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

Abstract

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.

The “True” Affinities of Metal Cations to p‐Sulfonatocalix[4]arene: A Thermodynamic Study at Neutral pH Reveals a Pitfall Due to Salt Effects in Microcalorimetry

“…Although the binding constants of cationic guests tend to be distinctly higher at neutral pH (compare data from competitive titrations in Table 1), the observed contrast in thermodynamic parameters is not expected, since ITC data for the complexation of several other guest molecules do not show such drastic pH changes 17. 19, 20, 46, 47 Presumably, the deviation is due to the presence of large amounts of counterions (ca. 80 m M , see above) and large amounts of host used in the previous study.…”

“…Thermodynamic parameters obtained from the simultaneous fitting of ITC titrations of divalent cations to SC4 in water at neutral pH (7.0) and 298.15 K. changes. [17,19,20,46,47] Presumably, the deviation is due to the presence of large amounts of counterions (ca. 80 mm, see above) and large amounts of host used in the previous study.…”

TGA/DTA–FTIR–MS coupling as analytical tool for confirming inclusion complexes occurrence in supramolecular host–guest architectures

“…This cation, in the presence of O 2 and/or H 2 O 2 , further produces extremely reactive radicals, such as HO • . This leads to the oxidation of biochemical important entities, such as lipid membranes, proteins and nucleic acids [2,10]. In this sense, current research in the domain is focused on the reduction of viologens toxicity and thus to exploit their redox potential for pharmacological interest.…”

Amphiphilic p-Sulfonatocalix[4]arene as “Drug Chaperone” for Escorting Anticancer Drugs

“…Pyridinium was chosen as a binding moiety for amphiphilic p -sulfonatocalixarene instead of viologen because the high toxicity of viologen poses considerable risks to human health36. 1 H NMR measurements were performed to explore the binding behavior of pyridinium tags with calixarene.…”