Rhodamine hydrazide-linked naphthalimide derivative: Selective naked eye detection of Cu2+, S2− and understanding the therapeutic potential of the copper complex as an anti-cervical cancer agent

Abstract

A naphthalimide-labeled rhodamine hydrazone derivative HL has been synthesized, characterized and examined in metal ion recognition. It shows selective colorimetric detection of Cu2+ over a number of other metal ions with a detection limit of 1.66 × 10−7 M in CH3CN/HEPES buffer (v/v = 2:1, pH = 6.8). The spirolactam ring of rhodamine and the imino-phenol motif of naphthalimide in HL are involved in complexation of Cu2+ as shown by single crystal X-ray. Single crystal of the copper-complex is prepared by utilizing NaSCN and it is characterized as CuL(SCN). The emergence of new absorption at 550 nm in UV–vis and the pink color of the solution reveal the selective interaction toward Cu2+. HL is characterized as a fluorescence resonance energy transfer (FRET) system that remains ‘turned OFF’ while spirolactam ring exists. In the presence of Cu2+, FRET is ‘turned ON’ via the opening of spirolactam ring to give emission at 580 nm which is less intense due to the quenching effect of Cu2+ ion. The complexation is reversible and the ensemble of Cu2+.HL selectively recognizes S2− over a series of different anions involving a color change from pink to colorless via the formation of spirolactam ring. The copper complex CuL(SCN) is further employed to understand its efficacy as a therapeutic agent. The complex is cytotoxic to high-risk HPV positive cervical cancer cell lines like SiHa and HeLa and is efficient in the generation and accumulation of reactive oxygen species (ROS). The complex also initiates nuclear blebbing and shows DNA degradation as understood by DNA laddering assay.