Non-covalent interactions and adsorption affinities of doxycycline and tetracycline with the (010) and (001) surfaces of hydroxyapatite. A DFT and experimental study

Understanding the antibiotic interaction processes with hydroxyapatite (HA) surface is crucial for designing effective antibiotic release systems for treating inflammatory processes in calcified tissues. In this study, we investigated the non-covalent interactions and adsorption sites of the antibiotics doxycycline (DOX) and tetracycline (TC) on the (001) and (010) HA surfaces using transmission electron microscopy. The needle-shaped HA nanoparticles exhibited PO4-rich (010-PO4) and PO4-deficient (010-OH) surfaces. Adsorption isotherms of nearly stoichiometric HA (Ca10(PO4)6(OH)2) demonstrated Langmuir-Freundlich kinetics, with DOX showing a greater affinity than TC for the HA surface. Density functional theory atomistic simulations with three configurations of DOX and TC interacting with the 001, 010-PO4, and 010-OH surfaces revealed van der Waals interactions and hydrogen bonds at the interface. However, DOX exhibited higher adsorption energy than TC. Both molecules preferred to interact with the 010-PO4 surface in their stable configurations. However, the it-cation interactions between the aromatic ring of DOX and the Ca atoms on the HA surface were not observed in TC. Our findings further our understanding of the non-covalent interactions and adsorption sites of cyclines on the HA surface, thus promoting the design of more effective antibiotic release systems.