A molecular-logic gate for COX-2 and NAT based on conformational and structural changes: visualizing the progression of liver disease

Abstract

Lighting up the relevant lesion boundaries during operations is vital for guiding the effective resection of hepatopathic tissue. We envisioned that molecular-logic gates, which are known for their excellent digital correlation between input and output signals, could be used to facilitate differential visualization of lesion boundaries. Herein, a series of flexible molecules, naphthalene imide-indole derivatives (IAN) were prepared and evaluated as molecular-logic gates. The input and output signals of the IAN derivatives were successfully used to highlight different hepatopathic regions in order to facilitate boundary differentiation. The IAN derivatives produce different signals due to collaborative changes in the conformation and structure. The hepatopathy-related enzymes (COX-2 and NAT) were used to induce conformational and structural changes in IAN derivatives. Based on these enzyme induced synergistic effects, IAN can sensitively emit different coloured signals such as green, cyan and blue (output signals) as a function of the different input signals, i.e. the different activity of COX-2 and NAT in solution and living cells. Significantly, the IAN derivatives were successfully used to distinguish the boundaries of hepatopathic lesions in tissues after spraying with IAN derivatives (mild cirrhosis, severe cirrhosis, in addition to early and late hepatocellular carcinoma) under a hand held lamp at 365 nm by naked eye.