Role of Electron-Driven Proton-Transfer Processes in the Ultrafast Deactivation of Photoexcited Anionic 8-oxoGuanine-Adenine and 8-oxoGuanine-Cytosine Base Pairs

Xiuxiu Wu, Tolga Karsili, Wolfgang Domcke
2017 Molecules  
It has been reported that 8-oxo-7,8-dihydro-guanosine (8-oxo-G), which is the main product of oxidative damage of DNA, can repair cyclobutane pyrimidine dimer (CPD) lesions when incorporated into DNA or RNA strands in proximity to such lesions. It has therefore been suggested that the 8-oxo-G nucleoside may have been a primordial precursor of present-day flavins in DNA or RNA repair. Because the electron transfer leading to the splitting of a thymine-thymine pair in a CPD lesion occurs in the
more » ... otoexcited state, a reasonably long excited-state lifetime of 8-oxo-G is required. The neutral (protonated) form of 8-oxo-G exhibits a very short (sub-picosecond) intrinsic excited-state lifetime which is unfavorable for repair. It has therefore been argued that the anionic (deprotonated) form of 8-oxo-G, which exhibits a much longer excited-state lifetime, is more likely to be a suitable cofactor for DNA repair. Herein, we have investigated the exited-state quenching mechanisms in the hydrogen-bonded complexes of deprotonated 8-oxo-G − with adenine (A) and cytosine (C) using ab initio wave-function-based electronic-structure calculations. The calculated reaction paths and potential-energy profiles reveal the existence of barrierless electron-driven inter-base proton-transfer reactions which lead to low-lying S 1 /S 0 conical intersections. The latter can promote ultrafast excited-state deactivation of the anionic base pairs. While the isolated deprotonated 8-oxo-G − nucleoside may have been an efficient primordial repair cofactor, the excited states of the 8-oxo-G − -A and 8-oxo-G − -C base pairs are likely too short-lived to be efficient electron-transfer repair agents. Molecules 2017, 22, 135 2 of 14 the nonradiative decay of the lowest excited states of cytosine (C) [5, 7] , uracil (U) [8, 12] , adenine (A) [9] [10] [11] 13, 14] , guanine (G) [40] [41] [42] [43] , and thymine (T) [15, 44, 45] . At somewhat elevated excitation energies, CIs arising from so-called πσ* states associated with acidic groups are also known to play a role in the photodynamics of the nucleobases. Apart from direct UV excitation, lesions in DNA are also formed by radical-induced oxidation of DNA-leading to oxidized bases such as 8-oxo-guanine (8-oxo-G). Additional paths for UV-induced DNA damage are the formation of radical species either via dissociation or ionization [46, 47] . 8-oxo-G is one of the most common lesions found in oxidatively damaged DNA [48] [49] [50] . The oxidation of G to 8-oxo-G substantially reduces the redox potential and enables it to form base pairs with adenine. This may lead to the replacement of G-C pairs by A-T pairs during replication, which is a mutagenic feature common in many forms of cancer [51, 52] . Despite these adverse effects, the lower redox potential of 8-oxo-dG (cf. G) makes it a viable candidate for protecting DNA by scavenging highly oxidizing species such as OH radicals [53] . It has also been demonstrated that 8-oxo-G is capable of repairing lesions of cyclobutane pyrimidine dimers (CPD) [54, 55] . In the proposed mechanism, the photoexcited state of 8-oxo-G transfers an electron to the CPD, initiating thereby bond cleavage between the pyrimidine bases. This finding suggests that 8-oxo-G may have played an analogous role to modern flavins in prebiotic redox processes [54], rendering its excited state dynamics of particular interest. Recently, Kohler, Matsika, and coworkers investigated the ultrafast excited-state dynamics of neutral and anionic 8-oxo-deoxyguanosine (8-oxo-dG) in D 2 O solution with femtosecond transient absorption spectroscopy and ab initio calculations [26] . 8-oxo-dG exists in its anionic (deprotonated) form at pH > 7 [56]. The neutral form was found to deactivate to the electronic ground state in <1 ps, whereas the anionic form exhibits a significantly longer excited-state lifetime of~43 ps [26] . Correspondingly, the latter shows a significant quantum yield for fluorescence [26] . More recent fluorescence up-conversion and theoretical studies led to the conclusion that neutral 8-oxo-G exhibits an ultrafast radiationless decay via two CIs which are accessible by certain out-of-plane deformations of guanine, whilst the longer lifetime of anionic 8-oxo-G − was attributed to the existence of sizable barriers along the reaction paths connecting the Franck-Condon region to the S 1 /S 0 CIs [57]. This mechanism was also explored by Changenet-Barret et al. for the neutral form [58] . An alternative interpretation is provided by recent studies by Tuna et al. who performed ab initio calculations of excited-state reaction paths for electron/proton transfer between sugar and base for the neutral and anionic forms of the 8-oxo-dG nucleoside, highlighting a barrierless and therefore efficient electron/proton-transfer radiationless deactivation mechanism in the neutral form, while a barrier was found to exist along this reaction path in the anionic form [23] . This finding provides an alternative explanation for the substantially longer excited-state lifetime of the deprotonated form of the 8-oxo-dG nucleoside compared to the neutral form. In double-stranded DNA, nucleobases are organized in horizontally oriented hydrogen-bonded base pairs and vertically oriented stacks stabilized by π-π interactions. Both architectural motifs may modify the dynamics of the intrinsic decay paths of the individual nucleobases by providing additional decay channels by which the excited-state populations can evolve. Such modifications have been studied, for example, by Crespo-Hernandez and co-workers who have shown that base stacking of A-T DNA oligomers leads to the formation of intra-strand excimer states with lifetimes of 50-150 ps [59] with additional decay features that are somewhat longer lived [60, 61] . Kohler and co-workers recently studied the excited-state dynamics of a π-stacked dinucleotide containing the 8-oxo-G − anion at the 5 -end and neutral A at the 3 -end, using time-resolved transient UV-pump IR-probe spectroscopy. They found that UV excitation of the dinucleotide leads to prompt electron transfer from 8-oxo-G − to the π-stacked A, generating a neutral 8-oxo-G radical and an A radical anion [62, 63] . For stacked base pairs, the inter-base hydrogen bonds provide additioinal paths along which coupled electron/proton transfer reactions can occur [64, 65] . Molecules 2017, 22, 135 3 of 14 Sobolewski and Domcke and de Vries and coworkers proposed a photoprotective role of excited-state proton transfer in the G-C Watson-Crick (WC) base pair [27, 34, 35, 66] . In these theoretical and experimental studies, the authors suggested that ultrafast excited-state deactivation occurs by inter-base electron-driven proton transfer (EDPT) from G to C. The ab initio electronic-structure calculations identified a low-lying 1 ππ* charge-transfer (CT) state (arising via an electron promotion from a G-centered π orbital to a C-centered π* orbital). The CT state drives the transfer of a proton from guanine to cytosine. While the CT state is stabilized by the proton transfer, the ground state is destabilized, which results in a barrierless reaction path leading to a low-energy CI of the S 1 state with the S 0 state. These findings are supported by pump-probe experiments in solution [21] as well as by recent transient UV pump and IR probe experiments in the gas phase [22] . The inter-base EDPT reaction was shown to be the main path by which internal conversion to the ground state proceeds in the G-C WC base pair in the gas phase and in the bulk DNA environment [27, [29] [30] [31] [32] [34] [35] [36] 66] . For the A-T WC base pair, EDPT has also been identified as an efficient deactivation path after photoexcitation by ab initio calculations [28, 30, 33] , although an experimental verification of the predicted ultrashort lifetime of the A-T WC base pair is still lacking.
doi:10.3390/molecules22010135 pmid:28098833 fatcat:dwgkifbxunfuto6wpmszuxa2du