Crystal Structure of β‐Cyclodextrin‐Felbinac Inclusion Complex

Abstract

The crystal structure of the inclusion complex of β-cyclodextrin (β-CD) synthesized with felbinac (4-biphenylacetic acid) was determined by single crystal X-ray diffraction at 150 K. The complex contains two β-CDs, two felbinac molecules, twenty-two water molecules in the asymmetric unit, and could be formulated as (C 42 H 70 O 35 ) 2 •(C 14 H 12 O 2 ) 2 •22(H 2 O). In the crystal lattice, the two β-CD moieties form a head-to-head dimer jointed through hydrogen bonds, and the felbinacs that interact by face-to-face π-π stacking are included in the β-CD dimer cavity with their carboxyl groups protruding out from cavity opening. In crystals the dimer units of β-CD are stacked in an intermediate type (IM) that consists of closely packed β-CD dimer layers.

β‐Cyclodextrin Encapsulation of Synthetic AHLs: Drug Delivery Implications and Quorum‐Quenching Exploits

“…Our investigation into the association behavior of synthetic AHLs with β‐CD began with 1 , principally because the association of its carboxylic acid precursor (4‐biphenylacetic acid, BPAA) with β‐CD is well‐known through both solubility studies and X‐ray crystallography [39–41] . The crystal structure of the {β‐CD:BPAA} inclusion complex, solved by Wang and co‐workers, indicated that the biphenyl region of BPAA docks within the host's hydrophobic cavity [41] .…”

“…Our investigation into the association behavior of synthetic AHLs with β‐CD began with 1 , principally because the association of its carboxylic acid precursor (4‐biphenylacetic acid, BPAA) with β‐CD is well‐known through both solubility studies and X‐ray crystallography [39–41] . The crystal structure of the {β‐CD:BPAA} inclusion complex, solved by Wang and co‐workers, indicated that the biphenyl region of BPAA docks within the host's hydrophobic cavity [41] . This SAHLA also has biological relevance as a broad spectrum QS antagonist, capable of inhibiting the TraR 15 ( Agrobacterium tumefaciens , Ti plasmid replication and conjugation), [42–44] LuxR 15 ( Vibrio fischeri , bioluminescence), [45,46] and QscR [47] ( P. aeruginosa , “antivirulence′”) [48] .…”

2-(Biphenyl-4-yl)acetic acid (felbinac)

“…Although the single-crystal structures of inclusion complexes between felbinac and both heptakis-(2,3,6-tri-O-methyl)-βcyclodextrin and β-cyclodextrin have been published (Harata et al, 1992;Wang et al, 2009), that of the pure compound has not been reported. The molecular structure is shown in Figure 1.…”

“…Hydrogen bonds between carboxylic acid groups of felbinac are disrupted in the published felbinac-cyclodextrin structures (Harata et al, 1992;Wang et al, 2009). In the inclusion complex between felbinac and heptakis-(2,3,6-tri-Omethyl)-β-cyclodextrin (Harata et al, 1992), no dimers are formed; in that between felbinac and β-cyclodextrin (Wang et al, 2009), face-to-face π-π stackings form the basis for dimer formation.…”

“…Hydrogen bonds between carboxylic acid groups of felbinac are disrupted in the published felbinac-cyclodextrin structures (Harata et al, 1992;Wang et al, 2009). In the inclusion complex between felbinac and heptakis-(2,3,6-tri-Omethyl)-β-cyclodextrin (Harata et al, 1992), no dimers are formed; in that between felbinac and β-cyclodextrin (Wang et al, 2009), face-to-face π-π stackings form the basis for dimer formation. Hydrogen bonds between carboxylic acid groups of felbinac are disrupted in the complexes with tryptamine (Koshima et al, 1998) and 1,2-diphenylethylenediamine (Imai et al, 2007) due to ionic interactions with the amine functions.…”