Solubility enhancement of ibuprofen using tri-ureasil-PPO hybrid: structural,cytotoxic, and drug release investigation

Herein, we used tri-ureasil organic–inorganic hybrid material (tU5000) in order to enhance the solubility of nonsteroidal anti-inflammatory drugs and fine tuning the drug delivery profile. For the first time, we used tU5000 as a film-forming agent in order to provide an alternative vehicle for transdermal drug delivery systems which the cell viability of practically 100 % for the highest and the lowest tested concentrations of pure tU5000 indicated that the material was not cytotoxic. The physicochemical properties of the tU5000 drug carrier and drug-loaded hybrids were systematically studied using powder X-ray diffraction, differential scanning calorimetry, small-angle X-ray scattering, and Fourier-transform infrared spectroscopy. The structural changes of tU5000 as well as the relationships between the drug content and in vitro drug release behaviors were investigated. The results showed that the ibu molecules were homogeneously distributed in the tU5000 xerogels contributing to fine-tuning the drug delivery profile. Considering the ability to incorporated high drug content, simple and mild preparation procedure by one-pot sol–gel route, high stability of the materials, sustained-release property, this class of hybrid based on polymers and inorganic compounds may have potential applications in the design of pharmaceutical formulation as ophthalmic (contact lenses), transdermal (patches) and implantable (soft tissue) drug delivery systems.     

Hydrophilic–oleophobic coatings on cellulosic materials by plasma assisted polymerization in liquid phase and fluorosurfactant complexation

Materials with hydrophilic–oleophobic properties are of relevance due to their application to different fields such as self-cleaning coatings, liquid–liquid separation membranes and functional textiles for different technical applications. In this work, hydrophilic–oleophobic coatings have been deposited on cellulosic materials (filter paper and bleached cotton) by means of plasma assisted polymerization of acrylic acid solutions in water followed by cationic fluorosurfactant complexation. Chemical composition of the coatings on cellulosic materials was characterized by means of FTIR–ATR and XPS whereas their morphology was studied by SEM. Hydrophilic–oleophobic behavior was characterized by means of contact angle and wetting time. Additionally wetting properties of cationic, anionic and non-ionic surfactant solutions on the hydrophilic–oleophobic coatings were used to characterize the polyelectrolyte electrostatic forces upon the functionalized layer.     

A Dynamic Model for Cellulosic Biomass Hydrolysis: a Comprehensive Analysis and Validation of Hydrolysis and Product Inhibition Mechanisms

The objective of this study is to perform a comprehensive enzyme kinetics analysis in view of validating and consolidating a semimechanistic kinetic model consisting of homogeneous and heterogeneous reactions for enzymatic hydrolysis of lignocellulosic biomass proposed by the U.S. National Renewable Energy Laboratory (Kadam et al., Biotechnol Prog 20(3):698–705, 2004) and its variations proposed in this work. A number of dedicated experiments were carried out under a range of initial conditions (Avicel® versus pretreated barley straw as substrate, different enzyme loadings and different product inhibitors such as glucose, cellobiose and xylose) to test the hydrolysis and product inhibition mechanisms of the model. A nonlinear least squares method was used to identify the model and estimate kinetic parameters based on the experimental data. The suitable mathematical model for industrial application was selected among the proposed models based on statistical information (weighted sum of square errors). The analysis showed that transglycosylation plays a key role at high glucose levels. It also showed that the values of parameters depend on the selected experimental data used for parameter estimation. Therefore, the parameter values are not universal and should be used with caution. The model proposed by Kadam et al. (Biotechnol Prog 20(3):698–705, 2004) failed to predict the hydrolysis phenomena at high glucose levels, but when combined with transglycosylation reaction(s), the prediction of cellulose hydrolysis behaviour over a broad range of substrate concentrations (50–150 g/L) and enzyme loadings (15.8–31.6 and 1–5.9 mg protein/g cellulose for Celluclast and Novozyme 188, respectively) was possible. This is the first study introducing transglycosylation into the semimechanistic model. As long as these type of models are used within the boundary of their validity (substrate type, enzyme source and substrate concentration), they can support process design and technology improvement efforts at pilot and full-scale studies.     

A water- and sulfurization-free solution route to Cu2-xZn1+xSnS4

Zinc-rich/copper-poor Cu_2-xZn_1+xSnS₄ (x = 0.2, CZTS) has been successfully produced in film and powder form using two non-aqueous solutions (of metal salts and thiourea) without the need for sulfurization during the annealing phase. A reaction route is proposed and the choices of the solvents (water, ethyleneglycol, ethanol, methanol) and of the tin source (tin chloride pentahydrate or anhydrous) discussed and justified. A pure and coarse-grained material is obtained with a mix of metal salts in methanol and thiourea in ethylene glycol. The tin pentahydrate salt seems a better alternative to the commonly used anhydrous chloride.     

Distributed and multicore QuBiLS-MIDAS software v2.0: Computing chiral,fuzzy, weighted and truncated geometrical molecular descriptors based on tensor algebra

Advances to the distributed, multi-core and fully cross-platform QuBiLS-MIDAS software v2.0 ( http://tomocomd.com/qubils-midas ) are reported in this article since the v1.0 release. The QuBiLS-MIDAS software is the only one that computes atom-pair and alignment-free geometrical MDs (3D-MDs) from several distance metrics other than the Euclidean distance, as well as alignment-free 3D-MDs that codify structural information regarding the relations among three and four atoms of a molecule. The most recent features added to the QuBiLS-MIDAS software v2.0 are related (a) to the calculation of atomic weightings from indices based on the vertex-degree invariant (e.g., Alikhanidi index); (b) to consider central chirality during the molecular encoding; (c) to use measures based on clustering methods and statistical functions to codify structural information among more than two atoms; (d) to the use of a novel method based on fuzzy membership functions to spherically truncate inter-atomic relations; and (e) to the use of weighted and fuzzy aggregation operators to compute global 3D-MDs according to the importance and/or interrelation of the atoms of a molecule during the molecular encoding. Moreover, a novel module to compute QuBiLS-MIDAS 3D-MDs from their headings was also developed. This module can be used either by the graphical user interface or by means of the software library. By using the library, both the predictive models built with the QuBiLS-MIDAS 3D-MDs and the QuBiLS-MIDAS 3D-MDs calculation can be embedded in other tools. A set of predefined QuBiLS-MIDAS 3D-MDs with high information content and low redundancy on a set comprised of 20,469 compounds is also provided to be employed in further cheminformatics tasks. This set of predefined 3D-MDs evidenced better performance than all the universe of Dragon (v5.5) and PaDEL 0D-to-3D MDs in variability studies, whereas a linear independence study proved that these QuBiLS-MIDAS 3D-MDs codify chemical information orthogonal to the Dragon 0D-to-3D MDs. This set of predefined 3D-MDs would be periodically updated as long as new results be achieved. In general, this report highlights our continued efforts to provide a better tool for a most suitable characterization of compounds, and in this way, to contribute to obtaining better outcomes in future applications.     

Diels-Alder reaction mechanisms of substituted chiral anthracene: A theoretical study based on the reaction force and reaction electronic flux

Quantum chemical calculations were used to study the mechanism of Diels-Alder reactions involving chiral anthracenes as dienes and a series of dienophiles. The reaction force analysis was employed to obtain a detailed scrutiny of the reaction mechanisms, it has been found that thermodynamics and kinetics of the reactions are quite consistent: the lower the activation energy, the lower the reaction energy, thus following the Bell-Evans-Polanyi principle. It has been found that activation energies are mostly due to structural rearrangements that in most cases represented more than 70% of the activation energy. Electronic activity mostly due to changes in σ and π bonding were revealed by the reaction electronic flux (REF), this property helps identify whether changes on σ or π bonding drive the reaction. Additionally, new global indexes describing the behavior of the electronic activity were introduced and then used to classify the reactions in terms of the spontaneity of their electronic activity. Local natural bond order electronic population analysis was used to check consistency with global REF through the characterization of specific changes in the electronic density that might be responsible for the activity already detected by the REF. Results show that reactions involving acetoxy lactones are driven by spontaneous electronic activity coming from bond forming/strengthening processes; in the case of maleic anhydrides and maleimides it appears that both spontaneous and non-spontaneous electronic activity are quite active in driving the reactions.     

CO2 to CO: Photo- and Electrocatalytic Conversion Based on Re(I) Bis-Arene Frameworks: Synergisms Between Catalytic Subunits

Reduction of CO₂ to CO and H₂O is a two electron/two proton process. For this process, multinuclear complexes offer advantages by concentrating reduction equivalents more efficiently than mononuclear systems. We present novel complexes with [Re(η⁶-C₆H₆)₂]⁺ as scaffold conjugated to one or two catalytically active [Ru(dmbpy)(CO)₂Cl₂] subunits (dmbpy=5,5′-dimethyl-2,2′-bipyridine). The [Re(η⁶-C₆H₆)₂]⁺ scaffold was chosen due to its very high photo- and chemical stability, as well as the multiple degrees of freedom it offers for any conjugated functionalities. High efficiency and selectivity for the reduction of CO₂ to CO (over H₂ or HCOOH) is reported. TONs and TOFs were found to be comparable or higher than for the catalyst subunit without the rhenium framework. Cooperativity in photo- and electrocatalysis is observed for the complex comprising two catalytic subunits. The synergistic communication between the two catalytic subunits is responsible for the observed enhancement in both photo- and electrocatalytic performance. Confirmation of electronic communication between the two [Ru(dmbpy)(CO)₂Cl₂] subunits as well as the elucidation of a possible mechanism was supported by electrochemistry, IR-spectroelectrochemistry and DFT studies.     

Multicomponent Peptide Stapling as a Diversity‐Driven Tool for the Development of Inhibitors of Protein–Protein Interactions

Stapled peptides are chemical entities in‐between biologics and small molecules, which have proven to be the solution to high affinity protein–protein interaction antagonism, while keeping control over pharmacological performance such as stability and membrane penetration. We demonstrate that the multicomponent reaction‐based stapling is an effective strategy for the development of α‐helical peptides with highly potent dual antagonistic action of MDM2 and MDMX binding p53. Such a potent inhibitory activity of p53‐MDM2/X interactions was assessed by fluorescence polarization, microscale thermophoresis, and 2D NMR, while several cocrystal structures with MDM2 were obtained. This MCR stapling protocol proved efficient and versatile in terms of diversity generation at the staple, as evidenced by the incorporation of both exo‐ and endo‐cyclic hydrophobic moieties at the side chain cross‐linkers. The interaction of the Ugi‐staple fragments with the target protein was demonstrated by crystallography.     

Collective All‐Carbon Magnetism in Triangulene Dimers

Triangular zigzag nanographenes, such as triangulene and its π‐extended homologues, have received widespread attention as organic nanomagnets for molecular spintronics, and may serve as building blocks for high‐spin networks with long‐range magnetic order, which are of immense fundamental and technological relevance. As a first step towards these lines, we present the on‐surface synthesis and a proof‐of‐principle experimental study of magnetism in covalently bonded triangulene dimers. On‐surface reactions of rationally designed precursor molecules on Au(111) lead to the selective formation of triangulene dimers in which the triangulene units are either directly connected through their minority sublattice atoms, or are separated via a 1,4‐phenylene spacer. The chemical structures of the dimers have been characterized by bond‐resolved scanning tunneling microscopy. Scanning tunneling spectroscopy and inelastic electron tunneling spectroscopy measurements reveal collective singlet–triplet spin excitations in the dimers, demonstrating efficient intertriangulene magnetic coupling.