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


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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4


  1. 1.

    Gibb CLD, Stevens ED, Gibb BC (2001) C–H···X–R (X = Cl, Br, and I) hydrogen bonds drive the complexation properties of a nanoscale molecular basket. J Am Chem Soc 123(24):5849–5850

    CAS  Article  Google Scholar 

  2. 2.

    Liu S, Whisenhunt-Ioup SE, Gibb CLD, Gibb BC (2011) An improved synthesis of ‘octa-acid’ deep-cavity cavitand. Supramol Chem 23(6):480–485

    Article  Google Scholar 

  3. 3.

    Gan H, Benjamin CJ, Gibb BC (2011) Nonmonotonic assembly of a deep-cavity cavitand. J Am Chem Soc 133(13):4770–4773

    CAS  Article  Google Scholar 

  4. 4.

    Gibb CLD, Gibb BC (2004) Well-defined, organic nanoenvironments in water: the hydrophobic effect drives a capsular assembly. J Am Chem Soc 126(37):11408–11409

    CAS  Article  Google Scholar 

  5. 5.

    Jordan JH, Gibb BC (2015) Molecular containers assembled through the hydrophobic effect. Chem Soc Rev 44(2):547–585

    CAS  Article  Google Scholar 

  6. 6.

    Sullivan MR, Gibb BC (2015) Differentiation of small alkane and alkyl halide constitutional isomers via encapsulation. Org Biomol Chem 13(6):1869–1877

    CAS  Article  Google Scholar 

  7. 7.

    Gan H, Gibb BC (2013) Guest-mediated switching of the assembly state of a water-soluble deep-cavity cavitand. Chem Commun (Cambridge, U. K.) 49(14):1395–1397

    CAS  Article  Google Scholar 

  8. 8.

    Gibb CLD, Gibb BC (2014) Binding of cyclic carboxylates to octa-acid deep-cavity cavitand. J Comput Aided Mol Des 28(4):319–325

    CAS  Article  Google Scholar 

  9. 9.

    Sun H, Gibb CLD, Gibb BC (2008) Calorimetric analysis of the 1:1 complexes formed between a water-soluble deep-cavity cavitand, and cyclic and acyclic carboxylic acids. Supramol Chem 20(1&2):141–147

    CAS  Article  Google Scholar 

  10. 10.

    Gibb CLD, Gibb BC (2011) Anion binding to hydrophobic concavity is central to the salting-in effects of Hofmeister chaotropes. J Am Chem Soc 133(19):7344–7347

    CAS  Article  Google Scholar 

  11. 11.

    Carnegie RS, Gibb CLD, Gibb BC (2014) Anion complexation and the Hofmeister effect. Angew Chem Int Ed 53(43):11498–11500

    CAS  Article  Google Scholar 

  12. 12.

    Gibb CLD, Oertling EE, Velaga S, Gibb BC (2015) Thermodynamic profiles of salt effects on a host–guest system: new insight into the Hofmeister effect. J Phys Chem B 119(17):5624–5638

    CAS  Article  Google Scholar 

  13. 13.

    Sokkalingam P, Shraberg J, Rick SW, Gibb BC (2016) Binding hydrated anions with hydrophobic pockets. J Am Chem Soc 138(1):48–51

    CAS  Article  Google Scholar 

  14. 14.

    Gale PA, Steed JW (eds) (2012) Supramolecular chemistry: from molecules to nanomaterials, volume 1: concepts. Wiley, Sussex, p 235

    Google Scholar 

  15. 15.

    Turnbull WB, Daranas AH (2003) On the value of c: can low affinity systems be studied by isothermal titration calorimetry? J Am Chem Soc 125(48):14859–14866

    CAS  Article  Google Scholar 

  16. 16.

    Tellinghuisen J (2008) Isothermal titration calorimetry at very low c. Anal Biochem 373(2):395–397

    CAS  Article  Google Scholar 

  17. 17.

    Rekharsky MV, Inoue Y (2002) Solvent and guest isotope effects on complexation thermodynamics of alpha-, beta-, and 6-amino-6-deoxy-beta-cyclodextrins. J Am Chem Soc 124(41):12361–12371

    CAS  Article  Google Scholar 

  18. 18.

    Ben-Amotz D, Underwood R (2008) Unraveling water’s entropic mysteries: a unified view of nonpolar, polar, and ionic hydration. Acc Chem Res 41(8):957–967

    CAS  Article  Google Scholar 

  19. 19.

    Wang K, Sokkalingam P, Gibb BC (2016) ITC and NMR analysis of the encapsulation of fatty acids within a water-soluble cavitand and its dimeric capsule. Supramol Chem 28(1–2):84–90

    CAS  Article  Google Scholar 

  20. 20.

    Chodera JD, Mobley DL (2013) Entropy-enthalpy compensation: role and ramifications in biomolecular ligand recognition and design. Annu Rev Biophys 42:121–142

    CAS  Article  Google Scholar 

  21. 21.

    Laughrey ZR, Gibb CLD, Senechal T, Gibb BC (2003) Guest binding and orientation within open nanoscale hosts. Chem Eur J 9(1):130–139

    CAS  Article  Google Scholar 

  22. 22.

    Gibb CLD, Xi H, Politzer PA, Concha M, Gibb BC (2002) The synthesis and binding properties of nano-scale hydrophobic pockets. Tetrahedron 58(4):673–681

    CAS  Article  Google Scholar 

Download references


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.

Author information



Corresponding author

Correspondence to Bruce C. Gibb.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 4150 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation


  • Host-guest chemistry
  • Cavitand
  • Hydrophobic effect