Article pubs.acs.org/jced
Solubilities of Naringin Dihydrochalcone in Pure Solvents and Mixed Solvents at Different Temperatures Ning Tang and Weidong Yan* Department of Chemistry, Zhejiang University, Hangzhou, 310027, China S Supporting Information *
ABSTRACT: Naringin dihydrochalcone (naringin DC) is an intense sweetener and a strong antioxidant with potential applications in many food and pharmaceutical products. However, the poor solubility and stability of naringin DC in aqueous systems at room temperature severely limits its applications in these areas. The solubility of naringin dihydochalone was quantified in water, ethyl acetate, binary solvent mixtures of methanol + water and ethanol + water by a synthetic method at different temperatures. The solubility of naringin DC in a given solvent increases with the rising temperature. The experimental data were well correlated with an Apelblat equation and Universal Quasichemical model. Moreover, the physical properties and crystal habit of naringin DC were discussed through a thermogravimetric analyzer, a differential scanning colorimeter, and a scanning electron microscope.
■
INTRODUCTION Dihydrochalcones come from the family of bicyclic flavonoids, which was defined by the presence of two benzene rings joined by a saturated three carbon bridge.1 They usually exist in citrus fruits and apples,2 and exhibit higher antioxidant activities than the corresponding flavanones. Naringin DC (3,5-dihydroxy-4[3-(4-hydroxyphenyl) propanoyl] phenyl 2-O-(6-deoxy-α-Lmannopyranosyl)-β-L-glucopyranoside, CASRN: 18916-17-1, MW: 582.55, Figure 1) is a diglycoside of phloretin. When
measured the solubilities of naringin DC in some selected pure (water and ethyl acetate) and mixed (methanol (2) + water (3); ethanol (2) + water (3)) solvents at different temperatures with a modified apparatus,5 and the temperature-depend data were correlated with the Apelblat equation6−8 and UNIQUAC model,9 respectively.
■
EXPERIMENTAL SECTION Materials. The naringin dihydrochalone (white powder, > 0.90 mass fraction) was supplied by Skyherb Ingredients Co., Ltd. (China). A 10 g sample of naringin DC was dissolved in 200 mL of distilled water at 80 °C, stirred for 2 h, filtered, and cooled naturally to room temperature. After the sample was recrystallized three times and dried in a vacuum oven at 110 °C for 24 h, about 8 g of white needle-like solid was obtained, and it was stored in a desiccator to avoid moisture absorption. The purity of naringin DC was more than 0.99 mass fractions, determined by HPLC (Shimadzu LC-10AT). The water content of the prepared naringin DC was measured with the coulometric Karl Fischer titrator (DL32, METTLER TOLEDO, Switzerland) and found to be less than 0.45 wt %. All the used analytical grade organic solvents such as methanol, ethanol, and ethyl acetate were purchased from Sinopharm Chemica Reagent Co., Ltd. (China). The purities of these reagents were more than 0.99 mass fractions, determined by gas chromatography. Distilled deionized water was obtained from
Figure 1. Molecular structure of naringin dihydrochacone.
naringin is treated with potassium hydroxide or another strong base, and then catalytically hydrogenated, it becomes a naringin DC that is roughly 300−1800 times sweeter than sugar at threshold concentrations.3 Moreover, as a novel antioxidant, naringin DC has better free radical scavenging ability than its corresponding flavanone naringin. Although it is an intense sweetener and a strong antioxidant with potential applications in many food and pharmaceutical products,4 the poor solubility in aqueous systems severely restricts its applications in those products, and solubility data of naringin DC in solvents was lacking in the literature. We © XXXX American Chemical Society
Special Issue: Proceedings of PPEPPD 2016 Received: June 29, 2016 Accepted: November 8, 2016
A
DOI: 10.1021/acs.jced.6b00543 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 1. Source and Mass Fraction Purity of the Chemicals Used in This Work
a
chemicals
CAS registry number
source
initial mass fraction purity
purification method
final mass fraction purity
analysis method
naringin DC methanol ethanol ethyl acetate
18916-17-1 67-56-1 64-17-5 141-78-6
Skyherb Sinopharm Chemicals Sinopharm Chemicals Sinopharm Chemicals
0.90 0.995 0.995 0.995
recrystallization distillation distillation distillation
>0.99 >0.998 >0.998 >0.998
HPLCa GCb GC GC
High performance liquid chromatography. bGas chromatography.
Figure 2. SEM images of the naringin DC crystals in solvents (a) water; (b) ethyl acetate; (c) methanol (2) + water (3) (x2′ a = 0.099); (d) methanol (2) + water (3) (x2′ = 0.229); (e) ethanol (2) + water (3) (x2′ = 0.072). (a mole fraction of methanol or ethanol on a solute-free basis).
the distilled water generator (SZ-97, Shanghai Yarong Biochemical Instrument Co., Ltd. China). All the materials mentioned were shown in Table 1. Apparatus and Procedure. The solubility of naringin DC was measured by a synthetic method we used in our previous work.5 During weighing, the sample of naringin DC was kept from absorbing moisture as much as possible. All the apparatuses and experimental procedure are exactly the same as previously mentioned. In short, the measurements were carried out in an about 10 mL volume double-jacketed cylindrical glass equilibrium cell with a magnetic stirrer (COLOR SQUID, IKA) and a high precision platinum resistance thermometer (JM 6200, Tianjin Jinming Instrument CO., Ltd., China) with an uncertainty of u (T) = 0.01 K. A syringe needle for solvent injection was inserted into the cell below the surface of the liquid phase; it was linked by a precision glass injector (5000 μL, Shanghai Bolige Industry & Trade Co., Ltd., China), which was driven by a single channel syringe pump (LSP01-1A, Baoding Longer Precision Pump Co., Ltd., China). Predetermined masses of naringin dihydrochalone and solvent were weighted by a precision analytical balance (CP225D, Sartorius, Germany) with an uncertainty of u (m) = 0.01 mg. The solid and liquid mixture was continuously stirred, and it was kept in a constant temperature by a circulating water bath with a thermostat (THD-2006, Ningbo Tianheng Instrument Works Co., Ltd., China) with an uncertainty of u (T) = 0.01 K. A high definition visual camera with LED connected to a computer was put in front of the glass equilibrium cell to record the entire dissolution process.
This method was based on sequential addition of a known amount of solvent to completely dissolve the solute at a given temperature. Along with the increment of the solvent into the glass cell through the syringe, solid particles dissolved slowly. The addition of solvent was continued until the solid phase disappeared and the solution became clear. The mass of solvent injected into the cell can be calculated through the injected rate of the solvent, and the time from start to the last solid disappear which was recorded by video, and the known density of the solvent at a given temperature. The mole fraction solubility (x) of solute in a solvent can be calculated by eq 1: x=
mA /MA mA /MA + mB /MB
(1)
where mA and mB refer to the masses of the solute and solvent, respectively, while MA and MB represent the molecule weights of solute and solvent. Thermogravimetric Analysis and Different Scanning Calorimetry. Thermogravimetric analysis (TGA) was carried out for naringin dihydrochalone on a thermogravimetric analyzer (SDT Q600, TA Instruments, USA) at a heating rate of 10 K·min−1 under a nitrogen atmosphere. The melting point and enthalpy of fusion of naringin DC were determined using a differential scanning calorimeter (DSC Q100, TA Instruments, USA) in a nitrogen atmosphere and at a heating rate of 10 K·min−1 as well. Scanning Electron Microscopy. The crystal habit of naringin DC changes in morphology at different solvents was characterized using scanning electron microscopy (SEM) B
DOI: 10.1021/acs.jced.6b00543 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
Table 2. Mole Fraction 103x1 and ln x1 for Naringin Dihydrochacone in Different Solvents from Temperature T = 288.15K to 338.15K at Pressure p = 0.1 MPaa
(SU8010, Hitachi, JAPAN). The samples were evenly distributed on silicon SEM specimen stubs with double adhesive tape and the micrographs were received at 3.0 kV accelerating voltage.
■
T/K
103x1
ln x1
water 298.15 2.13 × 10−2 −10.7564 308.15 3.78 × 10−2 −10.1829 318.15 7.12 × 10−2 −9.5503 328.15 1.66 × 10−1 −8.7039 338.15 3.75 × 10−1 −7.8885 methanol (2) + water (3) (x2′b = 0.099) 288.15 4.25 × 10−2 −10.0659 298.15 1.11 × 10−1 −9.1104 308.15 2.71 × 10−1 −8.2134 318.15 7.27 × 10−1 −7.2272 328.15 2.48 −5.9999 ethanol (2) + water (3) (x2′= 0.033) 288.15 1.75 × 10−2 −10.9482 298.15 4.18 × 10−2 −10.0827 308.15 6.72 × 10−2 −9.6085 318.15 2.38 × 10−1 −8.3438 328.15 7.55 × 10−1 −7.1885
RESULTS AND DISCUSSION Physical Properties of Naringin Dihydrochalone. The results of TGA and DSC measurements of naringin DC were shown in Figure S1 and Figure S2 of Supporting Information. It can be seen that the decomposition temperature of naringin dihydrochalone is higher than 230 °C. The melting point (Tm) and molar enthalpy of fusion (ΔfusHm) of naringin DC are found to be 159.07 °C and 29.63 kJ·mol−1, u (Tm) = 0.2 K and ur (ΔfusHm) = 0.03, respectively. The onset theoretical values of the standard reference sample In are found to be melting point Tm = 159.60 °C and enthalpy fusion ΔfusHm = 28.44 kJ·mol−1, u (Tm) = 0.2 K and ur (ΔfusHm) = 0.03, respectively. From Figure S1, it can be seen that the loss mass of naringin DC was 2.09%, and Figure S2 showed the endothermic peak of water at 67.27 °C. Generally, these messages demonstrated the sample was readily absorbing moisture. SEM Analysis. The scanning electron micrographs of naringin DC in different solvents are shown in Figure 2. We have observed that the morphology of naringin DC crystals changed in different solvents during experimental process. These images demonstrated that Naringin DC shaped regularly in all the given solvents. Naringin DC existed ribbon-like in water, while in ethyl acetate it occurred as nano particles. Nano sheets and nano rods were investigated in methanol (2) + water (3) (x2′ = 0.099, mole fraction of methanol on a solute-free basis) and methanol (2) + water (3) (x2′ = 0.229, mole fraction of methanol on a solute-free basis), respectively. In the mixed solvent ethanol (2) + water (3) (x2′ = 0.072, mole fraction of ethanol on a solute-free basis), it formed in the shape of nano sticks. Solubility Data of Naringin Dihydrochalone. The solubilities (mole fraction x1 and lnx1) of naringin DC in pure and mixed solvents at different temperatures at atmospheric pressure are presented in Table 2 and plotted in Figure 3. Generally, it can be seen that the solubility of naringin DC in given solvent increases exponentially with the rising temperature. Obviously, the solubility of naringin DC in mixed solvents ethanol (2) + water (3) (x2′ = 0.072, mole fraction of ethanol on a solute-free basis) increased markedly with the increase of temperature. Compared with the solubility of naringin DC in pure water, the solubility in mixed solvents is largely due to the mole fraction of alcohols. We have measured that the solubility of naringin DC is more than 50 g/100 g of solvent at room temperature in pure methanol and ethanol. Usually, the solubility ability of naringin DC depends not only on the polarities of the solvent but also the intermolecular interactions and the ability of the solvent to form hydrogen bonds with naringin DC. As we can see from the chemical structure of naringin DC, the glycosidic bond may have a more significant influence on solubility. As the results showed in Figure 3, and combined with production practice, water and the ethanol (2) + water (3) (x2′ = 0.072, mole fraction of ethanol on a solute-free basis) system were usually selected as the solvents in the recrystallization of naringin DC. Calculation of the Solubility of Naringin DC with Apelblat Equation Model. The relationship between mole fraction solubility and temperature is described by the Apelblat equation, which has been widely used in the correlation of
T/K
103x1
ln x1
ethyl acetate 288.15 3.10 × 10−1 −8.0791 298.15 3.69 × 10−1 −7.9026 308.15 4.91 × 10−1 −7.6191 318.15 6.68 × 10−1 −7.3114 328.15 7.76 × 10−1 −7.1611 methanol (2) + water (3) (x2′ = 0.229) 288.15 6.31 × 10−1 −7.3685 298.15 1.57 −6.4544 308.15 4.22 −5.4661 318.15 11.05 −4.5050 328.15 22.47 −3.7957 ethanol (2) + water (3) (x2′ = 0.072) 288.15 4.56 × 10−2 −9.9953 298.15 2.71 × 10−1 −8.2125 308.15 7.43 × 10−1 −7.2048 318.15 6.94 −4.9701 328.15 21.06 −3.8604
a
Standard uncertainties u are u(T) = 0.01 K, u(p) = 5 Kpa, ur(x) = 0.03, u(x2′) = 0.001. bMole fraction of methanol or ethanol on a solute-free basis.
Figure 3. Solubility of naringin dihydrochacone in different solvents. ■, water; □, ethyl acetate; ▲, methanol (2) + water (3) (x2′a = 0.099); ▼, methanol (2) + water (3) (x2′ = 0.229); △, ethanol (2) + water (3) (x2′ = 0.033); ○, ethanol (2) + water (3) (x2′ = 0.072) (amole fraction of methanol or ethanol on a solute-free basis).
solubility data and temperature of massive substances. According to the equation, the mole fraction solubility of naringin DC can be calculated through eq 2: B ln x = A + + C ln T /K (2) T /K where x and T denote the calculated mole fraction solubility of the solute and absolute temperature (K), respectively. A, B, and C are the empirical model parameters and can be obtained to fit the experimental data by a nonlinear least-squares method. The values of parameters A, B, and C and the root-mean-square deviations (rmsd’s) are listed in the Table 3. The rmsd is defined as eq 3: C
DOI: 10.1021/acs.jced.6b00543 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
Article
With the experimental x1, ΔfusH, Tm, and T values known, the activity coefficients of naringin dihydrochalone in the selected solvents can be obtained from eq 5. The activity coefficient of naringin DC in eq 5 can be calculated by the universal quasichemical (UNIQUAC) equation, eq 6:
Table 3. Parameters and rmsd of the Apelblat Equation solvent
a
b /K
c
103rmsd
water ethyl acetate methanol (2) + water (3) (x2′a = 0.099) methanol (2) + water (3) (x2′ = 0.229) ethanol (2) + water (3) (x2′= 0.033) ethanol (2) + water (3) (x2′= 0.072)
−980.014 −87.458 −953.085
39366.771 1692.075 35100.753
146.943 12.975 145.005
3.51 × 10−3 0.02 0.04
27.622
−8840.952
−0.766
0.53
a
−1595.258
64996.241
239.924
ln γi = ln
8.86 × 10−3
− −507.481
10373.778
81.489
1.31
ϕi
+
xi ϕi xi
θ z q ln i + li 2 i ϕi ⎡
∑ xilj + qi⎢⎢1 − ln(∑ θτj ij) − ∑ ⎣
j
j
j
⎤ ⎥ ∑k θkτkj ⎥⎦ θτ j ji
(6)
where
Mole fraction of methanol or ethanol on a solute-free basis.
⎡ ∑N (x − x )2 ⎤1/2 i ,exp ⎥ i = 1 i ,cal rmsd = ⎢ ⎢⎣ ⎥⎦ N
rx i i , ∑j rjxj
ϕi = (3)
li =
where N is the number of experimental points, xi,cal and xi,exp represent the solubilities calculated from eq 2 and the experimental solubility values, respectively. From the data listed in Table 3, it can be seen that the calculated solubilities were in good agreement with the experimental values. Calculation of the Solubility of Naringin DC with UNIQUAC Equation Model. According to the solid−liquid equilibrium theory, the experimental data of naringin DC can be expressed as eq 4: ⎛ 1 ⎞ Δ H ⎛T ⎞ ΔCp ⎛ Tt ⎞ ⎜ ⎟⎟ = fus ⎜ t − 1⎟ − − 1⎟ ln⎜⎜ ⎝ ⎠ ⎝ ⎠ RTt T R T ⎝ γ1x1 ⎠ ΔCp T + ln t R T
qixi ∑j qjxj
z (ri − qi) − (ri − 1) 2
The coordination number z is set equal to 10; ri and qi are the structural parameters of pure solvent i. The structural parameters of naringin DC were calculated by the functional group approach.10 m
ri =
m
∑ niR i ,
qi =
i=1
∑ niQ i
(7)
i=1
where m is is the number of functional groups in the molecule and n is the repeating number of each function group. The structural parameters, Ri and Qi of function group i, were taken from Dortmund Data Bank (DDBST GmbH, Germany). Two adjustment parameters, τij and τji, are expressed by (4)
⎛ aij ⎞ ⎟, τij = exp⎜ − ⎝ RT ⎠
where γ1 and x1 refer to the activity coefficients and mole fractions of naringin dihydrochalone in the solution, respectively; ΔfusH refers to the enthalpy of fusion of the solute at melting temperature; T and Tt are the solid−liquid equilibrium temperature, and triple-point temperature of the solute, respectively; ΔCp is the distinction of the heat capacities for the solid and the liquid phases, and R is the gas constant. Since the distinctions of the heat capacities for the solid and the liquid phases of the solute were negligible, and the triplepoint temperature (Tt) is similar to the normal melting temperature (Tm), eq 4 could be simplified to eq 5: ⎛ 1 ⎞ Δ H ⎛T ⎞ ⎟⎟ = fus ⎜ m − 1⎟ ln⎜⎜ ⎠ RTm ⎝ T ⎝ γ1x1 ⎠
θi =
⎛ aji ⎞ ⎟ τji = exp⎜ − ⎝ RT ⎠
(8)
where aij and aji are interaction parameters. The binary solvent−solvent interaction parameters have been obtained directly from Dortmund Data Bank (DDBST GmbH, Germany). The binary solvent−solute interaction parameters were fitted to the experimental data by a nonlinear least-squares method. The interaction parameters obtained in this work together with the root-mean-square deviations (rmsd) are given in Table 4. As it can be seen from Tables 3 and 4, the results correlated with Apelblat and UNIQUAC model are both satisfactory. However, the results of the UNIQUAC model were better than the Apelblat equation. It means those parameters listed in Table 4 could be used to predict the solubilities of naringin DC at different temperatures.
(5)
Table 4. Parameters and RMSD of the UNIQUAC Equation
a
solvent
a12/(J·mol−1)
a21/(J·mol−1)
water ethyl acetate methanol (2) + water (3) (x2′a = 0.099) methanol (2) + water (3) (x2′ = 0.229) ethanol (2) + water (3) (x2′ = 0.033) ethanol (2) + water (3) (x2′ = 0.072)
4246.481 6196.772 3666.493 64584.285 1917.633 57093.223
1146.015 −1274.953 −1876.398 −1271.946 −3156.312 −3706.565
a13/(J·mol−1)
3705.065 71037.475 2822.174 57750.050
a31/(J·mol−1)
103rmsd
1698.478 812.756 1734.049 1390.165
1.95 × 10−2 2.10 × 10−2 0.40 4.44 0.06 6.38
Mole fraction of methanol or ethanol on a solute-free basis. D
DOI: 10.1021/acs.jced.6b00543 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
Journal of Chemical & Engineering Data
■
Article
CONCLUSIONS The mole fraction solubility of naringin DC has been measured in two pure solvents and four mixed solvents at different temperatures with a modified apparatus. Thermal analysis was carried out to determine the melting point, molar enthalpy of fusion, the decomposition point of naringin DC. The crystal habit of naringin DC in different solvents was obtained by scanning electron microscopy; they formed regular shapes in all the selected solvents. The solubility of naringin DC was found to increase significantly with the rising temperature. Experimental data of the solubility of naringin DC were correlated with both the Apelblat equation and the UNIQUAC equation. The results showed that calculated solubilities have satisfactory agreement with the experimental data by the selected models. The experimental data and correlation models in this work can be used in the production and purification process of naringin DC in industry in future research.
■
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.6b00543. TGA thermogram of naringin DC; experimental heat flow from DSC measurement of naringin DC (PDF)
■
AUTHOR INFORMATION
Corresponding Author
*Tel: +86-571-87951430. Fax: +86-571-8795189. E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
■
REFERENCES
(1) Nakamura, Y.; Watanabe, S.; Miyake, N.; Kohno, H.; Osawa, T. Dihydrochalcones: evaluation as novel radical scavenging antioxidants. J. Agric. Food Chem. 2003, 51, 3309−3312. (2) Tomás-Barberán, F. A.; Clifford, M. N. Flavanones, chalcones and dihydrochalcoes nature, occurrence and dietary burden. J. Sci. Food Agric. 2000, 80, 1073−1080. (3) Tomasik, P. Chemical and functional properties of food saccharides; CRC Press: Boca Raton, FL, 2003. (4) Surana, S.; Gokhale, S.; Rajmane, R.; Jadhav, R.; Jadhav, R. Nonsaccharide natural intense sweeteners. An overview of current status. Nat. Prod. Rad. 2006, 5, 270−278. (5) Tang, N.; Shi, W.; Yan, W. Modified method for measuring the solubility of pharmaceutical compounds in organic solvents by visual camera. J. Chem. Eng. Data 2016, 61, 35−40. (6) Apelblat, A.; Manzurola, E. Solubility of oxalic, malonic, succinic, adipic, maleic, malic, citric, and tartaric acids in water from 278.15 to 338.15 K. J. Chem. Thermodyn. 1987, 19, 317−320. (7) Mullin, J. W.Crystallization, 4th ed.; Butterworth-Heinemann: Oxford, U.K., 2001. (8) Lorimer, J. W.; Cohen-Adad, R.Thermodynamics of solubility; in experimental de-termination of solubilities; Hefter, G. T., Tomkins, R. P. T., Eds.; John Wiley & Sons: Chichester, U.K., 2003. (9) Prausnitz, J. M.; Lichtenthaler, R. N.; Azevedo, E. G. Molecular thermodynamics of fluid-phase equilibria, 3rd ed.; Prentice Hall: New York, 1999. (10) Fredenslund, A.; Jones, R. L.; Prausnitz, J. M. Groupcontribution estimation of activity coefficients in nonideal liquid mixtures. AIChE J. 1975, 21, 1086−1099.
E
DOI: 10.1021/acs.jced.6b00543 J. Chem. Eng. Data XXXX, XXX, XXX−XXX
