A Fluorescein-Substituted Perbrominated Dodecaborate Cluster as an Anchor Dye for Large Macrocyclic Hosts and Its Application in Indicator Displacement Assays

Abstract

Perhalogenated boron clusters derived from B 12 Br 12 2−, 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 (K a > 10 6 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 dodecaboratemodified fluorescein dye and CDs can be readily followed by optical titrations, which afforded a binding constant of ∼1 × 10 4 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. R esearch on anion recognition has received a great deal of attention within the supramolecular community. 1−4 Polyhedral closo-dodecaborates B 12 X 12 2− (X = H, F, Cl, Br, or I), prototypes of so-called superchaotropic anions, 5−8 have attracted more interest due to their globular icosahedral structure, delocalized charge, high stability, etc. Recently, the supramolecular chemistry of dodecaborates has been intensively studied, in particular, their binding to water-soluble macrocyclic host molecules such as cyclodextrins, 5,9,10 cucurbiturils, 11 and calixarenes. 12 Moreover, biological interactions of dodecaborates with proteins, peptides, and membranes were also observed. 13−18 Much effort has been devoted to the synthesis and functionalization of the parent dodecahydro-closo-dodecaborate anion, B 12 H 12 2− , 19−21 allowing diverse applications in boron neutron capture therapy (BNCT), 22,23 drug delivery, and other related biological and medical fields. 24−26 However, perhalogenated decaborate and dodecaborate derivatives such as B 10 X 9 R 2− and B 12 X 11 R 2− (X = Cl, Br, or I), which are interesting due to their high thermal and redox stability, chemical inertness, superchaotropicity, and high membrane activity, 6,13 have received less attention in regard to their functionalization. 27 However, the monoalkylation of B 12 X 11 OH 2− and B 12 X 11 NH 3 − clusters has recently been reported, 27−30 thus encouraging the development of synthetic methods for new derivatives, especially B 12 Br 11 OR 2− , to expand their host−guest chemistry and potential applications.Cyclodextrins (CDs) are a class of macrocyclic host molecules that have a truncated cone shape with a hydrophilic ou...

Alkoxy Substituted Brominated closo-Dodecaborates with Functionalized Aliphatic Spacers

“…bromopentyl)phthalimide moiety took place under the same or representative conditions (dimethoxyethane/NaH/reflux, CH3CN/K2CO3/reflux), justifying our approach of utilizing 4 as a precursor. [9,14] The transformation from a terminal bromine group to a hydroxyl group was also examined. Based on a previously reported method, stirring (NBu4)2•4 in DMSO/H2O at 80 ℃ resulted in the formation of (NBu4)2•8 in a good yield.…”

“…Thus far, the structures of the B12Br12 2species have generally been limited to simple alkoxylated structures ([B12X11OR] 2-/ aminated ([B12X11NHR] 2-). [7][8][9] Therefore, to increase the utility of chaotropic membrane transporters based on anionic boron clusters, a versatile method for the derivatization of [B12X12] 2is important.…”

Host–Guest Chemosensor Ensembles based on Water-Soluble Sulfonated Calix[n]arenes and a Pyranoflavylium Dye for the Optical Detection of Biogenic Amines

“…Supramolecular chemistry provides a wide range of receptor molecules, particularly macrocycles, that can be used as hosts in a variety of applications, garnering considerable interest from the scientific community. In terms of structural diversity, macrocycles, include cyclodextrins, , cucurbiturils, , crown ethers, cryptands, pillararenes, and calixarenes, , to give some examples. On the other hand, guest molecules are generally small molecules or ions that benefit from the host–guest interactions to improve their stability and bioavailability or even to tune their spectroscopic features, namely, colorimetric and fluorescent properties.…”

Large anion binding in water

“…43 Another carboxyfluorescein dye of this type, with B 12 Br 11 OR 2− as the anchoring unit, has also been reported. 157 Other hybrid organic–inorganic derivatives of dodecaborate clusters were synthesized by tethering nitroanilines to the B 12 H 12 2− anion. 158 These new aniline-substituted dodecaborates showed higher basicity than the parent nitroanilines and were able to form stable inclusion complexes with β- and γ-CD.…”