Cationic sulfonium functionalization renders Znsalens with high fluorescence, good water solubility and tunable cell-permeability

Abstract

In this study, we report for the first time that incorporation of cationic sulfonium to the Znsalens skeleton achieves water soluble fluorescent metal complex probes for living cell imaging. To circumvent Znsalen aggregation arising from intermolecular Zn⋯O interactions (found between Zn and the phenoxyl group of another Znsalen molecule), we synthesized a series of sulfonium Znsalens based on alkylation of the 3-thioether or 3,5-dithioether moieties of salicylaldehydes. Such functionalization not only provides positive charge(s) to enhance electrostatic repulsion, but also increases steric hindrance, which renders the Znsalen complex water soluble as a monomeric species in aqueous media as revealed by diffusion ordered NMR spectroscopy (DOSY). More interestingly, these sulfonium Znsalens display “switched on” fluorescence when compared to thioether analogues, which was attributed to the electron-withdrawing sulfonium moiety that perturbs the photoinduced electron transfer (PET) process as suggested by computational calculations based on time-dependent density functional theory (TD-DFT). Most interestingly, live cell imaging experiments showed that modulation of the sulfonium moieties, such as the number or alkyl substituents, significantly tunes the cell-permeability of the fluorescent Znsalens. Thus, this study has demonstrated the importance of sulfonium functionalization on dissociating the intermolecular metal–ligand interactions and thus, modulating water solubility, photophysical properties and even cell-permeability of the fluorophores, which provides a new approach to the design of functional metal complexes for biological studies.