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

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