DockSurf: A Molecular Modeling Software for the Prediction of Protein/Surface Adhesion.

The elucidation of structural interfaces between proteins and inorganic surfaces is a crucial aspect of bionanotechnology development. Despite its significance, the interfacial structures between proteins and metallic surfaces are yet to be fully understood, and the lack of experimental investigation has impeded the development of many devices. To overcome this limitation, we suggest considering the generation of protein/surface structures as a molecular docking problem with a homogenous plan as the target. To this extent, we propose a new software, DockSurf, which aims to quickly propose reliable protein/surface structures. Our approach considers the conformational exploration with Euler's angles, which provide a cartography instead of a unique structure. Interaction energies were derived from quantum mechanics computations for a set of small molecules that describe protein atom types and implemented in a Derjaguin, Landau, Verwey, and Overbeek potential for the consideration of large systems such as proteins. The validation of DockSurf software was conducted with molecular dynamics for corona proteins with gold surfaces and provided enthusiastic results. This software is implemented in the RPBS platform to facilitate widespread access to the scientific community.

Tuning the photochemical ring-closing reaction efficiency in diarylethene-based photoswitches through engineering of internal charge transfer.

The photochemical quantum yield is one of the key features for a photoswitch and its tuning is challenging. In an attempt to tackle this issue within the popular diarylethene-based switches, we have explored the potential to use internal charge transfer (CT), a readily controllable parameter, for an effective modulation of the photocyclization quantum yield. For this, a homogeneous family of terarylenes, a sub-class of diarylethenes, with different CT characters, but the same photochromic core was designed and its photochromic properties were fully investigated. A clear correlation was found between the cyclization quantum yield and the CT character of the switch. More precisely, almost linear relationships were established between the ring-closing quantum yield and (i) the electron density variation accompanying the S0 → S1 transition and (ii) the percentage of LUMO on the reactive carbon atoms. Such a correlation was rationalized by a joint spectroscopic analysis and theoretical modelling of both ground and first excited states, introducing the concept of "early" or "late" photochromes. Encouragingly, such a potentally predictive model also seemed relevant when applied to some other diarylethene-based switches reported in the literature.

Functionalized maghemite nanoparticles for enhanced adsorption of uranium from simulated wastewater and magnetic harvesting.

Maghemite (γ-Fe2O3) nanoparticles (MNPs) were functionalized with 3-aminopropyltriethoxysilane (APTES) to give APTES@Fe2O3 (AMNP) which was then reacted with diethylenetriamine-pentaacetic acid (DTPA) to give a nanohybrid DTPA-APTES@Fe2O3 (DAMNP). Nano-isothermal titration calorimetry shows that DTPA complexation with uranyl ions in water is exothermic and has a stoichiometry of two DTPA to three uranyl ions. Density functional theory calculations indicate the possibility of several complexes between DTPA and UO22+ with different stoichiometries. Interactions between uranyl ions and DAMNP functional groups are revealed by X-photoelectron and Fourier transform infrared spectroscopies. Spherical aberration-corrected Scanning Transmission Electron Microscopy visualizes uranium on the particle surface. Adsorbent performance metrics were evaluated by batch adsorption studies under different conditions of pH, initial uranium concentration and contact time, and the results expressed in terms of equilibrium adsorption capacities (qe) and partition coefficients (PC). By either criterion, performance increases from MNP to AMNP to DAMNP, with the maximum uptake at pH 5.5 in all cases: MNP, qe = 63 mg g-1, PC = 127 mg g-1 mM-1; AMNP, qe = 165 mg g-1, PC = 584 mg g-1 mM-1; DAMNP, qe = 249 mg g-1, PC = 2318 mg g-1 mM-1 (at 25 °C; initial U concentration 0.63 mM; 5 mg adsorbent in 10 mL of solution; contact time, 3 h). The pH maximum is related to the predominance of mono- and di-cationic uranium species. Uptake by DAMNPs follows a pseudo-first-order or pseudo-second-order kinetic model and fits a variety of adsorption models. The maximum adsorption capacity for DAMNPs is higher than for other functionalized magnetic nanohybrids. This adsorbent can be regenerated and recycled for at least 10 cycles with less than 10% loss in activity, and shows high selectivity. These findings suggest that DAMNP could be a promising adsorbent for the recovery of uranium from nuclear wastewaters.

New Quinoid Bio-Inspired Materials Using Para-Azaquinodimethane Moiety.

Quinoid single molecules are regarded as promising materials for electronic applications due to their tunable chemical structure-driven properties. A series of three single bio-inspired quinoid materials containing para-azaquinodimethane (p-AQM) moiety were designed, synthesized and characterized. AQM1, AQM2 and AQM3, prepared using aldehydes derived from almonds, corncobs and cinnamon, respectively, were studied as promising quinoid materials for optoelectronic applications. The significance of facile synthetic procedures is highlighted through a straightforward two-step synthesis, using Knoevenagel condensation. The synthesized molecules showed molar extinction coefficients of 22,000, 32,000 and 61,000 L mol-1 cm-1, respectively, for AQM1, AQM2 and AQM3. The HOMO-LUMO energy gaps were calculated experimentally, theoretically showing the same trends: AQM3 < AQM2 < AQM1. The role of the aryl substituent was studied and showed an impact on the electronic properties. DFT calculations show planar structures with quinoidal bond length alternation, in agreement with the experimental results. Finally, these bio-based materials showed high thermal stabilities between 290 °C and 340 °C and a glassy behavior after the first heating-cooling scan. These results highlight these bio-based single molecules as potential candidates for electronic or biomedical applications.

Competitive Photoisomerization and Energy Transfer Processes in Fluorescent Multichromophoric Systems.

Multichromophoric systems showing both fluorescence and photoisomerization are fascinating, with complex interchromophoric interactions. The experimental and theoretical study of a series of compounds, bearing a variable number of 4-dicyanomethylene-2-tert-butyl-6-(p-(N-(2-azidoethyl)-N-methyl)aminostyryl)-4H-pyran (DCM) units are reported. The photophysical properties of multi-DCM derivatives, namely 2DCM and 3DCM, were compared to the single model azido-functionalized DCM, in the E and Z isomers. The (EE)-2DCM and (EEE)-3DCM were synthesized via the click reaction. Steady-state spectroscopy and photokinetics experiments under UV or visible irradiation indicated the presence of intramolecular energy transfer processes among the DCM units. Homo- and hetero-energy transfer processes between adjacent chromophores were confirmed by fluorescence anisotropy and decays. Molecular dynamics simulations for 2DCM were carried out and analyzed using a Markov state model, providing geometrical parameters (orientation and distance between chromophores) and energy transfer efficiency. This work contributes to a better understanding and rationalization of multiple energy transfer processes occuring within multichromophoric systems.

An accurate vibrational signature in halogen bonded molecular crystals.

The far infrared (FIR) and Raman fingerprints of the halogen bond in two representative 1D halogen bonded networks based on the recognition of TFIB, tetrafluorodiiodobenzene, with piperazine or azopyridine, have been accurately identified. It was demonstrated that the signature of the halogen bonding in the solid state, especially the N⋯I signal can be simply and directly evidenced in the far infrared region. The DFT theoretical calculations identified the N⋯I interaction in the molecular crystals and allowed estimation of the corresponding energies and distances of the involved halogen bonds, in accordance with the cristallographic data.

Photoisomerization of a 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran analog dye: a combined photophysical and theoretical investigation.

A combination of experimental and theoretical investigations of a photoisomerizable analog of 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran (DCM) dye molecule is presented. We provide evidence that the 4 main isomers and conformers of DCM contribute to its photochemical and photophysical processes. The absorption and emission spectra, as well as time-resolved fluorescence experimental results, are discussed and compared to DFT/TDDFT calculations. The E ↔ Z isomerization is induced photochemically, whereas the s-cis ↔ s-trans conformational interconversion is a thermal process which may also happen during irradiation. The photoreaction pathways from the first excited state down to the ground state are shown to be mediated by two conical intersections, as revealed using spin-flip TDDFT calculations. The rationalization of these isomerization schemes provides important insights into the photophysical properties of DCM, responsible for its photoswitchable fluorescence.

A Photo- and Redox-Driven Two-Directional Terthiazole-Based Switch: A Combined Experimental and Computational Investigation.

Terthiazoles with redox-active substituents like an N-methyl pyridinium group and ferrocene have been synthesized and their photo- and electro-chromic behaviors were investigated. The presence of two lateral N-methyl pyridinium substituents in the structure of terthiazole proved to be effective in inducing not only the reductive ring-closure of the terthiazole core but also its oxidative ring-opening reaction, leading to the first terarylene-based switch able to fully operate both photochemically and electrochemically. Moreover, the large increase in the redox potential between its open and closed form (700 mV) means that a part of the photon energy necessary to trigger the cyclization is stored in the form of chemical potential available for other works. Introduction of a second redox-active unit such as ferrocene onto the central thiazolyl moiety is found to inhibit the photochromism of the switch but not its redox switchability, which, instead, got improved for the ring-opening reaction via the redox properties of the ferrocenyl unit. The optical and redox properties of the switch in its different oxidation states are analyzed with the aid of DFT calculations in order to rationalize different switching processes.

Triangulenium dyes: the comprehensive photo-absorption and emission story of a versatile family of chromophores.

The triangulenium dyes constitute a family of versatile chromophores whose impressive photo-absorption and emission properties are currently highlighted in numerous novel experimental applications. In this investigation, we provide a comprehensive TDDFT characterization of their spectroscopic properties elucidating the origin of their large and complex absorption and emission vibronic spectra spread over the (whole) visible region. More precisely, by benchmarking the performance of 10 commonly-used exchange-correlation density functionals belonging to different classes of approximation, we develop and validate a computational protocol allowing the accurate modeling of both the position and optical line-shape of their vibrationally-resolved absorption and emission band structures. We find that semilocal approximations provide the best estimate of the structure of the vibronic spectra, however they spuriously and strongly underestimate their position. We finally show that global-hybrid density functionals mixing between 20 and 30% of exact-like exchange are an excellent compromise to get a satisfactory estimate of both of these properties.

Four Major Channels Detected in the Cytochrome P450 3A4: A Step toward Understanding Its Multispecificity.

We computed the network of channels of the 3A4 isoform of the cytochrome P450 (CYP) on the basis of 16 crystal structures extracted from the Protein Data Bank (PDB). The calculations were performed with version 2 of the CCCPP software that we developed for this research project. We identified the minimal cost paths (MCPs) output by CCCPP as probable ways to access to the buried active site. The algorithm of calculation of the MCPs is presented in this paper, with its original method of visualization of the channels. We found that these MCPs constitute four major channels in CYP3A4. Among the many channels proposed by Cojocaru et al. in 2007, we found that only four of them open in 3A4. We provide a refined description of these channels together with associated quantitative data.

Photoinduced Electron Transfer (PET)-Mediated Fragmentation of Picolinium-Derived Redox Probes.

The photolysis of covalently linked N-alkyl picolinium phenylacetate-carbazole dyads was analyzed experimentally and by using density functional theory (DFT) and time dependent-DFT (TD-DFT) calculations. In contrast to earlier observations efficient one and two-photon fragmentations conditions were found for 15 c (δu =0.16 GM at 730 nm) opening the way for the design of a novel class of "caged" compounds.

Alkyl-Modified Gold Surfaces: Characterization of the Au-C Bond.

The surface of gold can be modified with alkyl groups through a radical crossover reaction involving alkyliodides or bromides in the presence of a sterically hindered diazonium salt. In this paper, we characterize the Au-C(alkyl) bond by surface-enhanced Raman spectroscopy (SERS); the corresponding peak appears at 387 cm-1 close to the value obtained by theoretical modeling. The Au-C(alkyl) bond energy is also calculated, it reaches -36.9 kcal mol-1 similar to that of an Au-S-alkyl bond but also of an Au-C(aryl) bond. In agreement with the similar energies of Au-C(alkyl) and Au-S-(alkyl), we demonstrate experimentally that these groups can be exchanged on the surface of gold.

Some Theoretical and Experimental Insights on the Mechanistic Routes Leading to the Spontaneous Grafting of Gold Surfaces by Diazonium Salts.

The spontaneous grafting of diazonium salts on gold may involve the carbocation obtained by heterolytic dediazonation and not necessarily the radical, as usually observed on reducing surfaces. The mechanism is addressed on the basis of DFT calculations and experiments carried out under conditions where the carbocation and the radical are produced selectively. The calculations indicate that the driving force of the reaction leading from a gold cluster, used as a gold model surface, and the carbocation to the modified cluster is higher than that of the analogous reaction starting from the radical. The experiments performed under conditions of heterolytic dediazonation show the formation of thin films on the surface of gold. The grafting of a carbocation is therefore possible, but a mechanism where the cleavage of the Ar-N bond is catalyzed by the surface of gold cannot be excluded.

Light-induced piston nanoengines: ultrafast shuttling of a styryl dye inside cucurbit[7]uril.

The combination of photoactive styryl(pyridinium) dyes and cucurbit[7]uril (CB[7]) in an integrated supramolecular system allowed us to design a novel high speed molecular machine based on the fully reversible shuttling motion of the dye inside the CB[7] host cavity. The driving force of this movement is the electrostatic potential change after the occurrence of intramolecular charge transfer in the excited state of the dye molecule that can be externally controlled by light. Steady-state and time-resolved optical spectroscopy as well as DFT calculations provided an unambiguous evidence for the ultrafast piston-like movement of the system between two states. The shuttling process occurs in the picosecond timescale and its bistability depends on the strength of the dye donor fragment.

Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers.

Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

Association of symmetrical alkane diols with pyridine: DFT/GIAO calculation of 1 H NMR chemical shifts.

Proton nuclear magnetic resonance (NMR) shifts of the free diol and of its 1 : 1 and 1 : 2 hydrogen-bonded complexes with pyridine have been computed for five symmetrical alkane diols on the basis of density functional theory, by applying the gauge-including atomic orbital method to geometry-optimized conformers. For certain conformers, intramolecular OH···OH interactions, evidenced by high NMR OH proton shifts, are further enhanced on going from the free diol to the corresponding 1 : 1 diol/pyridine complex. This is confirmed by atoms-in-molecules and non-covalent interaction plots. The computed OH and CH proton shifts for the diol and the two complexes correlate well with values obtained by analysing data from the NMR titration of the diols in benzene against pyridine. Shift values for the diols in neat pyridine are calculated by weighting the shifts of the various protons in the three forms (free diol, 1 : 1 and 1 : 2 diol/pyridine complexes) according to the experimentally determined association constants. The results are in good agreement with those observed, and after empirical scaling, the root mean square difference is 0.18 ppm. Copyright © 2016 John Wiley & Sons, Ltd.

SCC-DFTB parameters for simulating hybrid gold-thiolates compounds.

We present a parametrization of a self-consistent charge density functional-based tight-binding scheme (SCC-DFTB) to describe gold-organic hybrid systems by adding new Au-X (X = Au, H, C, S, N, O) parameters to a previous set designed for organic molecules. With the aim of describing gold-thiolates systems within the DFTB framework, the resulting parameters are successively compared with density functional theory (DFT) data for the description of Au bulk, Aun gold clusters (n = 2, 4, 8, 20), and Aun SCH3 (n = 3 and 25) molecular-sized models. The geometrical, energetic, and electronic parameters obtained at the SCC-DFTB level for the small Au3 SCH3 gold-thiolate compound compare very well with DFT results, and prove that the different binding situations of the sulfur atom on gold are correctly described with the current parameters. For a larger gold-thiolate model, Au25 SCH3 , the electronic density of states and the potential energy surfaces resulting from the chemisorption of the molecule on the gold aggregate obtained with the new SCC-DFTB parameters are also in good agreement with DFT results.

A surface acoustic wave sensor functionalized with a polypyrrole molecularly imprinted polymer for selective dopamine detection.

A surface acoustic wave sensor operating at 104 MHz and functionalized with a polypyrrole molecularly imprinted polymer has been designed for selective detection of dopamine (DA). Optimization of pyrrole/DA ratio, polymerization and immersion times permitted to obtain a highly selective sensor, which has a sensitivity of 0.55°/mM (≈ 550 Hz/mM) and a detection limit of ≈ 10 nM. Morphology and related roughness parameters of molecularly imprinted polymer surfaces, before and after extraction of DA, as well as that of the non imprinted polymer were characterized by atomic force microscopy. The developed chemosensor selectively recognized dopamine over the structurally similar compound 4-hydroxyphenethylamine (referred as tyramine), or ascorbic acid,which co-exists with DA in body fluids at a much higher concentration. Selectivity tests were also carried out with dihydroxybenzene, for which an unexpected phase variation of order of 75% of the DA one was observed. Quantum chemical calculations, based on the density functional theory, were carried out to determine the nature of interactions between each analyte and the PPy matrix and the DA imprinted PPy polypyrrole sensing layer in order to account for the important phase variation observed during dihydroxybenzene injection.

Computing cavities, channels, pores and pockets in proteins from non-spherical ligands models.

MOTIVATION: Identifying protein cavities, channels and pockets accessible to ligands is a major step to predict potential protein-ligands complexes. It is also essential for preparation of protein-ligand docking experiments in the context of enzymatic activity mechanism and structure-based drug design. RESULTS: We introduce a new method, implemented in a program named CCCPP, which computes the void parts of the proteins, i.e. cavities, channels and pockets. The present approach is a variant of the alpha shapes method, with the advantage of taking into account the size and the shape of the ligand. We show that the widely used spherical model of ligands is most of the time inadequate and that cylindrical shapes are more realistic. The analysis of the void parts of the protein is done via a network of channels depending on the ligand. The performance of CCCPP is tested with known substrates of cytochromes P450 (CYP) 1A2 and 3A4 involved in xenobiotics metabolism. The test results indicate that CCCPP is able to find pathways to the buried heminic P450 active site even for high molecular weight CYP 3A4 substrates such as two ketoconazoles together, an experimentally observed situation. AVAILABILITY: Free binaries are available through a software repository at http://petitjeanmichel.free.fr/itoweb.petitjean.freeware.html CONTACT: michel.petitjean@univ-paris-diderot.fr.

Substituent effects on the photochromic properties of benzothiophene-based derivatives.

Five diarylethene photochromic derivatives, the structures of which incorporate a central benzothiophene unit, a left-hand thiazole group, and a right-hand benzothiophene group, have been prepared. The compound with a thiazole unit with no substituent on the reaction-center carbon atom reveals an unprecedented transformation upon light irradiation. When the 4-position of thiazole is protected by a methyl group, the compounds show high photosensitivity and photochromic properties. In this case, light irradiation affords new compounds with [5]helicene structures featuring the highest redshifted absorption maxima reported to date.