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Stationary phases (SPs) based on silica matrices functionalized with amino groups linked to their surface through alkyl chains of various length have found remarkable success in performing HILIC separations, showing really effective resolution towards a wide typology of compounds of biological interest, such as carbohydrates, nucleosides, purine and pyrimidine bases. Recently, we developed an operationally simple procedure, named DNBA-M, non-destructive for the analysed SP, designed to quantify the density of basic groups (typically amino groups) chemically bonded to the surface of porous solids. In the present study the DNBA-M procedure has been suitably modified to allow the quantification of any typology of amino groups present on silica matrices packed into HPLC columns. The new approach, named OC-DNBA-M, has been successfully validated through analysis of two HPLC columns packed with aminopropyl-silica matrices. Afterwards, it was also demonstrated as the OC-DNBA-M procedure may allow the effective and in-depth analysis of the structural composition characterizing SPs packed inside HPLC columns, in which amino-groups have been differently and only partially involved in following ureidic functionalizations. It was also proved how the analysed columns can be readily re-employed for the chromatographic applications for which they have been designed, without appreciable deterioration of the respective discrimination abilities.

Many biologically active compounds feature low solubility in aqueous media and, thus, poor bioavailability. The formation of the host-guest complex by using calixarene-based macrocycles (i.e., resorcinol-derived cyclic oligomers) with a good solubility profile can improve solubilization of hydrophobic drugs. Herein, we explore the ability of resorc[4]arenes to self-assemble in polar solutions, to form supramolecular aggregates, and to promote water-solubility of an isoflavone endowed with anti-cancer activity, namely Glabrescione B (GlaB). Accordingly, we synthesized several architectures featuring a different pattern of substitution on the upper rim including functional groups able to undergo acid dissociation (i.e., carboxyl and hydroxyl groups). The aggregation phenomenon of the amphiphilic resorc[4]arenes has been investigated in a THF/water solution by UV–visible spectroscopy, at different pH values. Based on their ionization properties, we demonstrated that the supramolecular assembly of resorc[4]arene-based systems can be modulated at given pH values, and thus promoting the solubility of GlaB.

The ability of some zwitterionic natural deep eutectic solvents (NADESs) based on N,N,N-trimethylglycine (TMG) and carboxylic acids (oxalic, glycolic and phenylacetic) to act as environmentally friendly solvents for CO2 capture has been investigated. The solubility of CO2 in the NADESs was measured gravimetrically at different temperatures in the range 298.15–333.15 K, and at different pressures in the range 0.1–4 MPa. The effect of the adopted experimental conditions has been discussed. The highest uptake has been observed for phenylacetic acid/TMG DES at 313.15 K and 4 MPa (45.5 mg CO2/g DES). The efficiency of this NADES as CO2 sorbent when reused in subsequent capture cycles has been evaluated. This work might open new perspectives in developing the most appropriate combination of HBA and HBD components of the DESs and the most appropriate operative conditions for an environmentally friendly CO2 capture.

The effect of entrapped beta-cyclodextrin (beta-CD) on the stability of multilamellar vesicles (MLVs) of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), prepared by the dehydration-rehydration method, was studied by monitoring the release of 5(6)-carboxyfluorescein encapsulated into the liposomes. Different hydrophobic guests, such as Fullerene C(60), have been incorporated into the POPC bilayer in order to modify the membrane composition. The kinetic results as well as ESI-MS measurements evidenced that the destabilizing activity of beta-CD is due to the formation of beta-CD inclusion complexes and the consequent removal of selected bilayer constituents from the liposomal membrane. Hence, when beta-CD was added to the liposomes in the form of a strong, water-soluble 2:1 beta-CD/C(60) inclusion complex, such a destabilizing effect was not observed. However, the same beta-CD/C(60) inclusion complex does not form as a result of C(60) extraction from the bilayer. This may be attributed either to the overwhelming concentration of POPC with respect to C(60) and/or to the fact that C(60) is largely aggregated in the bilayer. Turbidimetric and fluorimetric determinations of lamellarity and entrapped volume of the studied MLVs provided further evidence of the alteration of the liposomal bilayer as a consequence of the addition of beta-CD and/or the presence of the studied guests.

A comparative thermodynamic investigation of the keto-enol interconversion reaction has been performed in several organic solvents and room-temperature ionic liquids (RTILs) to evaluate the role of the solvent and the effect of the ionic composition of RTILs. The tautomeric constant (KT) values at different temperatures have been analyzed in terms of the van't Hoff relationship to give the relevant thermodynamic parameters. The ΔG° values are the results of quite different combinations of the ΔH° and ΔS° values depending on the nature of the solvent. As expected, in conventional solvents, the tautomeric equilibrium is enthalpically disfavored and entropically favored by the increase in solvent polarity. In ionic liquids, the nature of the anion seems to play a primary role in the thermodynamics of the reaction that is endothermic and enthalpically driven in PF6- and TF2N-based RTILs and exothermic but entropically driven in BF4-based RTILs. The cation effect on the thermodynamics of the reaction is more complex and is consistent with a prevalence of the alkyl side chain segregation in the organization of the ILs.

Solute-solvent interactions on the keto-enol tautomerism of 2-nitrocyclohexanone in several organic solvents and room-temperature ionic liquids (RTILs) have been analyzed in terms of multiparameter equations. Permittivity and cohesive pressure values of the RTILs, unavailable by direct measurements, have been derived.

The presence of micelles from cationic and zwitterionic surfactants increases the apparent acidity of either the keto and the enol forms of 2-phenylacetylfuran ( 2PAF ) and 2-phenylacetylthiophene ( 2PAT ). This effect can be attributed to the affinity of the surfactant micelles for the enolate of the two substrates. Although the equilibrium constants for keto–enol tautomerism of 2PAF and 2PAT , K T =[enol]/[ketone]=p K a KH −p K a EH , do not change much, the presence of micelles provides an efficient method for producing appreciable quantities of the enolates under mild experimental conditions and in aqueous solutions. The obtained rate-profiles for the ketonisation reactions and the consistency of the kinetic rate constants over a wide range of ‘pH’ in several overlapping buffers indicate that the pH of the aqueous pseudophase (but not that at the micellar surface) can be controlled by buffers. Moreover, the increase of the acidity and the decrease of the ‘water’ rate of ketonisation of the enols of 2PAF and 2PAT upon addition of surfactants allow the uncovery of a metal ion catalysed pathway that cannot be observed in absence of surfactants.

The ability of several organic compounds [alcohols 1 and 2, the corresponding phosphate esters 3 and 4 and their sodium salts 5 and 6 as well as some commercial surfactants such as C14DMAO (7, zwitterionic), SDS (8, anionic) and CTABr (9, cationic)] to produce supramolecular complexes with β-cyclodextrin has been investigated by four different techniques (ESI-MS, surface tension measurements, UV/Vis and 1H NMR spectroscopy). The data collected have allowed information about the formation of complexes and the location of the guest in the host to be gained. Comparison of the results obtained for phosphate esters and their salts, for both saturated and unsaturated derivatives, has made it possible to evaluate the factors that affect the stability of the supramolecular complexes under the different experimental conditions used. © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

The equilibrium constants for the keto-enol tautomerism of 2-phenacylfuran (2PF), KT = (enol)/(ketone), have been determined in water and in aqueous solutions of CTAB (cetyltrimethylammonium bromide) by combining the pKa KH for ionization of the ketone, directly measured in aqueous NaOH solutions, and the pKa EH for ionization of the enol, obtained from the corresponding rate profile of ketonization. Comparison of these equilibrium constants with those reported for some previously studied phenylacetyl- and phenacyl- heterocycles highlights the effect of an adjacent furyl group on keto-enol tautomerism. Moreover, it has been shown that micelles from cationic (CTAB) and zwitterionic (3-N,N-(dimethyl-N- myristylammonium)propanesulfonate) surfactants decrease the rate of ketonization of the enolate of 2PF and/or increase the apparent acidity of the keto form. These effects have been related to the affinity of the surfactant micelles for the enolate of 2PF. To the contrary, anionic surfactants (SDS: sodium dodecyl sulfate) do not display appreciable effects on the acidity of the keto form or on the kinetics of ketonization of the enol form of 2PF.

Kinetic data on the enolization reaction of 3-acetyl-5-methylisoxazole, 5-acetyl-3-methylisoxazole, 3(5)-acetylpyrazole and some previously studied acetylheterocycles have been the object of a comprehensive ab initio analysis. Enolization rate constants were measured spectrophotometrically by the halogen trapping technique at 25 °C and ionic strength of 0.3 mol dm−3 in water, in acetate buffers, in dilute hydrochloric acid, in dilute sodium hydroxide and in the presence of some metal ion salts. In the spontaneous (water) and base (acetate) catalysed reactions the ketones investigated are generally more reactive than acetophenone, according to the electron-withdrawing effect of the heterocyclic ring compared with the benzene ring. In particular, acetylisoxazoles, 3(5)-acetylpyrazole and acetylthiazoles are more reactive than acetylfurans, 2-acetylpyrrole and acetylthiophenes respectively, and this can be attributed to the additional effect of the second heteroatom in the heterocyclic moiety. On the other hand, the compounds investigated are generally less reactive than acetophenone in the H3O+-catalysed reaction. Ab initio calculations on the relative stability of the protonated and unprotonated forms of the substrates investigated have been compared with the kinetic results obtained in acid solutions. As far as the metal ion catalysis is concerned, an approach in terms of ΔΔE can give an estimate of the combined contributions of charge densities and frontier orbitals to the interaction of the substrate with the metal ion catalyst. A comparison of experimental metal activating factor values and ab initio calculations outlines the importance of charge density on the carbonyl oxygen atom of acetylheterocycles with one heteroatom. An analogous comparison for acetylheterocycles with two heteroatoms suggests the formation of a chelate complex or transition state, in which the metal ion coordinates both the carbonyl oxygen and the aza nitrogen, whenever these two atoms are suitably placed within the molecular structure of the acetylheterocycle. Copyright © 2002 John Wiley & Sons, Ltd.

Rate constants for the enolisation reactions of title compounds have been measured by their rates of halogenation at 25 °C in water, in several buffers, in dilute hydrochloric acid, in dilute sodium hydroxide, and in the presence of some metal ion salts. The results have been compared with those previously obtained from the corresponding reactions of acetophenone and a number of other acetyl heterocycles. Electronegativity of the heteroatoms and the “π-excessive” nature of the heterocyclic rings appear to be the main factors determining the relative reactivities in the acid-catalysed reactions. Bronsted β values and isotope effects, kH/kD, point to a more symmetrical transition state for the investigated acetyl heterocycles than that for acetophenone in the general base-catalysed reaction. Metal-activating factors (MAF), i.e. the catalytic constant for metal-ion (Cu2+, Zn2+, and Ni2+) catalysis, kM, relative to that for proton catalysis, kH, are discussed as an empirical measure of the “hard or soft” character of the carbonyl groups in acyl heterocycles.

The keto–enol tautomerism of some cyclic 2-nitroalkanones was studied in cyclohexane. Keto–enol equilibrium constants, KT, at 25 °C were obtained from 1H NMR spectra. The relative enol content for the investigated ketones as a function of ring size decreases in the order 6 > 7 > 11 > 12 > 15. This trend apparently is different from that observed in water. Density functional theory (DFT) calculations have been performed to rationalize the effects of ring size and of the solvent on tautomerism. The acidity constants, KaKH, for the different keto tautomers were measured spectrophotometrically at 25 °C in buffered aqueous solutions. No simple correlations between KaKH and ring size was observed, and this is in agreement with a DFT analysis performed on the same compounds.

Inductive and mesomeric effects of the [60]fulleropyrrolidine (Pyr=C60) and the [60]fullerene (C60) molecular frameworks have been investigated by linear free energy relationship analyses. The electronic effects of these moieties have been studied by expressly designing [60]fulleropyrrolidine derivative 1, which has a C–H bond α to both a carbonyl group (C–Hα) and a C60 cage. The extent of polarization of such a bond was then used to probe electron-withdrawing perturbation induced by the fullerene sphere. Thermodynamic measurements based on both theoretical and experimental approaches allowed the acidity of ketone 1 to be measured; this resulted in about a 1 × 106-fold increase in acidity with respect to that of the structurally correlated acetophenone. Experimental and theoretical kinetic determinations were used to determine the stereolability of ketone 1, which was, in fact, chiral due to the stereogenic carbon α to the carbonyl group. Also, these results confirmed the very strong tendency for the C60 sphere to promote breaking of the C–Hα bond. Thismeans that the Pyr=C60 and C60 fragments are able to express electron-withdrawing effects stronger than those of halogen atoms, but less effective than those of carbonyl derivatives (e.g., ketones, carboxylic acids or acyl derivatives). Finally, the σp, σI and σR– descriptors of inductive and/or mesomeric effects were successfully estimated for both Pyr=C60 and C60 fragments thanks to the integrated use of an original procedure based on semi-empirical calculations and Hammett/Taft correlations involving mono- or dual-parameter equations.

The equilibrium constants for ion pair formation of some pyridines have been evaluated by spectrophotometric titration with trifluoroacetic acid in different ionic liquids. The basicity order is the same in ionic liquids and in water. The substituent effect on the equilibrium constant has been discussed in terms of the Hammett equation. Pyridine basicity appears to be less sensitive to the substituent effect in ionic liquids than in water.

While the solvent effect on the rate of tautomerization of 2-nitrocyclohexanone in several organic solvents appears to depend essentially on the permittivity of the solvent, a different behavior is observed in some ionic liquids. In particular the rate of the reaction in ionic liquids (ILs) is much faster than expected solely on the basis of the permittivity of the studied ILs. However, if more solvent parameters are taken into consideration (namely the polarizability, H-bond acidity, and cohesive pressure of the solvent) one comprehensive linear solvation energy relationship (LSER) for both organic and IL media can be obtained and no special "ionic liquid effect" can be highlighted. The kinetic results have also been discussed in terms of the Bronsted equation. It turns out that on passing from molecular solvents to ILs the transition state structure of the enolization reaction becomes markedly enolate-like (Bronsted beta value close to 1).

The rates of tautomerization of 2-nitrocyclohexanone (2-NCH) have been measured spectrophotometrically at 25.0 +/- 0.1 degrees C in several organic aprotic solvents and their binary mixtures. In cyclohexane the reaction is effectively catalyzed by bases and inhibited by acids while the so-called "spontaneous reaction" appears essentially due to autocatalysis. Apparent second order rate constants (k(app)(B)) for the reaction catalyzed by triethylamine (TEA) and pyridine (Pyr) have been obtained. From the experimental k(app)(B) values rate constants for the enolization (k(1)(B)) and ketonization (k(-1)(B)) reactions have been calculated. A Kamlet-Taft type linear solvation energy relationship (LSER) adequately accounts for the observed solvent effects. Activation parameters for both reactions show that solvent effects are mainly entropic in origin and that there is a shift of the transition state from a ketone-like to an enol-like structure on passing from less to more polar solvents.

An effective strategy to assess and modulate the stereolability of chiral a substituted ketones (CaSKs) is presented. The tendency of CaSKs to retain or change their configuration in water is analyzed as a function of thermodynamic proton-release attitude of a asymmetric atoms inside the structures by linear Bronsted correlations. A molecular modeling procedure was developed to analyze and suggest chemical modifi- cations of CaSKs in view to obtain the desired grade of stereochemical stability. The approach was employed to predict the tendency to enantiomerize in water of two ketones (1 and 2) endowed with inhibitory activity against monoamine oxidases (MAOs) and the results were confirmed by experimental kinetics measurements per- formed in organic medium. As a demonstration of practical potentialities of the approach, four new structures, conceived as simple chemical modifications of 1 and 2, were designed to improve/reduce the stereostability grade of the starting anti-MAO ketones. The possibility to extend easily the procedure to other classes of C� � H acids appears of interest. Chirality 21:24-34, 2009. V V C 2008 Wiley-Liss, Inc.

The keto-enol tautomerism of 2-nitrocyclohexanone (2-NCH) was studied in aqueous solution under different experimental conditions. Ketonization rate constants were measured spectrophotometrically at 25 degrees C at an ionic strength of 0.4 mol dm-3 (NaCl) in diluted hydrochloric acid, in diluted sodium hydroxide, and in several buffers by using NaHSO3 as the scavenger of the keto form. A value of pK(a)(EH) = 4.78 for the enol form was obtained from the rate-pH profile of the reaction. A value of pK(a)(KH) = 5.97 for the keto form was directly obtained from the UV-vis spectra of 2-NCH recorded at different pHs. The equilibrium constant for the keto-enol tautomerism, pK(T) = -log([enol]/[ketone]) = 1.19, was obtained by combining the two pKa values (pK(T) = pK(a)(KH) - pK(a)(EH)). A comparison of these results with the corresponding values (Keefe, J. R.; Kresge, A. J. In The Chemistry of Enols; Rappoport, Z., Ed.; WileySons: New York, 1990; pp 399-480) for cyclohexanone shows the dramatic effects of an alpha-nitro substituent on the keto-enol acidities and the tautomerization constant of alicyclic ketones. Rates and equilibria were discussed in the light of the Brønsted equation, the principle of nonperfect synchronization, and the Marcus theory. It turns out that, on passing from nitroalkanes to nitroketones, the resonance contribution to pKa and deprotonation rate decreases, being overwhelmed by steric and inductive effects.

The rates of Z-E isomerization of azobenzene and seven 4-substituted derivatives (CH3, CF3, OCH3, n-Butyl, Ot-Butyl, Br, F) have been investigated at 25 °C in ethanol, in methanol, in methanol/water mixtures and in aqueous solutions of ionic and non-ionic micelles by recording in the dark the spectral changes observed after exposure to UV light of the samples. The competitive contributions of the rotation vs. inversion mechanisms by which the isomerization of azobenzenes can occur have emerged from V-shaped Hammett plots. The obtained rate constants can be used as polarity indicators of the different micro-heterogeneous media with two main advantages with respect to other probes. Firstly they are not affected by hydrogen bonding between the substrate and the environment, as in the case of push-pull azobenzenes. Secondly, the derived substrate-independent Hammett ρ values allow to separate the effects of orientation of the probe from the polarity of the supramolecular aggregate.

The cationic large unilamellar mixed liposomes from 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and didodecyldimethylammonium bromide (DDAB) or dioctadecyldimethylammonium bromide (DODAB) were prepared. The influence of the addition of Triton X-100 (TX-100) or octaethylene glycol mono-n-dodecylether (C12E8) on the membrane integrity was investigated turbidimetrically. The stability of the liposomal systems was estimated by monitoring fluorimetrically at 25 degrees C the rate of spontaneous and surfactant-induced release of entrapped 5(6)-carboxyfluorescein (CF). In order to evaluate the interaction of the cationic DODAB guest with the host POPC membrane, the main phase transition temperatures (T-m) were determined by electron paramagnetic resonance spectroscopy (EPR). All the results obtained show that the presence of DODAB and DDAB stabilizes the POPC liposomes. The extent of stabilization depends on the concentration and nature of the cationic guest. (C) 2011 Elsevier Ireland Ltd. All rights reserved.