Time-resolved infra-red studies of photo-excited porphyrins in the presence of nucleic acids and in HeLa tumour cells: insights into binding site and electron transfer dynamics

Keane, P. M. ORCID: https://orcid.org/0000-0003-2828-8512, Zehe, C. ORCID: https://orcid.org/0000-0002-3213-5669, Poynton, F. E., Bright, S. A., Estayalo-Adrián, S. ORCID: https://orcid.org/0000-0002-2896-7059, Devereux, S. J., Donaldson, P. M. ORCID: https://orcid.org/0000-0002-0305-9142, Sazanovich, I. V. ORCID: https://orcid.org/0000-0002-8000-7645, Towrie, M., Botchway, S. W., Cardin, C. J. ORCID: https://orcid.org/0000-0002-2556-9995, Williams, D. C., Gunnlaugsson, T. ORCID: https://orcid.org/0000-0003-4814-6853, Long, C. ORCID: https://orcid.org/0000-0002-9484-8744, Kelly, J. M. ORCID: https://orcid.org/0000-0002-3706-1777 and Quinn, S. J. ORCID: https://orcid.org/0000-0002-7773-8842 (2022) Time-resolved infra-red studies of photo-excited porphyrins in the presence of nucleic acids and in HeLa tumour cells: insights into binding site and electron transfer dynamics. Physical Chemistry Chemical Physics, 24 (44). pp. 27524-27531. ISSN 1463-9076 doi: 10.1039/d2cp04604k

Abstract/Summary

Cationic porphyrins based on the 5,10,15,20-meso-(tetrakis-4-N-methylpyridyl) core (TMPyP4) have been studied extensively over many years due to their strong interactions with a variety of nucleic acid structures, and their potential use as photodynamic therapeutic agents and telomerase inhibitors. In this paper, the interactions of metal-free TMPyP4 and Pt(II)TMPyP4 with guanine-containing nucleic acids are studied for the first time using time-resolved infrared spectroscopy (TRIR). In D2O solution (where the metal-free form exists as D2TMPyP4) both compounds yielded similar TRIR spectra (between 1450–1750 cm−1) following pulsed laser excitation in their Soret B-absorption bands. Density functional theory calculations reveal that vibrations centred on the methylpyridinium groups are responsible for the dominant feature at ca. 1640 cm−1. TRIR spectra of D2TMPyP4 or PtTMPyP4 in the presence of guanosine 5'-monophosphate (GMP), double-stranded {d(GC)5}2 or {d(CGCAAATTTGCG)}2 contain negative-going signals, ‘bleaches’, indicative of binding close to guanine. TRIR signals for D2TMPyP4 or PtTMPyP bound to the quadruplex-forming cMYC sequence {d(TAGGGAGGG)}2T indicate that binding occurs on the stacked guanines. For D2TMPyP4 bound to guanine-containing systems, the TRIR signal at ca. 1640 cm−1 decays on the picosecond timescale, consistent with electron transfer from guanine to the singlet excited state of D2TMPyP4, although IR marker bands for the reduced porphyrin/oxidised guanine were not observed. When PtTMPyP is incorporated into HeLa tumour cells, TRIR studies show protein binding with time-dependent ps/ns changes in the amide absorptions demonstrating TRIR's potential for studying light-activated molecular processes not only with nucleic acids in solution but also in biological cells.

Additional Information	This article has a correction published on 18.08.2023, please see: https://doi.org/10.1039/D3CP90155F
Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/109097
Identification Number/DOI	10.1039/d2cp04604k
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Additional Information	This article has a correction published on 18.08.2023, please see: https://doi.org/10.1039/D3CP90155F
Publisher	Royal Society of Chemistry
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