Molecular Structure of Biotin. Results of two Independent Crystal Structure Investigations

The three-dimensional crystal structure of d-(+)-biotin, the coenzyme responsible for the fixation and transfer of carbon dioxide in biological systems, has been determined by x-ray diffraction techniques in two laboratories independently. The results of the two determinations are compared and discussed in terms of the mode of nucleophilic activation of the coenzyme. Of particular relevance may be the participation of the ureido carbonyl oxygen as acceptor of a strong hydrogen bond (O ··· O distance 2.54 Å) which may cause the observed lengthening of the ureido carbonyl bond to 1.25 Å and shortening of the carbonyl carbon-nitrogen bonds to 1.33 and 1.35 Å. These results suggest a partial delocalization of the electronic charge within the ureido group, and are supportive of a proposed activation via polarization mechanism. A close intramolecular nonbonded contact involving the nitrogen atom proximal to the valeryl chain probably precludes carboxylation from that side of the molecule.