Ind. Eng. Chem. Res.

2010, 49, 13951401

1395

Measurement and Modeling Solubility of Aqueous Multisolute Amino-Acid Solutions

Jan-Bernd Grosse Daldrup, Christoph Held, Feelly Ruether, Gerhard Schembecker, and Gabriele Sadowski*,
Laboratory of Plant and Process Design and Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, Technische UniVersita t Dortmund, Emil-Figge-Strasse 70, 44227 Dortmund, Germany

The solubilities of the ternary mixtures L-alanine/L-leucine, L-alanine/L-valine, and L-leucine/L-valine in water were measured at 303 and 323 K. The solubilities of seven binary, eight ternary, and one quaternary aminoacid systems were modeled using the PC-SAFT equation of state. For this purpose, new parameters for L-aspartic acid, L-glutamic acid, L-leucine, and L-tyrosine are presented. The model excellently reproduces binary solubility data with a linear temperature-dependent binary interaction parameter for the solute-solvent interaction. PCSAFT allows for a very good prediction of the solubility behavior of ternary mixtures over a wide range of temperature and concentration. The aqueous mixture with three amino acids is then predicted without any further adjustment with an average relative deviation of 3.34%.
Introduction The increasing amounts of chemicals produced from biological feed and by fermentation pose an interesting challenge for the design of downstream processes due to the high complexity of the mixtures created in the production process. An example for the importance of such chemicalssproduced in biotechnological processessis the produced amount of amino acids which increased from a total amount of approximately 1650 ktons/ year in 19961 to 2450 ktons/year in 20062 and 2980 ktons/year in 2008.3 As most of these amino acids are produced by protein hydrolysis or fermentation, the solubility, its pH dependence, and the inuence of the cosolute concentration (e.g., other amino acids) are of interest for the design of downstream processes. Basic solubility data of binary aqueous amino-acid solutions is readily available in the literature (e.g., several books4,5). Although the solubility data available for multisolute solutions are rather sparse, Kuramochi et al.6 gave an overview of solutions of two amino acids in water. Most of the cited references dealt with racemic mixtures of amino acids and their solubility behavior with another amino acid (see Table 1). In this work the binary solubilities of L-alanine, L-leucine, and L-valine in water as well as the ternary and quaternary solubility behavior of three pairs of amino acids in water were measured. The solubilities were modeled with the PC-SAFT model proposed by Gross and Sadowski7,8 which was also used by Fuchs et al.9 for amino-acid solubilities. To describe the solubilities measured in this work and given in the literature, the parameters of L-alanine, L-valine, glycine, L-aspartic acid, L-glutamic acid, L-leucine, and L-tyrosine were tted to our own and literature data. The melting enthalpies and temperatures of L-alanine and L-valine were determined according to the group contribution method by Marrero and Gani10 (see Parameter Estimation). Measurement of Solubilities The amino acids used were provided by Evonik AG and Merck KGaA with a purity of >99.0%; they were used without
* To whom correspondence should be addressed. Tel.: +49 231 755 2635. Fax: +49 231 755 2572. E-mail: g.sadowski@bci.tu-dortmund.de. Laboratory of Plant and Process Design. Laboratory of Thermodynamics.
Figure 1. Solubility of leucine in water between 260 and 380 K. Symbols: experimental data (Carta and Tola,28 Kurosawa,12 Dalton and Schmidt,26 Budavari17). Line: PC-SAFT calculation (temperature-dependent kij between water and L-leucine, see Table 4). Table 1. Literature Dealing with Multisolute Amino Acid Solutions amino acids glycine, L-leucine, L-tyrosine, L-cystine L-isoleucine, L-leucine, L-valine L-isoleucine, L-leucine, L-valine glycine + DL-aspartic acid; glycine + DL-phenylalanine reference Carta et al.11 Kurosawa et al.12-14 Givand et al.15 Soto et al.16

further purication. Due to divergent data for L-leucine (see Figure 1) and to ensure the substance purity for L-leucine, L-alanine, and L-valine, the solubilities of the single-solute systems were measured. For this purpose the amino acids were placed in glass vials (20 mL) and puried water was added. These vials were placed in a rotary oven with a temperature deviation of (0.3 C and allowed to equilibrate for 48 h. From these vials a sample of 2 mL of solution was withdrawn with a preheated syringe with a syringe lter (pore size 0.45 m). The sample was weighed with an accuracy of 0.01 mg, and the solvent was evaporated in a drying chamber and afterward weighed again. In order to ensure a total evaporation of the solvent, the sample was placed back in the drying chamber and

10.1021/ie900913c 2010 American Chemical Society Published on Web 12/16/2009

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Table 2. Assigned Groupsa and Amount of Groups Used for the Determination of the Melting Temperature and Enthalpy with the Group Contribution Method by Marrero and Gani10 group no.a
L-Ala L-Asp L-Glu

Gly

L-Leu

L-Tyr

L-Val

First Order CH3 CH2 CH C aCH aC-CH2 OH aC-OH COOH CH2NH2 CHNH2 (CH3)2CH CHm(NHn)COOH (m, n in 0, ..., 0.2) AROMRINGs1s4 HOOC(CHn)mCOOH- (m > 2, n in 0, ..., 0.2)
a

1 2 3 4 15 21 29 30 31 54 55 1 26 106 1

1 1 2

2 1 1 4 1

2 1

1 1

2 1

2 1

1 1

1 1 1 1

1 1 1

1 1 1 1

Second Order 1 Third Order 1 1 Numbered according to ref 10. 1 1 1 1 1

was reweighed after 24 h. This gravimetric method was used to determine the amount of amino acid in saturated solutions in binary mixtures and the total amount of amino acids in ternary mixtures. As a typical example, Figure 1 shows the solubility of L-leucine versus system temperature. It can be seen that our data agree excellently with those of other authors. The data of Budavari17 do not match the other results, which might indicate the use of D- or DL- instead of L-leucine. In the case of ternary mixtures the ratio of the amino acids was determined by HPLC. For the determination of the ratio of amino acids in multiple mixtures, the dried solutes were dissolved in 15 mL of water. From this solution 100 L was taken and diluted with 1 mL of eluent. HPLC was performed on a Merck automated HPLC analyzer with an isocratic eluent prole. The solid phase used was an amino phase from Macherey & Nagel (EC250/3 Nucleosil 100-5-NH2 RP). The eluent was an acetonitrile-water mixture with an potassium phosphate buffer (65.8 wt % acetonitrile (HPLC grade), 34.2 wt % puried water, 0.769 g of potassium hydrogen phosphate, and 1.830 g of potassium dihydrogen phosphate/kg of solvent, pH 7.2). The pH value was adjusted by adding concentrated phosphoric acid. For the determination of the concentration, 10 L of sample was injected. The volume ow of the eluent was varied between 0.5 and 1 mL/min. To ensure a pure solid phase, X-ray diffraction measurements were performed with amino acids of 99.0% purity and the solid phase after the solubility measurement. Modeling of Solubilities Based on the phase equilibrium conditions for solid and liquid phasessassuming pure solid phases and neglecting the inuence of the heat capacitiessthe solubility of component i at atmospheric pressure can be calculated according to Prausnitz18 and Gmehling et al.:19 xL i ) 1 T exp 1 - SL RT L T i 0i

(see Tables 2 and 4) and adjusted to the solubility curve within SL the given deviation (dev(T SL 0i ) ) 7.6% and dev(h0i ) ) 15.7%). The inuence of cosolutes on the solubility of component i is expressed only by the activity coefcients (L i ), which change with different composition and temperature. There are different possibilities to calculate activity coefcients of ternary mixtures; e.g., the UNIFAC method was used in the work of Kuramochi et al.6 and Kurosawa et al.,13 and the NRTL,16 the hard sphere model,16 and the SAFT equation of state were applied by Ji and Feng.20 The model used in the current work is the PC-SAFT equation of state. With this model the residual Helmholtz energy can be calculated as the sum of different contributions such as hardchain repulsion, dispersive (van der Waals) interactions, and associative (hydrogen bonding) interactions. Aresidual ) Ahard chain + Adispersion + Aassociation (2) The equations for hard-chain and dispersion contributions can be found in refs 7 and 8. The association term was used as suggested in ref 21. To describe an associating compound, ve pure-component parameters are required: the segment number (m), the segment diameter (), the dispersion-energy parameter AiBi ), and the associa( /k), the association-energy parameter ( hb AiBi ). tion-volume parameter (hb To describe binary systems, the conventional Berthelot-Lorentz combining rules are applied, and only one binary parameter is introduced, correcting the dispersion-energy parameter for the mixture of component i and j in eq 4: 1 ij ) (i + j) 2
ij

(3) (4) (5)

) (1 - kij)

i j

SL SL The quantities h0 i and T 0i represent the enthalpy and the temperature of melting of the pure substance i, respectively. However, they are not available for amino acids as they decompose before melting. Thus, the values were estimated with the group contribution method proposed by Marrero and Gani10

[ ( )]
hSL 0i

kij ) kij,25 C + kij,T(T - 298.15 K)

(1)

To improve the accuracy of the model, the binary parameter which describes the interactions of solvent and solute was determined with a linear temperature dependency if necessary; see eq 5. This procedure is commonly used (see e.g. ref 22) when very accurate ts for low solubility values are desired. We applied linear temperature-dependent binary parameters for four amino acid-water pairs in this work (see Table 4). To describe the unlike solute-solute interactions in ternary mix-

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Table 3. PC-SAFT Parameters for Water m 1.2047 see eq 8 /k 353.95 N 2
24

1397

AiBj hb /k

iBj kA hb

2425.67

0.0451

tures, the binary parameter is assumed to be constant (i.e., temperature independent) and was tted to the experimental data of the solute with the lower solubility. For cross-association systems in this study, the strength of cross-associating interactions between two associating substances can be described by applying simple mixing and combining rules, as suggested by Wolbach and Sandler.23
AiBj hb

1 ) ( 2

AiBi hb

AjBj hb )

(6)

iBj A hb )

AiBi AjBj hb hb

(1/2)(ii + jj)

iijj

(7)

Thus, no adjustable correction parameters have to be introduced in the association term. The PC-SAFT parameters used for the modeling are given in Tables 3 and 4, where N denotes the number of the association sites acting as proton donators and as proton acceptors. Most amino acids are modeled with two association sites, with the amino group acting as a proton acceptor and the acid group acting as a donor. As amino acids are zwitterionic molecules, the overall charge is mostly neutral and the ionic character is not regarded in modeling. We used a temperature-dependent segment diameter for water as described by Cameretti and Sadowski.24 The calculation for the segment diameter is given in eq 8, where represents the segment diameter and T is the temperature (in kelvin): (T) ) 2.7927 + 10.11 exp(- 0.01775T) 1.417 exp(- 0.01146T) Parameter Estimation The PC-SAFT parameters of glycine, DL-alanine, and L-valine have already been determined in previous works by Fuchs et al.9 and Cameretti and Sadowski.24 In this work, the parameters for glycine, L-alanine, L-valine, L-aspartic acid, L-glutamic acid (-form), L-leucine, and L-tyrosine were tted to different

experimental data, such as solubilities, binary mixture densities, and amino acid activity coefcients (see Table 4). With the obtained parameters, not only solubilities but also solution densities and (water and amino acid) activity coefcients can be described (see Table 4). L-Aspartic acid and L-glutamic acid were assumed to exist in a neutrally charged form in aqueous solution. On the one hand, this differs from the real solutions as both amino acids are not only present as neutral zwitterions but also present as anions and cations (e.g., L-glutamic acid, pI ) 3.2175). On the other hand, we describe this by applying more than one association site acting as acidic groups. Furthermore, some of the former parameters were readjusted as the values of the melting properties were unphysically high (e.g., 24 TSL L-valine ) 1800 K ). Now the values of the melting temperatures are more reasonable (for L-alanine, TSL ) 692.4 K, and for L-valine, T SL ) 680.0 K). The parameters used for the modeling are listed in Tables 3 and 4, as are the average absolute deviation (AAD, see eq 9) and the average relative deviation (ARD, see eq 10) of the calculated binary data to the experimental data. AAD ) 1 |(ycalc - yexp k )| NP k)1 k
NP ycalc k 1 1 - exp NP k)1 yk

NP

(9)

ARD )

|(

)|

(10)

Considered Ternary and Quaternary Mixtures We considered ternary and quaternary mixtures of amino acids in water with one pure amino acid in the solid phase. Thus, mixtures forming a solid solution, such as L-leucine12 L-isoleucine-water, are not included. Furthermore, the solubility of amino acids in water is pH-dependent (e.g., refs 9, 28, and 34). This dependency is expressed by an increased solubility at pH values near the pKa values of the amino acid. We rst do not take into account the pH inuence; hence, the considered amino acids shall possess similar isoelectric points and pKa

(8)

Table 4. Pure-Component and Binary PC-SAFT Parameters for Amino Acids, Calculated10 and Adjusted Melting Properties, and Deviations between Correlated and Experimental Data parameter m /k [K] N AiBi hb /k [K] iBi A hb T SL [K] hSL/R [K] SL T calc [K] SL hcalc /R [K] kij,25 C(H2O) kij,T(H2O) solution density T range [K] ARD [%] AAD [kg/m3] solubility T range [K] ARD [%] AAD [mol/kg] amino acid activity coeff T range [K] ARD [%] AAD
L-Ala L-Asp L-Glu

Gly 4.8495 2.3270 216.96 2 2598.06 0.0393 714.3 2109.3 462.50 3415.7 -6.12 10-2 ref 25 298 0.09 0.96 ref 5 298-373 2.88 0.13 ref 32 298 1.64 0.01

L-Leu

L-Tyr

L-Val

5.4647 2.5222 287.59 2 3176.60 0.0819 692.4 2543.7 580.58 2749.4 -6.12 10-2 2.91 10-4 ref 25 298 0.20 0.23 this work 288-346 1.05 0.02 ref 30 298 0.07 <0.01

2.9998 3.3668 207.74 3 3265.67 0.0436 619.0 2802.7 595.43 3241.3 -1.92 10-4 ref 26 298 0.03 0.25 ref 5 273-373 5.68 0.01 n.a.

3.0248 3.4781 164.54 3 2536.56 0.0160 586.8 3022.6 596.0 3558.8 -1.29 10-1 this work 298.43 0.01 0.1 ref 29 278-342 2.23 <0.01 ref 31 310 0.14 <0.01

8.3037 2.7000 330.00 2 3600.00 0.0200 620.9 4499.8 582.55 3330.3 -6.30 10-2 4.09 10-4 ref 27 298 0.03 0.25 this work 288-346 1.98 <0.01 n.a.

8.1390 2.2798 289.37 3 2500.00 0.0400 542.5 5000.3 601.67 4764.0 -2.77 10-4 2.90 10-4 ref 28 298-318 0.01 0.02 ref 5 273-373 5.68 0.01 n.a.

6.5370 2.7211 397.07 2 3332.49 0.0386 680.0 3197.2 581.83 3012.8 -6.15 10-2 3.85 10-4 ref 27 298 0.02 0.17 this work 303-346 2.30 0.02 ref 33 298 0.18 <0.01

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L-Leucine

Table 5. Model Mixtures Consisting of at Least Two Amino Acids in Water aqueous solutions containing
L-Glu

Table 9. Solubility Data: Ternary Solutions of L-Alanine and in Water T [K] 303 303 303 303 323 323 323 323 T [K] 303 303 303 303 323 323 323 323
L-Val

reference Jin and Chao Carta11 Carta11 Carta11 this work Kurosawa et al.;13 this work this work this work
35

[mol/kgwater]

L-Leu

(solid) [mol/kgwater]

and L-Asp and Gly L-Leu and L-Tyr L-Tyr and Gly L-Leu and L-Ala L-Leu and L-Val L-Ala and L-Val L-Ala, L-Leu, and L-Val
L-Leu

0.0388 ( 0.0020 0.0925 ( 0.0049 0.2512 ( 0.0045 0.3611 ( 0.0003 0.1635 ( 0.0124 0.0751 ( 0.0083 0.4121 ( 0.0035 0.5346 ( 0.0016
L-Val

0.1755 ( 0.0030 0.1720 ( 0.0040 0.1602 ( 0.0040 0.1518 ( 0.0016 0.1913 ( 0.0138 0.1851 ( 0.0086 0.1716 ( 0.0040 0.1528 ( 0.0048
L-Leu

Table 6. Solubility Data: Binary Solutions of L-Alanine, L-Leucine, and L-Valine in Water T [K] 288 293 298 303 308 314 318 324 334 346
L-Leucine L-Ala

(solid) [mol/kgwater]

[mol/kgwater]

[mol/kgwater]

L-Leu

[mol/kgwater]

L-Val

[mol/kgwater]

1.7204 ( 0.0109 1.7774 ( 0.0362 1.8117 ( 0.0186 1.9747 ( 0.0103 2.0696 ( 0.0055 2.1989 ( 0.0104 2.3107 ( 0.0056 2.4573 ( 0.0046 2.7455 ( 0.0065 3.0450 ( 0.0117

0.1585 ( 0.0005 0.1603 ( 0.0005 0.1644 ( 0.0011 0.1721 ( 0.0004 0.1773 ( 0.0005 0.1865 ( 0.0003 0.1947 ( 0.0010 0.2057 ( 0.0003 0.2306 ( 0.0014 0.2612 ( 0.0026

0.5179 ( 0.0037 0.5287 ( 0.0034 0.5578 ( 0.0053 0.5741 ( 0.0002 0.6028 ( 0.0009 0.6594 ( 0.0030 0.7300 ( 0.0039

0.5255 ( 0.0021 0.5208 ( 0.0016 0.5195 ( 0.0011 0.5200 ( 0.0046 0.6021 ( 0.0018 0.6025 ( 0.0024 0.6028 ( 0.0061 0.5997 ( 0.0061

0.0127 ( 0.0020 0.0271 ( 0.0004 0.0744 ( 0.0002 0.1077 ( 0.0026 0.0206 ( 0.0009 0.0397 ( 0.0011 0.0963 ( 0.0054 0.1384 ( 0.0060

Table 7. Solubility Data: Ternary Solutions of L-Alanine and in Water T [K] 303 303 303 303 323 T [K] 303 303 323 323 323
L-Ala

[mol/kgwater]

L-Leu

(solid) [mol/kgwater]

0.5621 ( 0.0041 0.9478 ( 0.0213 1.3861 ( 0.0048 1.8320 ( 0.0276 1.0957 ( 0.0296
L-Ala

0.1532 ( 0.0035 0.1427 ( 0.0005 0.1324 ( 0.0021 0.1221 ( 0.0017 0.1835 ( 0.0040
L-Leu

(solid) [mol/kgwater]

[mol/kgwater]

1.9503 ( 0.0031 1.9335 ( 0.0012 2.3148 ( 0.0047 2.2486 ( 0.0102 2.2817 ( 0.0024

0.0819 ( 0.0025 0.1214 ( 0.0022 0.0905 ( 0.0016 0.1789 ( 0.0039 0.1359 ( 0.0020

Table 8. Solubility Data: Ternary Solutions of L-Alanine and L-Valine in Water T [K] 303 303 303 303 323 323 323 T [K] 303 303 303 303 323 323 323
L-Ala

[mol/kgwater]

L-Val

(solid) [mol/kgwater]

0.1576 ( 0.0039 0.3334 ( 0.0028 0.8865 ( 0.0018 0.2360 ( 0.0128 0.4596 ( 0.0061 1.1363 ( 0.0111 1.7412 ( 0.0066
L-Ala

0.5233 ( 0.0018 0.5116 ( 0.0043 0.4904 ( 0.0005 0.5813 ( 0.0110 0.5608 ( 0.0056 0.5025 ( 0.0270 0.4828 ( 0.0093
L-Val

with data from the literature (refs 5, 35, and 36), as does the solubility of L-valine (refs 5 and 13), whereas the solubility of L-leucine is difcult to compare to data found in the literature as these are highly divergent (see Figure 1; refs 11, 12, 17, and 26). Our measured L-leucine solubility does match the data of Kurosawa12 so that the kij between L-leucine and water has been adjusted to our own experimental data. Figure 2 illustrates the solubility of L-tyrosine in water, a very low-soluble amino acid. It can be seen that all the available literature data agree well with each other except for the data presented by Carta and Tola,28 where small deviations can be observed. Thus, we adjusted the kij between water and L-tyrosine to the data from the other authors, yielding an excellent modeling result. The investigated ternary systems consist of two amino acids which are L-alanine, L-valine, or L-leucine in water. We focus on these three amino acids as we also present a quaternary system consisting of all these molecules later on. In Tables 7-9 all our measured data for these ternary systems are shown. From the solubility behavior of the measured solutions it becomes obvious that these mixtures form eutectic systems. This is also afrmed by the X-ray diffraction measurements, which show no change in the peak positions of the pure substances and the substance after solubility measurement. Moreover, also Kurosawa12 detected an eutectic for the ternary mixture L-leucineL-valine-water.

(solid) [mol/kgwater]

[mol/kgwater]

1.8939 ( 0.0107 1.9059 ( 0.0120 1.8924 ( 0.0037 1.9249 ( 0.0050 2.3968 2.3899 ( 0.0189 2.4002 ( 0.0044

0.0926 ( 0.0029 0.2323 ( 0.0048 0.3296 ( 0.0021 0.0458 ( 0.0029 0.1382 0.3611 ( 0.0120 0.0628 ( 0.0016

values. The mixtures of amino acids fullling these criteria are listed in Table 5. Results and Discussion The experimental solubilities of the considered systems are listed in Tables 6-9 and in Table 11. In Table 6, our experimental binary solubilities (one amino acid in water) are presented. The single-solute solubility of L-alanine agrees well
Figure 2. Solubility of L-tyrosine in water between 290 and 360 K. Symbols: experimental data (Carta and Tola,28 Drautz,37 Sober,5 Hitchcock,38 Dalton and Schmidt26). Line: PC-SAFT calculation (temperature-dependent kij between water and L-tyrosine, see Table 4).

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Figure 3. Ternary mixture L-alanine-L-leucine-water. Symbols: experimental data (this work). Line: PC-SAFT calculation (kij between L-alanine and L-leucine set to 0.02). Table 10. Binary Interaction Parameter kij, AAD, and ARD of the Treated Systems main solute/cosolute Ala/Val Ala/Leu Asp/Glu Leu/Ala Leu/Val Leu/Gly Leu/Tyr Glu/Asp Gly/Leu Gly/Tyr Tyr/Leu Tyr/Gly Val/Leu Val/Ala av deviation data this work this work Jin35 this work this work Carta11 Carta11 Jin35 Carta11 Carta11 Carta11 Carta11 this work this work kij 0 0.02 0 0.02 0 0.07 0 0 0.07 0.02 0 0.02 0 0 ARD [%] 1.60 2.44 6.67 1.38 5.64 1.29 (7.38) 0.92 (6.05) 3.51 3.25 (7.41) 4.76 (11.71) 1.78 (16.21) 2.08 (13.35) 2.95 4.32 3.04 (6.47) AAD [mol/kg] 0.03 0.06 <0.01 <0.01 0.01 0.01 <0.01 <0.01 0.13 0.20 <0.01 <0.01 0.02 0.02 0.03

Figure 4. Ternary mixture L-valine-L-leucine-water. Symbols: experimental data (Kurosawa et al.13). Line: PC-SAFT calculation (kij between L-valine and L-leucine set to 0).

As an example, the solubility behavior of the mixture is illustrated in Figure 3. It can be observed that for this system the measured solubility of the precipitating amino acid decreases with increasing amount of the cosolute. As the amino acid parameters are already xed (Table 4), the solubility behavior of the ternary system can directly be predicted with PC-SAFT. Although the prediction (with no additional interaction parameters) already yields good results, we applied a constant kij (between L-alanine and L-valine, tted to one solubility point at 313 K) to this system to improve the modeling. Moreover, the temperature extrapolation to 333 K can be safely performed, as shown in Figure 3. The deteriorative effect of both solutes on the solubility of the other amino acid can thus be described satisfactorily. The deviation between modeled and measured data is given in Table 10 (AAD and ARD), where the binary kij parameter between two solutes used for the calculations is also given. Figure 4 illustrates the solubility data for the system L-valineL-leucine-water. Our experimental work compares well with the data presented by Kurosawa.12 As for L-alanine-L-leucinewater, the measured data show a decrease in solubility with increasing amount of cosolute. This behavior can be predicted with PC-SAFT (kij ) 0); i.e., no additional adjustment is necessary to describe the experimental data. The AADs and the ARDs for this system are summarized in Table 10. Again, the model is able to predict the solubility at different temperatures without applying any temperature-dependent ternary parameters.
L-alanine-L-leucine-water

The mixture L-valine-L-alanine-water (results are not shown here) has a similar solubility behavior as described above. PC-SAFT is able to predict the solubilities without using additional kij parameters. The AAD and ARD are listed in Table 10. Beside the solubilities measured in this work, experimental data from literature was also modeled with PC-SAFT. One data set used was measured by Carta.11 Figures 1 and 2 (solubilities of L-leucine and L-tyrosine in water) already reveal that the data from Carta and Tola28 differ from other data.5,26,37 The same is valid for glycine. Comparing L-leucine (our data at 298 K) with data presented by Carta and Tola gives an ARD of 8.37%, comparing data for L-tyrosine (Drauz et al.37 at 298 K) with data from Carta and Tola gives an ARD of 37.83%, and comparing data for glycine (Sober5 at 298 K) with data from Carta and Tola gives an ARD of 5.17%. These differences in the single-solute data can also be observed in the ternary systems. To test whether the model can predict solubility behavior qualitatively, we readjusted the two-solute solubility data from Carta and Tola to the single-solute solubilities; i.e., the difference of the single-solute data supplied by Carta and Tola to the binary data used for parameter tting was calculated for each temperature. This calculated difference was subtracted from the ternary data, thus shifting the ternary data but leaving it with the same slope. The result can be seen in Figures 5 and 6, where the original data and the adjusted data of the mixture L-leucine-L-tyrosine-water and the PC-SAFT calculations are illustrated. It can be observed that the solubility behavior differs from the systems shown previously: Whereas the solubility of L-leucine slightly decreases with increasing amount of cosolute, the solubility of L-tyrosine increases with increasing amount of cosolute. Despite this opposite solubility inuence of both cosolutes, this behavior can be predicted well with PC-SAFT without applying additional ternary parameters (Figure 6). Temperature extrapolation is also possible within the shown temperature range (298-318 K). This is also valid for the other ternary mixtures. The AAD and the ARD of all modeled mixtures are shown in Table 10, where the deviation between model and adjusted values is given and the deviation between model and original values is given in parentheses. In Figure 7, the mixture L-glutamic acid-L-aspartic acid-water measured by Jin and Chao35 is illustrated. In this system, both amino acids exist beside the neutral form as anions and cations. In the modeling they are treated equally with two acidic and one basic association sites. Obviously,

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Table 11. Solubility Data: Quaternary Solution, Experimental (Single Data Points) and Modeled Data calcd solubility ARD [mol/kgwater] [mol/kgwater] [mol/kgwater] [mol/kgwater] [%]
L-Leu L-Val L-Ala L-Ala

T [K]

Solid 2.3397 2.3416 Solid 1.5337 0.9987 Solid 1.2030 1.2432 0.5390 0.5364 7.00 6.86 3.34 0.1581 0.1686 3.22 2.41 2.3419 2.3523 0.09 0.46

323 323 323 323 323 323 av deviation

0.1149 0.0991 0.1633 0.1727 0.1129 0.1280

0.3743 0.3377
L-Leu

0.3865 0.3916
L-Val

0.5038 0.5019

Figure 5. Ternary mixture L-leucine-L-tyrosine-water. Symbols: original experimental data.11 Line: PC-SAFT calculation (kij between L-leucine and L-tyrosine set to 0).

solubility behavior at 298, 313, and 333 K. No adjustment of additional interaction parameters is necessary (kij ) 0) with small AAD and ARD values in Table 10. In addition to the ternary systems described containing L-alanine, L-leucine, and L-valine, our experimental solubility data of the quaternary mixture of L-alanine-L-leucine-L-valine in water can also be validated by the model. Our measured values as well as the predicted results for the main-solute solubility at given cosolute concentrations are listed in Table 11. Furthermore, the ARD is given, which is with 3.34% in a quite reasonable range for a model prediction, especially in view of the fact that no additional parameters are needed in addition to those already xed in the ternary system. Conclusion The single-solute solubilities of L-alanine, L-leucine, and were determined experimentally in a temperature range from 288 to 346 K. The ternary mixtures of pairs of these amino acids in water were measured at 303 and 323 K and were found to have an eutectic behavior. Finally, also the solubility behavior of one quaternary system containing three amino acids was measured. The PC-SAFT equation of state was applied to model the solubility of multicomponent aqueous amino-acid systems. Universal parameter sets were presented whichsnext to solubility calculationssalso allow for solution density and component activity coefcient modeling. To improve the solubility of one amino acid in water, the binary interaction parameter kij was extended with a linear temperature dependency if necessary. The ternary solubility behavior was described with only one temperature-independent parameter between the two solutes that was adjusted to the ternary solubility data. To model solubilities in ternary mixtures given in the literature and in this work, new parameter sets for L-aspartic acid, L-glutamic acid, L-tyrosine, and L-leucine were determined. In total, eight ternary mixtures were modeled with an average relative deviation of 3.04%. With the knowledge of the binary interaction parameters gathered from binary mixtures, multiple mixtures containing more than three components can be modeled without any further adjustment. An example is the quaternary mixture L-alanineL-leucine-L-valine in water with an average relative deviation between modeled and experimental solubility of 3.34%.
L-valine

Figure 6. Ternary mixture L-leucine-L-tyrosine-water. The data used were adjusted by subtracting the difference of the binary data at each temperature from the ternary data. Symbols: adjusted experimental data. Line: PC-SAFT calculation (kij between L-leucine and L-tyrosine set to 0).

Figure 7. Ternary mixture L-glutamic acid-L-aspartic acid-water. Symbols: experimental data (Jin and Chao35). Line: PC-SAFT calculation (kij between L-glutamic acid and L-aspartic acid set to 0).

the solubility of each solute increases with addition of the second solute. In contrast to the other ternary amino acid systems presented, a benecial effect of both cosolutes on each other can be observed. Applying the pure-component PCSAFT parameters allows for a very good prediction of the systems

Nomenclature
AbbreViations SLE ) solid-liquid equilibrium

Ind. Eng. Chem. Res., Vol. 49, No. 3, 2010 Symbols A ) Helmholtz energy [J] ) segment diameter [] /kB ) energy parameter, dispersion [K] m ) number of segments N ) number of association sites AiBj hb /k ) energy parameter, association [K] AiBi hb ) association volume T ) temperature [K] hSL/R ) melting enthalpy [K] kij,25 C(H2O) ) binary interaction parameter at 25 C kij,T(H2O) ) temperature-dependent interaction parameter [1/K] NP ) number of measured values R ) ideal gas constant [J/mol K] x ) mole fraction ) activity coefcient dev( ) ) deviation of a value [%] Superscripts L ) liquid phase SL ) melting/phase change calc ) calculated exp ) experimental Subscripts 0 ) reference state 0i ) pure substance i i ) substance i solute-solute ) solute-solute interaction

1401

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ReceiVed for reView June 3, 2009 ReVised manuscript receiVed October 9, 2009 Accepted November 19, 2009 IE900913C