1H-NMR Spectroscopy Study of the Formation of Inclusion Complexes between Cucurbit[7]uril and Ciprofloxacin, Levofloxacin, and Lomefloxacin.

Abstract

Owing to the recent detection of pharmaceutical residues in aquatic environments, the development of methods for their removal has attracted increasing research attention. Considering the rich host-guest chemistry of cucurbit[7]uril (CB[7]), which can form stable inclusion complexes with various compounds, we envisioned that CB[7] could be used for capturing pharmaceutical residues in aquatic environments. In this study, using ¹H-NMR spectroscopy, we examined the formation of inclusion complexes between CB[7] and new quinolone antibiotics that have been linked to the emergence of resistant bacteria, that is, ciprofloxacin hydrochloride monohydrate (CPFX), levofloxacin hydrochloride (LVFX), lomefloxacin hydrochloride (LFLX), and pazufloxacin mesylate (PZFX). The results showed that CPFX, LVFX, and LFLX formed inclusion complexes with CB[7] at a molar ratio of 1 : 1, with complex formation constants (K) of 0.529, 0.877, and 3.65 (×10⁴ M^-1), respectively, whereas PZFX did not. This difference was attributed to the presence or absence of a piperazine ring, indicating that it is a critical feature for the formation of inclusion complexes with CB[7]. In addition, the thermodynamic parameters calculated using van't Hoff plots revealed that LVFX and LFLX with a methyl group on the piperazine ring expel high-energy water from the cavity of CB[7] more efficiently, resulting in larger K values. Because the piperazine ring structure is commonly found in many drugs, CB[7] can be expected to capture other drugs apart from those evaluated in this study. Therefore, CB[7] is a promising candidate as a host molecule for use in drug removal in aquatic environments through host-guest chemistry.