Effects of solvent on formation of sulfamerazine solvates

doi:10.11949/0438-1157.20190642

Abstract

Abstract:

The solvent compounds of sulfamethylpyrimidine were screened in 17 kinds of solvents, such as alcohols, esters and amides, and the sulfamerazine solvates were investigated by powder X-ray diffraction, thermal gravimetric analysis, scanning electron microscopy and Fourier transform infrared spectroscopy. The results showed that sulfamerazine can form four solvates with N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone and dimethylsulfoxide respectively. TGA results showed that they all belong to the type of 1∶1 stoichiometric solvates. SEM results indicated that the morphology of the crystals changed significantly after the formation of the solvates, the morphology of the crystal changed from block shape to sheet and rod crystal. FTIR characterization analysis confirmed that the solvent and the solute molecules formed intermolecular hydrogen bonds in the solvates. The physicochemical properties of the used solvents for the screening were analyzed, and the results showed that the corresponding solvates were easy to form in the solvents with strong hydrogen bond acceptor ability. The packing efficiency of molecules in crystals further confirmed that sulfamerazine form hydrogen bond solvates. The changes of molecular packing, structure synthons and hydrogen bond network before and after the formation of solvates were determined according to the single crystal structures of compounds. Sulfamerazine form Ⅱ and its solvates formed a one-dimensional leader hydrogen bond network. For three solvates, in addition to the hydrogen bond network formed between the molecules of sulfamerazine, another hydrogen atom in the amino group of sulfamerazine was bonded to the oxygen atom of the solvent molecule to form an intermolecular N—H…O hydrogen bond.The results showed that the hydrogen bond played a decisive role in the supramolecular self-assembly process between the solute and the solvent, then affected the formation of solvates.

Key words: sulfamerazine, solvent properties, hydrogen bond acceptor ability, intermolecular hydrogen bond

摘要：

采用悬浮转化法对磺胺甲基嘧啶溶剂化合物在醇类、酯类和酰胺类等17种溶剂中进行了筛选研究，采用粉末 X 射线衍射、热重分析、扫描电镜和傅里叶红外光谱对磺胺甲基嘧啶溶剂化合物进行了表征，成功制备出磺胺甲基嘧啶与N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮溶剂化物和二甲基亚砜的4种溶剂化合物。热重结果表明它们均属于化学计量比为1∶1的溶剂化合物；扫描电镜分析发现在溶剂化合物形成过程中，晶体的形态由接近正方体的块状晶体变为片状与棒状晶体；傅里叶红外表征分析证实了溶剂化合物中溶剂与溶质分子形成分子间氢键。分析所用的17种溶剂的分子结构、氢键供体和受体能力等性质，确定了磺胺甲基嘧啶容易与氢键受体能力强的溶剂形成相应溶剂化合物。对比分析了晶体中分子的堆积效率，进一步证实了磺胺甲基嘧啶形成氢键溶剂化合物。根据磺胺甲基嘧啶和溶剂化合物的单晶结构，分析氢键溶剂化合物形成前后分子堆积、结构合成子和氢键网络的变化，磺胺甲基嘧啶晶型Ⅱ及其溶剂化合物的四种结构中均形成一维的椅子形氢键网络，对于三种溶剂化合物，除了磺胺甲基嘧啶分子间形成的氢键网络，磺胺甲基嘧啶分子氨基中另一个氢原子与溶剂分子的氧原子相连形成分子间N—H…O氢键。结果表明氢键在溶质与溶剂间的超分子自组装过程中起决定作用，是影响溶剂化合物形成的关键因素。

关键词: 磺胺甲基嘧啶, 溶剂性质, 氢键受体能力, 分子间氢键

CLC Number:

TQ 028.8

Xia ZHANG, Ling ZHOU, Qiuxiang YIN. Effects of solvent on formation of sulfamerazine solvates[J]. CIESC Journal, 2020, 71(2): 680-687.

张霞, 周玲, 尹秋响. 溶剂对磺胺甲基嘧啶溶剂化合物形成的影响[J]. 化工学报, 2020, 71(2): 680-687.

Figures/Tables 10

Fig.1 XPRD patterns of products obtained from screening solvents

Fig.2 TGA and DSC curves of SMZ solvates

Fig.3 SEM images of SMZ and SMZ solvates

Fig.4 FTIR of different SMZ solvate

Table 1 Properties of used solvents and obtained forms

溶剂	α	β	π*	SMZ晶型
N-甲基吡咯烷酮	00	77	92	溶剂化合物
N,N-二甲基乙酰胺	00	76	88	溶剂化合物
N,N-二甲基甲酰胺	00	69	88	溶剂化合物
二甲基亚砜	00	76	100	溶剂化合物
甲酰胺	71	48	97	晶型Ⅱ
乙腈	19	40	75	晶型Ⅱ
甲醇	98	66	60	晶型Ⅱ
乙醇	86	75	54	晶型Ⅱ
正丙醇	84	90	52	晶型Ⅱ
异丙醇	76	84	48	晶型Ⅱ
正丁醇	84	84	47	晶型Ⅱ
仲丁醇	79	84	40	晶型Ⅱ
甲酸乙酯	00	36	61	晶型Ⅱ
乙酸甲酯	00	42	60	晶型Ⅱ
乙酸乙酯	00	45	55	晶型Ⅱ
乙酸丙酯	00	40	—	晶型Ⅱ
丙酮	08	43	71	晶型Ⅱ

Fig.5 Molecular structures of some solvents used for solvates investigated herein

Table 2 Crystallographic data for SMZ form Ⅱ and SMZ solvates (SMZ-DMF, SMZ-DMA and SMZ-NMP)

参数	SMZ form Ⅱ^①	SMZ-DMF^②(1∶1)	SMZ-DMA^③(1∶1)	SMZ-DMA(1∶1)	SMZ-NMP(1∶1)
分子式	C₁₁H₁₂N₄O₂S	C₁₄H₁₉N₅O₃S	C₁₅H₂₁N₅O₃S	C₁₅H₂₁N₅O₃S	C₁₆H₂₁N₅O₃S
分子量	264.3	337.41	351.44	351.43	363.44
晶系	正交	三斜	三斜	三斜	三斜
空间群	Pn2₁a	$P 1 ˉ$	$P 1 ˉ$	$P 1 ˉ$	$P 1 ˉ$
a/?	14.474(2)	9.774(2)	7.6792(15)	7.8727(16)	9.516(2)
b/?	21.953(2)	12.556(3)	8.3101(17)	8.3117(17)	13.137(3)
c/?	8.203(1)	14.659(3)	15.125(3)	15.506(3)	15.146(4)
α/(°)	90	76.58(3)	93.13(3)	95.01(3)	105.224(8)
β/(°)	90	77.57(3)	101.81(3)	102.38(3)	94.743(4)
γ/(°)	90	86.18(3)	104.77(3)	105.83(3)	92.175(7)
晶胞体积/?³	2606.48	1708.6(6)	907.7(4)	941.916	1817.22
Z	8	1	2	2	4
Z'	2	0.5	1	1	2
R1/%	4.7	7.25	6.41	6.71	4.03
GOF	n/a	n/a	n/a	1.023	1.092

Table 2 Crystallographic data for SMZ form Ⅱ and SMZ solvates (SMZ-DMF, SMZ-DMA and SMZ-NMP)

参数	SMZ form Ⅱ^①	SMZ-DMF^②(1∶1)	SMZ-DMA^③(1∶1)	SMZ-DMA(1∶1)	SMZ-NMP(1∶1)
分子式	C₁₁H₁₂N₄O₂S	C₁₄H₁₉N₅O₃S	C₁₅H₂₁N₅O₃S	C₁₅H₂₁N₅O₃S	C₁₆H₂₁N₅O₃S
分子量	264.3	337.41	351.44	351.43	363.44
晶系	正交	三斜	三斜	三斜	三斜
空间群	Pn2₁a	$P 1 ˉ$	$P 1 ˉ$	$P 1 ˉ$	$P 1 ˉ$
a/?	14.474(2)	9.774(2)	7.6792(15)	7.8727(16)	9.516(2)
b/?	21.953(2)	12.556(3)	8.3101(17)	8.3117(17)	13.137(3)
c/?	8.203(1)	14.659(3)	15.125(3)	15.506(3)	15.146(4)
α/(°)	90	76.58(3)	93.13(3)	95.01(3)	105.224(8)
β/(°)	90	77.57(3)	101.81(3)	102.38(3)	94.743(4)
γ/(°)	90	86.18(3)	104.77(3)	105.83(3)	92.175(7)
晶胞体积/?³	2606.48	1708.6(6)	907.7(4)	941.916	1817.22
Z	8	1	2	2	4
Z'	2	0.5	1	1	2
R1/%	4.7	7.25	6.41	6.71	4.03
GOF	n/a	n/a	n/a	1.023	1.092

Fig.6 Packing coefficients of SMZ form Ⅱ and its solvates

Fig.7 Crystal packing in different crystal structures

Table 3 Hydrogen bonding data for SMZ form Ⅱ and SMZ solvates (SMZ-DMF, SMZ-DMA and SMZ-NMP)

化合物	SMZ分子间N—H…N氢键/?	SMZ分子间N—H…O氢键/?	SMZ分子与溶剂分子间N—H…O氢键/?
SMZ form Ⅱ	2.899, 2.947	3.056	—
SMZ-DMF	2.896, 2.911	3.032	2.875, 2.832
SMZ-DMA	2.897	3.02	2.829
SMZ-NMP	2.918	3.047	2.851

References 30

1	Infantes L, Fábián L, Motherwell W D S. Organic crystal hydrates: what are the important factors for formation[J]. CrystEngComm, 2007, 9(1): 65-71.
2	Lee A Y, Erdemir D, Myerson A S. Crystal polymorphism in chemical process development[J]. Annu. Rev. Chem. Biomol. Eng., 2011, 2: 259-280.
3	Brittain H G. Polymorphism in Pharmaceutical Solids[M]. USA: CRC Press, 2009: 76-138.
4	Qiao Y, Qiao R, He Y, et al. Instrumental analytical techniques for the characterization of crystals in pharmaceutics and foods[J]. Cryst. Growth Des., 2017, 17(11): 6138-6148.
5	Chieng N, Rades T, Aaltonen J. An overview of recent studies on the analysis of pharmaceutical polymorphs[J]. J. Pharm. Biomed. Anal., 2011, 55(4): 618-644.
6	Minkov V S, Beloborodova A A, Drebushchak V A, et al. Furosemide solvates: can they serve as precursors to different polymorphs of furosemide?[J]. Cryst. Growth Des., 2014, 14(2): 513-522.
7	Yang L, Hao H, Zhou L, et al. Crystal structures and solvent-mediated transformation of the enantiotropic polymorphs of 2, 3, 5-trimethyl-1, 4-diacetoxybenzene[J]. Ind. Eng. Chem. Res., 2013, 52(49): 17667-17675.
8	Mirmehrabi M, Rohani S, Murthy K S, et al. Improving the filterability and solid density of ranitidine hydrochloride form 1[J]. J. Pharm. Sci., 2004, 93(7): 1692-1700.
9	Black S N, Cuthbert M W, Roberts R J, et al. Increased chemical purity using a hydrate[J]. Cryst. Growth Des., 2004, 4(3): 539-544.
10	Wirth D D, Stephenson G A. Purification of dirithromycin. Impurity reduction and polymorph manipulation[J]. Org. Process Res. Dev., 1997, 1(1): 55-60.
11	孙佳, 李想, 鲍颖, 等. 磺胺嘧啶 N-甲基吡咯烷酮溶剂化合物脱溶剂动力学研究[J]. 化工学报, 2016, 67(6): 2349-2354.
	Sun J, Li X, Bao Y, et al.The study of desolvation kinetics of sulfadiazine N-methylpyrrolidone solvate[J]. CIESC Journal, 2016, 67(6): 2349-2354.
12	Wu S, Chen M, Li K, et al. Solvent penetration mediated phase transformation for the preparation of aggregated particles with well-defined shape[J]. CrystEngComm, 2016, 18(48): 9223-9226.
13	Wu S, Du S, Chen M, et al. Crystal structures and phase behavior of sulfadiazine and a method for preparation of aggregates with well-performance[J]. Chem. Eng. Technol., 2017, 41(3): 532-540.
14	Walsh R D B, Bradner M W, Fleischman S, et al. Crystal engineering of the composition of pharmaceutical phases[J]. Chemical Communications, 2003, (2): 186-187.
15	Aljohani M, Pallipurath A R, McArdle P, et al. A comprehensive cocrystal screening study of chlorothiazide[J]. Cryst. Growth Des., 2017, 17(10): 5223-5232.
16	Fleischman S G, Kuduva S S, McMahon J A, et al. Crystal engineering of the composition of pharmaceutical phases multiple-component crystalline solids involving carbamazepine[J]. Cryst. Growth Des., 2003, 3(6): 909-919.
17	黄耀辉, 尹秋响, 张霞, 等. 药物共晶的合成和结构分析[J]. 化工学报, 2017, 68(2): 509-518.
	Huang Y H, Yin Q X, Zhang X, et al. Synthesis and structural analysis of pharmaceutical co-crystals[J]. CIESC Journal, 2017, 68(2): 509-518.
18	Blagden N, Davey R J, Lieberman H F, et al. Crystal chemistry and solvent effects in polymorphic systems sulfathiazole[J]. J. Chem. Soc., Faraday Trans., 1998, 94(8): 1035-1044.
19	Zhang X, Zhou L, Wang C, et al. Insight into the role of hydrogen bonding playing in the molecular self-assembly process of sulfamethazine solvates[J]. Cryst. Growth Des., 2017, 17: 6151-6157.
20	Aitipamula S, Chow P S, Tan R B H. The solvates of sulfamerazine: structural, thermochemical, and desolvation studies[J]. CrystEngComm, 2011, 14(2): 691-699.
21	Saluja H, Mehanna A, Panicucci R, et al. Hydrogen bonding: between strengthening the crystal packing and improving solubility of three haloperidol derivatives[J]. Molecules, 2016, 21(6): 719-728.
22	Marcus Y. The properties of organic liquids that are relevant to their use as solvating solvents[J]. Cheminform, 1994, 25(12): 409-416.
23	Gu C H, Li H, Gandhi R B, et al. Grouping solvents by statistical analysis of solvent property parameters: implication to polymorph screening[J]. Int. J. Pharm., 2004, 283(1/2): 117-125.
24	Price C P, Glick G D, Matzger A J. Dissecting the behavior of a promiscuous solvate former[J]. Angew. Chem. Int. Ed. Engl., 2006, 45(13): 2062-2066.
25	Vippagunta S R, Brittain H G, Grant D J W. Crystalline solids[J]. Advanced Drug Delivery Reviews, 2001, 48(1): 3-26.
26	Tessler L, Goldberg I. Crystal structures of aripiprazole, a new anti-psychotic drug, and of its inclusion compounds with methanol, ethanol and water[J]. J. Inclusion Phenom. Macrocyclic Chem., 2006, 55(3/4): 255-261.
27	Be̅rziņš A, Skarbulis E, Actiņš A. Structural characterization and rationalization of formation, stability, and transformations of benperidol solvates[J]. Cryst. Growth Des., 2015, 15(5): 2337-2351
28	Be̅rziņš A, Skarbulis E, Rekis T, et al. On the formation of droperidol solvates: characterization of structure and properties[J]. Cryst. Growth Des., 2014, 14(5): 2654-2664.
29	Zhang Q, Lu L, Dai W, et al. Polymorphism and isomorphism of Huperzine A solvates: structure, properties and form transformation[J]. CrystEngComm, 2014, 16(10): 1919.
30	Kitaigorodskii A I. Organic Chemical Crystallography[M]. New York: Consultants Bureau, 1961.

[1]	Zehao MI, Er HUA. DFT and COSMO-RS theoretical analysis of SO₂ absorption by polyamines type ionic liquids [J]. CIESC Journal, 2023, 74(9): 3681-3696.
[2]	Xiaolong HU, Wenxue GONG, Yi PENG, Yang HU, Ying TANG, Hui HE, Wenyuan LI, Zhongxing ZHAO, Zhenxia ZHAO. Construction of NM88(D)/COF-OMe composite via ligand-induced interfacial growth strategy for highly efficient photo-Fenton degradation of antibiotic sulfamerazine under visible light [J]. CIESC Journal, 2021, 72(9): 4730-4739.