Combining spectroscopic techniques to unravel the binding of an osmium polypyridyl probe to G-quadruplex structures in solution Mark Stitch 1 , Kateřina Peterková 2 , Rayhaan Boota 3 , Alannah S. Chalkley 1 , Jeremy C. Simpson 1 , Peter Podbevšek 2 , Janez Plavec 2 , Paul A. Scattergood 3 , Paul I. P. Elliot 3 and Susan J. Quinn 1 1 UCD, Ireland, 2 National Institute of Chemistry, Slovenia, 3 University of Huddersfield, UK NIR luminescent probes for different DNA sequences and structures are key diagnostic tools. An important target structure is quadruplex DNA (G4), formed by guanine(G)-rich sequences, which are over-expressed in oncogene promoter regions. 1 The Quinn group has previously studied G4 binding of a ruthenium polypyridyl complexes containing an intercalating dppz (dipyrido[3,2-a:2’,3’-c]phenazine) ligand. 2 In this work the preparation and photophysical characterisation of a related osmium complex, [Os(TAP) 2 (dppz)] [ 1 ] is reported. 1 absorbs red light, allowing deeper tissue penetration while the NIR emission at 750 nm avoids autofluorescence, enabling improved cellular detection. The emission of 1 is enhanced in the presence of DNA, with greater enhancement observed in the presence of AT over GC sequences and shows enantiomeric sensitivity to TA over AT steps in model DNA sequences. 3 Additionally, 1 is found to bind strongly to G4 structures formed in the cMYC promoter region, with enantiomeric luminescence sensitivity. Results from Time-resolved Infrared (TRIR) reports on the DNA bases (region 1600- 1800 cm -1 ) affected by the excited state, which combined with solution NMR studies indicate binding at the terminal guanine base stack. 4 Finally, the emission of the complex is also visualised in the nuclear envelope of dividing cells. 3 References 1. S. Neidle, J. Med. Chem., 2016, 59 , 5987−6011. 2. S. Devereux, et al ., Chem. Eur. J., 2020, 10 , 2165. 3. M. Stitch , R. Boota, A. S. Chalkley, T. D. Keene, J. C. Simpson, P. A. Scattergood, P. I. Elliott, S. J. Quinn, Inorg. Chem. , 2022, 61 , 14947−14961. 4. K. Peterková + , M. Stitch + , R. Boota, P. A. Scattergood, P. I. Elliott, M. Towrie, P. Podbevšek, J. Plavec, S. J. Quinn, Chem. Eur. J., 2023,doi.org/10.1002/chem.202203250
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