Supramolecular Hydrogels Consisting of Nanofibers Increase the Bioavailability of Curcuminoids in Inflammatory Skin Diseases

The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammatory skin diseases. Our work shows that this constraint can be overcome upon their incorporation into supramolecular hydrogels assembled from a gemini-imidazolium amphiphilic gelator. Three structural CCMoid analogues were used to prepare supramolecular hydrogels, and it was observed that the concentration of both the gelator and CCMoid and the proportion of solvents influence the self-assembly process. Moreover, the mechanical properties of the nanostructured gels were studied to find the optimum gels, which were then further characterized microscopically, and their ability to release the CCMoid was evaluated. The physicochemical properties of the CCMoids play a fundamental role in the interaction with the gelator, influencing not only the gelation but also the morphology at the microscopic level, the mechanical properties, and the biopharmaceutical behavior such as the amount of CCMoid released from the gels. The nanostructured supramolecular hydrogels, which contain the CCMoids at much lower concentrations (μg/mL) in comparison to other products, promote the penetration of the CCMoids within the skin, but not their transdermal permeation, thus preventing any possible systemic effects and representing a safer option for topical administration. As a result, the CCMoid-containing hydrogels can effectively reduce skin inflammation in vivo, proving that these supramolecular systems are excellent alternatives in the treatment of inflammatory skin diseases

Supramolecular Hydrogels Consisting of Nanofibers Increase the Bioavailability of Curcuminoids in Inflammatory Skin Diseases

The low bioavailability of curcuminoids (CCMoids) limits their use in the treatment of inflammatory skin diseases. Our work shows that this constraint can be overcome upon their incorporation into supramolecular hydrogels assembled from a gemini-imidazolium amphiphilic gelator. Three structural CCMoid analogues were used to prepare supramolecular hydrogels, and it was observed that the concentration of both the gelator and CCMoid and the proportion of solvents influence the self-assembly process. Moreover, the mechanical properties of the nanostructured gels were studied to find the optimum gels, which were then further characterized microscopically, and their ability to release the CCMoid was evaluated. The physicochemical properties of the CCMoids play a fundamental role in the interaction with the gelator, influencing not only the gelation but also the morphology at the microscopic level, the mechanical properties, and the biopharmaceutical behavior such as the amount of CCMoid released from the gels. The nanostructured supramolecular hydrogels, which contain the CCMoids at much lower concentrations (μg/mL) in comparison to other products, promote the penetration of the CCMoids within the skin, but not their transdermal permeation, thus preventing any possible systemic effects and representing a safer option for topical administration. As a result, the CCMoid-containing hydrogels can effectively reduce skin inflammation in vivo, proving that these supramolecular systems are excellent alternatives in the treatment of inflammatory skin diseases.This work was supported by the projects PID2020-115663GB-C3-2, PID2019-108794GB-I00, and PID2020–115631GB-I00 funded by MCIN/AEI/10.13039/501100011033 from the Ministerio de Ciencia e Innovación. We thank AGAUR for a grant to consolidated research groups 2017SGR1277. A.G.-C. and N.A.-A. acknowledge the financial support from the Spanish Ministry Science, through the “Severo Ochoa” Programme for Centres of Excellence (FUNFUTURE) (2020-2023). A.G.-C. also acknowledges a Ramon y Cajal Grant (RYC-2017-22910).With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

On Predicting Mössbauer Parameters of Iron-Containing Molecules with Density-Functional Theory

The performance of six frequently used density functional theory (DFT) methods (RPBE, OLYP, TPSS, B3LYP, B3LYP*, and TPSSh) in the prediction of Mössbauer isomer shifts(δ) and quadrupole splittings (ΔEQ) is studied for an extended and diverse set of Fe complexes. In addition to the influence of the applied density functional and the type of the basis set, the effect of the environment of the molecule, approximated with the conducting-like screening solvation model (COSMO) on the computed Mössbauer parameters, is also investigated. For the isomer shifts the COSMO-B3LYP method is found to provide accurate δ values for all 66 investigated complexes, with a mean absolute error (MAE) of 0.05 mm s–1 and a maximum deviation of 0.12 mm s–1. Obtaining accurate ΔEQ values presents a bigger challenge; however, with the selection of an appropriate DFT method, a reasonable agreement can be achieved between experiment and theory. Identifying the various chemical classes of compounds that need different treatment allowed us to construct a recipe for ΔEQ calculations; the application of this approach yields a MAE of 0.12 mm s–1 (7% error) and a maximum deviation of 0.55 mm s–1 (17% error). This accuracy should be sufficient for most chemical problems that concern Fe complexes. Furthermore, the reliability of the DFT approach is verified by extending the investigation to chemically relevant case studies which include geometric isomerism, phase transitions induced by variations of the electronic structure (e.g., spin crossover and inversion of the orbital ground state), and the description of electronically degenerate triplet and quintet states. Finally, the immense and often unexploited potential of utilizing the sign of the ΔEQ in characterizing distortions or in identifying the appropriate electronic state at the assignment of the spectral lines is also shown

Determination of Curcuminoids by Liquid Chromatography with Diode Array Detection: Application to the Characterization of Turmeric and Curry Samples

Background: A simple, rapid and efficient method for the determination of curcumin and other polyphenols in turmeric and curry samples was here developed. The method relied on sample extraction with methanol and extract analysis by liquid chromatography with diode array detection (HPLC-DAD). Methods: The separation of components was carried out in reversed-phase mode using an elution gradient based on 0.1% (v/v) formic acid aqueous solution and acetonitrile as the components of the mobile phase. Chromatograms were recorded at 420 nm for specific monitoring of curcumin and related compounds. Results: Extraction and separation conditions were optimized by experimental design and multicriteria response functions. Figures of merit were established under the selected experimental conditions. In general, repeatability of peak areas were better than 0.4%, detection limits were below 0.006 mg L-1 and quantitative recoveries expressed as a percentage were about 100 ± 2. The method was applied to quantify curcuminoids in commercial samples. It was found that apart from curcumin, demethoxycurcumin and bisdemethoxycurcumin, other related molecules also occurred in the samples. In this regard, a tentative elucidation of possible unknown curcuminoids was attempted by liquid chromatography coupled to mass spectrometry. Conclusion: Differences in the compositional profiles among samples were encountered to be relevant, so that the resulting HPLC-DAD data was exploited for chemometric characterization of turmeric and curry samples. Samples were successfully discriminated according to matrix types, species varieties and origins.This work was financed by the Spanish Ministry of Economy and Competitiveness through the projects CTQ2014-56324-CO2-P1, MAT2014-53500-R, MAT2016-77852-C2-1-R and the “Severo Ochoa” Programme for Cen-ters of Excellence in R&D (SEV-2015-0496), and by Gener-alitat de Catalunya with project 2014SGR377.Peer reviewe

Novel Zn(II) Coordination Polymers Based on the Natural Molecule Bisdemethoxycurcumin

This article introduces a new family of coordination polymers (CPs) that contains a natural biocompatible curcumin derivative, the bisdemethoxycurcumin (BDMC), coordinated to Zn(II) centers. The reaction between BDMC and zinc acetate, performed under mild conditions in ethanol, provides a new 1D phase termed BDMCZn-1. In addition, dimensionality and porosity of this network have been expanded by studying the reaction occurring between three species, the BDMC, the Zn(II) and a ditopic co-linker: 1,2-bis(4-pyridyl)ethylene, 1,3-bis(4- pyridyl)propane or 4,4'-bipyridine. In total, seven new CPs are presented, named as BDMCZnx. The structures of five of them could be elucidated by single crystal X-ray diffraction. Moreover, we show that the combination of the latest technique with solid-state 13C nuclear magnetic resonance is a powerful tool set to analyze the coordination modes of the BDMC, providing insight into the two unresolved structures. In the achievement of the new CPs, we further discuss the coordination capacity of BDMC, the relevance of solvents and supramolecular interactions.This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 R&D programme (ERC-724981). We also acknowledge the Spanish Government, Ministerio de Ciencia e Innovación (projects CTQ2017-83632, CTQ2015-68370-P and PGC2018-098630-B-I00 - MAT2016-77852-C2-1-R, and Ramon y Cajal grant RYC-2017-22910) and the Generalitat de Catalunya for the grant 2017SGR1277. C.D., N.A.A., A.L.P., A.G.C., and L.R.C. acknowledge the financial support through the “Severo Ochoa” program for Centres of Excellence in R&D (SEV-2015-0496) under the FUNMAT-FIP-2016 fellowship. Special thanks to the Alba synchrotron for the possibility of carrying out the measurements of the crystals in the experiments AV-2017042211, AV-2018052864, AV-2018072912, and AV-2019023285 at beamline BL13–XALOC. This work (L.R.C.) has been done in the framework of the doctoral program “Chemistry” of the Universitat Autònoma de Barcelona.Peer reviewe

Crystalline Curcumin bioMOF obtained by precipitation in supercritical CO2and structural determination by Electron Diffraction Tomography

8sinoneThis article analyzes the use of supercritical CO2green technology in the reactive crystallization processes involved in the formation of a bioMOF that contains curcumin and ZnIImetal centers. A new phase with a [Zn(curcumin)]ncomposition, termed sc-CCMOF-1, is presented. The developed scCO2protocol allows high yields of the small-sized crystalline material, which was characterized by the use of the recently developed electron diffraction tomography method applied to the resolution of submicrometric crystals. A remarkable 3D macrostructure with a complex morphology was obtained. To analyze the crystallization mechanism, multiple identical runs were performed under similar experimental conditions to study in each time period the crystal growth progress ex situ by X-ray diffraction and scanning electron microscopy. These experiments indicated that the process to achieve the sc-CCMOF-1 in a crystalline form involves the formation of amorphous or semicrystalline metastable phases that derived into hierarchical stable and crystalline nanoflower aggregates. In addition, a potential therapeutic application of the bioMOF has been tested by studying the released of the curcumin molecule at neutral pH.nonePortolés-Gil, Nuria; Lanza, Arianna; Aliaga-Alcalde, Núria; Ayllón, José A.; Gemmi, Mauro; Mugnaioli, Enrico*; López-Periago, Ana M.; Domingo, ConcepciónPortolés-Gil, Nuria; Lanza, Arianna; Aliaga-Alcalde, Núria; Ayllón, José A.; Gemmi, Mauro; Mugnaioli, Enrico; López-Periago, Ana M.; Domingo, Concepció