Enhancing Membrane Permeability of Fluorescein-Type Chromophore Through Covalent Attachment of Chlorinated...

Anionic boron clusters, such as [B₁₂X₁₂]^2- (X = Cl, Br, I), have attracted attention in pharmaceuticals due to their unique superchaotropic properties. In particular, [B₁₂Br₁₂]^2- (1) has demonstrated strong interactions with biomolecules, facilitating cargo translocation across plasma membranes. In this study, we investigated the effect of covalently attaching chlorinated dodecaborate moiety [B₁₂Cl₁₁O-]^2- to 6-carboxyfluorescein (6-FAM) (3) via a PEG3 linker to form conjugate (4). We compared the membrane permeability of this covalent conjugate with that of non-covalent interactions between 6-FAM (3) and [B₁₂Cl₁₂]^2- (2). Live-cell fluorescence imaging revealed that the covalent conjugate exhibited enhanced membrane permeability and water solubility while maintaining low cytotoxicity. These results highlight the potential of covalent conjugation with boron clusters for improving the cellular uptake of hydrophilic cargos.