Linear Solvation Energy Relationship Method Research Articles

Equilibrium Solubility and Dissolution Property Analysis of 2-Nitrophenylacetic Acid in 13 Pure Solvents at Elevated Temperatures

This work was devoted to the equilibrium solubility of 2-nitrophenylacetic acid in 13 neat solvents ethylene glycol (EG), methanol, ethanol, acetonitrile, n-propanol, isopropanol, water, n-butanol, N,N-dimethylformamide (DMF), isobutanol, cyclohexane, ethyl acetate, and 1,4-dioxane ranging from 283.15 to 328.15 K. All determinations were made by the shake-flask technique at a pressure of p = 101.2 kPa. The mole fraction solubility magnitudes of 2-nitrophenylacetic acid increased gradually with the rising investigated temperature and presented a decreasing trend in the 13 neat solvents: DMF > (1,4-dioxoane, methanol) > ethanol (ethyl acetate) > n-propanol > n-butanol > isopropanol > EG > acetonitrile > isobutanol > water > cyclohexane. The method of linear solvation energy relationships was employed here to inspect the solvent–solvent and solute–solvent interactions. The solvent descriptors of the Hildebrand solubility parameter and polarizability/dipolarity presented great influence upon the solubility magnitudes of the solute 2-nitrophenylacetic acid. The obtained solubility values in mole fraction were correlated mathematically via four models/equations, namely, λh, non-random two-liquid, Apelblat, and Wilson. The maximum value of relative average deviation (RAD) was 3.68 × 10–2, and the maximum value of root-mean-square deviations was 116.78 × 10–4. The RAD values by using the Apelblat equation were smaller than that by using the other equations/models for a fixed solvent. Additionally, the dissolution properties, activity coefficient, and reduced excess enthalpy under the conditions of infinite dilution were obtained through the Wilson model.

Biapenem in binary aqueous mixtures of N,N-dimethylformamide, N-methyl-2-pyrrolidone, isopropanol and ethanol: Solute-solvent and solvent-solvent interactions, solubility determination and preferential solvation

This work mainly aimed to study the mole fraction solubility of biapenem in four binary solutions of N,N-dimethylformamide (DMF, 1) + water (2), isopropanol (1) + water (2), N-methyl-2-pyrrolidone (NMP, 1) + water (2) and ethanol (1) + water (2). Experiments were performed through a common static equilibrium method at temperatures from 283.15 to 323.15 K. The maximum solubility magnitudes were observed in pure solvent of DMF/NMP/isopropanol/ethanol for each solution. The achieved biapenem solubility was mathematically described by using two famous co-solvency models, Jouyban-Acree and van’t Hoff-Jouyban-Acree. The calculated relative average deviations were not greater than 4.20%; and root-mean-square deviations, not greater than 7.45 × 10−6. The linear solvation energy relationships method put forward by Kamlet and Taft was employed to examine the influence of solvent descriptors upon biapenem solubility behaviour. The principal contributors to solvent effect was hydrogen bond acidity for DMF/NMP mixtures; and hydrogen bond acidity and non-specific dipolarity-polarizability for isopropanol/ethanol mixtures. Quantitative local mole fractions of DMF (NMP, isopropanol or ethanol) and water nearby the biapenem were analyzed through Inverse Kirkwood–Buff integrals method. For the isopropanol/ethanol + water mixtures within water-rich compositions, biapenem was preferentially solvated by isopropanol/ethanol; while within intermediate and co-solvent-rich compositions, by water. However, for the DMF/NMP mixture within entire composition ranges, the absolute δx1,3 values were all smaller than 1.0 × 10−2, consequently biapenem was not preferentially solvated by DMF/NMP or water.

4-Chloro-6-pyrimidinylferrocene modified silica gel: A novel multiple-function stationary phase for mixed-mode chromatography

A novel multi-function and mixed-mode stationary phase based on 4-chloro-6-pyrimidinylferrocene modified silica (NFcS) was synthesized and characterized by infrared spectroscopy, elemental analysis and thermogravimetric analysis. Linear solvation energy relationship method was successfully employed to evaluate the new phase with a set of 27 solutes including aromatic and aliphatic compounds. Multiple mechanisms including hydrophobic, π–π, hydrogen-bonding, charge-transfer, acid–base equilibrium and anion-exchange interactions are involved. Based on these interactions, successful separation could be achieved among polycyclic aromatic hydrocarbons, mono-substituted benzenes, aromatic amines, phenols, quinolines, pyridines and nucleosides in reversed-phase (RP) or normal-phase (NP) chromatography. Inorganic anions were also shown to be individually separated in anion-exchange chromatography by using the same column. Moreover, the results here also demonstrated that NFcS based stationary phase could effectively reduce the adverse effect of residual silanol in the separation process. Such stationary phase with characteristics of multi-interaction mechanism and mixed-mode separation is potential for the analysis of complex samples. The NFcS column was successfully employed for the analysis of plant growth regulators in Fruit.

Spectrofluorimetric determination of the antineoplastic agent lomustine based on the sensitizing effect of β-cyclodextrin.

The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding on the photophysical properties of the antineoplastic drug lomustine were analysed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The LSER method enabled the overall solvent effects to be quantitatively estimated and separated into specific and non-specific contributions. The molecular encapsulation of lomustine by β-cyclodextrin (β-CD) has been studied using fluorescence spectroscopy. The results are discussed in terms of the binding parameter and the effect of the solvent used. It was concluded that β-CD forms a 1:1 inclusional complex with lomustine in acetonitrile solution and its association constant was calculated to be 500 M(-1). In addition, and for the first time, a simple, rapid and high sensitive fluorimetric method for the determination of lomustine was developed based upon the enhancement effect produced through complex formation with β-CD. The new approach for the quantification of lomustine in the presence of β-CD was described in aqueous and organic solutions. Better limits of detection (0.31 µg ml(-1)) and quantification (1.05 µg ml(-1)) were obtained in aqueous solution with respect to those obtained in organic solvent.

Development of a V-shape bis(tetraoxacalix[2]arene[2]triazine) stationary phase for High performance liquid chromatography

A new stationary phase for high-performance liquid chromatography was prepared by covalently bonding a V-shape cage heteroatom-bridged calixarene onto silica gel using 3-aminopropyltriethoxysilane as coupling reagent. The structure of the new material was characterized by infrared spectroscopy, elemental analysis and thermogravimetric analysis. Linear solvation energy relationship method was successfully employed to evaluate the new phase with a set of 34 solutes. The retention characteristic of the new phase shows significant similarities with ODS, as well as distinctive features. Multiple mechanisms including hydrophobic, hydrogen bonding, π–π and n–π interaction are involved. The chromatographic behavior of the phase was illustrated by using alkylbenzenes, aromatics positional isomers and flavonoids as probes. Moreover, inorganic anions were individually separated in anion-exchange mode by using the same column. Thus, multi-interaction mechanisms and mixed-mode separation of the new phase can very likely guarantee its excellent chromatographic performance for the analysis of complex samples. The column has been successfully employed for the analysis of clenbuterol in animal urine, and it is demonstrated to be suitable and a competitive alternative analytical method for the determination of clenbuterol.

Application of the LSER method for investigation of intermolecular interactions of porous polymer surface with organic molecules

The contributions of intermolecular interactions into the molar change of free energy -ΔF of sorption on the surface of porous polymers of various natures were studied by the linear solvation-energy relationship (LSER) method. It was shown that a high correlation coefficient does not ensure reliability of the results obtained. The applicability of the LSER equations for investigation of the polarity of polymer sorbents was analyzed.

Solvation-based modeling vapor pressures of (solvent + salt) systems with the application of Cox equation

A solvation model framework, based on the LSER (linear solvation energy relationship) principles, is proposed for correlating vapor pressures of (solvent+salt) systems. The LSER method basely uses a linear combination of several solvatochromic indices of solvents to describe their physical properties. The assumption inherent in the solvation-based vapor pressure approach is attributed to an additional effect of several physical quantities, i.e. the vapor pressure of a pure solvent estimated by the Cox equation, the salt concentration, the solvatochromic indicators of the solvent and the physical properties of the ionic salt species. It has been performed independently two structural forms of the generalized solvation model, i.e. the integrated property-basis model using nine physical descriptors USMIP (the unified solvation model with the integrated properties) and the reduced property-basis one. Also, a simplified concentration-dependent vapor pressure model is presented. The observed vapor pressure data of fifteen (solvent+salt) and two (solvent (1)+solvent (2)+salt) systems have been processed to establish the basis for the model reliability analysis using a log-ratio objective function. The proposed vapor pressure approaches reproduce the observed performance relatively accurately, yielding the overall design factors of 1.065 and 1.072 for the solvation-based models with the integrated and reduced properties and 1.017 for the concentration-based model, respectively. Both the integrated property-basis and reduced property-basis solvation models were able to simulate satisfactorily the vapor pressure data of a binary solvent mixture involving a salt, yielding an overall mean error of 5.7%.

A new 14-membered tetraazamacrocycle-bonded silica stationary phase for reversed-phase high-performance liquid chromatography

A new high-performance liquid chromatography stationary phase has been prepared by covalently bonding 14-membered tetraazamacrocycle to silica gel using γ-chloropropyltrimethoxylsilane as coupling agent. The structure of the new material was characterized by infrared spectroscopy and elemental analysis. With 32 solutes including aromatic and aliphatic compounds, the linear solvation energy relationship method was successfully used to chromatographically evaluate the new phase in reversed phase mode. The retention property of the new phase shows evident similarity with that of ODS stationary phase, as well as distinctive, unique retention characteristics. The separations of n-alkylbenzene, carbamate and organophosphorus pesticides with diversified functional groups as well as phenolic compounds demonstrate that in addition to hydrophobic interaction, dipole–dipole interaction and hydrogen bonding interaction plus acid–base equilibrium could also be simultaneously offered by this new stationary phase, as a result excellent chromatographic performances are guaranteed.

Electronic and Cytotoxic Properties of 2-Amino-naphtho[2,3-b]furan-4,9-diones

The electronic properties of a new set of cytotoxic 2-amino-naphtho[2,3-b]furan-4,9-dione derivatives (1-8) are evaluated. The electron delocalization of these compounds is described by means of their redox potentials and solvatochromic properties. The large solvatochromism of their intramolecular electron transfer band is analyzed using the linear solvation energy relationship method. In addition, this method determined the importance of the molecular environment, quantifying the interactions that compounds (1-8) establish with their surrounding media, with the capacity of acting as hydrogen-bond acceptors (HBA) and hydrogen-bond donors (HBD) and the dipolarity/polarizability being the most significant ones. As a result, a relationship between the electronic and the cytotoxic properties of these compounds is proposed.

Characterization of the surface properties of nitrogen-enriched carbons by inverse gas chromatography methods

The characterization of the surface properties of carbonaceous materials by inverse gas chromatography (IGC) techniques is described. The cokes investigated were produced by the co-pyrolysis of a coal-tar pitch (CTP) with different amounts of polyacrylonitrile (PAN) as a possible method to synthesize carbonaceous materials enriched in nitrogen. IGC at infinite dilution and LSER (linear solvation energy relationship) techniques were used to determine the physical and chemical surface properties of the cokes. In general, the surface free energy of adsorption is due to both dispersive and specific interactions. The dispersive component of the surface free energy was determined using n-alkane probes. For the specific component, which is primarily due to acid–base interactions, different polar probes were used. The LSER method was applied to improve our understanding of the adsorption process in terms of molecular interactions. We show that, to characterize dispersive interactions using n-alkanes, the LSER and IGC methods are equivalent. On the other hand, with both methods we find that all the samples present acidic and basic characteristics. However, the sensitivity of the LSER method does not allow us to discriminate between the three samples in terms of specific interactions.

The characterization of nitrogen-enriched activated carbons by IR, XPS and LSER methods

The aim of this work is to study the efficiency of the nitrogen enrichment by urea of lignites and the induced changes of the adsorptive properties towards volatile organic compounds (VOCs) of the activated carbons derived from these modified precursors. The study is made using infrared and X-ray photoelectrons spectroscopies and the LSER (linear solvation energy relationship) modeling. Four activated lignites derived from the same raw material, original or enriched with nitrogen, are characterized in this way. The effect of the chemical treatment by urea and of the burn-off amount are investigated in term of evolution of the chemistry of the studied materials. The influence of these parameters on the selective behavior of the activated lignites towards two pairs of VOCs is also discussed in terms of molecular interactions using the LSER approach. The results show that the chemical treatment of the raw material is successful, leading to significant enrichment with nitrogen under pyridinic form at the surface of the activated carbons. Moreover, they reveal some selective properties well explained by the LSER analysis and spectroscopic measurements. The selective character of the studied materials is modulated by the duration of the activation step.

Linear solvation energy relationship parameters of some pure liquid organic compounds from solvatochromic investigations

The partitioning of an organic solute between an aqueous and an organic phase is governed by the properties of the phase forming aqueous/organic system as well as by the properties of the solute. As organic solutes are often highly diluted in such systems the infinite dilution partition coefficient is of particular interest. Partition coefficients at infinite dilution are often described using quantitative structure–activity relationships (QSAR), e.g. the linear solvation energy relationship (LSER) method of Kamlet and coworkers. The LSER method requires five parameters for the characterization of a solute j: a volume parameter v j , a polarity parameter π j , a parameter for the polarizability δ j , and two parameters describing the capability of the solute to undergo hydrogen bonding as a proton acceptor β j (basicity parameter) and as a proton donor α j (acidity parameter). This contribution reports new experimental data for the polarity parameter π j and the basicity parameter β j of about 90 liquid organic compounds. Such parameters can be used to predict thermodynamic properties such as the octanol–water partition coefficient or to develop methods for estimating such parameters.

Prediction of partition coefficient and toxicity for benzaldehyde compounds by their capacity factors and various molecular descriptors

The log K ow and log S w values of 14 substituted benzaldehyde compounds were determined by the shake-flask method. Acute toxicities of 14 substituted benzaldehyde compounds to Daphnia magna were recorded. Their capacity factors ( k′) were determined by reversed phased high-performance liquid chromatography (RP-HPLC) on C 18 column and methanol–water eluent. Molecular connectivity indices, the linear solvation energy relationships (LSER) parameters, and quantum chemical parameters were calculated for the tested chemicals and used to develop quantitative structure-retention relationship (QSRR) and quantitative structure-property/activity relationship (QSPR/QSAR). Results demonstrated that the molecular connectivity indices, LSER parameters, and quantum chemical parameters could be used to predict the k ′ for compounds studied, LSER method was more accurate. The results also show that chromatographic retention data, log k ′ , can be used to predict log K ow and log S w for tested compounds. The log k w ′ can be directly utilized as hydrophobic descriptors to predict the toxicity to D. Magna for benzaldehyde compounds.

Optimization of HPLC conditions for the separation of complex crude mixtures produced in the synthesis of therapeutic peptide hormones

The solid phase peptide synthesis (SPPS) method is usually used for the synthesis of new peptides of pharmaceutical interest. However, the final drug product commonly results in complex mixtures, where the target peptide must be separated from the undesired impurities. The linear solvation energy relationships method (LSER) is used here in order to rapidly optimize the separation of the analytes present in the complex crude mixtures which are formed during the synthesis of peptide hormones with therapeutic interest, such as; carbetocin, eledoisin, leuprolide, goserelin and triptorelin. Resolution data for adjacent solute pairs may easily be predicted from these relationships. Separation under optimum conditions provides useful information about the purity of the target peptide and allows characterization of the mixture components by LC-ES-MS. In addition conditions for the preparative purification of the candidates could be extrapolated from these analytical data.

Possibilities and pitfalls in defining selectivity in HPLC

Definition of chromatographic selectivity and the different selectivity terms, for example column selectivity, mobile phase selectivity, and temperature selectivity are discussed briefly. For classification of solvent selectivity the Rohrschneider-McReynolds system, the solvent selectivity triangle (SST) concept, the solubility parameter approach, and the linear solvation energy relationships (LSER) are compared. Shortcomings of the SST concept and application of the LSER method for the prediction of selectivity are discussed.

Determination and estimation of water solubilities and octanol/water partition coefficients for derivates of benzanilides

A shake-flask method was used to determine the water solubilities (Sw) and the octanol/water partition coefficients(Kow) of 14 derivates of benzanilides. The results showed that the octanol/water partition coefficients were correlated (r= −0.93) with Sw. The linear solvation energy relationship(LSER) and molecular connectivity methods have been used to establish correlation equation successfully. The LSER method was used to predict these partitioning properties more accurately. The estimated values were well fitted with observed ones.

Comparison of predictive methods for Henrys Law Coefficients of organic chemicals

Predictive methods proposed in the literature for estimating Henrys Law Coefficient (HLC) of organic chemicals are reviewed and compared. Five different models developed from the following methods are discussed: solubility–vapor pressure method; group/bond contribution method; linear solvation energy relationship method; and, molecular connectivity method. The models reviewed cover over 450 chemicals belonging to several different chemical families. Experimental variability and inter-laboratory variances of measured HLC data are summarized to establish acceptance limits for the predictive models. The five predictive models are compared and evaluated on the basis of quality of predictions and predictive errors for a common set of 150 chemicals.

Partition Coefficients for Environmentally Important, Multifunctional Organic Compounds in Hexane + Water

Experimental results for the partition coefficient of 41 substances (several phenol, indole, biphenyl, and naphthalene derivates, polycyclic aromatic compounds, and polyfunctional haloaromatics) in hexane + water at 298.15 K are reported. Partition coefficients were measured by reversed phase high-performance liquid chromatography and the shake-flask method. The experimental results are compared successfully to predictions by the linear solvation energy relationship method.

Evaluation of the effect of organic modifier on p K values of diuretics in mobile phases used in LC

The dissociation p K values of a series of diuretics in 10, 30, 40, 50 and 70% (w/w) acetonitrile–water mixed solvents at 25°C were determined according to the criteria endorsed by IUPAC. The series of diuretics chosen includes compounds with differences in molecular structures and physico-chemical properties. Acidic compounds (loop diuretics, such as furosemide, bumetanide and ethacrynic acid), weakly acidic (thiazides, such as chlorthiazide and trichlormethiazide), neutral (aldosterone antagonists, such as canrenone) and basic compounds (potassium-sparing diuretics, such as amiloride and triamterene) were all considered. The variation of the p K values obtained over the whole composition range studied can be explained by taking into account the preferential solvation of ionizable compounds in acetonitrile–water mixtures. Moreover, in order to obtain p K values in any of the unlimited number of possible binary solvent acetonitrile–water mixtures, relationships between p K values and different bulk properties were examined, and the linear solvation energy relationships method (LSER) was applied to study the correlations of p K values with the solvatochromic parameters π*, α and β of acetonitrile–water mixtures. The equations obtained allowed calculation of the p K values of diuretics in any acetonitrile–water mixtures up to 70% (w/w) and thus permitted the acid–base behaviour of these important substances in the widely used acetonitrile–water media to be known.

Protonation equilibria of quinolone antibacterials in acetonitrile-water mobile phases used in LC

Ionization constants of nine quinolone antibacterials in acetonitrile-water mixtures containing 0, 5.5, 10, 16.3, 25, 30, 40, 50 and 70% (w/w) acetonitrile were obtained and assignment of these p K values to the several potentially ionizable functional groups was made. The variation of the p K values obtained over the whole composition range studied can be explained by consideration of the preferential solvation of electrolytes in acetonitrile-water mixtures. In order to obtain p K values in any of the unlimited number of possible binary solvent acetonitrile-water mixtures, relationships between p K values and different bulk properties (such as dielectric constant) were examined. The linear solvation energy relationships method, LSER, was applied to study the correlation of p K values with the solvatochromic parameters of acetonitrile-water mixtures. The equations obtained allow calculation of the p K values of the quinolone antimicrobials in any acetonitrile-water mixtures up to 70% (w/w) and thus permit the knowledge of the acid-base behaviour of these important antimicrobials in the widely used acetonitrile-water media.