Article pubs.acs.org/jced
Solubilities of Rutaecarpine in Twelve Organic Solvents from (283.2 to 323.2) K Jie-Ping Fan,*,†,‡ Yan-Long Xie,† Ze-You Tian,† Rui Xu,† Yu Qin,† Lie Li,† Jian-Hang Zhu,†,‡ and Xue-Hong Zhang§ †
Key Laboratory of Poyang Lake Ecology and Bio-Resource Utilization of Ministry of Education, ‡School of Environmental and Chemical Engineering, and §School of Foreign Language, Nanchang University, Nanchang 330031, China S Supporting Information *
ABSTRACT: The solubilities of rutaecarpine in 12 organic solvents (dichloromethane, ethyl acetate, acetone, trichloromethane, ethoxyethane, butyl alcohol, isopropyl alcohol, ethyl alcohol, methyl alcohol, cyclohexane, hexane, and pentane) were measured over the temperature range of (283.2 to 323.2) K. The solubilities of rutaecarpine in selected organic solvents increase with the increasing of the temperature and were correlated by the modified Apelblat equation and a simplified thermodynamic equation. The dissolution enthalpy and entropy of rutaecarpine in these solvents were calculated using the van’t Hoff equation. The results showed that the dissolution process was endothermic and entropy-driven.
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INTRODUCTION
EXPERIMENTAL SECTION Materials. The rutaecarpine (Figure 1, CAS No.: 84-26-4) (≥ 0.98 purity) was purchased from Shaanxi Sciphar
Rutaecarpine is one of the main active alkaloids of Evodiae f ructus which has long been used to treat gastrointestinal disorders, anti-inflammatory, headaches, and postpartum hemorrhage.1−3 Rutaecarpine possesses extensive biological and pharmacological properties, such as the antihypertensive, antithrombotic effects, and cardiovascular biological effects.3 To obtain a high yield and separation efficiency in the separation and purification processes, the knowledge of the solubility of rutaecarpine in different solvents is very important.4−6 Only at 298.15 K, the solubilities of rutaecarpine with the different purities were measured in several solvents (ethyl alcohol, isopropyl alcohol, Tween-80, or PEG-400, et al.) by Chen et al.;7 moreover, Choi et al.8 reported the solubilities of rutaecarpine in water, ethyl alcohol, various oils, or surfactant at room temperature. However, the solubilities of rutaecarpine in these organic solvents were not systematically studied. Therefore, in this work, the solubilities of rutaecarpine in dichloromethane, ethyl acetate, acetone, trichloromethane, ethoxyethane, butyl alcohol, isopropyl alcohol, ethyl alcohol, methyl alcohol, cyclohexane, hexane, and pentane were measured at T = (283.2, 293.2, 303.2, 313.2, and 323.2) K by an analytical method in which the various phases in equilibrium are characterized by chemical analysis.9 Because of the boiling points of dichloromethane, ethoxyethane, and pentane were lower than 313.2 K, the solubilities of rutaecarpine in these solvents were measured at T = (283.2, 285.2, 293.2, 298.2, and 303.2) K. The solubility in this article is defined as mole fraction equilibrium solubility of rutaecarpine in selected solvents at different temperatures. © XXXX American Chemical Society
Figure 1. Structure of rutaecarpine.
Biotechnology Co. Ltd., Xi’an, China. All organic solvents were analytical grade (the Damao Chemical Reagents Co., Tianjin, China) and were used without further treatment. The detailed information about the purity of the solvents is listed in Table 1. Solubility Measurement. The solubilities of rutaecarpine in selected solvents were measured by an analytical method according to a literature method10,11 and our previous works.5,6 After an equilibrium state was reached, the composition of the solutions was characterized by high-performance liquid chromatography (HPLC). More details of the experimental setups and procedures have been described in our previous works.5,6 In the present work, the relative uncertainties of the experimental data were within ± 0.029 which results from the Received: February 5, 2013 Accepted: May 30, 2013
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Table 1. Purity and CAS Number of the Solvents solvent
mass fraction
CAS no.
solvent
mass fraction
CAS no.
dichloromethane ethyl acetate acetone trichloromethane ethoxyethane butyl alcohol
0.995 0.995 0.995 0.990 0.995 0.995
75-09-2 141-78-6 67-64-1 67-66-3 60-29-7 71-36-3
isopropyl alcohol ethyl alcohol methyl alcohol cyclohexane hexane pentane
0.997 0.997 0.995 0.995 0.950 0.990
67-63-0 64-17-5 67-56-1 110-82-7 110-54-3 109-66-0
Table 2. Experimental Mole Fraction Equilibrium Solubility (x) of Rutaecarpine in Various Solvents over the Range T = (283.2 to 323.2) K at Atmospheric Pressure Ta/K 283.2 288.2 293.2 298.2 303.2 283.2 293.2 303.2 313.2 323.2 283.2 293.2 303.2 313.2 323.2 283.2 293.2 303.2 313.2 323.2 a
104 x Dichloromethane 14.1913 16.1787 18.2076 19.5889 22.4284 Trichloromethane 2.8708 5.1061 9.2215 21.0776 48.4972 Isopropyl Alcohol 0.7941 1.2747 1.9153 2.9189 4.5912 Cyclohexane 0.0624 0.1143 0.1728 0.2517 0.3777
Ta/K
104 x Ethyl Acetate 10.3889 12.3026 15.2513 19.4846 25.5032 Ethoxyethane 2.3966 2.7257 3.1280 3.9645 4.5442 Ethyl Alcohol 0.9751 1.4340 2.0336 2.7886 3.9432 Hexane 0.0617 0.1212 0.1625 0.2625 0.3969
283.2 293.2 303.2 313.2 323.2 283.2 288.2 293.2 298.2 303.2 283.2 293.2 303.2 313.2 323.2 283.2 293.2 303.2 313.2 323.2
Ta/K 283.2 293.2 303.2 313.2 323.2 283.2 293.2 303.2 313.2 323.2 283.2 293.2 303.2 313.2 323.2 283.2 288.2 293.2 298.2 303.2
104 x Acetone 7.3542 9.7190 12.8823 14.8860 19.6402 Butyl Alcohol 1.8591 2.6615 3.6922 5.7739 9.5510 Methyl Alcohol 0.6609 0.8181 1.1669 1.6067 2.2914 Pentane 0.0431 0.0689 0.0967 0.1530 0.2474
Standard uncertainty u is u(T) = ± 0.1 K. The relative standard uncertainty for the mole fractions ur(x) is 0.029.
uncertainties in the temperature measurement, weighing procedure, and instabilities of the water bath. Analytical Procedures. The structure and purity of rutaecarpine were identified by the UV, 1HNMR spectra, and HPLC (Figures S1 and S2). All data are in very good agreement with previously published reference data.12−14 The concentrations of rutaecarpine were determined by HPLC (Agilent 1100, Agilent Technologies, USA). All chromatographic analysis was performed on a Hypersil BDS-C18 column (4.6 × 200 mm, 5 μm) at 303.2 K. Detection was at the wavelength of 345 nm. The mobile phase was methyl alcohol/ water (68:32, v/v) at a flow rate of 1.0 mL·min−1.
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Figure 2. Apelblat plots of the mole fraction equilibrium solubility (ln x) of rutaecarpine in different solvents (■, dichloromethane; ●, ethyl acetate; ▲, acetone; ▼, trichloromethane; ◀, ethoxyethane; ▶, butyl alcohol; ◆, isopropyl alcohol; ▲, ethyl alcohol; ▼, methyl alcohol; ★, cyclohexane; ●, hexane; ■, pentane) verse 1/T with a curved line to correlate the data.
RESULTS AND DISCUSSION The solubility data of rutaecarpine in trichloromethane, dichloromethane, acetone, ethyl acetate, butyl alcohol, isopropyl alcohol, ethyl alcohol, methyl alcohol, ethoxyethane, cyclohexane, pentane, and hexane at various temperatures are listed in Table 2 (see also Figure 2). The solubilities of rutaecarpine in dichloromethane, ethoxyethane, and pentane were measured below 303.2 K because of the relatively lower boiling point of these solvents. The results indicated that the solubility of rutaecarpine in these solvents increased with the
rising of temperature. Compared with earlier published data,8,9 the solubilities of rutaecarpine in ethyl alcohol and isopropyl alcohol are approximate to those in this work, and the solubilities in other organic solvents mentioned in this work were not measured in the previous report. According to the B
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Table 3. Parameters of Equations 1 and 2 Correlated from Experimental Data for Rutaecarpine in Different Solvents eq 1
a
eq 2
solvent
A
B
104 rmsda
102 RADb
a
b
c
104 rmsda
102 RADb
dichloromethane ethyl acetate acetone trichloromethane ethoxyethane butyl alcohol isopropyl alcohol ethyl alcohol methyl alcohol cyclohexane hexane pentane
−1898.0236 −2055.7474 −2190.7425 −6443.5134 −2833.9182 −3688.7206 −3967.3401 −3166.9108 −2883.3981 −4028.3364 −4120.2617 −7353.2299
0.1516 0.3415 0.5316 14.4553 1.6424 4.3654 4.5548 1.9461 0.4890 2.2944 2.6140 13.5975
0.2570 0.6993 0.4063 3.2184 0.0894 0.4429 0.0817 0.0345 0.0641 0.0054 0.0075 0.0062
1.2090 3.8025 2.3096 11.7429 2.4924 6.5238 2.2886 0.8444 4.7425 3.6566 4.7233 3.6792
46.1695 −293.9136 33.3652 −929.5245 −506.6079 −513.6522 −142.4066 −35.9036 −349.2655 218.5737 131.4857 −763.2152
−3916.1096 11193.2574 −3669.0952 36059.7291 19455.0567 19635.3253 2649.6808 −1462.7084 12864.5002 −13766.4396 −9922.7877 26713.3721
−6.8886 43.8385 −4.8916 140.6352 76.0816 77.1749 21.8945 5.6389 52.1068 −32.2215 −19.1995 116.2835
0.2686 0.0589 0.4184 0.2830 0.0964 0.0560 0.0316 0.0256 0.0212 0.0062 0.0091 0.0030
1.2101 0.3016 2.2057 1.7254 2.1490 1.4155 1.2693 0.8546 1.7512 2.8033 5.1648 2.5830
rmsd is the root-mean-square deviation calculated by eq 3. bRAD is the relative average deviations calculated by eq 4.
solubility data, the solubilities of rutaecarpine were quite diverse in different solvents. The solubilities of rutaecarpine in moderate-polarity solvent, for example, trichloromethane, dichloromethane, acetone, and ethyl acetate, are relatively higher than those in both relatively low (e.g., cyclohexane, hexane, and pentane) and high (e.g., isopropyl alcohol, ethyl alcohol, and methyl alcohol) polarity solvent. In this work, a simplified thermodynamic equation and the modified Apelblat equation were used to describe the solubility behavior of rutaecarpine. The simplified thermodynamic equation was expressed as eq 115−17 ln x =
A +B T
In Table 3 the results indicated that eqs 1 and 2 can both correlate the experimental solubility of the rutaecarpine in these solvents at various temperatures. But comparing with the rmsd’s and RADs in Table 3, the results show that the correlated results of eq 2 were a little better than those of eq 1. The van’t Hoff equation can also be used to predict solubility, which can be expressed as eq 5:19−21 ΔHd ΔSd + (5) RT R where x is the mole fraction equilibrium solubility, ΔHd and ΔSd are the dissolution enthalpy and entropy, respectively, R is the gas constant, and T is the absolute temperature. In Figure 3 ln x = −
(1)
where x is the mole fraction equilibrium solubility of rutaecarpine in the organic solvent, A and B are parameters, and T is the equilibrium temperature (K). The data for solubilities of rutaecarpine in all solvents were correlated with eq 1, and the results are shown in Table 3. The solubilities of the rutaecarpine in various solvents could be also correlated by modified Apelblat equation (eq 2):5,18,19 ln(x) = a +
b + c ln(T ) T
(2)
where a, b, and c are the parameters of the equation. The parameters of a, b, and c were obtained by using a nonlinear regression and are given in Table 3. In Figure 2 the modified Apelblat equation plots were obtained from the nonlinear fit of ln x versus 1/T. The root-mean-square deviations (rmsd’s), together with the relative average deviations (RADs) for the simplified thermodynamic equation and the modified Apelblat equation are also listed in Table 3. The rmsd is described as eq 3. ⎡ ∑n (x c − x )2 ⎤1/2 i i ⎥ rmsd = ⎢ i = 1 ⎢⎣ ⎥⎦ n
Figure 3. van’t Hoff plots of the mole fraction equilibrium solubility (ln x) of rutaecarpine in different solvents (■, dichloromethane; ●, ethyl acetate; ▲, acetone; ▼, trichloromethane; ◀, ethoxyethane; ▶, butyl alcohol; ◆, isopropyl alcohol; ▲, ethyl alcohol; ▼, methyl alcohol; ★, cyclohexane; ●, hexane; ■, pentane) verse 1/T with a straight line to correlate the data.
the van’t Hoff equation plots were obtained from the linear fit of ln x versus 1/T. The ΔHd and ΔSd of rutaecarpine were presented in Table 4, which were calculated from the slope and intercept of these plots. According to Table 4, within the experimental temperature the dissolution process of rutaecarpine in the solvent was endothermic. The positive ΔHd and ΔSd indicated that the dissolution of rutaecarpine in these solvents was an entropy-driven process.
(3)
where n was the number of experimental points; xci and xi were the calculated and experimental solubility of rutaecarpine, respectively. The RADs are calculated by eq 4:20 RAD =
1 n
n
∑ i=1
xi − xic xi
(4) C
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Province Young Scientists (Jinggang Star) Cultivation Plan (20112BCB23002), Natural Science Foundation of Jiangxi, China (No. 2007GQH1752), Natural Science Foundation of Jiangxi Province Department of Education (No. GJJ09420), Open Foundation of Key Laboratory of Poyang Lake Ecology, Bio-Resource Utilization of Ministry of Education (No. Z04998), and Special Funds for Graduate Student Innovation in Jiangxi Province (No. YC2011-S005 and YC2012-S017) are gratefully acknowledged.
Table 4. Dissolution Enthalpy (ΔHd) and Entropy (ΔSd) of Rutaecarpine Together with the Correlation Coefficients (R2) of eq 4 in Different Solvents solvent
ΔHd/(kJ·mol−1)
ΔSd/(J·mol−1·K−1)
R2
dichloromethane ethyl acetate acetone trichloromethane ethoxyethane butyl alcohol isopropyl alcohol ethyl alcohol methyl alcohol cyclohexane hexane pentane
15.7802 17.0915 18.2138 53.5714 23.5612 30.6680 32.9845 26.3297 23.9726 33.4916 34.2559 61.1348
1.2604 2.8392 4.4197 120.1814 13.6549 36.2939 37.8686 16.1799 4.0655 19.0756 21.7328 113.0496
0.9902 0.9792 0.9907 0.9774 0.9812 0.9785 0.9978 0.9993 0.9828 0.9940 0.9865 0.9941
Notes
The authors declare no competing financial interest.
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CONCLUSIONS The solubilities of rutaecarpine in 12 organic solvents have been measured over the temperature range of (283.2 to 323.2) K. The results showed that the solubilities of rutaecarpine in all selected solvents increase with the rising temperatures. The experimental data of the solubilities of rutaecarpine were correlated by a simplified thermodynamic equation with two parameters and the modified Apelblat equation with three parameters. The results indicated that the two equations can be used to correlate the solubility data of rutaecarpine, and the modified Apelblat equation is a little better than the simplified thermodynamic equation. The calculated data were in good agreement with the experimental solubility, which verified the feasibility of correlating the solubility of rutaecarpine in all selected solvents. Based on the solubility data, the ΔHd and ΔSd of rutaecarpine in the selected organic solvents were calculated by using van’t Hoff equation, the results indicated that the dissolution of rutaecarpine in the solvent was an endothermic and entropy-driven process. Comparing with our previous work,5 the structures of rutaecarpine and evodiamine are very similar, the solubilities of them in all selected solvents increase with the rising temperatures. The dissolution of them in the solvent were endothermic and entropy-driven process. The solubility of evodiamine in trichloromethane is the highest, while the solubility of rutaecarpine in dichloromethane is the highest of all selected solvents. Moreover, the solubility of evodiamine in ethoxyethane is very small, but the solubility of rutaecarpine in ethoxyethane is relatively higher. So the differences of solubility in different solvents can be used to separate evodiamine and rutaecarpine from their mixtures.
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ASSOCIATED CONTENT
S Supporting Information *
1
H NMR and UV spectra and HPLC-DAD chromatogram of rutaecarpine. This material is available free of charge via the Internet at http://pubs.acs.org.
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REFERENCES
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] (J.-P. Fan). Fax: +86 791 83969594. Tel.: +86 791 83969583. Funding
Financial support from the National Natural Science Foundation of China (No. 20806037 and 20876131), Jiangxi D
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(17) Li, Y.; Wang, F.; Xu, L.; Jin, H.; Ren, B. Solubilities of cefodizime disodium in aqueous alcohol mixtures at atmospheric pressure and different temperatures. Fluid Phase Equilib. 2010, 298, 246−252. (18) Lei, Z.; Hu, Y.; Yang, W.; Li, L.; Chen, Z.; Yao, J. Solubility of 2(2,4,6-trichlorophenoxy)ethyl bromide in methanol, ethanol, propanol, isopropanol, acetonitrile, n-heptane, and acetone. J. Chem. Eng. Data 2011, 56, 2714−2719. (19) Chen, F.; Zhao, M.; Liu, C.; Peng, F.; Ren, B. Determination and correlation of the solubility for diosgenin in alcohol solvents. J. Chem. Thermodyn. 2012, 50, 1−6. (20) Wang, K.; Hu, Y.; Yang, W.; Guo, S.; Shi, Y. Measurement and correlation of the solubility of 2,3,4,5-tetrabromothiophene in different solvents. J. Chem. Thermodyn. 2012, 55, 50−55. (21) Jim, M.; Kim, K.-J. Solubility of forms I and II of clopidogrel hydrogen sulfate in formic acid, N-methylpyrrolidone, and N,Ndimethylformamide. J. Chem. Eng. Data 2012, 57, 598−602.
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