The synthesis, thermal behaviour, spectral and structural characterization, and in silico prediction of pharmacokinetic parameters of tetraalkylammonium salts of non-steroidal anti-inflammatory drug nimesulide

Abstract

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 P2₁/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, ¹H NMR, ¹³C 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.