Chloramphenicol center dot cyclodextrin inclusion compounds: co-dissolution and mechanochemical preparations and antibacterial action

Abstract

beta-Cyclodextrin (beta CD) inclusion compounds of chloramphenicol in the solid-state were prepared via two different procedures, co-crystallisation from aqueous solution and the solvent-free method of co-grinding. Chloramphenicol inclusion into permethylated beta CD (TRIMEB) was also performed by co-dissolution in ethanol. The co-crystallisation procedure was the best for preparing chloramphenicol center dot beta CD in 1 : 1 stoichiometry in high purity, while with the co-grinding treatment and the same starting proportion, a complete inclusion was not achieved. Microcrystals of chloramphenicol center dot beta CD inclusion compound presented polymorphism, crystallising simultaneously in the triclinic P1 or monoclinic C2 space groups. Only crystals of the latter were suitable for single-crystal diffraction and data for the guest atoms was comprised of a smeared-out electron cloud, so theoretical calculations were used to propose their plausible geometry and location inside the host molecules. The co-grinding procedure curbed polymorphism and allowed the preparation of chloramphenicol center dot beta CD in the amorphous state; chloramphenicol center dot TRIMEB prepared by co-dissolution of the components in a 1 : 1 proportion was also an amorphous material. The influence of inclusion with beta CD and TRIMEB on the antimicrobial performance of chloramphenicol was evaluated, and both inclusion compounds demonstrated selective action against Enterococcus faecalis strains ATCC 29212 and A33562 and Listeria monocytogenes ATCC 7644. Chloramphenicol center dot TRIMEB also had higher activity against the E. faecalis strains A35906, 9308 and E4856 and against Listeria inocua.