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 .

Chemical Science
|September 21, 2020
PubMed

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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