The Use of Flavylium Salts as Dynamic Inhibitor Moieties for Human Cb5R

Authors would like to acknowledge the Biochemistry Department in the Faculty of Medicine at the Universidad Autónoma de Madrid for the equipment and support for some of the required reagent purchases. FCT/MCTES is also acknowledged for supporting the National Portuguese NMR Network (ROTEIRO/0031/2013-PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI, PORL. We thank José Paulo da Silva for the HRMS-ESI analysis. Publisher Copyright: © 2022 by the authors.Cytochrome b5 reductase (Cb5R) is a flavoprotein that participates in the reduction of multiple biological redox partners. Co-localization of this protein with nitric oxide sources has been observed in neurons. In addition, the generation of superoxide anion radical by Cb5R has been observed. A search for specific inhibitors of Cb5R to understand the role of this protein in these new functions has been initiated. Previous studies have shown the ability of different flavonoids to inhibit Cb5R. Anthocyanins are a subgroup of flavonoids responsible for most red and blue colors found in flowers and fruits. Although usually represented by the flavylium cation form, these species are only stable at rather acidic pH values (pH ≤ 1). At higher pH values, the flavylium cation is involved in a dynamic reaction network comprising different neutral species with the potential ability to inhibit the activities of Cb5R. This study aims to provide insights into the molecular mechanism of interaction between flavonoids and Cb5R using flavylium salts as dynamic inhibitors. The outcome of this study might lead to the design of improved specific enzyme inhibitors in the future.publishersversionpublishe

Aggregation of p-Sulfonatocalixarene-Based Amphiphiles and Supra-Amphiphiles

p-Sulfonatocalixarenes are a special class of water soluble macrocyclic molecules made of 4-hydroxybenzenesulfonate units linked by methylene bridges. One of the main features of these compounds relies on their ability to form inclusion complexes with cationic and neutral species. This feature, together with their water solubility and apparent biological compatibility, had enabled them to emerge as one the most important host receptors in supramolecular chemistry. Attachment of hydrophobic alkyl chains to these compounds leads to the formation of macrocyclic host molecules with amphiphilic properties. Like other oligomeric surfactants, these compounds present improved performance with respect to their monomeric counterparts. In addition, they hold their recognition abilities and present several structural features that depend on the size of the macrocycle and on the length of the alkyl chain, such as preorganization, flexibility and adopted conformations, which make these molecules very interesting to study structure-aggregation relationships. Moreover, the recognition abilities of p-sulfonatocalixarenes enable them to be applied in the design of amphiphiles constructed from non-covalent, rather than covalent, bonds (supramolecular amphiphiles). In this review, we summarize the developments made on the design and synthesis of p-sulfonatocalixarenes-based surfactants, the characterization of their self-assembly properties and on how their structure affects these properties

Worldwide Usage of International Classification of Primary Care

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Cucurbit[7]uril: surfactant host-guest complexes in equilibrium with micellar aggregates

In order to compare the formation of host–guest complexes between b-cyclodextrin (b-CD) or cucurbit[7]uril (CB7) and cationic surfactants we studied the hydrolysis of 4-methoxybenzenesulfonyl chloride (MBSC). The selected surfactants allowed the length of the hydrocarbon chain to be varied between 6 and 18 carbon atoms. Contrary to the expected behaviour, the values of the binding constants between CB7 and surfactants are independent of the alkyl chain length of the surfactant. In the case of b-CD, however, a clear dependence of the binding constant on the hydrophobic character of the surfactant was observed. The values obtained with CB7 are significantly higher than those obtained with b-CD and these differences are explained to be a consequence of electrostatic interactions of the surfactants with the portals of CB7. It was found that a small percentage of uncomplexed CB7 was in equilibrium with the cationic micelles and this percentage increased on increasing the hydrophobic character of the surfactant

Insights into the Structure of the Supramolecular Amphiphile Formed by a Sulfonated Calix[6]arene and Alkyltrimethylammonium Surfactants

In this work, we have studied the interactions between the water-soluble <i>p</i>-sulfonatocalix­[6]­arene and cationic surfactants octyltrimethylammonium bromide below the cmc and dodecyltrimethylammonium bromide above the cmc, by saturation transfer difference (STD) NMR spectroscopy. From the STD build-up curves, we have obtained the T1 independent cross relaxation rates, and the results show that the interactions established between the cationic headgroup of the surfactant and the OMe group of the macrocycle play an important role in the stabilization of the complex, both below and above the cmc

Unveiling the formation 1: 2 supramolecular complexes between cucurbit[7]uril and a cationic calix[4]arene derivative

The formation of host-guest complexes between cucurbit[7]uril (CB7) and a tetracationic calix[4]arene derivative in the so-called cone conformation was investigated by H-1 NMR, DOSY NMR, isothermal titration calorimetry and ESI-MS. The results point to the formation of 1: 1, 1: 2 and 2: 1 CB7:calixarene complexes with binding constants of 3 x 10(6) M-1, approximate to 2 x 10(2) M-1, and 9 x 10(4) M-1 respectively. The study demonstrates, on one hand, that despite having four potential recognition sites, the calixarene only binds two CB7 molecules and, on the other, that for sterically crowded binding motifs that prevent CB7 inclusion with optimized hydrophobic and ion-dipole interactions, the formation of 1:2 complexes can be observed most likely due to formation of external binding of the cationic moieties to the CB7 carbonyl portals.FCT (Portugal)Portuguese Foundation for Science and TechnologyMICINN (Spain)Spanish GovernmentERDFEuropean Union (EU) [UID/QUI/50006/2019, UID/Multi/04326/2019, ALG-01-0145-FEDER-022121 PTDC/QUI-COL/32351/2017, CEECIND/00466/2017, CTQ2017284354-P, GR 2007/085, IN607C 2016/03, ED431G/09]info:eu-repo/semantics/publishedVersio