Structure of a potent neuromuscular blocking agent: Caracurine-II dimethochloride octahydrate, [C₄₀H₄₄N₄O₂]²⁺·2CI⁻·8H₂O

Abstract

Crystals of this calabash curare alkaloid, space groupP2₁; havea=12.695(4), Å,b=7.424(2) Å,c=21.762(6) Å,β=98.03(5)°,Z=2,F(000)=884. The structure was solved by direct methods and refined by least squares toR=0.10. The alkaloid cation, with two-fold molecular symmetry, has a highly fused ring system and is structurally rigid. This determination provides accurate stereochemical parameters for those atoms and groups (N⁺ centers, aromatic rings, and hydrogen bond acceptors) postulated by various theories as involved in binding to the acetylcholine receptor. In the crystal, layers of alkaloid cations parallel to thebc plane alternate with layers containing two Cl⁻ ions and eight water molecules distributed almost randomly over ten sites. Electrostatic attractions between N⁺ and Cl⁻ bind the alternating layers together. Each one of the ten sites is, on average, 4.60 Å from one or two N⁺, allowing the two Cl₋ ions to be disordered. Binding interactions within the alkaloid layers are solely van der Waals attractions. Within each H²O/C1⁻ layer there is a complex hydrogen bond system, including four infinite spirals parallel to theb axis, with an average bonding distance of 2.94 Å. There are no hydrogen bonds between layers. The possible relevance to the activity of the alkaloid of its ability to organize large amounts of water is discussed.