A Fluorescein-Substituted Perbrominated Dodecaborate Cluster as an Anchor Dye for Large Macrocyclic Hosts and Its Application in Indicator Displacement Assays
Jinling Zhang, Detlef Gabel, Khaleel I. Assaf, Werner M. Nau
Abstract
Perhalogenated boron clusters derived from B12Br122–, a superchaotropic dianion with a globular icosahedral shape, serve as inorganic cavity binders for cyclodextrins (CDs), in particular for large CDs (γ-CD and δ-CD), with high binding affinity (Ka > 106 M–1) in aqueous solution. This opens the door for applications of this anchoring moiety by linking it to organic residues, prominently fluorescent dyes. We report here the synthesis of a novel fluorescein-substituted perbrominated dodecaborate cluster by a copper(I)-catalyzed azide–alkyne click reaction. The formation of host–guest inclusion complexes between the dodecaborate-modified fluorescein dye and CDs can be readily followed by optical titrations, which afforded a binding constant of ∼1 × 104 M–1 with γ-CD; that is, the cluster functionalization allows binding of an otherwise nonbinding dye to the macrocycle (“anchor dye”). The formation of the 1:1 host–guest inclusion complex between the dye and γ-CD occurs over a broad range of pH values, which allows its application as a sensitive reporter pair according to the indicator displacement method, e.g., for drug detection. In addition, the substituted dye shows outer-wall binding to cucurbiturils through the dodecaborate moiety, leading to the formation of aggregates and significant fluorescence quenching of the dye.