利用溶质-溶剂模型预测晶体成核的难易

摘要/Abstract

摘要： 成核作为结晶的初始阶段,直接影响着晶体产品的结构、手性、纯度、晶型和粒径分布等性质。但由于成核具有随机性,通过实验成核不仅耗时耗力而且很难洞悉分子间的相互作用。本文选择结构相似的对羟基苯甲酸乙酯(EP)、对羟基苯甲酸丙酯(PP)和对羟基苯甲酸丁酯(BP)为模型物质,计算了EP、PP和BP在四种不同的有机溶剂(乙醇、乙酸乙酯、丙酮、乙腈)中单个溶质分子和单个溶剂分子的结合能。不论是EP、PP还是BP与各溶剂的相互作用大小都服从乙醇>乙酸乙酯>丙酮>乙腈。因此,可以预测EP、PP和BP在乙醇中成核最慢,在乙酸乙酯和丙酮中成核较慢,在乙腈中成核最快。当溶剂相同的时候,EP最难成核,其次是PP,BP容易成核,预测的结果与实验结果一致。本研究证明利用溶质-溶剂(1∶1)模型可以预测成核的难易,进而有利于筛选溶剂,提高实验效率。

关键词: 结晶, 成核, 结合能, 溶质-溶剂模型, 密度泛函理论, 对羟基苯甲酸酯

Abstract: As the initial stage of crystallization, nucleation directly affects the structure, chirality, purity, crystal forms and particle size distribution of crystal products. However, due to the random nature of nucleation, experimental methods are not only time-consuming and laborious, but also difficult to understand the molecular interactions. In this paper, ethyl paraben (EP), propyl paraben (PP) and butyl paraben (BP) with similar structure were selected as model substances, and the binding energies of single solute and single solvent molecules of EP, PP and BP in four different organic solvents (ethanol, ethyl acetate, acetone, acetonitrile) were calculated. The interaction of EP, PP and BP with each solvent decreases in the following order: ethanol>ethyl acetate>acetone>acetonitrile. Therefore, it can be predicted that EP, PP and BP nucleate slowest in ethanol, slower in ethyl acetate and acetone, and fastest in acetonitrile. When the solvent is the same, EP is the most difficult to nucleate, followed by PP, and BP is easy to nucleate. The predicted results are consistent with the experimental results. This study proves that the solute-solvent (1∶1) model can predict the difficulty of nucleation, which is conducive to solvent screening and improve experimental efficiency.

Key words: crystallization, nucleation, binding energy, solute-solvent model, density functional theory, paraben

中图分类号:

TQ460
O78

王广乐, 王冲, 李海朝, 秦亚茹, 杨金芳, 时文亚, 赖国军. 利用溶质-溶剂模型预测晶体成核的难易[J]. 人工晶体学报, 2023, 52(3): 501-509.

WANG Guangle, WANG Chong, LI Haichao, QIN Yaru, YANG Jinfang, SHI Wenya, LAI Guojun. Prediction of Crystal Nucleation Difficulty Using Solute-Solvent Model[J]. JOURNAL OF SYNTHETIC CRYSTALS, 2023, 52(3): 501-509.

参考文献

[1] LEWIS A, SECKLER M, KRAMER H J M, et al. Industrial crystallization: fundamentals and applications[M]. United Kingdom: TJ International Ltd. Padstow Cornwall, 2015.
[2] DAVEY R J, SCHROEDER S L M, TER HORST J H. Nucleation of organic crystals: a molecular perspective[J]. Angewandte Chemie, 2013, 52(8): 2166-2179.
[3] REVALOR E, HAMMADI Z, ASTIER J P, et al. Usual and unusual crystallization from solution[J]. Journal of Crystal Growth, 2010, 312(7): 939-946.
[4] MARIE F E, FLATEN S M Induction time studies of calcium carbonate in ethylene glycol and water[J]. Chemical Engineering Research and Design, 2010, 88(12): 1659-1668.
[5] CAMACHO CORZO D M, BORISSOVA A, HAMMOND R B, et al. Nucleation mechanism and kinetics from the analysis of polythermal crystallisation data: methyl stearate from kerosene solutions[J]. CrystEngComm, 2014, 16(6): 974-991.
[6] MEALEY D, ZEGLINSKI J, KHAMAR D, et al. Influence of solvent on crystal nucleation of risperidone[J]. Faraday Discussions, 2015, 179: 309-328.
[7] DEIJ M A, TER HORST J H, MEEKES H, et al. Polymorph formation studied by 3D nucleation simulations. Application to a yellow isoxazolone dye, paracetamol, and l-glutamic acid[J]. The Journal of Physical Chemistry B, 2007, 111(7): 1523-1530.
[8] ZEGLINSKI J, KUHS M, DEVI K R, et al. Probing crystal nucleation of fenoxycarb from solution through the effect of solvent[J]. Crystal Growth & Design, 2019, 19(4): 2037-2049.
[9] HAMAD S, MOON C, CATLOW C R A, et al. Kinetic insights into the role of the solvent in the polymorphism of 5-fluorouracil from molecular dynamics simulations[J]. The Journal of Physical Chemistry B, 2006, 110(7): 3323-3329.
[10] KHAMAR D, ZEGLINSKI J, MEALEY D, et al. Investigating the role of solvent-solute interaction in crystal nucleation of salicylic acid from organic solvents[J]. Journal of the American Chemical Society, 2014, 136(33): 11664-11673.
[11] ZEGLINSKI J, KUHS M, KHAMAR D, et al. Crystal nucleation of tolbutamide in solution: relationship to solvent, solute conformation, and solution structure[J]. Chemistry, 2018, 24(19): 4916-4926.
[12] FRISCH M J, TRUCKS G W, SCHLEGEL H B, et al. GAUSSIAN 09[M]. Gaussian Inc: Wallingford, CT, 2009.
[13] GRIMME S. Semiempirical GGA-type density functional constructed with a long-range dispersion correction[J]. Journal of Computational Chemistry, 2006, 27(15): 1787-1799.
[14] BECKE A D. Density-functional thermochemistry. III. The role of exact exchange[J]. The Journal of Chemical Physics, 1993, 98(7): 5648-5652.
[15] WEIGEND F, AHLRICHS R. Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: design and assessment of accuracy[J]. Physical Chemistry Chemical Physics: PCCP, 2005, 7(18): 3297-3305.
[16] CHARNOCK C, FINSRUD T. Combining esters of para-hydroxy benzoic acid (parabens) to achieve increased antimicrobial activity[J]. Journal of Clinical Pharmacy and Therapeutics, 2007, 32(6): 567-572.
[17] SONI M G, TAYLOR S L, GREENBERG N A, et al. Evaluation of the health aspects of methyl paraben: a review of the published literature[J]. Food and Chemical Toxicology: an International Journal Published for the British Industrial Biological Research Association, 2002, 40(10): 1335-1373.
[18] MA Y, MARQUIS R E. Irreversible paraben inhibition of glycolysis by streptococcus mutans GS-5[J]. Letters in Applied Microbiology, 1996, 23(5): 329-333.
[19] ŘEZÁČ J, HOBZA P. Benchmark calculations of interaction energies in noncovalent complexes and their applications[J]. Chemical Reviews, 2016, 116(9): 5038-5071.
[20] YANG H Y, SVÄRD M, ZEGLINSKI J, et al. Influence of solvent and solid-state structure on nucleation of parabens[J]. Crystal Growth & Design, 2014, 14(8): 3890-3902.
[21] CHAI Y H, WANG L P, BAO Y, et al. Investigating the solvent effect on crystal nucleation of etoricoxib[J]. Crystal Growth & Design, 2019, 19(3): 1660-1667.
[22] LIU Y, XU S J, ZHANG X, et al. Unveiling the critical roles of aromatic interactions in the crystal nucleation pathway of flufenamic acid[J]. Crystal Growth & Design, 2019, 19(12): 7175-7184.