Ab initio determination of the electron affinities of DNA and RNA nucleobases

High-level quantum-chemical ab initio coupled-cluster and multiconfigurational perturbation methods have been used to compute the vertical and adiabatic electron affinities of the five canonical DNA and RNA nucleobases: uracil, thymine, cytosine, adenine, and guanine. The present results aim for the accurate determination of the intrinsic electron acceptor properties of the isolated nucleic acid bases as described by their electron affinities, establishing an overall set of theoretical reference values at a level not reported before and helping to rule out less reliable theoretical and experimental data and to calibrate theoretical [email protected] [email protected] [email protected] [email protected]

Theoretical Study of the Hydroxyl Radical Addition to Uracil and Photochemistry of the Formed U6OH^• Adduct

Hydroxyl radical (^•OH) is produced in biological systems by external or endogenous agents. It can damage DNA/RNA by attacking pyrimidine nucleobases through the addition to the C5C6 double bond. The adduct resulting from the attachment at the C5 position prevails in the experimental measurements, although the reasons for this preference remain unclear. The first aim of this work is therefore to shed light on the comprehension of this important process. Thus, the thermal ^•OH addition to the C5C6 double bond of uracil has been studied theoretically by using DFT, MP2, and the multiconfigurational CASPT2//CASSCF methodologies. The in-vacuo results obtained with the latter protocol plus the analysis of solvent effects support the experimental observation. A significant lower barrier height is predicted for the C5 pathway with respect to that of the C6 route. In contrast to the C5 adduct, the C6 adduct is able to absorb visible light. Hence, the second aim of the work is to study the photochemistry of this species using the CASPT2//CASSCF methodology within the framework of the photochemical reaction path approach (PRPA). The nonradiative decay to the ground state of this compound has been characterized. A photoreactive character is predicted for the C6 adduct in the excited states according to the presence of excited-state minima along the main decay channel. Finally, a new mechanism of photodissociation has been explored, which implies the photoinduced regeneration of the canonical nucleobase by irradiating with visible light, being therefore relevant in RNA protection against damage by reactive oxygen species

Mechanism of the OH Radical Addition to Adenine from Quantum-Chemistry Determinations of Reaction Paths and Spectroscopic Tracking of the Intermediates

The OH radical is a well-known mediator in the oxidation of biological structures like DNA. Over the past decades, the precise events taking place after reaction of DNA nucleobases with OH radical have been widely investigated by the scientific community. Thirty years after the proposal of the main routes for the reaction of ^•OH with adenine (Vieira, A.; Steenken, S. J. Am. Chem. Soc. 1990, 112, 6986−6994), the present work demonstrates that the OH radical addition to C4 position is a minor pathway. Instead, the dehydration process is mediated by the A5OH adduct. Conclusions are based on density functional theory calculations for the ground-state reactivity and highly accurate multiconfigurational computations for the excited states of the radical intermediates. The methodology has been also used to study the mechanism giving rise to the mutagens 8-oxoA and FAPyA. Taking into account the agreement between the experimental data and the theoretical results, it is concluded that addition to the C5 and C8 positions accounts for at least ∼44.5% of the total ^•OH reaction in water solution. Finally, the current findings suggest that hydrophobicity in the DNA/RNA surroundings facilitates the formation of 8-oxoA and FAPyA

Origin of the Absorption Maxima of the Photoactive Yellow Protein Resolved via Ab Initio Multiconfigurational Methods

We discuss the role of the protein in controlling the absorption spectra of photoactive yellow protein (PYP), the archetype xanthopsin photoreceptor, using quantum mechanics/molecular mechanics (QM/MM) methods based on ab initio multireference perturbation theory, combined with molecular dynamics (MD) simulations. It is shown that in order to get results in agreement with the experimental data, it is necessary to use a model that allows for a proper relaxation of the whole system and treats the states involved in the electronic spectrum in a balanced way, avoiding biased results due to the effect of nonrepresentative electrostatic interactions on the chromophore

Relaxation Mechanisms of 5‑Azacytosine

The photophysics and deactivation pathways of the noncanonical 5-azacytosine nucleobase were studied using the CASPT2//CASSCF protocol. One of the most significant differences with respect to the parent molecule cytosine is the presence of a dark ¹(<i>n</i>_Nπ*) excited state placed energetically below the bright excited state ¹(ππ*) at the Franck–Condon region. The main photoresponse of the system is a presumably efficient radiationless decay back to the original ground state, mediated by two accessible conical intersections involving a population transfer from the ¹(ππ*) and the ¹(<i>n</i>_Nπ*) states to the ground state. Therefore, a minor contribution of the triplet states in the photophysics of the system is expected, despite the presence of a deactivation path leading to the lowest ³(ππ*) triplet state. The global scenario on the photophysics and photochemistry of the 5-azacytosine system gathered on theoretical grounds is consistent with the available experimental data, taking especially into account the low values of the singlet–triplet intersystem crossing and fluorescence quantum yields observed

On the Deactivation Mechanisms of Adenine–Thymine Base Pair

In this contribution, the multiconfigurational second-order perturbation theory method based on a complete active space reference wave function (CASSCF/CASPT2) is applied to study all possible single and double proton/hydrogen transfers between the nucleobases in the adenine–thymine (AT) base pair, analyzing the role of excited states with different nature [localized (LE) and charge transfer (CT)], and considering concerted as well as step-wise mechanisms. According to the findings, once the lowest excited states, localized in adenine, are populated during UV irradiation of the Watson–Crick base pair, the proton transfer in the N–O bridge does not require high energy in order to populate a CT state. The latter state will immediately relax toward a crossing with the ground state, which will funnel the system to either the canonical structure or the imino–enol tautomer. The base pair is also capable of repairing itself easily since the imino–enol species is unstable to thermal conversion

Tuning the Photophysical Properties of <i>anti</i>-B₁₈H₂₂: Efficient Intersystem Crossing between Excited Singlet and Triplet States in New 4,4′-(HS)₂-<i>anti</i>-B₁₈H₂₀.

The tuning of the photophysical properties of the highly fluorescent boron hydride cluster <i>anti</i>-B₁₈H₂₂ (<b>1</b>), by straightforward chemical substitution to produce 4,4′-(HS)₂-<i>anti</i>-B₁₈H₂₀ (<b>2</b>), facilitates intersystem crossing from excited singlet states to a triplet manifold. This subsequently enhances O₂(¹Δ_g) singlet oxygen production from a quantum yield of Φ_Δ ∼ 0.008 in <b>1</b> to 0.59 in <b>2</b>. This paper describes the synthesis and full structural characterization of the new compound 4,4′-(HS)₂-<i>anti</i>-B₁₈H₂₀ (<b>2</b>) and uses UV–vis spectroscopy coupled with density functional theory (DFT) and ab initio computational studies to delineate and explain its photophysical properties

Tuning the Photophysical Properties of <i>anti</i>-B₁₈H₂₂: Efficient Intersystem Crossing between Excited Singlet and Triplet States in New 4,4′-(HS)₂-<i>anti</i>-B₁₈H₂₀.

The tuning of the photophysical properties of the highly fluorescent boron hydride cluster <i>anti</i>-B₁₈H₂₂ (<b>1</b>), by straightforward chemical substitution to produce 4,4′-(HS)₂-<i>anti</i>-B₁₈H₂₀ (<b>2</b>), facilitates intersystem crossing from excited singlet states to a triplet manifold. This subsequently enhances O₂(¹Δ_g) singlet oxygen production from a quantum yield of Φ_Δ ∼ 0.008 in <b>1</b> to 0.59 in <b>2</b>. This paper describes the synthesis and full structural characterization of the new compound 4,4′-(HS)₂-<i>anti</i>-B₁₈H₂₀ (<b>2</b>) and uses UV–vis spectroscopy coupled with density functional theory (DFT) and ab initio computational studies to delineate and explain its photophysical properties

Proton/Hydrogen Transfer Mechanisms in the Guanine–Cytosine Base Pair: Photostability and Tautomerism

Proton/hydrogen-transfer processes have been broadly studied in the past 50 years to explain the photostability and the spontaneous tautomerism in the DNA base pairs. In the present study, the CASSCF/CASPT2 methodology is used to map the two-dimensional potential energy surfaces along the stretched NH reaction coordinates of the guanine–cytosine (GC) base pair. Concerted and stepwise pathways are explored initially <i>in vacuo</i>, and three mechanisms are studied: the stepwise double proton transfer, the stepwise double hydrogen transfer, and the concerted double proton transfer. The results are consistent with previous findings related to the photostability of the GC base pair, and a new contribution to tautomerism is provided. The C-based imino-oxo and imino-enol GC tautomers, which can be generated during the UV irradiation of the Watson–Crick base pair, have analogous radiationless energy-decay channels to those of the canonical base pair. In addition, the C-based imino-enol GC tautomer is thermally less stable. A study of the GC base pair is carried out subsequently taking into account the DNA surroundings in the biological environment. The most important stationary points are computed using the quantum mechanics/molecular mechanics (QM/MM) approach, suggesting a similar scenario for the proton/hydrogen-transfer phenomena <i>in vacuo</i> and in DNA. Finally, the static model is complemented by <i>ab initio</i> dynamic simulations, which show that vibrations at the hydrogen bonds can indeed originate hydrogen-transfer processes in the GC base pair. The relevance of the present findings for the rationalization of the preservation of the genetic code and mutagenesis is discussed