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A molecular-logic gate for COX-2 and NAT based on conformational and structural changes: visualizing the progression
Yuehua Chen1, Yuzhu Wang2, Yonggang Yang1
1Henan Key Laboratory of Green Chemical Media and Reactions , Ministry of Education , Henan Key Laboratory of Organic Functional Molecules and Drug Innovation , School of Chemistry and Chemical Engineering , School of Physics , Henan Normal University , Xinxiang 453007 , P. R. China .
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.
Insights
Molecular-logic gates derived from naphthalene imide-indole (IAN) derivatives enable precise visualization of liver lesion boundaries. These IAN molecules act as probes, emitting distinct colors to differentiate hepatopathic tissues during surgery.
Area of Science:
- Chemical Biology
- Molecular Imaging
- Surgical Oncology
Background:
- Accurate identification of hepatopathic tissue boundaries is crucial for effective surgical resection.
- Molecular-logic gates offer potential for precise signal correlation between molecular inputs and outputs.
- Developing targeted probes for visualizing diseased tissue remains a significant challenge in liver surgery.
Purpose of the Study:
- To develop and evaluate naphthalene imide-indole (IAN) derivatives as molecular-logic gates for differentiating hepatopathic lesion boundaries.
- To investigate the enzyme-responsive signaling mechanism of IAN derivatives for targeted imaging.
- To assess the in vivo applicability of IAN derivatives in distinguishing various stages of liver disease.
Main Methods:
- Synthesis and characterization of naphthalene imide-indole (IAN) derivatives.
- Evaluation of IAN derivatives as molecular-logic gates responsive to hepatopathy-related enzymes (COX-2 and NAT).
- In vitro and in vivo testing of IAN derivatives for differential visualization of liver lesions under UV light.
Main Results:
- IAN derivatives successfully functioned as molecular-logic gates, producing distinct color signals (green, cyan, blue) based on enzyme activity.
- Enzyme-induced conformational and structural changes in IAN derivatives mediated the observed signal outputs.
- IAN derivatives effectively distinguished boundaries of various hepatopathic lesions, including cirrhosis and hepatocellular carcinoma, in tissue samples by naked eye.
Conclusions:
- Naphthalene imide-indole derivatives serve as effective molecular-logic gates for visualizing hepatopathic lesion boundaries.
- The enzyme-responsive signaling mechanism of IAN provides a novel approach for differential diagnosis in liver disease.
- IAN derivatives demonstrate significant potential for intraoperative guidance in liver surgery.
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