version date: 1 December 2006 conformation of acetylcholine, that is, to the disposition of the dihedral or torsional angles of the molecule NH (11) lla)τ0. (11b)τ60.7° (1le)τ73.5° Fig. 7 Spatial representation of clonidine(11) showing corresponding dihedral angles(t); (lla),structure drawn in program ChemDraw and converted to Chem3D; (11b), structure minimized by molecular mechanics, MM2 and (llc) structure showing systematic changes by molecular dynamics To improve the understanding of the different conformations of acetylcholine the students are trained to do the Newman projection of the central atoms of the drug, O(3)- C(4)-C(5)-N(6), in the Chem3D program and to gradually analyze the torsional angles of the molecule. The torsional or dihedral angle(t)can be considered as the one formed by two defined planes as A-X-Y and X-Y-B of four atoms linked in the A-X-Y-B order. The projection shows the spatial relative disposition of the ester and quaternary ammonium groups In the main"View"menu of Chem3D, it is possible to select"Settings"and then Movies"to manually rotate only bond C(4)-C(5)in the X-Y axis of the projection. After each 60 rotation, the dihedral angle is altered and a new conformation is generated totaling six different conformations. At each change of the dihedral angle, the steric (gauche ) and synplanar(eclipse-like)are calculated by the MM2 program, which only &2 energies corresponding to the forms antiperiplanar(star-like)synclinal(gauche ) anticlin considers the internuclear lengths and angles, Table 1. It is possible, in thi s experimen calculate the minimal global steric energy and predict the most stable preferential conformation of acetylcholine. The positive(0-180%)and negative(180-0%)rotation faces are really considered as a complete 360 movement in the X-Y axis, to facilitate graphic representation and interpretation of the results <www.iupac.org/publications/cd/medicinalchemistry/>10 conformation of acetylcholine, that is, to the disposition of the dihedral or torsional angles of the molecule. 2 1 3 4 2 4 3 1 2 4 3 1 (11a) τ 0.5 º (11b) τ 60.7 º (11c) τ 73.5 º HN NH N Cl Cl (11) Fig. 7 Spatial representation of clonidine (11) showing corresponding dihedral angles (τ); (11a), structure drawn in program ChemDraw and converted to Chem3D; (11b), structure minimized by molecular mechanics, MM2 and (11c) structure showing systematic changes by molecular dynamics. To improve the understanding of the different conformations of acetylcholine the students are trained to do the Newman projection of the central atoms of the drug, O(3)- C(4)-C(5)-N(6), in the Chem3D program and to gradually analyze the torsional angles of the molecule. The torsional or dihedral angle (τ) can be considered as the one formed by two defined planes as A-X-Y and X-Y-B of four atoms linked in the A-X-Y-B order. The projection shows the spatial relative disposition of the ester and quaternary ammonium groups. In the main “View” menu of Chem3D, it is possible to select “Settings” and then “Movies” to manually rotate only bond C(4)-C(5) in the X-Y axis of the projection. After each 60° rotation, the dihedral angle is altered and a new conformation is generated, totaling six different conformations. At each change of the dihedral angle, the steric energies corresponding to the forms antiperiplanar (star-like) synclinal (gauche), anticlinal (gauche), and synplanar (eclipse-like) are calculated by the MM2 program, which only considers the internuclear lengths and angles, Table 1.7 It is possible, in this experiment, to calculate the minimal global steric energy and predict the most stable preferential conformation of acetylcholine. The positive (0–180°) and negative (180–0°) rotation faces are really considered as a complete 360° movement in the X-Y axis, to facilitate graphic representation and interpretation of the results. <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006