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]

Photoinduced Formation Mechanism of the Thymine–Thymine (6–4) Adduct

The photoinduced mechanism leading to the formation of the thymine–thymine (6–4) photolesion has been studied by using the CASPT2//CASSCF approach over a dinucleotide model in vacuo. Following light absorption, localization of the excitation on a single thymine leads to fast singlet–triplet crossing that populates the triplet ³(nπ*) state of thymine. This state, displaying an elongated C₄O bond, triggers (6–4) dimer formation by reaction with the C₅C₆ double bond of the adjacent thymine, followed by a second intersystem crossing, which acts as a gate between the excited state of the reactant and the ground state of the photoproduct. The requirement of localized excitation on just one thymine, whose main decay channel (by radiationless repopulation of its ground state) is nonphotochemical, can rationalize the experimentally observed low quantum yield of formation for the thymine–thymine (6–4) adduct

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

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

On the N₁–H and N₃–H Bond Dissociation in Uracil by Low Energy Electrons: A CASSCF/CASPT2 Study

The dissociative electron-attachment (DEA) phenomena at the N₁–H and N₃–H bonds observed experimentally at low energies (<3 eV) in uracil are studied with the CASSCF/CASPT2 methodology. Two valence-bound π^– and two dissociative σ^– states of the uracil anionic species, together with the ground state of the neutral molecule, are proven to contribute to the shapes appearing in the experimental DEA cross sections. Conical intersections (CI) between the π^– and σ^– are established as the structures which activate the DEA processes. The N₁–H and N₃–H DEA mechanisms in uracil are described, and experimental observations are interpreted on the basis of two factors: (1) the relative energy of the (U–H)⁻ + H fragments obtained after DEA with respect to the ground-state equilibrium structure (S₀) of the neutral molecule (threshold for DEA) and (2) the relative energy of the CIs also with respect to S₀ (band maxima). The π₁^– state is found to be mainly responsible for the N₁–H bond breaking, whereas the π₂^– state is proved to be involved in the cleavage of the N₃–H bond

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

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

Distinct Photophysics of the Isomers of B₁₈H₂₂ Explained

The photophysics of the two isomers of octadecaborane(22), <i>anti</i>- and <i>syn</i>-B₁₈H₂₂, have been studied by UV–vis spectroscopic techniques and theoretical computational methods. In air-saturated hexane, <i>anti</i>-B₁₈H₂₂ shows fluorescence with a high quantum yield, Φ_F = 0.97, and singlet oxygen O₂(¹Δ_g) production (Φ_Δ ∼ 0.008). Conversely, isomer <i>syn</i>-B₁₈H₂₂ shows no measurable fluorescence, instead displaying much faster, picosecond nonradiative decay of excited singlet states. Computed potential energy hypersurfaces (PEHs) for both isomers rationalize these data, pointing to a deep S₁ minimum for <i>anti</i>-B₁₈H₂₂ and a conical intersection (CI) between its S₀ and S₁ states that lies 0.51 eV higher in energy. Such an energy barrier to nonradiative relaxation is not present in the PEH of <i>syn</i>-B₁₈H₂₂, and the system therefore has sufficient initial energy on excitation to reach the (S₀/S₁) CI and to then decay to the ground state without fluorescence. The computational analysis of the geometries at stationary points along the PEH of both isomers shows that the determining factor for the dissimilar photophysics of <i>anti</i>- and <i>syn</i>-B₁₈H₂₂ may be due to the significant differences in the geometrical rearrangements at their respective conical intersections. Thus, the <i>syn</i> isomer shows one very large, B–B elongation of 1.2 Å from 1.8 Å in the ground state to 3.0 Å at the CI, whereas the <i>anti</i> isomer shows smaller elongations (below 1 Å) in several B–B connectivities at its (S₀/S₁)_CI. The absorbed energy in S₁ for the <i>anti</i>-B₁₈H₂₂ is therefore redistributed vibrationally into several regions of the molecule rather than almost completely into a single vibrational mode as in the case for the <i>syn</i> isomer. The consequent prolonged S₁ lifetime for the <i>anti</i> isomer allows for relaxation via fluorescence

Combined Theoretical and Experimental Study of the Photophysics of Asulam

The photophysics of the neutral molecular form of the herbicide asulam has been described in a joint experimental and theoretical, at the CASPT2 level, study. The unique π → π* aromatic electronic transition (f, ca. 0.5) shows a weak red-shift as the polarity of the solvent is increased, whereas the fluorescence band undergoes larger red-shifts. Solvatochromic data point to higher dipole moment in the excited state than in the ground state (μ_g < μ_e). The observed increase in p<i>K</i>_a in the excited state (p<i>K</i>_a* – p<i>K</i>_a, ca. 3) is consistent with the results of the Kamlet–Abboud–Taft and Catalán et al. multiparametric approaches. Fluorescence quantum yield varies with the solvent, higher in water (ϕ_f = 0.16) and lower in methanol and 1-propanol (approx. 0.02). Room temperature fluorescence lifetime in aqueous solution is (1.0 ± 0.2) ns, whereas the phosphorescence lifetime in glassy EtOH at 77 K and the corresponding quantum yield are (1.1 ± 0.1) s and 0.36, respectively. The lack of mirror image symmetry between modified absorption and fluorescence spectra reflects different nuclear configurations in the absorbing and emitting states. The low value measured for the fluorescence quantum yield is justified by an efficient nonradiative decay channel, related with the presence of an easily accessible conical intersection between the initially populated singlet bright ¹(L_a ππ*) state and the ground state (gs/ππ*)_CI. Along the main decay path of the ¹(L_a ππ*) state the system undergoes an internal conversion process that switches part of the population from the bright ¹(L_a ππ*) to the dark ¹(L_b ππ*) state, which is responsible for the fluorescence. Additionally, singlet–triplet crossing regions have been found, a fact that can explain the phosphorescent emission detected. An intersystem crossing region between the phosphorescent state ³(L_a ππ*) and the ground state has been characterized, which contributes to the nonradiative deactivation of the excitation energy

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

Objective: To document the recovery of vascular services in Europe following the first COVID-19 pandemic peak. Methods: An online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March - May 2020, "period 1"), and then again between May and June ("period 2") and June and July 2020 ("period 3"). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume. Results: The impact of the pandemic continued to be felt well after countries' first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence. Conclusion: Centres reported a broad return of services approaching pre-pandemic "normal" by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.The aim of this study was to inform vaccination prioritization by modelling the impact of vaccination on elective inpatient surgery. The study found that patients aged at least 70 years needing elective surgery should be prioritized alongside other high-risk groups during early vaccination programmes. Once vaccines are rolled out to younger populations, prioritizing surgical patients is advantageous