Conformational Flexibility of Choline Derivatives

Abstract

CHOLINERGIC substrates have been found in a gauche conformation (G), skewed about the Cα–Cβ bond of the (CH3)3N+–CH2–CH2–O cholinic fragment in a number of crystal structures1–11. Sulphur and selenium isologues, on the other hand, with the (CH3)3N–CH2–CH2–(S,Se) group, are normally in the extended trans conformations (T)10,12,13. In agreement with the assumption that the reduced spectrum of biological activity of many rigid analogues and Cα or Cβ substituted derivatives of acetylcholine can be partially ascribed to the reduction in conformational flexibility14–17, a theoretical investigation18 predicted the existence of four almost isoenergetic conformations TTTT, TGTT, TTGT and TGGT about the ψ0, ψ1, ψ2 and ψ3 internal rotation angles schematically represented in Fig. 1.