Theoretical Insight into the Intrinsic Ultrafast Formation of Cyclobutane Pyrimidine Dimers in UV-Irradiated DNA: Thymine versus Cytosine

Serrano-Pérez, Juan José; González-Ramírez, Israel; Coto, Pedro B.; Merchán, Manuela; Serrano‐Andrés, Luis

doi:10.1021/jp806794x

Cited by 61 publications

(76 citation statements)

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“…This is particularly true for those conformations maximizing the overlap between the π structures of stacked nucleobases, which formed favorable excimer arrangements. [4][5][6][7] They were shown to yield the most stable structures leading to the photoreactive arrangements, in agreement with the higher yields obtained for photoproducts with cis-type parallel face-to-face conformations for the base pairs. 1, 4 We attributed the low yield measured for the CBC formation as compared to CBT to the stable excimer conformations, found in CC combinations lower in energy than the CI structure and opposite to what occurs in TT pairs.…”

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confidence: 76%

Cyclobutane Pyrimidine Photodimerization of DNA/RNA Nucleobases in the Triplet State

Climent

González-Ramírez

González‐Luque

et al. 2010

J. Phys. Chem. Lett.

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The photoinduced formation of cyclobutane pyrimidine dimers in the triplet excited state of the DNA/RNA pyrimidine nucleobases pairs has been studied at the CASPT2 level of theory. A stepwise mechanism through the triplet state of the homodimer is proposed for the pairs of nucleobases cytosine, thymine, and uracil involving a singlet-triplet crossing intermediary structure of biradical character representing the most favorable triplet state conformation of the nucleobases as found in the DNA environment. The efficiency of the mechanism will be modulated by two factors: the effectiveness of the triplet-triplet energy transfer process from a donor photosensitizer molecule, which relates to the relative position of the intermediate in the three acceptor systems, determined here to be lower in energy in the thymine and uracil dimers than in the cytosine pairs, and that of the intersystem crossing process toward the ground state of the photoproduct. SECTION Dynamics, Clusters, Excited StatesO ne of the most notorious examples of evidence of the photosensitivity of the genetic material to the action of ultraviolet (UV) light is the photoinduced formation of cyclobutane pyrimidine dimers (CBPyr or Pyr<>Pyr, see Figure 1) by pairs of DNA/RNA intrastrand adjacent pyrimidine nucleobases. 1 Those adducts constitute a major source of photoinduced DNA/RNA lesions, leading even to photomutagenesis and photocarcinogenesis, particularly in cellular DNA. 2 The process takes place in biological environments, solvents, and in the solid phase. 1 Femtosecond spectroscopy has proved that thymine (T) dimerization is an ultrafast photoreaction in which cyclobutane thymine dimers (CBT) are fully formed ∼1 ps after UV illumination. 3 Theoretical determinations have confirmed in thymine and cytosine (C) dimers a mechanism for a corresponding ultrafast nonadiabatic photoreaction mediated by the presence of a conical intersection (CI), an energy-degenerate structure between the low-lying singlet excited (S 1 ) and the ground state (S 0 ). 4-7 In those quantum-chemical CASPT2 studies, the [2 þ 2] photocycloaddition reaction leading to the formation of CBT and cyclobutane cytosine (CBC) dimers was characterized in the singlet manifold. 4-7 Barrierless relaxation paths from favorable conformations of the nucleobases were shown to lead from an initially irradiated singlet state to a shearing-type CI structure, in which the nucleobases ethylenic C 5 -C 6 and C 5 0 -C 6 0 bonds laid parallel (parallelogram-type) and elongated, connecting the S 1 and S 0 states and allowing an efficient internal conversion process. Intrastrand nucleobase sequence and relative orientations were also proven to be essential for an efficient photoreaction to take place. This is particularly true for those conformations maximizing the overlap between the π structures of stacked nucleobases, which formed favorable excimer arrangements. 4-7 They were shown to yield the most stable structures leading to the photoreactive arrangements, in agreement with the higher yields ob...

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confidence: 76%

Cyclobutane Pyrimidine Photodimerization of DNA/RNA Nucleobases in the Triplet State

Climent

González-Ramírez

González‐Luque

et al. 2010

J. Phys. Chem. Lett.

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“…100,109 Concerning the photochemical reactivity of Pyr, theoretical calculations have mainly focused 10 on the formation of cyclobutane dimers in a concerted process from the singlet excited state. [110][111][112][113][114] However, as stated above, in the case of photosensitised Pyr<>Pyr formation, [2+2] photocycloaddition occurs from the triplet manifold. In spite of its importance, up to now this reaction pathway has only 15 been considered by two research teams.…”

Section: Theoretical Calculationsmentioning

confidence: 99%

Photosensitised pyrimidine dimerisation in DNA

et al. 2011

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aTriplet-mediated pyrimidine (Pyr) dimerisation is a key process in photochemical damage to DNA. 5It may occur in the presence of a photosensitiser, provided that a number of requirements are fulfilled, such as favourable intersystem crossing quantum yield and high triplet energy. The attention has been mainly focused on cyclobutane pyrimidine dimers, as they are by far the most relevant Pyr photoproducts obtained by sensitisation. The present perspective deals with the involved chemistry, not only in DNA but also in its simple building blocks. It also includes the 10 photophysical characterisation of the Pyr triplet excited states, as well as a brief discussion of the theoretical aspects.

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“…For example, a recently developed method called semiclassical electron-radiation-ion dynamics, a kind of real-time electrodynamics starting from the Ehrenfest theorem, was reported to give reasonable results for excited-state DNA bases [171]. [174,175], π-stacking and excited-state delocalization (charge transfer, excimers/ exciplexes, and excitons) [140,[176][177][178], and excited-state dynamics [144]. In this section we overview recent results of computational efforts directed toward understanding the photoexcitation in DNA strands.…”

Section: Nonadiabatic Dynamicsmentioning

confidence: 99%

“…Using CASPT2 calculations, Merchán, Serrano-Andrés, and coworkers [175,328] rationalized the lower dimerization yield of cytosine compared with thymine: the former has a stable singlet excimer that needs to overcome a barrier (though small) to reach the S 0 /S 1 conical intersection, while this process is downhill in the latter. The authors also proposed a barrierless non-concerted dimerization mechanism in the triplet manifold, the efficiency of which relies on the ease of the S 0 /T 1 intersystem crossing [175,328].…”

Section: Pyrimidine Dimerizationmentioning

confidence: 99%

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Computational Modeling of Photoexcitation in DNA Single and Double Strands

Lü

Lan

Thiel

2014

Topics in Current Chemistry

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The photoexcitation of DNA strands triggers extremely complex photoinduced processes, which cannot be understood solely on the basis of the behavior of the nucleobase building blocks. Decisive factors in DNA oligomers and polymers include collective electronic effects, excitonic coupling, hydrogen-bonding interactions, local steric hindrance, charge transfer, and environmental and solvent effects. This chapter surveys recent theoretical and computational efforts to model real-world excited-state DNA strands using a variety of established and emerging theoretical methods. One central issue is the role of localized vs delocalized excitations and the extent to which they determine the nature and the temporal evolution of the initial photoexcitation in DNA strands.

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Theoretical Insight into the Intrinsic Ultrafast Formation of Cyclobutane Pyrimidine Dimers in UV-Irradiated DNA: Thymine versus Cytosine

Cited by 61 publications

References 10 publications

Cyclobutane Pyrimidine Photodimerization of DNA/RNA Nucleobases in the Triplet State

Cyclobutane Pyrimidine Photodimerization of DNA/RNA Nucleobases in the Triplet State

Photosensitised pyrimidine dimerisation in DNA

Computational Modeling of Photoexcitation in DNA Single and Double Strands

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