Challenges in simulating light-induced processes in DNA

© 2016 by the authors; licensee MDPI, Basel, Switzerland. In this contribution, we give a perspective on the main challenges in performing theoretical simulations of photoinduced phenomena within DNA and its molecular building blocks. We distinguish the different tasks that should be involved in the simulation of a complete DNA strand subject to UV irradiation: (i) stationary quantum chemical computations; (ii) the explicit description of the initial excitation of DNA with light; (iii) modeling the nonadiabatic excited state dynamics; (iv) simulation of the detected experimental observable; and (v) the subsequent analysis of the respective results. We succinctly describe the methods that are currently employed in each of these steps. While for each of them, there are different approaches with different degrees of accuracy, no feasible method exists to tackle all problems at once. Depending on the technique or combination of several ones, it can be problematic to describe the stacking of nucleobases, bond breaking and formation, quantum interferences and tunneling or even simply to characterize the involved wavefunctions. It is therefore argued that more method development and/or the combination of different techniques are urgently required. It is essential also to exercise these new developments in further studies on DNA and subsystems thereof, ideally comprising simulations of all of the different components that occur in the corresponding experiments

A Static Picture of the Relaxation and Intersystem Crossing Mechanisms of Photoexcited 2‑Thiouracil

Accurate excited-state quantum chemical calculations on 2-thiouracil, employing large active spaces and up to quadruple-ζ quality basis sets in multistate complete active space perturbation theory calculations, are reported. The results suggest that the main relaxation path for 2-thiouracil after photoexcitation should be S₂ → S₁ → T₂ → T₁, and that this relaxation occurs on a subpicosecond time scale. There are two deactivation pathways from the initially excited bright S₂ state to S₁, one of which is nearly barrierless and should promote ultrafast internal conversion. After relaxation to the S₁ minimum, small singlet–triplet energy gaps and spin–orbit couplings of about 130 cm^–1 are expected to facilitate intersystem crossing to T₂, from where very fast internal conversion to T₁ occurs. An important finding is that 2-thiouracil shows strong pyramidalization at the carbon atom of the thiocarbonyl group in several excited states

Intersystem Crossing Pathways in the Noncanonical Nucleobase 2‑Thiouracil: A Time-Dependent Picture

The deactivation mechanism after ultraviolet irradiation of 2-thiouracil has been investigated using nonadiabatic dynamics simulations at the MS-CASPT2 level of theory. It is found that after excitation the S₂ quickly relaxes to S₁, and from there intersystem crossing takes place to both T₂ and T₁ with a time constant of 400 fs and a triplet yield above 80%, in very good agreement with recent femtosecond experiments in solution. Both indirect S₁ → T₂ → T₁ and direct S₁ → T₁ pathways contribute to intersystem crossing, with the former being predominant. The results contribute to the understanding of how some noncanonical nucleobases respond to harmful ultraviolet light, which could be relevant for prospective photochemotherapeutic applications

Cyclobutane Thymine Photodimerization Mechanism Revealed by Nonadiabatic Molecular Dynamics

The formation of cyclobutane thymine dimers is one of the most important DNA carcinogenic photolesions induced by ultraviolet irradiation. The long debated question whether thymine dimerization after direct light excitation involves singlet or triplet states is investigated here for the first time using nonadiabatic molecular dynamics simulations. We find that the precursor of this [2 + 2] cycloaddition reaction is the singlet doubly π²π*² excited state, which is spectroscopically rather dark. Excitation to the bright ¹ππ* or dark ¹nπ* excited states does not lead to thymine dimer formation. In all cases, intersystem crossing to the triplet states is not observed during the simulated time, indicating that ultrafast dimerization occurs in the singlet manifold. The dynamics simulations also show that dimerization takes place only when conformational control happens in the doubly excited state

Femtosecond Intersystem Crossing in the DNA Nucleobase Cytosine

Ab initio molecular dynamics including nonadiabatic and spin–orbit couplings on equal footing is used to unravel the deactivation of cytosine after UV light absorption. Intersystem crossing (ISC) is found to compete directly with internal conversion in tens of femtoseconds, thus making cytosine the organic compound with the fastest triplet population calculated so far. It is found that close degeneracy between singlet and triplet states can more than compensate for very small spin–orbit couplings, leading to efficient ISC. The femtosecond nature of the ISC process highlights its importance in photochemistry and challenges the conventional view that large singlet–triplet couplings are required for an efficient population flow into triplet states. These findings are important to understand DNA photostability and the photochemistry and dynamics of organic molecules in general

Solvatochromic Effects on the Absorption Spectrum of 2‑Thiocytosine

The solvatochromic effects of six different solvents on the UV absorption spectrum of 2-thiocytosine have been studied by a combination of experimental and theoretical techniques. The steady-state absorption spectra show significant shifts of the absorption bands, where in more polar solvents the first absorption maximum shifts to higher transition energies and the second maximum to lower energies. The observed solvatochromic shifts have been rationalized using three popular solvatochromic scales and with high-level multireference quantum chemistry calculations including implicit and explicit solvent effects. It has been found that the dipole moments of the excited states account for some general shifts in the excitation energies, whereas the explicit solvent interactions explain the differences in the spectra recorded in the different solvents

Efficient and Flexible Computation of Many-Electron Wave Function Overlaps

A new algorithm for the computation of the overlap between many-electron wave functions is described. This algorithm allows for the extensive use of recurring intermediates and thus provides high computational efficiency. Because of the general formalism employed, overlaps can be computed for varying wave function types, molecular orbitals, basis sets, and molecular geometries. This paves the way for efficiently computing nonadiabatic interaction terms for dynamics simulations. In addition, other application areas can be envisaged, such as the comparison of wave functions constructed at different levels of theory. Aside from explaining the algorithm and evaluating the performance, a detailed analysis of the numerical stability of wave function overlaps is carried out, and strategies for overcoming potential severe pitfalls due to displaced atoms and truncated wave functions are presented

OpenMolcas: From source code to insight

In this article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with post calculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory and new electronic and muonic basis sets