Structure and properties of (hydroxy)alkylammonium salts of flurbiprofen

Interactions with hydrogen atoms strongly affect the structure of salts of the anti-inflammatory drug flurbiprofen. With cations of the form H3N+C(CH3)3-n(CH2OH)n for n = 0-3 charge-assisted hydrogen bonding is the most obvious feature. In the t-butylammonium (n = 0) salt successive R43(10) rings are formed by +N-H…OCO- interactions. With n = 1 the additional OH is disordered and has little effect. However, n = 2 changes the pattern: now one +N-H…OCO- and one O-H…OCO- hydrogen bond link a cation to a carboxylate anion. When n = 3, this motif persists in one polymorph. However, another polymorph has two independent anions related by pseudo-translation and two independent cations related by a pseudo-glide, while extensive disorder results from application of the “opposite” pseudo-symmetry operation. Enantiomer discrimination at flurbiprofen sites depends on the environment of H and CH3 in the HCCH3 group. Hirshfeld surfaces show normal van der Waals contacts around ordered methyl groups but tight contacts around major sites for disordered ones, which become worse around the minor sites. Similar effects are observed in the vicinity of the fluorine atoms in the fluorophenyl rings. Whereas the major sites for disordered atoms and the sites for ordered atoms are involved in normal or slightly short van der Waals contacts, the minor sites suffer from tighter contacts.
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