Article
pubs.acs.org/jced
Solubility of Aloe-Emodin in Five Imidazolium-Based Ionic Liquids
Li Ge, Dan Li, Yunfei Long, Jing Su, and Kedi Yang*
School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, China
ABSTRACT: The solubility of aloe-emodin in five imidazolium-based ionic
liquids (ILs), 1-decyl-3-methylimidazolium chloride ([C10mim]Cl), 1-hexyl-
3-methylimidazolium hexafluorophosphate ([C6mim]PF6), 1-hexyl-3-meth-
ylimidazolium tetrafluoroborate ([C6mim]BF4), 1-butyl-3-methylimidazo-
lium tetrafluoroborate ([C4mim]BF4), and 1-butyl-3-methylimidazolium
bis(methylsulfonyl)amide ([C4mim]NTF2) was measured respectively from
(295.55 to 363.55) K at atmospheric pressure using a laser monitoring
observation method combined with high performance liquid chromatography
(HPLC). A simplified dual-parameters equation and λh equation were used
to correlate the experimental solubility data of aloe-emodin in investigated
ILs and exhibited good agreement.
■ INTRODUCTION
Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-9,10-anthrace-
nedione, CASRN: 481-72-1) is an important natural
anthraquinone compound widely found in plants of Aloe vera
L, Rheum Palmatum L, Cassia obtusifolia L and other species of
the asphodelaceae and the polygonaceae families. Its structural
formula is given in Figure 1. The aloe-emodin and its extract
Figure 1. Molecular structure of aloe-emodin.
has been used widely around the world in medicine, cosmetics
and toiletries.1 In recent years, the pharmacological actions of
aloe-emodin were reported to include laxative, antibacterial and
anticancer, and in particular, it was found to inhibit N-
acetyltransferase activity and gene expression in human
malignant melanoma cells and to have antiproliferative and
pro-apoptotic effects on gastric and tongue cancer cells.2−5
Aloe-emodin is sparingly soluble in water and mainly
obtained from plant materials by extraction with different
organic solvents or their mixtures. However, because of
increased safety requirements for operating personnel and
consumers, extraction by organic solvents is faced with a heavy
challenge owing to the volatility, flammable and toxicity of
these solvents. Therefore the desire to reduce the use of organic
solvents in bioactive substances extraction processes has led to
the development of alternative solvents, such as ionic liquids
(ILs). In the past decade, there has been a great interest in ILs
as separation and chemical reaction media because of their
unique physical and chemical properties of low vapor pressure
and high thermal and chemical stability, etc.6−9 Some studies
have revealed the ability of ILs to extract natural organic
© 2013 American Chemical Society 2405
compounds since Huddleston et al. reported the extraction of
substituted-benzene derivatives using ILs [Bmim]PF6 ini-
tially.10−15 As for aloe-emodin, there is no reported solubility
data in various ILs to date; data that is important in order to
select a proper IL or to simulate and design extraction
processes.
Imidazole-types ILs are frequently used media in separation
and chemical reaction processes. In the present work, the
solubility of aloe-emodin in five imidazolium-based ILs has
been measured using a laser monitoring observation method
combined with high performance liquid chromatography
(HPLC). The effects of imidazolium-based IL types and
temperature on solubility are discussed, and the solubility data
are correlated with two empirical equations.
■
EXPERIMENTAL SECTION
Materials. Aloe-emodin (mass fraction > 98.5 %) was
purchased from Shanxi Ciyuan Biological Technology Co., Ltd.,
(Xi’an, China). It was recrystallized twice in ethanol, dried in a
vacuum oven at T = 378.5 K for 24 h, and stored in a desiccator
before use. The purity of the aloe-emodin crystal was more
than 99.8 % mass fraction, determined on Agilent 1100 HPLC
system (Agilent, USA). 1-Decyl-3-methylimidazolium chloride
([C10mim]Cl), 1-hexyl-3-methylimidazolium hexafluorophos-
phate ([C6mim]PF6), 1-butyl-3-methylimidazolium tetrafluor-
oborate ([C4mim]BF4), 1-hexyl-3-methylimidazolium tetra-
fluoroborate ([C6mim]BF4), and 1-butyl-3-methylimidazolium
bis(methylsulfonyl)amide ([C4mim]NTF2) were purchased
from Lanzhou Greenchem ILS, LICP. CAS (Lanzhou,
China). These ILs were distilled in a rotary evaporator for 4
h and dried at 398.5 K under vacuum for 24 h to remove the
potential residual solvents and water prior to use. The HPLC
Received: January 9, 2013
Accepted: July 29, 2013
Published: August 15, 2013
dx.doi.org/10.1021/je400028k | J. Chem. Eng. Data 2013, 58, 2405−2409
Journal of Chemical & Engineering Data
Table 1. Ionic Liquids Used for the Solubility Determination of Aloe-Emodin
purity of the ILs used in this experiment were higher than 99.5
%, determined on Agilent 1100 HPLC system according to the
method of Jiang et al.16 with slight modification, and their water
content was less than 1000 ppm (Table 1), measured by Karl
Fisher titration method on V20 titrator (Mettler Toledo,
Switzerland).
Apparatus and Procedure. A purpose-made glass tube
(10 mL) with a Teflon-coated magnetic stirrer and a glass
jacket (about 500 mL) was used to prepare a saturated solution
of aloe emodin in ILs. The excess solid solute (aloe-emodin,
about 10 mg) and ILs (about 7 mL) were accurately weighed
respectively on Sartorius type BS 112 analytical balance with
accuracy of ± 0.1 mg, and put into the test tube. Then the test
tube was sealed up by a Teflon stopper with a precise
thermometer (± 0.01 K), and the inlet/outlet of jacket was
connected to a thermostatic water circulator with temperature
accuracy of ± 0.01 K. The mixture was stirred and heated to
expected temperature value. The dissolution equilibrium of
solute in ILs was monitored by a laser detection system
composed of a laser generator and a laser receiver. The test
tube was placed between the laser generator and receiver to
enable the laser beam to pass through from one side to another.
At the beginning, the laser through the tube was sheltered by
the suspended solid solute in ILs, and the laser power received
was low. As more and more solid solute dissolved, the received
laser power strengthened. When the received power reached
the maximum value and remained unchanged, the dissolution
of the sample in ILs reached solid−liquid equilibrium. After
that, the undissolved solid and solution were allowed to settle
for elutriation, and than the clear saturated solution of 100 μL
were withdrawn by preheated glass syringe. The glass syringe
with saturated solution was weighed on a Sartorius type 1712
analytical balance with an uncertainty of ± 0.01 mg. The
saturated solution was injected into the volumetric flask (5 mL)
immediately to prevent precipitating. Subsequently, the glass
syringe with the remaining solution was weighed, therefore the
mass of saturated solution put into volumetric flask could be
2406
Article
calculated. The solution of sample was diluted to the mark with
methanol for HPLC analysis.
Chromatographic Conditions. The solubility of aloe-
emodin was determined on an Agilent 1100 HPLC system. The
analysis was carried out on a Zorbax SB-C18 column (150 mm
× 4.6 mm, 5.0 μm) by an external standard method. A mobile
phase composed of methanol and 0.2 % phosphoric acid
aqueous solution, with volume fraction of 90:10, was used to
run the separation at a flow rate of 1.0 mL·min−1. The injected
volumes of sample and reference standard solution were 10 μL.
The detective wavelength was set at 254 nm. All chromato-
graph procedures were performed at room temperature. The
average relative uncertainty of HPLC analysis of the aloe-
emodin was less than 1.8% (n = 5).
■
RESULTS AND DISCUSSION
The mole fraction solubility data of aloe-emodin in five
imidazolium-based ILs are presented in Table 2 and more
visually expressed in Figure 2. In this work, each measurement
was repeated three times at the same condition, and the
reported solubility data are the average values.
According to the model of molecular thermodynamics for
the solubility of solid in liquid, the temperature (T)
dependence of solubility (x) can be correlated with the
following simplified dual parameters equation17
B
ln x = A +
T (1)
where x is the mole fraction solubility of aloe-emodin, T is an
absolute temperature (K), and A and B are the empirical
parameters. The two parameters A and B were obtained by
least-squares fit from the experimental data and listed in Table
3 together with the root-mean-square deviations (rmsd). The
rmsd is defined as
⎡1 n ⎤1/2
rmsd = ⎢ ∑ (x cal exp 2 ⎥
−x )
⎢⎣ n ⎥⎦
n=1 (2)
dx.doi.org/10.1021/je400028k | J. Chem. Eng. Data 2013, 58, 2405−2409
Journal of Chemical & Engineering Data Article

Table 2. Mole Fraction Solubility xa of Aloe-Emodin in Five

Imidazolium-Based ILs at Temerature T and Pressure p =
0.1 MPab
T/K 103xexp 103x1cal 103x2cal
[C10mim]Cl
307.15 0.193 0.198 0.200
310.85 0.222 0.220 0.221
314.05 0.244 0.240 0.241
317.55 0.267 0.265 0.265
321.25 0.284 0.292 0.291
325.15 0.326 0.324 0.322
334.05 0.398 0.405 0.403
340.35 0.483 0.472 0.470
349.65 0.580 0.584 0.587
[C4mim]BF4
300.55 0.217 0.221 0.230
306.35 0.250 0.254 0.260 Figure 2. Solubility of aloe-emodin in [C4mim]NTF2 (◇), [C6mim]-
311.85 0.285 0.288 0.291 BF4 (▽), [C4mim]BF4 (○), [C10mim]Cl (□), [C6mim]PF6 (△).
317.05 0.320 0.324 0.324 Solid lines are values calculated by the dual-parameter eq 1 and dash
321.35 0.353 0.356 0.353 lines are values calculated by the λh eq 3 with the parameters from
Table 2.
325.15 0.381 0.386 0.381
331.35 0.464 0.438 0.431
⎛ 1 − x ⎞⎟ ⎛1 1 ⎞
343.35 0.549 0.554 0.543
ln⎜1 + λ = λh⎜ − ⎟
363.55 0.789 0.793 0.801 ⎝ x ⎠ ⎝T Tm ⎠ (3)
[C6mim]PF6
304.15 0.172 0.192 0.200 where Tm is the melting point temperature of the aloe-emodin.
308.05 0.203 0.208 0.215 The value of λ is identified as the approximate mean association
313.55 0.246 0.233 0.238 number of solute molecules, which reflects the nonideality of
317.15 0.250 0.251 0.254 the solution system, and h estimates the excess mixing enthalpy
321.15 0.280 0.271 0.273 of solution.19 Both parameters λ and h were obtained from the
327.25 0.315 0.304 0.304 experimental data by nonlinear least-squares fit and their values
332.75 0.332 0.336 0.336 are listed in Table 3.
347.25 0.424 0.431 0.433 From Table 2 and Table 3, it is seen that the calculated
[C6mim]BF4 solubilities are in good agreement with the experimental values,
311.35 0.247 0.254 0.256 which indicates that both the dual-parameters equation and the
314.75 0.282 0.288 0.290 λh equation are appropriate to describe the solubility of aloe-
318.15 0.321 0.327 0.328
emodin in selected imidazolium-based ILs for the present work.
322.25 0.392 0.379 0.379
A comparison of the fitted rmsd value for each IL (Table 3)
326.95 0.462 0.446 0.445
shows that the correlated result according to eq 1 is a little
333.35 0.551 0.553 0.551
better than that of eq 3.
338.15 0.652 0.647 0.645
Also, as can be seen from Figure 2, the solubility of aloe-
341.75 0.706 0.726 0.723
emodin in hydrophobic ILs, [C10mim]Cl, [C6mim]PF6,
352.55 1.014 1.009 1.012
[C4mim]NTF2, and hydrophilic ILs [C4mim]BF4, [C6mim]BF4
[C4mim]NTF2
improves with the increase of temperature over the investigated
295.55 1.013 1.063 1.114
temperature range, which is similar to the dissolution process of
311.35 1.694 1.666 1.684
solid solute in common organic solvents. When the temper-
324.95 2.409 2.368 2.351
335.65 3.058 3.061 3.023
ature deviates from the room temperature, the dependence of
343.55 3.750 3.662 3.621
the solubility of aloe-emodin on temperature becomes more or
352.05 4.419 4.401 4.384
less remarkable. Especially, the solubility of aloe-emodin in
360.75 5.194 5.265 5.317
[C4mim]NTF2 is more sensitive to temperature than that in
a exp other investigated ILs in this work. However, from the
x is the experimental value; x1cal and x2cal are the calculated value
experimental data, it is clearly observed that the solubility of
with dual-parameter and λh equation, respectively. bStandard
uncertainties u are u(T) = 0.05 K, ur(x) = 0.02. aloe-emodin is largely governed by the molecular structure of
the used ILs. The solubility values of aloe-emodin in
[C4mim]NTF2 approximate that of emodin in ethanol,20 and
are remarkably higher than that in other ILs at the same
where n is the number of experimental points, xexp represents temperature. This phenomenon may be majorly attributed to
the experimental value of solubility and xcal represents the the strong hydrogen bonding between the −OH groups of
solubility calculated from eq 1. aloe-emodin and (CF3SO2)2N− anion of [C4mim]NTF2. The
The λh in eq 3 is another widely used value to describe the π−π interaction and hydrophobic interaction between aloe-
relationship between the mole fraction solubility (x) and emodin and IL molecules were not the main dissolution
temperature (T) for solid−liquid phase equilibrium18 mechanisms.21,22
2407 dx.doi.org/10.1021/je400028k | J. Chem. Eng. Data 2013, 58, 2405−2409
Journal of Chemical & Engineering Data Article

Table 3. Parameters of Dual-Parameter eq 1 and λh eq 3 Correlated According to Experimental Molar Fraction Solubility of
Aloe-Emodin in Five Imidazolium-Based ILs
dual-parameter equation λh equation
ILs A B 105 rmsd λ h 105 rmsd
[C10mim]Cl 0.3908 −2739.9 0.5802 0.003137 779349.4 0.6420
[C4mim]BF4 −1.0379 −2218.5 0.9475 0.001594 1063095.2 1.3292
[C6mim]PF6 −2.0448 −1981.2 2.4749 0.000845 1652577.1 2.9345
[C6mim]BF4 3.5234 −3674.5 1.0541 0.01211 289088.3 1.0509
[C4mim]NTF2 2.0049 −2616.2 15.0808 0.01857 120887.8 22.3377

For a real solution, the dissolution enthalpy (ΔHd) and in the degree of order of the system due to the alignment
entropy (ΔSd) can be calculated with the van’t Hoff eq 423 disruption of ILs molecules while aloe-emodin were dissolved.

ln x = −
ΔHd
RT
+
ΔSd
R (4) ■ CONCLUSIONS
The solubility of aloe-emodin in five pure imidazolium-based
where x is the mole fraction solubility. The van’t Hoff plots (ln ILs, [C4mim]BF4, [C6mim]BF4, [C6mim]PF6, [C10mim]Cl,
x versus 1/T) are shown in Figure 3, and are obtained from the and [C4mim]NTF2 was determined, respectively, by the laser
monitoring observation method combined with HPLC at
atmospheric pressure. The solubilities of aloe-emodin in these
ILs increased with rising temperature. The IL [C4mim]NTF2
exhibited good dissolubility to aloe-emodin and may be an
alternative to organic solvents for aloe-emodin extraction. The
experimental data were correlated with the simplified dual-
parameters equation and λh equation. The calculated solubility
values of aloe-emodin showed good agreement with the
experimental values. The experimental solubility data and
correlation equations in this work may be used as essential data
and a reference for the extraction process of aloe-emodin in
imidazolium-based ILs.

Figure 3. The van’t Hoff plots of ln x versus 1/T in [C10mim]Cl(□),
[C4mim]BF4(○), [C6mim]BF4(△), [C6mim]PF6 (▽), and [C4mim]-
NTF2 (◇).
linear fit of solubility data of aloe-emodin at different
temperature. The ΔHd and ΔSd and standard deviation (SD)
are shown in Table 4. In this binary system composed of aloe-
emodin and ILs, because of the intramolecular and
intermolecular hydrogen bonding of the aloe-emodin mole-
cules, as well as the intermolecular strong association of ILs
molecules, which majorly resulted from the electrostatic action
between cations and anions, the interactions between aloe-
emodin and ILs molecules are not strong enough to destroy the
original association in ILs, and thus the dissolution process of
aloe-emodin in ILs is expressed as the endothermic process,
that is, ΔHd > 0. From Table 4, the positive ΔHd and ΔSd
revealed that the dissolution process of aloe-emodin was an
entropy-driven process, which is possibly induced by reduction
■ AUTHOR INFORMATION
Corresponding Author
*E-mail: kdyang@163.com. Tel.: 0086-771-3233718. Fax:
0086-771-3233718.
Funding
This research work was financially supported by the National
Natural Science Foundation of China (No. 21166002).
Notes
The authors declare no competing financial interest.
■ REFERENCES
(1) Aysan, E.; Bektas, H.; Ersoz, F. A new approach to postoperative
peritoneal adhesions: Prevention of peritoneal trauma by aloe vera gel.
Eur. J. Obstet. Gynecol. Reprod. Biol. 2010, 149, 195−198.
(2) Fenig, E.; Nordenberg, J.; Beery, E.; Sulkes, J.; Wasserman, L.
Combined effect of aloe-emodin and chemotherapeutic agents on the
proliferation of an adherent variant cell line of Merkel cell carcinoma.
Oncol. Rep. 2004, 11, 213−217.
(3) Lin, S. Y.; Yang, J. H.; Hsia, T. C.; Lee, J. H.; Chiu, T. H.; Wei, Y.
H.; Chung, J. G. Effect of inhibition of aloe-emodin on N-
acetyltransferase activity and gene expression in human malignant
melanoma cells (A375.S2). Melanoma Res. 2005, 15, 489−494.
(4) Guo, J.; Xiao, B.; Liu, Q.; Gong, Z.; Le, Y. Suppression of C-myc
expression associates with anti-proliferation of aloe-emodin on gastric
cancer cells. Cancer Invest. 2008, 26, 369−374.

Table 4. Dissolution Enthalpy (ΔHd) and Entropy (ΔSd) of Aloe-Emodin in Five Imidazolium-Based ILs

ILs [C10mim]Cl [C4mim]BF4 [C6mim]PF6 [C6mim]BF4 [C4mim]NTF2

ΔHd (kJ mol−1) 22.87 18.75 17.51 30.89 22.15
ΔSd (J mol−1K−1) 60.96 49.73 43.63 87.75 75.30
SD 0.01979 0.0236 0.05173 0.02586 0.02465

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Journal of Chemical & Engineering Data Article

(5) Chiu, T. H.; Lai, W. W.; Hsia, T. C.; Yang, J. S.; Lai, T. Y.; Wu, P.
P.; Ma, C. Y.; Yeh, C. C.; Ho, C. C.; Lu, H. F.; Wood, W. G.; Chung, J.
G. Aloe-emodin induces cell death through s-phase arrest and caspase-
dependent pathways in human tongue squamous cancer SCC-4 cells.
Anticancer Res. 2009, 29, 4503−4511.
(6) Berthod, A.; Ruiz, A. M.; Carda, B. S. Ionic liquids in separation
techniques. J. Chromatogr. A. 2008, 1184, 6−18.
(7) Hallett, J. P.; Welton, T. Room-temperature ionic liquids:
Solvents for synthesis and catalysis. Chem. Rev. 2011, 111, 3508−3576.
(8) Plechkova, N. V.; Seddon, K. R. Applications of ionic liquids in
the chemical Industry. Chem. Soc. Rev. 2008, 37, 123−150.
(9) Werner, S.; Haumann, M.; Wasserscheid, P. Ionic liquids in
chemical engineering. Annu. Rev. Chem. Biomol. Eng. 2010, 1, 203−
230.
(10) Huddleston, J. G.; Willauer, H. D.; Swatloski, R. P.; Visser, A. E.;
Rogers, R. D. Room temperature ionic liquids as novel media for
“clean” liquid−liquid extraction. Chem. Commun. 1998, 16, 1765−
1766.
(11) Gu, Y. L.; Shi, F.; Yang, H. Z.; Deng, Y. Q. Leaching separation
of taurine and sodium sulfate solid mixture using ionic liquids. Sep.
Purif. Technol. 2004, 35, 153−159.
(12) Du, F. Y.; Xiao, X. H.; Luo, X. J.; Li, G. K. Application of ionic
liquids in the microwave-assisted extraction of polyphenolic
compounds from medicinal plants. Talanta. 2009, 78, 1177−1184.
(13) Zeng, H.; Wang, Y. Z.; Kong, J. H.; Nie, C.; Yuan, Y. Ionic
liquid-based microwave-assisted extraction of rutin from Chinese
medicinal plants. Talanta. 2010, 83, 582−590.
(14) Poole, C. F.; Poole, S. K. Extraction of organic compounds with
room temperature ionic liquids. J. Chromatogr. A. 2010, 16, 2268−86.
(15) Wei, Z. F.; Zu, Y. G.; Fu, Y. J.; Wang, W.; Luo, M.; Zhao, C. J.;
Pan, Y. Z. Ionic liquids-based microwave-assisted extraction of active
components from pigeon pea leaves for quantitative analysis. Sep. Purif.
Technol. 2013, 102, 75−81.
(16) Jiang, X. H.; Sun, X. W.; Zhao, S. Q.; Fu, D. B. Determination of
ionic liquids and high B. P. organic compounds by reversed-phase
HPLC. Anal. Test. Technol. Instrum. 2002, 16, 195−198.
(17) Prausnitz, J. M.; Lichtenthaler, R. N.; Azevedo, E. G. Molecular
Thermodynamics of Fluid-Phase Equilibria, 3rd ed.; Prentice Hall:
Englewood Cliffs, NJ, 1999.
(18) Buchowski, H.; Ksiazczak, A.; Pietrzyk, S. Solvent activity along
a saturation line and solubility of hydrogen-bonding solids. J. Phys.
Chem. 1980, 84, 975−979.
(19) Wei, D. W.; Li, H.; Liu, C.; Wang, B. H. The effect of
temperature on the solubility of 11-cyanoundecanoic acid in
cyclohexane, n-hexane, and water. Ind. Eng. Chem. Res. 2011, 50,
2473−2477.
(20) Lv, Y. C.; Lin, Q.; Luo, G. S.; Dai, Y. Y. Solubility of emodin in
alcohols. Chin. J. Chem. Eng. 2009, 17, 251−253.
(21) Hu, X. S.; Li, Y. X.; Cui, D.; Chen, B. H. Separation of ethyl
acetate and ethanol by room temperature ionic liquids with the
tetrafluoroborate anion. J. Chem. Eng. Data 2008, 53, 427−433.
(22) Martak, J.; Schlosser, S. Extraction of lactic acid by
phosphonium ionic liquids. Sep. Purif. Technol. 2007, 57, 483−494.
(23) Mullin, J. W. Crystallization, 4rd ed.; Butterworth-Heinemann:
Oxford, 2001.

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