Structure modeling, synthesis and X-ray diffraction determination of an extra-large calixarene-based coordination cage and its application in drug delivery

Abstract

An extra-large octahedral coordination cage (CIAC-114) was designed and modeled based on Co₄-p-tert-butylsulfonylcalix[4]arene (Co₄-(SC4A-SO₂)) subunits and 4,4′,4′′-(benzene-1,3,5-triyl-tris(benzene-4,1-diyl))tribenzoate (BBB) ligands via the isomorphic replacement approach built from an analogous cage structure with a smaller size. X-ray crystallography revealed that the crystals obtained through solvothermal synthesis exhibited the anticipated structure. Each CIAC-114 cage is assembled by six tetranuclear Co₄-(SC4A-SO₂) units as vertices, which bear a four-fold rotational symmetry, and eight tripodal BBB ligands as linkers, which hold a D_3h symmetry. Among its analogues CIAC-114 has the largest overall peripheral diameter of 5.4 nm and an internal cavity of 2.7 nm. After treatment by supercritical CO₂, a single crystal sample of CIAC-114 transformed into amorphous material with the retention of the cage skeleton, which demonstrated good adsorption properties towards a small drug molecule, ibuprofen (Ibu), evidenced by IR spectroscopy, ¹H NMR spectroscopy, N₂ sorption analysis, and drug release experiments. The Ibu release experiment in phosphate buffered saline solution (pH = 7.4) revealed that CIAC-114 exhibited a slow drug release behavior.