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

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 (K(assoc) < 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.