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

• Published in: Chemistry, an Asian journal an Asian journal, 2012-11, Vol.7 (11), p.2607-2614
• Main Authors: Hisaki, Ichiro, Hiraishi, Eri, Sasaki, Toshiyuki, Orita, Hideo, Tsuzuki, Seiji, Tohnai, Norimitsu, Miyata, Mikiji
• Format: Article
• Language: English
• Subjects: CH/pi interactions; Chemistry; Cinchona - chemistry; Cinchona alkaloids; Cinchona Alkaloids - chemistry; Crystallography, X-Ray; crystals; double helix; Hydrogen Bonding; Molecular Conformation; Plant Bark - chemistry; Quinine - chemistry; supramolecular chemistry
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201200566

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 P21 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) Å3. 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 (32) 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. CH/π interactions: A nearly three‐decade mystery of Cinchona alkaloids is that the guest‐free crystal has been unknown only in the case of quinine. In this study, the missing crystal structure, which has a hydrogen‐bonded pseudo 32 double‐helical motif (see graphic), is finally revealed.