Explicit Modelling of Spectral Bandshapes by a Mixed Quantum-Classical Approach: Solvent Order and Temperature Effects in the Optical Spectra of Distyrylbenzene.

The absorption and emission spectral shapes of a flexible organic probe, the distyrylbenzene (DSB) dye, are simulated accounting for the effect of different environments of increasing complexity, ranging from a homogeneous, low-molecular- weight solvent, to a long-chain alkane, and, eventually, a channel-forming organic matrix. Each embedding is treated explicitly, adopting a mixed quantum-classical approach, the Adiabatic Molecular Dynamics - generalized vertical Hessian (Ad-MD|gVH) model, which allows a direct simulation of the environment-induced constraining effects on the vibronic spectral shapes. In such a theoretical framework, the stiff modes of the dye are described at a quantum level within the harmonic approximation, including Duschinsky mixing effects, while flexible degrees of freedom of the solute (e. g. torsions) and those of the solvent are treated classically by means of molecular dynamics sampling. Such a setup is shown to reproduce the distinct effects exerted by the different environments in varied thermodynamic conditions. Besides allowing for a first-principles rationale on the supramolecular mechanism leading to the experimental spectral features, this result represents the first successful application of the Ad-MD|gVH method to complex embeddings and supports its potential application to other heterogeneous environments, such as for instance, pigment-protein complexes or organic dyes adsorbed into metal-organic frameworks.

Dynamic effects on the nonlinear optical properties of donor acceptor stenhouse adducts: insights from combined MD + QM simulations.

The second-order nonlinear optical (NLO) responses of a donor-acceptor stenhouse adduct (DASA) are investigated by using a computational approach combining molecular dynamics simulations and density functional theory (DFT) calculations. Specific force fields for the open and closed photoswitching forms are first parameterized and validated according to the Joyce protocol, in order to finely reproduce the geometrical features and potential energy surfaces of both isomers in chloroform solution. Then, DFT calculations are performed on structural snapshots extracted at regular time steps of the MD trajectories to address the influence of the thermalized conformational dynamics on the NLO responses related to hyper-Rayleigh scattering (HRS) experiments. We show that accounting for the structural dynamics largely enhances the HRS hyperpolarizability (ßHRS) compared to DFT calculations considering solely equilibrium geometries, and greatly improves the agreement with experimental measurements. Furthermore, we show that the NLO responses of the NLO-active open form are correlated with the bond order alternation along the triene bridge connecting the donor and acceptor moieties, which is rationalized using simple essential state models.

Spanish Cross-Cultural Adaptation and Validation of the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score.

CONTEXT: There are no available questionnaires in Spanish that assess the function and performance of shoulder and elbow in overhead sports. The Kerlan-Jobe Orthopaedic Clinic (KJOC) score is a reference tool for this purpose. We aimed to cross-culturally adapt and investigate its measurement properties in Spanish overhead athletes. DESIGN: Cross-cultural adaptation followed the steps of direct translation, back translation, comprehensibility analysis, and review by the Committee of Experts. Then, symptomatic and asymptomatic overhead athletes were invited to complete an electronic version of the Spanish adaptation (KJOC-Sp). The structural validity was evaluated through an exploratory factor analysis with principal axis factoring. Hypotheses were tested for known-groups and convergent validity, studying the correlation with the Shoulder Pain and Disability Index and the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaires in symptomatic athletes. Cronbach alpha was calculated for internal consistency and intraclass correlation coefficient (ICC)2,1 for test-retest reliability. Floor and ceiling effects and time to completion were also calculated. RESULTS: The KJOC-Sp maintained the content of the original version and was adapted to the new population. One hundred participants (41 females and 59 males) with a mean age of 22.4 (5.9) years participated in the study of measurement properties. The factor analysis revealed a 1-factor solution. Symptomatic participants scored significantly lower than asymptomatic, with a large effect size (P < .001; r = .67). Correlations were of -.60 (P < .05) with the Shoulder and Pain Disability Index questionnaire and -0.66 (P < .05) with the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaire. Cronbach alpha was .98 (95% confidence interval, .97-.98) and the ICC2,1 was .96 (95% confidence interval .93-.98). No floor or ceiling effects were observed among the symptomatic athletes, while mean time to completion was 121 seconds. CONCLUSION: The KJOC-Sp is equivalent to the original score, aside from valid and reliable, without floor or ceiling effects in symptomatic athletes and with a low time consumption.

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/.

Unraveling the contributions to the spectral shape of flexible dyes in solution: insights on the absorption spectrum of an oxyluciferin analogue.

We present a computational investigation of the absorption spectrum in water of 5,5-spirocyclopropyl-oxyluciferin (5,5-CprOxyLH), an analogue of the emitter compound responsible for the bioluminescence in fireflies. Several factors participate in determining the 5,5-CprOxyLH's spectral shape: (i) the contribution of the four close-energy excited states, which show significant non-adiabatic couplings, (ii) the flexible molecular structure and (iii) the specific interactions established with the surrounding environment, which strongly couple the protic solvent dynamics with the dye's spectral response. To tackle the challenge to capture and dissect the role of all these effects we preliminarily investigate the role of non-adiabatic couplings with quantum dynamics simulations and a linear vibronic coupling model in the gas phase. Then, we account for both the molecular flexibility and solvent interactions by resorting to a mixed quantum classical protocol, named Adiabatic Molecular Dynamics generalized Vertical Gradient (Ad-MD|gVG), which is built on a method recently proposed by some of us. It is rooted in the partition between stiff degrees of freedom of the dye, accounted for at the vibronic level within the harmonic approximation, and flexible degrees of freedom of the solute (and of the solvent), described classically through a sampling based on Molecular Dynamics (MD). Ad-MD|gVG avoids spurious effects arising in the excited state Hessians due to non-adiabatic couplings, and can therefore be applied to account for the contributions of the first four excited states to the 5,5-CprOxyLH absorption spectrum. The final simulated spectrum is in very good agreement with the experiment, especially when the MD is driven by a refined quantum-mechanically derived force-field. More importantly, the origin of each separate contribution to the spectral shape is appropriately accounted for, paving the way to future applications of the method to more complex systems or alternative spectroscopies, as emission or circular dichroism.

Vibrationally resolved two-photon electronic spectra including vibrational pre-excitation: Theory and application to VIPER spectroscopy with two-photon excitation.

Following up on our previous work on vibrationally resolved electronic absorption spectra including the effect of vibrational pre-excitation [von Cosel et al., J. Chem. Phys. 147, 164116 (2017)], we present a combined theoretical and experimental study of two-photon-induced vibronic transitions in polyatomic molecules that are probed in the VIbrationally Promoted Electronic Resonance experiment using two-photon excitation (2P-VIPER). In order to compute vibronic spectra, we employ time-independent and time-dependent methods based on the evaluation of Franck-Condon overlap integrals and Fourier transformations of time-domain correlation functions, respectively. The time-independent approach uses a generalized version of the FCclasses method, while the time-dependent approach relies on the analytical evaluation of Gaussian moments within the harmonic approximation, including Duschinsky rotation effects. For the Coumarin 6 dye, two-dimensional 2P-VIPER experiments involving excitation to the lowest-lying singlet excited state (S1) are presented and compared with corresponding one-photon VIPER spectra. In both cases, coumarin ring modes and a CO stretch mode show VIPER activity, albeit with different relative intensities. Selective pre-excitation of these modes leads to a pronounced redshift of the low-frequency edge of the electronic absorption spectrum, which is a prerequisite for the VIPER experiment. Theoretical analysis underscores the role of interference between Franck-Condon and Herzberg-Teller effects in the two-photon experiment, which is at the root of the observed intensity distribution.

What do we know about the epidemiology of avoidant/restrictive food intake disorder in children and adolescents? A systematic review of the literature.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) was a new diagnosis in DSM-5. This systematic review explores what is known to date about the epidemiology of ARFID in children and adolescents. METHOD: Embase, Medline and PsycInfo were used to identify studies meeting inclusion criteria. PRISMA guidelines were followed. RESULTS: Thirty studies met inclusion criteria, with most coming from specialised eating disorder services where prevalence rates were 5%-22.5%. Three studies from specialist feeding clinics showed the highest prevalence rates, ranging from 32% to 64%. Studies from non-clinical samples reported ARFID prevalence estimates ranging from 0.3% to 15.5%. One study, using national surveillance methodology, reported the incidence of ARFID in children and adolescents reaching clinical care to be 2.02 per 100,000 patients. Psychiatric comorbidity was common, especially anxiety disorders (9.1%-72%) and autism spectrum disorder (8.2%-54.75%). CONCLUSION: The current literature on the epidemiology of ARFID in children and adolescents is limited. Studies are heterogeneous with regard to setting and sample characteristics, with a wide range of prevalence estimates. Further studies, especially using surveillance methodology, will help to better understand the nature of this disorder and estimate clinical service needs.

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 applied.

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|gVH), 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 interactions.

Nonadiabatic Vibrational Resonance Raman Spectra from Quantum Dynamics Propagations with LVC Models. Application to Thymine.

We present a viable protocol to compute vibrational resonance Raman (vRR) spectra for systems with several close-lying and potentially coupled electronic states. It is based on the parametrization of linear vibronic coupling (LVC) models from time-dependent density functional theory (TD-DFT) calculations and quantum dynamics propagations of vibronic wavepackets with the multilayer version of the multiconfiguration time-dependent Hartree (ML-MCTDH) method. Our approach is applied to thymine considering seven coupled electronic states, comprising the three lowest bright states, and all vibrational coordinates. Computed vRR at different excitation wavelengths are in good agreement with the available experimental data. Up to 250 nm the signal is dominated by the lowest HOMO → LUMO transition, whereas at 233 nm, in the valley between the two lowest energy absorption bands, the contributions of all the three bright states, and their interferences and couplings, are important. Inclusion of solvent (water) effects improves the agreement with experiment, reproducing the coalescence of vibrational bands due to CC and C═O stretchings. With our approach we disentangle and assess the effect of interferences between the contribution of different quasi-resonant states to the transition polarizability and the effect of interstate couplings. Our findings strongly suggest that in cases of close-lying and potentially coupled states a simple inclusion of interference effects is not sufficient, and a fully nonadiabatic computation should instead be performed. We also document that for systems with strong couplings and quasi-degenerate states, the use of HT perturbative approach, not designed for these cases, may lead to large artifacts.

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 designed 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 sensing.

Quantum and semiclassical dynamical studies of nonadiabatic processes in solution: achievements and perspectives.

We concisely review the main methodological approaches to model nonadiabatic dynamics in isotropic solutions and their applications. Three general classes of models are identified as the most used to include solvent effects in the simulations. The first model describes the solvent as a set of harmonic collective modes coupled to the solute degrees of freedom, and the second as a continuum, while the third explicitly includes solvent molecules in the calculations. The issues related to the use of these models in semiclassical and quantum dynamical simulations are discussed, as well as the main limitations and perspectives of each approach.

Ab Initio Partition Functions and Thermodynamic Quantities for the Molecular Hydrogen Isotopologues.

In this work, we calculate the partition functions and thermodynamic quantities of molecular hydrogen isotopologues using the rovibrational energy levels provided by the highly accurate ab initio adiabatic potential energy functions recently determined by Pachucki and Komasa (Pachucki, K.; Komasa, J. J. Chem. Phys. 2014, 141, 224103). The partition functions are calculated by including all bound energy levels of the isotopologues, up to their dissociation limits, plus the quasi-bound levels lying below the centrifugal potential barriers. For the homonuclear isotopologues, H2, D2, and T2, we also determine the partition functions and thermodynamic quantities of the normal mixtures using the statistical treatment recently proposed by Colonna et al. (Colonna, G.; D'Angola, A.; Capitelli, M. Int. J. Hydrogen Energy 2012, 37, 9656) based on the definition of the partition function of the mixture, which avoids inconsistencies in the values of the thermodynamic quantities depending directly on the internal partition function, in the high-temperature limit.

Counterion-Mediated Crossing of the Cyanine Limit in Crystals and Fluid Solution: Bond Length Alternation and Spectral Broadening Unveiled by Quantum Chemistry.

Absorption spectra of cyanine⊕·Br⊖ salts show a remarkable solvent dependence in non/polar solvents, exhibiting narrow, sharp band shapes in dichloromethane but broad features in toluene; this change was attributed to ion pair association, stabilizing an asymmetric dipolar structure, similar to the situation in the crystal (Bouit, P.-A., et al. J. Am. Chem. Soc. 2010, 132, 4328). Our density functional theory (DFT)-based quantum mechanics/molecular mechanics (QM/MM) calculations of the crystals evidence the crucial role of specific asymmetric anion positioning on the lowering of the symmetry. Molecular dynamics (MD) simulations prove the ion pair association in nonpolar solvents. Time-dependent DFT vibronic calculations in toluene show that ion pairing indeed stabilizes an asymmetric dipolar structure in the electronic ground state. This largely broadens the absorption spectrum in very reasonable agreement with experiment, while the principal pattern of vibrational modes is retained. The current findings allow us to establish a unified picture of the symmetry breaking of polymethine dyes in fluid solution.

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 residues.

Predicting fluorescence quantum yields for molecules in solution: A critical assessment of the harmonic approximation and the choice of the lineshape function.

For the rational design of new fluorophores, reliable predictions of fluorescence quantum yields from first principles would be of great help. However, efficient computational approaches for predicting transition rates usually assume that the vibrational structure is harmonic. While the harmonic approximation has been used successfully to predict vibrationally resolved spectra and radiative rates, its reliability for non-radiative rates is much more questionable. Since non-adiabatic transitions convert large amounts of electronic energy into vibrational energy, the highly excited final vibrational states deviate greatly from harmonic oscillator eigenfunctions. We employ a time-dependent formalism to compute radiative and non-radiative rates for transitions and study the dependence on model parameters. For several coumarin dyes, we compare different adiabatic and vertical harmonic models (AS, ASF, AH, VG, VGF, and VH), in order to dissect the importance of displacements, frequency changes, and Duschinsky rotations. In addition, we analyze the effect of different broadening functions (Gaussian, Lorentzian, or Voigt). Moreover, to assess the qualitative influence of anharmonicity on the internal conversion rate, we develop a simplified anharmonic model. We address the reliability of these models considering the potential errors introduced by the harmonic approximation and the phenomenological width of the broadening function.

Intraresidual Correlated Motions in Peptide Chains.

We investigate the interresidual and intraresidual correlations between dihedral displacements of adjacent residues within model polyalanine peptides by analyzing extensive molecular dynamics trajectories. Correlations are evaluated individually at different residue conformations covering the whole (ϕi,ψi)-space. From these, we draw maps that unveil an unprecedented strong intramolecular correlation displaying opposite (correlated/anticorrelated) behaviors at different conformations. Both interresidual and intraresidual correlations arise from the propensity of the peptide to minimize the overall atomic displacements.

Applications of Developmental Psychopathology.

Developmental psychopathology studies the basic mechanisms, including not only biological factors but also environmental and social factors that may interact with them, by means of which developmental pathways deviate toward pathological or typical outcomes. Family studies conducted during the last century show substantial evidence of heritability among psychiatric disorders. Besides, a large number of genes implicated in shaping the development of the central nervous system have been related to psychiatric conditions. In addition, there is a wide range of stressors and harmful agents that, when acting on sensitive developmental periods, might damage brain function and generate or precipitate psychopathology over time. All these factors have the potential to change the way disorders with a neurodevelopmental origin are expressed, including their age of appearance and clinical manifestations. Both symptoms and social impairment need to be considered in clinical evaluations, as treatment is unlikely to be effective if the problem has not been characterized correctly or if the patients' particular characteristics, which change throughout development, are not taken into consideration.

A computational study of the vibrationally-resolved electronic circular dichroism spectra of single-chain transoid and cisoid oligothiophenes in chiral conformations.

We simulate the vibronic profile of the electronic circular dichroism (ECD) spectra of oligothiophenes in cisoid and transoid chiral arrangements. We consider oligomers of different lengths, from two to fifteen units, and investigate extensively how the ECD spectral shapes depend on the inter-ring torsions. In general, the molecular structures we consider are not stationary points of the ground state potential energy surface. Therefore, in order to perform vibronic calculations, we present a new computational protocol able to define reduced-dimensionality models where the effect of the off-equilibrium modes is removed. This is done adopting a description of the vibrational motions in curvilinear internal coordinates, and vertical harmonic models coupled with an iterative application of projectors to define energy Hessians, and therefore effective normal modes, in the space complementary to the one of the off-equilibrium coordinates. Although we consider both Franck-Condon and Herzberg-Teller contributions, the results show that transoid twisted ribbons always give rise to monosignated ECD spectra, while bi-signated and multi-signated spectra are expected for cisoid helices. These findings are explained on the basis of the different transition strengths of the lowest electronic states imparted by the different spatial arrangement, that is almost linear for transoid structures and more globular for cisoid ones. We predicted the chiroptical response of a large number of possible molecular arrangements. These data are employed to critically discuss the experimental ECD of polythiophenes in different experimental conditions, forming either aggregates or host-guest complexes. The method here proposed to perform vibronic calculations in reduced-dimensionality models is of general applicability and its potential interest goes beyond the practical application presented here.