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Binding of carboxylate and trimethylammonium salts to octa-acid and TEMOA deep-cavity cavitands

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In participation of the fifth statistical assessment of modeling of proteins and ligands (SAMPL5), the strength of association of six guests (38) to two hosts (1 and 2) were measured by 1H NMR and ITC. Each host possessed a unique and well-defined binding pocket, whilst the wide array of amphiphilic guests possessed binding moieties that included: a terminal alkyne, nitro-arene, alkyl halide and cyano-arene groups. Solubilizing head groups for the guests included both positively charged trimethylammonium and negatively charged carboxylate functionality. Measured association constants (K a ) covered five orders of magnitude, ranging from 56 M−1 for guest 6 binding with host 2 up to 7.43 × 106 M−1 for guest 6 binding to host 1.

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The authors gratefully acknowledge the support of the National Institutes of Health (GM 098141). The authors also acknowledge the Louisiana Board of Regents enhancement grant (Grant LEQSF-(2002-03)-ENH-TR-67) used to purchase the X-ray diffractometer.

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Correspondence to Bruce C. Gibb.

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Sullivan, M.R., Sokkalingam, P., Nguyen, T. et al. Binding of carboxylate and trimethylammonium salts to octa-acid and TEMOA deep-cavity cavitands. J Comput Aided Mol Des 31, 21–28 (2017).

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