Sorption Studies of Tetracycline Antibiotics on Hydroxyapatite (001) Surface-A First-Principles Insight

Abstract

Owing to the limitations of traditional systemic drug delivery in the treatment of bone diseases with side effects on normal cells, the selection of materials with high affinities for bones, as targeting ligands to modify drug carriers, has become an important research topic. Tetracyclines (TCs) have an adsorption effect on hydroxyapatite (HAp). Thus, they can be used as bone-targeting ligands and combined with drug carriers. In this study, density functional theory is used to analyze the interaction mechanism of TC, oxytetracycline (OTC), chlortetracycline, and HAp. We calculate the electrostatic potential (ESP) and molecular orbitals to predict the possible binding sites of TCs on the HAp surface. The adsorption energy is used to compare the affinities of the three TCs to HAp. An independent gradient model analysis is performed to study the weak interaction between TCs and HAp. The coordination bond between TCs and the HAp surface is evaluated by conducting a charge density difference analysis. The results show that OTC has the highest affinity to HAp because the introduction of hydroxyl groups change the adsorption configuration of OTC. Thus, OTC adsorbed on HAp in a broken-line shape exposes more binding sites. This study provides a theoretical basis for TCs as bone-targeting ligands in treating bone diseases and in improving the safety of treatment by selecting different bone-targeting ligands.

Keywords: bone targeting; density functional theory; drug delivery; hydroxyapatite; tetracycline.

Scheme 1

Chemical structures of TC, OTC, and CTC.

Figure 1

ESP of HAp. The blue area represents a positive ESP exhibiting electrophilic properties, whereas the red area represents a negative ESP exhibiting nucleophilic properties.

Figure 2

ESPs of (A) TC, (B) OTC, and (C) CTC molecules (two-side view). The blue area represents a positive ESP exhibiting electrophilic properties, whereas the red area represents a negative ESP exhibiting nucleophilic properties.

Figure 3

HOMOs and LUMOs of HAp.

Figure 4

HOMOs and LUMOs of TC, OTC, and CTC.

Figure 5

Stable adsorption structures of (A) TC, (B) OTC, and (C) CTC on the HAp surface.

Figure 6

IGM between the two fragments of TCs and HAp.

Figure 7

Charge density difference analyses of (A) TC, (B) OTC, and (C) CTC (two side views).