Molecular Recognition on the Multisite Binding Surface of the Keplerate {Mo₇₂Fe₃₀} Giving Supramolecular Texturing and Modulating the Function of Guest Molecules

Molecular recognition underlies structure formation in supramolecular architectures either in materials or in living systems. Here, we used the nanoscale nontoxic Keplerate-type polyoxometalate (POM) {Mo₇₂Fe₃₀} as a template for the recognition of two different guest molecules [tetracycline (TC) and doxorubicin (DOX)] on the textured surface. By means of single crystal X-ray analysis and X-ray photoelectron spectroscopy (XPS), we revised the key features of the {Mo₇₂Fe₃₀} structure, showcasing the guest dimolybdenum units' {Mo₂} location under the hexagonal pores and dynamic exchange of these units during dissolution in an aqueous medium. Based on the clarified POM structure, we demonstrated how the small differences between the TC and the DOX molecules can be recognized by the Keplerate surface, revealing the nature of the binding sites─{Mo₆}/{FeO₆} for TC and {FeO₆} for DOX. Furthermore, using the Monte-Carlo method, we calculated the statistical distribution of the guest molecules in the stoichiometric compounds {Mo₇₂Fe₃₀}@TC₁₂ and {Mo₇₂Fe₃₀}@DOX₁₂, displaying the supramolecular ordering of the DOX species and randomization of the TC as a result of different coordinations to the POM surface. The produced {Mo₇₂Fe₃₀}@TC₁₂ and {Mo₇₂Fe₃₀}@DOX₁₂ associates were evaluated for bioactivity, showing how their interaction with POM can modulate the biological function of guest molecules.