The structure of vitamin B12. I. An outline of the crystallographic investigation of vitamin B12

Abstract

Abstract The structure of vitamin B12 has been examined by the X-ray analysis of four different crystal structures, air-dried and wet vitamin B 12, the selenocyanate derivative of B12, and a hexacarboxylic acid prepared by the degradation of the vitamin by Cannon, Johnson and Todd. The analysis turned on the possibility of identifying some of the atomic positions in the molecule in very confused appproximate electron density distributions calculated using only evidence of cobalt or cobalt and selenium contributions to phase the terms employed in the calculation. The recognition of atomic sites depended on a general knowledge of atomic sizes and geometry, on chemical evidence of the existence of a nucleotide-like group in the B12 crystals, and on the presence, immediately surrounding each cobalt atom, of a nucleus which was identical in very different crystals. Once the positions of the atoms in the nucleus and nucleotide were identified, the refinement of the electron density distributions in the different crystals proceeded in a fairly direct manner to establish the arrangement of all the remaining atoms in the molecules. The atomic arrangements found lead to the deduction of the chemical structure of a large part of the vitamin B12 molecule and of the stereochemical organization of the whole. Of particular interest is the evident relation of the molecular nucleus found to porphyrins of type I I I and to porphobilinogen.