Visible-Near-Infrared and Fluorescent Copper Sensors Based on Julolidine Conjugates: Selective Detection and Fluorescence Imaging in Living Cells

• Published in: Chemistry : a European journal Vol. 17; no. 40; pp. 11152 - 11161
• Main Authors: Maity, Debabrata, Manna, Arun K., Karthigeyan, D., Kundu, Tapas K., Pati, Swapan K., Govindaraju, T.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 26.09.2011; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: bioimaging; Chemistry; Chemistry, Multidisciplinary; chemosensors; copper; Copper - chemistry; fluorescence; Fluorescent Dyes - chemistry; Hydrazines - chemistry; Ligands; Molecular Structure; Physical Sciences; Protein Binding; Quantum Theory; Schiff Bases - chemistry; Science & Technology; Sensitivity and Specificity; Solutions; Spectrometry, Fluorescence - methods; Spectroscopy, Near-Infrared - methods; visible-near infrared; MOLECULAR CALCULATIONS; EFFECTIVE CORE POTENTIALS; visible-near infrared; CU2+ IONS; MECHANISMS; NEURODEGENERATIVE DISEASES; ZINC; chemosensors; CHEMOSENSOR; OFF-ON; fluorescence; bioimaging; CHEMISTRY; copper; BACTERIAL-INFECTION
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201101906

We present novel Schiff base ligands julolidine–carbonohydrazone 1 and julolidine–thiocarbonohydrazone 2 for selective detection of Cu2+ in aqueous medium. The planar julolidine‐based ligands can sense Cu2+ colorimetrically with characteristic absorbance in the near‐infrared (NIR, 700–1000 nm) region. Employing molecular probes 1 and 2 for detection of Cu2+ not only allowed detection by the naked eye, but also detection of varying micromolar concentrations of Cu2+ due to the appearance of distinct coloration. Moreover, Cu2+ selectively quenches the fluorescence of julolidine–thiocarbonohydrazone 2 among all other metal ions, which increases the sensitivity of the probe. Furthermore, quenched fluorescence of the ligand 2 in the presence of Cu2+ was restored by adjusting the complexation ability of the ligand. Hence, by treatment with ethylenediaminetetraacetic acid (EDTA), thus enabling reversibility and dual‐check signaling, julolidine–thiocarbonohydrazone (2) can be used as a fluorescent molecular probe for the sensitive detection of Cu2+ in biological systems. The ligands 1 and 2 can be utilized to monitor Cu2+ in aqueous solution over a wide pH range. We have investigated the structural, electronic, and optical properties of the ligands using ab initio density functional theory (DFT) combined with time‐dependent density functional theory (TDDFT) calculations. The observed absorption band in the NIR region is attributed to the formation of a charge‐transfer complex between Cu2+ and the ligand. The fluorescence‐quenching behavior can be accounted for primarily due to the excited‐state ligand 2 to metal (Cu2+) charge‐transfer (LMCT) processes. Thus, experimentally observed characteristic NIR and fluorescence optical responses of the ligands upon binding to Cu2+ are well supported by the theoretical calculations. Subsequently, we have employed julolidine–thiocarbonohydrazone 2 for reversible fluorescence sensing of intracellular Cu2+ in cultured HEK293T cells. Seeing is believing: The julolidine–carbonohydrazone and julolidine–thiocarbonohydrazone ligands detect Cu2+ colorimetrically with characteristic absorbance in the near‐infrared (NIR, 700–1000 nm) region, which allows the detection of different concentrations of Cu2+ by the naked eye due to the appearance of distinct coloration. Fluorescent julolidine–thiocarbonohydrazone reversibly senses intracellular Cu2+ in cultured HEK293T cells (see figure).