Crystal and Molecular Structure of d,l-Dethiobiotin. Role of Sulfur in Biotin Stereochemistry

The crystal structure of d,l-dethiobiotin (C₁₀H₁₈N₂O₃) has been accurately determined using x-ray diffraction techniques and refined to a residual of 0.055. The crystals are monoclinic, space group P2₁/a, with cell constants (at 22 ± 3 °C) a = 29.9166 (2) Á, b = 4.9990 (1) Å, c = 7.7561 (1)Å, β = 97.855(2)°, and Z = 4. The ureido moiety in dethiobiotin displays unusual bond lengths for the C═O (1.244 (4) Å) and two C—N bonds (1.346 (4) and 1.347 (4) A). The ureido oxygen accepts a strong hydrogen bond from the carboxyl group of a neighboring molecule (O…O, 2.633 Å H…O, 1.83 Å) and is also hydrogen bonded to N(1′). These results lend support to the theory of activation of biotin by increased acidity of the N H groups and the increased nucleophilicity of nitrogen, stabilized by hydrogen bonds to the ureido oxygen. Since both the C-N bond lengths are very nearly equal, the reason for the preferential carboxylation at N(1′) is not electronic but steric, due to a close nonbonded contact (3.042 Å) of a carbon atom of the caproic acid chain to the proximal nitrogen. Lack of sulfur in dethiobiotin does not change the dimensions of the ureido moiety from those observed in biotin, indicating no dominant C…S transannular interaction as suggested by others. The 2-imidazolidone ring in dethiobiotin is markedly nonplanar, and the caproic acid chain is in the trans planar zig-zag conformation, indicating an important role for sulfur in stabilizing both the planarity of the imidazolidone ring and the twisted conformation of the side chain found in biotin.