Comparison of Binding Affinities of Water-Soluble Calixarenes with the Organophosphorus Nerve Agent Soman (GD) and Commonly-Used Nerve Agent Simulants

Abstract

The formation of inclusion complexes of the water-soluble p-sulfonatocalix[n]arenes, where n = 4 or 6, with the Chemical Warfare Agent (CWA) GD, or Soman, and commonly used dialkyl methylphosphonate simulants has been studied by experimental solution NMR methods and by Molecular Mechanics (MMFF) and semi-empirical (PM6) calculations. Complex formation in non-buffered and buffered solutions is driven by the hydrophobic effect, and complex stoichiometry determined as 1:1 for all host:guest pairs. Low affinity complexes (Kassoc < 100 M−1) are observed for all guests, attributed to poor host–guest complementarity and the role of buffer cation species accounts for the low affinity of the complexes. Comparison of CWA and simulant behavior adds to understanding of CWA–simulant correlations and the challenges of simulant selection.

Identification of organophosphorus simulants for the development of next-generation detection technologies

“…Here, we identify three trends, one for the phosphoryl species and two for the sulfonyl species. The two trends identified for the sulfonyl species correspond to the two different classes of sulfonate molecules present within the library of simulants studied, those substituted with a toluene group (16)(17)(18)(19)(20) and those substituted with a methyl group (21)(22)(23)(24)(25)(26). As the limitation of the experimental association constant determination methodology is ≈10 M −1 , we suggest that any values incorporating ≤10 M −1 may be considered inappropriate when included into a model such as this and should be treated with caution.…”

“…It is therefore vital to consider the appropriate properties of any simulant chosen to aid in the development of novel OP CWA detection, decontamination, or remediation methodologies. [21][22][23][24] Recently, work undertaken by Snurr and Mendonca, has shown that density functional theory (DFT) can be used to study the mechanism of OP hydrolysis, which has resulted in the development of a quantitative structure activity relationship (QSAR) model that enables the identification of appropriate OP CWA simulants for decontamination purposes. 25 However, when considering supramolecular technologies, the moiety target is often selective coordination of the polar PvO functionality.…”

“…Compounds 11-15 are commercially available species commonly used to simulate OP CWAs. The structures of simulants 5-10 and 16-26 were designed to fulfil the following criteria: charge neutrality; not readily ionised under experimental conditions; containing a single electrophilic site (S or P); and containing a single HBA centre (either a PvO (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), or OvSvO (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)).…”

Supramolecular Sensing of Chemical Warfare Agents

“…Sambrook and co‐workers studied also the ability of p ‐sulfonatocalix[n]arenes (n=4 and 6) to recognize Soman in water [72] . Binding affinity values, calculated by NMR titrations, are low with both calixarene derivatives (calix‐4 shows a K=75 M −1 , while calix‐6 shows a K=10 M −1 ).…”

<p>Needle-shaped amphoteric calix[4]arene as a magnetic nanocarrier for simultaneous delivery of anticancer drugs to the breast cancer cells</p>

“…12 Since calixarenes can be modified by different functionalization at the lower and/or upper rims of the molecule, the calixarene derivatives provide useful platforms for anchoring a variety of binding units for ions and neutral molecules, and incorporating functional groups, such as ester, ether, ketone, amide, and carboxylic acid groups, exhibit excellent binding abilities. [13][14][15][16] Their structures have unique three-dimensional surface, which correspondence: ramin Karimian chemical Injuries research center, systems Biology and Poisonings Institute, Baqiyatallah University of Medical sciences, Mollasadra street, sheykh Baha'i street, Tehran 1435915371, Iran Tel +98 912 610 1850 email karimian.r@gmail.com made them as one of the best-known host molecules and used in the biomedical applications of supramolecular systems based on host-guest interactions. 17,18 A particular interest was generated by the possibility of using calixarenes as vehicles in drug delivery and other pharmacological contexts.…”