Javier Cerezo

Insights for an Accurate Comparison of Computational Data to Experimental Absorption and Emission Spectra: Beyond the Vertical Transition Approximation.

In this work we carefully investigate the relationship between computed data and experimental electronic spectra. To that end, we compare both vertical transition energies, EV, and characteristic frequencies of the spectrum like the maximum, ν(max), and the center of gravity, M(1), taking advantage of an analytical expression of M(1) in terms of the parameters of the initial- and final-state potential energy surfaces. After pointing out that, for an accurate comparison, experimental spectra should be preliminarily mapped from wavelength to frequency domain and transformed to normalized lineshapes, we simulate the absorption and emission spectra of several prototypical chromophores, obtaining lineshapes in very good agreement with experimental data. Our results indicate that the customary comparison of experimental ν(max) and computational EV, without taking into account vibrational effects, is not an adequate measure of the performance of an electronic method. In fact, it introduces systematic errors that, in the investigated systems, are on the order of 0.1-0.3 eV, i.e., values comparable to the expected accuracy of the most accurate computational methods. On the contrary, a comparison of experimental and computed M(1) and/or 0-0 transition frequencies provides more robust results. Some rules of thumbs are proposed to help rationalize which kind of correction one should expect when comparing EV, M(1), and ν(max).

Harmonic Models in Cartesian and Internal Coordinates to Simulate the Absorption Spectra of Carotenoids at Finite Temperatures

When large structural displacements take place between the ground state (GS) and excited state (ES) minima of polyatomic molecules, the choice of a proper set of coordinates can be crucial for a reliable simulation of the vibrationally resolved absorption spectrum. In this work, we study two carotenoids that undergo structural displacements from GS to ES minima of different magnitude, from small displacements for violaxanthin to rather large ones for β-carotene isomers. Their finite-temperature (77 and 300 K) spectra are simulated at the harmonic level, including Duschinsky effect, by time-dependent (TD) and time-independent (TI) approaches, using (TD)DFT computed potential energy surfaces (PES). We adopted two approaches to construct the harmonic PES, the Adiabatic (AH) and Vertical Hessian (VH) models and, for AH, two reference coordinate frames: Cartesian and valence internal coordinates. Our results show that when large displacements take place, Cartesian coordinates dramatically fail to describe curvilinear displacements and to account for the Duschinsky matrix, preventing a realistic simulation of the spectra within the AH model, where the GS and ES PESs are quadratically expanded around their own equilibrium geometry. In contrast, internal coordinates largely amend such deficiencies and deliver reasonable spectral widths. As expected, both coordinate frames give similar results when small displacements occur. The good agreement between VH and experimental line shapes indicates that VH model, in which GS and ES normal modes are both evaluated at the GS equilibrium geometry, is a good alternative to deal with systems exhibiting large displacements. The use of this model can be, however, problematic when imaginary frequencies arise. The extent of the nonorthogonality of the Dushinsky matrix in internal coordinates and its correlation with the magnitude of the displacement of the GS and ES geometries is analyzed in detail.

Absorption and emission spectral shapes of a prototype dye in water by combining classical/dynamical and quantum/static approaches.

We study the absorption and emission electronic spectra in an aqueous solution of N-methyl-6-oxyquinolinium betaine (MQ), an interesting dye characterized by a large change of polarity and H-bond ability between the ground (S0) and the excited (S1) states. To that end we compare alternative approaches based either on explicit solvent models and density functional theory (DFT)/molecular-mechanics (MM) calculations or on DFT calculations on clusters models embedded in a polarizable continuum (PCM). In the first approach (ClMD), the spectrum is computed according to the classical Franck-Condon principle, from the dispersion of the time-dependent (TD)-DFT vertical transitions at selected snapshots of molecular dynamics (MD) on the initial state. In the cluster model (Qst) the spectrum is simulated by computing the quantum vibronic structure, estimating the inhomogeneous broadening from state-specific TD-DFT/PCM solvent reorganization energies. While both approaches provide absorption and emission spectral shapes in nice agreement with experiment, the Stokes shift is perfectly reproduced by Qst calculations if S0 and S1 clusters are selected on the grounds of the MD trajectory. Furthermore, Qst spectra better fit the experimental line shape, mostly in absorption. Comparison of the predictions of the two approaches is very instructive: the positions of Qst and ClMD spectra are shifted due to the different solvent models and the ClMD spectra are narrower than the Qst ones, because MD underestimates the width of the vibrational density of states of the high-frequency modes coupled to the electronic transition. On the other hand, both Qst and ClMD approaches highlight that the solvent has multiple and potentially opposite effects on the spectral width, so that the broadening due to solute-solvent vibrations and electrostatic interaction with bulk solvent is (partially) counterbalanced by a narrowing of the contribution due to the solute vibrational modes. Qst analysis evidences a pure quantum broadening effect of the spectra in water due to vibronic progressions along the solute/solvent H-bonds.

Modeling Solvent Broadening on the Vibronic Spectra of a Series of Coumarin Dyes. From Implicit to Explicit Solvent Models.

We present a protocol to estimate the solvent-induced broadening of electronic spectra based on a model that explicitly takes into account the environment embedding the solute. Starting from a classical approximation of the solvent contribution to the spectrum, the broadening arises from the spread of the excitation energies due to the fluctuation of the solvent coordinates, and it is represented as a Gaussian line shape that convolutes the vibronic spectrum of the solute. The latter is computed in harmonic approximation at room temperature with a time-dependent approach. The proposed protocol for the computation of spectral broadening exploits molecular dynamics (MD) simulations performed on the solute-solvent system, keeping the solute degrees of freedom frozen, followed by the computation of the excitation properties with a quantum mechanics/molecular mechanics (QM/MM) approach. The factors that might influence each step of the protocol are analyzed in detail, including the selection of the empirical force field (FF) adopted in the MD simulations and the QM/MM partition of the system to compute the excitation energies. The procedure is applied to a family of coumarin dyes, and the results are compared with experiments and with the predictions of a very recent work (Cerezo et al., Phys. Chem. Chem. Phys. 2015, 17, 11401-11411), where an implicit model was adopted for the solvent. The final spectra of the considered coumarins were obtained without including ad hoc phenomenological parameters and indicate that the broadenings computed with explicit and implicit models both follow the experimental trend, increasing as the polarity change from the initial to the final state increases. More in detail, the implicit model provides larger estimations of the broadening that are closer to the experimental evidence, while explicit models appear to better capture relative differences arising from different solvents or different solutes. Possible inaccuracies of the adopted FF that may lead to the observed underestimation are analyzed in detail.

Antioxidant properties of β-carotene isomers and their role in photosystems: insights from Ab initio simulations.

In this work we investigate the effect of cis isomerizations and conformational changes on the antioxidant activity of β-carotene, one of the most important pigments in nature. The electrodonating (ω(-)) and electroaccepting (ω(+)) powers of the most relevant isomers of β-carotene are first evaluated in polar and nonpolar solvents using density functional theory (DFT), and these quantities are then used to establish an antioxidant scale of the isomers. The electrodonating power, which is directly related to the antioxidant activity, is shown to provide a very good correlation with the experimental data. Next, we compute the intermediate twisted structures of the β-carotene isomers generated by partial rotation of every single bond in the polyenic chain. The electrodonating and electroaccepting powers are evaluated for each of these intermediate structures along with their maximum absorption wavelengths, which are computed using time-dependent DFT (TD-DFT). The trends observed for both the electrodonating power and the maximum absorption wavelength can be rationalized in terms of the effective conjugated chain length of the structure resulting from single bond rotations. The results obtained are used to analyze the conformational distribution of β-carotene in the well-resolved photosystem I (PS-I) of purple cyanobacteria. It is then shown that the isomers present in this photosystem are those having the lowest calculated relative energies and that those with enhanced antioxidant activity are preferentially located in the inner core of the protein complex.

Atomistic molecular dynamics simulations of the interactions of oleic and 2-hydroxyoleic acids with phosphatidylcholine bilayers.

Fatty oleic acid (OA) and, recently, its derivative 2-hydroxyoleic acid (2OHOA) have been reported to display an important therapeutic activity. To understand better these therapeutic effects at the molecular and cellular levels, in this work we have carried out molecular dynamics simulations to elucidate the structural and dynamical changes taking place in model 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers upon insertion of rising concentrations of these two fatty acids. The simulations are performed using a united-atoms model to describe both the phospholipids and the fatty acids. The process of insertion of the fatty acids from the aqueous phase into the bilayers is simulated first, showing that it is feasible and may lead to some degree of phase separation within the bilayer. The interactions of the embedded homogeneously dispersed fatty acids with the phospholipid chains of the bilayers are then simulated at different concentrations of the fatty acids. The results from these simulations show that accumulation of OA and 2OHOA up to high concentrations induces only small structural changes in the bilayers. An increase of the mobility of the lipid and fatty acid chains at rising fatty acid concentrations is also observed, which is more marked for the fatty acid chains, along with an enhancement of the permeability of the bilayers to the hydrophobic penetrant.

Labelling Herceptin with a novel oxaliplatin derivative: a computational approach towards the selective drug delivery

AbstractThe clinical use of platinum(II)-based drugs has serious side effects due to the non-specific reactions with both malignant and normal cells. To circumvent such major drawback, novel metallodrugs might be combined with suitable carrier molecules, as antibodies, to ensure selective attacks on tumours while sparing healthy tissues. In this contribution, we investigate the stability of a novel oxaliplatin derivate drug embedded in Herceptin (trastuzumab), an antibody which is able to recognise breast cancer cells, by using a wide panel of theoretical tools: docking, molecular dynamics and quantum calculations. Our calculations reveal the binding mechanism: the drug initially interacts non-covalently with the Pro40A and Asp167A residues, and the nitrogen of His171B subsequently replaces one of the water molecules coordinated to the platinum center, where the latter step reversibly fixes the drug into the antibody. These data might be used to further rationalise the synthesis of improved drugs beyond classical platinum(II) derivatives by improving the ligand-protein coupling mode. Graphical AbstractA wide panel of theoretical tools is used to determine the chemical interactions stablished between a novel platinum(II)-based drug when linked to the Herceptin antibody.

Optical Properties of Diarylethenes with TD-DFT: 0-0 Energies, Fluorescence, Stokes Shifts, and Vibronic Shapes.

This contribution is an investigation of both the structures and optical properties of a set of 14 diverse, recently synthesized diarylethenes using Time-Dependent Density Functional Theory (TD-DFT) at the ωB97X-D/6-31G(d) level of theory. The linear response (LR) and state-specific (SS) versions of the Polarizable Continuum Model (PCM) have been adopted to account for the bulk solvation effects and their relative performances were critically accessed. It is shown, for the first time in the case of nontrivial diarylethenes, that TD-DFT provides good agreement between the experimental absorption-fluorescence crossing points (AFCPs) and their theoretical counterparts when a robust model accounting for both geometrical relaxation and vibrational corrections is used instead of the vertical approximation. On the other hand, the theoretical estimates for the Stokes shifts based on the vertical transition energies were found to be in disagreement with respect to experiment, prompting us to simulate the absorption/emission vibronic band shapes. It is proved that difficulties associated with the breakdown of the harmonic approximation in Cartesian coordinates exist for the investigated system, and we show how they can be at least partially overcome by means of a vertical approach including Duschinsky effects. Our results provide a valuable basis to rationalize the experimental vibronic structure of both emission and absorption bands and are expected to be a significant asset to the understanding of the optical properties of diarylethene derivatives.

Comparing classical approaches with empirical or quantum-mechanically derived force fields for the simulation electronic lineshapes: application to coumarin dyes

The simulation of optical properties in complex and heterogeneous systems, as those involved in photovoltaic devices, requires efficient protocols able to account for the complexity of the environment. An usual procedure is based on molecular dynamics (MD) sampling and subsequent computation of the transition properties, at quantum mechanics/molecular mechanics (QM/MM) level, adopting, e.g., time-dependent density functional theory for the QM part. In this work, we adopt such protocol to simulate the spectra of two structurally related coumarin dyes employed as sensitizers in solar cells, c343 and nkx-2586, and we focus on gas-phase results with the scope to investigate in detail the impact of two key aspects of the protocol: the choice of the force field (FF) and the classical approximation of the spectra. We start from the selection of a FF able to accurately describe the intramolecular interactions in the system, comparing the predictions of a generic empirical force field (namely, GAFF) and a molecule-specific quantum-mechanically derived FF. The MD simulations generated by adopting each FF are analysed in terms of the sampled normal mode distributions, providing a rationale to understand the features (position and width) of the absorption spectra simulated from the distribution of vertical energies. By comparing those simulations with classical, semiclassical and fully quantum formulations of the vibronic lineshapes based on harmonic models, we demonstrate the necessity of high-quality FFs. Notwithstanding this, our results highlight that irrespective of the choice between the two FFs, the largest errors arise from the classical description of the fast nuclear motions (e.g. bond stretchings), thus emphasizing the need to account for quantum effects in order to achieve an accurate simulation of the spectrum. We further analyse the spectra simulated using a number of harmonic models of the initial and final states at either QM or FF levels, pointing out the occurrence of remarkable inaccuracies due to the large differences in the QM and FF normal modes. This problem is inherent to the fixed functional forms associated to any MM FF, and our results indicate a convenient route to avoid it. This knowledge is a prerequisite towards the goal of developing hybrid quantum/classical QM/MM approaches for the calculations of spectra in complex environments.

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 dynamics.