Linear Solvation Energy Relationships Research Articles

Bifonazole dissolved in numerous aqueous alcohol mixtures: Solvent effect, enthalpy–entropy compensation, extended Hildebrand solubility parameter approach and preferential solvation

The accessible mole fraction solubility of bifonazole in n-propanol/methanol/isopropanol/propylene glycol (PG) (1) + water (2) mixtures at 298.15 K was investigated in the light of molecular interactions between solvent and solute via extended Hildebrand solubility approach (EHSA). For aqueous methanol/PG systems within entire mole fraction range of methanol/PG, aqueous n-propanol system within mole fraction range of n-propanol from 0 to 0.8 and aqueous isopropanol system within mole fraction range of isopropanol from 0 to 0.7, the solute–solvent interaction energies are larger than the ones of geometric mean for regular solution, asserting that there exists some association between bifonazole and mixtures; whereas within the other composition regions for the aqueous isopropanol/n-propanol systems, the solutions consisting of bifonazole present regular behavior at several solubility points. The inverse Kirkwood–Buff integrals tool was utilized to investigate the local mole fractions of bifonazole in the solutions of alcohol (1) + water (2) in the light of the solubility. For the aqueous solutions of isopropanol/n-propanol with middle and isopropanol/n-propanol-rich mole fractions, preferential solvation of bifonazole was observed for isopropanol/n-propanol. Bifonazole was not solvated preferentially by PG/methanol in the above composition regions for aqueous PG/methanol mixtures. The solvent effect was quantitatively described by modeling the solubility change by means of the linear solvation energy relationships. The solubility parameter and dipolarity-polarizability of system descriptors presented the dominant contributions to variation of solubility values. The transfer and dissolution properties, e.g. entropy, Gibbs free energy change and enthalpy were calculated. In addition, the analysis of enthalpy–entropy compensation was performed, specifying that the variation of bifonazole solubility in the four aqueous alcohol solutions was controlled by two different mechanisms, enthalpy-driven and entropy-driven.

Solubility and thermodynamic aspects of etonogestrel in several aqueous co-solvent solutions

The current work was devoted to the investigation on equilibrium solubility, Hansen solubility parameter, solvation performance and dissolution thermodynamics of etonogestrel in binary aqueous blends of the cosolvents {n-propanol, N,N-dimethylformamide (DMF), ethanol or isopropanol} by experimentation and several mathematical relationships. The solubility determination was conducted under atmospheric pressure (101.2 kPa) from 278.15 to 323.15 K through the common shake-flask method. The maxima of etonogestrel solubility expressed in mole fraction scale at 323.2 K were observed as 8.713 × 10−3 for ethanol, 16.81 × 10−3 for n-propanol, 19.52 × 10−3 for isopropanol and 121.4 × 10−3 for DMF; while the minimum was 0.01477 × 10−3 for pure water at 278.15 K. The solubility performance of etonogestrel was deeply considered by means of Hansen solubility parameter concept. The obtained equilibrium solubility was computationally expressed by modified Jouyban–Acree–van’t Hoff model, mixture response surface (MRS) model, modified Wilson model and Jouyban–Acree model with the relative average deviations of no higher than 7.12%. The relative prominence of solvent–solvent and solute–solvent molecule interactions on etonogestrel solubility variation specified the dipolarity-polarizability and solubility parameter of solution descriptors that was studied in terms of the linear solvation energy relationships. The extended Hildebrand solubility approach was used to inspect the solubility data at 298.15 K acquiring the correlation coefficient of >0.9999. The quantitative investigation on preferential solvation of etonogestrel by solvent species in different solutions was made by the inverse Kirkwood–Buff integrals technique in terms of numerous solution properties. Positive preferential solvation parameters for cosolvents of isopropanol, DMF, ethanol and n-propanol in aqueous solutions with cosolvent-rich and intermediate scopes suggested the preferential solvation of etonogestrel by the cosolvents (isopropanol/DMF/ethanol/n-propanol). It was assumed that etonogestrel acted as a Lewis acid in these composition ranges with the isopropanol/DMF/ethanol/n-propanol molecules. Thermodynamic analysis of dissolution properties and enthalpy–entropy compensation demonstrated an entropy-driven mechanism and endothermic process for etonogestrel dissolved in different blended solvents.

Investigation on the Hansen solubility parameter, solvent effect and thermodynamic analysis of indapamide dissolution and molecular dynamics simulation

In this work, the dissolution behavior of indapamide (IDP) in different solvents was researched. Solubility of IDP in methanol, ethanol, acetonitrile, 1-propanol, ethyl acetate, 2-propanol, 2-butanone, acetone, toluene and cyclohexane at series temperatures (278.15 K-318.15 K) was determined. The outcomes indicated that the solubility of IDP increased with increasing temperature. At a certain temperature, the mole solubility sequence of IDP was acetone > 2-butanone > methanol > ethanol > 1-propanol > acetonitrile > 2-propanol > ethyl acetate > toluene > cyclohexane. The Hansen solubility parameter (HSP) was used to evaluate ability of solvent to dissolve and explain the solubility behavior of IDP. Solvent effect was discussed by Kamlet and Taft linear solvation energy relationship (KAT-LSER) model, and the hydrogen bonds interactions (HBA) and nonspecific dipolarity/polarizability interactions had more advantageous impact on solubility of IDP. Moreover, molecular dynamics (MD) simulation was employed to construct the dissolving model and provide molecular level understanding the solute–solvent interaction in dissolution process of IDP. In addition, the experimental solubility data of IDP was correlated by Apelblat model, λh model, NRTL model and Wilson model. The applicability of these models were evaluated by Akaike Information Criterion analysis. The relative average deviation (RAD) and root-mean-square deviation (RMSD) values were no greater than 2.94% and 5.03 × 10−4, respectively. These four thermodynamic models were able to correlate the solubility data well and the Apelblat model was the best correlation model of these four models. Finally, the dissolution thermodynamic properties were obtained by van't Hoff analysis. The all positive values of thermodynamic properties indicated that the dissolution of IDP was an endothermic and entropy driven process.

Solubility, Hansen solubility parameter, solvent effect and preferential solvation of benorilate in aqueous mixtures of isopropanol, N,N-dimethylformamide, ethanol and N-methyl-2-pyrrolidinone

This contribution was devoted to the equilibrium solubility profile, solute–solvent and solvent–solvent interactions and solvation behavior of benorilate in aqueous binary mixtures of the cosolvent (i.e. ethanol, N-methyl-2-pyrrolidinone (NMP), isopropanol and N,N-dimethylformamide (DMF)) together with several mathematical associations. All experiments were conducted by a shake-flask method under ambient pressure of 101.2 kPa from 278.15 to 318.15 K. The maximum scale of equilibrium benorilate solubility in neat cosolvent at T = 318.15 K; while the minimum one was observed in pure water at 278.15 K. The equilibrium benorilate solubility was analyzed by using the Hildebrand and Hansen solubility parameters. Various solubility models including Jouyban–Acree–van’t Hoff, modified Wilson, Jouyban–Acree and mixture response surface (MRS) were employed to fit the mole fraction solubility data, attaining the average relative deviations (RAD) of no more than 9.62%. The relative significance of molecular interactions of solvent–solvent and solute–solvent species upon the equilibrium solubility of benorilate at 298.15 K analyzed through the linear solvation energy relationships specified that the dominant contributions to solubility variation were observed as solubility parameter and dipolarity-polarizability of systems. The solubility data was investigated by means of the extended Hildebrand solubility approach gaining relative average deviation values of no higher than 3.71%. In terms of solution properties, a quantitative analysis on preferential solvation of benorilate was conducted by inverse Kirkwood–Buff integrals method. The preferential solvation parameters for neat cosolvent were recorded as positive in cosolvent-rich and intermediate regions in solutions, suggesting that benorilate was preferentially solvated by the cosolvents. In the above composition regions, it is conjectured that benorilate is performing as a Lewis acid with the cosolvent molecules.

Perspective on the Future Approaches to Predict Retention in Liquid Chromatography.

The demand for rapid column screening, computer-assisted method development and method transfer, and unambiguous compound identification by LC/MS analyses has pushed analysts to adopt experimental protocols and software for the accurate prediction of the retention time in liquid chromatography (LC). This Perspective discusses the classical approaches used to predict retention times in LC over the last three decades and proposes future requirements to increase their accuracy. First, inverse methods for retention prediction are essentially applied during screening and gradient method optimization: a minimum number of experiments or design of experiments (DoE) is run to train and calibrate a model (either purely statistical or based on the principles and fundamentals of liquid chromatography) by a mere fitting process. They do not require the accurate knowledge of the true column hold-up volume V0, system dwell volume Vdwell (in gradient elution), and the retention behavior (k versus the content of strong solvent φ, temperature T, pH, and ionic strength I) of the analytes. Their relative accuracy is often excellent below a few percent. Statistical methods are expected to be the most attractive to handle very complex retention behavior such as in mixed-mode chromatography (MMC). Fundamentally correct retention models accounting for the simultaneous impact of φ, I, pH, and T in MMC are needed for method development based on chromatography principles. Second, direct methods for retention prediction are ideally suited for accurate method transfer from one column/system configuration to another: these quality by design (QbD) methods are based on the fundamentals and principles of solid-liquid adsorption and gradient chromatography. No model calibration is necessary; however, they require universal conventions for the accurate determination of true retention factors (for 1 < k < 30) as a function of the experimental variables (φ, T, pH, and I) and of the true column/system parameters (V0, Vdwell, dispersion volume, σ, and relaxation volume, τ, of the programmed gradient profile at the column inlet and gradient distortion at the column outlet). Finally, when the molecular structure of the analytes is either known or assumed, retention prediction has essentially been made on the basis of statistical approaches such as the linear solvation energy relationships (LSERs) and the quantitative structure retention relationships (QSRRs): their ability to accurately predict the retention remains limited within 10-30%. They have been combined with molecular similarity approaches (where the retention model is calibrated with compounds having structures similar to that of the targeted analytes) and artificial intelligence algorithms to further improve their accuracy below 10%. In this Perspective, it is proposed to adopt a more rigorous and fundamental approach by considering the very details of the solid-liquid adsorption process: Monte Carlo (MC) or molecular dynamics (MD) simulations are promising tools to explain and interpret retention data that are too complex to be described by either empirical or statistical retention models.

Measurement and correlation of solubility, Hansen solubility parameters and thermodynamic behavior of Clozapine in eleven mono-solvents

Mole-fraction solubility of Clozapine (CLZ) in eleven mono-solvents (methanol, ethanol, n-propanol, isopropanol, acetone, 1,2-dichloroethane, benzene, toluene, N,N-Dimethylformamide (DMF), n-Methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO)) at varied temperatures (from 283.15 K to 333.15 K at 5 K intervals) was experimentally determined by a classic gravimetric method under an atmosphere pressure of 0.101 MPa. The mole solubility of CLZ in the selected mono-solvents exhibited a positive relation with temperature. In addition, the solubility sequence of CLZ at 298.15 K is: DMF > DMSO > NMP > 1,2-dichloroethane > acetone > methanol > benzene > n-propanol > ethanol > toluene > isopropanol. The Hansen solubility parameters (HSPs) and solvents polarity were applied to explore this solubility behavior. The KAT-LSER model was calculated to investigate the solvent effect based on linear solvation energy relationships concept. Four thermodynamic models including the modified Apelblat model, Wilson model, NRTL model and UNIQUAC model were employed to correlate the experimental solubility, which indicated that both modified Apelblat model and NRTL model were more suitable in correlation with the measured solubility data. Furthermore, the solution thermodynamic properties (ΔdisGo, ΔdisHoand ΔdisSo) of CLZ in the selected eleven solvents were calculated by van't Hoff equation, and the positive values of ΔdisHo and ΔdisSo indicated that the dissolution process of CLZ in the measured mono-solvents was endothermic and entropy-driven.

Linear solvation energy relationships in the determination of phospholipids by supercritical fluid chromatography

The separation of phospholipids was studied using supercritical fluid chromatography. The 2-ethylpyridine (2-EP), hybrid fluoro-phenyl (FP), C18, 2-picolylamine (2-PIC), 1-aminoanthracene (1-AA), DIOL and ethylene bridged hybrid (BEH) were used as stationary phases. Methanol with 0.1% formic acid was used as a co-solvent. For the first time, the linear solvation energy relationships (LSER) were used to evaluate the retention mechanism of phospholipid by SFC. Based on Abrahamʼs equation, the stationary phases were classified according to their interaction properties. The retention mechanism of phospholipid at SFC is based on different interactions depend on columns type. Moreover, structural descriptors of the target compounds were used to describe their chromatographic retention behavior under the optimized SFC conditions.

Synthesis and (fluoro)solvatochromism of two 3-styryl-2-pyrazoline derivatives bearing benzoic acid moiety: A spectral, crystallographic and computational study

In this work we report the synthesis of two fluorescent 2-pyrazoline derivatives exhibiting remarkable (fluoro)solvatochromic behavior. The pyrazolines were synthesized in one step from the corresponding monocarbonyl curcuminoids and 4-hydrazinobenzoic acid in high yield and purity and were fully characterized by means of NMR and FT-IR spectroscopy and HRMS spectrometry. The structure of the novel derivative 2 was also characterized by means of X-ray crystallography. Both compounds were studied computationally in the gas phase. Additionally, the effects of solvent polarity on the absorption and fluorescence spectra of these derivatives were investigated in a solvent group consisting of various neat molecular solvents exhibiting hydrogen bond donating (HBD), hydrogen bond accepting (HBA), and/or dipolar behavior. The solvent effects observed were quantified and rationalized by employing suitable multiparametric Linear Solvation Energy Relationships (LSERs) involving dipolarity, HBD-acidity and HBA-basicity terms. The contribution of each of these parameters provided insights on the predominant solute-solvent interactions occurring in solution. Importantly, some differences in the (fluoro)solvatochromic aptitude/behavior were revealed among the derivatives and they were rationalized on the basis of their structural diversity.

Assessing the potential of para-donor and para-acceptor substituted 5-benzylidenebarbituric acid derivatives as push–pull electronic systems: Experimental and quantum chemical study

Electronic interactions in donor-π-linker-acceptor systems with barbituric acid as an electron acceptor and possible electron donor were investigated to screen promising candidates with a push–pull character based on experimental and quantum chemical studies. The tautomeric properties of 5-benzylidenebarbituric acid derivatives were studied with NMR spectra, spectrophotometric determination of the pKa values, and quantum chemical calculations. Linear solvation energy relationships (LSER) and linear free energy relationships (LFER) were applied to the spectral data - UV frequencies and 13C NMR chemical shifts. The experimental studies of the nature of the ground and excited state of investigated compounds were successfully interpreted using a computational chemistry approach including ab initio MP2 geometry optimization and time-dependent DFT calculations of excited states. Quantification of the push–pull character of barbituric acid derivatives was performed by the 13CNMR chemical shift differences, Mayer π bond order analysis, hole-electron distribution analysis, and calculations of intramolecular charge transfer (ICT) indices. The results obtained show, that when coupled with a strong electron-donor, barbituric acid can act as the electron-acceptor in push–pull systems, and when coupled with a strong electron-acceptor, barbituric acid can act as the weak electron-donor.

Evodiamine in several binary aqueous co-solvents: Solubility measurement and modeling, Hansen solubility parameter, preferential solvation and apparent dissolution and transfer properties

Equilibrium solubilities of evodiamine were determined in four aqueous mixtures of methanol, isopropanol, acetone and ethanol over their full mass fraction range via the shake-flask approach covering from 283.15 to 323.15 K. The solubility profiles showed maxima in the neat cosolvents. The temperature and the mixture composition dependence of evodiamine solubility in mole fraction scale was well described by using five well-known models involving NRTL, Jouyban-Acree, van't Hoff-Jouyban-Acree, UNIQUAC and Wilson. The means of the relative deviations were recorded as 5.40%, 0.98% and 0.48% for the Wilson, UNIQUAC and NRTL models, respectively. The Jouyban-Acree and van't Hoff-Jouyban-Acree models resulted in the calculated relative average and root-mean-square deviations lower than 6.83% and 9.19 × 10−6, respectively. Hansen solubility parameter was utilized to disclose the solubility behavior of evodiamine. We also employed the linear solvation energy relationships to detect which intermolecular interactions were mainly responsible for the observed solvent effect upon solubility behavior. This analysis revealed the highlighted role of cavity term and dipolarity-polarizability of solvent in solubility variation of evodiamine. Solubility data was further examined by using the inverse Kirkwood-Buff integrals method in order to analysis the preferential solvation of evodiamine in the mixtures. Results showed the selective solvation of evodiamine by organic solvent in intermediate and organic solvent-rich compositions, and by water in water-rich compositions. The thermodynamic quantities including the apparent molar dissolution enthalpy, molar dissolution entropy and molar Gibbs energy, and the relative contribution of dissolution enthalpy and dissolution entropy to the dissolution Gibbs energy change for dissolution of evodiamine were calculated in each binary mixture. Moreover, the transfer properties were derived and discussed.

Amphipathic carbon quantum dots-functionalized silica stationary phase for reversed phase/hydrophilic interaction chromatography

Carbon quantum dots (CQDs) are considered as good chromatographic separation materials. However, due to the hydrophily of the synthesized CQDs, their applications in HPLC are limited to HILIC for separating strong polar compounds only. In this work, a novel amphipathic CQDs with both hydrophobicity and hydrophily is developed as mixed-mode stationary phase for RPLC/HILIC. To give CQDs certain hydrophobicity, 1,8-diaminooctane is chosen as one of the carbon sources for introducing alkyl chain into CQDs. The amphipathic CQDs modified silica (CQDs/SiO2) stationary phase has typical characteristic of RPLC/HILIC. Both hydrophobic and hydrophilic compounds including alkylbenzenes, polycyclic aromatic hydrocarbons, nucleosides and bases, amino acids, β-adrenoceptor blockers and agonists, sulfonamides, antibiotics and alkaloids obtain satisfactory separation on this CQDs/SiO2 column. 14 nucleosides and bases commonly existing in living organisms achieve good separation on this amphipathic CQDs/SiO2 column within 25 min and the resolutions reach 1.33–13.83 with an average column efficiency of 18,800. The retention mechanism of this novel CQDs/SiO2 column is investigated by linear solvation energy relationship model. It is found that hydrophobic interaction, π-π stacking, hydrogen-bonding and electrostatic interactions are main retention interactions under RPLC mode. This work provides a new approach for synthesis of amphipathic CQDs. Also, it indicates that amphipathic CQDs with versatile functional properties have great prospect in separation science.

Luminescence feature of new 3,6-di(thiazolidin-5-one-2-yl)-carbazole derivative: synthesis, photophysical properties, density functional theory studies, and crystal shape effect.

A new carbazole chromophore conjugated with substituted thiazolidine-4-one (CzPT) was synthesized by applying the Knoevenagel reaction between 3,6-diformyl-N-hexylcarbazole and ethyl 2-aceto-2-(5-oxo-3-phenylthiazolidin-2-ylidene)acetate. The chemical structure of the new derivative (CzPT) was elucidated by spectral studies. The CzPT absorption spectra in different solvents exhibited a red shift for λmax by increasing solvent polarity. Bands at 430-474 nm appeared and were attributed to intramolecular charge transfer with high π-π* characteristics. CzPT fluorescence spectra exhibited a red shift after increasing the solvent polarity. To understand the Stokes' shift ( behaviour of the CzPT derivative referring to the polarity of solvents, Lippert-Mataga and linear solvation-energy relationship (LSER) models were employed in which the LSER exhibited respectable results compared with Lippert-Mataga (r2 = 0.9707). Moreover, time-dependent density functional theory absorption spectra in hexane and dimethylformamide showed that λmax had a major contribution in the highest occupied molecular orbital to lowest unoccupied molecular orbital transition in both solvents. In addition, the reduced uniformity of crystal features may lead to dislocation or anomalous arrangement of crystals with irregular spacing, which automatically enhances the optical properties of such crystals.

Concentration-dependent adsorption of organic contaminants by graphene nanosheets: quantum-mechanical models.

Adsorption is the key process in the expression of environmentally relevant physicochemical and toxicological properties of carbon nanomaterials. However, the adsorption of organic contaminants on to nanomaterials is a highly complex phenomenon, owing to the heterogeneity of adsorption sites, for example, on graphene surface as well as due to multiple factors operative during the adsorption, particularly, at the quantum-mechanical level. For predicting the concentration-dependent adsorption coefficients of organic contaminants by carbon nanomaterials, one option has been to rely on the existing linear-solvation energy relationship (LSER) models. The present work on the adsorption of aromatic and aliphatic organic contaminants by graphene nanosheets reveals that the existing LSER models are prone to failure when tested for internal and external validation using an external prediction set of compounds unknown to the model. As an alternative to the LSERs, the present work reports pure quantum-mechanical models developed using computational only quantum-mechanical descriptors. The reliability of the quantum-mechanical models was tested using state-of-the-art validation procedures employing an external prediction set of compounds. The proposed quantum-mechanical models reveal mean polarizability, zero-point vibrational energy, and its electron-correlation contribution to be the key descriptors in the prediction of adsorption coefficients of organic contaminants by graphene nanosheets.

Characterization of stationary phases in supercritical fluid chromatography including exploration of shape selectivity

Achiral packed column supercritical fluid chromatography (SFC) has shown an important regain of interest in academic and industrial laboratories in the recent years. In relation to this increased concern, major instrument manufacturers have designed some stationary phases specifically for SFC use. SFC stationary phases have been widely examined over the last two decades, based on the use of linear solvation energy relationships (LSER), which relate analyte retention to its properties and to the interaction capabilities of the chromatographic system. The method provides some understanding on retention mechanisms (normal phase, reversed phase or mixed-mode) and the possibility to compare stationary phases on a rational basis, especially through a spider diagram providing a visual classification. The latter can be used as a primary tool to select complementary stationary phases to be screened for any separation at early stages of method development, before optimization steps.In this context, the characterization of the 14 columns from the Shim-pack UC series (Shimadzu Corporation, Kyoto, Japan), which are dedicated to SFC and more broadly to unified chromatography (UC), was performed, using the LSER methodology. As in previous works, seven descriptors, including five Abraham descriptors (E, S, A, B, V) and two descriptors describing positive and negative charges (D− and D+) were first employed to describe interactions with neutral and charged analytes. Secondly, two more descriptors were introduced, which were previously employed solely for the characterization of enantioselective systems and expressing shape features of the analytes (flexibility F and globularity G). They brought additional insight into the retention mechanisms, showing how spatial insertion of the analytes in some stationary phases is contributing to shape separation capabilities and how folding possibilities in flexible molecules is unfavorable to retention in other stationary phases.

Synthesis of 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazol-5(4H)-one and 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazole-5(4H)-thione and solvent effects on their infrared spectra in organic solvents

In the present study novel 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazol-5(4H)-one (compound (4)) and 4-(4-ethyl-phenyl)-3-(4-methyl-phenyl)-1,2,4-oxadiazole-5(4H)-thione (compound (5)) were synthesized. These oxadiazole ring derivatives were characterized by IR, 1H NMR, 13C NMR and HRMS analyses. The solvent effects on CO, CN and CS stretching vibrational frequencies (ν(CO), ν(CN) and ν(CS)) of synthesized compounds were investigated experimentally using attenuated total reflection (ATR) infrared spectroscopy and compared with the theoretical results assigned using the potential energy distribution (PED) contributions. Furthermore, the ν(CO), ν(CN) and ν(CS) of compound (4) and compound (5) were correlated with empirical solvent parameters such as the solvent acceptor numbers, the Swain equation, the Kirkwood-Bauer-Magat equation, and the linear solvation energy relationships. Apart from the linear effects investigated in similar studies, solvent-induced vibrational shifts were investigated using the quadratic equation. The prediction capabilities of empirical solvent parameters were statistically compared. It was found that the linear solvation energy relationships show better correlation than the other empirical solvent parameters. Additionally, the quadratic equation provided more accurate predictions for the vibrational frequency locations than the Swain and the linear solvation energy relationships equations.

Antisolvent effect on the crystallization of fosfomycin phenylethylamine by acetone: Solubility measurement and thermodynamic mechanism analysis

AbstractAntisolvent crystallization of fosfomycin phenylethylamin (FPEA) by acetone is demonstrated by measuring its solubility in binary solvents of (ethanol + acetone) and (water + acetone) at 293.15 K. The solubility (g/g) of FPEA always decreased with the increase of acetone composition and correlations were proposed to sufficiently represent the data. Excess solubilities (mole fraction) of FPEA were always positive with maximum and well correlated by the simplified‐modified‐Wilson equation. Effects of various solvent properties on the solubility were analyzed by the solvatochromic KAT linear solvation energy relationship, which revealed the decrease of solvent's hydrogen bond donation ability should be the most essential characteristics of the antisolvent. Finally, by analyzing its surrounding solvent composition using the inverse Kirkwood–Buff integrals method, we found FPEA was preferentially solvated by water in acetone–water due to the strong acidic behavior of water, while, because of different competing interactions in acetone–ethanol, FPEA was preferentially solvated by acetone in ethanol‐rich region while by ethanol in acetone‐rich region.

Equilibrium solubility, Hansen solubility parameter, dissolution thermodynamics, transfer property and preferential solvation of zonisamide in aqueous binary mixtures of ethanol, acetonitrile, isopropanol and N,N-dimethylformamide

The present contribution was devoted to the equilibrium solubility profile, thermodynamics of dissolution process and solvation performance of zonisamide in aqueous binary mixtures of acetonitrile, ethanol, isopropanol and N,N-dimethylformamide (DMF) by using experiment and mathematical correlations. A shake-flask method was used throughout all experimental process under ambient pressure of 101.2 kPa from 278.15 to 323.15 K. The maximum magnitude of equilibrium solubility of zonisamide in neat acetonitrile/ethanol/isopropanol/DMF at T = 323.2 K was recorded as 23.28 × 10−3, 4.460 × 10−3, 3.522 × 10−3 and 136.4 × 10−3 (mole fraction), respectively; while the minimum one was recorded in pure solvent of water (0.01783 × 10−3 at 278.15 K). The solubility behavior of the drug zonisamide was analyzed through Hansen solubility parameter. The solubility data was represented computationally by various models such as the modified Jouyban–Acree–van’t Hoff, Jouyban–Acree, and general single model (GSM), achieving the overall relative average deviations of less than 8.23 %. The relative prominence of interactions of solvent-solvent and solute-solvent molecules upon zonisamide solubility studied through the linear solvation energy relationships indicated that the chief contributions to solubility variation were dipolarity-polarizability and solubility parameter of solutions. The determined solubility data at 298.15 K was analyzed by using the extended Hildebrand solubility approach gaining correlation coefficient of 0.86. According to several solution properties, a quantitative study on preferential solvation was performed by the technique of inverse Kirkwood–Buff integrals. The preferential solvation parameters for neat solvents of isopropanol, acetonitrile, ethanol and DMF were positive in isopropanol/acetonitrile/ethanol/DMF-rich and intermediate proportions in solutions, suggesting that the drug zonisamide was preferentially solvated by the cosolvents (isopropanol/acetonitrile/ethanol/DMF). In these composition regions, it is conjectured that zonisamide is acting as a Lewis acid with the molecules of isopropanol/acetonitrile/ethanol/DMF. Thermodynamic dissolution calculation exhibited an entropy-driven and endothermic dissolution of the drug zonisamide in all the isopropanol/acetonitrile/ethanol/DMF + water mixtures. In addition, the evaluation of enthalpy–entropy compensation specified an enthalpy-driven mechanism for the solvation of zonisamide. The investigation on transfer properties indicated more advantageous solubilization capability in intermediate proportions of isopropanol/acetonitrile/ethanol/DMF.

Ionic liquids: "normal" solvents or nanostructured fluids?

Ionic liquids (ILs) are a class of non-conventional solvents, which, for almost two decades, have continued to generate burgeoning interest in different fields of present-day chemical research with few similar precedents. Among the various aspects related to ILs, a topic worthy of in-depth analysis is their influence on organic reactivity and reaction rates. In light of this, the present short review aims to provide an overview of the literature from 2010 to the present day that addresses this issue. In particular, we herein present two main different viewpoints by which the solvent effect of ILs is explained: the first is mainly based on considering the bulk polarity of ILs and linear solvation energy relationships, while the other treats ILs as nanostructured fluids. In both cases, studies dealing with IL mixtures are also covered. Finally, literature addressing the area of supramolecular catalysis "by" or "in" ILs is also reported. This is one of the few reviews covering these specific aspects, aiming to provide a useful framework to guide future research into the effects of ILs on organic reactivity.

Synthesis of a new organic probe 4-(4 acetamidophenylazo) pyrogallol for spectrophotometric determination of Bi(III) and Al(III) in pharmaceutical samples

Abstract A modern development discusses the synthesis and validity of simple, sensitive, and versatile spectrophotometric methods for Bi(III) and Al(III) determination in pharmaceutical formulations have been conducted. In the present paper, 4-(4 acetamidophenylazo) pyrogallol has been synthesized as a new organic compound, 4-APAP, by coupling pyrogallol in a regulated pH medium with diazotized p-aminoacetanilide. 4-APAP was identified by methods of FT-IR, 1H-NMR, 13C-NMR, and thermal analysis (thermogravimetry and differential scanning calorimetry). Solvatochromic activity was also studied in solvents with different polarities. The Kamlet and Taft linear solvation energy relationship was used to correlate shifts in UV-Visible spectra of 4-APAP with Kamlet-Taft parameters (α, β, and π*). The optimum assay conditions showed linearity from 0.3–13 to 0.5–11 μg·mL−1 for Bi(III) and Al(III), respectively. Molar absorptivity values were 3.365 × 104 and 0.356 × 104 L·mol−1·cm−1 for Bi(III) and Al(III), with similar Sandell's sensitivity measures of 0.006 and 0.008 μg·cm−2. Detection limits and quantification limits were 0.013 and 0.043 μg·mL−1 for Bi(III), respectively, and 0.018 and 0.059 μg·mL−1 for Al(III) with the relative standard deviation for determination of both metal ions using 4-APAP probe being &lt;2.0%. The validity, accuracy, and efficiency of the approaches were demonstrated by the determination of Bi(III) and Al(III) in different formulations.

Solvent polarity indicators based on bithiophene carboxamidine hydrochloride salt derivatives

The photophysical properties of water soluble 5′-(4-methoxyphenyl)-2,2′-bithiophene-5-carboxamidine hydrochloride salt (MBTCH) and 5′-(3,5-dimethoxyphenyl)-2,2′-bithiophene-5-carboxamidine hydrochloride salt (DMBTCH) were studied in different solvents. The absorption spectra of MBTCH and DMBTCH show very weak solvent dependence, while the fluorescence emission spectra show bathochromic shift of about 35 nm and 48 nm on changing the solvent from cyclohexane to DMSO for DMBTCH and MBTCH, respectively. In protic solvents further bathochromic shift is observed in case of DMBTCH. The excited state time resolved decay of MBTCH and DMBTCH were measured over the entire fluorescence spectra and fitted very well with bi-exponential function in all solvents. Correlation of MBTCH and DMBTCH photophysical properties with ETN (Reichardt’s normalized polarity parameter) was successful when the solvents are classified according to their hydrogen bonding properties, namely, protic and aprotic solvent categories. Reichardt-Ravi equation was used to determine dipole moment changes, Δμ, in both categories of solvents. Several multiple linear regression solvation energy relationships were used to assess the dependence of the photophysical properties on specific and non-specific properties of the solvents, such as Kamlet-Taft, Catalán and Laurence et al. relationships. These relationships have shown that hydrogen bonding interactions (specific interactions) and dipolar interaction (non-specific) competes strongly in their contribution to the photophysical properties of the studied compounds with slight domination of the latter.