Study Of Preferential Solvation Research Articles

Solvatochromism, preferential solvation and excited state dipole moments of flufenamic acid in different solvent polarities

The influence of pure solvent and binary solvent mixtures on the optical properties of non-steroidal anti-inflammatory drug (NSAID) molecule, specifically flufenamic acid (FLA), has been studied using absorption and fluorescence spectroscopic techniques. A bathochromic shift is observed in the emission wavelength of FLA with an increase in the solvent polarity of pure solvents, attributed to the highest stability of the excited state. The spectral properties are correlated with Lippert–Mataga, solvent polarity parameter, Kamlet, and Catalan solvent polarity parameters, suggesting that both general and specific solvent effects influence the spectral properties, with general solvent effects dominating over specific solvent effects. Preferential solvation studies have been carried out in tetrahydrofuran (THF) and water solvent mixture, revealing variations in the preference for solvation of FLA as a function of the mole fraction of water. Solvatochromic data are utilized to estimate the excited state dipole moment in pure solvents using different solvatochromic methods, revealing that the excited state dipole moment of FLA is higher than its ground state counterpart. The increase in dipole moment in the excited state compared to the ground state is explained based on intramolecular charge transfer (ICT), with elaboration and discussion on the possible resonance structure corresponding to ICT, inferring the more polar nature of the excited state compared to the ground state. The effect of solute polarizability on the excited state dipole moment and change in dipole moment is also discussed.

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions.

Rosuvastatin (RST) is a poorly water-soluble drug responsible for limited in vivo dissolution and subsequently low oral systemic absorption (poor bioavailability). The mole fraction solubility values of RST in various ratios of binary mixtures "{PEG400 (1) + water (2)}" at 298.15 K were employed to investigate the preferential solvation (PS) of RST (3) by the binary components. Moreover, the GastroPlus program predicted the drug dissolution/absorption rates, plasma drug concentration, and compartmental regional drug absorbed from a conventional tablet as compared to the RST-loaded (PEG400 + water) mixture (at x 1 = 0.5) in healthy subjects (considering the fast condition). Fedors' method was adopted to estimate the values of molar volume (314.8 cm3·mol-1) and Hildebrand solubility parameter (28.08 MPa1/2) of RST. The results of inverse Kirkwood-Buff integrals showed the PS of RST by PEG400 as observed in all studied ratios of the binary mixture. The highest PS value (δx 1,3 = 1.65 × 10-2) for RST by PEG400 was attained at x 1 = 0.5. Finally, the GastroPlus program predicted the maximum dissolution rate [20 mg within 15 min as compared to pure RST (1.5 mg within 15 min)]. Moreover, the program predicted increased in vivo oral absorption (1.2 μg/mL) and enhanced regional absorption (95.3%) of RST from upper segments of the gastrointestinal tract for the RST-loaded PEG400 + water mixture in humans as compared to conventional tablets (87.5% as total regional absorption and 0.88 μg/mL as in vivo absorption). Hence, the present binary system ferrying RST can be a promising strategy to control systemic dyslipidemia after oral or subcutaneous administration.

Preferential solvation study of (Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) in {NMP + Water } co-solvent mixture and GastroPlus software based in vitro simulation

(Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) (SE11) is a newly synthesized benzylidine thiazolidinedione to inhibit aldose reductase (AR) to control Diabetes Mellitus (DM) and related complications. This reported compound exhibits poor water solubility and based on Hansen solubility parameter (HSP) considerations NMP (N-methyl-2-pyrrolidone) is expected to be a suitable co-solvent. SE11 was soluble in various ratios of (NMP + water) mixture at 298.15 K. Moreover, preferential-solvation (PS) of SE11 by the mixed components was investigated (thermodynamic functional parameters and Kirkwood-Buff integrals) followed by in-vitro dissolution, and simulation (GastroPlus) of dissolution data for the best fit of Weibull model. Hansen solubility parameters (HSP) analysis suggested NMP as the most relevant solvent for SE11 solubility at 298 K and predicted physicochemical properties. In PS, the molar-volume (214.0 cm3·mol−1), Hildebrand solubility parameter (31.11 MPa1/2), and molecular-radius (0.44 nm) of SE11 were calculated. The inverse Kirkwood-Buff integral computational analysis showed that the PS of SE11 through NMP was found in all explored ratios. The highest value (δx1,3 = 0.67 × 10–2) of PS was obtained at x1 = 0.60–0.65 in NMP. Finally, the GastroPlus software simulated in vitro dissolution profile and the impact of shape factor on release behaviour followed by computational assessment. Hence, the explored binary mixture can be used as a suitable approach to treat systemic DM.

Preferential Solvation Study of the Synthesized Aldose Reductase Inhibitor (SE415) in the {PEG 400 (1) + Water (2)} Cosolvent Mixture and GastroPlus-Based Prediction.

(Z)-N-Benzyl-2-{2,4-dioxo-5-(4-prop-2-yl-1-yloxyl)benzylidene)thiazolin-3-yl)}acetamide (SE415) is a novel aldose reductase inhibitor used in the management of diabetes mellitus (DM) and associated complications. Herein, the drug was solubilized (mole fraction solubility) in a “PEG 400 (polyethylene glycol 400) + water” mixture of various ratios at 298.15 K. We reported the preferential solvation of SE415 by PEG 400 using Kirkwood–Buff integrals, the thermodynamic functional parameter, in vitro dissolution, and GastroPlus-based predictions for in vivo performance. The result of Hansen solubility parameter analysis suggested PEG 400 as a suitable solvent for SE415 solubilization at 298.0 K, followed by prediction of several physicochemical properties. In the preferential solvation study, the molar volume, Hildebrand solubility parameters, and the molecular radius of SE415 were estimated as 258.4 cm3·mol–1, 27.62 MPa1/2, and 0.468 nm, respectively, using Fedors’ method. The inverse Kirkwood-Buff integrals indicated that the preferential solvation of SE415 by PEG 400 occurred in all studied ratios of the (PEG 400 + water) mixtures. The maximum value (δx1,3 = 1.21 × 10–2) of the preferential solvation of SE415 by PEG 400 was achieved at x1 = 0.15. Then, using GastroPlus software, the maximum dissolution, improved in vivo oral absorption, and high regional compartmental absorption (total 99.0%) of SE415 in humans were predicted. Finally, the solubility data were correlated/predicted using various cosolvency models with satisfactory results. Thus, the binary cosolvent system can be a promising approach for enhanced oral absorption in controlling DM and associated complications in humans.

Rutaecarpine dissolved in binary aqueous solutions of methanol, ethanol, isopropanol and acetone: Solubility determination, solute-solvent and solvent-solvent interactions and preferential solvation study

The main objective of this work was to report the mole fraction solubility of rutaecarpine in four binary solutions of methanol (1) + water (2), isopropanol (1) + water (2), acetone (1) + water (2) and ethanol (1) + water (2) acquired through the saturation shake-flask technique. All experiments were conducted at temperatures from 283.15 K to 323.15 K. The maximum solubility was observed in the pure solvent of methanol/ethanol/isopropanol/acetone for each solution. The achieved rutaecarpine solubility in mole fraction was mathematically described by two common co-solvency models, namely Jouyban-Acree model and van’t Hoff-Jouyban-Acree model. The calculated relative average deviations were no more than 6.78%; and root-mean-square deviations, no more than 23.69 × 10−6. The linear solvation energy relationships suggested by Kamlet and Taft was used to examine the effect of solvent descriptors on the behaviour of rutaecarpine solubility. The Hildebrand solubility parameter and dipolarity-polarizability were predominant contributors to solvent effect for the four mixtures studied. The local mole fractions of methanol (acetone, isopropanol or ethanol) and water nearby the solute rutaecarpine were quantitatively analyzed through an Inverse Kirkwood–Buff integrals method. For these mixtures within intermediate and methanol/ethanol/isopropanol/acetone-rich compositions, rutaecarpine was preferentially solvated by the methanol/ethanol/isopropanol/acetone; while within water-rich compositions, by the water.

Stereoelectronics of the Hydrogen-Bond-Induced Fluorescence Quenching of 3-Aminofluorenones with Alcohols.

Two derivatives of 3-amino-9-fluorenone (1) bearing one (2) and two methyl (3) groups flanking the carbonyl group are prepared. Comparison of their photophysical properties show that all suffer efficient radiationless deactivation in the presence of alcohols. Preferential solvation studies with mono alcohols reveal that a single H-bonding interaction quenches the excited states of 1 and 2, but not that of 3. In contrast, a single molecule of ethylene glycol quenches all three. These results are interpreted in a quenching mechanism similar to one proposed by Inoue and co-workers, but where an out-of-plane H-bond with the carbonyl group gives rise to an emissive species, while an in-plane H-bond results in quenching.

Influence of Solvent Environment on Photophysical Properties of 3-(Piperidin-1-yl)-4H-benzo[de]anthracen-7(11bH)-one

The absorption and emission spectra of the benzanthrone derivative 3-(piperidin-1-yl)-4H-benzo[de]anthracen-7(11bH)-one [3-P4H-BDA] have been investigated in different solvents of varying polarities. The quantum yield (Φf) and lifetime (τ) values of this molecule were measured in various solvents. The radiative rate constant (Kr) and non-radiative rate constants (Knr) were also calculated. The nature of solute–solvent interactions was studied using Lippert plots and the Kamlet–Abboud–Taft polarity scale. Further, preferential solvation studies were carried out for the 3-P4H-BDA molecule in ethanol–DMSO and benzene–DMSO binary solvent mixtures. Ground state and excited state dipole moments of the 3-P4H-BDA molecule were calculated from the experimental results using the solvatochromic method and theoretically using the B3LYP/6-311 + G(d,p) method. Experimental values are in good agreement with the theoretical results. The HOMO–LUMO energy gap (eV), absorption and emission maxima in nm were calculated for the 3-P4H-BDA molecule using the B3LYP/6-311 + G(d,p) method. Also, ionization potential (I), electron affinity (A), electronegativity (χ), hardness (η) and softness (σ), global electrophilicity (ω) and chemical potential were calculated.

Intramolecular Hydrogen-Bonding Effects on the Fluorescence of PRODAN Derivatives.

The effects of intramolecular hydrogen-bonding on the fluorescence behavior of three derivatives of 6-propionyl-2-dimethylaminonaphthalene are reported. The H-bonding effects are revealed through comparisons with corresponding reference compounds in which the H-bond-donating hydroxyl groups are replaced with methoxy groups. In toluene, intramolecular H bonding gives rise to a dramatic increase in the fluorescence intensity but only a slight red shift in the position. This behavior is attributed to decreased efficiency in intersystem crossing due to an increase in the energy of the n → π* triplet state. The intramolecular H bond does not induce quenching in acetonitrile; however, in the presence of a very small concentration of methanol, a dual intramolecular, intermolecular H-bonding arrangement does lead to partial quenching as revealed by preferential solvation studies.

Solvation structure of sodium chloride (Na+–Cl−) ion pair in dimethyl sulfoxide–acetonitrile mixtures

Constrained molecular dynamics method has been used to compute the potentials of mean force (PMFs) of Na+-Cl− in dimethyl sulfoxide (DMSO)–acetonitrile (AN) binary mixtures. The PMFs are confirmed by calculating the residence times of the ion pair at various inter-ionic separations. Contact ion pairs (CIPs) are found to be more stable than the solvent shared ion pairs (SShIPs). The stabilities of CIPs generally increase with increase in the mole fraction of AN. The running coordination number analysis shows that the coordination number of Na+ in pure acetonitrile is 4.6, close to the experimental value by FTIR and refractometric study. The preferential solvation study through the excess coordination numbers shows that both Na+ and Cl− are preferentially solvated by DMSO, unlike the water–DMSO mixtures.

A conductivity study of preferential solvation of lithium ion in acetonitrile-dimethyl sulfoxide mixtures

The electrical mobility of LiPF6 in acetonitrile–dimethyl sulfoxide (ACN–DMSO) mixtures, a potential electrolyte in oxygen cathodes of lithium-air batteries, has been studied using a very precise conductance technique, which allowed the determination of the infinite dilution molar conductivity and association constant of the salt in the whole composition range. In the search for preferential Li+ ion solvation, we also measured the electrical conductivity of tetrabutylammonium hexafluorophosphate (TBAPF6), a salt formed by a bulky cation, over the same composition range. The results show a qualitative change in the curvature of the LiPF6 molar conductivity composition dependence for ACN molar fraction (xACN)∼0.95, which was not observed for TBAPF6. The dependence of the measured Li/Li+ couple potential with solvent composition also showed a pronounced change around the same composition. We suggest that these observations can be explained by Li+ ion preferential solvation by DMSO in ACN–DMSO mixtures with very low molar fractions of DMSO.

2,5-PRODAN derivatives as highly sensitive sensors of low solvent acidity.

Two 5-acyl-2-dimethylaminonaphthalene derivatives, one with a propionyl group and the other with a fused cyclohexanone ring, are investigated as sensors of H-bond-donating ability in protic solvents of low solvent acidity. Their fluorescence is highly quenched in protic solvents, and the quenching order of magnitude is linearly related to the H-bond-donating ability of the solvent as quantified by the solvent acidity (SA) scale. As the solvent acidity increases from 0.15 to 0.40, the fluorescence for both is quenched by more than a factor of ten; thus, they are extremely sensitive sensors of the hydrogen-bond-donating ability in this weakly acidic range. Preferential solvation studies suggest that quenching occurs from a doubly H-bonded excited state.

UV–Vis spectroscopic study of preferential solvation and intermolecular interactions in methanol/1-propanol/acetonitrile by means of solvatochromic probes

Solvatochromic UV–Vis shifts of four indicators (4-nitroaniline, 4-nitroanisole, 4-nitrophenol and N,N-dimethyl-4-nitroaniline) have been measured at 298.15K in the ternary mixture methanol/1-propanol/acetonitrile (MeOH/1-PrOH/MeCN) in a total of 22mole fractions, along with 18 additional mole fractions for each of the corresponding binary mixtures, MeOH/1-PrOH, 1-PrOH/MeCN and MeOH/MeCN. These values, combined with our previous experimental results for 2,6-diphenyl-4-(2,4,6-triphenylpyridinium-1-yl)phenolate (Reichardt’s betaine dye) in the same mixtures, permitted the computation of the Kamlet–Taft solvent parameters, α, β, and π*. The rationalization of the spectroscopic behavior of each probe within each mixture’s whole mole fraction range was achieved through the use of the Bosch and Rosés preferential solvation model. The applied model allowed the identification of synergistic behaviors in MeCN/alcohol mixtures and thus to infer the existence of solvent complexes in solution.Also, the addition of small amounts of MeCN to the binary mixtures was seen to cause a significant variation in π*, whereas the addition of alcohol to MeCN mixtures always lead to a sudden change in α and β. The behavior of these parameters in the ternary mixture was shown to be mainly determined by the contributions of the underlying binary mixtures.

On-line preferential solvation studies of polymers by coupled chromatographic-Fourier transform infrared spectroscopic flow-cell technique

Qualitative and quantitative comparison between liquid chromatography (LC) and LC coupled with Fourier transform infrared spectroscopy (LC-FTIR) to evaluate preferential solvation phenomenon of polymers in a mixed solvent has been performed. These studies show that LC-FTIR technique leads to detailed structural information without the requirement for determination of additional parameters for quantitative analysis except calibration. Appropriate experimental conditions for preferential solvation study have been established by variation of polymer concentration, molar mass and eluent content.

Preferential solvation of acridine in binary mixtures

Preferential solvation studies of acridine have been investigated using optical absorption technique. The preferential solvation parameter shows that in dimethyl formamide (DMF) + ethanol mixture, the acridine is preferentially solvated by ethanol in DMF rich region and by DMF in ethanol rich region. In the case of DMF + Carbon tetrachloride mixture acridine is preferentially solvated by DMF.

Study of preferential solvation of 2,6-diaminoanthraquinone in binary mixtures by absorption and fluorescence studies

The role of solute–solvent and solvent–solvent interaction on the preferential solvation characteristics of 2,6-diaminoanthraquinone (DAAQ) has been analysed by monitoring the optical absorption and fluorescence emission spectra. Binary mixtures consist of dimethylformamide (DMF)–ethanol (EtOH), DMF–dimelthylsulfoxide (DMSO), benzene (BZ)–DMF and acetonitrile (ACN)–DMF. The optical absorption spectra maximum and emission spectra maximum of DAAQ show the changes with varying the solvents and change in the composition in the case of binary mixtures. Non-ideal solvation characteristics are observed in all binary mixtures. It is found that at certain concentrations two mixed solvents interact to form a common structure with a ν 12 (wave number in cm −1) value not always intermediate ( ν 1 and ν 2) between the values of the solvents mixed. Synergistic effect is observed in the case of DMF–EtOH mixtures. The preferential solvation parameters local mole fraction X 2 L , solvation index δ S2, exchange constant K 12 are calculated in all binary mixtures expect in the case of DMF–BZ mixture and DMF–EtOH mixture in the ground state. We have also monitored excitation wavelength effect on the probe molecule in aprotic polar and protic polar solvents.

A fluorescence spectroscopy study of preferential solvation in binary solvents

Published data are reviewed on the dynamics of nonspecific preferential solvation in binary solvents, as obtained by fluorescence spectroscopy (in particular, by magnetic spin fluorescence method) using probe molecules in which strong charge redistribution yielding dipoles and ion pairs takes place upon excitation. The dynamics of preferential solvation of the excited probe in a binary solvent is described by a sequence of consecutive equilibrium reactions, in which each step is the absorption of a molecule of the polar component by the solvation shell of the excited probe, where transport from the bulk solution occurs via translational diffusion. The characteristic effect of the time saturation of solvation is attributed to the energetically unfavorable process of interface formation between the solvation shell, which a polar nanosized cluster, and the homogeneous binary mixture. Such polar clusters may affect the course of photochemical reactions involving charged species or particles with a large dipole moment. Simple model concepts, such as the Frenkel theory of heterophase fluctuations, the Onsager model, and the Hildebrand theory of solubility used for the description of the physical picture of preferential solvation, are considered.

Ultrasonic relaxation study of preferential solvation in quasi-two-components aqueous solutions of amides and zinc salts

To investigate the effect of preferential solvation the ultrasonic attenuation (2–50 MHz) and velocities (3 MHz) of ZnCl 2 and 2-chloroacetamide (ClCH 2CONH 2) in water and its quasi-binary mixtures with the ratio (ZnCl 2 + ClCH 2CONH 2):H 2O=1:55 at 298.15 K have been measured. The creation of specific complexes in the ClCH 2CONH 2–H 2O–ZnCl 2 system have a relaxational character which, within the measurements of ultrasonic absorption in the frequency range 2–50 MHz, have been observed. On the base of these properties the kinetic and dynamic parameters of the observed relaxation have been calculated. To bring into relief the influence of Cl atom in the 2-chloroacetamide molecules for complexation process it has been investigated also the system AA–H 2O–ZnCl 2. The next step of searching was to investigate the system of CHAA–H 2O–ZnBr 2, to reduce the influence of Cl atom within ZnCl 2 molecule at the complexation process. The main aim of presented study was to investigate the possibility of complexation in the aqueous solutions of ZnCl 2 with the part of 2-ClCH 2CONH 2 (CHAA). With regard of big complexing ability of zinc, there exist a theoretical possibility of attachment CHAA to the inner coordination sphere of zinc through chloride atom. There can create here outer-sphere as well as inner-sphere complexes. As a results the observed relaxation processes have been attributed to creation and disintegration the following complexes: Zn(H 2O) 2(CHAA) 4 2+ and Zn 2+(H 2O) 3(CHAA)Cl 2 −.

Study of Preferential Solvation in Mixed Binary Solvent as a Function of Solvent Composition and Temperature by UV−Vis Spectroscopic Method

Preferential solvation of N-ethyl-4-cyanopyridinium iodide and 2,6-diphenyl-4(2,4,6-triphenyl-1-pyridino)phenolate [Reichardt's ET(30) dye] has been studied in ethanol + tetrahydrofuran, ethanol + acetonitrile and acetonitrile + tetrahydrofuran binary mixtures as a function of temperature and composition of mixed binary solvents. It has been found that besides solute−solvent interaction, solvent−solvent interaction plays an important role in determining the solvation characteristics.

Study of Preferential Solvation in Binary Mixtures by Means of Frequency-Domain Fluorescence Spectroscopy

The preferential solvation of 8-N,N-(dimethylamino)-11H-indeno[2,1-a]pyrene, Py(S)DMA, in its transient charge transfer (CT) state in binary solvents such as toluene/DMSO liquid mixtures was studied by means of frequency-domain fluorometry. The data obtained were considered within the following kinetic scheme: the preferential solvation was described by the system of consecutive reversible reactions of which each step is associated with the absorption of one DMSO molecule in the first solvation shell of the fluoresent Py(S)DMA dipolar CT molecule. The rate constants of the first two reversible elementary processes (i.e., the decay of solvation complexes of Py(S)DMA with one and two polar molecules, k21 5 1.1 10 9 s 21 and k22 5 1.4 10 9 s 21 ) were determined.

FT-Raman spectroscopic study of preferential solvation and ionic association in lithium and silver triflate solutions in acrylonitrile/N,N-dimethylformamide mixed solvent

Solutions of lithium or silver trifluoromethanesulfonate (triflate) in a mixed solvent formed by acrylonitrile (ACN) and N,N-dimethylformamide (DMF) have been studied by FT-Raman spectroscopy. The composition of the solvation sphere in both ions is calculated through the study of the modifications induced by the presence of the salt in the nitrile CN stretching at 2228cm−1 and in the NC anti-symmetric stretching of DMF at 658cm−1. DMF preferentially solvates both cations. The preference is less pronounced in the case of Ag+, although it is very remarkable that Li+ is solvated exclusively by DMF molecules in the equimolar mixed solvent. The total average solvation number remains virtually constant in Ag+ (n=3.5±0.1) and is augmented in Li+ when the molar fraction of DMF increases. This observation arises as a direct consequence of the degree of ionic association, which is evaluated through studying the components of the triflate anion SO symmetric stretching band at 1032cm−1. Lithium triflate is considerably associated in those samples rich in ACN. However, the situation changes completely in the equimolar samples, with a high concentration of spectroscopically free anions. These results are explained considering the corresponding dielectric constants of both co-solvents and their different donating ability. In silver triflate solutions, the degree of ionic association is low and remains approximately constant despite the changes in the composition of the mixed solvent, which indicates that the silver ion is solvated very effectively by both co-solvents.