Photoisomerization transition state manipulation by entangled two-photon absorption.

We demonstrate how two-photon excitation with quantum light can influence elementary photochemical events. The azobenzene trans → cis isomerization following entangled two-photon excitation is simulated using quantum nuclear wave packet dynamics. Photon entanglement modulates the nuclear wave packets by coherently controlling the transition pathways. The photochemical transition state during passage of the reactive conical intersection in azobenzene photoisomerization is strongly affected with a noticeable alteration of the product yield. Quantum entanglement thus provides a novel control knob for photochemical reactions. The distribution of the vibronic coherences during the conical intersection passage strongly depends on the shape of the initial wave packet created upon quantum light excitation. X-ray signals that can experimentally monitor this coherence are simulated.

Imaging conical intersection dynamics during azobenzene photoisomerization by ultrafast X-ray diffraction.

X-ray diffraction is routinely used for structure determination of stationary molecular samples. Modern X-ray photon sources, e.g., from free-electron lasers, enable us to add temporal resolution to these scattering events, thereby providing a movie of atomic motions. We simulate and decipher the various contributions to the X-ray diffraction pattern for the femtosecond isomerization of azobenzene, a textbook photochemical process. A wealth of information is encoded besides real-time monitoring of the molecular charge density for the cis to trans isomerization. In particular, vibronic coherences emerge at the conical intersection, contributing to the total diffraction signal by mixed elastic and inelastic photon scattering. They cause distinct phase modulations in momentum space, which directly reflect the real-space phase modulation of the electronic transition density during the nonadiabatic passage. To overcome the masking by the intense elastic scattering contributions from the electronic populations in the total diffraction signal, we discuss how this information can be retrieved, e.g., by employing very hard X-rays to record large scattering momentum transfers.

Double Thionated Pyrimidine Nucleobases: Molecular Tools with Tunable Photoproperties.

Sulfur-substituted nucleobases are DNA and RNA base derivatives that exhibit extremely efficient photoinduced intersystem crossing (ISC) dynamics into the lowest-energy triplet state. The long-lived and reactive triplet states of sulfur-substituted nucleobases are crucial due to their wide range of potential applications in medicine, structural biology, and the development of organic light-emitting diodes (OLEDs) and other emerging technologies. However, a comprehensive understanding of non-negligible wavelength-dependent changes in the internal conversion (IC) and ISC events is still lacking. Here, we study the underlying mechanism using joint experimental gas-phase time-resolved photoelectron spectroscopy (TRPES) and theoretical quantum chemistry methods. We combine 2,4-dithiouracil (2,4-DTU) TRPES experimental data with computational analysis of the different photodecay processes, which are induced by increasing excitation energies along the entire linear absorption (LA) ultraviolet (UV) spectrum. Our results show how the double-thionated uracil (U), i.e., 2,4-DTU, appears as a versatile photoactivatable instrument. Multiple decay processes can be initiated with different ISC rates or triplet-state lifetimes that resemble the distinctive behavior of the singly substituted 2- or 4-thiouracil (2-TU or 4-TU). We obtained a clear partition of the LA spectrum based on the dominant photoinduced process. Our work clarifies the reasons behind the wavelength-dependent changes in the IC, ISC, and triplet-state lifetimes in doubly thionated U, becoming a biological system of utmost importance for wavelength-controlled applications. These mechanistic details and photoproperties are transferable to closely related molecular systems such as thionated thymines.

Modus Operandi of a Pedalo-Type Molecular Switch: Insight from Dynamics and Theoretical Spectroscopy.

Molecular switches which can be triggered by light to interconvert between two or more well-defined conformation differing in their chemical or physical properties are fundamental for the development of materials with on-demand functionalities. Recently, a novel molecular switch based on a the azodicarboxamide core has been reported. It exhibits a volume-conserving conformational change upon excitation, making it a promising candidate for embedding in confined environments. In order to rationally implement and efficiently utilize the azodicarboxamide molecular switch, detailed insight into the coordinates governing the excited-state dynamics is needed. Here, we report a detailed comparative picture of the molecular motion at the atomic level in the presence and absence of explicit solvent. Our hybrid quantum mechanics/molecular mechanics (QM/MM) excited state simulations reveal that, although the energy landscape is slightly modulated by the solvation, the light-induced motion is dominated by a bending-assisted pedalo-type motion independent of the solvation. To support the predicted mechanism, we simulate time-resolved IR spectroscopy from first principles, thereby resolving fingerprints of the light-induced switching process. Our calculated time-resolved data are in good agreement with previously reported measured spectra.

Environment-Driven Coherent Population Transfer Governs the Ultrafast Photophysics of Tryptophan.

By combining UV transient absorption spectroscopy with sub-30-fs temporal resolution and CASPT2/MM calculations, we present a complete description of the primary photoinduced processes in solvated tryptophan. Our results shed new light on the role of the solvent in the relaxation dynamics of tryptophan. We unveil two consecutive coherent population transfer events involving the lowest two singlet excited states: a sub-50-fs nonadiabatic La → Lb transfer through a conical intersection and a subsequent 220 fs reverse Lb → La transfer due to solvent-assisted adiabatic stabilization of the La state. Vibrational fingerprints in the transient absorption spectra provide compelling evidence of a vibronic coherence established between the two excited states from the earliest times after photoexcitation and lasting until the back-transfer to La is complete. The demonstration of response to the environment as a driver of coherent population dynamics among the excited states of tryptophan closes the long debate on its solvent-assisted relaxation mechanisms and extends its application as a local probe of protein dynamics to the ultrafast time scales.

Automatized protocol and interface to simulate QM/MM time-resolved transient absorption at TD-DFT level with COBRAMM.

We present a series of new implementations that we recently introduced in COBRAMM, the open-source academic software developed in our group. The goal of these implementations is to offer an automatized workflow and interface to simulate time-resolved transient absorption (TA) spectra of medium-to-big chromophore embedded in a complex environment. Therefore, the excited states absorption and the stimulated emission are simulated along nonadiabatic dynamics performed with trajectory surface hopping. The possibility of treating systems from medium to big size is given by the use of time-dependent density functional theory (TD-DFT) and the presence of the environment is taken into account employing a hybrid quantum mechanics/molecular mechanics (QM/MM) scheme. The full implementation includes a series of auxiliary scripts to properly setup the QM/MM system, the calculation of the wavefunction overlap along the dynamics for the propagation, the evaluation of the transition dipole moment at linear response TD-DFT level, and scripts to setup, run and analyze the TA from an ensemble of trajectories. Altogether, we believe that our implementation will open the door to the easily simulate the time-resolved TA of systems so far computationally inaccessible.

Coherent vibrational modes promote the ultrafast internal conversion and intersystem crossing in thiobases.

Thionated nucleobases are obtained by replacing oxygen with sulphur atoms in the canonical nucleobases. They absorb light efficiently in the near-ultraviolet, populating singlet states which undergo intersystem crossing to the triplet manifold on an ultrashort time scale with a high quantum yield. Nonetheless there are still important open questions about the primary mechanisms responsible for this ultrafast transition. Here we track both the electronic and the vibrational ultrafast excited-state dynamics towards the triplet state for solvated 4-thiothymidine (4TT) and 4-thiouracil (4TU) with sub-30 fs broadband transient absorption spectroscopy in the ultraviolet. A global and target analysis allows us to simultaneously resolve the contributions of the different electronically and vibrationally excited states to the whole data set. Our experimental results, combined with state-of-the-art quantum mechanics/molecular mechanics simulations and Damped Oscillation Associated Spectra (DOAS) and target analysis, support that the relaxation to the triplet state is mediated by conical intersections promoted by vibrational coherences through the population of an intermediate singlet state. In addition, the analysis of the coherent vibrational dynamics reveals that, despite sharing the same relaxation mechanism and similar chemical structures, 4TT and 4TU exhibit rather different geometrical deformations, characterized by the conservation of planarity in 4TU and its partial rupture in 4TT.

iSPECTRON: A simulation interface for linear and nonlinear spectra with ab-initio quantum chemistry software.

We introduce iSPECTRON, a program that parses data from common quantum chemistry software (NWChem, OpenMolcas, Gaussian, Cobramm, etc.), produces the input files for the simulation of linear and nonlinear spectroscopy of molecules with the Spectron code, and analyzes the spectra with a broad range of tools. Vibronic spectra are expressed in term of the electronic eigenstates, obtained from quantum chemistry computations, and vibrational/bath effects are incorporated in the framework of the displaced harmonic oscillator model, where all required quantities are computed at the Franck-Condon point. The program capabilities are illustrated by simulating linear absorption, transient absorption and two dimensional electronic spectra of the pyrene molecule. Calculations at two levels of electronic structure theory, time-dependent density functional theory (with NWChem) and RASSCF/RASPT2 (with OpenMolcas) are presented and compared where possible. The iSPECTRON program is available online at https://github.com/ispectrongit/iSPECTRON/ and distributed open source under the terms of the Educational Community License version 2.0 (ECL 2.0).

Manipulating Core Excitations in Molecules by X-Ray Cavities.

Core excitations on different atoms are highly localized and therefore decoupled. By placing molecules in an x-ray cavity the core transitions become coupled via the exchange of cavity photons and form delocalized hybrid light-matter excitations known as core polaritons. We demonstrate these effects for the two inequivalent carbon atoms in 1,1-difluoroethylene. Polariton signatures in the x-ray absorption, two-photon absorption, and multidimensional four-wave mixing signals are predicted.

Parameterization of a linear vibronic coupling model with multiconfigurational electronic structure methods to study the quantum dynamics of photoexcited pyrene.

With this work, we present a protocol for the parameterization of a Linear Vibronic Coupling (LVC) Hamiltonian for quantum dynamics using highly accurate multiconfigurational electronic structure methods such as RASPT2/RASSCF, combined with a maximum-overlap diabatization technique. Our approach is fully portable and can be applied to many medium-size rigid molecules whose excited state dynamics requires a quantum description. We present our model and discuss the details of the electronic structure calculations needed for the parameterization, analyzing critical situations that could arise in the case of strongly interacting excited states. The protocol was applied to the simulation of the excited state dynamics of the pyrene molecule, starting from either the first or the second bright state (S2 or S5). The LVC model was benchmarked against state-of-the-art quantum mechanical calculations with optimizations and energy scans and turned out to be very accurate. The dynamics simulations, performed including all active normal coordinates with the multilayer multiconfigurational time-dependent Hartree method, show good agreement with the available experimental data, endorsing prediction of the excited state mechanism, especially for S5, whose ultrafast deactivation mechanism was not yet clearly understood.

Near-Ultraviolet Circular Dichroism and Two-Dimensional Spectroscopy of Polypeptides.

A fully quantitative theory of the relationship between protein conformation and optical spectroscopy would facilitate deeper insights into biophysical and simulation studies of protein dynamics and folding. In contrast to intense bands in the far-ultraviolet, near-UV bands are much weaker and have been challenging to compute theoretically. We report some advances in the accuracy of calculations in the near-UV, which were realised through the consideration of the vibrational structure of the electronic transitions of aromatic side chains.

Ultrafast Spectroscopy of Photoactive Molecular Systems from First Principles: Where We Stand Today and Where We Are Going.

Computational spectroscopy is becoming a mandatory tool for the interpretation of the complex, and often congested, spectral maps delivered by modern non-linear multi-pulse techniques. The fields of Electronic Structure Methods, Non-Adiabatic Molecular Dynamics, and Theoretical Spectroscopy represent the three pillars of the virtual ultrafast optical spectrometer, able to deliver transient spectra in silico from first principles. A successful simulation strategy requires a synergistic approach that balances between the three fields, each one having its very own challenges and bottlenecks. The aim of this Perspective is to demonstrate that, despite these challenges, an impressive agreement between theory and experiment is achievable now regarding the modeling of ultrafast photoinduced processes in complex molecular architectures. Beyond that, some key recent developments in the three fields are presented that we believe will have major impacts on spectroscopic simulations in the very near future. Potential directions of development, pending challenges, and rising opportunities are illustrated.

A Unified Experimental/Theoretical Description of the Ultrafast Photophysics of Single and Double Thionated Uracils.

Photoinduced processes in thiouracil derivatives have lately attracted considerable attention due to their suitability for innovative biological and pharmacological applications. Here, sub-20 fs broadband transient absorption spectroscopy in the near-UV are combined with CASPT2/MM decay path calculations to unravel the excited-state decay channels of water solvated 2-thio and 2,4-dithiouracil. These molecules feature linear absorption spectra with overlapping ππ* bands, leading to parallel decay routes which we systematically track for the first time. The results reveal that different processes lead to the triplet states population, both directly from the ππ* absorbing state and via the intermediate nπ* dark state. Moreover, the 2,4-dithiouracil decay pathways is shown to be strongly correlated either to those of 2- or 4-thiouracil, depending on the sulfur atom on which the electronic transition localizes.

Spectral Tuning and Photoisomerization Efficiency in Push-Pull Azobenzenes: Designing Principles.

This work demonstrates how push-pull substitution can induce spectral tuning toward the visible range and improve the photoisomerization efficiency of azobenzene-based photoswitches, making them good candidates for technological and biological applications. The red-shifted bright ππ* state (S2) behaves like the lower and more productive dark nπ* (S1) state because less potential energy along the planar bending mode is available to reach higher energy unproductive nπ*/S0 crossing regions, which are responsible for the lower quantum yield of the parent compound. The stabilization of the bright ππ* state and the consequent increase in isomerization efficiency may be regulated via the strength of push-pull substituents. Finally, the torsional mechanism is recognized here as the unique productive route because structures with bending values attributable to the inversion mechanism were never detected, out of the 280 ππ* time-dependent density functional theory (RASPT2-validated) dynamics simulations.

Modern quantum chemistry with [Open]Molcas.

MOLCAS/OpenMolcas is an ab initio electronic structure program providing a large set of computational methods from Hartree-Fock and density functional theory to various implementations of multiconfigurational theory. This article provides a comprehensive overview of the main features of the code, specifically reviewing the use of the code in previously reported chemical applications as well as more recent applications including the calculation of magnetic properties from optimized density matrix renormalization group wave functions.

Tailoring Spectral and Photochemical Properties of Bioinspired Retinal Mimics by in Silico Engineering.

Controlling the spectral tunability and isomerization activity is currently one of the hot topics in the design of photoreversible molecular switches for application in optoelectronic devices. The present work demonstrates how to manipulate the absorption of the retinal protonated Schiff base (rPSB) chromophore over the entire visible range by targeted functionalization of the retinal backbone. Moreover, a correlation between the vertical excitation energy and the profile of the potential energy surface of the bright excited state responsible for the photoreactivity of rPSB is established. This correlation was exploited to rank the functionalized rPSBs into different classes with characteristic photoisomerization activity. Eventually, the synergic effects of functionalization and of external electric fields in the range of a few MV cm-1 were applied to achieve reversable and regioselective control of the photoisomerization propensity of selected rPBS derivatives.

Exploring the capabilities of optical pump X-ray probe NEXAFS spectroscopy to track photo-induced dynamics mediated by conical intersections.

X-ray spectroscopy is gaining a growing interest in the scientific community, as it represents a versatile and powerful experimental toolbox for probing the dynamics of both core and valence electronic excitations, nuclear motions and material structure, with element and site specificity. Among the various X-ray based techniques, near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, which investigates the energy and probability of resonant core-to-valence transitions, has started to be applied to organic molecules: a recent UV-pump X-ray probe time-resolved NEXAFS experiment [Wolf et al., Nat. Commun., 2017, 8, 1] has shown the capability of the technique to provide information about the ultrafast internal conversion between the bright ππ* and the dark nπ* electronic states of the nucleobase thymine. In the present contribution we introduce an accurate theoretical approach for the simulation of NEXAFS spectra of organic molecules, employing azobenzene as a test case. The electronic structure calculations, which provide both energy levels and transition probabilities of core-to-valence excitations, were here performed with a high level multiconfigurational method, the restricted active space self consistent field (RASSCF/RASPT2). GS- and nπ*-NEXAFS spectra were obtained on the top of key molecular geometries (as the optimized cis, trans and conical intersection(s) structures) as well as along the fundamental isomerization coordinates (namely, symmetric and asymmetric bendings of the phenyl rings, and torsion around the central dihedral). We eventually characterize and explain the origin of the simulated signals, highlighting the specific signatures that make it possible to follow the excited state evolution from the nπ* Franck-Condon point, towards the conical intersection(s).

Modeling multidimensional spectral lineshapes from first principles: application to water-solvated adenine.

In this discussion we present a methodology to describe spectral lineshape from first principles, providing insight into the solvent-solute molecular interactions in terms of static and dynamic disorder and how these shape the signals recorded experimentally in linear and nonlinear optical spectroscopies, including two-dimensional electronic spectroscopy (2DES). Two different strategies for simulating the lineshape are compared: both rely on the same evaluation of the coupling between the electronic states and the intra-molecular vibrations, while they differ in describing the influence exerted by the diverse water configurations attained along a molecular dynamics (MD) simulation. The first method accounts for such water arrangements as first order perturbations on the adenine energies computed for a single reference (gas phase) quantum calculation. The second method requires computation of the manifold of excited states explicitly at each simulation snapshot, employing a hybrid quantum mechanics/molecular mechanics (QM/MM) scheme. Both approaches are applied to a large number of states of the adenine singlet excited manifold (chosen because of its biological role), and compared with available experimental data. They give comparable results but the first approach is two orders of magnitude faster. We show how the various contributions (static/dynamic disorder, intra-/inter-molecular interactions) sum up to build the total broadening observed in experiments.

X-ray linear and non-linear spectroscopy of the ESCA molecule.

Linear and nonlinear X-ray spectroscopy hold the promise to provide a complementary tool to the available ample body of terahertz to UV spectroscopic techniques, disclosing information about the electronic structure and the dynamics of a large variety of systems, spanning from transition metals to organic molecules. While experimental free electron laser facilities continue to develop, theory may take the lead in modeling and inspiring new cutting edge experiments, paving the way to their future use. As an example, the not-yet-available two-dimensional coherent X-ray spectroscopy (2DCXS), conceptually similar to 2D-NMR, is expected to provide a wealth of information about molecular structure and dynamics with an unprecedented level of detail. In the present contribution, we focus on the simulation of linear and non-linear (2DCXS) spectra of the ESCA molecule. The molecule has four inequivalent carbon K-edges and has been widely used as a benchmark for photoelectron spectroscopy. Two theoretical approaches for the computation of the system manifold of states, namely, TDDFT and RASSCF/RASPT2, are compared, and the possible signals that may appear in a 2DCXS experiment and their origin are surveyed.

Observation of the Sub-100 Femtosecond Population of a Dark State in a Thiobase Mediating Intersystem Crossing.

We combined sub-30 fs broadband transient absorption spectroscopy in the ultraviolet with state-of-the-art quantum mechanics/molecular mechanics simulations to study the ultrafast excited-state dynamics of the sulfur-substituted nucleobase 4-thiouracil. We observed a clear mismatch between the time scales for the decay of the stimulated emission from the bright ππ* state (76 ± 16 fs, experimentally elusive until now) and the buildup of the photoinduced absorption of the triplet state (225 ± 30 fs). These data provide evidence that the intersystem crossing occurs via a dark state, which is intermediately populated on the sub-100 fs time scale. Nonlinear spectroscopy simulations, extrapolated from a detailed CASPT2/MM decay path topology of the solvated system together with an excited state mixed quantum-classical nonadiabatic dynamics, reproduce the experimental results and explain the experimentally observed vibrational coherences. The theoretical analysis rationalizes the observed different triplet buildup times of 4- and 2-thiouracil.