FCclasses3: vibrationally-resolved spectra simulated at the edge of the harmonic approximation

We introduce FCclasses3, a code to carry out vibronic simulations of electronic spectra and nonradiative rates, based on the harmonic approximation. Key new features are: implementation of the full family of vertical and adiabatic harmonic models, vibrational analysis in curvilinear coordinates, extension to several electronic spectroscopies and implementation of time-dependent approaches. The use of curvilinear valence internal coordinates allows the adoption of quadratic model potential energy surfaces (PES) of the initial and final states expanded at arbitrary configurations. Moreover, the implementation of suitable projectors provides a robust framework for defining reduced-dimensionality models by sorting flexible coordinates out of the harmonic subset, so that they can then be treated at anharmonic level, or with mixed quantum classical approaches. A set of tools to facilitate input preparation and output analysis is also provided. We show the program at work in the simulation of different spectra (one and two-photon absorption, emission and resonance Raman) and internal conversion rate of a typical rigid molecule, anthracene. Then, we focus on absorption and emission spectra of a series of flexible polyphenyl molecules, highlighting the relevance of some of the newly implemented features. The code is freely available at http://www.iccom.cnr.it/en/fcclasses/Ministerio de Ciencia e Innovacion, Grant/Award Number: PID2019-110091GB-I00; Ministerio de Universidades, Plan de Recuperacion, Transformación y Resiliencia, Grant/Award Number: CA2/RSUE/2021-00890; Universidad Autonoma de Madri

On the role of entropy in the stabilization of α-helices

Protein folding evolves by exploring the conformational space with a subtle balance between enthalpy and entropy changes which eventually leads to a decrease of free energy upon reaching the folded structure. A complete understanding of this process requires, therefore, a deep insight into both contributions to free energy. In this work, we clarify the role of entropy in favoring the stabilization of folded structures in polyalanine peptides with up to 12 residues. We use a novel method referred to as K2V that allows us to obtain the potential-energy landscapes in terms of residue conformations extracted from molecular dynamics simulations at conformational equilibrium and yields folding thermodynamic magnitudes, which are in agreement with the experimental data available. Our results demonstrate that the folded structures of the larger polyalanine chains are stabilized with respect to the folded structures of the shorter chains by both an energetic contribution coming from the formation of the intramolecular hydrogen bonds and an entropic contribution coming from an increase of the entropy of the solvent with approximate weights of 60 and 40%, respectively, thus unveiling a key piece in the puzzle of protein folding. In addition, the ability of the K2V method to provide the enthalpic and entropic contributions for individual residues along the peptide chain makes it clear that the energetic and entropic stabilizations are basically governed by the nearest neighbor residue conformations, with the folding propensity being rationalized in terms of triads of residuesThis work was partially supported by the Spanish AgenciaEstatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE) under Project CTQ2016-79345-P and by the Fundación Séneca under Project 20789/PI/18. We thank the computational assistance provided by J.F.Hidalgo of the Servicio de Infraestructuras TIC de ATIC

On the role of entropy in the stabilization of α-Helixes

Protein folding evolves by exploring the conformational space with a subtle balance between enthalpy and entropy changes which eventually leads to a decrease of free energy upon reaching the folded structure. A complete understanding of this process requires, therefore, a deep insight into both contributions to free energy. In this work, we clarify the role of entropy in favoring the stabilization of folded structures in polyalanine peptides with up to 12 residues. We use a novel method referred to as K2V that allows us to obtain the potential-energy landscapes in terms of residue conformations extracted from molecular dynamics simulations at conformational equilibrium and yields folding thermodynamic magnitudes, which are in agreement with the experimental data available. Our results demonstrate that the folded structures of the larger polyalanine chains are stabilized with respect to the folded structures of the shorter chains by both an energetic contribution coming from the formation of the intramolecular hydrogen bonds and an entropic contribution coming from an increase of the entropy of the solvent with approximate weights of 60 and 40%, respectively, thus unveiling a key piece in the puzzle of protein folding. In addition, the ability of the K2V method to provide the enthalpic and entropic contributions for individual residues along the peptide chain makes it clear that the energetic and entropic stabilizations are basically governed by the nearest neighbor residue conformations, with the folding propensity being rationalized in terms of triads of residuesThis work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE) under Project CTQ2016-79345-P and by the Fundación Séeneca under Project 20789/PI/18. We thank the computational assistance provided by J. F. Hidalgo of the Servicio de Infraestructuras TIC de ATICA

The resonance raman spectrum of cytosine in water: analysis of the effect of specific solute–solvent interactions and non-adiabatic couplings

In this contribution, we report a computational study of the vibrational Resonance Raman (vRR) spectra of cytosine in water, on the grounds of potential energy surfaces (PES) computed by time-dependent density functional theory (TD-DFT) and CAM-B3LYP and PBE0 functionals. Cytosine is interesting because it is characterized by several close-lying and coupled electronic states, challenging the approach commonly used to compute the vRR for systems where the excitation frequency is in quasi-resonance with a single state. We adopt two recently developed time-dependent approaches, based either on quantum dynamical numerical propagations of vibronic wavepackets on coupled PES or on analytical correlation functions for cases in which inter-state couplings were neglected. In this way, we compute the vRR spectra, considering the quasi-resonance with the eight lowest-energy excited states, disentangling the role of their inter-state couplings from the mere interference of their different contributions to the transition polarizability. We show that these effects are only moderate in the excitation energy range explored by experiments, where the spectral patterns can be rationalized from the simple analysis of displacements of the equilibrium positions along the different states. Conversely, at higher energies, interference and inter-state couplings play a major role, and the adoption of a fully non-adiabatic approach is strongly recommended. We also investigate the effect of specific solute–solvent interactions on the vRR spectra, by considering a cluster of cytosine, hydrogen-bonded by six water molecules, and embedded in a polarizable continuum. We show that their inclusion remarkably improves the agreement with the experiments, mainly altering the composition of the normal modes, in terms of internal valence coordinates. We also document cases, mostly for low-frequency modes, in which a cluster model is not sufficient, and more elaborate mixed quantum classical approaches, in explicit solvent models, need to be applie

Adiabatic-Molecular Dynamics Generalized Vertical Hessian Approach: A Mixed Quantum Classical Method to Compute Electronic Spectra of Flexible Molecules in the Condensed Phase

We present a general mixed quantum classical method that couples classical molecular dynamics (MD) and vibronic models to compute the shape of electronic spectra of flexible molecules in the condensed phase without, in principle, any phenomenological broadening. It is based on a partition of the nuclear motions of the solute + solvent system in "soft" and "stiff" vibrational modes and an adiabatic hypothesis that assumes that stiff modes are much faster than soft ones. In this framework, the spectrum is rigorously expressed as a conformational integral of quantum vibronic spectra along the stiff coordinates only. Soft modes enter at the classical level through the conformational distribution that is sampled with classical MD runs. In each configuration, reduced-dimensionality quadratic Hamiltonians are built in the space of the stiff coordinates only, thanks to a generalization of the Vertical Hessian harmonic model and an iterative application of projectors in internal coordinates to remove soft modes. Quantum vibronic spectra, specific for each sampled configuration of the soft coordinates, are then computed at the desired temperature with efficient time-dependent techniques, and the global spectrum simply arises from their average. For consistency of the whole procedure, classical MD runs are performed with quantum-mechanically derived force fields, parameterized at the same level of theory selected for generating the quadratic Hamiltonians along the stiff coordinates. Application to N-methyl-6-oxyquinolinium betaine in water, dithiophene in ethanol, and cyanidine in water is presented to show the performance of the methodThis work has received funding from the European Union’s Horizon 2020 research and innovation programme MSCA-ITN under grant agreement no. 765266 (LightDyNAmics). Computational resources provided by the Centro de Cálculo Científico at Universidad Autónoma de Madrid (CCC-UAM) and by SCBI (Supercomputing and Bioinformatics) center of Universidad de Málaga are also acknowledged. D.A. and F.A. acknowledge financial support from Spanish “Ministerio de Economía y Competitividad” (project CTQ2015-65816-R). D.A. acknowledges Fundación Ramón Areces (Spain) for funding his postdoctoral stay at ICCOM-CNR Pisa. J.C. and D.A. acknowledge the Pisa Unit of ICCOM-CNR for hospitality

Mixed Quantum/Classical Method for Nonadiabatic Quantum Dynamics in Explicit Solvent Models: The ππ∗/nπ∗ Decay of Thymine in Water as a Test Case

We present a novel mixed quantum classical dynamical method to include solvent effects on internal conversion (IC) processes. All the solute degrees of freedom are represented by a wavepacket moving according to nonadiabatic quantum dynamics, while the motion of an explicit solvent model is described by an ensemble of classical trajectories. The mutual coupling of the solute and solvent dynamics is included within a mean-field framework and the quantum and classical equations of motions are solved simultaneously. As a test case we apply our method to the ultrafast ππ∗ → nπ∗ decay of thymine in water. Solvent dynamical response modifies IC yield already on the 50 fs time scale. This effect is due to water librational motions that stabilize the most populated state. Pure static disorder, that is, the existence of different solvent configurations when photoexcitation takes place, also has a remarkable impact on the dynamicsThe support of MIUR (PRIN 2010-2011 prot. 2010ERFKXL) is acknowledged. J.C. acknowledges the Fundacioń Ramoń Areces for funding his Postdoctoral position in Pisa and the fellowship provided by “Fundacioń Seńeca − Agencia de Ciencia y Tecnología de la Regioń de Murcia” through the “Saavedra-Fajardo” program (20028/SF/16). R.I. thanks the Université Paris-Saclay (Chaire d’Alembert No. 2016-10751). Y. L. acknowledges the financial support from the China Scholarship Council (CSC, No. 201506220064) and Y.L. and N. L. a generous grant of computer time from the Norwegian Programme for Supercomputing. N. L. also acknowledges the National Nature Science Foundation of China (Grant No. 21573129). The authors gratefully acknowledge G. Worth for making available the Quantics code and for useful discussion

Turn on fluorescence sensing of Zn2+ based on fused isoindole-imidazole scaffold

Optical chemosensors caused a revolution in the field of sensing due to their high specificity, sensitivity, and fast detection features. Imidazole derivatives have offered promising features in the literature as they bear suitable donor/acceptor groups for the selective analytes in the skeleton. In this work, an isoindole-imidazole containing a Schiff base chemosensor (1-{3-[(2-Diethylamino-ethylimino)-methyl]-2-hydroxy-5-methyl-phenyl}-2H-imidazo[5,1-a]isoindole-3,5-dione) was de-signed and synthesized. The complete sensing phenomena have been investigated by means of UV-Vis, fluorescence, lifetime measurement, FT-IR, NMR and ESI-MS spectroscopic techniques. The optical properties of the synthesized ligand were investigated in 3:7 HEPES buffer:DMSO medium and found to be highly selective and sensitive toward Zn2+ ion through a fluorescence turn-on response with detection limit of 0.073 µm. Furthermore, this response is effective in gel form also. The competition studies reveal that the response of the probe for Zn2+ ion is unaffected by other relevant metal ions. The stoichiometric binding study was performed utilizing Job’s method which indicated a 1:1 sensor–Zn2+ ensemble. Computational calculations were performed to pinpoint the mechanism of sensin

Non-phenomenological description of the time-resolved emission in solution with quantum-classical vibronic approaches-application to coumarin C153 in methanol

We report a joint experimental and theoretical work on the steady-state spectroscopy and time-resolved emission of the coumarin C153 dye in methanol. The lowest energy excited state of this molecule is characterized by an intramolecular charge transfer thus leading to remarkable shifts of the time-resolved emission spectra, dictated by the methanol reorganization dynamics. We selected this system as a prototypical test case for the first application of a novel computational protocol aimed at the prediction of transient emission spectral shapes, including both vibronic and solvent effects, without applying any phenomenological broadening. It combines a recently developed quantum–classical approach, the adiabatic molecular dynamics generalized vertical Hessian method (Ad-MD (Formula presented.) VH), with nonequilibrium molecular dynamics simulations. For the steady-state spectra we show that the Ad-MD|gVH approach is able to reproduce quite accurately the spectral shapes and the Stokes shift, while a ∼0.15 eV error is found on the prediction of the solvent shift going from gas phase to methanol. The spectral shape of the time-resolved emission signals is, overall, well reproduced, although the simulated spectra are slightly too broad and asymmetric at low energies with respect to experiments. As far as the spectral shift is concerned, the calculated spectra from 4 ps to 100 ps are in excellent agreement with experiments, correctly predicting the end of the solvent reorganization after about 20 ps. On the other hand, before 4 ps solvent dynamics is predicted to be too fast in the simulations and, in the sub-ps timescale, the uncertainty due to the experimental time resolution (300 fs) makes the comparison less straightforward. Finally, analysis of the reorganization of the first solvation shell surrounding the excited solute, based on atomic radial distribution functions and orientational correlations, indicates a fast solvent response (≈100 fs) characterized by the strengthening of the carbonyl–methanol hydrogen bond interactions, followed by the solvent reorientation, occurring on the ps timescale, to maximize local dipolar interactionsThis research was funded by ICSC—Centro Nazionale di Ricerca in High Performance Computing, Big Data and Quantum Computing, funded by European Union—NextGenerationEU— PNRR, Missione 4 Componente 2 Investimento 1.4 (F.S and G.P); MICINN Project PID2019-110091GBI00 (JC); H2020-LC-SC3-2020-RES-RIA-101006839 project “CONDOR” and MUR-PNRR (NEST— Network 4 Energy Sustainable Transition, Estended Partnership—PE000002 (SG, BV and NA

Caracterización teórica de la acción de ácidos grasos y carotenoides en membranas y fotosistemas.

En esta Tesis abordamos la caracterización de ácidos grasos y carotenoides en sistemas de gran relevancia biológica, como lo son las membranas celulares y los fotosistemas. Empleamos para ello técnicas computacionales tanto de la mecánica cuántica como de la mecánica molecular, que ofrecen una descripción detallada, a escala atómica, de los fenómenos químicos que tienen lugar en estos entornos. Así, en este trabajo se construyen modelos para caracterizar la actividad antioxidante de los carotenoides basados en cálculos de la teoría del funcional de la densidad (DFT), al tiempo que se desarrollan campos de fuerza empíricos para describir la conformación y las interacciones moleculares de ácidos grasos y carotenoides en los medios biológicos, que permiten su simulación mediante la dinámica molecular. Las perturbaciones estructurales producidas por los ácidos grasos con insaturaciones cis sobre las membranas juegan un papel clave en la acción terapéutica que muestran estas moléculas, y nuestros resultados muestran, específicamente, el efecto del ácido oleico y el ácido 2-hidroxioleico, destacando las diferencias entre ambos que conducen a su diferenciada actividad terapéutica. En el caso de los carotenoides, resultan más relevantes, sin embargo, las perturbaciones que produce el entorno de la membrana celular o el fotosistema sobre su cadena conjugada. La conformación de esta cadena es la que marca la actividad antioxidante y espectroscópica de estas moléculas, lo que se relaciona con su acción terapéutica. Las propiedades espectroscópicas de los carotenoides resultan de gran importancia para explicar su acción biológica en fotosistemas y, por ello, se han estudiado más detenidamente para dos carotenoides: beta-caroteno y violaxantina. Hemos caracterizado, mediante cálculos DFT y DFT dependientes del tiempo (TD-DFT) y usando modelos armónicos, las superficies de energía potencial de los estados electrónicos de baja energía entre los que se produce el transito de dipolo permitido en estas moléculas, simulando además el correspondiente espectro electrónico con resolución vibracional por medio de técnicas de la espectroscopía computacional, en formulaciones independientes y dependientes del tiempo. Nuestros resultados proporcionan espectros electrónicos de estos carotenoides a temperatura criogénica y temperatura ambiente, que pueden compararse directamente con los experimentales. ABSTRACT: In this Thesis, we perform the characterization of both fatty acids and carotenoids within relevant biological systems as cell membranes and photosystems. To that end, we apply computational techniques, both at quantum mechanics and molecular mechanics levels, which provide a detailed atomistic description of the chemical phenomena that take place within such environments. Concretely, in this work, models are constructed to characterize the antioxidant activity of carotenoids based on Density Functional Theory (DFT) calculations, and empiric force fields are also developed in order to describe the conformation and intermolecular interactions of fatty acids and carotenoids within the complex biological environments, thus allowing their simulations by means of molecular dynamics techniques. The structural perturbations produced by the fatty acids cis double bonds play a key role in the therapeutic mechanisms of these molecules, and our results show, specifically, the effect of oleic acid and 2-hydroxyoleic acid, highlighting the differences between them that eventually lead to their distinct therapeutic activity. In the case of carotenoids, however, the perturbations that the complex environment of the lipid bilayer or the photosystem induce on their conjugated chain reveals more important. The conformation of such hydrocarbon chain actually dictates the antioxidant and spectroscopic properties of these molecules, which, in turn, are related with their therapeutic activity. The spectroscopic properties of carotenoids are extremely important for their biological activity within photosystems and, therefore, they have been evaluated more in detail for two carotenoids: beta-carotene and violaxanthin. We have characterized, through DFT and Time Dependent DFT (TD-DFT) computations and using harmonic models, the potential energy surfaces of the low lying electronic states between which the allowed dipole transition in these molecules occur, also simulating the corresponding vibrationally resolved electronic spectrum by means of computational spectroscopic techniques, both adopting time independent and time dependent approaches. Our results provide the spectra at both cryogenic and room temperature, directly comparable with the experimental ones