硫氰酸红霉素溶解动力学研究

doi:10.11949/0438-1157.20251177

摘要/Abstract

摘要：

溶剂萃取法在抗生素及其他生物活性物质的分离与纯化中发挥着重要作用。本研究利用分子动力学模拟探讨了硫氰酸红霉素在丙酮溶液中的溶解与分散行为。采用GROMACS 2023软件，并基于GAFF力场构建了包含40个硫氰酸红霉素分子的模型，对不同固液比与温度条件下的分散行为进行了分析。结果表明，当固液比为1：3 （g：mL）温度为318.15 K时，体系分散效果最佳，溶解度和分散度均显著提高。通过氢键分析、径向分布函数（RDF）和均方位移（MSD）等指标，定量评估了体系在不同条件下的结构和动力学特征。基于模拟预测结果，设计并开展了相应的溶剂萃取实验，实验结果与模拟趋势一致，进一步证明了模拟预测的可靠性。本研究表明，分子动力学模拟能够在实验前有效预测体系的最优操作条件，并为实验设计提供理论指导。该方法不仅有助于揭示硫氰酸红霉素在丙酮体系中的溶解机理，也为溶剂萃取工艺的优化提供了有价值的参考。

关键词: 溶剂萃取, 分子动力学, 氢键, 径向分布函数, 均方位移

Abstract:

Solvent extraction plays a key role in separating and purifying antibiotics and other bioactive compounds. In this study, molecular dynamics (MD) simulations were employed to explore the dissolution and dispersion behavior of erythromycin thiocyanate in acetone. Using GROMACS 2023 with the GAFF force field, a model containing 40 erythromycin thiocyanate molecules was constructed to examine dispersion characteristics under different solid-liquid ratios and temperatures. The results revealed that appropriate solvent ratio and temperature can reduce molecular aggregation and enhance solvation with acetone. When the solid-liquid ratio was 1:3 (g:mL) and the temperature was 318.15 K, the system achieved the most uniform molecular dispersion, and solubility increased markedly. Structural and dynamic properties were quantitatively characterized through hydrogen-bond analysis, radial distribution functions (RDF), and mean square displacement (MSD). Based on simulation predictions, solvent extraction experiments were conducted for verification. The experimental data agreed well with the simulated trend, confirming the predictive reliability of the MD approach. This work demonstrates that molecular dynamics simulation can effectively guide experimental design and provides molecular-level insights for optimizing solvent extraction of erythromycin thiocyanate.

Key words: solvent extraction, molecular dynamics, hydrogen bond, radial distribution function, mean square displacement

中图分类号:

O643

孙英华, 王一宁, 宋赛依, 李武英, 夏淑倩. 硫氰酸红霉素溶解动力学研究[J]. 化工学报, DOI: 10.11949/0438-1157.20251177.

Yinghua SUN, Yining WANG, Saiyi SONG, Wuying LI, Shuqian XIA. Study on dissolution kinetics of erythromycin thiocyanate[J]. CIESC Journal, DOI: 10.11949/0438-1157.20251177.

图/表 17

图1 分子几何结构（a）红霉素，（b）硫氰酸根（SCN-），（c）丙酮

Fig.1 Molecular geometry of erythromycin thiocyanate (a) erythromycin, (b) thiocyanate ion, and (c) acetone

图2 包含硫氰酸红霉素和丙酮的MD模拟初始模型

Fig.2 MD simulation initial model including erythromycin thiocyanate and acetone

表1 盒子中红霉素、硫氰酸根及丙酮的数量

Table 1 Numbers of erythromycin， thiocyanate ions， and acetone molecules in the simulation box

固液比/（g:mL）	分子、离子数量
固液比/（g:mL）	丙酮	红霉素	硫氰酸根（SCN^-）
1:2	862	40	40
1:2.5	1080	40	40
1:3	1294	40	40
1:3.5	1510	40	40
1:4	1726	40	40
1:4.5	1940	40	40

表2 红霉素分子中的原子电荷

Table 2 Atomic charge in erythromycin molecules

Number	Atom	Charge	Number	Atom	Charge
1	C1	0.382	60	H60	-0.0590
2	C2	0.232	61	H61	0.0866
3	C3	0.372	62	H62	-0.0181
4	O4	-0.490	63	H63	-0.0181
5	C5	0.791	64	H64	0.403
6	C6	-0.438	65	H65	0.107
7	O7	-0.553	66	H66	0.107
8	C8	0.207	67	H67	0.107
9	C9	-0.0753	68	H68	0.412
10	C10	0.288	69	H69	0.120
11	C11	0.486	70	H70	0.120
12	C12	-0.095	71	H71	0.120
13	C13	0.0985	72	H72	0.411
14	C14	-0.315	73	H73	-0.068
15	C15	0.554	74	H74	0.0680
16	C16	-0.0871	75	H75	0.0680
17	C17	0.340	76	H76	0.0315
18	C18	0.162	77	H77	0.0822
19	C19	0.286	78	H78	0.447
20	O20	-0.494	79	H79	0.0676
21	C21	0.819	80	H80	0.0676
22	C22	0.0580	81	H81	0.0676
23	C23	0.137	82	H82	0.118
24	O24	-0.639	83	H83	0.118
25	C25	-0.391	84	H84	0.118
26	O26	-0.590	85	H85	0.397
27	C27	-0.397	86	H86	0.0669
28	O28	-0.703	87	H87	0.0669
29	O29	-0.546	88	H88	0.0669
30	C30	0.593	89	H89	0.0356
31	O31	-0.479	90	H90	0.0356
32	C32	-0.311	91	H91	0.0356
33	C33	0.239	92	C92	-0.170
34	C34	0.0497	93	H93	0.0626
35	O35	-0.629	94	H94	0.0422
36	N36	-0.205	95	H95	0.0422
37	C37	-0.151	96	H96	0.0422
38	C38	-0.348	97	C97	-0.494
39	O39	-0.620	98	C98	-0.481
40	C40	-0.255	99	H99	0.122
41	O41	-0.444	100	H100	0.122
42	C42	0.0898	101	H101	0.122
43	O43	-0.548	102	H102	0.131
44	O44	-0.483	103	H103	0.131
45	H45	-0.0509	104	H104	0.131
46	H46	-0.0198	105	C105	-0.369
47	H47	-0.0857	106	H106	0.0996
48	H48	0.114	107	H107	0.0996
49	H49	0.114	108	H108	0.0996
50	H50	0.0118	109	C109	-0.175
51	H51	-0.1349	110	H110	0.0414
52	H52	0.0352	111	H111	0.0414
53	H53	0.0352	112	H112	0.0414
54	H54	0.0106	113	C113	0.437
55	H55	0.0768	114	H114	0.00945
56	H56	0.0768	115	C115	-0.403
57	H57	0.0768	116	H116	0.0969
58	H58	0.0447	117	H117	0.0969
59	H59	-0.00492	118	H118	0.0969

图3 硫氰酸红霉素在丙酮溶液中的体系平衡性质随时间的变化曲线：(a)温度；(b)压力；(c)密度和(d)RMSD

Fig.3 Time evolution of system equilibrium properties of erythromycin thiocyanate in acetone solution: (a) temperature; (b) pressure; (c) density; and (d) RMSD

图4 (a)不同固液比条件下硫氰酸红霉素分子间氢键数量随时间变化；(b)1:3 (g:mL)固液比条件下硫氰酸红霉素与丙酮分子间的氢键数目随时间的变化

Fig.4 (a)The number of hydrogen bonds between erythromycin thiocyanate molecules changed with time under different solid-liquid ratios. (b)The number of hydrogen bonds between erythromycin thiocyanate and acetone molecules changed with time under 1:3 (g:mL) solid-liquid ratio

表3 不同固液比条件下氢键的寿命及衰减速率

Table 3 H-bond lifetimes and decay rates at different solid-liquid ratios

	不同固液比（g:mL）
	1:2	1:2.5	1:3	1:3.5	1:4	1:4.5
τ_(E–E)(ps)	8.75	6.77	3.11	3.89	4.32	4.54
k_(E–E)	0.114	0.148	0.322	0.257	0.231	0.22
τ_(E–A) (ps)	2.57	3.78	6.45	4.35	4.79	3.98
k_(E–A)	0.389	0.265	0.155	0.23	0.209	0.251

图5 (a)不同温度条件下硫氰酸红霉素分子间氢键数量随时间变化；(b)不同温度条件下硫氰酸红霉素分子与丙酮分子间的氢键数目随时间的变化

Fig.5 (a) Time evolution of the number of intermolecular hydrogen bonds between erythromycin thiocyanate molecules at different temperatures, (b) Time evolution of the number of hydrogen bonds between erythromycin thiocyanate and acetone molecules at different temperatures

表4 不同温度条件下氢键的寿命及衰减速率

Table 4 H-bond lifetimes and decay rates at different temperatures

	不同温度（K）
	303.15	308.15	313.15	318.15	323.15	328.15
τ_(E–E) (ps)	7.01	6.84	5.71	3.11	2.44	1.31
k_(E–E)	0.143	0.146	0.175	0.322	0.41	0.763
τ_(E–A) (ps)	3.73	3.59	5.56	6.55	4.73	3.87
k_(E–A)	0.268	0.279	0.18	0.153	0.212	0.258

图6 30 ns时丙酮和硫氰酸红霉素体系H-O对的径向分布函数（RDF）：(a)固液比对RDF的影响；(b)温度对RDF的影响

Fig.6 Radial distribution functions (RDFs) of H-O pairs between acetone and erythromycin thiocyanate at 30 ns: (a) effect of solid-liquid ratio; (b) effect of temperature

图7 不同固液比（黄色：硫氰酸红霉素分子，蓝色：丙酮分子）团簇在30 ns时的快照注:簇中距离最长的两个原子之间的长度值(单位:Å )已被标出

Fig.7 Snapshots of clusters with different solid-liquid ratios (yellow: erythromycin thiocyanate molecule, blue: acetone molecule)at 30 nsThe length value ( unit : Å ) between the two longest atoms in the cluster is also marked

图8 不同温度团簇在30 ns时的快照注:簇中距离最长的两个原子之间的长度值(单位:Å )已被标出

Fig.8 Snapshots of clusters with different temperatures ratios at 30 nsThe length value ( unit : Å ) between the two longest atoms in the cluster is also marked

图9 硫氰酸红霉素-硫氰酸红霉素(E-E)、硫氰酸红霉素-丙酮(E-A)在不同固液比条件下的非成键相互作用能随时间的变化

Fig.9 The change of non-bond interaction energy of erythromycin thiocyanate-erythromycin thiocyanate(E-E) and erythromycin thiocyanate-acetone(E-A) with time under different solid-liquid ratio conditions

图10 E-E、E-A在不同温度条件下的非成键相互作用能随时间的变化

Fig.10 The change of non-bond interaction energy of E-E and E-A with time under different temperature conditions

图11 硫氰酸红霉素团簇的均方位移（MSD）随时间的变化：(a)不同固液比条件；(b)不同温度条件

Fig. 11 Mean square displacement (MSD) of erythromycin thiocyanate clusters as a function of time: (a) under different solid-liquid ratios; (b) at different temperatures

图12 (a)系统模型；(b)在固液比为1:3 (g:mL)丙酮溶液中分散过程中不同时间点的团簇快照

Fig.12 (a) System model; (b) Cluster snapshots at different time points during dispersion in acetone solution with a solid-liquid ratio of 1:3 (g:mL)

图13 萃取实验条件对硫氰酸红霉素收率的影响：(a)固液比，(b)温度和(c)pH

Fig 13 The effects of extraction conditions on the yield of erythromycin thiocyanate were as follows : (a) Solid-liquid ratio, (b) temperature and (c) pH

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