Getting the Big Ones to Pack: Crystal Structure of Vitamin K2 With a Chaperone.

Packing into a crystal lattice is not easy for flexible molecules with an irregular shape, as all molecules have to adopt the same conformation in order to fit into the same position of a well-ordered lattice. When numerous conformations are populated at the crystallization temperature, crystal growth can be impaired. The larger and more flexible the analyte to be crystallized, the greater the challenge to obtain single crystals suitable for x-ray crystallography. Here we show how vitamin K2, a natural product with a rigid, bicyclic menaquinone head group and a long flexible terpenoid chain, can be crystallized. A second-generation chaperone and an optimized protocol gave co-crystals that diffract to a resolution of 0.8 Å. The chaperone employed was 1,3,5,7-tetrakis(2-fluoro-4-methoxyphenyl)adamantane (TFM). The protocol involved seeding with crystals selected from the conglomerate of an initial run, and a three-stage temperature protocol. The x-ray crystal structure shows layers of chaperones and vitamin K2 molecules, with back-folding of the terpene chains of the latter. Together with another structure showing layers of chaperone and solvent, this confirms that tetraaryladamantanes can facilitate crystallization in more ways than by just filling voids in their packing arrangements.