Mechanistic Insights into Hyaluronic Acid Induced Peptide Nanofiber Organization in Supramolecular Hydrogels.

Composite hydrogels composed of low-molecular-weight peptide self-assemblies and polysaccharides are gaining great interest as new types of biomaterials. Interactions between polysaccharides and peptide self-assemblies are well reported, but a molecular picture of their impact on the resulting material is still missing. Using the phosphorylated tripeptide precursor Fmoc-FFpY (Fmoc, fluorenylmethyloxycarbonyl; F, phenylalanine; Y, tyrosine; p, phosphate group), we investigated how hyaluronic acid (HA) influences the enzyme-assisted self-assembly of Fmoc-FFY generated in situ in the presence of alkaline phosphatase (AP). In the absence of HA, Fmoc-FFY peptides are known to self-assemble in nanometer thick and micrometer long fibers. The presence of HA leads to the spontaneous formation of bundles of several micrometers thickness. Using fluorescence recovery after photobleaching (FRAP), we find that in the bundles both (i) HA colocalizes with the peptide self-assemblies and (ii) its presence in the bundles is highly dynamic. The attractive interaction between negatively charged peptide fibers and negatively charged HA chains is explained through molecular dynamic simulations that show the existence of hydrogen bonds. Whereas the Fmoc-FFY peptide self-assembly itself is not affected by the presence of HA, this polysaccharide organizes the peptide nanofibers in a nematic phase visible by small-angle X-ray scattering (SAXS). The mean distance d between the nanofibers decreases by increasing the HA concentration c, but remains always larger than the diameter of the peptide nanofibers, indicating that they do not interact directly with each other. At a high enough HA concentration, the nematic organization transforms into an ordered 2D hexagonal columnar phase with a nanofiber distance d of 117 Å. Depletion interaction generated by the polysaccharides can explain the experimental power law variation d∼c-1/4 and is responsible for the bundle formation and organization. Such behavior is thus suggested for the first time on nano-objects using polymers partially adsorbing on self-assembled peptide nanofibers.

Critical Analysis of Association Constants between Calixarenes and Nitroaromatic Compounds Obtained by Fluorescence. Implications for Explosives Sensing.

The binding behaviour of two ureido-hexahomotrioxacalix[3]arene derivatives bearing naphthyl (1) and pyrenyl (2) fluorogenic units at the lower rim towards selected nitroaromatic compounds (NACs) was evaluated. Their affinity, or lack of it, was determined by UV-Vis absorption, fluorescence and NMR spectroscopy. Different computational methods were also used to further investigate any possible complexation between the calixarenes and the NACs. All the results show no significant interaction between calixarenes 1 and 2 and the NACs in either dichloromethane or acetonitrile solutions. Moreover, the fluorescence quenching observed is only apparent and merely results from the absorption of the NACs at the excitation wavelength (inner filter effect). This evidence is in stark contrast with reports in the literature for similar calixarenes. A naphthyl urea dihomooxacalix[4]arene (3) is also subject to the inner filter effect and is shown to form a stable complex with trinitrophenol; however, the equilibrium association constant is greatly overestimated if no correction is applied (9400 M-1 vs 3000 M-1), again stressing the importance of taking into account the inner filter effect in these systems.

Implementation of a soft grading system for chemistry in a Moodle plugin.

We report a novel approach for grading chemical structure drawings for remote teaching, integrated into the Moodle platform. Typically, existing online platforms use a binary grading system, which often fails to give a nuanced evaluation of the answers given by the students. Therefore, such platforms are unevenly adapted to different disciplines. This is particularly true in the case of chemical structures, where most questions simply cannot be evaluated on a true/false basis. Specifically, a strict comparison of candidate and expected chemical structures is not sufficient when some tolerance is deemed acceptable. To overcome this limitation, we have developed a grading workflow based on the pairwise similarity score of two considered chemical structures. This workflow is implemented as a Moodle plugin, using the Chemdoodle engine for drawing structures and communicating with a REST server to compute the similarity score using molecular descriptors. The plugin ( https://github.com/Laboratoire-de-Chemoinformatique/moodle-qtype_molsimilarity ) is easily adaptable to any academic user; both embedding and similarity measures can be configured.

Encapsulated Neutral Ruthenium Catalyst for Substrate-Selective Oxidation of Alcohols.

The neutral complex dichloro-{diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)-(4-trifluoro-methylphenyl)methyl]phosphonate} (p-cymene)-ruthenium(II) was encapsulated inside a self-assembled hexameric host obtained upon reaction of 2,8,14,20-tetra-undecyl-resorcin[4]arene and water. The formation of an inclusion complex was inferred from a combination of spectral measurements (MS, UV/Vis spectroscopy, 1 H and DOSY NMR). The 31 P and 19 F NMR spectra are consistent with motions of the ruthenium complex inside the self-assembled capsule. Molecular dynamics simulations carried out on the inclusion complex confirmed these intra-cavity movements and highlighted possible supramolecular interactions between the ruthenium first coordination sphere ligands and the inner part (aromatic rings) of the capsule. The embedded ruthenium complex was assessed in the catalytic oxidation (using NaIO4 as oxidant) of mixtures of three arylmethyl alcohols into the corresponding aldehydes. The reaction kinetics were shown to vary as a function of the substrates' size, with the oxidation rate varying in the order benzylalcohol >4-phenyl-benzylalcohol >9-anthracenemethanol. Control experiments realized in the absence of hexameric capsule did not allow any discrimination between the substrates.

Liquid-Liquid Extraction of the Eu(III) Cation by BTP Ligands into Ionic Liquids: Interfacial Features and Extraction Mechanisms Investigated by MD Simulations.

What happens at the ionic-liquid (IL)/water interface when the Eu3+ cation is complexed and extracted by bis(dimethyltriazinyl) pyridine "BTP" ligands has been investigated by molecular dynamics and potential of mean force simulations on the interface crossing by key species: neutral BTP, its protonated BTPH+ form, Eu3+, and the Eu(BTP)33+ complex. At both the [BMI][Tf2N]/water and [OMI][Tf2N]/water interfaces, neither BTP nor Eu(BTP)33+ are found to adsorb. The distribution of Eu(BTP)23+ and Eu(BTP)3+ precursors of Eu(BTP)33+, and of their nitrate adducts, implies the occurrence of a stepwise complexation process in the interfacial domain, however. The analysis of the ionic content of the bulk phases and of their interface before and after extraction highlights the role of charge buffering by interfacial IL cations and anions, by different amounts depending on the IL. Comparison of ILs with octanol as the oil phase reveals striking differences regarding the extraction efficiency, the affinity of Eu(BTP)33+ for the interface, the effects of added nitric acid and of counterions (NO3- vs Tf2N-), charge neutralization mechanisms, and the extent of "oil" heterogeneity. Extraction into octanol is suggested to proceed via adsorption at the surface of water pools, nanoemulsions, or droplets, with marked counterion effects.

Cold-spray ionization mass spectrometry of the choline chloride-urea deep eutectic solvent (reline).

Cold-Spray Ionization mass spectrometry (CSI-MS) that can be compared to an electrospray ionization (ESI) source acting with a nebulizing gas cooled by liquid nitrogen is used for analyzing reline as Deep Eutectic Solvent (DES). The association of cholinium chloride salts with urea molecules is evidenced in negative CSI-MS through the chloride adduct formation. The structure of the supramolecular assemblies forming the reline ions that are observed on CSI mass spectra is rationalized by chemical quantum calculations. The theoretical studies indicate that the ionic network organization is only supported by a maximization of hydrogen bonds of the chlorides with the hydroxyl and methyl moieties of the cholinium cations and the amino groups of urea. The studies of gas-phase fragmentation of the supra-molecular ionic assemblies detected in CSI-MS are performed using the in-source collision-induced dissociation experiments. The experimental measurements in CSI-MS, interpreted at the light of the molecular modelization results, suggest that the insertion of urea in adducts of chlorides with cholinium cations does not lead to the most stable ions.

Dihomooxacalix[4]arene-Based Fluorescent Receptors for Anion and Organic Ion Pair Recognition.

Fluorescent dihomooxacalix[4]arene-based receptors 5a-5c, bearing two naphthyl(thio)ureido groups at the lower rim via a butyl spacer, were synthesised and obtained in the cone conformation in solution. The X-ray crystal structures of 1,3- (5a) and 3,4-dinaphthylurea (5b) derivatives are reported. Their binding properties towards several anions of different geometries were assessed by 1H-NMR, UV-Vis absorption and fluorescence titrations. Structural and energetic insights of the naphthylurea 5a and 5b complexes were also obtained using quantum mechanical calculations. The data showed that all receptors follow the same trend, the association constants increase with the anion basicity, and the strongest complexes were obtained with F-, followed by the oxoanions AcO- and BzO-. Proximal urea 5b is a better anion receptor compared to distal urea 5a, and both are more efficient than thiourea 5c. Compounds 5a and 5b were also investigated as heteroditopic receptors for biologically relevant alkylammonium salts, such as the neurotransmitter γ-aminobutyric acid (GABA·HCl) and the betaine deoxycarnitine·HCl. Chiral recognition towards the guest sec-butylamine·HCl was also tested, and a 5:2 selectivity for (R)-sec-BuNH3+·Cl- towards (P) or (M) enantiomers of the inherently chiral receptor 5a was shown. Based on DFT calculations, the complex [(S)-sec-BuNH3+·Cl-/(M)-5a] was indicated as the more stable.

Enzymatic Degradation of Graphene Quantum Dots by Human Peroxidases.

Carbon-based nanomaterials have demonstrated to be potent candidates for biomedical applications. Recently, graphene quantum dots (GQDs) have emerged as an attractive tool for bioimaging, biosensing, and therapy. Hence, studying their biodegradability in living systems is essential to speed up the translation toward real clinical innovations. Here, the enzymatic degradation of GQDs using human myeloperoxidase and eosinophil peroxidase is investigated. Transmission electron microscopy, fluorescence, and Raman spectroscopy are used to evaluate the biodegradation of GQDs. Signs of degradation by both enzymes are observed already after a few hours of incubation with each enzyme, being more evident after a couple of days of treatment. Molecular dynamics simulations show intimate interactions between the enzymes and the GQDs. The conformation of both peroxidases is slightly altered to favor the interactions, while the GQD sheets distort a little to adapt to the surface of the enzymes. The biodegradability of the GQDs ensures their real potential in the practical biomedical applications.

Protected Amino Acid-Based Hydrogels Incorporating Carbon Nanomaterials for Near-Infrared Irradiation-Triggered Drug Release.

Molecular gels formed by the self-assembly of low-molecular-weight gelators have received increasing interest because of their potential applications in drug delivery. In particular, the ability of peptides and amino acids to spontaneously self-assemble into three-dimensional fibrous network has been exploited in the development of hydrogels. In this context, we have investigated the capacity of binary mixtures of aromatic amino acid derivatives to form hydrogels. Carbon nanomaterials, namely oxidized carbon nanotubes or graphene oxide, were incorporated in the two most stable hydrogels, formed by Fmoc-Tyr-OH/Fmoc-Tyr(Bzl)-OH and Fmoc-Phe-OH/Fmoc-Tyr(Bzl)-OH, respectively. The structural and physical properties of these gels were assessed using microscopic techniques and rheology. Circular dichroism and molecular dynamics simulations demonstrated that the hydrogel formation was mainly driven by aromatic interactions. Finally, a model hydrophilic drug (l-ascorbic acid) was loaded into the hybrid hydrogels at a high concentration. Under near-infrared light irradiation, a high amount of drug was released triggered by the heat generated by the carbon nanomaterials, thus offering interesting perspectives for controlled drug delivery.

Formation of Aqueous Biphasic Systems with an Ionic Liquid Induced by Metallic Salts: Nanoscopic Views from Molecular Dynamics Simulations.

The formation of aqueous biphasic systems (ABSs) based on aqueous ionic liquid (IL)/salt mixtures has been investigated via molecular dynamics simulations (with IL butyl-methyl-imidazolium triflate; salts NaCl, CsCl, SrCl2, and EuCl3). The analysis of ion distributions, solvation, and mutual interactions during the dynamics reveals the heterogeneity of all solutions due to ion segregation into mutually exclusive IL and salt domains, even in monophasic solutions ("ionic sociology"). Ion segregation and ABS formation are found to increase with (i) the salt content and (ii) the IL content, (iii) in the order Na+ < Sr2+ < Eu3+, and (iv) when the IL ion "polarity" is diminished, following experimental trends. The structuration of the solution is rationalized as a synergistic water transfer from the best donating ion pair (first hydration shell of hydrophobic moieties of IL ions) to the best accepting pair (M n+ and Cl- ions, beyond their first shell). In ABSs, the IL- and salt-containing phases are linked by a well-defined "interface" that decreases in width when MCl n becomes more hydrophilic and/or more concentrated. In the IL-rich phase of ABSs, the hydration of IL ions and their mutual interactions are shown to be similar to those displayed at aqueous interfaces.

Liquid-liquid extraction of pertechnetic acid (TcVII) by tri-n-butyl phosphate: where is the proton? A molecular dynamics investigation.

We report a molecular dynamics study on pertechnetic acid (PTA) extraction from water to an oil phase containing either pure TBP (tri-n-butyl phosphate) or a TBP/n-hexane mixture, with the main aim to understand the state of the acid (associated TcO(4)H vs dissociated TcO(4)(-)H(+)) and its "complexation" by TBP. Experimentally, Tc(VII) is extracted from acidic water to TBP:alkane solutions in 1:3 or 1:4 Tc:TBP ratio, suggesting that three or four TBPs coordinate to TcO(4)H or TcO(4)(-). According to simulations in TBP solution, however, neither TcO(4)H nor TcO(4)(-) species displays specific coordination to TBP. We thus investigated several hypothetical states of the proton of the dissociated pertechnetic acid in organic phases and at their aqueous interfaces, comparing "pH neutral" to nitric acid containing systems. Proton hydrates are shown to coordinate 3-4 TBPs, in the form of H(3)O(+)(TBP)(3) and H(5)O(2)(+)(TBP)(4) hydrogen-bonded adducts, whereas TBPH(+) binds 1 TBP. The MD and PMF results complemented by those of QM investigations suggest that Tc(VII) is extracted as TcO(4)(-)(H(3)O)(+)(TBP)(3) or TcO(4)(-)(H(5)O(2))(+)(TBP)(4) contact ion pairs instead of the neutral form TcO(4)H of the acid. They explain why nitric acid promotes the Tc(VII) extraction. Comparison between nitric acid (mainly extracted via its neutral form NO(3)H) and pertechnetic acid is discussed.

Complexation of Cs+, K+ and Na+ by norbadione A triggered by the release of a strong hydrogen bond: nature and stability of the complexes.

Norbadione A (NBA) is a pigment present in edible mushrooms which is presumed to selectively complex Cs(+) cations. Due to a very uncommon complexation mechanism, we used a combination of several experimental techniques, including (1)H-NMR, (133)Cs-NMR, isothermal calorimetric, potentiometric titrations and molecular dynamics MD simulations to determine the nature of the complexed species, as well as their stability constants for the NBA-M(+) systems (M(+) = Cs(+), K(+), Na(+)) in methanol:water 80:20 solutions at 25.0 degrees C. We show that almost no complexation occurs below pH 7.5, as long as a proton, involved in a strong hydrogen bond, bridges both carboxylic and enolic groups of each pulvinic moiety of NBA. Thus, neutralization of that proton is necessary to both set free potential coordination sites and to trigger a conformational change, two conditions needed to bind successively a first, then a second metallic cation. The stability constants determined in this study are in good agreement with each other, leading to the stability order Cs(+) > K(+) > Na(+) for both mono- and bimetallic complexes, which is the reversed order to the one generally observed for low molecular weight carboxylic ligands in water. According to MD simulations in solution, complexation involves a mixture of Z/E isomers and conformers of NBA with a broad diversity of binding modes. Some pH and environment dependent aggregation phenomena are considered to also contribute to the binding process, and to possibly explain the accumulation of radionuclides in mushrooms.

Solvation of uranium hexachloro complexes in room-temperature ionic liquids. A molecular dynamics investigation in two liquids.

We report a molecular dynamics study of the solvation of UCl(6)(-), UCl(6)(2-), and UCl(6)(3-) complexes in the [BMI][Tf(2)N] and [MeBu(3)N][Tf(2)N] ionic liquid cations based on the same anion (bis(trifluoromethylsulfonyl)imide (Tf(2)N-)) and the butyl-3-methyl-imidazolium+ (BMI+) or methyl-tri-n-butyl-ammonium (MeBu(3)N+) cation, respectively. The comparison of two electrostatic models of the complexes (ionic model with -1 charged halides versus quantum mechanically derived charges) yields similar solvation features of a given solute. In the two liquids, the first solvation shell of the complexes is positively charged and evolves from purely cationic in the case of UCl(6)(3-) to a mixture of cations and anions in the case of UCl(6)(-). UCl(6)(3-) is exclusively "coordinated" to BMI+ or MeBu(3)N+ solvent cations that mainly interact via their CH aromatic protons or their N-Me group, respectively. Around the less charged UCl(6)(-) complex, the cations interact via the less polar moieties (butyl chains of BMI+ or MeBu(3)N+) and the anions display nonspecific interactions. In no case does the uranium atom further coordinate solvent ions. According to an energy components analysis, UCl(6)(3-) interacts more attractively with the [BMI][Tf(2)N] liquid than with [MeBu(3)N][Tf(2)N], while UCl(6)(-) does not show any preference, suggesting a significant solvation effect of the redox properties of uranium, also supported by free energy perturbation simulations. The effect of ionic liquid (IL) humidity is investigated by simulating the three complexes in 1:8 water/IL mixtures. In contrast to the case of "naked" ions (e.g., lanthanide(3+), UO2(2+), alkali, or halides), water has little influence on the solvation of the UCl(6)(n-) complexes in the two simulated ILs, as indicated by structural and energy analysis. This is in full agreement with the experimental observations (Nikitenko, S. I.; et al. Inorg. Chem. 2005, 44, 9497).

Photophysical and structural impact of phosphorylated anions associated to lanthanide complexes in water.

A new ligand, LC, bis-[(6'-carboxy-2,2'-bipyridine-6-yl)]phenylphosphine oxide, in which the tridentate 6-carboxy-2,2'-bipyridyl arms are directly linked to a phenylphosphine oxide fragment, has been synthesized. The corresponding [Ln.LC]Cl.xH2O complexes (Ln = Eu, x = 4, and Tb, x = 3) were isolated from solutions containing equimolar amounts of LC and hydrated LnCl3 salts and characterized by elemental analysis, mass spectrometry, and infrared spectroscopy. The interactions of the Eu complex with various anions (AMP(2-), ADP3-, ATP,4- HPO4(2-), and NO3-) were studied by titration experiments, using UV-vis, luminescence spectroscopy, and excited-state lifetime measurements. The results are in keeping with strong interactions with the ADP3-, ATP4-, and phosphate anions in TRIS/HCl buffer (0.01 M, pH = 7.0), as revealed by the determination of the conditional stepwise association constants. These values are higher than the one determined for ligand LB, bis[(6'-carboxy-2,2'-bipyridine-6-methyl-yl)]-n-butylamine (Delta log K approximately 1-2). The interaction of complexes [Ln.LB]+ and [Ln.LC]+ with nitrate, monohydrogenophosphate, methyl phosphate (MeP2-), methyldiphosphate (MeDP3-), and methyltriphosphate (MeTP4-) anions was investigated by means of quantum mechanical (QM) calculations. The results, combined with data on the photophysical impact of the sequential competitive binding of anions to the Eu complexes in water, suggest that LB is too flexible to ensure a good coordination pocket, while the molecular structure of ligand LC stabilizes both the formation of the lanthanide complexes and its adducts with ATP.

Ab initio molecular dynamics of liquid 1,3-dimethylimidazolium chloride.

Density-functional-based Car-Parrinello molecular dynamics (CPMD) simulations have been performed for the ionic liquid 1,3-dimethylimidazolium chloride, [dmim]Cl, at 438 K. The local structure of the liquid is described in terms of various partial radial distribution functions and anisotropic spatial distributions, which reveal a significant extent of hydrogen bonding. The cation-anion distribution simulated with the BP86 functional is in qualitative agreement with the structural model derived from neutron diffraction data for the liquid, whereas the theoretical cation-cation distribution shows less satisfactory accord. Population analyses indicate noticeable charge transfer from anions to cations, and specific CH...Cl hydrogen bonds are characterized in terms of donor-acceptor interactions between lone pairs on Cl and antibonding sigma(CH) orbitals.

Peroxovanadate imidazole complexes as catalysts for olefin epoxidation: density functional study of dynamics, 51V NMR chemical shifts, and mechanism.

A density functional study of [VO(O(2))(2)(Im)](-) (1, Im = imidazole) is presented, calling special attention to effects of dynamics and solvation on the (51)V chemical shift. According to Car-Parrinello molecular dynamics simulations, rotation of the Im ligand can be fast in the gas phase, but is more hindered in aqueous solution. In the latter, bonding between Im and V is reinforced, and dynamic averaging of GIAO-B3LYP magnetic shieldings affords a gas-to-liquid shift of ca. -100 ppm for delta((51)V). A complete catalytic cycle has been characterized for olefin epoxidation mediated by 1, using H(2)O(2) as oxidant. The rate-determining step is indicated to be initial oxygen atom transfer from 1 to the substrate via a spiro-like transition state. Substituent effects on this barrier are examined, and a significant decrease (by 2-6 kcal/mol) is revealed upon removal of the Im proton or upon complexation with a H-bond acceptor. Implications for the mechanism of the oxidative chemistry of vanadium-dependent haloperoxidases and requirements for prospective biomimetic analogues are discussed.