Advertisement

Solvent Hydrogen Isotope Effects

  • Katharine B. J. Schowen

Abstract

Biological and biochemical processes are affected by the partial or complete replacement of solvent protium oxide (H2O) by deuterium oxide (D2O) (1) Although some very simple organisms (certain algae, bacteria, etc.) have survived complete replacement of protium by deuterium, differences in morphology and metabolism are very apparent. Not surprisingly, deuterium substitution affects virtually all aspects of metabolism and physiological function. Higher plants, after experiencing impaired chlorophyll synthesis and inhibition of cell division, will cease to grow after ~ 70% D exchange Mammals (unable to survive much more than 25% D incorporation) show evidence of severe difficulty with protein synthesis, decreased enzyme levels, decreased erythrocyte production, impaired carbohydrate metabolism, hormone imbalance, central nervous system disturbance, difficulty with mitosis, and increasingly impaired reproductive capability. Most of these consequences are directly or indirectly attributable to changes in the rates of biochemical reactions.

Keywords

Isotope Effect Heavy Water Fractionation Factor Kinetic Isotope Effect Isotopic Fractionation Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    J. J. Katz and H. L. Crespi, in: Isotope Effects in Chemical Reactions ( C. J. Collins and N. S. Bowman, eds.), pp. 286–363, Van Nostrand Reinhold, New York (1970).Google Scholar
  2. 2.
    J. A. K. Harmony, R. H. Himes, and R. L. Schowen, The monovalent cation-induced association of formyltetrahydrofolate synthetase subunits: A solvent isotope effect, Biochemistry 14, 5379–5386 (1975).PubMedCrossRefGoogle Scholar
  3. 3.
    L. L. Houston, J. Odell, Y. C. Lee, and R. H. Himes, Solvent isotope effects on microtubule polymerization and depolymerization, J. Mol. Biol. 87, 141–146 (1974).PubMedCrossRefGoogle Scholar
  4. 4.
    T. C. French and G. G. Hammes, Relaxation spectra of ribonuclease. II. Isomerization of ribonuclease at neutral pH values, J. Am. Chem. Soc. 87, 4669–4673 (1965).PubMedCrossRefGoogle Scholar
  5. 5.
    M.-S. Wang, R. D. Gandour, J. Rodgers, J. L. Haslam, and R. L. Schowen, Transition-state structure for a conformation change of ribonuclease, Bioorg. Chem. 4, 392–406 (1975).CrossRefGoogle Scholar
  6. 6.
    E. Pollock, J. L. Hogg, and R. L. Schowen, One-proton catalysis in the deacetylation of acetyl-a-chymotrypsin, J. Am. Chem. Soc. 95, 968 (1973).PubMedCrossRefGoogle Scholar
  7. 7.
    M. L. Bender, G. E. Clement, F. J. Kézdy, and H. D’A. Heck, The correlation of the pH (pD) dependence and the stepwise mechanism of a-chymotrypsin-catalyzed reactions, J. Am. Chem. Soc. 86, 3680–3690 (1964).CrossRefGoogle Scholar
  8. 8.
    a) J. P. Elrod, R. D. Gandour, J. L. Hogg, M. Kise, G. M. Maggiora, R. L. Schowen, and K. S. Venkatasubban, Proton bridges in enzyme catalysis, Faraday Symp. Chem. Soc. 10, 145–153 (1975). (b) J. P. Elrod, Comparative mechanistic study of a set of serine hydrolases using the proton inventory technique and beta-deuterium probe, Ph.D. thesis, University of Kansas, Lawrence (1975).Google Scholar
  9. 9.
    R. Mason and C. A. Ghiron, An isotope effect on the esterase and protease activity of trypsin, Biochim. Biophys. Acta 51, 377–378 (1961).PubMedCrossRefGoogle Scholar
  10. 10.
    R. L. Schowen, in: Isotope Effects on Enzyme Catalyzed Reactions (W. W. Cleland, M. H. O’Leary, and D. B. Northrup, eds.), pp. 64–99, University Park Press, Baltimore (1977).Google Scholar
  11. 11.
    D. M. Quinn, M. Patterson, R. Jarvis, G. Ranney, and R. L. Schowen, Changes in catalytic coupling in the action of amidohydrolases and serine hydrolases with changes in substrate structure (paper in preparation).Google Scholar
  12. 12.
    G. M. Maggiora and R. L. Schowen, in: Bioorganic Chemistry (E. E. van Tamelen, ed.), Vol. 1, pp. 173–229. Academic Press, New York (1977).Google Scholar
  13. 13.
    K. S. Venkatasubban, Proton bridges in enzymic and nonenzymic amide solvolysis, Ph.D. thesis, University of Kansas, Lawrence (1975).Google Scholar
  14. 14.
    L. M. Konsowitz and B. S. Cooperman, Solvent isotope effect in inorganic pyrophosphatasecatalyzed hydrolysis of inorganic pyrophosphate, J. Am. Chem. Soc. 98, 1993–1995 (1976).PubMedCrossRefGoogle Scholar
  15. 15.
    J.Bigeleisen and M. Wolfsberg, Theoretical and experimental aspects of isotope effects in chemical kinetics, Adv. Chem. Phys. 1 15–76 (1,958).CrossRefGoogle Scholar
  16. 16.
    P. M. Laughton and R. E. Robertson, in: Solute-Solvent Interactions ( J. F. Coetzee and C. D. Ritchie, eds.), pp. 400–538, Dekker, New York (1969).Google Scholar
  17. 17.
    E. M. Arnett and D. R. McKelvey, in: Solute-Solvent Interactions ( J. F. Coetzee and C. D. Ritchie, eds.), pp. 344–399, Dekker, New York (1969).Google Scholar
  18. 18.
    V. Gold, in: Advances in Physical Organic Chemistry (V. Gold, ed.), Vol. 7, pp. 259–331, Academic Press, New York (1969).Google Scholar
  19. 19.
    V. Gold, in: Hydrogen-Bonded Solvent Systems ( A. K. Covington and P. Jones, eds.), pp. 295–300, Taylor and Francis, Ltd., London (1968).Google Scholar
  20. 20.
    R. L. Schowen, Mechanistic deductions from solvent isotope effects, Prog. Phys. Org. Chem. 9, 275–332 (1972).CrossRefGoogle Scholar
  21. 21.
    E. K. Thornton and E. R. Thornton, in: Isotope Effects in Chemical Reactions (C. J. Collins and N. S. Bowman, eds.), pp. 213–286, Van Nostrand Reinhold, New York (1970).Google Scholar
  22. 22.
    A. J. Kresge, Solvent isotope effect in H2O-D20 mixtures, Pure Appl. Chem. 8, 243–258 (1964).CrossRefGoogle Scholar
  23. 23.
    J. Albery, in: Proton-Transfer Reactions ( E. Caldin and V. Gold, eds.), pp. 263–315, Chapman & Hall, London (1975).Google Scholar
  24. 24.
    K. B. Wiberg, The deuterium isotope effect, Chem. Rev. 55, 713–743 (1955).CrossRefGoogle Scholar
  25. 25.
    V. Gold and D. P. N. Satchell, The principles of hydrogen isotope exchange reactions in solution, Q. Rev. Chem. Soc. 9, 51–72 (1955).CrossRefGoogle Scholar
  26. 26.
    R. F. W. Bader, Ph.D. thesis in Organic Chemistry, Massachusetts Institute of Technology, Cambridge (1958).Google Scholar
  27. 27.
    R. A. More O’Ferrall, G. W. Koeppl, and A. J. Kresge, Solvent isotope effects upon proton transfer from the hydronium ion, J. Am. Chem. Soc. 93, 9–20 (1971).CrossRefGoogle Scholar
  28. 28.
    R. L. Kay and D. F. Evans, The conductance of the tetraalkylammonium halides in deuterium oxide solutions at 25°, J. Phys. Chem. 69, 4216–4221 (1965).CrossRefGoogle Scholar
  29. 29.
    a) C. A. Bunton and V. J. Shiner, Acid-base equilibria in deuterium oxide solutions, J. Am. Chem. Soc. 83, 42–47 (1961). (b) C. A. Bunton and V. J. Shiner, Isotope effects in deuterium oxide solution. Part II. Reaction rates in acid, alkaline and neutral solution, involving only secondary solvent effects, J. Am. Chem. Soc. 83, 3207–3214 (1961). (c) C. A. Bunton and V. J. Shiner, Isotope effects in deuterium oxide solution. Part III. Reactions involving primary effects, J. Am. Chem. Soc. 83, 3214–3220 (1961).CrossRefGoogle Scholar
  30. 30.
    a) C. G. Swain and R. F. W. Bader, The nature of the structure difference between light and heavy water and the origin of the solvent isotope effect, Tetrahedron 10, 182–199 (1960). (b) C. G. Swain, R. F. W. Bader, and E. R. Thornton, A theoretical interpretation of isotope effects in mixtures of light and heavy water, Tetrahedron 10, 200–211 (1960). (c) C. G. Swain and E. R. Thornton, Calculated isotope effects for reactions of lyonium ion in mixtures of light and heavy water, J. Am. Chem. Soc. 83, 3884–3889 (1961). (d) C. G. Swain and E. R. Thornton, Calculated isotope effects for reactions of lyoxide ion or water in mixtures of light and heavy water, J. Am. Chem. Soc. 83, 3890–3896 (1961).CrossRefGoogle Scholar
  31. 31.
    F. Westheimer, The magnitude of the primary kinetic isotope effect for compounds of hydrogen and deuterium, Chem. Rev. 61, 265–273 (1961).CrossRefGoogle Scholar
  32. 32.
    J. Bigeleisen, Correlation of kinetic isotope effects with chemical bonding in three-centre reactions, Pure Appl. Chem. 8, 217–242 (1964).CrossRefGoogle Scholar
  33. 33.
    R. P. Bell, Isotope effects and the nature of proton-transfer transition states, Discuss. Faraday Soc. 39, 16–24 (1965).CrossRefGoogle Scholar
  34. 34.
    A. V. Willi and M. Wolfsberg, The influence of “bond making and bond breaking” in the transition state on hydrogen isotope effects in linear three-centre reactions, Chem. Ind. (London) 1964, 2097–2098.Google Scholar
  35. 35.
    R. A. More O’Ferrall and J. Kouba, Model calculations of primary hydrogen isotope effects, J. Chem. Soc. B 1967, 985–990.Google Scholar
  36. 36.
    W. J. Albery, Isotope effects in proton transfer reactions, Trans. Faraday Soc. 63, 200–206 (1967).CrossRefGoogle Scholar
  37. 37.
    R. A. More O’Ferrall, in: Proton-Transfer Reactions ( E. Caldin and V. Gold, eds.), pp. 201–261, Chapman & Hall, London (1975).Google Scholar
  38. 38.
    R. E. Weston, Jr., Transition-state models and hydrogen isotope effects, Science 158, 332–342 (1967).PubMedCrossRefGoogle Scholar
  39. 39.
    M. J. Goldstein, Kinetic isotope effects and organic reaction mechanisms, Science 154, 1616–1621 (1966).PubMedCrossRefGoogle Scholar
  40. 40.
    A. V. Willi, Predictions of isotope effects in Sh.2 reactions, Z. Phys. Chem. (Frankfurt am Main) 66, 317–328 (1969).CrossRefGoogle Scholar
  41. 41.
    a) M. Wolfsberg and M. J. Stern, Validity of some approximation procedures used in the theoretical calculation of isotope effects, Pure Appl. Chem. 8, 225–242 (1964). (b) M. Wolfsberg and M. J. Stern, Secondary isotope effects as probes for force constant changes, Pure Appl. Chem. 8, 325–338 (1964).CrossRefGoogle Scholar
  42. 42.
    M. J. Stern and M. Wolfsberg, Simplified procedure for the theoretical calculation of isotope effects involving large molecules, J. Chem. Phys. 45, 4105–4124 (1966).CrossRefGoogle Scholar
  43. 43.
    P. Salomaa, Solvent deuterium isotope effects on acid—base reactions. Part I. Thermodynamic theory and its simplifications, Acta Chem. Scand. 23, 2095–2106 (1969).CrossRefGoogle Scholar
  44. 44.
    P. Salomaa, A. Vesala, and S. Vesala, Solvent deuterium isotope effects on acid—base reactions. Part II, Variation of the first and second acidity constants of carbonic and sulfurous acids in mixtures of light and heavy water, Acta Chem. Scand. 23, 2107–2115 (1969).CrossRefGoogle Scholar
  45. 45.
    V. Gold, Rule of the geometric mean: Its role in the treatment of thermodynamic and kinetic deuterium solvent isotope effects, Trans. Faraday Soc. 64, 2770–2779 (1968).CrossRefGoogle Scholar
  46. 46.
    W. J. Albery and M. H. Davies, Effect of the breakdown of the rule of the geometric mean on fractionation factor theory, Trans. Faraday Soc. 65, 1059–1065 (1969).CrossRefGoogle Scholar
  47. 47.
    C. G. Swain, D. A. Kuhn, and R. L. Schowen, Effect of structural changes in reactants on the position of hydrogen—bonding hydrogens and solvating molecules in transition states. The mechanism of tetrahydrofuran formation from 4-chlorobutanol, J. Am. Chem. Soc. 87, 1553–1561 (1965).CrossRefGoogle Scholar
  48. 48.
    P. Salomaa, L. L. Schaleger, and F. A. Long, Solvent deuterium isotope effects on acid—base equilibria, J. Am. Chem. Soc. 86, 1–7 (1964).CrossRefGoogle Scholar
  49. 49.
    A. K. Covington, R. A. Robinson, and R. G. Bates, The ionization constant of deuterium oxide from 5 to 50°, J. Phys. Chem. 70, 3820–3824 (1966).CrossRefGoogle Scholar
  50. 50.
    V. Gold and B. M. Lowe, Measurement of solvent isotope effects with the glass electrode. Part I. The ionic product of D2O and D2O—H2O mixtures, J. Chem. Soc. A 1967, 936–943.Google Scholar
  51. 51.
    M. Goldblatt and W. M. Jones, Ionization constants of T2O and D2O at 25’ from cell emf’s. Interpretation of the hydrogen isotope effects in emf’s, J. Chem. Phys. 51, 1881–1894 (1969).CrossRefGoogle Scholar
  52. 52.
    L. Pentz and E. R. Thornton, Isotope effects on the basicity of 2-nitrophenoxide, 2,4-dinitrophenoxide, hydroxide, and imidazole in protium oxide—deuterium oxide mixtures, J. Am. Chem. Soc. 89 6931–6938 (1967), and references cited.CrossRefGoogle Scholar
  53. 53.
    V. Gold, The fractionation of hydrogen isotopes between hydrogen ions and water, Proc. Chem. Soc. London 1963, 141–143.Google Scholar
  54. 54.
    A. J. Kresge and A. L. Allred, Hydrogen isotope fractionation in acidified solutions of protium and deuterium oxide, J. Am. Chem. Soc. 85, 1541 (1963).CrossRefGoogle Scholar
  55. 55.
    J. F. Mata-Segreda, Chemical models for aqueous biodynamical processes, Ph.D. thesis, University of Kansas, Lawrence (1975).Google Scholar
  56. 56.
    J. E. Leffler, Parameters for the description of transition states, Science 117, 340–341 (1953).PubMedCrossRefGoogle Scholar
  57. 57.
    G. A. Vidulich, D. F. Evans, and R. L. Kay, The dielectric constant of water and heavy water between 0 and 40°, J. Phys. Chem. 71, 656–662 (1967).CrossRefGoogle Scholar
  58. 58.
    V. K. LaMer and J. P. Chittum, The conductance of salts (potassium acetate) and the dissociation constant of acetic acid in deuterium oxide, J. Am. Chem. Soc. 58, 1642–1644 (1936).CrossRefGoogle Scholar
  59. 59.
    a) P. Gross, H. Steiner, and F. Krauss, On the decomposition of diazoacetic ester catalysed by protons and deuterons, Trans. Faraday Soc. 32, 877–879 (1936). (b) P. Gross and A. Wischin, On the distribution of picric acid between benzene and mixtures of light and heavy water, Trans. Faraday Soc. 32, 879–883 (1936). (c) P. Gross, H. Steiner, and H. Suess, The inversion of cane sugar in mixtures of light and heavy water, Trans. Faraday Soc. 32, 883–889 (1936).CrossRefGoogle Scholar
  60. 60.
    a) J. C. Hornel and J. A. V. Butler, The rates of some acid-and base-catalysed reactions, and the dissociation constants of weak acids in “heavy” water, J. Chem. Soc. 1936, 1361–1366. (b) W. J. C. Orr and J. A. V. Butler, The kinetic and thermodynamic activity of protons and deuterons in water—deuterium oxide solutions, J. Chem. Soc. 1937, 330–335. (c) W. E. Nelson and J. A. V. Butler, Experiments with heavy water on the acid hydrolysis of esters and the alkaline decomposition of diacetone alcohol, J. Chem. Soc. 1938, 957–962.Google Scholar
  61. 61.
    C. R. Hopper, R. L. Schowen, K. S. Venkatasubban, and H. Jayaraman, Proton inventories of the transition states for solvation catalysis and proton-transfer catalysis. Decomposition of the tetrahedral intermediate in amide methanolysis, J. Am. Chem. Soc. 95, 3280–3283 (1973).CrossRefGoogle Scholar
  62. 62.
    J. Elrod, R. D. Gandour, M. Hegazi, J. L. Hogg, J. Mata, D. Quinn, K. B. Schowen, R. L. Schowen, and K. S. Venkatasubban, Notes on the proton inventory technique, a handbook prepared by the Bio-organic Chemical Dynamics Group, Department of Chemistry, University of Kansas, Lawrence (1974).Google Scholar
  63. 63.
    K. Mikkelsen and S. O. Nielsen, Acidity measurements with the glass electrode in H2O and D2O mixtures, J. Phys. Chem. 64, 632–637 (1960).CrossRefGoogle Scholar
  64. 64.
    P. K. Glasoe and F. A. Long, Use of glass electrodes to measure acidities in deuterium oxide, J. Phys. Chem. 64, 188–191 (1960).CrossRefGoogle Scholar
  65. 65.
    A. K. Covington, M. Paabo, R. A. Robinson, and R. G. Bates, Use of the glass electrode in deuterium oxide and the relation between the standardized pD (pap) scale and the operational pH in heavy water, Anal. Chem. 40, 700–706 (1968).CrossRefGoogle Scholar
  66. 66.
    K. B. J. Schowen, J. K. Lee, and R. L. Schowen, Dynamical mechanism of action of the glass electrode, unpublished paper (No. 121) presented at the 10th Midwest Regional Meeting of the American Chemical Society, University of Iowa, Iowa City, November 7–8, 1974.Google Scholar
  67. 67.
    W. J. Dixon, ed., Biomedical Computer Programs,University of California Press, Berkeley and Los Angeles (1968), pp. 289–296, Program BMDO5R Polynomial Regression.Google Scholar
  68. 68.
    C. K. Rule and V. K. LaMer, Dissociation constants of deutero acids by e.m.f. measurements, J. Am. Chem. Soc. 60, 1974–1981 (1938).CrossRefGoogle Scholar
  69. 69.
    R. P. Bell, The Proton in Chemistry, Cornell University Press, Ithaca, N.Y. (1959), Chap. XI.Google Scholar
  70. 70.
    E. Halevi, F. A. Long, and M. A. Paul, Acid—base equilibria in solvent mixtures of deuterium oxide and water, J. Am. Chem. Soc. 83, 305–311 (1961).CrossRefGoogle Scholar
  71. 71.
    a) R. G. Bates, Determination of pH: Theory and Practice, 2nd ed., Wiley-Interscience, New York (1973), Chap. 8, pp. 211–253. (b) M. Paabo and R. G. Bates, Standards for a practical scale of pD in heavy water, Anal. Chem. 41, 283–285 (1969).Google Scholar
  72. 72.
    K. B. Schowen, E. E. Smissman, and W. F. Stephen, Jr., Base—catalyzed and cholinesterase-catalyzed hydrolysis of acetylcholine and optically active analogs, J. Med. Chem. 18, 292–300 (1975).PubMedCrossRefGoogle Scholar
  73. 73.
    M. W. Hunkapiller, M. D. Forgac, and J. H. Richards, Mechanism of action of serine pro-teases: Tetrahedral intermediate and concerted proton transfer, Biochemistry 15, 5581–5588 (1976).PubMedCrossRefGoogle Scholar
  74. 74.
    V. Gold and M. A. Kessick, Proton transfer to olefins, Discuss. Faraday Soc. 39, 84–93 (1965).CrossRefGoogle Scholar
  75. 75.
    M. D. Zeidler, in: Water: A Comprehensive Treatise (F. Franks, ed.), Vol. 2, pp. 529–584, Plenum Press, New York (1973); see pp. 540–541.Google Scholar
  76. 76.
    A. Hvidt and S. O. Nielsen, in: Advances in Protein Chemistry (C. B. Anfinsen, Jr., M. L. Anson, J. T. Edsall, and F. M. Richards, eds.), Vol. 21, pp. 287–386, Academic Press, New York (1966).Google Scholar
  77. 77.
    F. M. Richards and H. W. Wyckoff, in: The Enzymes, 3rd ed. (P. D. Boyer, ed.), Vol. 4, pp. 647–806, Academic Press, New York (1971).Google Scholar
  78. 78.
    J. S. Scarpa, D. D. Mueller, and I. M. Klotz, Slow hydrogen-deuterium exchange in a nona-helical polyamide, J. Am. Chem. Soc. 89, 6024–6030 (1967).CrossRefGoogle Scholar
  79. 79.
    M. L. Bender and G. A. Hamilton, Kinetic isotope effects of deuterium oxide on several a-chymotrypsin-catalyzed reactions, J. Am. Chem. Soc. 84, 2570–2576 (1962).CrossRefGoogle Scholar
  80. 80.
    G. Robillard and R. G. Shulman, High resolution nuclear magnetic resonance study of the histidine—aspartate hydrogen bond in chymotrypsin and chymotrypsinogen, J. Mol. Biol. 71, 507–511 (1972).PubMedCrossRefGoogle Scholar
  81. 81.
    R. L. Schowen, Chapter 2 in this volume.Google Scholar
  82. 82.
    A. J. Kresge, Solvent isotope effects and the mechanism of chymotrypsin action, J. Am. Chem. Soc. 95, 3065–3067 (1973).Google Scholar
  83. 83.
    R. A. Fisher and F. Yates, Statistical Tables for Biological, Agricultural and Medical Research, 5th ed., Oliver & Boyd, Edinburgh (1957), pp. 47–55.Google Scholar
  84. 84.
    S. S. Minor and R. L. Schowen, One-proton solvation bridge in intramolecular carboxylate catalysis of ester hydrolysis, J. Am. Chem. Soc. 95, 2279–2281 (1973).CrossRefGoogle Scholar
  85. 85.
    S. L. Johnson, General base and nucleophilic catalysis of ester hydrolysis and related reactions, Adv. Phys. Org. Chem. 5, 237–330 (1967).CrossRefGoogle Scholar
  86. 86.
    D. M. Blow, J. J. Birktoft, and B. S. Hartley, Role of a buried acid group in the mechanism of action of chymotrypsin, Nature (London) 221, 337–340 (1969).CrossRefGoogle Scholar
  87. 87.
    G. S. Hammond, A correlation of reaction rates, J. Am. Chem. Soc. 77, 334–338 (1955).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • Katharine B. J. Schowen
    • 1
  1. 1.Department of ChemistryBaker UniversityBaldwin CityUSA

Personalised recommendations