Structural and Electronic Properties of Novel Azothiophene Dyes: A Multilevel Study Incorporating Explicit Solvation Effects.

Among azobenzene derivatives, azothiophenes represent a relatively recent family of compounds that exhibit similar characteristics as dyes and photoreactive systems. Their technological applications are extensive thanks to the additional design flexibility conferred by the heteroaromatic ring. In this study, we present a comprehensive investigation of the structural and electronic properties of novel dyes derived from 3-thiophenamine, utilizing a multilevel approach. We thoroughly examined the potential energy surfaces of the E and Z isomers for three molecules, each bearing different substituents on the phenyl ring at the para position relative to the diazo group. This exploration was conducted through quantum chemistry calculations at various levels of theory, employing a continuum solvent model. Subsequently, we incorporated an explicit solvent (a dimethyl sulfoxide-water mixture) to simulate the most stable isomers using classical molecular dynamics, delivering a clear picture of the local solvation structure and intermolecular interactions. Finally, a hybrid quantum mechanics/molecular mechanics (QM/MM) approach was employed to accurately describe the evolution of the solutes' properties within their environment, accounting for finite temperature effects.

Structural and Vibrational Properties of Carboxylates Intercalated into Layered Double Hydroxides: A Joint Computational and Experimental Study.

Layered double hydroxides (LDHs) are fascinating clay-like materials that display versatile properties, making them an extremely fertile playground for diverse applications, ranging from bio-compatible materials to the pharmaceutical industry to catalysis and photocatalysis. When intercalating organic and bio-organic species between the inorganic layers, such materials are named hybrid LDHs. The structure-property relation in these systems is particularly relevant, since most of the properties of the materials may be fine-tuned if a comprehensive understanding of the microscopic structure in the interlamellar space is achieved, especially with respect to the reorganization under water uptake (swelling). In this work, we combined experiments and simulations to rationalize the behavior of LDHs intercalating three carboxylates, the general structure of which can be given as [Mg4Al2(OH)12]A2-·XH2O (with A2- = succinate, aspartate, or glutamate and X representing increasing water content). Following this strategy, we were able to provide an interpretation of the different shapes observed for the experimental water adsorption isotherms and for the evolution of the infrared carboxylate band of the anions. Apart from small differences, due to the different reorganization of the conformational space under confinement, the behavior of the two amino acids is very similar. However, such behavior is quite different in the case of succinate. We were able to describe the different response of the anions, which has a significant impact on the isotherm and on the size of the interlamellar region, in terms of a different interaction mechanism with the inorganic layer.

Hydration effects on the vibrational properties of carboxylates: From continuum models to QM/MM simulations.

The presence of carboxyl groups in a molecule delivers an affinity to metal cations and a sensitivity to the chemical environment, especially for an environment that can give rise to intermolecular hydrogen bonds. Carboxylate groups can also induce intramolecular interactions, such as the formation of hydrogen bonds with donor groups, leading to an impact on the conformational space of biomolecules. In the latter case, the protonation state of the amino groups plays an important role. In order to provide an accurate description of the modifications induced in a carboxylated molecule by the formation of hydrogen bonds, one needs a compromise between a quantum chemical description of the system and the necessity to take into account explicit solvent molecules. In this work, we propose a bottom-up approach to study the conformational space and the carboxylate stretching band of (bio)organic anions. Starting from the anions in a continuum solvent, we then move to calculations using a microsolvation approach including one explicit water molecule per polar group, immersed in a continuum. Finally, we run QM/MM molecular dynamics simulations to analyze the solvation properties and to explore the anions conformational space. The results thus obtained are in good agreement with the description given by the microsolvation approach and they bring a more detailed description of the solvation shell and of the intermolecular hydrogen bonds.

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.

Optical properties of photodynamic therapy drugs in different environments: the paradigmatic case of temoporfin.

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) - a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based on the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into cells, is fundamental to achieve the desired effect on malignant tissues via PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments -in vacuo, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

Short- and Long-Range Solvation Effects on the Transient UV-Vis Absorption Spectra of a Ru(II)-Polypyridine Complex Disentangled by Nonequilibrium Molecular Dynamics.

Evidence of subtle effects in the dynamic reorganization of a protic solvent in its first- and farther-neighbor shells, in response to the sudden change in the solute's electronic distribution upon excitation, is unveiled by a multilevel computational approach. Through the combination of nonequilibrium molecular dynamics and quantum mechanical calculations, the experimental time evolution of the transient T1 absorption spectra of a heteroleptic Ru(II)-polypyridine complex in ethanol or dimethyl sulfoxide solution is reproduced and rationalized in terms of both fast and slow solvent re-equilibration processes, which are found responsible for the red shift and broadening experimentally observed only in the protic medium. Solvent orientational correlation functions and a time-dependent analysis of the solvation structure confirm that the initial, fast observed red shift can be traced back to the destruction-formation of hydrogen bond networks in the first-neighbor shell, whereas the subsequent shift, evident in the [20-500] ps range and accompanied by a large broadening of the signal, is connected to a collective reorientation of the second and farther solvation shells, which significantly changes the electrostatic embedding felt by the excited solute.

Dynamical and Environmental Effects on the Optical Properties of an Heteroleptic Ru(II)-Polypyridine Complex: A Multilevel Approach Combining Accurate Ground and Excited State QM-Derived Force Fields, MD and TD-DFT.

An integrated multilevel approach is here built by combining classical molecular dynamic (MD) simulations, time-dependent density functional theory (TD-DFT) calculations, and solvation dynamics linear response (LR) analysis, and successively employed to investigate the optical properties and solvation structure of a prototypical heteroleptic Ru(II)-polypyridyl complex, widely employed in dye sensitized solar cells. The MD simulations are performed with an accurately parametrized intramolecular force field (FF), specifically derived from the quantum chemical (DFT) description of the molecule, both for its singlet and triplet ground states. Solvent effects, in ethanol (EtOH) and dimethyl sulfoxide (DMSO), are taken into account at different levels of approximation, going from a totally implicit description (polarizable continuum) to an hybrid explicit/implicit scheme. Our results show that the developed FFs were able to accurately describe and preserve the octahedral coordination of the Ru(II) center along the MD trajectories, yielding an accurate picture of the solute dynamics. Noticeably, the dynamical effects and the inclusion of an explicit microsolvation shell were found to be crucial to get a good agreement with the experimental absorption spectrum in EtOH, in both shape and positions of the main bands. The significant experimental blue-shift of the two low-energy bands in DMSO, that is not reproduced by the simulated thermal-averaged spectra, is, instead, attributed to deprotonation phenomena of the carboxylic groups, induced by the strong nucleophilic character of the solvent. Finally, analysis of the solvent response shows that the structural changes in the first solvation shell, following the metal-ligand to ligand charge transfer excitation, cause, in the protic medium the breakdown of the linear response approximation, which, on the contrary, holds for DMSO.

Electronic Interactions in Iminophosphorane Superbase Complexes with Carbon Dioxide.

Iminophosphoranes or phosphazenes are an important class of compounds with increasing use in synthetic organic chemistry as neutral organic superbases exhibiting low nucleophilicity. Their electronic structure and therefore their properties strongly depend on substitution, but there have been very few theoretical studies devoted to this topic, and more specifically to the formation of electron donor-acceptor complexes of iminophosphoranes with electrophiles. In this work, we have investigated the interaction with carbon dioxide at different ab initio levels. Carbon dioxide usually behaves as a Lewis acid and the reaction with iminiphosphoranes has been described as a nonconventional aza-Wittig process leading to isocyanates. The reaction can be conducted in supercritical CO2 conditions (carbon dioxide acts as both solvent and reactant), which is a promising strategy in the context of green chemistry. Our calculations have been carried out at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVTZ level for model systems and at the M06-2X/6-611+G(d,p) level for a larger species used in experiments. The electronic interactions and the interaction energies are analyzed and discussed in detail using the natural bond orbital method. Proton affinities and gas-phase basicities are provided as well.

Modeling Solvation in Supercritical CO2.

In recent decades, a microscopic understanding of solute-solvent intermolecular interactions has been key to advances in technologies based on supercritical carbon dioxide. In many cases, computational work has provided the impetus for new discoveries, shedding new light on important concepts such as the local structure around the solute in the supercritical medium, the influence of the peculiar properties of the latter on the molecular behavior of dissolved substances and, importantly, CO2 -philicity. In this Review, the theoretical work that has been relevant to these developments is surveyed and, by presenting some crucial open questions, the possible routes to achieving further progress based on the interplay between theory and experiments is discussed.

Dipole and quadrupole polarizabilities of the water molecule as a function of geometry.

Dipolar, dipole-quadrupole and quadrupole-quadrupole static polarizabilities of the water molecule have been determined by ab initio calculations at coupled cluster level of theory with single, double and perturbative triple excitations CCSD(T) with an aug-cc-pVTZ basis set using a finite field and field-gradient method. The geometry dependence of polarizability tensor components has been explored and modeled by power series expansion in bond length and angle variations up to sum of powers equal to 4. The results provide a very detailed description of the static polarizability of water up to quadrupolar rank which can be used for the test and development of novel accurate polarizable interaction potentials for modeling aqueous solutions. © 2016 Wiley Periodicals, Inc.

Driving Forces Controlling Host-Guest Recognition in Supercritical Carbon Dioxide Solvent.

The formation of supramolecular host-guest complexes is a very useful and widely employed tool in chemistry. However, supramolecular chemistry in non-conventional solvents such as supercritical carbon dioxide (scCO2 ), one of the most promising sustainable solvents, is still in its infancy. In this work, we explored a successful route to the development of green processes in supercritical CO2 by combining a theoretical approach with experiments. We were able to synthesize and characterize an inclusion complex between a polar aromatic molecule (benzoic acid) and peracetylated-ß-cyclodextrin, which is soluble in the supercritical medium. This finding opens the way to wide, environmental friendly, applications of scCO2 in many areas of chemistry, including supramolecular synthesis, reactivity and catalysis, micro and nano-particle formation, molecular recognition, as well as enhanced extraction processes with increased selectivity.

Geometry-dependent distributed polarizability models for the water molecule.

Geometry-dependent distributed polarizability models have been constructed by fits to ab initio calculations at the coupled cluster level of theory with up to noniterative triple excitations in an augmented triple-zeta quality basis set for the water molecule in the field of a point charge. The investigated models include (i) charge-flow polarizabilities between chemically bonded atoms, (ii) isotropic or anisotropic dipolar polarizabilities on oxygen atom or on all atoms, and (iii) combinations of models (i) and (ii). For each model, the polarizability parameters have been optimized to reproduce the induction energy of a water molecule polarized by a point charge successively occupying a grid of points surrounding the molecule. The quality of the models is ascertained by examining their ability to reproduce these induction energies as well as the molecular dipolar and quadrupolar polarizabilities. The geometry dependence of the distributed polarizability models has been explored by changing bond lengths and HOH angle to generate 125 molecular structures (reduced to 75 symmetry-unique ones). For each considered model, the distributed polarizability components have been fitted as a function of the geometry by a Taylor expansion in monomer coordinate displacements up to the sum of powers equal to 4.

Hydration Effect on Amide I Infrared Bands in Water: An Interpretation Based on an Interaction Energy Decomposition Scheme.

The sensitivity of some infrared bands to the local environment can be exploited to shed light on the structure and the dynamics of biological systems. In particular, the amide I band, which is specifically related to vibrations within the peptide bonds, can give information on the ternary structure of proteins, and can be used as a probe of energy transfer. In this work, we propose a model to quantitatively interpret the frequency shift on the amide I band of a model peptide induced by the formation of hydrogen bonds in the first solvation shell. This method allows us to analyze to what extent the electrostatic interaction, electronic polarization and charge transfer affect the position of the amide I band. The impact of the anharmoniticy of the pontential energy surface on the hydration induced shift is elucidated as well.

Water interactions with hydrophobic groups: assessment and recalibration of semiempirical molecular orbital methods.

In this work, we present a study of the ability of different semiempirical methods to describe intermolecular interactions in water solution. In particular, we focus on methods based on the Neglect of Diatomic Differential Overlap approximation. Significant improvements of these methods have been reported in the literature in the past years regarding the description of non-covalent interactions. In particular, a broad range of methodologies has been developed to deal with the properties of hydrogen-bonded systems, with varying degrees of success. In contrast, the interactions between water and a molecule containing hydrophobic groups have been little analyzed. Indeed, by considering the potential energy surfaces obtained using different semiempirical Hamiltonians for the intermolecular interactions of model systems, we found that none of the available methods provides an entirely satisfactory description of both hydrophobic and hydrophilic interactions in water. In addition, a vibrational analysis carried out in a model system for these interactions, a methane clathrate cluster, showed that some recent methods cannot be used to carry out studies of vibrational properties. Following a procedure established in our group [M. I. Bernal-Uruchurtu, M. T. C. Martins-Costa, C. Millot, and M. F. Ruiz-López, J. Comput. Chem. 21, 572 (2000); W. Harb, M. I. Bernal-Uruchurtu, and M. F. Ruiz-López, Theor. Chem. Acc. 112, 204 (2004)], we developed new parameters for the core-core interaction terms based on fitting potential energy curves obtained at the MP2 level for our model system. We investigated the transferability of the new parameters to describe a system, having both hydrophilic and hydrophobic groups, interacting with water. We found that only by introducing two different sets of parameters for hydrophilic and hydrophobic hydrogen atom types we are able to match the features of the ab initio calculated properties. Once this assumption is made, a good agreement with the MP2 reference is achieved. The results reported in this work provide therefore a direction for future developments of semiempirical approaches that are still required to investigate chemical processes in biomolecules and in large disordered systems.

Vibrational energy relaxation of the amide I mode of N-methylacetamide in D2O studied through Born-Oppenheimer molecular dynamics.

The vibrational relaxation of the amide I mode of deuterated N-methylacetamide in D2O solution is studied through nonequilibrium simulations using the semiempirical Born-Oppenheimer molecular dynamics (SEBOMD) approach to describe the whole solute-solvent system. Relaxation pathways and lifetimes are determined using the instantaneous normal mode (INM) analysis. The relaxation of the amide I mode is characterized by three different time scales; most of the excess energy (80%) is redistributed through intramolecular vibrational energy redistribution processes, with a smaller contribution (20%) of intermolecular energy flowing into the solvent. The amide II mode is found to contribute modestly (7%) to the relaxation mechanism. The amide I mode and the total vibrational energy decay curves obtained using SEBOMD and INM are in satisfactory agreement with the experimental measurements.

Taste for chiral guests: investigating the stereoselective binding of peptides to ß-cyclodextrins.

Obtaining compounds of diastereomeric purity is extremely important in the field of biological and pharmaceutical industry, where amino acids and peptides are widely employed. In this work, we theoretically investigate the possibility of chiral separation of peptides by ß-cyclodextrins (ß-CDs), providing a description of the associated interaction mechanisms by means of molecular dynamics (MD) simulations. The formation of host/guest complexes by including a model peptide in the macrocycle cavity is analyzed and discussed. We consider the terminally blocked phenylalanine dipeptide (Ace-Phe-Nme), in the L- and D-configurations, to be involved in the host/guest recognition process. The CD-peptide free energies of binding for the two enantiomers are evaluated through a combined approach that assumes: (1) extracting a set of independent molecular structures from the MD simulation, (2) evaluating the interaction energies for the host/guest complexes by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations carried out on each structure, for which we also compute, (3) the solvation energies through the Poisson-Boltzmann surface area method. We find that chiral discrimination by the CD macrocycle is of the order of 1 kcal/mol, which is comparable to experimental data for similar systems. According to our results, the Ace-(D)Phe-Nme isomer leads to a more stable complex with a ß-CD compared to the Ace-(L)Phe-Nme isomer. Nevertheless, we show that the chiral selectivity of ß-CDs may strongly depend on the secondary structure of larger peptides. Although the free energy differences are relatively small, the predicted selectivities can be rationalized in terms of host/guest hydrogen bonds and hydration effects. Indeed, the two enantiomers display different interaction modes with the cyclodextrin macrocavity and different mobility within the cavity. This finding suggests a new interpretation for the interactions that play a key role in chiral recognition, which may be exploited to design more efficient and selective chiral separations of peptides.

Intermolecular structure and collective dynamics of supercritical fluoroform studied by molecular dynamics simulations.

The density dependence of the local structure and of collective dynamics of a polar fluid fluoroform along an isotherm at a temperature of 1.03 T(c), in the near-critical (NC) region, were studied by classical molecular dynamics (MD) simulations. In the case of local structure we focus on local density inhomogeneities and on orientational pair correlations that are relevant to dielectric properties and light scattering intensities. Our results show that the density dependence of the frequency shifts of fluoroform ν(2) and ν(3) modes correlates well with that of intermolecular dipole-dipole interactions. Our study of collective dynamics deals with dipole and polarizability anisotropy relaxation, experimentally accessible through far-infrared absorption, depolarized light scattering, and optical Kerr effect. Our MD simulations were performed using an all-atom nonpolarizable potential model of fluoroform. Contributions of induced dipoles to dielectric properties were included using first-order perturbation theory, and this approach was also used to include interaction-induced contributions to polarizability anisotropy relaxation. For interactions involving induced dipoles, we calculated and compared the results of a distributed polarizability model to a model with a single polarizable site located at the center-of-mass. Using a projection scheme that allows us to identify the contributions from different relaxation mechanisms, we found that dipole relaxation is dominated by collective reorientation, while in the case of polarizability anisotropy, relaxation processes related to translational dynamics make a major contribution over most of the fluid density range. The dielectric properties of fluoroform in the NC region were calculated and compared to the corresponding measurements. We found the dielectric constant and the far-infrared absorption spectrum to be in good agreement with experiments.

A new glimpse into the CO(2)-philicity of carbonyl compounds.

We report a theoretical study on non-conventional structures of 1:1 complexes between carbon dioxide and carbonyl compounds. These structures have never been reported before but are relevant for understanding the solubility of carbonyl compounds in supercritical CO(2). The work is based on the results of ab initio calculations at the MP2 and CCSD(T) levels using aug-cc-pVDZ and aug-cc-pVTZ basis sets. Investigated systems include aldehydes, ketones and esters, together with some fluorinated derivatives. The results are interpreted in terms of natural bond orbital analyses. Harmonic vibrational frequency calculations have also been done in order to compare them with available experimental data. We show for the first time that complexes where CO(2) behaves globally as a Lewis base are stable in the case of ketones and esters, but not in the case of aldehydes, and their stability is similar to that of traditional complexes in which CO(2) behaves as a Lewis acid. This finding considerably modifies the concept of CO(2)-philicity and may have important ramifications in the development of green reactions in supercritical CO(2).

Cavity closure dynamics of peracetylated ß-cyclodextrins in supercritical carbon dioxide.

Structural properties of peracetylated ß-cyclodextrin in supercritical carbon dioxide were investigated by means of molecular dynamics simulations. The study indicated a strong reduction of the cavity accessibility to guest molecules, compared to native ß-cyclodextrin in water. Indeed, the cavity is self-closed during the largest part of the simulation, which agrees well with suggestions made on the basis on high-pressure NMR experiments. Self-closure happens because one glucose unit undergoes a main conformational change (from chair to skew) that brings one of the acetyl groups in the wide rim of the cyclodextrin to the cavity interior. This arrangement turns out to be quite favorable, persisting for several nanoseconds. In addition to the wide rim self-closure, a narrow rim self-closure may also occur, though it is less likely and exhibits short duration (<1 ns). Therefore, the number of solvent molecules reaching the cavity interior is much smaller than that found in the case of native ß-cyclodextrin in water after correction to account for different molar densities. These findings support the weak tendency of the macromolecule to form host-guest complexes in this nonconventional medium, as reported by some experiments. Finally, Lewis acid/base interactions between the acetyl carbonyl groups and the solvent CO(2) molecules were analyzed through ab initio calculations that revealed the existence of a quite favorable four-member ring structure not yet reported. The ensemble of these results can contribute to establish general thermodynamic principles controlling the formation of inclusion complexes in supercritical CO(2), where the hydrophilicity/hydrophobicity balance is not applicable.