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.

Do Deep Eutectic Solvents Form Uniform Mixtures Beyond Molecular Microheterogeneities?

We have performed small-angle neutron scattering in a momentum transfer range (0.05 < Q < 0.5 Å-1) to study long-range order and concentration fluctuations in deep eutectic solvents (DESs) and their aqueous solutions. Ethaline (choline chloride/ethylene glycol), glycerol/lactic acid, and menthol/decanoic acid mixtures were selected to illustrate individually the case of ionic, nonionic, and hydrophobic mixtures. Carefully designed isotopic labeling was used to emphasize selectively the spatial correlations between the different solvent components. For ethaline DESs and their aqueous solutions, a weak low-Q peak observed only for certain compositions and some partial structure factors revealed the mesoscopic segregation of ethylene glycol molecules that do not participate in the solvation of ionic units, either because they are in excess with respect to the eutectic stoichiometry (1:4 neat ethaline) or substituted by water (4w-ethaline and higher aqueous dilutions). For the nonionic hydrophilic solutions, such a mesoscopic segregation was not observed. This indicates that the better balanced interactions between the three nonionic H-bonded components (water, lactic acid, and glycerol) favor homogeneous mixing. For the hydrophobic DESs, we observed an excess of coherent scattering intensity centered at Q = 0, which could be reproduced by a model of noninteracting spherical domains. Local concentration fluctuations are not excluded either. However, unlike liquid mixtures with a tendency to demix, we have found no evidence of expansion of domains with different compositions to a large scale.

Electron Transfer Kinetics in a Deep Eutectic Solvent.

Electron transfer (ET) kinetic rate constants ks in Ethaline (1:2 choline chloride + ethylene glycol) have been measured for two common redox couples (ferrocene/ferrocenium and ferrocyanide/ferricyanide) on a glassy carbon electrode and compared with ET kinetics in ionic liquids and classical organic solvents in the same conditions (acetonitrile and water). Particular care has been taken to treat ohmic drop in DES. For both couples, we found that ET rate constants are just a little lower than those measured in classical solvents (around 50% or less). These results contrast with ET rates in ionic liquids where electron transfers are considerably slower (100 times lower). Data are discussed as a function of the solvent relaxation time using Marcus Theory for an adiabatic electron transfer.

Di- and heptavalent nicotinic analogues to interfere with α7 nicotinic acetylcholine receptors.

In the field of nicotinic acetylcholine receptors (nAChRs), recognized as important therapeutic targets, much effort has been dedicated to the development of nicotinic analogues to agonize or antagonize distinct homo- and heteropentamers nAChR subtypes, selectively. In this work we developed di- and heptavalent nicotinic derivatives based on ethylene glycol (EG) and cyclodextrin cores, respectively. The compounds showed a concentration dependent inhibition of acetylcholine-induced currents on α7 nAChR expressed by Xenopus oocytes. Interesting features were observed with the divalent nicotinic derivatives, acting as antagonists with varied inhibitory concentrations (IC50) in function of the spacer arm length. The best divalent compounds showed a 16-fold lowered IC50 compared to the monovalent reference (12 vs 195 µM). Docking investigations provide guidelines to rationalize these experimental findings.