Stepwise photosensitized thymine dimerization mediated by an exciton intermediate
Stepwise photosensitized thymine dimerization mediated by an exciton intermediate
Clemens Rauer 0 1
Juan J. Nogueira 0 1
Philipp Marquetand 0 1
Leticia Gonza´ lez 0 1
0 Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna , Vienna , Austria
1 & Clemens Rauer
Cyclobutane thymine dimerization is the most prominent DNA photoinduced damage. While the ultrafast mechanism that proceeds in the singlet manifold is nowadays well established, the triplet-state pathway is not completely understood. Here we report the underlying mechanism of the photosensitized dimerization process in the triplet state. Quantum chemical calculations, combined with wavefunction analysis, and nonadiabatic molecular dynamics simulations demonstrate that this is a stepwise reaction, traversing a long-lived triplet biradical intermediate, which is characterized as a Frenkel exciton with very small charge-transfer character. The low yield of the reaction is regulated by two factors: (i) a relatively large energy barrier that needs to be overcome to form the exciton intermediate, and (ii) a bifurcation of the groundstate potential-energy surface that mostly leads back to the Franck-Condon region because dimerization requires a very restricted combination of coordinates and velocities at the event of non-radiative decay to the ground state.
Graphical abstract; DNA; Thymine dimerization; Quantum chemical calculations; Non-adiabatic dynamics; Wavefunction analysis; Charge transfer
Introduction
The formation of cyclobutane thymine ThiT dimers
between two adjacent thymine bases is the most frequent
DNA damage under UV radiation [
1
]. This photolesion,
which can take place in both the singlet and triplet
manifolds, has been extensively investigated spectroscopically
[
2–7
] and computationally [
8–15
]. The triplet pathway is a
much slower process [
7
] and exhibits a smaller yield [
6, 16
]
than the singlet mechanism due to inefficient intersystem
crossing. As a consequence, this pathway yields very weak
spectroscopic signals that preclude unambiguous
statements regarding the mechanism [
5–7
]. In order to enhance
the triplet signals, photosensitization is commonly used,
increasing the ThiT dimerization yield [
5, 17–19
]. This
enhancement can also play a role with photosensitizers
acting as phototoxic drugs [
20
]. Photosensitization
involves intersystem crossing of a photosensitizer after
excitation, transferring its electronic energy to a
Fig. 1 Chemical formula and electronic arrangement of two
thymines for a the local triplet state (3L) and b biradical triplet states (3BR).
Schematic representation of c a local state, d a Frenkel exciton state,
and e a charge-resonance state. The black rectangles represent the
thymine monomers. The black arrow connects the hole (red circle)
and the electron (blue circle) generated after excitation.
Delocalization length (DL) and charge-transfer (CT) contribution are also
indicated (color figure online)
neighboring thymine, which is then promoted to the lowest
triplet state.
Using the photosensitizer 20-methoxyacetophenone and
the dinucleotide TpT, stationary and time-resolved
experiments provided two time constants, 22.5 and 62 ns, for the
decay of the TpT in the triplet manifold [
5
]. These
constants have been related to a local triplet state (3L, see
Fig. 1a, c), which is populated after triplet–triplet energy
transfer (TTET) from the photosensitizer, and a biradical
triplet state (3BR, see Fig. 1b, d, e), which can be formed
from 3L. Quantum chemical calculations [
14
] suggested
that the ThiT dimerization is triggered by the formation of
the biradical intermediate, but the barrierless pathway
calculated for the transition from 3L to 3BR is in conflict
with the experimental lifetime of 22.5 ns assigned to the 3L
species. This conflict is likely caused by the use in the
theoretical study of a perfectly stacked geometrical
configuration with Cs symmetry, which is hardly achieved in a
DNA strand or in a TpT dimer due to the geometrical
constraints of the sugar-phosphate backbone. Recent
quantum mechanics/molecular mechanics (QM/MM)
calculations have found a small barrier of 0.15 eV separating
the 3L and 3BR minima, in better agreement with the
experimental lifetime of 22.5 ns assigned to the 3L species
[
15
].
An intriguing question in the dimerization process is the
character of the 3BR state. Calculations showed that the
excited electronic density of 3BR is distributed over the
two thymine units [
14
] and spectroscopic measurements
suggested that dimerization involves the participation of
delocalized triplet states [
18
]. However, electronic
delocalization over the two monomers can correspond to two
different electronic states: (i) a Frenkel exciton, in which
two local excitations are coupled (Fig. 1d), or a
chargeresonance state, in which two charge-transfer states with
charge flow in opposite directions are combined (Fig. 1e)
[
21
]. It has (...truncated)