Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

Beilstein J Org Chem. 2018 Jul 19:14:1840-1845. doi: 10.3762/bjoc.14.157. eCollection 2018.

Abstract

Based on the indicator displacement assay (IDA) approach, we herein report the fluorescence "switch-on" sensing and quantitative detection of bisphosphonates (BPs), a class of drugs extensively used in the treatment of patients with various skeletal diseases. Guanidinium-modified calix[5]arene (GC5A) affords strong binding on the micromolar to nanomolar level towards BPs dominantly via multiple salt bridge interactions, which was evaluated by fluorescence competitive titrations. Fluorescent IDA enables the highly sensitive and label-free detection of BPs in buffer solution, and more importantly, in artificial urine. Calibration lines were therefore set up in untreated artificial urine, allowing for quantifying the concentrations of BPs in the biologically relevant low range.

Keywords: bisphosphonate; calixarene; fluorescence sensing; indicator displacement assay; macrocyclic chemistry.