Influence of the Sequence Dependent Ionization Potentials of Guanines on the Luminescence Quenching of Ru-Labeled Oligonucleotides:  A Theoretical and Experimental Study

Abstract

The luminescence quenching by electron transfer of a nonintercalating [Ru(TAP) 2 DIP] 2+ complex, which is covalently linked to different guanine containing oligonucleotide duplexes, is compared to the sequence dependent ionization potentials of guanines as estimated from Hartree-Fock calculations on regular B-DNA by means of Koopmans theorem. From these experimental and theoretical results, it is demonstrated that the ionization potential of the guanines has a major influence on the efficiency of hole injection by the groove binding [Ru(TAP) 2 DIP] 2+ complex in a type I photooxidation of DNA. Because the photoelectron transfer between the complex and DNA takes place on a nanosecond time scale, nanosecond molecular dynamics simulations were performed for two of the sequences in order to check for the possible influence of the dynamical fluctuations in the DNA structure on the ionization potential. IP fluctuations up to 0.5 eV were observed on a picosecond time scale along the molecular dynamics trajectories. However, these fluctuations scatter statistically around the value calculated for regular B-DNA and are thus not relevant for the slow photoelectron transfer with a nonintercalating [Ru(TAP) 2 DIP] 2+ complex.

Photocrosslinking in Ruthenium‐Labelled Duplex Oligonucleotides

“…of the involved guanine residues upon first examination. [18] This is in agreement with quenching by electron transfer as previously demonstrated by flash photolysis of this complex with guanosine monophosphate. [15] Such a charge transfer process with a guanine residue generates a photoadduct [16] and therefore, the percentage quenching should also correlate with the percentage photoadduct produced.…”

“…[17,18] t M is the pre-exponential weighted average lifetime [t M (Sa i t i )/ (Sa i )] and t M0 the corresponding value for the reference sequence (Ru0' for Ru6 and Ru7, and Ru0 for the other sequences). Luminescence decay was monitored at 650 nm (l exc 379 nm) and analysed according to a sum of exponential functions: I(t) S[a i exp(À t/t i )].…”

“…[18] [e] Position of the guanine residue on the complementary strand as compared to the anchoring site of the complex. think this rough model is complementary to the experimental results and can help to interpret some of the data discussed above.…”

“…The percentage quenching has been correlated to the calculated ionisation potential of the guanine residues in the different sequences. [18] Therefore, the formation of a photoadduct that generates an irreversible photocrosslinking of the two strands has been attributed to an initial charge transfer process.…”

Oxidation effect on double H-bonded imidazole–adenine–imidazole trimer

“…In addition, oxidative damage to DNA plays a key role in mutagenesis and carcinogenesis, which has attracts considerable interest recently [28][29][30][31][32][33][34]. Therefore, only the oxidation effect on double H-bonded IAI trimer is investigated in the following sections.…”