Rybczyńska Małgorzata, Sikorski Artur
Faculty of Chemistry, University of Gdańsk, W. Stwosza 63, 80-308, Gdańsk, Poland.
Sci Rep. 2023 Oct 12;13(1):17268. doi: 10.1038/s41598-023-44557-x.
The synthesis, spectral properties, thermal analysis, structural characterization and in silico prediction of pharmacokinetic parameters of tetramethylammonium (compound 1) and tetraethylammonium (compound 2) salt of nimesulide were described in this article. Both compounds crystallize in the monoclinic P2/n space group, with one tetraalkylammonium cation and one nimesulide anion in the asymmetric unit and their crystal structures are stabilized by C-H···O hydrogen bonds between ions. Additionally, structures of title compounds are stabilized by π-π interactions (compound 1), or C-H···π interactions (compound 2) between nimesulide anions. The TG and DSC measurements show that compound 1 melts at a temperature higher than nimesulide, whereas the compound 2 melts at a temperature lower than nimesulide. The MALDI-TOF, H NMR, C NMR and ATR-FTIR analyses confirm the SCXRD study, that in compounds 1 and 2 nimesulide exists in an ionized form. Studies performed by SWISS ADME and ProTOX II tools, predict to be oral bioavailability of both salts obtained, and one of them (compound 1) is predicted to be well-absorbed by digestive system, while both compounds obtained are classified into toxicity class 4.
本文描述了尼美舒利的四甲基铵盐（化合物1）和四乙基铵盐（化合物2）的合成、光谱性质、热分析、结构表征以及药代动力学参数的计算机预测。两种化合物均结晶于单斜P2/n空间群，不对称单元中含有一个四烷基铵阳离子和一个尼美舒利阴离子，其晶体结构通过离子间的C-H···O氢键得以稳定。此外，标题化合物的结构还通过尼美舒利阴离子之间的π-π相互作用（化合物1）或C-H···π相互作用（化合物2）得以稳定。热重（TG）和差示扫描量热（DSC）测量表明，化合物1的熔点高于尼美舒利，而化合物2的熔点低于尼美舒利。基质辅助激光解吸电离飞行时间质谱（MALDI-TOF）、氢核磁共振（¹H NMR）、碳核磁共振（¹³C NMR）和衰减全反射傅里叶变换红外光谱（ATR-FTIR）分析证实了单晶X射线衍射（SCXRD）研究的结果，即化合物1和2中的尼美舒利以离子化形式存在。通过SWISS ADME和ProTOX II工具进行的研究预测了所获得的两种盐的口服生物利用度，其中一种（化合物1）预计可被消化系统良好吸收，而所获得的两种化合物均被归类为4类毒性。
