Theoretical study on ferrocenyl hydrazones inclusion complexes with β-cyclodextrin and its three methylated derivatives

Abstract

Molecular interactions of ferrocenyl hydrazones (FcHZ) inclusion complexes with β-cyclodextrin (BCD), methyl-β-cyclodextrin (MEB), 2,6-di-O-methyl-β-cyclodextrin (DIMEB) and 2,3,6-tri-O-methyl-β-cyclodextrin (TRIMEB) in order to enhance their aqueous solubility and anti-mycobacterial efficiency were investigated by semi-empirical PM7 method and B3LYP/m6-31G* calculations. Simulation results suggest the complex formations of FcHZ with BCD, MEB, DIMEB and TRIMEB are possible with 1:1 host–guest molecular ratio. Two different binding modes of the FcHZ inside the BCD and MEB cavities were found. The ferrocene fragment of FcHZ molecule was entrapped in the cavity, located near the wider rim of BCD and MEB in both orientations (A and B). The hydrazone aromatic fragment of FcHZ cannot be completely embedded inside the hydrophobic cavity of BCD. It points downward from the narrower rim of BCD in orientation A and point upward from the wider rim of BCD in orientation B. Only orientation B was found in 1:1 inclusion complex of FcHZ agents with DIMEB and TRIMEB due to the effect of methyl group substitutions at the primary hydroxyl groups, which located at the narrower rim of cyclodextrins. The entering pathways of the FcHZ molecule into the molecular cavity of the BCD, MEB, DIMEB and TRIMEB were also discussed.