Photoswitchable Molecular Units with Tunable Nonlinear Optical Activity: A Theoretical Investigation.

The first-, second-, and third-order molecular nonlinear optical properties, including two-photon absorption of a series of derivatives, involving two dithienylethene (DTE) groups connected by several molecular linkers (bis(ethylene-1,2-dithiolato)Ni- (NiBDT), naphthalene, quasilinear oligothiophene chains), are investigated by employing density functional theory (DFT). These properties can be efficiently controlled by DTE switches, in connection with light of appropriate frequency. NiBDT, as a linker, is associated with a greater contrast, in comparison to naphthalene, between the first and second hyperpolarizabilities of the "open-open" and the "closed-closed" isomers. This is explained by invoking the low-lying excited states of NiBDT. It is shown that the second hyperpolarizability can be used as an index, which follows the structural changes induced by photochromism. Assuming a Förster type transfer mechanism, the intramolecular excited-state energy transfer (EET) mechanism is studied. Two important parameters related to this are computed: the electronic coupling (VDA) between the donor and acceptor fragments as well as the overlap between the absorption and emission spectra of the donor and acceptor groups. NiBDT as a linker is associated with a low electronic coupling, VDA, value. We found that VDA is affected by molecular geometry. Our results predict that the linker strongly influences the communication between the open-closed DTE groups. The sensitivity of the molecular nonlinear optical properties could assist with identification of molecular isomers.

Tailoring Colors by O Annulation of Polycyclic Aromatic Hydrocarbons.

The synthesis of O-doped polyaromatic hydro- carbons in which two polycyclic aromatic hydrocarbon sub units are bridged through one or two O atoms has been achieved. This includes high-yield ring-closure key steps that, depending on the reaction conditions, result in the formation of furanyl or pyranopyranyl linkages through intramolecular C-O bond formation. Comprehensive photophysical measurements in solution showed that these compounds have exceptionally high emission yields and tunable absorption properties throughout the UV/Vis spectral region. Electrochemical investigations showed that in all cases O annulation increases the electron-donor capabilities by raising the HOMO energy level, whereas the LUMO energy level is less affected. Moreover, third-order nonlinear optical (NLO) measurements on solutions or thin films containing the dyes showed very good values of the second hyperpolarizability. Importantly, poly(methyl methacrylate) films containing the pyranopyranyl derivatives exhibited weak linear absorption and NLO absorption compared to the nonlinearity and NLO refraction, respectively, and thus revealed them to be exceptional organic materials for photonic devices.

Compilation of Data and Modelling of Nanoparticle Interactions and Toxicity in the NanoPUZZLES Project.

The particular properties of nanomaterials have led to their rapidly increasing use in diverse fields of application. However, safety assessment is not keeping pace and there are still gaps in the understanding of their hazards. Computational models predicting nanotoxicity, such as (quantitative) structure-activity relationships ((Q)SARs), can contribute to safety evaluation, in line with general efforts to apply alternative methods in chemical risk assessment. Their development is highly dependent on the availability of reliable and high quality experimental data, both regarding the compounds' properties as well as the measured toxic effects. In particular, "nano-QSARs" should take the nano-specific characteristics into account. The information compiled needs to be well organized, quality controlled and standardized. Integrating the data in an overarching, structured data collection aims to (a) organize the data in a way to support modelling, (b) make (meta)data necessary for modelling available, and (c) add value by making a comparison between data from different sources possible.Based on the available data, specific descriptors can be derived to parameterize the nanomaterial-specific structure and physico-chemical properties appropriately. Furthermore, the interactions between nanoparticles and biological systems as well as small molecules, which can lead to modifications of the structure of the active nanoparticles, need to be described and taken into account in the development of models to predict the biological activity and toxicity of nanoparticles. The EU NanoPUZZLES project was part of a global cooperative effort to advance data availability and modelling approaches supporting the characterization and evaluation of nanomaterials.

A Computational Study of the Interaction and Polarization Effects of Complexes Involving Molecular Graphene and C60 or a Nucleobases.

A systematic analysis of the molecular structure, energetics, electronic (hyper)polarizabilities and their interaction-induced counterparts of C60 with a series of molecular graphene (MG) models, CmHn, where m = 24, 84, 114, 222, 366, 546 and n = 12, 24, 30, 42, 54, 66, was performed. All the reported data were computed by employing density functional theory and a series of basis sets. The main goal of the study is to investigate how alteration of the size of the MG model affects the strength of the interaction, charge rearrangement, and polarization and interaction-induced polarization of the complex, C60-MG. A Hirshfeld-based scheme has been employed in order to provide information on the intrinsic polarizability density representations of the reported complexes. It was found that the interaction energy increases approaching a limit of -26.98 kcal/mol for m = 366 and 546; the polarizability and second hyperpolarizability increase with increasing the size of MG. An opposite trend was observed for the dipole moment. Interestingly, the variation of the first hyperpolarizability is relatively small with m. Since polarizability is a key factor for the stability of molecular graphene with nucleobases (NB), a study of the magnitude of the interaction-induced polarizability of C84H24-NB complexes is also reported, aiming to reveal changes of its magnitude with the type of NB. The binding strength of C84H24-NB complexes is also computed and found to be in agreement with available theoretical and experimental data. The interaction involved in C60 B12N12H24-NB complexes has also been considered, featuring the effect of contamination on the binding strength between MG and NBs.

Stability and binding effects of silver(I) complexes at lipoxygenase-1.

An anti-inflammatory complex of Ag(I), namely [Ag(tpp)3(asp)](dmf) [tpp = triphenylphosphine, aspH = aspirin, dmf = N,N-dimethylformamide], was synthesized in an attempt to develop novel metallotherapeutic molecules. STD (1)H NMR experiments were used to examine if this complex binds to LOX-1. The (1)H NMR spectra in buffer Tris/D2O betrayed the existence of two complexes: the complex of aspirin and the complex of salicylic acid produced after deacetylation of aspirin. Nevertheless, the STD spectra showed that only the complex of salicylic acid is bound to the enzyme. Molecular docking and dynamics were used to complement our study. The complexes were stabilized inside a large LOX-1 cavity by establishing a network of hydrogen bonds and steric interactions. The complex formation with salicylic acid was more favorable. The in silico results provide a plausible explanation of the experimental results, which showed that only the complex with salicylic acid enters the binding cavity.

Elucidation of conformational states, dynamics, and mechanism of binding in human κ-opioid receptor complexes.

Opioid G protein-coupled receptors (GPCRs) have been implicated in modulating pain, addiction, psychotomimesis, mood and memory, among other functions. We have employed the recently reported crystal structure of the human κ-opioid receptor (κ-OR) and performed molecular dynamics (MD), free energy, and ab initio calculations to elucidate the binding mechanism in complexes with antagonist JDTic and agonist SalA. The two systems were modeled in water and in DPPC lipid bilayers, in order to investigate the effect of the membrane upon conformational dynamics. MD and Atoms in Molecules (AIM) ab initio calculations for the complexes in water showed that each ligand was stabilized inside the binding site of the receptor through hydrogen bond interactions that involved residues Asp138 (with JDTic) and Gln115, His291, Leu212 (with SalA). The static description offered by the crystal structure was overcome to reveal a structural rearrangement of the binding pocket, which facilitated additional interactions between JDTic and Glu209/Tyr139. The role of Glu209 was emphasized, since it belongs to an extracellular loop that covers the binding site of the receptor and is crucial for ligand entrapment. The above interactions were retained in membrane complexes (SalA forms additional hydrogen bonds with Tyr139/312), except the Tyr139 interaction, which is abolished in the JDTic complex. For the first time, we report that JDTic alternates between a "V-shape" (stabilized via a water-mediated intramolecular interaction) and a more extended conformation, a feature that offers enough suppleness for effective binding. Moreover, MM-PBSA calculations showed that the more efficient JDTic binding to κ-OR compared to SalA (ΔGJDTic = -31.6 kcal mol(-1), ΔGSalA = -9.8 kcal mol(-1)) is attributed mostly to differences in electrostatic contributions. Importantly, our results are in qualitative agreement with the experiments (ΔGJDTic,exp = -14.4 kcal mol(-1), ΔGSalA,exp = -10.8 kcal mol(-1)). This study provides previously unattainable information on the dynamics of human κ-OR and insight on the rational design of drugs with improved pharmacological properties.

On the vibrational linear and nonlinear optical properties of compounds involving noble gas atoms: HXeOXeH, HXeOXeF, and FXeOXeF.

The vibrational (hyper)polarizabilities of some selected Xe derivatives are studied in the context of Bishop-Kirtman perturbation theory (BKPT) and numerical finite field methodology. It was found that for this set of rare gas compounds, the static vibrational properties are quite large, in comparison to the corresponding electronic ones, especially those of the second hyperpolarizability. This also holds for the dc-Pockels ß(-ω;ω,0), Kerr γ(-ω;ω,0,0) and electric field second harmonic generation γ (-2ω;ω,ω,0) effects, although the computed nuclear relaxation (nr) vibrational contributions are smaller in magnitude than the static ones. HXeOXeH was used to study the effects of electron correlation, basis set, and geometry. Geometry effects were found to lead to noticeable changes of the vibrational and electronic second hyperpolarizability. A limited study of the effect of Xe insertion to the nr vibrational properties is also reported. Assessment of the results revealed that Xe insertion has a remarkable effect on the nr (hyper)polarizabilities. In terms of the BKPT, this is associated with a remarkable increase of the electrical and mechanical anharmonicity terms. The latter is consistent with the anharmonic character of several vibrational modes reported for rare gas compounds.

Performance of density functional theory in computing nonresonant vibrational (hyper)polarizabilities.

A set of exchange-correlation functionals, including BLYP, PBE0, B3LYP, BHandHLYP, CAM-B3LYP, LC-BLYP, and HSE, has been used to determine static and dynamic nonresonant (nuclear relaxation) vibrational (hyper)polarizabilities for a series of all-trans polymethineimine (PMI) oligomers containing up to eight monomer units. These functionals are assessed against reference values obtained using the Møller-Plesset second-order perturbation theory (MP2) and CCSD methods. For the smallest oligomer, CCSD(T) calculations confirm the choice of MP2 and CCSD as appropriate for assessing the density functionals. By and large, CAM-B3LYP is the most successful, because it is best for the nuclear relaxation contribution to the static linear polarizability, intensity-dependent refractive index second hyperpolarizability, static second hyperpolarizability, and is close to the best for the electro-optical Pockels effect first hyperpolarizability. However, none of the functionals perform satisfactorily for all the vibrational (hyper)polarizabilities studied. In fact, in the case of electric field-induced second harmonic generation all of them, as well as the Hartree-Fock approximation, yield the wrong sign. We have also found that the Pople 6-31+G(d) basis set is unreliable for computing nuclear relaxation (hyper)polarizabilities of PMI oligomers due to the spurious prediction of a nonplanar equilibrium geometry.

Theoretical modelling of photoswitching of hyperpolarisabilities in ruthenium complexes.

Static excited-state polarisabilities and hyperpolarisabilities of three Ru(II) ammine complexes are computed at the density functional theory (DFT) and several correlated ab initio levels. Most accurate modelling of the low energy electronic absorption spectrum is obtained with the hybrid functionals B3LYP, B3P86 or M06 for the complex [Ru(II)(NH3)5(MeQ(+))](3+) (MeQ(+)=N-methyl-4,4'-bipyridinium, 3) in acetonitrile. The match with experimental data is less good for [Ru(II)(NH3)5L](3+) (L=N-methylpyrazinium, 2; N-methyl-4-{E,E-4-(4-pyridyl)buta-1,3-dienyl}pyridinium, 4). These calculations confirm that the first dipole- allowed excited state (FDAES) has metal-to-ligand charge-transfer (MLCT) character. Both the solution and gas-phase results obtained for 3 by using B3LYP, B3P86 or M06 are very similar to those from restricted active-space SCF second-order perturbation theory (RASPT2) with a very large basis set and large active space. However, the time-dependent DFT λ(max) predictions from the long-range corrected functionals CAM-B3LYP, LC-ωPBE and wB97XB and also the fully ab initio resolution of identity approximate coupled-cluster method (gas-phase only) are less accurate for all three complexes. The ground state (GS) two-state approximation first hyperpolarisability ß(2SA) for 3 from RASPT2 is very close to that derived experimentally via hyper-Rayleigh scattering, whereas the corresponding DFT-based values are considerably larger. The ß responses calculated by using B3LYP, B3P86 or M06 increase markedly as the π-conjugation extends on moving along the series 2→4, for both the GS and FDAES species. All three functionals predict substantial FDAES ß enhancements for each complex, increasing with the π-conjugation, up to about sevenfold for 4. Also, the computed second hyperpolarisabilities γ generally increase in the FDAES, but the results vary between the different functionals.

Structural and static electric response properties of highly symmetric lithiated silicon cages: theoretical predictions.

It is shown by density functional theory calculations that high symmetry silicon cages can be designed by coating with Li atoms. The resulting highly symmetric lithiated silicon cages (up to D(5d) symmetry) are low-lying true minima of the energy hypersurface with binding energies of the order of 4.6 eV per Si atom and moderate highest occupied molecular orbital-lowest unoccupied molecular orbital gaps. Moreover, relying on a systematic study of the electric response properties obtained by ab initio (Hartree-Fock, MP2, and configuration interaction singles (CIS)) and density functional (B3LYP, B2PLYP, and CAM-B3LYP) methods, it is shown that lithium coating has a large impact on the magnitude of their second hyperpolarizabilities resulting to highly hyperpolarizable species. Such hyperpolarizable character is directly connected to the increase in the density of the low-lying excited states triggered by the interaction between the Si cage and the surrounding Li atoms.

Molecular simulations of fluoxetine in hydrated lipid bilayers, as well as in aqueous solutions containing ß-cyclodextrin.

Fluoxetine, which is a well-known antidepressant drug, is studied in hydrated cholesterol-free and cholesterol-containing lipid bilayers through unbiased and biased atomistic molecular dynamics simulations. The latter are conducted for the calculation of the potential of mean force (PMF) of fluoxetine along an axis perpendicular to the two leaflets of the bilayer. The PMF indicates that the drug prefers to reside inside the lipid phase and allows us to calculate important thermodynamic properties, such as the Gibbs energy difference of partitioning from the water to the lipid phase and the Gibbs energy barrier for hopping events between the two leaflets of the bilayer. The results from the biased simulations are in accord with the mass density profiles calculated from the unbiased simulations. Moreover, we estimate the effect of fluoxetine mole fraction on the order parameters of the lipid alkyl chains and on the area per lipid. It is also found that fluoxetine forms a hydrogen bond network with lipids and water molecules penetrating into the lipid phase. In addition, fluoxoetine is studied in detail in aqueous solutions containing ß-cyclodextrin. It is observed from unbiased molecular dynamics simulations that the two aforementioned molecules form a noncovalent complex spontaneously and the calculated binding free energy is in agreement with the literature.

On the stability, electronic structure, and nonlinear optical properties of HXeOXeF and FXeOXeF.

The electronic ground state, stability, and linear and nonlinear optical properties of HXeOXeF and FXeOXeF have been studied theoretically by employing complete active space valence bond (CASVB), multistate complete active space perturbation theory (MS-CASPT2), and coupled cluster methods. It is shown that the oxygen inserted between the two Xe atoms significantly modifies the ground-state electronic configuration of the formed derivative by increasing the closed-shell contribution (σ(2)) and removing the diradicaloid character observed in HXe(2)F. The electronic charge distribution has been analyzed by employing the atoms-in-molecules (AIM) method. The dissociation channels of HXeOXeF and FXeOXeF have been studied in detail. It was found that these compounds are metastable, protected by substantial energy barriers and, thus, they can be prepared under appropriate conditions. Both two- and three-body dissociation reactions have been considered. The effects of inserting O in HXe(2)F and substituting H (HXeOXeF) by F, leading to FXeOXeF, on the energy barriers are discussed. The significant effects of the inserted oxygen on the polarizability and even more on the first hyperpolarizability have been computed and rationalized.

In silico study of levodopa in hydrated lipid bilayers at the atomistic level.

This article presents atomistic molecular dynamics and umbrella sampling simulations of levodopa at various concentrations in hydrated cholesterol-free 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. Levodopa is the standard medication for Parkinson's disease and is marketed under various trade names; in the context of this article, the levodopa molecule is mostly studied in its zwitterionic form but some results concerning the neutral levodopa are presented as well for comparison purposes. The motivation is to study in detail how levodopa behaves in different hydrated lipid membranes, primarily from the thermodynamic point of view, and reveal aspects of mechanism of its permeation through them. Dependencies of properties on the levodopa concentration are also investigated. Special attention is paid to the calculation of mass density profiles, order parameters and self-diffusion coefficients. Levodopa zwitterions, which form a hydrogen bond network with water and phospholipid molecules, are found to be preferentially located at the water/lipid interface, as well as in the aqueous phase surrounding the cholesterol-free and cholesterol-containing bilayers. This is concluded from the potentials of mean force calculated by umbrella sampling simulations as levodopa is transferred from the lipid to the aqueous phase along an axis perpendicular to the two leaflets of the membranes.

Theoretical investigations of the IR spectroscopy of Ni(C(2)S(2)H(2))(2). A case study of the P_VMWCI(2) algorithm including anharmonic effects.

The near infrared (NIR) spectra of bis(ethylene-1,2-dithiolato)nickel, Ni(C(2)S(2)H(2))(2) are fully interpreted here by applying a method developed for efficient automatic computation of both the infrared wave numbers and the intensities. The employed procedure uses parallel variational multiple window configuration interaction wave functions, the so-named P_VMWCI(2) algorithm, which incorporates both the mechanical and the electric anharmonic effects. It is shown that inclusion of anharmonicities is crucial for correctly assigning the fundamental, combination, and overtone vibrational frequencies in the infrared spectrum of the target system, for which conflicting assignments are found in literature.

Linear and nonlinear optical properties of triphenylamine-functionalized C60: insights from theory and experiment.

In the present study we report on the linear and nonlinear optical properties of C(60)-triphenylamine (TPhA) hybrids. The synthesized materials were prepared following the 1,3-dipolar cycloaddition of azomethine ylides onto the skeleton of C(60) forming the TPhA-based monoadduct, equatorial bis-adduct and dumbell C(60). Complementary spectroscopic techniques, such as NMR, MALDI-TOF-MS, and ATR-IR are applied for the structural characterization of the hybrid materials, while intermolecular electronic interactions are investigated by UV-Vis measurements. In all considered cases, C(60) serves as an acceptor while the triphenylamine unit is chosen as a donor. In order to investigate the dependence of the second-order hyperpolarizability on the architecture of the systems (D-A, A-D-A) we use a Z-scan technique employing 532 nm, 35 ps laser pulses. We have found that the total second-order hyperpolarizability of the C(60)-TphA-C(60) system is several times larger than that of TPhA-C(60). The results of experimental measurements are supported by quantum-chemical calculations.

Electronic and vibrational contributions to first hyperpolarizability of donor-acceptor-substituted azobenzene.

In this study we report on the electronic and vibrational (hyper)polarizabilities of donor-acceptor-substituted azobenzene. It is observed that both electronic and vibrational contributions to the electric dipole first hyperpolarizability of investigated photoactive molecule substantially depend on the conformation. The contributions to the nuclear relaxation first hyperpolarizability are found to be quite important in the case of two considered isomers (cis and trans). Although the double-harmonic term is found to be the largest in terms of magnitude, it is shown that the total value of the nuclear relaxation contribution to vibrational first hyperpolarizability is a result of subtle interplay of higher-order contributions. As a part of the study, we also assess the performance of long-range-corrected density functional theory in determining vibrational contributions to electric dipole (hyper)polarizabilities. In most cases, the applied long-range-corrected exchange-correlation potentials amend the drawbacks of their conventional counterparts.

Linear and nonlinear optical properties of a series of Ni-dithiolene derivatives.

Some linear and nonlinear optical (NLO) properties of Ni(SCH)(4) and several of its derivatives have been computed by employing a series of basis sets and a hierarchy of methods (e.g., HF, DFT, coupled cluster, and multiconfigurational techniques). The electronic structure of Ni(SCH)(4) has been also analyzed by using CASSCF/CASPT2, ab initio valence bond, and DFT methods. In particular we discuss how the diradicaloid character (DC) of Ni(SCH)(4) significantly affects its NLO properties. The quasidegeneracy of the two lowest-energy singlet states 1 (1)A(g) and 1 (1)B(1u), the clear DC nature of the former, and the very large number of low-lying states enhance the NLO properties values. These particular features are used to interpret the NLO properties of Ni(SCH)(4). The DC of the considered derivatives has been estimated and correlated with the NLO properties. CASVB computations have shown that the structures with Ni(II) are the dominant ones, while those with Ni(0) and Ni(IV) have negligible weight. The weights of the four diradical structures were discussed in connection with the weight of the structures, where all the electrons are paired. Comparative discussion of the properties of Ni(SCH)(4) with those of tetrathia fulvalene demonstrates the very large effect of Ni on the properties of the Ni-dithiolene derivatives. A similar remarkable effect on the NLO properties is produced by one or two methyl or C(3)S groups. The considered Ni-dithiolene derivatives have exceptionally large NLO properties. This feature in connection with their other physical properties makes them ideal candidates for photonic applications.

On the origin of the large electron correlation contribution to the hyperpolarizabilities of some diacetylene rare gas compounds.

A comprehensive study of the linear and nonlinear molecular optical properties of HRgC(4)H, where Rg = Ar,Kr,Xe, has been performed. Dynamical electron correlation effects were computed by employing the coupled cluster methodology. A large electron correlation contribution to the nonlinear properties of HArC(4)H has been revealed. This contribution decreases by increasing the atomic number of the inserted rare gas atom. In order to interpret the origin of this noteworthy property, the complete active space self-consistent field method was employed. We have performed a systematic study of the linear and nonlinear electric properties by modifying the active space. The calculations have shown the significant contribution of the doubly excited sigma(*2) configuration and a negligible contribution of pi(*2). A quite remarkable discrepancy between numerically and analytically evaluated hyperpolarizabilities has also been observed for HArC(4)H. This was attributed to the contribution of near degenerate states.

Computational investigation of fullerene-DNA interactions: Implications of fullerene's size and functionalization on DNA structure and binding energetics.

DNA is the building block of life, as it carries the biological information controlling development, function and reproduction of all organisms. However, its central role in storing and transferring genetic information can be severely hindered by molecules with structure altering abilities. Fullerenes are nanoparticles that find a broad spectrum of uses, but their toxicological effects on living organisms upon exposure remain unclear. The present study examines the interactions of a diverse array of fullerenes with DNA, by means of Molecular Dynamics and MM-PBSA methodologies, with special focus on structural deformations that may hint toxicity implications. Our results show that pristine and hydroxylated fullerenes have no unwinding effects upon DNA structure, with the latter displaying binding preference to the DNA major groove, achieved by both direct formation of hydrogen bonds and water molecule mediation. Fluorinated derivatives are capable of penetrating DNA structure, forming intercalative complexes with high binding affinities.

Advantages and limitations of classic and 3D QSAR approaches in nano-QSAR studies based on biological activity of fullerene derivatives.

In this contribution, the advantages and limitations of two computational techniques that can be used for the investigation of nanoparticles activity and toxicity: classic nano-QSAR (Quantitative Structure-Activity Relationships employed for nanomaterials) and 3D nano-QSAR (three-dimensional Quantitative Structure-Activity Relationships, such us Comparative Molecular Field Analysis, CoMFA/Comparative Molecular Similarity Indices Analysis, CoMSIA analysis employed for nanomaterials) have been briefly summarized. Both approaches were compared according to the selected criteria, including: efficiency, type of experimental data, class of nanomaterials, time required for calculations and computational cost, difficulties in the interpretation. Taking into account the advantages and limitations of each method, we provide the recommendations for nano-QSAR modellers and QSAR model users to be able to determine a proper and efficient methodology to investigate biological activity of nanoparticles in order to describe the underlying interactions in the most reliable and useful manner.