DFT and docking studies of rhodostreptomycins A and B and their interactions with solvated/nonsolvated Mg²⁺ and Ca²⁺ ions

Abstract

The interactions of L-aminoglucosidic stereoisomers such as rhodostreptomycins A (Rho A) and B (Rho B) with cations (Mg²⁺, Ca²⁺, and H⁺) were studied by a quantum mechanical method that utilized DFT with B3LYP/6-311G**. Docking studies were also carried out in order to explore the surface recognition properties of L-aminoglucoside with respect to Mg²⁺ and Ca²⁺ ions under solvated and nonsolvated conditions. Although both of the stereoisomers possess similar physicochemical/antibiotic properties against Helicobacter pylori, the thermochemical values for these complexes showed that its high affinity for Mg²⁺ cations caused the hydration of Rho B. According to the results of the calculations, for Rho A–Ca²⁺(H₂O)₆, ΔH = −72.21 kcal mol⁻¹; for Rho B–Ca²⁺(H₂O)₆, ΔH = −72.53 kcal mol⁻¹; for Rho A–Mg²⁺(H₂O)₆, ΔH = −72.99  kcal mol⁻¹ and for Rho B–Mg²⁺(H₂O)₆, ΔH = −95.00  kcal mol⁻¹, confirming that Rho B binds most strongly with hydrated Mg²⁺, considering the energy associated with this binding process. This result suggests that Rho B forms a more stable complex than its isomer does with magnesium ion. Docking results show that both of these rhodostreptomycin molecules bind to solvated Ca²⁺ or Mg²⁺ through hydrogen bonding. Finally, Rho B is more stable than Rho A when protonation occurs.