The Structure of Methylcob(III)alamin in Aqueous Solution – A Water Molecule as Structuring Element of the Nucleotide Loop

The solution structure of methylcob(III)alamin (MeCbl; 3 ), a natural organometallic corrinoid‐B 12 cofactor whose crystal structure was published in 1985, was established by NMR‐spectroscopic analyses of 3 in aqueous solution. The full set of unambiguously assigned 1 H, 13 C, and amide 15 N signals was consistent with identical constitutional and configurational properties of 3 in solution and in the crystal. Specifically investigated were the conformational characteristics of 3 in solution, in particular of its unique Co‐coordinating nucleotide moiety. An extensive set of NOE‐derived distance constraints was acquired for this purpose, and of angle constraints, based on three‐bond coupling constants. These data were used to calculate the solution structure of 3 . Our data revealed that the conformation of the nucleotide loop of 3 differs significantly in aqueous solution and in the crystalline state and indicated the presence of a specific H 2 O molecule `bound' via cooperative H‐bonds to three H‐bonding functionalities of the nucleotide loop. The observed conformational differences are attributed to structuring contributors to the nucleotide conformation that differ in solution and in the crystal. Most of these can be assigned to H 2 O molecules, whose position in the crystal is controlled, in part, by the specific crystal packing.