Linear Solvation Free Energy Relationship Research Articles

Solvent, structural, quantum chemical study and antioxidative activity of symmetrical 1-methyl-2,6-bis[2-(substituted phenyl)ethenyl]pyridinium iodides

15 symmetric 1-methyl-2,6-bis[2-(substituted phenyl)ethenyl]pyridinium iodides were synthesized in this work. Their structures were characterized using IR, 1H and 13C NMR, and UV–Vis spectroscopy. DFT calculations indicated that s-trans/s-trans conformation prevail in all compounds. The effects of specific and non-specific solvent–solute interactions on the UV–Vis absorption maxima shifts were evaluated using linear solvation-free energy relationships (LSER), i.e., Kamlet–Taft and Catalan models. A linear free energy relationship (LFER) in the form of single substituent parameter equations (SSP) was used to postulate quantitative structure–property relations of substituent effect on NMR data. TD-DFT results showed dependence of electronic transition on the substituent effects. The push–pull character of these compounds was analyzed by differences in 13C chemical shift of the ethylenic double bond in 2- and 6-positions of cross-conjugated with pyridinum central ring. Also, the quotient of the occupations for the bonding π and anti-bonding π* orbitals of this bond was considered. Good correlations of the selected parameter between double bond lengths with π*/π and 13C chemical shift differences of the bridging group proved them to be adequate descriptor of push–pull character. Synthesized compounds were screened for the antioxidant activity, using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical methods, and results demonstrated moderate antioxidant potential.

Using binary mixtures of dicationic ionic liquids for determination of activity coefficients at infinite dilution by gas–liquid chromatography

This work is the continuation of our investigation into using dicationic ionic liquids (ILs) as stationary phase in gas chromatography (Tabar Heydar K, Nazifi M, Sharifi A, Mirzaei M, Gharavi H, Ahmadi SH, J. Chromatographia 76 (2013) 165). In this work, the activity coefficients at infinite dilution of 23 various solutes (alkanes, aromatics, alcohols, aldehydes, ketones, amines, chloroalkanes, ethers) have been measured in the two binary mixtures of ILs: 1,12-di(N-methylpyrrolidinium)dodecane–bis(trifluoromethylsulfonyl)imide/1,12-di(3-methylimidazolium)dodecane–bis(trifluoromethylsulfonyl)imide (1:1), [C12(mpy)2]–[(NTf2)2]/[C12(mim)2]–[(NTf2)2] and 1,12-di(N-methylpyrrolidinium)dodecane–bis(trifluoromethylsulfonyl)imide/1,12 di(3-methylimidazolium)dodecane–tetrafluoroborate (1:1), [C12(mpy)2]–[(NTf2)2]/[C12(mim)2]–[(BF4)2], by gas–liquid chromatography (GLC) in the temperature range from 313 to 343K. The same operations were performed on the neat IL: 1, 12-di(N-methylpyrrolidinium)dodecane–bis(trifluoromethylsulfonyl)imide, [C12(mpy)2]–[(NTf2)2] at T=313 and 323K, in order to make a comparison between different ILs.These mixtures of dicationic ILs with different anions and the neat IL have been investigated in this study for the first time. Moreover, the solvation interactions between solvents and solute molecules at 313, 343 and 373K have been determined via Abraham solvation parameter model (linear solvation free energy relationship [LSFER] model). The selectivities for the octane/linear alcohols, octane/polar compounds, cyclohexane/aromatics were obtained from experimental activity coefficient data at 313K, and compared with other ILs from the literature. The result of this comparison confirms that these ILs are potentially excellent solvents for the separation of alkanes/alcohols, alkanes/polar compounds and aliphatic/aromatic mixtures.

Solvent effect on the absorption and fluorescence spectra of 7-acetoxy-6-(2,3-dibromopropyl)-4,8-dimethylcoumarin: Determination of ground and excited state dipole moments

The ground state (μg) and excited state (μe) dipole moments of 7-acetoxy-6-(2,3-dibromopropyl)-4,8-dimethylcoumarin (abbreviated as 7ADDC) are estimated from solvatochromic shifts of absorption and fluorescence spectra as a function of the dielectric constant (ε) and refractive index (n). While the ground state dipole moment is determined by using Bilot–Kawski method, the excited state dipole moment is calculated by using Bilot–Kawski, Lippert–Mataga, Bakhshiev, Kawski–Chamma–Viallet and Reichardt correlation methods. Excited state dipole moment is observed as larger than the ground state dipole moment due to substantial π-electron density redistribution. The ground state and excited state dipole moments are observed as parallel to each other with angle of 0°. Solute–solvent interactions are analyzed by means of linear solvation free energy relationships (LSER) using dielectric constant function (f(ε)), refractive index function (f(n)) and Kamlet–Taft parameters (α and β). Atomic charges, electron densities and molecular orbitals are calculated in vacuum and with solvent effect by using both DFT and TDDFT methods. Solvent accessible surface, molecular electrostatic potential (MEP) and electrostatic potential (ESP) are visualized as a result of DFT calculations.

Structural and spectroscopic study of Al(III)–3-hydroxyflavone complex: Determination of the stability constants in water–methanol mixtures

Stoichiometry and apparent stability constant (KC) of the complex formed between Al(III) and 3-hydroxyflavone were determined in methanol and water–methanol mixtures (% water w/w: 3.11; 6.15; 10.4; 15.2; 19.9 and 25.3) by UV–vis spectroscopy at 25.0°C and constant ionic strength (0.05M, sodium chloride). Stoichiometry of the complex (1:2, metal:ligand) is not modified with an increase in water percentage in the analyzed interval. The value of KC in methanol is greater than in the binary solutions. The effects of changing solvent composition on KC data were explained by linear solvation free energy relationships using the solvatochromic parameter of Kamlet and Taft (α, β and π*). Multiple linear regression analysis indicates that the hydrogen bond donating ability (α) of the solvent and non-specific interactions (π*) play an important role in the degree of occurrence of the reaction. The effect of temperature on KC was also analyzed by assessing standard entropy and enthalpy variations of the reaction in methanol. Finally, the structure of the complex was investigated using FTIR spectroscopy and DFT calculations. The ligand exhibits small structural changes upon complexation, localized on the chelating site. The calculated vibrational frequencies of the complex were successfully compared against the experimental values.

Effects of intramolecular hydrogen bonding and solvent composition on acidity of some dihydroxy-thioxanthone derivatives in methanol–water binary solvents

► The acidity constant of some new dihydroxy thioxanthone derivatives was determined. ► The effect of inter and intra hydrogen bonding on acidity constants were explained. ► The effect of solvent composition (methanol–water) was also investigated. ► 1,3-Dihydroxy derivative unexpectably showed one ionization step. ► The findings of this article are of especial importance for analytical applications. The acidity constant of four recently synthesized dihydroxy-thioxanthone derivatives (i.e., 1,4-dihydroxy; A1, 3-methyl-1,4-dihydroxy; A2, 2,3-dihydroxy; A3 and 1,3-dihydroxy; A4) in methanol–water binary mixed solvents were determined by multivariate analysis of spectrophotometric-pH-metric data. The solutes A1, A2 and A3 exhibited two ionization steps whereas one ionization step was observed for A4, attributed to the strong intramolecular hydrogen-bonding formed between the hydrogen of 1-hydroxy and its neighbor carbonyl group. The effects of molecular structure on the acid–base behavior of solutes were discussed mainly based on intra and intermolecular hydrogen bonding. The effects of solvent composition on the acidity constant were explained through linear solvation free energy relationship (LSFER) study. It was found that each ionization step of each solute can be modeled by different reduced models of Kamlet–Taft, proposing that they behave differently. Finally, the effect of solvent composition on the calculated pure absorption spectra of the different acid–base species was investigated.

Aggregation of imidazolium based ionic liquids in binary methanol–water solvents: A linear solvation free energy relationship study

Aggregation behavior of an imidazolium based ionic liquid (IL), namely 1-dodecyl-3-methylimidazolium chloride [C 12mim][Cl] and a surfactant with the same aliphatic chain, dodecyl trimethylammonium chloride (DTAC), are studied and compared in different mole fractions of methanol–water binary solvents using conductometry. From the conductivity data, micellar parameters including critical micelle concentration (CMC), degree of counter ion dissociation (α) and Gibbs free energy of micellization (ΔG°mic) for both species were calculated as a function of methanol mole fraction. It was found that similar to the surfactant DTAC, the ionic liquid [C 12mim][Cl] forms micellar aggregation in pure water and methanol as well as in their binary mixtures. The CMC values for both compounds were increased up to a methanol mole fraction of 0.5 and then decreased at higher mole fractions. This was attributed to the preferential solvation and formation of methanol–water cluster in binary mixed solvents. The changes in CMC of [C 12mim][Cl] and DTAC as a function of methanol mole fraction were also described by changing in solvatochromic properties of solvents through linear solvation free energy relationship (LSFER) study. A linear relationship between log (CMC) and two solvatochromic Kamlet-Taff parameters including polarity/polarizability (π*) and hydrogen-bond basicity (β) was observed.

Partition Coefficients of Methyl Methacrylate and Acetone between Polymer and Compressed Carbon Dioxide Phases by an in situ Infrared Spectroscopy Method

Partition coefficients of methyl methacrylate and acetone between some polymer and compressed gaseous carbon dioxide phases were determined by an in situ Fourier transform infrared (FTIR) spectroscopy method with a special designed high pressure IR cell at 318.2 K and 2.0−7.0 MPa. At the same temperature and pressure, the partition coefficient for methyl methacrylate was higher than that for acetone between the same polymer and subcritical carbon dioxide. For most solute/polymer/CO2 systems, the partition coefficient of solute between the polymer and compressed gaseous carbon dioxide decreased with the pressure increase. Only for a methyl methacrylate/poly(methyl methacrylate)/CO2 system, the partiton coefficient was not sensitive to the pressure change at pressures lower than 3.9 MPa. A linear solvation free energy relationship was used to estimate the main tendency of the pressure dependency. With the pressure dependent polarizability−dipolarity parameter of carbon dioxide, the calculated results were in accord with some experimental results.

Reversed-phase high performance liquid chromatography (RP-HPLC) characteristics of some 9,10-anthraquinone derivatives using binary acetonitrile–water mixtures as mobile phase

The retention behavior of 28 synthesized 9,10-anthraquinone derivatives in a reversed-phase (RP) high performance liquid chromatography (HPLC) system has been studied on a C18-RP column using acetonitrile–water mixtures as mobile phase. The influences of the composition of mobile phase and the solute structure on the retention times of 9,10-anthraquinone derivatives were investigated by linear solvation free energy relationship (LSFER) and quantitative structure-retention relationship (QSRR) analyses. Among different solvatochromic parameters of solvent systems, their polarity/polarizability parameter ( π*) was identified as the controlling factor affecting retention behavior of these compounds. A four-parametric QSRR model was obtained between solute structures and retention indices. Finally, a unified model containing both the molecular structure parameters and mobile phase properties was developed to describe the chromatographic behavior of the systems studied. The resulted QSRR models could explain and predict higher than 90% of variances in the retention indices. Among the solvent properties, polarity/polarizability parameter ( π*), and among the solute properties, HATS5v (leverage-weighted autocorrelation of lag 5/weighted by atomic van der Waals volumes, GETAWAY descriptors), Mor14p (3D-MoRSE-signal 14/weighted by atomic polarizabilities, 3D-MoRSE descriptors), GATS5p (Geary autocorrelation-lag 5/weighted by atomic polarizabilities, 2D autocorrelations) and R6u+(R maximal autocorrelation of lag 6/unweighted, GETAWAY descriptors) were identified as controlling factors in the RP-HPLC behavior of 9,10-anthraquinone derivatives in actonitrile–water binary solvents.

Characterization of a novel pyridinium bromide surface confined ionic liquid stationary phase for high-performance liquid chromatography under normal phase conditions via linear solvation energy relationships

Utilizing linear solvation free energy relationship methodology, a novel pyridinium bromide surface confined ionic liquid (SCIL) stationary phase was characterized under normal phase high-performance liquid chromatographic conditions. A limited set of neutral aromatic probe solutes were utilized to rapidly assess the utility of the LSER model, using mobile phases of hexane modified with 2-propanol. The excellent correlation of the global fit across the mobile phase composition range used in this study for the experimental and calculated retention values ( R 2 = 0.994) indicates that the LSER model is an appropriate model of characterizing this polar bonded phase under normal phase conditions. For a limited subset of compounds, retention on the pyridinium bromide SCIL stationary phase is more highly correlated with that obtained on a cyano column than on a diol column under NP conditions.

Lipophilicity Measurement of Drugs by Reversed Phase HPLC over Wide pH Range Using an Alkaline-Resistant Silica-Based Stationary Phase, XBridgeTM Shield RP18

We propose a reversed phase HPLC (RP-HPLC) with an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18), for the determination of the lipophilicity of drugs with diverse chemical nature ranging from acidic to basic. A set of 40 model compounds with well-defined solvatochromic parameters was selected to allow a broad distribution of structural properties. The chromatographic results showed that the lipophilicity index log k(w) obtained with XBridge Shield RP(18) was well correlated with experimental log P(oct) values (r(2)=0.96). Linear solvation free-energy relationship (LSER) analyses revealed that the retention mechanism of the stationary phase and 1-octanol/water partitioning were controlled by almost the same balance of intermolecular forces (hydrophobicity as expressed by the van der Waals volume V(w), H-bond acceptor basicity beta, and dipolarity/polarizability pi*). The results showed that XBridge Shield RP(18) phase overcomes the shortcomings of the silica-based stationary phases, the application of which to lipophilicity measurements had been limited to neutral and acidic compounds.

Spectrophotometric determination of acidity constants by two-rank annihilation factor analysis

Annihilation of the contribution of one chemical component from the original data matrix is a general method in rank annihilation factor analysis (RAFA). However, RAFA is not applicable for studying the protonation equilibria of multiprotic acids. In this work, a two-rank annihilation factor analysis (TRAFA) method was proposed for determination of the acidity constants of diprotic acids. After recording the electronic absorbance spectra of the acids at different pH, the contributions of both H 2A and A 2− were annihilated from the absorbance data, which made feasible the determination of two successive acidity constants. The method was validated by analysis of simulated data and its application to the determination of the acidity constants of calmagite, as a reference compound. A close agreement was obtained between the resulted values by TRAFA and the declared values. Indeed, the method was used for determination of the acidity constants of two new chromenone derivatives in binary solvents mixtures of methanol and water. The effects of changing solvent composition on acidity constant data were explained by linear solvation free energy relationships (LSFER) utilizing solvatochromic parameters.

Electrokinetic chromatographic characterization of novel pseudo‐phases based on N‐alkyl‐N‐methylpyrrolidinium ionic liquid type surfactants

MEKC and linear solvation free energy relationships (LSFERs) have been used to characterize the solute distribution between water and self-assemblies formed from ionic liquid type mono-chain cationic surfactants containing a cyclic pyrrolidinium head group. Several features of the solvation environment afforded by these micellar solutions were found to be quite different from that of CTAB, a structurally analogous cationic surfactant with a conventional, acyclic quaternary ammonium head group. None of the LSFER coefficients were found to vary in any systematic way with increasing alkyl chain length for these unique surfactants. Overall, however, these surfactants display different behavior than do all known cationic detergents such as CTAB. In chemical terms, pseudo-phases formed by these N-alkyl-N-methylpyrrolidinium bromides interact more strongly with polar compounds and less strongly with compounds having nonbonding or pi-electrons and are more cohesive compared to the well-studied CTAB.

Distribution of amines in water/AOT/ n-hexane reverse micelles: influence of the amine chemical structure

The distribution of different aliphatic and aromatic amines: n-butylamine (n-BA), isobutylamine (i-BA), tert-butylamine (t-BA), piperidine (PIP), N, N-dimethylaniline (DMA) and N-methylaniline (MA) in water/sodium 1,4-bis(2-ethylhexyl)sulfosuccinate(AOT)/ n-hexane reverse micelles was investigated by steady-state fluorescence measurements. The partition constants were measured by an indirect method based on the effect that amine partitioning exert on the bimolecular rate of the reaction between a microphase incorporated fluorophore (Ru(bpy) 2+ 3) and the quencher, (Fe(CN) 3− 6). For MA, that can act as a quencher of the fluorophore a direct method was used. The results show that primary amines have larger partition constants than the secondary ones. For tertiary amines the distribution constants were practically negligible. Laser flash photolysis experiments confirmed that tertiary amines, both aliphatic and aromatic, are not incorporated to the micellar pseudophase. The effect of the amine structure on the partition constant was analyzed through linear solvation free energy relationships (LSER) using solute parameters and compared with those obtained for alcohols. Hydrogen bond interactions with the AOT polar heads appear to be the main driving force for the distribution of amines between the organic and micellar pseudophases, whereas the size of the alkyl or aromatic group tends to hinder it.

Solvatochromic Linear Solvation Energy Relationships (LSER) for Solubility of Gases in Various Solvents by Target Factor Analysis

A linear solvation free energy relationship has been conducted to study the effects of solvent and solute properties on the free energy of solvation of inert gases and normal alkanes in different solvents. Factor analysis combined with target factor analysis was used to identify and quantify the factors controlling the variation of free energies of solvation, without the need to postulate any priori hypothetical method. Factor analysis of the solvation data revealed that there are two factors affecting the solubility of both types of gases in non-polar as well as polar solvents. Target testing of the solvent parameters indicated that the Hildebrand solubility parameter of solvents is the major factor controlling the solubility of gases. Moreover, it was found that the coefficient of the Hildebrand solubility parameter in the linear solvation free energy equations has linear correlation with energy of vaporization and Lennard-Jones force parameter of inert gases and number of carbon atoms and energy of vaporization of normal alkanes.

Lipophilicity Measurement by Reversed‐Phase High‐Performance Liquid Chromatography (RP‐HPLC): A Comparison of Two Stationary Phases Based on Retention Mechanisms

AbstractThe mechanisms of retention of two recent stationary phases of interest in lipophilicity measurements, namely of the silica‐based Discovery‐RP‐Amide‐C16 phase and the polymer‐based ODP‐50‐4B phase, were assessed and compared. A set of 41 model solutes and drugs with well‐defined solvatochromic parameters were selected to allow a broad distribution of property spaces. The chromatographic results showed that, under the conditions of study, the lipophilicity index log kw obtained with the former stationary phase was more closely related to experimental log Poct values than was log kw obtained with the ODP‐50‐4B phase. Linear solvation/free‐energy relationship (LSER) analyses showed that the retention mechanisms of the two stationary phases are different, retention on the Discovery‐RP‐Amide‐C16 phase and partitioning in octan‐1‐ol/H2O being controlled by the same balance of intermolecular forces (Van der Waals volume Vw, H‐bond acceptor basicity β, and dipolarity/polarizability π*).

Abraham model in gas chromatography of phenol pollutants

Chromatographic data of some selected phenol pollutants were determined and used to derive the linear solvation free energy relationships (LSERs). The Abraham model was used to correlate retention time, retention index and correction coefficient of phenols with solute parameters. Linear solvation free energy relationship can be used for prediction and verification of experimental data. Although phenols are derivatized prior their determination, the Abraham parameters of underivatized phenols can be used for modelling, but the ∑ α 2 H parameter must be neglected as the derivatized phenols loose their ability to donate proton. Gas–liquid partition coefficient on hexadecane is the most important parameter when phenols are separated on non-polar phases. The effects of other parameters are not so well defined. The replacement of log L 16 term by the logarithm of octanol–water partitioning coefficient does not improve the relationships.

Structural Properties Governing Retention Mechanisms on Immobilized Artificial Membrane (IAM) HPLC Columns

The aims of this study were to investigate whether three commercially available immobilized artificial membrane (IAM) HPLC columns yield collinear data for neutral compounds, and whether IAM scales are distinct from the log Poct (partition coefficient in the octanol/H2O system) scale. With these objectives, the retention mechanisms on the IAM HPLC columns were analysed by linear solvation free-energy relationships (LSERs). A set of 68 neutral model compounds with known solvatochromic parameters and log Poct values was investigated, allowing a regular and broad exploration of property space. The resulting solvatochromic equations clearly indicate that the three IAM stationary phases retain small neutral solutes by a balance of intermolecular forces closely resembling those underlying partitioning in octanol/H2O and retention on a reversed-phase LC-ABZ HPLC column. For all systems, the solute's size and hydrogen-bond-acceptor basicity are the two predominant factors, whereas dipolarity/polarisability and hydrogen-bond-donor acidity play only minor roles.

The relative partitioning of neutral and ionised compounds in sodium dodecyl sulfate micelles measured by micellar electrokinetic capillary chromatography

The rational use of micelles in quantitative structure–activity and quantitative structure–permeation relationships implies a good knowledge of the nature of recognition forces underlying solute–micelle association. The aims of this study were to unravel the intermolecular interaction forces responsible for the association of neutral and ionised compounds with negatively charged sodium dodecyl sulfate (SDS) micelles, using micellar electrokinetic capillary chromatography (MEKC). The MEKC capacity factors (log k MEKC) of 36 neutral model solutes were analysed by linear solvation free-energy relationships (LSERs). The results indicate that the size and H-bond acceptor strength of solutes are mainly responsible for their MEKC retention. Compared to n-octanol, the SDS micelles are more cohesive and stronger H-bond donors. Strong attractive electrostatic interactions govern solute–micelle association for positively charged compounds and micelles of the opposite charge, whereas repulsive electrostatic interactions occur between negatively charged solutes and micelles of the same charge. The capacity factors measured for the ionised forms of the acids and bases under study (log k I MEKC) indeed lie on two distinct plateau, about −1.0 for the former and about 2.0 for the latter and depend on the solute’s charge more than on its chemical structure. Thus, the derivation of a diff(log k N–I MEKC) value, defined as the difference between the log k MEKC values of the neutral and charged species, strongly correlates with the respective log k N MEKC value and does not afford additional information.

Solubility of Excited States in Micelles: The Nucleophilic Aromatic Photosubstitution of 3-Nitrophenyl Ethers in Anionic Micellar Solution

The alkaline photohydrolysis of a series of n-alkyl 3-nitrophenyl ethers was investigated in aqueous micellar solutions of the anionic detergent sodium dodecyl sulfate (SDS). Although SDS micelles strongly inhibit the OH- mediated photohydrolysis of the hydrophobic n-decyl ether, they have very little effect on the photohydrolysis of the corresponding n-butyl ether and actually increase the quantum yield for photohydrolysis of the ethyl and methyl ethers. This unexpected behavior is shown to be the consequence of a rather large decrease in the micellar solubility of the 3-nitrophenyl ether chromophore upon excitation to the triplet state, coupled with a micellar effect on the decomposition of the intermediate sigma complex. On the basis of recent linear solvation free energy relationship analyses of solute incorporation into SDS micelles, this change in micellar solubility is attributed to an enhancement of the hydrogen bond basicity in the excited triplet state of the 3-nitrophenyl ether chromophore.

A Linear Solvation Free Energy Relationship Analysis of Solubilization in Mixed Cationic−Nonionic Micelles

Incorporation coefficients for binding of 29 nonionic solutes to cationic/nonionic mixed micelles (1:1 molar ratio of hexadecyltrimethylammonium bromide (CTAB)/ polyoxyethylene[23]dodecyl ether (Brij 35)) were employed to establish a linear solvation free energy relationship (LSER) based on five solute parameters. Comparison of this LSER with those for solute incorporation into micelles of the pure, unmixed detergents indicates that hydrogen-bonding interactions are the predominant contributors to the nonidealities of solubilization in the mixed micelle.