Novel Synthons in Sulfamethizole Cocrystals: Structure-Property Relations and Solubility | Sciact - CRIS-system of Boreskov Institute of Catalysis

Novel Synthons in Sulfamethizole Cocrystals: Structure-Property Relations and Solubility Full article

Journal

Crystal Growth and Design
ISSN: 1528-7483 , E-ISSN: 1528-7505

Output data

Year: 2015, Volume: 15, Number: 7, Pages: 3498-3510 Pages count : 13 DOI: 10.1021/acs.cgd.5b00587

Tags

Equilibrium solubilities, Hydrogen bonding interactions, Intermolecular interactions, Powder X-ray diffraction (pXRD), Single crystal x-ray diffraction, Solvent crystallizations, Structure property relation, Therapeutic activity

Authors

Suresh K. ¹ , Minkov V.S. ^2,3 , Namila K.K. ¹ , Derevyannikova E. ^2,3 , Losev E. ^2,3 , Nangia A. ¹ , Boldyreva E.V. ^2,3

Affiliations

1	School of Chemistry, University of Hyderabad, Central University, P.O., Prof. C. R. Rao Road, Hyderabad, India
2	Novosibirsk State University, 2 Pirogov str., Novosibirsk, Russian Federation
3	Institute of Solid State Chemistry and Mechanochemistry SB RAS, 18 Kutateladze, Novosibirsk, Russian Federation

© 2015 American Chemical Society. The sulfamethizole antibiotic drug has rich hydrogen bond functionalities (donors: amine NH<inf>2</inf> and imine NH; acceptors: sulfonyl O, thiazolidine N and S, and imidine N), which makes it a functionally diverse molecule to form cocrystals. A cocrystal screen of sulfamethizole (SMT) with COOH, NH<inf>2</inf>, pyridine, and CONH<inf>2</inf> functional group containing coformers, e.g., p-aminobenzoic acid (PABA), vanillic acid (VLA), p-aminobenzamide (ABA), 4,4-bipyridine (BIP), suberic acid (SBA), oxalic acid (OA), and adipic acid (ADP), resulted in six cocrystals and one salt, namely, SMT-ADP (1:0.5), SMT-PABA (1:1), SMT-VLA (1:1), SMT-ABA (1:1), SMT-BIP (1:1), SMT-SBA (1:0.5), and SMT-OA (1:1). The novel crystalline adducts were synthesized by liquid-assisted cogrinding and isothermal solvent crystallization. In addition to single-crystal X-ray diffraction, the phase composition of the powder samples was confirmed by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). Hydrogen bonding interactions between the coformers and SMT are analyzed as six different synthons. In addition to strong N-H⋯O and O-H⋯N hydrogen bonds, the cocrystal structures are sustained by weak C-H⋯O hydrogen bonds. The not so common chalcogen-chalcogen (S⋯O) type II intermolecular interaction in SMT-ADP cocrystal and chalcogen-nicogen (S⋯N) type II interaction in SMT-BIP cocrystal were observed. The products were characterized by vibrational spectroscopy to obtain information on the strengths of the intermolecular interactions. Solubility and dissolution experiments on SMT-ADP, SMT-SBA, and SMT-OA showed a lower intrinsic dissolution rate (IDR) and equilibrium solubility compared to SMT in 0.1 N HCl medium, which is ascribed to stronger N-H⋯O, N-H⋯N, and O-H⋯O hydrogen bonds and better crystal packing. The decreased IDR could be useful in controlled/extended release of SMT to improve therapeutic activity of the drug by minimizing its fast systemic elimination in vivo. Furthermore, we observed that SMT-OA salt is formed spontaneously when the components were mixed in acidic medium (0.1 N HCl), whereas in neutral medium (phosphate buffer) no SMT-OA salt formation was observed. (Figure Presented).

Suresh K. , Minkov V.S. , Namila K.K. , Derevyannikova E. , Losev E. , Nangia A. , Boldyreva E.V.
Novel Synthons in Sulfamethizole Cocrystals: Structure-Property Relations and Solubility
Crystal Growth and Design. 2015. V.15. N7. P.3498-3510. DOI: 10.1021/acs.cgd.5b00587 WOS Scopus РИНЦ ANCAN OpenAlex

Submitted:	Apr 28, 2015
Published online:	Jun 22, 2015
Published print:	Jul 1, 2015

Web of science:	WOS:000357435800052
Scopus:	2-s2.0-84934779574
Elibrary:	23980416
Chemical Abstracts:	2015:1027563
Chemical Abstracts (print):	163:124969
OpenAlex:	W2509924851

DB	Citing
Web of science	61
Scopus	60
OpenAlex	61