Crystallization thermodynamics of L-phenylalanine in methanol-water solvent

doi:10.11949/j.issn.0438-1157.20180893

Abstract

Abstract:

The solubility and supersolubility of L-phenylalanine anhydrate in methanol-water mixed solvent were studied in the temperature range of 293.15—322.15 K, and the crystalline metastable zone of L-phenylalanine anhydrate was obtained. The nucleation order and rate was calculated. Meanwhile, the in?uences of temperature and cooling rate on the width of metastable zone were explored. The water activity of transformation at 297.15 K and 302.15 K were measured, the phase diagram of L-phenylalanine-methanol-water at that temperature was obtained through solubility property. The solubility data were correlated by the modified Apelblat equation, λh equation and van t Hoff equation. The results showed that the solubility of L-phenylalanine obviously increased with the increase of temperature and the decrease of the methanol content; the width of metastable zone decreased with increasing temperature and decreasing cooling rate; the water activity of transformation increased with the increase of temperature.

Key words: L-phenylalanine, solubility, Apelblat equation, ternary phase diagram, metastable zone

摘要：

在293.15~322.15 K温度范围内，研究L-苯丙氨酸无水物在甲醇-水混合溶剂中溶解度和超溶解度特性，得到L-苯丙氨酸无水物结晶介稳区，计算了成核级数及成核速率，考察了不同初始温度和降温速率对介稳区宽度的影响，并通过研究L-苯丙氨酸297.15 K和302.15 K的转晶水活度，依据溶解度特性绘制L-苯丙氨酸-甲醇-水在该温度下的三元相图。溶解度数据用Apelblat方程、λh方程关联、van t Hoff方程拟合。结果表明，L-苯丙氨酸无水物溶解度随温度的升高而增大，随甲醇体积分数的增加而减小；L-苯丙氨酸无水物结晶介稳区宽度在相同条件下，随初始温度的升高，降温速率的降低变窄；L-苯丙氨酸转晶水活度随温度的升高而增大。

关键词: L-苯丙氨酸, 溶解度, Apelblat方程, 三元相图, 介稳区

CLC Number:

TQ 026.5

Xiaoxue CAO, Shaochang JI, Wenjie KUANG, Anping LIAO, Ping LAN, Jinyan ZHANG. Crystallization thermodynamics of L-phenylalanine in methanol-water solvent[J]. CIESC Journal, 2019, 70(4): 1255-1262.

曹小雪, 吉绍长, 匡雯婕, 廖安平, 蓝平, 张金彦. 甲醇-水溶剂中L-苯丙氨酸结晶热力学[J]. 化工学报, 2019, 70(4): 1255-1262.

Figures/Tables 12

Fig.1 Structure of L-Phe

Fig.2 Mole fraction of L-Phe in methanol-water solvent mixtures

Table 1 Experimental solubility of L-Phe in methanol-water solvent mixtures

T/K	x ^exp×10³	x ^cal,Apel×10³	x ^cal, ^λh ×10³	x ^{cal,van’t Hoff} ×10³	T/K	x ^exp ×10³	x ^cal,Apel ×10³	x ^cal, ^λh ×10³	x ^{cal,van’t Hoff} ×10³
V _methanol∶V _water =4∶6					V _methanol∶V _water =2∶8
322.15	3.29	3.27	3.37	3.33	322.15	3.49	3.52	3.67	3.62
317.15	2.97	3.00	3.02	3.00	317.15	3.36	3.32	3.34	3.32
312.15	2.70	2.72	2.71	2.70	312.15	3.09	3.08	3.03	3.02
307.15	2.46	2.45	2.42	2.42	307.15	2.78	2.82	2.75	2.75
302.15	2.20	2.18	2.15	2.16	302.15	2.53	2.54	2.49	2.50
297.15	1.94	1.92	1.91	1.92	297.15	2.27	2.25	2.24	2.26
293.15	1.68	1.72	1.73	1.74	293.15	2.02	2.02	2.06	2.08
V _methanol∶V _water =3∶7					V _methanol∶V _water =15∶85
322.15	3.42	3.43	3.52	3.48	322.15	3.57	3.59	3.66	3.64
317.15	3.18	3.15	3.17	3.15	317.15	3.38	3.36	3.38	3.36
312.15	2.85	2.87	2.85	2.85	312.15	3.15	3.13	3.11	3.10
307.15	2.55	2.59	2.56	2.56	307.15	2.86	2.89	2.85	2.86
302.15	2.38	2.32	2.29	2.29	302.15	2.64	2.64	2.62	2.62
297.15	2.03	2.05	2.04	2.05	297.15	2.40	2.40	2.39	2.40
293.15	1.83	1.84	1.85	1.86	293.15	2.20	2.20	2.23	2.22
V _methanol∶V _water =25∶75					V _methanol∶V _water =1∶9
322.15	3.46	3.47	3.60	3.55	322.15	3.62	3.66	3.70	3.69
317.15	3.24	3.21	3.24	3.21	317.15	3.52	3.44	3.45	3.44
312.15	2.93	2.94	2.91	2.90	312.15	3.21	3.22	3.20	3.21
307.15	2.62	2.65	2.60	2.60	307.15	2.99	3.00	2.98	2.98
302.15	2.38	2.36	2.32	2.33	302.15	2.74	2.78	2.76	2.76
297.15	2.09	2.08	2.07	2.08	297.15	2.56	2.55	2.56	2.56
293.15	1.84	1.85	1.88	1.89	293.15	2.40	2.38	2.40	2.40

Table 2 Regressed parameters and calculated root-mean-square deviation (RMSD) for L-Phe in methanol-water solvent mixtures by Apelblat equation

V _methanol∶V _water	A	B	C	R ²	RMSD
4∶6	169.60	?9805.76	?25.09	0.9970	3.49×10^?5
3∶7	178.46	?10150.70	?26.43	0.9949	1.67×10^?5
25∶75	246.33	?13260.89	?36.51	0.9983	2.63×10^?5
2∶8	315.16	?16202.01	-46.84	0.9926	1.86×10^?5
15∶85	149.99	?8473.50	?22.39	0.9981	3.15×10^?5
1∶9	80.57	?5137.36	?12.16	0.9903	2.37×10^?5

Table 3 Regressed parameters and calculated root-mean-square deviation (RMSD) for L-Phe in methanol-water solvent mixtures by λh equation

V _methanol∶V _water	λ	h	R ²	RMSD
4∶6	0.042	48.74	0.9889	4.85×10^?5
3∶7	0.038	50.96	0.9908	5.22×10^?5
25∶75	0.041	48.55	0.9913	5.88×10^?5
2∶8	0.028	60.38	0.9865	7.45×10^?5
15∶85	0.018	78.15	0.9950	4.02×10^?5
1∶9	0.012	96.40	0.9945	4.15×10^?5

Table 4 Regressed parameters and calculated root-mean-square deviation (RMSD) for L-Phe in methanol-water solvent mixtures by van’t Hoff equation

V _methanol∶V _water	a	b	R ²	RMSD
4∶6	2110.23	0.84	0.9922	3.26×10^?5
3∶7	2037.10	0.66	0.9919	4.41×10^?5
25∶75	2050.55	0.73	0.9922	4.70×10^?5
2∶8	1813.77	0.0097	0.9858	6.31×10^?5
15∶85	1595.19	-0.66	0.9954	3.28×10^?5
1∶9	1399.38	-1.26	0.9932	3.83×10^?5

Table 5 Molar fraction data and stable crystal form of L-Phe in mixed solvents

溶液水体积分数/%	x×10³	稳定晶型	溶液水体积分数/%	x×10³	稳定晶型
297.15 K			302.15 K
40	1.79	anhydrous	70	2.38	anhydrous
50	1.81	anhydrous	75	2.38	anhydrous
60	1.93	anhydrous	80	2.53	anhydrous
65	1.97	anhydrous	85	2.64	anhydrous
70	2.03	anhydrous	87	2.67	anhydrous
75	2.08	anhydrous	90	2.74	anhydrous
80	2.27	anhydrous	93	2.83	anhydrous
81	2.30	anhydrous	94	2.88	anhydrous
82	2.34	anhydrous	95	2.92	anhydrous
83	2.36	anhydrous	96	2.89	anhydrous+monohydrate
84	2.38	anhydrous	97	2.94	monohydrate
85	2.40	anhydrous	99	2.98	monohydrate
86	2.47	anhydrous	100	3.01	monohydrate
88	2.50	anhydrous
89	2.37	anhydrous+monohydrate
90	2.46	monohydrate
100	2.57	monohydrate

Table 6 Parameters of Wilson equation

体系	(g ₁₂?g ₁₁)/(J/mol)	(g ₂₁?g ₂₂)/(J/mol)	$V 1 L$ /(cm³/mol)	$V 2 L$ /(cm³/mol)
甲醇+水	107.3832	469.5509	18.018883	39.57286

Table 6 Parameters of Wilson equation

体系	(g ₁₂?g ₁₁)/(J/mol)	(g ₂₁?g ₂₂)/(J/mol)	$V 1 L$ /(cm³/mol)	$V 2 L$ /(cm³/mol)
甲醇+水	107.3832	469.5509	18.018883	39.57286

Fig.3 Ternary phase diagram of L-Phe-methanol-water at 297.15 K and 302.15 K(All axis scales are in mass percentage)

Fig.4 Effect of temperature on metastable zone

Fig.5 Linear dependence lgΔT max with lgb for L-Phe

Fig.6 Dependence of nucleation rate on cooling rate for L-Phe

References 32

1	Lu J , Li Z , Jiang X L , et al . Solubility of L-phenylalanine in aqueous solutions[J]. Journal of Chemical Engineering of Japan, 2010, 43(9): 810–813.
2	Lu J , Lin Q , Li Z , et al . Solubility of L-phenylalanine anhydrous and monohydrate forms: experimental measurements and predictions[J]. Journal of Chemical & Engineering Data, 2012, 57(57): 1492-1498.
3	Lu J , Wang J , Li Z , et al . Characterization and pseudopolymorphism of L-phenylalanine anhydrous and monohydrate forms[J]. African Journal of Pharmacy and Pharmacology, 2012, 6(4): 269-277.
4	Li R R , Ye S F , Chen Y F . Solubility of sulfachloropyridazine in pure and binary solvent mixtures and investigation of intermolecular interactions[J]. Journal of Chemical & Engineering Data, 2018, 63(6): 2002-2008.
5	Chao Y , Lo T , Luo N . Selective production of L-aspartic acid and L-Phenylalanine by coupling reactions of aspartase and aminotransferase in escherichia coli[J]. Enzyme & Microbial Technology, 2000, 27(1): 19-25.
6	Xu H , Wei P , Zhou H , et al . Efficient production of L-phenylalanine catalyzed by a coupled enzymatic system of transaminase and aspartase[J]. Enzyme and Microbial Technology, 2003, 33(5): 537-543.
7	Edahiro J , Nakamura M , Seki M , et al . Enhanced accumulation of anthocyanin in cultured strawberry cells by repetitive feeding of L-phenylalanine into the medium[J]. Journal of Bioscience and Bioengineering, 2005, 99(1): 43-47.
8	Eyal A M , Bressler E . Industrial separation of carboxylic and amino acids by liquid membranes: applicability, process considerations and potential advantage[J]. Biotechnology & Bioengineering, 2010, 41(3): 287-295.
9	And C J L , Rousseau R W . Solubilities of and transformations between the anhydrous and hydrated forms of L-serine in water−methanol solutions[J]. Crystal Growth & Design, 2006, 6(8): 1808-1812.
10	Cuellar M C , Herreilers S N , Straathof A J J , et al . Limits of operation for the integration of water removal by membranes and crystallization of L-phenylalanine[J]. Industrial & Engineering Chemistry Research, 2009, 48(3): 1566-1573.
11	O’Mahony M A , Croker D M , Rasmuson A C , et al . Measuring the solubility of a quickly transforming metastable polymorph of carbamazepine[J]. Organic Process Research & Development, 2013, 17(3): 512-518.
12	Hanna M , Shan N , Cheney M L , et al . Solubility modeling and solvent effects of allopurinol in 15 neat solvents[J]. Journal of Chemical & Engineering Data, 2018, 63(9): 3551-3558.
13	Docherty R , Pencheva K , Abramov Y A . Low solubility in drug development: de-convoluting the relative importance of solvation and crystal packing[J]. Journal of Pharmacy & Pharmacology, 2015, 67(6): 847-856.
14	Fayjunessa R , Sarkar M R , Sultana R , et al . Study on dissolution improvement of allopurinol by co-grinding and fusion method using solid dispersion technique[J]. J. Biomed. Pharmaceut. Res., 2013, 2: 1-7.
15	Healy A M , Worku Z A , Kumar D , et al . Pharmaceutical solvates, hydrates and amorphous forms[J]. Advanced Drug Delivery Reviews, 2017, 117(1): 25-46.
16	Neglur R , Hosten E , Aucamp M , et al . Water and the relationship to the crystal structure stability of azithromycin[J]. Journal of Thermal Analysis & Calorimetry, 2018, 132(1): 373-384.
17	Carta R . Solubilities of L-cystine, L-tyrosine, L-leucine, and glycine in sodium chloride solutions at various pH values[J]. Journal of Chemical Thermodynamics, 1998, 30(3): 379-387.
18	Hazi M T , Lenka M , Sarkar D . Nucleation kinetics from metastable zone widths for sonocrystallization of L-phenylalanine[J]. Ultrasonics Sonochemistry, 2017, 36: 497-506.
19	Imran S , Hossain A , Mahali K , et al . Role of solubility and solvation thermodynamics on the stability of L-phenylalanine in aqueous methanol and ethanol solutions[J]. Journal of Molecular Liquids, 2018, 265(1): 693-700.
20	Zhang Y Z , Guo X , Tang P , et al . Solubility of 2,5-furandicarboxylic acid in eight pure solvents and two binary solvent systems at 313.15—363.15 K[J]. Journal of Chemical & Engineering Data, 2018, 63(5): 1316-1324.
21	Wang Z , Li Y , Fang W , et al . Salting effects on the solubility and transformation kinetics of L-phenylalanine anhydrate/monohydrate in aqueous solutions[J]. Industrial & Engineering Chemistry Research, 2012, 53(2): 521-529.
22	Zhou X , Fan J , Li N , et al . Solubility of L-phenylalanine in water and different binary mixtures from 288.15 to 318.15 K[J]. Fluid Phase Equilibria, 2012, 316(8): 26-33.
23	赵宏宇, 顾正彪, 程力, 等 . 莱鲍迪苷A在甲醇-水体系中溶解度与超溶解度的测定[J]. 食品工业科技, 2012, 33(11): 340-342.
	Zhao H Y , Gu Z B , Cheng L , et al . Determination of solubility and supersolubility of rebaudioside A in methanol aqueous solution[J]. Science and Technology of Food Industry, 2012, 33(11): 340-342.
24	Baluja S , Alnayab E A M , Hirapara A . Solubility and solution thermodynamics of hippuric acid in various solvents from 298.15 K to 328.15 K[J]. Journal of Molecular Liquids, 2017, 238: 84-88.
25	Chen L Z , Song L , Lan G C , et al . Solubility and metastable zone width measurement of 3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) in ethanol + water[J]. Chinese Journal of Chemical Engineering, 2017, 25(5): 646-651.
26	Buchowski H , Ksiazczak A , Pietrzyk S . ChemInform abstract: solvent activity along a saturation line and solubility of hydrogen-bonding solids [J]. Journal of Physical Chemistry, 1980, 84(9): 975-979.
27	Su J , Chao Q , Luo N , et al . Experimental measurement and modeling of the solubility of biotin in six pure solvents at temperatures from 298.15 K to 333.85 K[J]. Journal of Chemical & Engineering Data, 2014, 59(11): 3894-3899.
28	Xie Y , Shi H W , Du C B , et al . Solubility determination and modeling for 4,4 -dihydroxydiphenyl sulfone in mixed solvents of (acetone, ethyl acetate, or acetonitrile)+ methanol and acetone + ethanol from (278.15 to 313.15) K[J]. Journal of Chemical & Engineering Data, 2016, 61(10): 3519-3526.
29	Wilson G M . Vapor-liquid equilibrium(Ⅺ). A new expression for the excess free energy of mixing[J]. J. Am. Chem. Soc., 1964, 86(2): 127-130.
30	Cravo F M , Bessa L C B A , Abreu C R A , et al . Liquid-liquid equilibrium of systems containing triolein + (fatty acid/ partial acylglycerols/ester) + ethanol: experimental data and UNIFAC modeling[J]. Fluid Phase Equilibria, 2018, 476(B): 186-192.
31	Wang L , Feng H , Peng J , et al . Solubility, metastable zone width, and nucleation kinetics of sodium dichromate dihydrate[J]. Journal of Chemical & Engineering Data, 2015, 60(1): 185-191.
32	Belgacem Z B , Dousset X , Prévost H , et al . Polyphasic taxonomic studies of lactic acid bacteria associated with tunisian fermented meat based on the heterogeneity of the 16S-23S rRNA gene intergenic spacer region[J]. Archives of Microbiology, 2009, 191(9): 711-720.

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