A Highly Selective and Efficient Copper(II) – “Turn‐On” Fluorescence Imaging Probe for l‐Cysteine

Abstract

A simple copper(II) complex of the anthracenyl‐appended terpyridine ligand 4′‐(anthracen‐9‐yl)‐2,2′:6′,2′′‐terpyridine (L), [Cu(L)Cl2] (1, ESI‐MS, m/z = 507.08), is reported as a highly selective “turn‐on” optical imaging probe for l‐cysteine. Probe 1 shows a CuII/CuI redox potential [E1/2 = –0.194 V versus normal hydrogen electrode (NHE)] within a biologically viable range. The copper center in 1 adopts a square‐pyramidal geometry (τ = 0.0851), and the Cu–Npy bond (1.970 Å) of the middle pyridine (py) ring is shorter than the other two Cu–Npy bonds (2.069 and 2.040 Å). The Cu–Cl bonds (2.444 and 2.027 Å) are labile enough to be replaced by solvent molecules. The square‐based geometry is further supported by the A∥ value of 156.8 × 10–4 cm–1 determined by electron paramagnetic resonance (EPR) spectroscopy at 70 K. The d–d transition of 1 in acetonitrile/4‐(2‐hydroxyethyl)‐1‐piperazineethanesulfonic acid (acetonitrile/HEPES) buffer at pH 7.34 appears at λ =760 nm (ε = 198 m–1 cm–1), and the ligand‐based transitions are observed at λ = 327–384 nm. The ligand shows strong fluorescence at λ = 430 nm with a quantum yield of 11 %, but its emission intensity is completely quenched on coordination with Cu2+ ions, as in 1. Probe 1 detects l‐cysteine selectively through turn‐on fluorescence intensity at λem = 431 nm with a limit of detection of 1.9 × 10–8 m at pH 7.34. Interestingly, probe 1 is able to visualize exogenously added l‐cysteine in Henrietta Lack cervical cancer (HeLa) cells, human liver hepatocellular carcinoma (HepG2) cells, and human embryonic kidney 293 (HEK293) cells under identical conditions at pH 7.4 in confocal microscopy imaging.