Physicochemical properties and biological activity: thermodynamic properties of compounds related to acetylcholine assessed from depression of freezing-point and enthalpies of dilution.
1 Measurements have been made of the osmotic coefficients and enthalpies of dilution of acetylcholine and of compounds related to it in which the carbonyl and ether groups have been replaced by methylene and the trimethylammonium group by triethylammonium. All were iodides. Measurements were also made with tetraethylammonium iodide and agree with published values.2 Where necessary the affinities of the compounds for acetylcholine receptors in the guinea-pig ileum and frog rectus, or their activities relative to acetylcholine, have been measured.3 The osmotic coefficients were used to calculate activity coefficients and excess free energies, which have been used with the excess enthalpies to calculate the excess entropies of the solutions. These indicate that the ester and carbonyl groups have a marked ordering effect on the ions in water compared with methylene groups; the ether group has an intermediate effect.4 When the results are interpreted in terms of ion-pair formation they can be used to calculate the ion-association constants and enthalpies and entropies of formation of ion-pairs, and lead to similar conclusions: that the order associated with ion-pair formation is greater with the esters and ketones. There appears to be extensive ion-association in the concentrations (0.5 to 1M) usually used in n.m.r. studies.5 There is no obvious correlation between the effects of groups on water and their activity or affinity at muscarine-sensitive acetylcholine receptors but it is possible that ability to activate nicotine-sensitive receptors may be associated with an increase in order, though it would be necessary to study entropy changes in systems actually involving receptors in order to prove this. It is also necessary to suppose that ability to activate these receptors is limited to compounds with small onium groups.
D000109:Acetylcholine / Q000032:analysis* / Q000494:pharmacology; D000818:Animals; D001001:Anura; D002151:Calorimetry; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D004952:Esters; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007454:Iodides; D007659:Ketones; D008433:Mathematics; D009994:Osmolar Concentration; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D012007:Rectum / Q000187:drug effects; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D004952:Esters; D007454:Iodides; D007659:Ketones; D000644:Quaternary Ammonium Compounds; D000109:Acetylcholine