Crystal Structure of Quinine: The Effects of Vinyl and Methoxy Groups on Molecular Assemblies of Cinchona Alkaloids Cannot Be Ignored

Abstract

Quinine, one of Cinchona alkaloids, has been of great interest from medical, synthetic, and supramolecular viewpoints. However, unaccountably, the guest-free (GF) crystal of quinine containing no solvent or other molecules has not been reported for nearly three decades, although GF crystals of other Cinchona alkaloids, such as quinidine, cinchonidine, and cinchonine, are already known. In this study, we successfully revealed the crystal structure of quinine, which belongs to the P2(1) space group with the cell parameters of a=6.0587(1), b=19.2492(5), c=22.2824(7) Å, β=92.1646(11)°, and V=2596.83(12) Å(3). Interestingly, the crystal has three crystallographically independent molecules in the cell (Z'=3) that are connected through a N(quinoline)⋅⋅⋅H-O hydrogen bond to form a pseudo three-two-fold (3(2)) double-helical motif. The helical motif is completely different from those observed in GF crystals of other Cinchona alkaloids. Hierarchical comparison on the crystal structures of a series of Cinchona alkaloids including quinine clearly demonstrated that only small structural differences of a molecule, particularly the position of the vinyl group, cause a significant variety of assembly manner in the crystalline state. There have been no reports systematically demonstrating such steric effect in crystals of Cinchona alkaloids, and, therefore, the present system contributes to the design of desired functional crystal structures.

Vibrational analysis of cinchona alkaloids in the solid state and aqueous solutions

“…Crystal structures of guest‐free cinchona alkaloids are well‐known . Crystallographic data confirmed unequivocally that the most stable conformation of cinchona alkaloids is that of anti open α‐ψ‐C (for CN and CND— anti open α‐ψ ) as obtained from the theoretical calculations.…”

Computational insights into the inhibition of β-haematin crystallization by antimalarial drugs

“…The alkaloids QN and QD are diastereomers; X-ray crystal structures of both the free drugs 34,35 and their 1 : 1 complexes with FePPIX 16 are available. Our calculations on free QN indicated slightly different minimum energy structures in n-octanol and water, associated with rotations about the two C-C bonds adjacent to the hydroxy group; the difference in energy between the two conformers is ca.…”

Effect of Microwave Irradiation on the Catalytic Activity of Palladium Supported Catalysts in the One-Step Isomerisation of Cinchona Alkaloids to Δ3,10-Isobases

“…It is a stereo-differentiating element [3] imparting a variety their physicochemical properties and biological activity for quinidine 1a (antiarrhythmic agent) [4] versus quinine 2a (antimalarial activity) [5], and for cinchonine 1b versus cinchonidine 2b. All the four natural compounds, their derivatives and metal complexes have become more and more interesting catalysts for asymmetric syntheses [6].…”