The structure of vitamin B12, as we think of it today, is based on a fascinating complex of evidence obtained by X-ray analysis and by more traditional chemical means. We have reached a position in which we can almost say we “see” the molecule if not quite as clearly, perhaps, as we should like. We can assign positions in space to the atoms of this very large molecule within less than half an Ångstrom unit in two different crystal structures. We know its absolute configuration and the exact stereochemistry of all the different asymmetric centres present. Yet most of this knowledge rests on a way of using X-ray diffraction effects which is very far from rigid in its application. Part, at least, of our evidence that our method works at all is the character of the structure it has given us for B12 a structure that fits in an extraordinarily reasonable way with such a variety of observations, chemical and stereochemical and biogenetic, that it is impossible not to believe it is essentially correct.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Alicino, J.F.: Perchloric Acid Salt of Vitamin B12. J. Amer. Chem. Soc. 73, 4051 (1951).CrossRefGoogle Scholar
  2. 2.
    Beaven, G.H., E.R. Holiday, E.A. Johnson, B. Ellis and V. Petrow: The Chemistry of Antipernicious Anaemia Factors. VI. The Mode of Combination of Component α in Vitamin B12. J. Pharm. Pharmacol. 2, 944 (1950).CrossRefGoogle Scholar
  3. 3.
    Bernhauer, K., K. Blumberger und P. Petrides: Die Wirkung des „Vitamin-B12-Faktors III” bei der perniciösen Anämie. Arzneimittel-Forsch. 5, 442 (1955).Google Scholar
  4. 4.
    Bonnett, R., J.R. Cannon, V.M. Clark, A.W. Johnson, L.F.J. Parker, E. Lester Smith and A. Todd: Chemistry of the Vitamin B12 Group. Part V. The Structure of the Chromophoric Grouping. J. Chem. Soc. (London) 1957, 1158.Google Scholar
  5. 5.
    Bonnett, R., J.R. Cannon, A.W. Johnson, I. Sutherland, A.R. Todd and E. Lester Smith: The Structure of Vitamin B12 and its Hexacarboxylic Acid Degradation Product. Nature (London) 176, 328 (1955).CrossRefGoogle Scholar
  6. 6.
    Bonnett, R., J.R. Cannon, A.W. Johnson and A. Todd: Chemistry of the Vitamin B12 Group. Part. IV. The Isolation of Crystalline Nucleotide-free Degradation Products. J. Chem. Soc. (London) 1957, 1148.Google Scholar
  7. 7.
    Brink, C, D.C. Hodgkin, J. Lindsey, J. Pickworth, J.H. Robertson and J.G. White: X-ray Crystallographic Evidence on the Structure of Vitamin B12. Nature (London) 174, 1169 (1954).CrossRefGoogle Scholar
  8. 8.
    Brink, N.G., F.A. Kuehl, Jr. and K. Folkers: Vitamin B12. The Identification of Vitamin B12 as a Cyano-Cobalt Coordination Complex. Science (Washington) 112, 354 (1950).CrossRefGoogle Scholar
  9. 9.
    Brown, F.B. and E. Lester Smith: New Purines in B12 Vitamins. Proc. Biochem. Soc., Biochemic. J. 56, xxxiv (1954).Google Scholar
  10. 10.
    Calloman, H.J.: Studies in Molecular Spectroscopy. D. Phil. Thesis, Oxford University, 1954.Google Scholar
  11. 11.
    Cannon, J.R., A.W. Johnson and A.R. Todd: A Crystalline Nucleotide-free Degradation Product of Vitamin B12. Nature (London) 174, 1168 (1954).CrossRefGoogle Scholar
  12. 12.
    Cason, J., C. Gastaldo, D.L. Glusker, J. Allinger and L.B. Ash: Branched-Chain Fatty Acids. XXVII. Further Study of the Dependence of Rate of Amide Hydrolysis on Substitution Near the Amide Group. Relative Rates of Hydrolysis of Nitrile to Amide and Amide to Acid. J. Organ. Chem. (USA) 18, 1129 (1953).CrossRefGoogle Scholar
  13. 13.
    Cason, J. and H.J. Wolfhagen: Location of Branching Methyl Groups near Carboxyl by Rate Studies of Amide Hydrolysis. J. Organ. Chem. (USA) 14, 155 (1949).CrossRefGoogle Scholar
  14. 14.
    Coates, M.E. and S.K. Kon: Biological and Microbiological Activities of Purine and Benziminazole Analogues of Vitamin B12. Europäisches Symposion über Vitamin B12 und Intrinsic Factor, p. 72. Stuttgart: F. Enke. 1957.Google Scholar
  15. 15.
    Cooley, G., B. Ellis, V. Petrow, G.H. Beaven, E.R. Holiday and E.A. Johnson: Some Transformations of Vitamin B12b. J. Pharm. Pharmacol. 3, 271 (1951).CrossRefGoogle Scholar
  16. 16.
    Corcoran, J.W. and D. Shemin: On the Biosynthesis of Vitamin B12: the Mode of Utilisation of δ-Aminolevulmic Acid. Biochim. Biophys. Acta 25, 661 (1957).CrossRefGoogle Scholar
  17. 17.
    Ellis, B., V. Petrow and G.F. Snook: The Isolation of the Crystalline Antipernicious Anaemia Factor from Liver. J. Pharm. Pharmacol. 1, 60 (1949).Google Scholar
  18. 18.
    Fantes, K.H., J.E. Page, L.F.J. Parker and E. Lester Smith: Crystalline Anti-pernicious Anaemia Factor from Liver. Proc. Roy. Soc. (London) 136 B, 592 (1950).Google Scholar
  19. 19.
    Folkers. K. and D.E. Wolf: Chemistry of Vitamin B12. Vitamins and Horm. 12, 1 (1954).CrossRefGoogle Scholar
  20. 20.
    Friedrich, W. und K. Bernhauer: Beiträge zur Chemie und Biochemie der “Cobalamine”, I. Mitt.: Über die Alkylierung von B12-Faktor III und Vitamin B12. Chem. Ber. 89, 2030 (1956).CrossRefGoogle Scholar
  21. 21.
    — Beiträge zur Chemie und Biochemie der “Cobalamine”, II. Mitt.: Über den Abbau der “Cobalamine” mit Cer(III)-hydroxyd. 7-[D-Ribofuranosido]-adenin, ein Abbauprodukt des Pseudovitamins B12. Chem. Ber. 89, 2507 (1956).CrossRefGoogle Scholar
  22. 22.
    — Zur Chemie und Biochemie der “Cobalamine”, VII. Mitt. 2-Methyl mercaptoadenin-cobalamin-analogon, ein neuer B12-Faktor des Faulschlammes. Chem. Ber. 90, 1966 (1957).CrossRefGoogle Scholar
  23. 23.
    Heinrich, H.C. (Editor): Europäisches Symposion über Vitamin B12 und Intrinsic Factor. Stuttgart: F. Enke-Verlag. 1957.Google Scholar
  24. 24.
    Hodgkin, D.C., A.W. Johnson and A.R. Todd: The Structure of Vitamin B12. Chem. Soc. (London) Special Publications 3, 109 (1955).Google Scholar
  25. 25.
    Hodgkin, D. C, J. Kamper, J. Lindsey, M. Mackay, J. Pickworth, J.H. Robertson, C.B. Shoemaker; J.G. White, R.J. Prosen and K.N. Trueblood: The Structure of Vitamin B12. I. An Outline of the Crystallographic Investigation of Vitamin B12. Proc. Roy. Soc. (London) 242 A, 228 (1957).Google Scholar
  26. 26.
    Hodgkin, D. C, J. Kamper, M. Mackay, J. Pickworth, K.N. Trueblood and J.G. White: The Structure of Vitamin B12. Nature (London) 178, 64 (1956).CrossRefGoogle Scholar
  27. 27.
    Hodgkin, D. C, J. Pickworth, J.H. Robertson, K.N. Trueblood, R.J. Prosen and J.G. White: The Crystal Structure of the Hexacarboxylic Acid Derived from B12 and the Molecular Structure of the Vitamin. Nature (London) 176, 325 (1955).CrossRefGoogle Scholar
  28. 28.
    Hodgkin, D., M.W. Porter and R.C. Spiller: Crystallographic Measurements on the Anti-pernicious Anaemia Factor. Proc. Roy. Soc. (London) 136 B, 609 (1950).Google Scholar
  29. 29.
    Kamper, J. and D.C. Hodgkin: Some Observations on the Crystal Structure of a Chlorine-substituted Vitamin B12. Nature (London) 176, 551 (1955).CrossRefGoogle Scholar
  30. 30.
    Kuehl, F.A., Jr., C.H. Shunk and K. Folkers: Vitamin B12. XXIV. IXL-3,3-Dimethyl-2, 5-dioxo-4-hydroxy-pyrrolidine-4-propionic Acid Lactone and DL-3,3-Dimethyl-2,5-dioxopyrrolidine-4-propionic Acid, new Degradation Products. J. Amer. Chem. Soc. 77, 251 (1955).CrossRefGoogle Scholar
  31. 31.
    Luzzati, V.: Résolution d’une structure cristalline lorsque les positions d’une partie des atomes sont connues: Traitement statistique. Acta Crystallogr. 6, 142 (1953).CrossRefGoogle Scholar
  32. 32.
    Mathieson, A. McL.: The Direct Determination of Molecular Structure and Configuration of Moderately Complex Organic Compounds. Rev. Pure and Applied Chem. 5, 113 (1955).Google Scholar
  33. 33.
    Minot, G.R. and W.P. Murphy: Treatment of Pernicious Anaemia by a Special Diet. J. Amer. Med. Assoc. 87, 470 (1926).CrossRefGoogle Scholar
  34. 34.
    Pawelkiewicz, J. and K. Zodrow: The Synthesis of Free Porphyrins by Propionibacterium Shermanii. Acta Biochem. Polonica 3, 225 (1956).Google Scholar
  35. 35.
    Peerdeman, A.F., A.J. van Bommel and J.M. Bijvoet: Determination of Absolute Configuration of Optically Active Compounds by Means of X-rays. Proc. Acad. Sci. Amsterdam, B 54, 16 (1951).Google Scholar
  36. 36.
    Rickes, E.L., N.G. Brink, F.R. Koniuszy, T.N. Wood and K. Folkers: Crystalline Vitamin B12. Science (Washington) 107, 396 (1948).CrossRefGoogle Scholar
  37. 57.
    Schmid, H., A. Ebnöther und P. Karrer: Beitrag zur Kenntnis des Vitamins B12. Helv. Chim. Acta 36, 65 (1953).CrossRefGoogle Scholar
  38. 38.
    Shemin, D., J.W. Corcoran, C. Rosenblum and I.M. Miller: On the Biosynthesis of the Porphyrin-like Moiety of Vitamin B12. Science (Washington) 124, 272 (1956).CrossRefGoogle Scholar
  39. 39.
    Smith, E. Lester: The Isolation and Chemistry of Vitamin B12. Biochemical Society Symposia 13, 3 (1955).Google Scholar
  40. 40.
    Smith, E. Lester and L.F.J. Parker: Purification of Anti-pernicious Anaemia. Factor. Proc. Biochem. Soc., Biochemic. J. 43, VIII (1948).Google Scholar
  41. 41.
    Todd, A.R.: Vitamin B12. Österr. Chemiker-Zeitung 58, 113 (1957).Google Scholar
  42. 42.
    Todd, A.R. and A.W. Johnson: Vitamin B12. Rev. Pure and Applied Chem. 2, 23 (1952).Google Scholar
  43. 43.
    Vos, A.: to be published.Google Scholar
  44. 44.
    Watson, C.J.: Porphyrin Metabolism in Anemias. GEORGE MINOT Lecture. Arch. Internat. Medicine 99, 323 (1957).CrossRefGoogle Scholar
  45. 45.
    Wijmenga, H.G., W.L.C. Veer and J. Lens: Vitamin B12. II. The Influence of HCN on Some Factors of the Vitamin B12 Group. Biochim. Biophys. Acta 6, 229 (1950).CrossRefGoogle Scholar
  46. 46.
    Wolf, D.E., W.H. Jones, J. Valiant and K. Folkers: Degradation of Vitamin B12 to Dg-I-Amino-2-propanol. J. Amer. Chem. Soc. 72, 2820 (1950).CrossRefGoogle Scholar

Copyright information

© Wien · Springer-Verlag 1958

Authors and Affiliations

  • Dorothy Crowfoot Hodgkin
    • 1
  1. 1.OxfordUSA

Personalised recommendations