4.7 Article

Highly Effective Binding of Viologens by p-Sulfonatocalixarenes for the Treatment of Viologen Poisoning

Journal

JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 20, Pages 6402-6412

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jm900811z

Keywords

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Funding

  1. 973 Program [2006CB932900]
  2. NNSFC [20421202, 20673061, 20703025]
  3. Tianjin Natural Fund [07QTPJC29600]

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Viologens are showing an increasing number of scientific and technical applications in addition to their use as herbicides. However, their high toxicity poses considerable risks to human health, society, and the environment. In this context, we propose a new therapeutic protocol for the treatment of viologen poisoning. The mechanism of this new protocol is based on host-guest chemistry and involves the effective inhibition of viologen toxicity by the complexation of p-sulfonatocalix[n]arenes. NMR, ITC, and X-ray crystallography studies indicated that p-sulfonatocalix[n]arenes could form highly stable complexes with viologens. Electrochemical results showed that the highly effective binding could induce the reduction potentials of viologens to shift to more negative values. Further studies in mice showed that the ingestion of p-sulfonatocalix[n]arenes significantly decreased the mortality rate of viologen-poisoned mice with lung and liver protection. As a result, p-sulfonatocalix[n]arenes may have potential application in the clinical treatment of viologen poisoning.

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