Novel Molecular-Dynamics-Based Protocols for Phase Space Sampling in Complex Systems

The adequate exploration of the phase space of a chromophore is a fundamental necessity for the simulation of their optical and photophysical properties, taking into account the effects of vibrational motion and, most importantly, the coupling with a (non-homogeneous) molecular environment. A representative set of conformational snapshots around the Franck-Condon region is also required to perform non-adiabatic molecular dynamics, for instance in the framework of surface hopping. Indeed, in the latter case one needs to prepare a set of initial conditions providing a meaningful and complete statistical base for the subsequent trajectory propagation. In this contribution, we propose two new protocols for molecular dynamics-based phase space sampling, called “local temperature adjustment” and “individual QM/MM-based relaxation.” These protocols are intended for situations in which the popular Wigner distribution sampling procedure is not applicable—as it is the case when anharmonic or nonlinear vibrations are present—and where regular molecular dynamics sampling might suffer from an inaccurate distribution of internal energy or from inaccurate force fields. The new protocols are applied to the case of phase space sampling of [Re(CO)3(Im)(Phen)]+ (im, imidazole; phen, phenanthroline) in aqueous solution, showing the advantages and limitations of regular Wigner and molecular dynamics sampling as well as the strengths of the new protocols

Excited-states of a rhenium carbonyl diimine complex: solvation models, spin-orbit coupling, and vibrational sampling effects

Presentamos una investigación química cuántica de los estados excitados del complejo [Re (CO) 3 (Im) (Phen)] + (Im = imidazol; Phen = 1,10-fenantrolina) en solución que incluye acoplamientos de giro-órbita y muestreo vibracional. Para este objetivo, implementamos la mecánica cuántica / mecánica molecular (QM / MM) de incrustación electrostática en el conjunto de programas funcionales de densidad de Ámsterdam, adecuados para cálculos funcionales de densidad dependientes del tiempo que incluyen acoplamientos de órbita de espín. La nueva implementación se emplea para simular el espectro de absorción del complejo, que se compara con los resultados de la solvatación continua implícita y la inclusión de densidad congelada. Se utilizan simulaciones de dinámica molecular para muestrear las conformaciones del estado fundamental en la solución. Los resultados demuestran que cualquier estudio de los estados excitados de [Re (CO) 3 (Im) (Phen)] + en solución y su dinámica debe incluir un muestreo extenso de movimiento vibracional y acoplamientos de giro-órbita.We present a quantum-chemical investigation of the excited states of the complex [Re(CO)3(Im)(Phen)]+ (Im = imidazole; Phen = 1,10-phenanthroline) in solution including spin–orbit couplings and vibrational sampling. To this aim, we implemented electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) in the Amsterdam Density Functional program suite, suitable for time-dependent density functional calculations including spin–orbit couplings. The new implementation is employed to simulate the absorption spectrum of the complex, which is compared to the results of implicit continuum solvation and frozen-density embedding. Molecular dynamics simulations are used to sample the ground state conformations in solution. The results demonstrate that any study of the excited states of [Re(CO)3(Im)(Phen)]+ in solution and their dynamics should include extensive sampling of vibrational motion and spin–orbit couplings.• Austrian Science Fund. Proyecto I2883, para Sebastian Mai, Aurora Muñoz-Losa, Letizia González Herrero • Agence Nationale de la Recherche (ANR). Proyecto ANR-15-CE29-0027, para Hugo Gattuso, Maria Fumanal, Antonio Monari, Chantal Daniel • Financial Reporting Council y Labex CSC. Proyecto ANR-10-LABX-0026_CSC, para Maria Fumanal, Chantal Daniel • Action CM1405 - COSTpeerReviewe

Interaction of Iron II Complexes with B-DNA. Insights from Molecular Modeling, Spectroscopy, and Cellular Biology

We report the characterization of the interaction between B-DNA and three terpyridin iron II complexes. Relatively long time-scale molecular dynamics is used in order to characterize the stable interaction modes. By means of molecular modeling and UV-vis spectroscopy, we prove that they may lead to stable interactions with the DNA duplex. Furthermore, the presence of larger π-conjugated moieties also leads to the appearance of intercalation binding mode. Non-covalent stabilizing interactions between the iron complexes and the DNA are also characterized and evidenced by the analysis of the gradient of the electronic density. Finally, the structural deformations induced on the DNA in the different binding modes are also evidenced. The synthesis and chemical characterization of the three complexes is reported, as well as their absorption spectra in presence of DNA duplexes to prove the interaction with DNA. Finally, their effects on human cell cultures have also been evidenced to further enlighten their biological effects

Quantum Phenomena in Nanomaterials: Coherent Superpositions of Fine Structure States in CdSe Nanocrystals at Room Temperature

One of the most recent developments at the forefront of nanotechnology is the attempt to exploit quantum phenomena in nanometer scale materials, exploring novel applications of quantum effects. An effective exploitation of quantum phenomena must necessarily pass through a deep understanding of how to generate, manipulate, and characterize coherent superposition of quantum states in the nanosystems. However, despite the lively interest in this topic, the study of coherent effects in nanomaterials still represents relatively unexplored territory. Here we report an investigation on the ultrafast coherent dynamics of colloidal CdSe quantum dots (QDs) by the mean of two- dimensional electronic spectroscopy (2DES). The time evolution of specific coherent superpositions of fine structure levels in these nanomaterials is clearly demonstrated. The obtained results represent an important step forward toward a deeper understanding of quantum properties of nanomaterials

Photosensibilisation de l’ADN : modélisation des interactions entre la lumière et les systèmes moléculaires complexes

The work presented in this manuscript is based on the use of molecular modeling, simulation and theoretical chemistry in order to study the photosensitization of DNA; i.e. the enhancement of the sensitivity of DNA to light through the action of a photosensitizing agent. A first aspect has been to study the photophysical and photochemical pathways of several known sensitizers such as nileblue, nilered, BMEMC or an endogenous modified nucleobase, Pyo, in order to understand their mechanisms of photosensitization. The related phenomena that have been observed are electron transfers, triplet-triplet energy transfers, production of solvated electrons and two-photons activations. Moreover, two tools have been developed to study the interaction between photosensitizing agents and DNA; i) a protocol able to provide the binding free energy of drugs in their interaction pockets; ii) a tool based on the semi-empirical Frenkel Hamiltonian to model the electronic circular dichroism of biomacromolecular systems in a straightforward way. Then the effects of photoinduced lesions on the DNA structure and flexibility have been investigated; i.e. cylcopyrimidine dimers (CPD), pyrimidine(6-4)pyrimidone (6-4PP) and cluster abasic sites. Finally the recognition of damaged DNA strands by repair enzymes is presented and the implication on enzymatic activities has been highlighted. The reader can refer to the first section of the manuscript for a popularized presentation of the project contextLe travail présenté dans ce manuscrit est basé sur l’utilisation de la modélisation moléculaire, de la simulation et de la chimie théorique pour l’étude de la photosensibilisation de l’ADN ; c’est à dire l’augmentation de la sensibilité de l’ADN vis-à-vis de la lumière au travers de l’action d’agents photosensibilisants. Premièrement, les voies photophysiques et photochimiques de plusieurs molécules connues telles que nile bleu, nile rouge, BMEMC ou une base modifiée endogène, Pyo, ont été étudiés dans le but de comprendre leurs mécanismes de photosensibilisation. Les phénomènes associés qui ont été mis en évidence sont des transferts d’électrons et d’énergie, la production d’électrons solvatés et l’activation à deux photons. De plus, deux outils pour l’étude des interactions entre les molécules et l’ADN ont été dévellopés; i) un protocole calculatoire capable de fournir l’énergie libre d’interaction de drogues dans leurs poches; ii) un outil basé sur l’hamiltonien semi-empirique de Frenkel qui permet de modéliser le spectre de dichroïsme circulaire électronique de biomacromolécules. Ensuite, les effets de photolésions sur la structure et la flexibilité de l’ADN ont été étudiés ; i.e. les dimères de pyrimidines, la pyrimidine(6-4)pyrimidone (6-4PP) et les clusters de sites abasiques. Finalement, la reconnaissance de brins d’ADN lésés par des protéines de réparation et le rapport avec leurs activités enzymatiques a été analysé. Le lecteur peut se référer à la première partie de ce manuscrit pour une présentation vulgarisée du contexte de ce proje

DNA photosensitization : modeling the interaction between light and complex molecular systems

Le travail présenté dans ce manuscrit est basé sur l’utilisation de la modélisation moléculaire, de la simulation et de la chimie théorique pour l’étude de la photosensibilisation de l’ADN ; c’est à dire l’augmentation de la sensibilité de l’ADN vis-à-vis de la lumière au travers de l’action d’agents photosensibilisants. Premièrement, les voies photophysiques et photochimiques de plusieurs molécules connues telles que nile bleu, nile rouge, BMEMC ou une base modifiée endogène, Pyo, ont été étudiés dans le but de comprendre leurs mécanismes de photosensibilisation. Les phénomènes associés qui ont été mis en évidence sont des transferts d’électrons et d’énergie, la production d’électrons solvatés et l’activation à deux photons. De plus, deux outils pour l’étude des interactions entre les molécules et l’ADN ont été dévellopés; i) un protocole calculatoire capable de fournir l’énergie libre d’interaction de drogues dans leurs poches; ii) un outil basé sur l’hamiltonien semi-empirique de Frenkel qui permet de modéliser le spectre de dichroïsme circulaire électronique de biomacromolécules. Ensuite, les effets de photolésions sur la structure et la flexibilité de l’ADN ont été étudiés ; i.e. les dimères de pyrimidines, la pyrimidine(6-4)pyrimidone (6-4PP) et les clusters de sites abasiques. Finalement, la reconnaissance de brins d’ADN lésés par des protéines de réparation et le rapport avec leurs activités enzymatiques a été analysé. Le lecteur peut se référer à la première partie de ce manuscrit pour une présentation vulgarisée du contexte de ce projetThe work presented in this manuscript is based on the use of molecular modeling, simulation and theoretical chemistry in order to study the photosensitization of DNA; i.e. the enhancement of the sensitivity of DNA to light through the action of a photosensitizing agent. A first aspect has been to study the photophysical and photochemical pathways of several known sensitizers such as nileblue, nilered, BMEMC or an endogenous modified nucleobase, Pyo, in order to understand their mechanisms of photosensitization. The related phenomena that have been observed are electron transfers, triplet-triplet energy transfers, production of solvated electrons and two-photons activations. Moreover, two tools have been developed to study the interaction between photosensitizing agents and DNA; i) a protocol able to provide the binding free energy of drugs in their interaction pockets; ii) a tool based on the semi-empirical Frenkel Hamiltonian to model the electronic circular dichroism of biomacromolecular systems in a straightforward way. Then the effects of photoinduced lesions on the DNA structure and flexibility have been investigated; i.e. cylcopyrimidine dimers (CPD), pyrimidine(6-4)pyrimidone (6-4PP) and cluster abasic sites. Finally the recognition of damaged DNA strands by repair enzymes is presented and the implication on enzymatic activities has been highlighted. The reader can refer to the first section of the manuscript for a popularized presentation of the project contex

Nile blue and Nile red optical properties predicted by TD-DFT and CASPT2 methods: static and dynamic solvent effects

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Photophysics of chlorin e6: from one- and two-photon absorption to fluorescence and phosphorescence

We present the study of optical and photophysical properties of chlorin e6, a known photosensitizer producing singlet oxygen. The linear and non-linear optical properties have been studied taking into account the dynamical and vibrational effects both by using Wigner distribution or coupling with molecular dynamics. A force field correctly describing the out-of-plane vibrations has been properly parameterized. The photophysical study revealed a possible efficient population of the triplet manifold, from the S1 minimum region. Hence, fluorescence and singlet oxygen production are shown to coexist. Two-photon absorption high cross-section and far infrared absorption also suggest the possible use of chlorin e6 as an efficient sensitizer in two-photon absorption based phototherapy

Modeling DNA electronic circular dichroism by QM/MM methods and Frenkel Hamiltonian

International audienc

Steady-State Linear and Non-linear Optical Spectroscopy of Organic Chromophores and Bio-macromolecules

Bio-macromolecules as DNA, lipid membranes and (poly)peptides are essential compounds at the core of biological systems. The development of techniques and methodologies for their characterization is therefore necessary and of utmost interest, even though difficulties can be experienced due to their intrinsic complex nature. Among these methods, spectroscopies, relying on optical properties are especially important to determine their macromolecular structures and behaviors, as well as the possible interactions and reactivity with external dyes—often drugs or pollutants—that can (photo)sensitize the bio-macromolecule leading to eventual chemical modifications, thus damages. In this review, we will focus on the theoretical simulation of electronic spectroscopies of bio-macromolecules, considering their secondary structure and including their interaction with different kind of (photo)sensitizers. Namely, absorption, emission and electronic circular dichroism (CD) spectra are calculated and compared with the available experimental data. Non-linear properties will be also taken into account by two-photon absorption, a highly promising technique (i) to enhance absorption in the red and infra-red windows and (ii) to enhance spatial resolution. Methodologically, the implications of using implicit and explicit solvent, coupled to quantum and thermal samplings of the phase space, will be addressed. Especially, hybrid quantum mechanics/molecular mechanics (QM/MM) methods are explored for a comparison with solely QM methods, in order to address the necessity to consider an accurate description of environmental effects on spectroscopic properties of biological systems