 2 , James Wilton-Ely 1 1 Imperial College London, UK, 2 King’s College, UK
Carbon monoxide is a gasotransmitter produced endogenously in a breakdown of heme by heme oxygenase enzyme. 1 CO has been found to influence progression of cancer and targeted CO detection could help improve patient outcomes. 2 Ruthenium-based complexes have been described previously for detection of CO in solution and in cells by “turn-on” fluorescence. A versatile vinyl ligand is capable of targeting various biological structures and 2,1,3-benzothiadiazole (BTD) based ligands provide favourable coordination and selective displacement by CO while displaying stability toward reactive oxygen, nitrogen and sulfur species. 3,4 Three novel BODIPY-based ligand classes have been developed to aid CO detection in vivo and ex vivo . Firstly, an “always-on” fluorescent ligand has been developed that can bind to ruthenium centre as a carboxylate. A piperidine-based linker has been introduced to prevent quenching of the fluorescence. This ligand enables testing of the targeting abilities of the vinyl ligands when bound to ruthenium. Additionally, ligands with BTD attached to BODIPY in different positions have been prepared to combine favourable coordination and fluorescence properties. BTD has been attached in position 8 by using 5-formyl BTD as a precursor. The steric bulk of the ligand was shown to clash with the triphenylphosphine on ruthenium centre enough to displace some. Some alkyl groups on BODIPY core can be removed to reduce the bulk of the ligand. This mixture has however still shown favourable “turn-on” fluorescence upon reaction with CO. Finally, BTD-diterminated BODIPY with BTD in positions 3 and 5 was prepared to benefit from the additional quenching in the bimetallic ruthenium complex. A good quenching was displayed at high complex concentration, but this quenching tailed off at concentrations useful for fluorimetry, so reaction with CO can currently only be detected visually at high concentration. Some changes to the design that may change these properties are being explored. In summary, various novel BODIPY-based ligands have been synthesised, characterised (NMR, MS, UV-Vis and fluorescence spectroscopy) and attached to ruthenium, displaying favourable “always-on” or “turn-on” fluorescence upon reaction with CO. References 1. M. Maines, Annu. Rev. Pharmacol. , 1997, 37 , 517-554.G. Oláh, K. Módis, G. Törö, M. Hellmich, B. Szczesny and C. Szabo, Biochem.Pharmacol. , 2018, 149 , 186-204. 2. M. E. Moragues, A. Toscani, F. Sancenón, R. Martínez-Máñez, A. J. P. White and J. D. E. Wilton-Ely, J. Am. Chem. Soc. , 2014, 136 , 11930-11933 3. A. Toscani, C. Marín-Hernández, M. Moragues, F. Sancenón, P. Dingwall, N. Brown, R. Martínez-Máñez, A. White and J. D. E. T. Wilton-Ely, Chem. Eur. J. , 2015, 21 , 14529.
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