Deep Eutectic Solvents formed by chiral components as chiral reaction media and studies of their structural properties

We present the realization, the use as reaction media/chiral organocatalysts/acid catalysts and the structural properties of novel chiral Deep Eutectic Solvents. These liquids are formed by mixtures of chiral HBD and HBA molecules that are common, relatively cheap and commercially available (the two enantiomers of camphorsulfonic acid as HBD) or easily one-step synthesized molecules from commercially available compounds ((S)- and (R)-N,N,N-trimethyl-(1-phenylethyl)ammonium methanesulfonate as HBA). These liquids proved to be highly-structured as showed by different yields and enantiomeric excesses observed in a probe reaction, suggesting these liquids to form diastereoisomerically different liquids by changing one of the two enantiomers. Their structural features were analyzed via 1H Pulsed Field gradient Spin Echo (PGSE) NMR, NMR titration, 1H NMR analyses of formation and differences in the chemical shifts of the peaks of the liquids. Density Functional Theory (DFT) optimization helped to define the structures of these liquids. The methanesulfonate counterion of HBA molecule showed to be relevant in order to obtain these highly-structured liquids as it interacts specifically with the HBD. These chiral Deep Eutectic Solvents revealed to be promising novel high-structured media for enantioselective reactions

Use of a Zwitterionic Surfactant to Improve the Biofunctional Properties of Wool Dyed with an Onion (Allium cepa L.) Skin Extract

To improve the loadability and antioxidant properties of wool impregnated with onion skin extract, the introduction of SB3-14 surfactant in the dyeing process was evaluated. A preliminary investigation on the surfactant–quercetin interaction indicated that the optimal conditions for dye solubility, stability, and surfactant affinity require double-distilled water (pH = 5.5) as a medium and SB3-14 in a concentration above the c.m.c. (2.5 × 10−3 M). The absorption profile of textiles showed the flavonoid absorption band (390 nm) and a bathochromic feature (510 nm), suggesting flavonoid aggregates. The higher absorbance for the sample dyed with SB3-14 indicated greater dye uptake, which was further confirmed by HPLC analysis. The Folin–Ciocalteu method was applied to evaluate the total phenol content (TPC) released from the treated wool, while the assays FRAP, DPPH, ABTS, and ORAC were applied to evaluate the corresponding total antioxidant activity (TAC). Higher TPCs (about 20%) and TACs (5–55%) were measured with SB3-14, highlighting textiles with improved biofunctional properties. Spectrophotometric analyses were also performed with an artificial sweat. The potential cytotoxic effect of SB3-14 in both monomeric and aggregated forms, cell viability, and induction of apoptosis were evaluated in RAW 264.7 cells. These analyses revealed that SB3-14 is safe at concentrations below the c.m.c

Eco-Friendly 1,3-Dipolar Cycloaddition Reactions on Graphene Quantum Dots in Natural Deep Eutectic Solvent

Due to their outstanding physicochemical properties, the next generation of the graphene family-graphene quantum dots (GQDs)-are at the cutting edge of nanotechnology development. GQDs generally possess many hydrophilic functionalities which allow their dispersibility in water but, on the other hand, could interfere with reactions that are mainly performed in organic solvents, as for cycloaddition reactions. We investigated the 1,3-dipolar cycloaddition (1,3-DCA) reactions of the C-ethoxycarbonyl N-methyl nitrone 1a and the newly synthesized C-diethoxyphosphorylpropilidene N-benzyl nitrone 1b with the surface of GQDs, affording the isoxazolidine cycloadducts isox-GQDs 2a and isox-GQDs 2b. Reactions were performed in mild and eco-friendly conditions, through the use of a natural deep eutectic solvent (NADES), free of chloride or any metal ions in its composition, and formed by the zwitterionic trimethylglycine as the -bond acceptor, and glycolic acid as the hydrogen-bond donor. The results reported in this study have for the first time proved the possibility of performing cycloaddition reactions directly to the p-cloud of the GQDs surface. The use of DES for the cycloaddition reactions on GQDs, other than to improve the solubility of reactants, has been shown to bring additional advantages because of the great affinity of these green solvents with aromatic systems

Switching the three-component Biginelli-like reaction conditions for the regioselective synthesis of new 2-amino[1,2,4]triazolo[1,5-a]pyrimidines

: Among the eight different triazolopyrimidine isomers existing in nature, 1,2,4-triazolo[1,5-a]pyrimidine (TZP) is one of the most studied and used isomers in medicinal chemistry. For some years, our group has been involved in developing regioselective one-pot procedures for the synthesis of 2-amino-7-aryl-5-methyl- and 2-amino-5-aryl-7-methyl-TZPs of interest in the preparation of antiviral agents. In this work, taking advantage of a Biginelli-like multicomponent reaction (MCR), we report the identification of finely tunable conditions to regioselectively synthesize C-6 ester-substituted amino-TZP analogues, both in dihydro and oxidized forms. Indeed, the use of mild acidic conditions is strongly directed toward the regioselective synthesis of 5-aryl-7-methyl C-6-substituted TZP analogues, while the use of neutral ionic liquids shifted the regioselectivity towards 7-aryl-5-methyl derivatives. In addition, the novel synthesized scaffolds were functionalized at the C-2 position and evaluated for their antiviral activity against RNA viruses (influenza virus, flaviviruses, and SARS-CoV-2). Compounds 25 and 26 emerged as promising anti-flavivirus agents, showing activity in the low micromolar range

Novel low viscous, green and amphiphilic N-oxides/phenylacetic acid based Deep Eutectic Solvents

Four novel Deep Eutectic Solvents (DESs) were prepared by mixing phenylacetic acid (which is a natural mole- cule present in honey) with amine N-oxides, which are molecules easily biodegradable in nature. Three of these N-oxides are amphiphilic. The novel DESs have very low freezing points (from −34 °C to 20 °C) and they have very low viscosity, much lower than the most common and used DES in literature so far (choline chloride/urea mixture). The conductivity values resulted low and the ionicity analysis showed these DESs to be “super ionic”. Their polarity resulted high enough and it can be compared with other commonly used solvents or ionic liquids

Carbon-Carbon bond formation in acid deep eutectic solvent: chalcones synthesis via Claisen-Schmidt reaction

One of the most studied properties of novel organic solvents is represented by their use as media for many chemical reactions. In this field Ionic Liquids (ILs) and more recently Deep Eutectic Solvents (DESs) have been playing significant roles for their smart properties. DESs are increasing their relevance thanks to their low toxicity, and because of their simple and cheap preparation that can be carried out by simply mixing two compounds. In this work we present the studies of the use of an acid DES obtained from 3-(cyclohexyldimethylammonio)propane-1-sulfonate and (1S)-(+)-10-Camphorsulfonic acid (SB3-Cy / CSA) as reaction media and catalyst for carbon-carbon bond formation reaction via Claisen-Schmidt condensation. This powerful and widely used aldol condensation was performed without the use of any catalysts that are usually needed in this reaction, because of the presence of acid CSA in the DES components. We synthesised sixteen substituted chalcones from benzaldehydes and substituted benzaldehydes in combination with acetophenone and substituted acetophenones as probe reactions. The advantages of the use of this DES in this relevant reaction are represented by: the green properties of the media and its low toxicity; the absence of harmful acids to catalyse the aldol condensation because of the camphorsulfonic acid composing the DES mixture; the recycling and the re-use of the DES in subsequent reaction cycles; the mild conditions and the excellent conversions and yields observed

Convenient Esterification of Carboxylic Acids by SN2 Reaction Promoted by a Protic Ionic-Liquid System Formed in Situ in Solvent-Free Conditions

The reaction of esterification of benzoic acid with benzyl chloride was chosen as a model reaction to study the esterification by SN2 promoted by tertiary amine as deprotonating agent. The use of ionic liquid (IL) 1,3-dimethylimidazolium methanesulfonate [MMIm][OMs] as reaction medium has proven to give quantitative yield of the ester, but interestingly the reaction does occur even in solvent-free conditions, where the acid + the amine form a liquid system (a protic IL) in situ. This last methodology was extended to several carboxylic acids in conditions of atom economy (i.e., without excess of any reagent), giving moderately good yields of esters (54–78%) recovered by weight in pure form

Investigations on the Use of Deep Eutectic Solvents (DESs) as Promoters for the Conjugate Addition of α-Nitroketones to Electron-Poor Alkenes

DESs were profitably investigated as solvents and promoters of the conjugate reaction addition of cyclic and acyclic α-nitroketones to a variety of electron-poor alkenes. The best results were obtained conducing the reaction in betaine:1,2-propanediol (1 :5 molar ratio) DES at room temperature, and enones were demonstrated to be the most effective Michael acceptors. The same reaction conducted by using different molar ratios of the components in this DES showed the eutectic point to be the most effective in terms of the yields observed

Role of anionic micelles in self-assembling of fluorescent acridinium-based chemosensors for the detection of mercury (II) ions

novel off-on fluorescent sensing system for Hg2+ ions was prepared through self-assembly, by anionic surfactant micelles, of different combinations of 10-alkylacridinium perchlorates (as fluorophores, with a methyl or an n-octyl chain) and N,N-bis(p-alkyloxybenzyl)-3,6-dioxaoctane-1,8-diamines (as receptors, with a methyl or an n-dodecyl chain) in water solution. The fluorescence quenching observed in the absence of metal ions (“off” state), likely due to a photoinduced electron transfer (PET) mechanism from diamine to acridinium moiety, has demonstrated that a communication between the binding site and the signaling unit actually occurs. The addition of Hg2+ resulted in its incorporation in the micelle with the formation of a receptor-metal complex in competition with the PET process, accordingly the fluorescence emission of acridinium was restored (“on” state). The experimental data suggested that compartmentalization effects in the different micellar microenvironments, due to the different hydrophobic degree of the components, can affect the fluorescence response of the sensor and therefore its sensitivity. These systems showed good sensitivity in Hg2+ sensing and its concentration can be linearly determined according to the fluorescence quenching

Acid-base responsive probes for mercury(II) ions in aqueous solution

A simple ratiometric optical method for mercuric ion sensing has been developed using an ensemble of an indicator, such as 7-hydroxy-4-methylcoumarin (7H4MC) and bromothymol blue (BTB), and a receptor, such as N,N-bis(p-methoxybenzyl)-3,6-dioxaoctane-1,8-diamines (bis-pMDODA) and cryptand [2.2.2] (C222), in aqu- eous solution. The equilibrium between indicator and receptor is perturbed by adding Hg2+ ions (0.8–80 μM), due to the formation of a receptor-metal complex, resulting in a change of the UV/Vis spectra. Both sensitivity and selectivity are explained in terms of association constants between receptor and metal ions and equilibrium constants of the reaction between indicator and receptor. Indicator bromothymol blue has also presented a color variation from light blue to yellow upon coordination of Hg2+ to the receptor, which allows a metal naked-eye detection. The detection limit of the system was found to be about 3 μM and the relative standard deviation for five measurements of 20 μM concentration was 5.6%. BTB/7H4MC arrangement showed a particular selectivity over different interfering cations, suffering only interference from Cu2+ ions for Hg2+ sensing