Effect of pH on the formation of inclusion complexes between β-lactam antibiotics and 2-hydroxypropyl-β-cyclodextrin in aqueous solution

The complexation of beta-lactam antibiotics, amoxicillin (AMPC), ampicillin (ABPC) and benzylpenicillin (PCG), with 2-hydroxypropyl-beta-cyclodextrin (HPCD) was studied at various pH values using microcalorimetry, H-1 NMR spectroscopy, and molecular dynamic simulation. In the strong acid solution, two different types of inclusion complex with a 1:1 stoichiometry, Complex I with a phenyl ring of beta-lactam antibiotics penetrated into the cavity of HPCD and Complex II with a penam included in the cavity, were formed by hydrophobic interaction, and Complex II was more stable than Complex I. In aqueous solution at pHa parts per thousand yen4.5, only Complex I was formed, where the penam of PCG was more deeply penetrated into the cavity to keep it stable than those of AMPC and ABPC. The charged carboxyl-group on the penam was less affinity to form Complex II.