Structural Features of Sulfamethizole and Its Cocrystals: Beauty within

Yue Yuan; Duanxiu Li; Chenguang Wang; Shaodong Chen; Minmin Kong; Zongwu Deng; Changquan Calvin Sun; Hailu Zhang

doi:10.1021/acs.cgd.9b01060

Structural Features of Sulfamethizole and Its Cocrystals: Beauty within

Yue Yuan, Duanxiu Li, Chenguang Wang, Shaodong Chen, Minmin Kong, Zongwu Deng, Changquan Calvin Sun, Hailu Zhang

Pharmaceutics

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Sulfamethizole (SMZ) is an antibiotic drug with good solubility but short in vivo half-life. Thus, reducing the dissolution rate is expected to improve bioavailability and therapeutic activity through reducing the systemic elimination of SMZ. To this end, two novel pharmaceutical cocrystals, SMZ-sarcosine (SMZ-SAR) and SMZ-saccharin (SMZ-SAC), were designed and prepared according to the structural resemblance strategy. These cocrystals, along with a previously obtained SMZ-l-proline (SMZ-l-PRO) cocrystal, present an opportunity for detailed analysis of the crystal structure to identify key intermolecular interactions that guide their molecular assembly. ¹³C Solid state NMR data suggested more than one symmetry independent molecules in SMZ (Z′ > 1), which was confirmed by the SMZ crystal structure solved at 100 K (Z′ = 3). The amine-carboxylate synthon plays an important role in the intermolecular hydrogen bonding interactions of both SMZ-SAR and SMZ-l-PRO. In contrast, no strong intermolecular hydrogen bonding and I ···πstacking interactions between SMZ and SAC were observed in SMZ-SAC, which features a shape-fit structure. Additionally, all cocrystals demonstrated lower equilibrium solubility and intrinsic dissolution rates compared to SMZ. Therefore, they are suitable crystal forms for the possible improvement in therapeutic performance of SMZ.

Original language	English (US)
Pages (from-to)	7185-7192
Number of pages	8
Journal	Crystal Growth and Design
Volume	19
Issue number	12
DOIs	https://doi.org/10.1021/acs.cgd.9b01060
State	Published - Dec 4 2019

Bibliographical note

Funding Information:
We gratefully acknowledge support from the National Natural Science Foundation of China (Nos. 21874148, 21673279), the Youth Innovation Promotion Association of CAS (No. 2012242), and the China Postdoctoral Science Foundation (No. 2017LH045). C.W. and C.C.S. thank the Minnesota Supercomputing Institute (MSI) ( http://www.msi.umn.edu ) for providing the calculation resources. H.L.Z. also thanks Dr. Jianrong Wang (Shanghai Institute of Materia Medica) for valuable discussions.

Funding Information:
We gratefully acknowledge support from the National Natural Science Foundation of China (Nos. 21874148, 21673279), the Youth Innovation Promotion Association of CAS (No. 2012242), and the China Postdoctoral Science Foundation (No. 2017LH045). C.W. and C.C.S. thank the Minnesota Supercomputing Institute (MSI)

Publisher Copyright:
Copyright © 2019 American Chemical Society.

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@article{265cbc8c263d470784952f44971532f4,

title = "Structural Features of Sulfamethizole and Its Cocrystals: Beauty within",

abstract = "Sulfamethizole (SMZ) is an antibiotic drug with good solubility but short in vivo half-life. Thus, reducing the dissolution rate is expected to improve bioavailability and therapeutic activity through reducing the systemic elimination of SMZ. To this end, two novel pharmaceutical cocrystals, SMZ-sarcosine (SMZ-SAR) and SMZ-saccharin (SMZ-SAC), were designed and prepared according to the structural resemblance strategy. These cocrystals, along with a previously obtained SMZ-l-proline (SMZ-l-PRO) cocrystal, present an opportunity for detailed analysis of the crystal structure to identify key intermolecular interactions that guide their molecular assembly. 13C Solid state NMR data suggested more than one symmetry independent molecules in SMZ (Z′ > 1), which was confirmed by the SMZ crystal structure solved at 100 K (Z′ = 3). The amine-carboxylate synthon plays an important role in the intermolecular hydrogen bonding interactions of both SMZ-SAR and SMZ-l-PRO. In contrast, no strong intermolecular hydrogen bonding and I ···πstacking interactions between SMZ and SAC were observed in SMZ-SAC, which features a shape-fit structure. Additionally, all cocrystals demonstrated lower equilibrium solubility and intrinsic dissolution rates compared to SMZ. Therefore, they are suitable crystal forms for the possible improvement in therapeutic performance of SMZ.",

author = "Yue Yuan and Duanxiu Li and Chenguang Wang and Shaodong Chen and Minmin Kong and Zongwu Deng and Sun, {Changquan Calvin} and Hailu Zhang",

note = "Funding Information: We gratefully acknowledge support from the National Natural Science Foundation of China (Nos. 21874148, 21673279), the Youth Innovation Promotion Association of CAS (No. 2012242), and the China Postdoctoral Science Foundation (No. 2017LH045). C.W. and C.C.S. thank the Minnesota Supercomputing Institute (MSI) ( http://www.msi.umn.edu ) for providing the calculation resources. H.L.Z. also thanks Dr. Jianrong Wang (Shanghai Institute of Materia Medica) for valuable discussions. Funding Information: We gratefully acknowledge support from the National Natural Science Foundation of China (Nos. 21874148, 21673279), the Youth Innovation Promotion Association of CAS (No. 2012242), and the China Postdoctoral Science Foundation (No. 2017LH045). C.W. and C.C.S. thank the Minnesota Supercomputing Institute (MSI) Publisher Copyright: Copyright {\textcopyright} 2019 American Chemical Society.",

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doi = "10.1021/acs.cgd.9b01060",

language = "English (US)",

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T2 - Beauty within

AU - Yuan, Yue

AU - Li, Duanxiu

AU - Wang, Chenguang

AU - Chen, Shaodong

AU - Kong, Minmin

AU - Deng, Zongwu

AU - Sun, Changquan Calvin

AU - Zhang, Hailu

N1 - Funding Information: We gratefully acknowledge support from the National Natural Science Foundation of China (Nos. 21874148, 21673279), the Youth Innovation Promotion Association of CAS (No. 2012242), and the China Postdoctoral Science Foundation (No. 2017LH045). C.W. and C.C.S. thank the Minnesota Supercomputing Institute (MSI) ( http://www.msi.umn.edu ) for providing the calculation resources. H.L.Z. also thanks Dr. Jianrong Wang (Shanghai Institute of Materia Medica) for valuable discussions. Funding Information: We gratefully acknowledge support from the National Natural Science Foundation of China (Nos. 21874148, 21673279), the Youth Innovation Promotion Association of CAS (No. 2012242), and the China Postdoctoral Science Foundation (No. 2017LH045). C.W. and C.C.S. thank the Minnesota Supercomputing Institute (MSI) Publisher Copyright: Copyright © 2019 American Chemical Society.

PY - 2019/12/4

Y1 - 2019/12/4

N2 - Sulfamethizole (SMZ) is an antibiotic drug with good solubility but short in vivo half-life. Thus, reducing the dissolution rate is expected to improve bioavailability and therapeutic activity through reducing the systemic elimination of SMZ. To this end, two novel pharmaceutical cocrystals, SMZ-sarcosine (SMZ-SAR) and SMZ-saccharin (SMZ-SAC), were designed and prepared according to the structural resemblance strategy. These cocrystals, along with a previously obtained SMZ-l-proline (SMZ-l-PRO) cocrystal, present an opportunity for detailed analysis of the crystal structure to identify key intermolecular interactions that guide their molecular assembly. 13C Solid state NMR data suggested more than one symmetry independent molecules in SMZ (Z′ > 1), which was confirmed by the SMZ crystal structure solved at 100 K (Z′ = 3). The amine-carboxylate synthon plays an important role in the intermolecular hydrogen bonding interactions of both SMZ-SAR and SMZ-l-PRO. In contrast, no strong intermolecular hydrogen bonding and I ···πstacking interactions between SMZ and SAC were observed in SMZ-SAC, which features a shape-fit structure. Additionally, all cocrystals demonstrated lower equilibrium solubility and intrinsic dissolution rates compared to SMZ. Therefore, they are suitable crystal forms for the possible improvement in therapeutic performance of SMZ.

AB - Sulfamethizole (SMZ) is an antibiotic drug with good solubility but short in vivo half-life. Thus, reducing the dissolution rate is expected to improve bioavailability and therapeutic activity through reducing the systemic elimination of SMZ. To this end, two novel pharmaceutical cocrystals, SMZ-sarcosine (SMZ-SAR) and SMZ-saccharin (SMZ-SAC), were designed and prepared according to the structural resemblance strategy. These cocrystals, along with a previously obtained SMZ-l-proline (SMZ-l-PRO) cocrystal, present an opportunity for detailed analysis of the crystal structure to identify key intermolecular interactions that guide their molecular assembly. 13C Solid state NMR data suggested more than one symmetry independent molecules in SMZ (Z′ > 1), which was confirmed by the SMZ crystal structure solved at 100 K (Z′ = 3). The amine-carboxylate synthon plays an important role in the intermolecular hydrogen bonding interactions of both SMZ-SAR and SMZ-l-PRO. In contrast, no strong intermolecular hydrogen bonding and I ···πstacking interactions between SMZ and SAC were observed in SMZ-SAC, which features a shape-fit structure. Additionally, all cocrystals demonstrated lower equilibrium solubility and intrinsic dissolution rates compared to SMZ. Therefore, they are suitable crystal forms for the possible improvement in therapeutic performance of SMZ.

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Structural Features of Sulfamethizole and Its Cocrystals: Beauty within

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