Determination and Modeling of the Solubilities of Oleanolic Acid and

Article pubs.acs.org/jced

Determination and Modeling of the Solubilities of Oleanolic Acid and Ursolic Acid in Ethanol + Sodium Hydroxide + Water Mixed Solvents from T = 283.2 to 323.2 K Jie-Ping Fan,*,†,‡ Ya-Hui Cao,† Xue-Hong Zhang,§ Dai-Quan Jiang,† and Jia-Xin Yu† †

School of Resource, Environmental and Chemical Engineering, Nanchang University, Nanchang 330031, China Key Laboratory of Poyang Lake Ecology and Bio-Resource Utilization of Ministry of Education, Nanchang University, Nanchang 330031, China § School of Foreign Language, Nanchang University, Nanchang 330031, China ‡

S Supporting Information *

ABSTRACT: The solubilities of oleanolic acid (OA) and ursolic acid (UA) in ethanol + sodium hydroxide + water mixed solvents were measured at different temperatures (283.2, 298.2, 293.2, 298.2, 303.2, 308.2, 313.2, 318.2, and 323.2 K). The solubility of OA in the mixed solvents increased with temperature. However, the solubility of UA in the mixed solvents first increased with temperature, and then decreased with temperature. The solubilities of both OA and UA increased with the initial mole fraction of ethanol in the mixed solvents. The addition of NaOH could improve the solubilities of OA and UA in the aqueous ethanol solution. The solubility of OA was correlated with temperature by the van’t Hoff model, the modified Apelblat model and the λh model, and the results indicated that the λh model had better correlation. The solubility of UA was correlated with temperature only by an empirical cubic equation. gal,6 antiparasitic,7 antioxidative,8 immunomodulatory, and anti-HIV9,10 as well as anticancer properties are particularly notable. At present, OA and UA are obtained mainly from plant extracts due to their complicated structures which are difficult to synthesize. The knowledge about their solubilities in various solvents is very important to design a method for separation and purification of OA and UA.11 We have reported the solubilities of OA and UA in some organic solvents and ethanol + water mixed solvents,12,13 and the solubilities of OA and UA in water, alkaline solution, or ethanol + water mixed solvents have also been reported only at room temperature by other groups.14,15 Sodium hydroxide (NaOH) is often used to change the solubility of acid compounds because they can react with each other.11 In order to investigate the effect of NaOH on the dissolution of OA and UA, therefore, as a continuation of our

1. INTRODUCTION Oleanolic acid (OA) and ursolic acid (UA) (Figure 1) are pentacyclic triterpene acids widely found in plants, herbs, and other foods, and the two triterpene acids and their derivatives have attracted much attention due to their many pharmacological activities.1,2 Among these activities of OA and UA, their anti-inflammatory,3 hepatoprotective,4 antidiabetic,5 antifun-

Received: July 25, 2017 Accepted: September 27, 2017

Figure 1. Chemical structure of oleanolic acid (OA) and ursolic acid (UA). © XXXX American Chemical Society

A

DOI: 10.1021/acs.jced.7b00686 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

previous work,12,13 in this work the solubilities of OA and UA in ethanol + NaOH + water mixtures with different initial compositions over a temperature range of T = 283.2 to 323.2 K were determined by high performance liquid chromatography (HPLC) analysis method. Furthermore, the solubility data of OA was correlated by several models, including the van’t Hoff model, the modified Apelblat model, λh model, Jouyban−Acree model, Ma and Sun models, whereas the solubility of UA was correlated only by an empirical cubic model.

α=

Table 1. Sample Provenance and Mass Fraction Purity analysis method

UA

≥0.980

HPLC

OA

≥0.980

HPLC

Ethanol

≥0.995

GC

NaOH

≥0.96

Titration

chemicals

a

(1)

where me, mn, and mw represent the mass of ethanol, NaOH, and water, respectively; Me, Mn, and Mw are the molar mass of ethanol, NaOH, and water, respectively. The solubility was measured according to our previous work.16 First, an excess solid solute (OA or UA) was added into a vial with about 15.0 mL solvent, which was stoppered and sealed up with tape to prevent the solvent from escaping. Second, the vial was placed in a low temperature thermostatic reaction bath (type DFY5/40, Gongyi Yuhua Instrument Co., Ltd., China) with an uncertainty of ±0.1 K. The solution in the vial was stirred by an electric magnetic stirrer for about 48 h to make sure of the achievement of equilibrium, and then stood for another 12 h to obtain a upper clear saturated solution. Third, the solution about (0.4 to 0.8) mL in each vial was sampled with a preweighed and preheated syringe attached with a filter membrane (0.22 μm). The mass of the syringe with the saturated solution was measured on an analytical balance (type FA1104N, Shanghai, China) with a deviation of 0.1 mg. In order to prevent the solvent from escaping the needle was sealed with a silicon rubber during the weighing process. Finally, the solution in the injector which was thoroughly washed with methanol was added into a volumetric flask, and then the elution was also transferred into the volumetric flask. The solution in the volumetric flask was neutralized by hydrochloric acid and diluted with methanol to the mark, and then the amount of OA or UA in the solution was measured by HPLC. All of the experiments were conducted at least twice, and three samples were taken from each solvent at each temperature. In this work, the combined standard uncertainty was used to describe the standard uncertainties of the experimental solubility, and all of the relative standard uncertainties were within the range of 0.3 to 9.0%. The mole fraction solubility of OA or UA (x) in each solvent can be calculated by eq 2.

2. EXPERIMENTAL SECTION 2.1. Materials. The materials used in this article are listed in Table 1, all of which were used in experiments without any

mass fraction purity

me /Me me /Me + mn /M n + m w /M w

provenance Shananxi Sciphar Biotechnology Co. Ltd., Shanxi, China Shananxi Sciphar Biotechnology Co. Ltd., Shanxi, China Hengxin ChemicalPreparation Co. Ltd., Tianjin, China Hengxin Chemical Preparation Co. Ltd., Tianjin, China

High performance liquid chromatography. bGas chromatography.

further purification. Double-distilled water was prepared using a SZ-93 automatic dual water distiller (Shanghai Yarong biochemical instrument plant), and its purity was verified by pH and conductivity. 2.2. Solubility Measurements. One gram NaOH was dissolved in 99.0 g aqueous ethanol solution with different ethanol mass fraction of β (0.75, 0.65, 0.55, 0.45, 0.35, or 0.25) to obtain the ethanol + NaOH + water mixed solvent with different initial ethanol mole fraction of α (0.5351, 0.4174, 0.3210, 0.2407, 0.1728, or 0.1154). The initial ethanol mole fraction (α) in the mixture solvent without solutes can be calculated by eq 1.

x=

ms /Ms ms /Ms + me /Me + mn /M n + m w /M w

(2)

Figure 2. Representative DTG plots of OA (a) and UA (b) standard and precipitates in the mixed solvent. A: standard; B: α = 0.4174 at 308.2 K; C: α = 0.4174 at 323.2 K; D: α = 0.5351 at 308.2 K; E: α = 0.5351 at 323.2 K. B



Article

Figure 3. Representative PXRD patterns of OA (a) and UA (b) and precipitates in the mixed solvent. A: standard; B: α = 0.4174 at 308.2 K; C: α = 0.4174 at 323.2 K; D: α = 0.5351 at 308.2 K; E: α = 0.5351 at 323.2 K.

where ms, me, mn, and mw represent the mass of the solute, ethanol, NaOH, and water, respectively; Ms, Me, Mn, and Mw are the molar mass of the solute, ethanol, NaOH, and water, respectively. In order to investigate the effect of NaOH concentration, the solubilities of UA and OA were also measured in ethanol aqueous solution (β = 0.45 and 0.35) with different NaOH mass fractions (φ = 0, 0.010, 0.020. 0.025, and 0.030) at 298.2 K. 2.3. Evaluation of Data Correlation by the Models. The relative average deviation (RAD) and the root-meansquare deviation (RMSD) were employed to evaluate the accuracy and predict ability of some models which were used to correlate the solubility data of OA and UA in the mixed solvents, and RAD and RMSD can be calculated by eqs 3 and 4, respectively. RAD =

1 n

n

∑ i=1

xic − xi xi

⎡ ∑n (x c − x )2 ⎤1/2 i i ⎥ RMSD = ⎢ i = 1 ⎢⎣ ⎥⎦ n

collected on a Bede D1 diffractometer (Bede, UK) with Cu Ka radiation (k = 0.154056). TGA study was carried out using TGA 4000 (PerkinElmer, USA).

3. RESULTS AND DISCUSSION 3.1. Characterization of OA and UA. After sampling, the precipitates were separated from the solvent, and washed Scheme 1. Dissolution Scheme of UA or OA in Ethanol + Sodium Hydroxide + Water Mixed Solvents

successively by water and methanol to remove residual solvent. The precipitates were characterized by PXRD and differential thermogravimetric (DTG) analysis. The representative DTG curves of OA and UA standards and their precipitates in different solvents were presented in Figure 2. Compared with the DTG curve of OA standard in Figure 2a, the DTG curves of the precipitates in each solvent exhibited a new DTG peak at about 460 °C which could be ascribed to the thermal decomposition of sodium salt of OA formed during dissolving, so the results showed that OA could reacted with NaOH to form sodium salt (OANa) which coexisted with OA in the precipitate. However, compared with the DTG curve of UA standard in Figure 2b, the DTG curves of the precipitates in each solvent exhibited a few changes, indicating a little sodium salt of UA (UANa) coexisted with UA in the precipitate. The phenomena were completely proved by the composition data (shown in Table S1) of the precipitates calculated from the TG data. As shown in Table S1, the main component in the precipitates equilibrated with the saturated solution during the dissolution of OA was OANa, while the main component in the precipitates during the dissolution of UA was UA.

(3)

(4)

where n is the number of experimental points, xic and xi represent the calculated and experimental mole fraction solubility of OA or UA, respectively. 2.4. HPLC Conditions. The amount of OA or UA was determined by HPLC (Agilent 1100, Agilent Technologies, USA) which was composed of a vacuum degasser (type G1379A), a quaternary pump (typeG1311A), an auto sampler (type G1313A), and a diode-array detector (type G1315A). The detection wavelength was 210 nm, and the separation was performed on a Hypersil ODS column (4.6 × 200 mm, 5 μm) at 303.2 K with an acetonitrile−water mobile phase (90:10, v/ v) at a flow rate of 1.0 mL min−1. 2.5. Powder X-ray Diffraction (PXRD) and Thermogravimetric Analysis (TGA) Conditions. PXRD patterns were C



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Table 2. Experimental Mole Fraction Solubility of OA and UA (x) in Mixed Solvents with Various Initial Ethanol Mole Fractions (α) at Different Temperatures (p = 101.1 kPa)a T/Kb

α = 0.5351c

α = 0.4174

283.2 288.2 293.2 298.2 303.2 308.2 313.2 318.2 323.2

0.4342 ± 0.0071e 1.0465 ± 0.0051 1.262 ± 0.015 1.841 ± 0.019 2.551 ± 0.024 3.443 ± 0.059 5.162 ± 0.048 5.813 ± 0.056 6.43 ± 0.18

0.3802 ± 0.0047 0.5877 ± 0.0023 0.6843 ± 0.0059 1.271 ± 0.013 2.380 ± 0.034 2.974 ± 0.029 4.731 ± 0.044 5.772 ± 0.093 5.813 ± 0.061

283.2 288.2 293.2 298.2 303.2 308.2 313.2 318.2 323.2

4.2817 ± 0.0019 4.882 ± 0.019 5.756 ± 0.071 6.282 ± 0.071 7.370 ± 0.077 8.41 ± 0.15 8.100 ± 0.074 7.871 ± 0.095 6.080 ± 0.055

4.196 ± 0.014 4.398 ± 0.019 4.596 ± 0.065 4.850 ± 0.048 5.700 ± 0.050 6.952 ± 0.073 6.430 ± 0.061 6.034 ± 0.091 5.79 ± 0.18

α = 0.3210 103 x of OAd 0.2151 ± 0.0040 0.2540 ± 0.0090 0.392 ± 0.013 0.771 ± 0.016 1.584 ± 0.038 2.243 ± 0.027 2.731 ± 0.065 4.43 ± 0.16 4.904 ± 0.047 103 x of UA 3.9521 ± 0.0020 4.20 ± 0.19 4.212 ± 0.081 4.250 ± 0.037 5.590 ± 0.049 6.180 ± 0.072 6.040 ± 0.075 5.847 ± 0.053 4.460 ± 0.095

α = 0.2407

α = 0.1728

α = 0.1154

0.1377 ± 0.0027 0.1999 ± 0.0044 0.2381 ± 0.0096 0.3192 ± 0.0041 0.7243 ± 0.0091 1.262 ± 0.031 2.451 ± 0.080 3.052 ± 0.039 3.174 ± 0.079

0.0546 ± 0.0012 0.0673 ± 0.0017 0.1141 ± 0.0018 0.1729 ± 0.0050 0.1952 ± 0.0067 0.4653 ± 0.0058 1.124 ± 0.027 1.339 ± 0.023 1.712 ± 0.019

0.001246 ± 0.000050 0.002531 ± 0.000049 0.005758 ± 0.000058 0.006967 ± 0.000053 0.01473 ± 0.00024 0.02741 ± 0.00034 0.02893 ± 0.00045 0.04660 ± 0.00028 0.0923 ± 0.0017

2.2981 ± 0.0019 2.6472 ± 0.0020 2.740 ± 0.097 4.000 ± 0.046 4.770 ± 0.065 5.330 ± 0.050 5.256 ± 0.062 5.210 ± 0.071 4.360 ± 0.072

0.980 ± 0.025 0.9909 ± 0.0045 1.027 ± 0.045 2.910 ± 0.034 4.199 ± 0.081 4.710 ± 0.047 5.109 ± 0.053 5.171 ± 0.071 2.320 ± 0.047

0.02291 ± 0.00063 0.03986 ± 0.00069 0.04365 ± 0.00059 0.05101 ± 0.00067 0.1797 ± 0.0036 0.2068 ± 0.0057 0.2120 ± 0.0028 0.2316 ± 0.0026 0.2262 ± 0.0015

a Standard uncertainty u is u(p) = 1.0 kPa. bStandard uncertainty u is u(T) = 0.1 K. cα is the initial mole fraction of ethanol in the solvent mixtures, and standard uncertainty u is u(α) = 0.0001. dx denotes the mole fraction solubility of OA or UA. eThe standard uncertainty (±) of solubility was calculated using combined standard uncertainty.

Figure 4. Mole fraction solubility (x) of (A) OA and (B) UA in ethanol+NaOH+ water) mixed solvents with various initial mole fractions (α) of ethanol at different temperatures (T).

The representative PXRD patterns of OA and UA standards and precipitates in different solvents were presented in Figure 3, and the results of PXRD were similar to those of DTG. Compared with the PXRD pattern of OA standard, the PXRD patterns of the precipitates in the mixed solvent exhibited significant changes, indicating that there was a lot of OANa in the precipitates. The diffraction peaks (2θ = 6.02, 9.65, and 11.57) in Figure 3a can be assigned to the crystalline structure of OANa. However, compared with the PXRD pattern of UA standard, the PXRD patterns of the precipitates in the mixed solvent exhibited a few changes, indicating that there was a little UANa in the precipitates. The diffraction peaks (2θ = 8.84 and 19.75) can be attributed to the crystalline structure of UANa. 3.2. Solubility Values. The equilibrium during the dissolution of UA or OA was assumed in Scheme 1. From the Scheme 1, the dissolution of UA or OA included three equilibria, a solid−liquid equilibrium of UA or OA, a

solid−liquid equilibrium of UANa or OANa, and a chemical equilibrium between UANa or OANa and its sodium salt. In Table S1, the composition of precipitates equilibrated with the saturated solution proved that UA or OA could reacted with NaOH, then both UA or OA and its sodium salt were involved in the solid−liquid equilibrium. The mole fraction solubilities of OA and UA along with the standard uncertainties in the mixed solvents at different temperatures ranging from 283.2 to 323.2 K were presented in Table 2 and plotted in Figure 4. First, compared to our previous work,13 we found that the addition of NaOH would improve dissolution of OA and UA in the aqueous ethanol solution (NaOH = 0). We found an interesting phenomenon, the solubility of UA was lower than that of OA below 318.2 K in the aqueous ethanol solution reported in our previous work,13 however the solubility of UA was higher than that of OA below 318.2 K in the ethanol + NaOH + water mixed solvents in this work. These results D


0.5351 0.4174 0.3210 0.2407 0.1728 0.1154 = = = = = =

α α α α α α

showed the formation of sodium salt can improve the solubility of UA and OA in aqueous ethanol, and UANa had higher solubility than OANa, so the sodium salt had more important impact on the dissolution of UA and OA. Second, the results indicated that the solubility of OA in the ethanol + NaOH + water mixed solvents had a positive correlation with temperature and the initial mole fraction of ethanol. The solubility of UA increased with the initial ethanol mole fraction, however it first increased with temperature, and then decreased with temperature. These tendencies were consisted with the mole fraction changes of the sodium salt in the precipitates equilibrated with the saturated solution. As seen from the data in Table 2 and Table S1, in the same solvent system for OA dissolution, the system had smaller OANa mole fraction in the precipitate and larger solubility at higher temperature than those at lower temperature, e.g., in the mixed solvent (α = 0.4174) system, the mole fraction of OANa (0.5453) at 323.2 K was lower than that (0.8252) in the precipitate at 308.2 K. However, in the same solvent system for UA dissolution, the system had smaller UANa mole fraction in the precipitate and larger solubility at lower temperature than those at higher temperature, e.g., in the mixed solvent (α = 0.5351) system, the mole fraction of UANa (0.1092) at 308.2 K was lower than that (0.1338) in the precipitate at 323.2 K. So the results showed that the solubility of UA or OA was closely related to the amount of the sodium salt in the precipitate equilibrated with the saturated solution. The tendency of the solubility of UA with temperature can be explained by the property of UANa or salting out action, the detail reasons will be studied in our future work. The effect of the NaOH concentration on the solubilities of UA and OA were also presented in Table S2 and Figure S1. Compared to the solubility in the aqueous ethanol solution (NaOH = 0), the solubilities of OA and UA significantly increased after addition of NaOH. However, excessive addition of NaOH would decrease the solubilities of OA and UA due to the salting out action. 3.3. Correlation of Solubility with Temperature. In this work, the van’t Hoff model (eq 5),17−21 the modified Apelblat model (eq 6),17−21 and λh model (eq 7)17−22 were used to correlate the solubility of OA in different solvents with temperature. a ln x1 = +b (5) T /K

α is the mole fraction of ethanol in the solvent mixtures, and standard uncertainties u is u(α) = 0.0001. bA, B, and C are the parameters of the modified Apelblat model. cR2 is the determinate coefficient. RAD is the relative average deviation. eRMSD is the root-mean-square deviation. fa and b are the parameters of the van’t Hoff model. gλ and h are the parameters of the λh model.

2.1275 2.6942 2.9703 2.5383 1.2248 0.0365 0.0747 0.1580 0.3458 0.2621 0.2574 0.3800 0.9862 0.9777 0.9583 0.9532 0.9521 0.9767 −194.6110 −274.9290 11.7636 −289.3270 −145.6280 212.6172 −65163.9518 −90826.0831 −2709.2346 −96994.0006 −53615.9905 56824.8223 1321.1097 1864.5271 −64.8336 1966.1949 1001.1030 −1413.6920

10 RMSD RAD

R C B A

a

solvents

Article

ln x1 = A +

B + C ln(T /K ) T /K

⎡ ⎛1 λ(1 − x1) ⎤ 1 ⎞ ln⎢1 + ⎥ = λh⎜ − ⎟ x1 Tm ⎠ ⎦ ⎣ ⎝T

(6)

(7)

where x1 is the mole fraction solubility of OA at temperature T (K); a, b, A, B, C, λ, and h are parameters of the models. All models were fitted using the nonlinear regression, and the parameters together with the RAD and RMSD of the models were listed in Table 3. The fitting plots of the models were shown in Figure 5. As shown in Table 3 and Figure 5, overall the λh model was the most suitable method for correlating the experimental solubility of OA among the three models, because the λh model had the highest correlation coefficient (R2) and the smallest RAD and RMSD. As seen from Figure 6, the solubility of UA in the mixed solvents first increased with temperature, and then decreased

d

a

3.8544 5.1482 2.8752 3.6285 1.4386 0.0431 0.1880 0.3112 0.3269 0.4193 0.3509 0.1669 0.9612 0.9307 0.9665 0.9181 0.9434 0.9723 898.2323 516.7868 184.5030 210.2189 70.6490 125.6063 5.3699 10.3321 34.5871 31.3405 112.7286 79.2920 3.8656 5.1600 2.8826 3.6322 1.4397 0.0431 0.1888 0.3121 0.3278 0.4193 0.3505 0.1662 0.9609 0.9303 0.9663 0.9179 0.9433 0.9723 9.9133 11.4498 14.4524 14.7313 18.3933 21.4629

λ 10 RMSD RAD R b a

−4808.2886 −5323.0197 −6366.1944 −6579.7334 −7961.1231 −9954.1537

104 RMSD RAD R2 h

λh model

g

4 2

van’t Hoff model

f e

4 d

modified Apelblat model

2c b

Table 3. Parameters of the Modified Apelblat Model, van’t Hoff Model, and λh Model for OA in the Investigated Solvents with Various Initial Mole Fractions (α) of Ethanol


E



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Figure 5. Mole fraction solubility profiles of OA (x) correlated by the modified Apelblat model (A), the van’t Hoff model (B), and the λh model (C).

solubility of UA in the mixed solvents increased with the initial mole fraction of ethanol, and however it first increased and then decreased with the temperature. The results also indicated that the addition of NaOH could improve dissolution of OA and UA in the aqueous ethanol solution. The DTG and PXRD analysis showed that sodium salts of the solutes were formed during dissolving, which had an important effects on the dissolution of OA and UA. To correlate the solubility of OA with temperature, the λh model showed a better correlation than the modified Apelblat model and van’t Hoff model. The solubility of UA was only correlated by an empirical cubic model.

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Figure 6. Mole fraction solubility profiles of UA (x) correlated by the empirical cubic model.

with temperature, therefore the common models, such as van’t Hoff model, the modified Apelblat model, or λh model, could not correlate the data of UA. So an empirical cubic model (eq 8) was used in this work. x1 = a0T 3 + b0T 2 + c0T + d0

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.7b00686. The compositions (mole fraction) of representative precipitates equilibrated with the saturated solution during the dissolution of OA or UA, experimental mole fraction solubility of OA and UA (x) in mixed solvents with various initial NaOH mass fractions (φ) at 298.2 K, and effect of NaOH mass fraction in ethanol aqueous solution (β = 0.45 and 0.35) on the mole fraction solubility (x) of OA and UA at 298.2 K (PDF)

(8)

where x1 is the mole fraction solubility of UA at temperature T (K); a0, b0, c0, and d0 are parameters of the model. The parameters together with the RAD and RMSD of the mode (eq 8) were listed in Table 4. The fitting plots of the models were shown in Figure 6. The fitting results of the empirical cubic model (eq 8) were not bad and could be acceptable.

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AUTHOR INFORMATION

Corresponding Author

4. CONCLUSIONS The solubilities of OA and UA in the ethanol + NaOH + water mixed solvents were determined at different temperatures ranging from 283.2 to 323.2 K. OA had a positive correlation with temperature and the initial mole fraction of ethanol. The

* E-mail: [email protected]; Tel.: 086-791-83968583; Fax: 086-791-83968594. ORCID

Jie-Ping Fan: 0000-0002-9410-3670

Table 4. Parameters of the Cubic Function Model Correlated from Experimental Data for UA in the Investigated Solvents with Various Mole Fractions (α) ethanol+sodium hydroxide+water α α α α α α

= = = = = =

a

0.5351 0.4174 0.3210 0.2407 0.1728 0.1154

a0b −3.06 −2.15 −3.07 −2.27 −5.37 −1.41

× × × × × ×

b0 10−07 10−07 10−07 10−07 10−07 10−08

2.72 1.93 2.76 2.03 4.83 1.27

× × × × × ×

10−04 10−04 10−04 10−04 10−04 10−05

c0

d0

R2

RAD

104 RMSD

−0.0807 −0.0578 −0.0828 −0.0605 −0.1445 −0.0038

7.9611 5.7564 8.2626 5.9921 14.3932 0.3841

0.9734 0.8468 0.8863 0.9655 0.9513 0.9076

0.0249 0.0372 0.0401 0.0368 0.1240 0.2147

1.7773 2.8254 2.3094 1.9061 2.9639 0.2085

α is the mole fraction of ethanol in the solvent mixtures, and standard uncertainties u is u(α) = 0.0001. ba0, b0, c0,, d0 are the parameters of the empirical cubic equation. a

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Notes

(13) Fan, J. P.; Kong, T.; Zhang, X. H.; Zhang, L.; Tong, S.; Tian, Z. Y.; Zhu, J. H. Solubilities of oleanolic acid and ursolic acid in (ethanol + water) mixed solvents from T = (292.2 to 328.2) K. J. Chem. Thermodyn. 2012, 47, 372−375. (14) Jin, I. J.; Ko, Y. I.; Kim, Y. M.; Han, S. K. Solubilization of oleanolic acid and ursolic acid by cosolvency. Arch. Pharmacal Res. 1997, 20, 269−274. (15) Jäger, S.; Winkler, K.; Pfüller, U.; Scheffler, A. Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L. Planta Med. 2007, 73, 157−162. (16) Fan, J. P.; Zheng, B.; Liao, D. D.; Yu, J. X.; Cao, Y. H.; Zhang, X. H.; Zhu, J. H. Determination and modeling of the solubility of (limonin in methanol or acetone+water) binary solvent mixtures at T = 283.2 to 318.2 K. J. Chem. Thermodyn. 2016, 98, 353−360. (17) Fan, J. P.; Yang, X. M.; Xu, X. K.; Xie, Y. L.; Zhang, X. H. Solubility of rutaecarpine and evodiamine in (ethanol + water) mixed solvents at temperatures from 288.2 to 328.2 K. J. Chem. Thermodyn. 2015, 83, 85−89. (18) Jiang, S.; Qin, Y.; Wu, S.; Xu, S.; Li, K.; Yang, P.; Zhao, K.; Lin, L.; Gong, J. Solubility correlation and thermodynamic analysis of sorafenib free base and sorafenib tosylate in monosolvents and binary solvent mixtures. J. Chem. Eng. Data 2017, 62, 259−267. (19) Aniya, V.; De, D.; Mohammed, A. M.; Thella, P. K.; Satyavathi, B. Measurement and modeling of solubility of para-tert-butylbenzoic acid in pure and mixed organic solvents at different temperatures. J. Chem. Eng. Data 2017, 62, 1411−1421. (20) Shakeel, F.; Haq, N.; Salem-Bekhit, M. M.; Raish, M. Solubility and dissolution thermodynamics of sinapic acid in (DMSO+ water) binary solvent mixtures at different temperatures. J. Mol. Liq. 2017, 225, 833−839. (21) Shan, Y.; Fu, M.; Yan, W. Solubilities of 4′, 5, 7Triacetoxyflavanone in fourteen organic solvents at different temperatures. J. Chem. Eng. Data 2017, 62, 568−574. (22) Ha, E. S.; Kuk, D. H.; Ha, D. H.; Sim, W. Y.; Baek, I. H.; Kim, J. S.; Kim, M. S. Determination and correlation of solubility of sarpogrelate hydrochloride in eight solvents at different temperatures. J. Mol. Liq. 2017, 237, 141−145.

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support from the National Natural Science Foundation of China (Nos. 21366019, 20806037, and 20876131), Jiangxi Province academic and technical leaders of major academic disciplines (20162BCB22010), Key Laboratory of Coa1 Gasification and Energy Chemical Engineering of Ministry of Education (2016KY11-049), Jiangxi Province Young Scientists (Jinggang Star) Cultivation Plan (20112BCB23002), Jiangxi Province Higher School Science and Technology Landing Plan Projects (No. KJLD13012), Special Funds for Graduate Student Innovation in Jiangxi Province (No. YC2014-S013), and Jiangxi Province Undergraduate Innovation and Entrepreneurship Training Program (No. 201310403040) are gratefully acknowledged.

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REFERENCES

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Determination and Modeling of the Solubilities of Oleanolic Acid and

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