Neat Water Research Articles

Solubility of carvedilol in aqueous mixtures of a deep eutectic solvent at different temperatures

ABSTRACT Improving the solubility of carvedilol (CVD) as a poorly soluble drug in water is very important for increasing its bioavailability and its effectiveness. Co-solvency methods can be advantageous in this regard and deep eutectic solvents (DESs) with special characteristics can be applied as a co-solvent. This study provides the experimental solubility data of CVD in aqueous mixtures of a DES composed of choline chloride (ChCl) and ethylene glycol (EG) in the T = (293.15–313.15) K temperature range. The solubility of CVD rises with the increasing mass fraction of DES in aqueous mixtures of it. The maximum solubility is in the neat DES and the lowest one is related to the neat water. The van’t Hoff, the mixture response surface, Jouyban-Acree, Jouyban-Acree-van’t Hoff and λh mathematical models were applied to correlate the experimental solubility data. In addition, thermodynamic functions for the dissolution process of CVD were calculated from the experimental data.

Equilibrium solubility of vanillin in some (ethanol + water) mixtures: determination, correlation, thermodynamics and preferential solvation

Equilibrium mole fraction solubility of vanillin in nine aqueous-ethanolic mixtures, as well as in neat water and neat ethanol, was determined at seven temperatures from T = 293.15 to T = 323.15 K. Vanillin solubility in these mixtures was adequately correlated with several well-known correlation models with the mean percentage deviations of 5.9 to 18.3%. Respective apparent thermodynamic functions, i.e. Gibbs energy, enthalpy, and entropy, for the dissolution, mixing and solvation processes, were computed using the van’t Hoff and Gibbs equations. The enthalpy–entropy relationship for vanillin was non-linear in the plot of enthalpy vs. Gibbs energy of dissolution with positive slopes from neat water to the mixture of w1 = 0.10 and the interval 0.50 < w1 < 0.90 but negative in the interval 0.10 < w1 < 0.50 and from w1 = 0.90 to neat ethanol. Accordingly, in the first cases the vanillin transfer from more polar to less polar solvent systems is enthalpy-driven but entropy-driven for the last ones. Moreover, by means of the inverse Kirkwood-Buff integrals is observed that vanillin is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by ethanol molecules in mixtures of 0.23 < x1 < 1.00.

Segregation on the nanoscale coupled to liquid water polyamorphism in supercooled aqueous ionic-liquid solution.

The most intriguing hypothesis explaining many water anomalies is a metastable liquid-liquid phase transition (LLPT) at high pressure and low temperatures, experimentally hidden by homogeneous nucleation. Recent infrared spectroscopic experiments showed that upon addition of hydrazinium trifluoroacetate to water, the supercooled ionic solution undergoes a sharp, reversible LLPT at ambient pressure, possible offspring of that in pure water. Here, we calculate the temperature-dependent signature of the OH-stretching band, reporting on the low/high density phase of water, in neat water and in the same experimentally investigated ionic solution. The comparison between the infrared signature of the pure liquid and that of the ionic solution can be achieved only computationally, providing insight into the nature of the experimentally observed phase transition and allowing us to investigate the effects of ionic compounds on the high to low density supercooled liquid water transition. We show that the experimentally observed crossover behavior in the ionic solution can be reproduced only if the phase transition between the low- and high-density liquid states of water is coupled to a mixing-unmixing transition between the water component and the ions: at low temperatures, water and ions are separated and the water component is a low density liquid. At high temperatures, water and ions get mixed and the water component is a high-density liquid. The separation at low temperatures into ion-rich and ion-poor regions allows unveiling the polyamorphic nature of liquid water, leading to a crossover behavior resembling that observed in supercooled neat water under high pressure.

Comprehensive insight into solubility, dissolution properties and solvation behaviour of dapsone in co-solvent solutions

This research was mainly committed to the solubility profile, dissolution properties and solvation behavior for the systems formed by dapsone in aqueous solutions of ethanol/acetone/methanol (1) and non-aqueous solution of ethyl acetate (1) + ethanol (2) accompanied by numerous computational methodology. All experiments for solubility were conducted by using a shake-flask method at pressure p = 101.2 kPa and temperatures from 278.15 to 323.15 K. For each solvent solution system, the equilibrium solubility in magnitude of dapsone was recorded as highest in neat ethanol/ethyl acetate/methanol/acetone (1) at 323.15 K; and lowest in neat ethanol (2) or water (2) at 278.15 K. The three-dimensional Hansen solubility parameter was utilized here to investigate solubility performance. Numerous common relationships including modified van’t Hoff Jouyban–Acree model, mixture response surface model, Jouyban–Acree model, and modified Wilson model provided acceptable correlation consequences for the solubility magnitudes obtained with relative average deviations of < 12.33 %. The solubility magnitude at temperature of 298.15 K was also studied by the extended Hildebrand solubility approach, gaining RAD of < 3.24 %. By consideration of some accessible solution properties, the preferential solvation of dapsone was further examined through quantitation by employing the inverse Kirkwood–Buff integrals way. The positive parameters of preferential solvation in ethanol/acetone/methanol-rich and intermediate composition solutions indicates that the drug dapsone is preferentially solvated by ethanol/acetone/methanol. It can be speculated that dapsone performs as Lewis acid behavior with ethanol/acetone/methanol molecules in above composition regions. Nevertheless preferential solvation of dapsone is made neither by ethanol nor by ethyl acetate in the ethyl acetate + ethanol solution. The dissolution of dapsone in all studied systems was endothermic and entropy-driven process.

Unraveling the Mechanism of Aerobic Alcohol Oxidation by a Cu/pytl-β-Cyclodextrin/TEMPO Catalytic System under Air in Neat Water.

The mechanism for the oxidation of p-tolylmethanol to p-tolualdehyde catalyzed by a Cu/pytl-β-cyclodextrin/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidinyl-1-oxy) catalytic system under air in neat water is fully investigated by density functional theory (DFT). Four possible pathways (paths A → D) are presented. The calculated TOF = 0.67 h-1 for path A is consistent with the experimental TOF = 1.9 h-1 but much lower than that for path D (TOF = 1.1 × 105 h-1). The results demonstrate that path A is the dominant pathway under the optimal experimental conditions, even though path D is more kinetically favorable. This is because the concentration of precatalyst 11 [(pytl-β-CD)CuII(OH)] in path D is too low to start path D, so p-tolylmethanol oxidation can only proceed via path A. This finding implies that the relative concentration of precatalysts in a one-pot synthesis experiment plays a vital role in the aerobic alcohol oxidation reaction. Based on this finding, we speculate that the direct use of the presynthesized precatalyst 11 or addition of an appropriate amount of NaOH to the reaction solution, but with the total amount of the base added unchanged, is a good way to improve its catalytic activity. Meanwhile, the solvent water was not found to directly participate in the catalytic active sites for the oxidation of alcohols but rather inhibited it by forming the hydrogen-bonded network.

Unraveling the Influence of Osmolytes on Water Hydrogen-Bond Network: From Local Structure to Graph Theory Analysis.

Water structure in aqueous osmolyte solutions, deduced from the slight alteration in the water-water radial distribution function, the decrease in water-water hydrogen bonding, and tetrahedral ordering based only on the orientation of nearest water molecules derived from the molecular dynamics simulations, appears to have been perturbed. A careful analysis, however, reveals that the hydrogen bonding and the tetrahedral ordering around a water molecule in binary solutions remain intact as in neat water when the contribution of osmolyte-water interactions is appropriately incorporated. Furthermore, the distribution of the water binding energies and the water excess chemical potential of solvation in solutions are also pretty much the same as in neat water. Osmolytes are, therefore, well integrated into the hydrogen-bond network of water. Indeed, osmolytes tend to preferentially hydrogen bond with water molecules and their interaction energies are strongly correlated to their hydrogen-bonding capability. The graph network analysis, further, illustrates that osmolytes act as hubs in the percolated hydrogen-bond network of solutions. The degree of hydrogen bonding of osmolytes predominantly determines all of the network properties. Osmolytes like ethanol that form fewer hydrogen bonds than a water molecule disrupt the water hydrogen-bond network, while other osmolytes that form more hydrogen bonds effectively increase the connectivity among water molecules. Our observation of minimal variation in the local structure and the vitality of osmolyte-water hydrogen bonds on the solution network properties clearly imply that the direct interaction between protein and osmolytes is solely responsible for the protein stability. Further, the relevance of hydrogen bonds on solution properties suggests that the hydrogen-bonding interaction among protein, water, and osmolyte could be the key determinant of the protein conformation in solutions.

Measurement and correlation of solubility of lifitegrast in four mixtures of (diethylene glycol monoethyl ether, glycerol, PEG 400, and propylene glycol + water) from 288.15 K to 308.15 K

In this study, the solubility of lifitegrast was measured at various temperatures ranging from 288.15–308.15 K in four green solvents + water mixtures through a solid-liquid equilibrium via the shake-flask method. The experimental mole fraction solubility of lifitegrast increased with increasing temperature. The mole fraction solubility of lifitegrast increased as the mass fraction of green solvents increased at a constant temperature, except in diethylene glycol monoethyl ether (DEGME) + water mixtures. The mole fraction solubility of lifitegrast in neat polyethylene glycol 400 (PEG 400), which was approximately 33,600 times higher than in neat water at 298.15 K, was the highest solubility overall binary composition. Five models, including the van’t Hoff model, modified Apelblat model, simplified CNIBS/R-K model, Sun model, and Ma model were used to correlate and fit the experimental solubility data of lifitegrast in four green solvents + water mixtures. The thermodynamic parameters during the dissolution process of lifitegrast in four green solvents + water mixtures, such as enthalpy (ΔH°), Gibbs free energy (ΔG°), and entropy (ΔS°), were estimated using the modified van’t Hoff equation. The solubility data and correlation models could be useful for developing formulations during drug product development, such as eye drops based on these results.

Mizoroki-Heck carbon-carbon cross-coupling reactions by water-soluble palladium (II) complexes in neat water

Water-soluble palladium complexes were synthesized, characterized, tested as (pre)catalyst for Mizoroki-Heck carbon-carbon cross-coupling reactions in water. Cross-coupling of aryl iodides and bromides with methyl and ethyl acrylates was achieved at 140 °C. When styrene was employed as the substrate excellent conversion to trans-stilbene was observed using 5 mol% catalyst loading in the presence of TBAB. The catalysts are versatile and can couple various substrates in a non-toxic and benign solvent. After extraction of the organic product the catalyst containing aqueous layer could be recycled twice with a significant drop in the aryl halide conversion after the third recycle. No catalyst poisoning was observed in the mercury poisoning experiments with both catalysts and this proves that both catalytic systems function as molecular homogeneous catalysts.

Interplay of Interfacial Viscosity, Specific-Ion, and Impurity Adsorption Determines Zeta Potentials of Phospholipid Membranes.

Ion-specific induced changes of the ζ-potential of phospholipid vesicles are commonly used to quantify the affinity of different ions to the lipid interface. The negative ζ-potential of zwitterionic net-neutral phospholipid vesicles in neat water, which changes sign and increases in solutions of NaCl or KCl, is a phenomenon consistently observed in experiments but not fully understood theoretically. Using atomistic molecular dynamics simulations in the presence of applied electric fields which drive electroosmotic flows, in combination with an electrostatic continuum model based on the modified Poisson-Boltzmann and Helmholtz-Smoluchowski equations, we study the electrokinetic and electrostatic properties as well as the specific ion affinities to the phospholipid-water interface, in order to resolve these puzzling observations. Our modified continuum equations account for the dielectric profile at the lipid-water interface, ion-specific interactions between ions and the lipid-water interface, and the interfacial viscosity profile, which are all extracted from our atomistic simulations and rather accurately predict ion-density and electrostatic-potential distributions as well as ζ-potentials in comparison with our atomistic simulations. Our continuum model can explain experimental ζ-potentials only when we assume minute amounts of surface-active anionic impurities in the aqueous solution. In fact, the amount of impurities needed to explain the experimental data increases linearly with the salt concentration, suggesting that surface-active species, which might be already present in the lab water or lipid samples, could further be introduced through the added salt.

Unexpected behavior of sodium sulfate observed in experimental freezing and corrosion studies

AbstractThis article reports results from two distinct, originally unrelated studies that show unexpected behavior with respect to sodium sulfate solutions in contact with flat surfaces. On the one hand, we investigated immersion freezing of sulfate containing solutions (target salt was CaSO4 and Na2SO4 was used as one control) in the presence of flat sapphire‐0001 crystals using second‐harmonic generation (SHG) spectroscopy. Further control experiments were carried out with neat water and CaCl2. The SHG signals from CaSO4 and Na2SO4 solutions behave somewhat differently from those recorded for the two other cases, the neat water and CaCl2. The common pattern shows a decrease of the SHG signal with decreasing temperature down to about −15°C, whereupon the signal sharply drops, indicating freezing. With the Na2SO4 solution, although the signal initially follows closely the neat water curve, the trend increases sharply at about −10°C followed by a gradual decrease with further cooling. There is no plausible explanation for the distinct behavior of the Na2SO4 solution, and thermodynamic calculations do not suggest any precipitation of a sodium sulfate solid phase. At the end of the freeze–thaw cycle, the initial SHG for each system is retrieved, suggesting reversibility. On the other hand, in a separate investigation unrelated to the freezing study, it was repeatedly observed that sodium sulfate precipitates from solution on flat steel surfaces at room temperature. As in the freezing experiments, thermodynamic calculations for the bulk solution solubility of sodium sulfate indicate that precipitates should not be forming under the conditions of the studies. The crystals observed on the steel samples have snowflake shapes similar to one literature report. We conclude that Na2SO4 in the presence of flat surfaces shows unexpected behavior that should incite further detailed studies in the future to elucidate the phenomenon.

Solubility of coumarin in (ethanol + water) mixtures: Determination, correlation, thermodynamics and preferential solvation

Equilibrium mole fraction solubility of coumarin in nine aqueous-ethanolic mixtures, as well as in neat water and neat ethanol, was determined at seven temperatures from (293.15 to 323.15) K. Coumarin solubility in was adequately correlated with several well-known correlation models with the mean percentage deviations of 5.1–10.8%. The respective apparent thermodynamic functions (Gibbs energy, enthalpy, and entropy) for the dissolution, mixing and solvation processes were computed using the van’t Hoff and Gibbs equations. The enthalpy-entropy relationship for coumarin was non-linear in the plot of enthalpy vs. Gibbs energy of dissolution with negative slope from neat water to the mixture of w1 = 0.10 but positive from this mixture to neat ethanol. Accordingly, in the first case the coumarin transfer from neat water to the mixture of w1 = 0.10 is entropy-driven, which could be attributed to water molecules release originally bounded as “icebergs” around the non-polar groups of this drug. Otherwise, in mixtures of w1 ≥ 0.10 the driving mechanism for the transfer of coumarin from the more polar solvent systems to those less polar is the enthalpy, probably owing the better drug solvation. Moreover, by means of the inverse Kirkwood-Buff integrals is observed that apparently coumarin is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by ethanol molecules in mixtures of 0.23 < x1 < 1.00.

Solubility of sulfamerazine in (ethylene glycol + water) mixtures: Measurement, correlation, dissolution thermodynamics and preferential solvation

The equilibrium solubility of sulfamerazine (SMR) in neat ethylene glycol (EG) and nineteen {(EG) (1) + water (2)} mixtures is reported at temperatures from (278.15 to 318.15) K. Mole fraction solubility of SMR (x3) increases with temperature arising and also increases with the EG proportion increasing. It varies from 1.71 × 10−5 in neat water to 7.78 × 10−4 in neat EG at 298.15 K. Solubility behavior was correlated by the extended log-linear model of Yalkowsky, the Jouyban-Acree model, and Jouyban-Acree-van’t Hoff model and the obtained mean percentage deviations are 80.1%, 6.7% and 6.6%, respectively. From the variation of solubility with temperature, the apparent thermodynamic analysis of dissolution and mixing processes was performed in all the mixtures and neat solvents. From inverse Kirkwood-Buff integrals (IKBI) calculations is observed that SMR exhibits low negative preferential solvation parameters by EG in water-rich mixtures. Otherwise, SMR is preferentially solvated by EG in the interval (0.24 < x1 < 1.00).

Effect of Al2O3 and MgO nanofluids in heat pipe solar collector for improved efficiency

In this work, a heat pipe solar collector (HPSC) utilization system is proposed. An experimental system was designed to analyze the effect of nanofluid concentration on the efficiency of the solar collector. The HPSC system was investigated with low concentration of water-based Al2O3 and MgO as the working medium. To examine the structural and optical properties, the X-ray diffraction (XRD) and Fourier transform-infrared (FT-IR) were performed. The HSPC exhibited higher efficiency when they treated with MgO nanofluids. As the concentration of the nanofluid increases, the efficiency of the solar collector is increased irrespective of the working medium. Nevertheless, compared to the Al2O3, MgO reported superior efficiency irrespective of the concentration. Second, the entropy generation for MgO was lower and highest for the neat water. Further, the flow rate of the nanofluids increases the collector efficiency spikes. Experimental system shows that the maximum performance of the HPSC is possible by employing the nanofluids to the existing system in an optimized concentration.

Solubilization of Trans-Resveratrol in Some Mono-Solvents and Various Propylene Glycol + Water Mixtures.

This research deals with the determination of solubility, Hansen solubility parameters, dissolution properties, enthalpy–entropy compensation, and computational modeling of a naturally-derived bioactive compound trans-resveratrol (TRV) in water, methanol, ethanol, n-propanol, n-butanol, propylene glycol (PG), and various PG + water mixtures. The solubility of TRV in six different mono-solvents and various PG + water mixtures was determined at 298.2–318.2 K and 0.1 MPa. The measured experimental solubility values of TRV were regressed using six different computational/theoretical models, including van’t Hoff, Apelblat, Buchowski–Ksiazczak λh, Yalkowsly–Roseman, Jouyban–Acree, and van’t Hoff–Jouyban–Acree models, with average uncertainties of less than 3.0%. The maxima of TRV solubility in mole fraction was obtained in neat PG (2.62 × 10−2) at 318.2 K. However, the minima of TRV solubility in the mole fraction was recorded in neat water (3.12 × 10−6) at 298.2 K. Thermodynamic calculation of TRV dissolution properties suggested an endothermic and entropy-driven dissolution of TRV in all studied mono-solvents and various PG + water mixtures. Solvation behavior evaluation indicated an enthalpy-driven mechanism as the main mechanism for TRV solvation. Based on these data and observations, PG has been chosen as the best mono-solvent for TRV solubilization.

Phosphate Vibrations Probe Electric Fields in Hydrated Biomolecules: Spectroscopy, Dynamics, and Interactions.

Electric interactions have a strong impact on the structure and dynamics of biomolecules in their native water environment. Given the variety of water arrangements in hydration shells and the femto- to subnanosecond time range of structural fluctuations, there is a strong quest for sensitive noninvasive probes of local electric fields. The stretching vibrations of phosphate groups, in particular the asymmetric (PO2)− stretching vibration νAS(PO2)−, allow for a quantitative mapping of dynamic electric fields in aqueous environments via a field-induced redshift of their transition frequencies and concomitant changes of vibrational line shapes. We present a systematic study of νAS(PO2)− excitations in molecular systems of increasing complexity, including dimethyl phosphate (DMP), short DNA and RNA duplex structures, and transfer RNA (tRNA) in water. A combination of linear infrared absorption, two-dimensional infrared (2D-IR) spectroscopy, and molecular dynamics (MD) simulations gives quantitative insight in electric-field tuning rates of vibrational frequencies, electric field and fluctuation amplitudes, and molecular interaction geometries. Beyond neat water environments, the formation of contact ion pairs of phosphate groups with Mg2+ ions is demonstrated via frequency upshifts of the νAS(PO2)− vibration, resulting in a distinct vibrational band. The frequency positions of contact geometries are determined by an interplay of attractive electric and repulsive exchange interactions.

Solubility and dissolution thermodynamics of 5-fluorouracil in (ethanol + water) mixtures

Equilibrium mole fraction solubility of 5-fluorouracil (5-FU) in 19 aqueous-ethanolic mixtures, as well as in neat water and neat ethanol, was determined at seven temperatures from (293.15 to 323.15) K. 5-FU solubility in these mixtures was adequately correlated with several well-known correlation models. The respective apparent thermodynamic functions (Gibbs energy, enthalpy, and entropy) for the dissolution, mixing and solvation processes were computed using the van’t Hoff and Gibbs equations. The enthalpy–entropy relationship for 5-FU was non-linear in the plot of enthalpy vs. Gibbs energy of solution with variant but positive slope in almost all the composition regions. Thus, the driving mechanism for 5-FU transfer processes was the enthalpy. In addition, by means of the inverse Kirkwood-Buff integrals is observed that apparently 5-FU is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by ethanol molecules in ethanol-rich mixtures.

Evaluating the suppression effectiveness of hybrid nitrogen and water mist with a cup burner coflowing flame

SummaryThe suppression effectiveness of an intrinsically clean hybrid fire suppressant consisting of nitrogen and water mist was experimentally studied by a cup burner method with methane/air coflowing flame. A series of hybrid agents with different weight ratios of nitrogen and water mist (Sauter mean diameter: 12.6 μm) were tested and compared with nitrogen and water mist used alone. The minimum mass‐based extinction concentration (MEC) of neat nitrogen and water mist was measured as 32.1% and 15.2%, respectively. When combined, MEC of the hybrid agents fell between the limiting values of nitrogen and water mist used alone. An approximately linear relationship was shown for the suppression behavior of nitrogen and water mist in combination. The flow field of suppressants during the flame suppression process was studied by particle imaging velocimetry (PIV) technique. A small portion of water droplets near the flame front evaporated, which contributed to flame extinction by heat absorption and oxygen dilution. The remaining bulk mist was entrained vertically with the air flow, showing little effect on the flame base.

A Water/Toluene Biphasic Medium Improves Yields and Deuterium Incorporation into Alcohols in the Transfer Hydrogenation of Aldehydes

AbstractDeuterium labeling is an interesting process that leads to compounds of use in different fields. We describe the transfer hydrogenation of aldehydes and the selective C1 deuteration of the obtained alcohols in D2O, as the only deuterium source. Different aromatic, alkylic and α,β‐unsaturated aldehydes were reduced in the presence of [RuCl(p‐cymene)(dmbpy)]BF4, (dmbpy=4,4′‐dimethyl‐2,2′‐bipyridine) as the pre‐catalyst and HCO2Na/HCO2H as the hydrogen source. Moreover, furfural and glucose, were selectively reduced to the valuable alcohols, furfuryl alcohol and sorbitol. The processes were carried out in neat water or in a biphasic water/toluene system. The biphasic system allowed easy recycling, higher yields, and higher selective D incorporation (using D2O/toluene). The deuteration took place due to an efficient effective M–H/D+ exchange from D2O that allows the inversion of polarity of D+ (umpolung). DFT calculations that explain the catalytic behavior in water are also included.

Solubility, dissolution thermodynamics and preferential solvation of 4-nitroaniline in (ethanol + water) mixtures

ABSTRACT In this research, the equilibrium mole fraction solubility of 4-nitroaniline (4-NA) in some aqueous-ethanolic mixtures was determined at seven temperatures from (293.15 to 323.15) K. The respective apparent thermodynamic functions (Gibbs energy, enthalpy, and entropy) of the dissolution processes were computed using the van’t Hoff and Gibbs equations. The enthalpy-entropy relationship for 4-NA was non-linear in the plot of enthalpy vs. Gibbs energy of solution with negative slopes from neat water to the mixture w 1 = 0.10 and from w 1 = 0.20 to neat ethanol but positive slope from w 1 = 0.10 to w 1 = 0.20. Therefore, the driving mechanism for 4-NA transfer processes is the entropy in water-rich mixtures. Additionally, by means of the inverse Kirkwood-Buff integrals is observed that 4-NA is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by ethanol molecules in the mixtures of 0.23 ≤ x 1 ≤ 1.00.

Solubility, dissolution thermodynamics and preferential solvation of sulfadiazine in (N-methyl-2-pyrrolidone + water) mixtures

Solubility of sulfadiazine in {N-methyl-2-pyrrolidone (NMP) + water} mixtures from 278.15 K to 313.15 K has been determined and correlated by means of the Jouyban-Acree model. Discontinuous solubility trends are observed in NMP-rich mixtures at low temperatures. By using the van't Hoff and Gibbs equations the respective apparent thermodynamic quantities for the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy, were calculated. Non-linear enthalpy–entropy relationships were observed in the plot of enthalpy vs. Gibbs energy exhibiting negative but variant slopes in the composition region 0.00 < w1 < 0.60 and variant negative and positive slopes in the other mixtures for the first case. Otherwise, a variant negative slope from neat water to w1 = 0.80 but a positive slope from this mixture to neat NMP were observed for the second case. Based on the inverse Kirkwood-Buff integrals it follows that sulfadiazine is preferentially solvated by water molecules in water-rich mixtures but preferentially solvated by NMP molecules in mixtures 0.17 < x1 < 1.00 at 313.15 K.