Journal of Industrial and Engineering Chemistry 16 (2010) 490495

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Journal of Industrial and Engineering Chemistry

journal homepage: www.elsevier.com/locate/jiec

Solubility prediction of bioantioxidants for functional solvent by group contribution method

Kyung Ai Park b, Hyoung Jin Lee a, In Kwon Hong a,*
a b

Department of Chemical Engineering, Dankook University, 448-701, Republic of Korea Seoul Metropolitan Government Research Institute of Public Health and Environment, 427-070, Republic of Korea

A R T I C L E I N F O

A B S T R A C T

Article history: Received 29 October 2009 Accepted 1 December 2009 Keywords: Bioantioxidants Group contribution Solubility parameter Optimum solvent Fusion enthalpy

Bioantioxidants protect a living body from the damage and ageing caused by active oxygen. Typical bioantioxidants include epicatechin, caffeic acid, ascorbic acid, etc. This study focused on selecting the optimum solvent that can dissolve each bioantioxidants by calculating the solubility of various bioantioxidants in each specic solvent. The solubility parameters of the bioantioxidants were correlated with the van Krevelen group model, and the solubility of bioantioxidant for each solvent was then calculated from the interaction relationship between each solubility parameter of the bioantioxidant and optimal solvent selected. The solubility of the bioantioxidants was affected not only by the solubility parameters of the solute and solvents, but also by the fusion enthalpy of the solute at melting temperature. Then the fusion enthalpy was measured for each bioantioxidant. The equilibrium non-ideality between the solvent and bioantioxidants examined as a function of the solubility parameter and fusion enthalpy. The optimum solvent was selected for each bioantioxidant based on the quantitative solubility data. Each bioantioxidant showed slight non-ideality, which it was presented in the activity coefcient of the solution system. 2010 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.

1. Introduction Oxygen is in a stable molecular state that is essential for lifesupport through a process involving the specic metabolism in the living body. On the other hand, the process of utilizing oxygen produces undesirable components by products such as the superoxide radical, hydroxyl radical, hydrogen peroxide and singlet oxygen, which are known as active oxygen. These radical are also produced by physical, chemical, and environmental processes, caused by ultraviolet rays, stress and blood circulatory disturbances in the body. Active oxygen causes damage to the body cell membrane, DNA and all different cell structures, which result in a loss of their intrinsic function or degeneration according to the extent of damage. In addition, active oxygen causes protein denaturing through the oxidation of several amino acids. These deleterious processes cause problems, such as the transformation and isolation of nucleotides, breaking of chemical bonds and oxidative degradation of sugar, by damaging nucleic acid. As a result, these problems can cause harmful mutations or cancer in the body [14].

Bioantioxidants protects the body from the aging and damage caused by active oxygen. This study calculated the solubility of six bioantioxidant materials, ascorbic acid, citric acid, butylated hydroxytoluene (BHT), caffeic acid, epicatechin and epigallocatechin gallate, in several organic functional solvents (Fig. 1). The quantitative equilibrium equation contained the solubility parameter as well as the non-ideal correction parameter, the activity coefcient. To calculate this equilibrium equation, the solubility parameter was calculated using the group contribution and the fusion enthalpy as one variable of the activity was measured experimentally for each bioantioxidant. The Hansen solubility parameter (dd, dp, dh) model proposed by van Krevelen can be expressed as the total solubility parameter type as follows [5,6]:

d2 d2 d2 d2 t d p h

(1)

* Corresponding author. E-mail address: khong@dankook.ac.kr (I.K. Hong).

The total solubility parameter is composed of three contribution, dispersion, polarity, and hydrogen bonding effect, and used widely to select the optimal solvent for each solute. In addition, the solubility parameter is used in different industries for making compatibility prediction of polymers, chemical resistance, osmotic velocity, and surface specication of pigments, bers and llers. Liquids with a similar difference in solubility parameter are can be

1226-086X/$ see front matter 2010 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jiec.2010.01.060

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mixed with each other. Some solutes, including polymers may be dissolved in a solvent with a similar solubility parameter [79]. An equilibrium expression for the solid solute solubility in specic liquid solvent was established using the fugacity equality criteria between solid and liquid phases. In this system, the equilibrium solubility was calculated by the isofugacity criteria and non-ideality for the solute, and solvent molecular interactions were corrected by using the activity coefcient and Scatchard Hildebrand relation [10,11]. 2. Materials and methods 2.1. Materials and properties Six types of bioantioxidants (ascorbic acid, citric acid, butylated hydroxytoluene (BHT), caffeic acid, epicatechin, epigallocatechin gallate), were used as the solutes used for the solubility prediction. Fig. 1 shows their molecular structures. In this study, the equilibrium model of dissolution by liquidsolid equilibrium (LSE) and calculated bioantioxidant solubility was employed using the correlation with the solutes in the solid state and solvents in the liquid state at the normal temperatures. Twenty solvents were inspected including heptane, hexane, methanol, etc. Table 1 lists the molecular formula and physical properties of the six bioantioxidants. The calculation of functional group contribution was based on these molecular structures for the solubility parameter components. These molecular structures were decomposed into functional groups, and the contribution of each to the solubility parameter components, dispersion, polarity and hydrogen bonding contribution, was calculated by weighting the species and number of functional groups. 2.2. Solubility parameter of the bioantioxidants The solubility parameter concept, by Scatchard and Hildebrand, is that in any pure-species liquid there are certain attractive forces or internal pressure opposing the repulsive energy between the molecules. If two pure-species liquids have equal forces of attraction, then they should show ideal liquid solution behavior, the activity coefcients of the solution show 1.00. However, if this force of attraction between two liquids is different, then the more strongly attracting liquid squeezes out the less strongly attracting liquid, the mixture system represents non-ideality, the excess Gibbs energy deviates from zero and the activity coefcients

should be larger than 1.00, or smaller than 1.00. Overall, the behavior of the pair of solute and solvent shows a non-ideal state. For a larger difference between the force of attraction of the two liquids, a greater deviation from the zero excess Gibbs energy results in a larger the activity coefcient [10,11]. Scatchard and Hildebrand suggested that the force of attraction can be measured using the following equation: cohesive energy density

Duvap
VL

DHvap RT
VL

(2)

This cohesive energy concept is consistent with the internal pressure which overcome the external pressure.   @P Pi T P (3) @T V Then, the internal pressure may be derived from the thermodynamic equation of state and measured experimentally. The internal pressure is dened as the difference between the thermal pressure and the external pressure [12,13].     @U @P T P (4) @V T @T V It is a satisfying idea in terms of the equilibrium force between the escape and cohesive molecular motion. Liquids with a high latent heat of vaporization require a large energy input to overcome the strong intermolecular attractions to change to a vapor state. A denser liquid must have a higher intermolecular attractive force than one with a lower density molecule. Generally, the solubility parameter can be dened as the cohesive energy density or internal pressure, the molecular vaporization energy per unit volume; s p Duvap d cohesive energy density (5) VL The solubility can be correlated with the regular solution theory, which describe simultaneously the quantitative solubility data and non-ideality of the solute in solution. RT ln g 1 V L F2 d1 d2
2 2

(6)

If the solubility parameter hypothesis and regular solution theory are true, then each activity coefcients for solute and solvent can be calculated using, only the heats of vaporization and liquid densities of the pure species. This is not case, but the solubility

Fig. 1. Structural formula of the bioantioxidants.

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K.A. Park et al. / Journal of Industrial and Engineering Chemistry 16 (2010) 490495 Table 2 Functional group components for each functional group [16]. Molar mass (g/mol) 176.13 180.16 192.12 220.35 290 458 Functional group Functional group components Fdi CH3 CH2 5CH2 5CH OH O CO Ring 420 270 400 200 210 100 290 190 1270 1430 Fpi 0 0 0 0 500 400 770 0 110 110 0 0 0 770 0 Ehi 0 0 0 0 20,000 3000 2000 0 0 0 0 0 0 2000 0

Table 1 Molecular formula and physical properties of the bioantioxidants. Bioantioxidants Ascorbic acid Caffeic acid Citric acid BHT Epicatechin Epigallocatechin gallate Molecular formula C6H8O6 C9H8O4 C6H8O7 C15H24O C15H14O6 C22H19O11 Density (g/cm3) 1.65 1.48 1.67 1.05 1.593 1.9

parameter hypothesis has been productive enough that has been cited widely, and tables of solubility parameters are widely available for solvent identication [14,15]. 2.3. Group contribution calculation

70

The molecular cohesive energy is composed of three effective contributions, molecular dispersion force effect (Ed), permanent dipole interaction effect (EP) and hydrogen bonding effect (Eh). The total cohesive energy can be expressed as the summation of three contributions as follows: Ecoh Ed Ep Eh (7)

70 80 C5O 5 CH 290 80

where the total molecular cohesive energy (Ecoh) can be written as the energy density concept per molar unit volume. Each energy term was divided by the molar volume. Ecoh Ed Ep Eh V V V V (8)

can be calculated using Eq. (1) from the summation of each solubility parameter group component [1618]. 3. Results and discussion 3.1. Thermal properties analysis The six bioantioxidants were examined using differential scanning calorimetry (DSC) to identify the molecular cohesive energy. The molecular cohesive energy was then correlated with the experimental molecular fusion enthalpy data. DSC is a thermoanalytical technique in which the difference in the amount of heat required to increase the temperature of a sample and reference was measured as a function of temperature. DSC is used mainly to examine the thermoanalytical phenomena of phase transitions, such as melting of the phase transitions, exothermic molecular decompositions, or heat capacity change. These transitions involve endothermic energy changes or heat capacity changes that can be detected by DSC with great sensitivity. The methods used for thermal analysis are thermogravimetric analysis (TGA), differential thermal analysis (DTA), DSC, etc. In this study, DSC was used to obtain the experimental fusion enthalpy of the bioantioxidants. DSC is normally used to analyze phase transitions, such as melting or crystallization of a polymer. The analysis data for the experimental fusion enthalpy of bioantioxidants are shown in Table 4 at a heating rate of 10 8C min1. The table also lists the data for the melting endothermic onset and heat of fusion. This thermal

The solubility parameter that reects the dispersion effect, polarity effect, hydrogen bonding effect can be calculated from the quantitative considering group contribution proposed by Hoftyzer and van Krevelen (VKH). The group contribution method using the atomic group-atomic group interaction was used to predict the properties of molecules from the conguration, number and position of a specic group. Three types of solubility parameter components can be obtained using the group contribution method, which is expressed as: P F di dd V q P 2 Fpi (9) dp V rP Ehi dh V where dd, dp and dh are the dispersion force, polar force and hydrogen bonding force considering the solubility parameter, and V is the solvent molar volume. dd, dp and dh were calculated using the molecular functional group components presented in Table 2 and the numerical data is presented in Table 3. The polarity effect was the main contribution to the solubility parameter component of the bioantioxidants except BHT. The total solubility parameter
Table 3 Solubility parameter components of the bioantioxidants. Components of bioantioxidants

d-Components (J/cm3)1/2 dd dp
20.423 13.832 26.480 2.378 13.907 16.923

Total (J/cm3)1/2

dh
28.219 22.553 27.300 9.753 23.786 26.242

dt
39.509 32.592 42.467 21.007 32.305 36.232

Ascorbic acid Caffeic acid Citric acid Butylated hydroxytoluene (BHT) Epicatechin Epigallocatechin gallate

18.642 19.033 18.893 18.454 16.864 18.378

K.A. Park et al. / Journal of Industrial and Engineering Chemistry 16 (2010) 490495 Table 4 Thermal properties of the bioantioxidants (heating rate 10 8C min1). Components Ascorbic acid Caffeic acid Citric acid BHT Epicatechin Epigallocatechin gallate Melting endothermic onset (8C) 193.57 223.32 157.33 71.81 251.77 156 Heat of fusion, Dhfus (J/g) 267.2 152.8 238.7 86.61 195.4 138.1

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in Eq. (13) and the activity coefcient equation. The above expression, Eq. (13), was combined with the regular solution theory to obtain the expression, for the solubility as follows: ln x1
l

Dhfus
RT m

  2 2 Tm V a Fb da db 1 T RT

(14)

information for bioantioxidants was used to calculate the solute and solvent equilibrium characteristics [19,20]. 3.2. Liquidsolid equilibrium (LSE) The LSE can be calculated using an equation derived from the isofugacity criteria, e.g., where fiL is the fugacity of component i in the liquid phase and fiS is the fugacity of component i in the solid phase in the case of two phase equilibrium [10,11]: fiL fiS (10)

The solubility of a solute in a solvent can be calculated from this equation if the solubility parameter is known. This equation is the equilibrium state model that considers the non-ideal behavior of a solidliquid solution, where Va is the molar volume of a solute and Fb is the volume fraction of a solvent in a mixing solution. At innite dilute condition of the solution, the equation reported elsewhere can be used Fb [11]. In these systems, the solubility of bioantioxidants in the twenty specic solvents was calculated using Eq. (14), which is listed in Table 5. 3.3. 3D coordinate of the solubility parameters The solute dissolves better in a solvent with a similar total solubility parameter (dt) value. As shown in Eq. (1), the total solubility parameter is the distance between the three solubility parameter components, dispersive, polar and hydrogen bonding energy, in a three-dimensional coordinate system. Each total solubility parameter for each bioantioxidant was represented in 3D coordinates. In addition the solubility parameters for the twenty solvents were represented in 3D coordinates. The specic optimum solvent for dissolving each bioantioxidant could be predicted by illustrating the solubility parameters of the solute and solvent in three-dimensional space before calculating the solubility of the bioantioxidants quantitatively using Eq. (14) (Fig. 2). As a result, it could be predicted that ascorbic acid, epigallocatechin gallate are most soluble in UREA-R, and citric acid are most soluble in methanol, and caffeic acid are most soluble in ethanol, and epicatechin are most soluble in ethylene glycol, and BHT is most soluble in tetrahydrofuran (Fig. 3). The 3D coordinates of the solubility parameters are a very useful tool for selecting the best soluble solventsolute pair. 3.4. Activity coefcients of bioantioxidants Table 5 lists the solubility of bioantioxidants calculated for twenty different solvents using Eq. (14) [10,11]. The bioantiox-

In most cases, the LSE modied using Raoults law with activity coefcient may indicate that the following equilibrium equation, xL g L pL xS g S pS i i i i i i fiL pi , and xS i
S i

(11)

where the standard state when the g 1 are applied to the pure solid phase, is changed in the following manner: xL g L i i pi;solid phase pi;subcooled liquid (12)

At low pressure, the fugacity ratio of the liquid phase to the solid phase is represented with the solid phase fusion enthalpy and its melting temperature. ln x1 g 1

Dhfus 1 RT t;1 1 T t;1 =T

(13)

where x1 is the mole fraction in the liquid phase, g is the activity coefcient in the liquid phase, Dhfus is the molar enthalpy of fusion 1 of component 1, T is the absolute temperature of the mixture, and R is the universal gas constant. The triple point is similar to the melting point at 1 atm. Therefore, it is common to change Tm for Tt
Table 5 Solubility of bioantioxidants in the twenty functional solvents. Ascorbic acid Heptane Hexane Pentane Cyclohexane Toluene Xylene (meta) Benzene Diethyl ether Butyl acetate Tetrahydrofuran n-Propanol Ethyl acetate Acetone Methanol Ethanol Acetic acid Methyl hydroperoxide Acetamide Ethyleneglycol UREA-R 5.50 1015 2.55 1015 1.42 1015 2.18 1013 7.42 1016 4.47 1014 2.30 1014 2.65 1014 1.90 1012 7.27 1012 1.93 1008 1.51 1011 2.49 1011 1.85 1005 2.42 1007 2.14 1004 7.56 1004 b 2.74 1004 1.65 1004 a 1.01 1003 Caffeic acid 3.78 1007 2.26 1007 1.52 1007 4.17 1006 9.72 1008 1.51 1006 9.79 1007 1.07 1006 1.59 1005 3.55 1005 2.01 1003 5.43 1005 7.23 1005 b 1.03 1002 a 5.09 1003 1.02 1002 7.21 1004 3.76 1003 5.53 1003 1.71 1004 Citric acid

BHT 3.25 1002 2.33 1002 1.78 1002 1.25 1001 1.31 1002 7.39 1002 5.79 1002 b 6.10 1002 2.19 1001 a 2.81 1001 1.37 1001 3.10 1001 3.27 1001 1.51 1004 3.23 1002 1.13 1004 3.54 1011 4.73 1008 4.11 1007 1.92 1013

Epicatechin 3.34 1015 1.20 1015 5.49 1016 4.22 1013 2.30 1016 5.32 1014 2.23 1014 2.69 1014 6.88 1012 3.79 1011 5.01 1007 9.52 1011 1.78 1010 b 4.29 1004 7.83 1006 4.78 1004 9.78 1004 1.63 1003 a 1.49 1003 3.89 1004

Epigallocatechin gallate 7.11 1028 1.33 1028 3.70 1029 2.15 1024 8.99 1030 6.83 1026 1.62 1026 2.20 1026 2.38 1022 4.36 1021 1.05 1013 2.13 1020 6.31 1020 2.05 1007 2.30 1011 2.76 1007 2.89 1004 b 4.63 1005 1.73 1005 a 4.13 1004

2.08 1008 1.21 1008 7.94 1009 2.65 1007 4.99 1009 8.96 1008 5.67 1008 6.26 1008 1.12 1006 2.67 1006 2.61 1004 4.25 1006 5.82 1006 a 3.17 1003 8.47 1004 b 3.23 1003 7.45 1004 2.30 1003 2.85 1003 2.51 1004

a: 1st soluble solvent; b: 2nd soluble solvent (the soluble solvent pair was determined from the nearest distance between the solubility parameters of the solvent and solute in three-dimensional space).

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Fig. 2. Correlation between the solute and solvents, on a three-dimensional plot (~: solute, ^: rst soluble solvent, &: second soluble solvent) (1: heptane, 2: hexane 3: pentane, 4: cyclohexane, 5: toluene, 6: xylene (meta), 7: benzene, 8: diethyl ether, 9: butyl acetate, 10: tetrahydrofuran, 11: n-propanol, 12: ethyl acetate, 13: acetone, 14: methanol, 15: ethanol, 16: acetic acid, 17: methyl hydroperoxide, 18: acetamide, 19: ethylene glycol, and 20: UREA-R).

idants were most soluble in a solvent with a similar total solubility parameter value, as predicted. The non-ideality between the bioantioxidants and solvent was calculated using the activity coefcient. The activity coefcient was presented in equation (13). The solubility data for the bioantioxidants were distributed in 4.13 104 to 2.81 101. The non-ideality index, activity coefcients ranged from 1.002 to 2.040. The activity coefcients for each bioantioxidant-specic solvent pair were correlated graphically in Fig. 3. Caffeic acid showed the maximum value

Table 6 Solubility and activity coefcients of the bioantioxidants. Solutes (2) Ascorbic acid Caffeic acid Citric acid BHT Epicatechin Epigallocatechin gallate x2 103 1.01 5.09 3.17 281.00 1.49 0.413

Dsfus (J/mol K) 2
100.83 55.43 106.71 55.33 71.66 147.38

g2
1.043 2.040 1.070 1.253 1.100 1.002

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between the solubility parameters of the solvent and solute in three-dimensional space, i.e., solvent and bioantioxidant with most similar dt value. The equilibrium non-ideality was measured quantitatively using the activity coefcient for six species of solventbioantioxidant pairs. The numerical values ranged from 1.002 to 2.040 and showed a positive deviation from the ideal state. This activity coefcient is very important information for the solution and extraction process of bioantioxidants. Acknowledgement The present research was conducted by the research fund of Dankook University in 2009. References
[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] H.S. Choi, M.J. Lee, M.S. Na, M.Y. Lee, D.B. Choi, J. Ind. Eng. Chem. 15 (2009) 275. R. Adelman, R.L. Saul, B.N. Ames, Proc. Natl. Acad. Sci. U.S.A. 85 (1989) 2706. B.N. Ames, Science 221 (1983) 1256. P. Amstad, D. Cerutti, Environ. Health Perspect. 88 (1990) 77. H.J. Lee, I.K. Hong, J. Kor. Ind. Chem. 20 (2009) 346. J.H. Kang, S.T. Chung, K.H. Row, J. Ind. Eng. Chem. 8 (4) (2002) 354. Charles M. Hansen, Hansen Solubility Parameter: A User Hand Book, CRC Press, Boca Raton, 1999. C. Ozdemir, A. Guner, Eur. Polym. J. 43 (2007) 3068. S. Verheyen, P. Augustijns, R. Kinget, G. Van den Mooter, Int. J. Pharm. 228 (2001) 199. J.M. Prausnitz, R.N. Lichtenthaler, E.G. de Azevedo, Molecular Thermodynamics of Fluid-phase Equilibria, PTR, Prentice Hall, NJ, 1999. N. De Nervers, Physical and Chemical Equilibrium for Chemical Engineers, John Wiley & Sons, New York, 2002. J.O. Hireschfelder, C.F. Curtiss, R.B. Bird, Molecular Theory of Gasses and Liquids, John Wiley & Sons, New York, 1964. E.K. Goharshadi, M. Hesabi, J. Mol. Liquids 113 (2004) 125. M. Terada, R.H. Marchessault, Int. J. Biol. Macromol. 25 (1999) 207. K. Adamsk, A. Voelkel, K. Heberger, J. Chromatogr. A 1171 (2007) 90. D.W. van Krevelen, The Properties of Polymer, Elsevier, New York, 1990. A. Guner, Eur. Polym. J. 40 (2004) 1587. R. Ravindra, K.R. Krovvidi, A.A. Khan, Carbohydr. Polym. 36 (1998) 121. D.D. Back, L.R. Grzyll, M. Corrign, Thermochim. Acta 272 (1996) 53. A. Forster, J. Hempenstall, I. Tucker, T. Rades, Int. J. Pharm. 226 (2001) 147.

Fig. 3. Activity coefcient of the six bioantioxidants for representing the deviation from system ideality.

for non-ideality. It was not the maximum total solubility parameter, but showed the maximum dispersion solubility parameter component (dd-component) (Table 6). 4. Conclusions The aim of this study was to predict the solubility parameter for six bioantioxidants and twenty functional solvents using the group contribution method and calculate the quantitative equilibrium mole fraction for the optimum solutesolvent pairs. The total solubility parameter was calculated from three solubility parameters, molecular dispersion, polarity, and hydrogen bonding effect using the van Krevelen model, and the solubility was calculated using solidliquid equilibrium state model. The optimal solute solvent pair was determined from the nearest distance