Binding of acetylcholine and tetramethylammonium to a cyclophane receptor: anion's contribution to the cation-pi interaction.
The interaction of the lipophilic cyclophane 1 with several acetylcholine (ACh) and tetramethylammonium (TMA) salts has been investigated in deuteriochloroform to ascertain the influence of the counterion on the cation-pi interaction. Reliable association constants have been measured for 17 salts of commonly used anions; corresponding binding free energies -DeltaG degrees ranged from over 8 kJ mol(-1) down to the limit of detection. The dramatic dependence of the binding energy on the anion showed that the latter takes part in the process with a passive and adverse contribution, which inhibits cation binding even to complete suppression in unfavorable cases. Thermodynamic parameters for the association of 1 with TMA picrate demonstrate that binding is enthalpic in origin, showing a substantial enthalpy gain (DeltaH degrees = -16.7 kJ mol(-1)) and an adverse entropic contribution (DeltaS degrees = -27.9 J mol(-1) K(-1)). A correlation has been found between the "goodness" of anions as binding partners and the solubility of their salts. Conversion of the anion into a more charge-dispersed species, for example, conversion of chloride into dialkyltrichlorostannate, improves cation binding substantially, indicating that charge dispersion is a main factor determining the influence of the anion on the cation-pi interaction. DFT computational studies show that the variation of the binding free energy of TMA with the counterion is closely accounted for by the electrostatic potential (EP) of the ion pair: guest binding appears to respond to the cation's charge density exposed to the receptor, which is determined by the anion's charge density through a polarization mechanism. A value of -DeltaG degrees = 38.6 kJ mol(-1) has been extrapolated for the free energy of binding of TMA to 1 in chloroform but in the absence of a counterion. The transmission of electrostatic effects from the ion pair to the cation-pi interaction demonstrates that host-guest association is governed by Coulombic attraction, as long as factors (steric, entropic, solvation, etc.) other than pure electrostatics are not prevalent.
Bartoli
Sandra
S
CNR, Istituto di Chimica dei Composti Organometallici, Dipartimento di Chimica Organica, Università di Firenze, Polo Scientifico, I-50019 Sesto Fiorentino, Firenze, Italy.
Roelens
Stefano
S
D000109:Acetylcholine / Q000737:chemistry* / Q000378:metabolism; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D002725:Chloroform / Q000737:chemistry; D003903:Deuterium; D004988:Ethers, Cyclic / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D055672:Static Electricity; D013816:Thermodynamics; D000097566:Cyclophanes
D000109:Acetylcholine; D002412:Cations; D002725:Chloroform; D003903:Deuterium; D004988:Ethers, Cyclic; D008024:Ligands; D010880:Piperidines; D000644:Quaternary Ammonium Compounds; C121239:cyclophane 1; D000097566:Cyclophanes; C027917:tetramethylammonium