Understanding the factors controlling the photo-oxidation of natural DNA by enantiomerically pure intercalating ruthenium polypyridyl complexes through TA/TRIR studies with polydeoxynucleotides and mixed sequence oligodeoxynucleotides.

Páraic M Keane,Thorfinnur Gunnlaugsson,Susan J Quinn,Bjørn C Poulsen,Xue-Zhong Sun,Christine J Cardin,John M Kelly,Michael W George,Kyra O'Sullivan,Igor V Sazanovich,Fergus E Poynton,Michael Towrie

doi:10.1039/d0sc02413a

Abstract

Ruthenium polypyridyl complexes which can sensitise the photo-oxidation of nucleic acids and other biological molecules show potential for photo-therapeutic applications. In this article a combination of transient visible absorption (TrA) and time-resolved infra-red (TRIR) spectroscopy are used to compare the photo-oxidation of guanine by the enantiomers of [Ru(TAP)2(dppz)]2+ in both polymeric {poly(dG-dC), poly(dA-dT) and natural DNA} and small mixed-sequence duplex-forming oligodeoxynucleotides. The products of electron transfer are readily monitored by the appearance of a characteristic TRIR band centred at ca. 1700 cm−1 for the guanine radical cation and a band centered at ca. 515 nm in the TrA for the reduced ruthenium complex. It is found that efficient electron transfer requires that the complex be intercalated at a G-C base-pair containing site. Significantly, changes in the nucleobase vibrations of the TRIR spectra induced by the bound excited state before electron transfer takes place are used to identify preferred intercalation sites in mixed-sequence oligodeoxynucleotides and natural DNA. Interestingly, with natural DNA, while it is found that quenching is inefficient in the picosecond range, a slower electron transfer process occurs, which is not found with the mixed-sequence duplex-forming oligodeoxynucleotides studied.

Highlights

Ruthenium(II) polypyridyl complexes continue to attract considerable interest due to their tuneable chemical properties and wide range of potential applications.[1]
Each enantiomer must be examined as a distinct species, as both their binding behaviour and consequent reactivity may be expected to be different. To address these questions we have previously reported the transient visible absorption (TrA) and time-resolved infra-red (TRIR) spectroscopy of [Ru(TAP)2(dppz)]2+ enantiomers bound to a series of short (10-mer) oligodeoxynucleotides (ODNs) comprising a range of speci c AT- and GC-rich tracts.[7]
There is strong quenching of the emission at 635 nm for both enantiomers, with slightly more efficient quenching seen for D1 (Fig. 2a and Electronic supplementary information (ESI) Fig. S1c, d†)

Summary

Introduction

Ruthenium(II) polypyridyl complexes continue to attract considerable interest due to their tuneable chemical properties and wide range of potential applications.[1]. We have used steady-state spectroscopy, transient visible absorption (TrA) and time-resolved infra-red (TRIR) to (i) monitor the products and kinetics of reversible guanine photo-oxidation and (ii) to help identify the preferred binding sites in DNA.

Results

Conclusion