Analysis of the microcrystalline inclusion compounds of triclosan with β-cyclodextrin and its tris-O-methylated derivative

Solid 1:1 inclusion compounds of triclosan with native and permethylated β-cyclodextrin (β-CD and TRIMEB) were prepared by co-crystallisation and co-evaporation, respectively, and studied by FT-IR and 13C{1H} CP/MAS NMR spectroscopies, thermogravimetric analysis, X-ray diffraction and theoretical calculations. Results showed that triclosan inclusion into TRIMEB afforded an amorphous solid, whilst β-CD·triclosan is composed of microcrystals belonging to two different phases. In the phase featuring larger crystals, X-ray diffraction was carried out and the β-CD host units, packing head-to-head in infinite channels, were refined; the geometry for the included but highly disordered triclosan molecules was assessed by theoretical calculations. The bacterial growth inhibitory action of the inclusion compounds was studied in comparison to that of pure triclosan on Gram-negative (Salmonella, Escherichia) and Gram-positive strains (Bacillus, Listeria, Enterococcus and Staphylococcus) typically associated with human pathologies, and also on environmental bacteria isolated from different soil and water sources. The antimicrobial activities obtained in the present work showed that, of the two CD hosts, TRIMEB brings the most favourable carrier effect: it reduced the toxicity of triclosan against some of the environmental strains and afforded slightly higher action against virulent strains.

We isolated solid 1:1 inclusion compounds of triclosan with the hosts β-CD and TRIMEB and identified by single-crystal diffraction a new phase for β-CD·triclosan. The TRIMEB adduct was amorphous and displayed promising antimicrobial action, being more active than triclosan against ATCC 7644 strain of Listeria monocytogenes and the V583, ATCC 29212 and DSM 20478 strains of Enterococcus faecalis and less toxic against environmental strains from sweet water.Figure optionsDownload as PowerPoint slideHighlights
► Triclosan forms 1:1 solids with β-CD and TRIMEB, the latter being amorphous.
► β-CD·triclosan is microcrystalline and contains at least two different phases.
► Single-crystal diffraction on one of these showed host–guest dimers (2:2) with channel packing.
► Ab initio studies helped estimate the position of disordered triclosan inside the β-CD dimers.
► The inclusion of triclosan into TRIMEB is beneficial for antimicrobial action.