Advertisement

Intramolecular Reactions and the Relevance of Models

  • Richard D. Gandour

Abstract

In the past few years, there has been a growing interest in chemical models of enzyme action. In this large body of research, two distinct types of models emerge. The first type is mimetic models; i.e., the reactions model specific enzymes. This area will not be covered in this chapter, but the reader is referred to an excellent review by Fife(1) which covers this approach for three enzymic reactions. The second type is nonmimetic models; i.e., the reactions or interactions model a specific feature of the general process of enzyme catalysis. Among nonmimetic models are two further subdivisions. One subdivision encompasses catalysis by complexation, thus modeling the binding of the substrate to the protein. This subdivision includes reactions catalyzed by micelles, cyclodextrins, hydrophobic interactions in aqueous solution, chargetransfer complexes, and polar associations in apolar solvents. The other subdivision encompasses catalysis by functional groups, thus modeling catalysis by functional groups on side chains of the peptide backbone in the enzyme—substrate complex. This topic is our major concern in this chapter.

Keywords

Isotope Effect Rate Enhancement Rate Acceleration Ester Hydrolysis Entropy Loss 
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.
    T. H. Fife, Physical organic model systems and the problem of enzymatic catalysis, Adv. Phys. Org. Chem 11, 1–122 (1975).CrossRefGoogle Scholar
  2. 2.
    D. E. Koshland, Jr., Molecular geometry in enzyme action, J. Cell. Comp. Physiol. 47, Supp. 1, 217–234 (1956).CrossRefGoogle Scholar
  3. 3.
    D. E. Koshland, Jr., The comparison of non-enzymic and enzymic reaction velocities, J. Theor. Biol 2, 75–86 (1962).CrossRefGoogle Scholar
  4. 4.
    T. C. Bruice, Intramolecular catalysis and the mechanism of chymotrypsin actions, Brookhaven Symp. Biol 15, 52–84 (1962).PubMedGoogle Scholar
  5. 5.
    M. I. Page and W. P. Jencks, Entropie contributions to rate accelerations in enzymic and intramolecular reactions and the chelate effect, Proc. Nat. Acad. Sci. USA 68, 1678–1683 (1971).PubMedCrossRefGoogle Scholar
  6. 6.
    M. I. Page, Energetics of neighboring group participation, Chem. Soc. Rev 2, 295–323 (1973).CrossRefGoogle Scholar
  7. 7.
    W. P. Jencks, Binding energy, specificity, and enzymic catalysis: The Circe effect, Adv. Enzymol. Relat. Areas Mol. Biol 43, 219–410 (1975).PubMedGoogle Scholar
  8. 8.
    R. Lumry, in: The Enzymes, 2nd ed. (P. D. Boyer, ed.), Vol. 1, pp. 157–231, Academic Press, New York (1959).Google Scholar
  9. 9.
    W. P. Jencks, Catalysis in Chemistry and Enzymology, McGraw-Hill, New York (1969).Google Scholar
  10. 10.
    L. Schafer, S. J. Cyvin, and J. Brunwall, Zur Verschiebung von Schwingungsfrequenzen durch kinematische Kopplung, Tetrahedron 27, 6177–6179 (1971).CrossRefGoogle Scholar
  11. 11.
    R. A. Firestone and B. G. Christensen, Vibrational activation I. A source for the catalytic power of enzymes, Tetrahedron Lett. 1973, 389–392.Google Scholar
  12. 12.
    D. B. Cook and J. McKenna, A contribution to the theory of enzyme catalysis. The potential importance of vibrational activation entropy, J. Chem. Soc. Perkin Trans. 2 1974, 1223–1225.Google Scholar
  13. 13.
    L. Pauling, Molecular architecture and biological reactions, Chem. Eng. News 24, 1375–1377 (1946).CrossRefGoogle Scholar
  14. 14.
    R. Wolfenden, Analog approaches to the structure of the transition state in enzyme reactions, Acc. Chem. Res 5, 10–18 (1972).CrossRefGoogle Scholar
  15. 15.
    G. E. Lienhard, Enzymatic catalysis and transition-state theory, Science 180, 149–154 (1973).PubMedCrossRefGoogle Scholar
  16. 16.
    K. Schray and J. P. Klinman, The magnitude of enzyme transition state analog binding constants, Biochem. Biophys. Res. Commun 57, 641–648 (1974).PubMedCrossRefGoogle Scholar
  17. 17.
    S. Milstien and L. A. Cohen, Rate accelerations by stereopopulation control: Models for enzyme action, Proc. Nat. Acad. Sci. USA 67, 1143–1147 (1970).PubMedCrossRefGoogle Scholar
  18. 18.
    D. R. Storm and D. E. Koshland, Jr., A source for the special catalytic power of enzymes: Orbital steering, Proc. Nat. Acad. Sci. USA 66, 445–452 (1970).PubMedCrossRefGoogle Scholar
  19. 19.
    T. C. Bruice, in: The Enzymes, 3rd ed. (P. D. Boyer, ed.), Vol. 2, pp. 217–279, Academic Press, New York (1970).Google Scholar
  20. 20.
    T. C. Bruice, Some pertinent aspects of mechanism as determined with small molecules, Annu. Rev. Biochem 45 331–373 (1976).Google Scholar
  21. 21.
    S. Milstien and L. A. Cohen, Stereopopulation control. I. Rate enhancement in the lactonizations of o-hydroxyhydrocinnamic acids, J. Am. Chem. Soc. 94, 9158–9165 (1972).CrossRefGoogle Scholar
  22. 22.
    R. T. Borchardt and L. A. Cohen, Stereopopulation control. II. Rate enhancement of intra-molecular nucleophilic displacement, J. Am. Chem. Soc 94, 9166–9174 (1972).PubMedCrossRefGoogle Scholar
  23. 23.
    P. S. Hillery and L. A. Cohen, Stereopopulation control in the formation of cyclic anhydrides. Demonstrations of rate and equilibrium enhancement, general catalysis and duality of mechanism (manuscript in preparation).Google Scholar
  24. 24.
    T. C. Bruice and U. K. Pandit, The effect of geminal substitution, ring size and rotamer distribution on the intramolecular nucleophilic catalysis of the hydrolysis of monophenyl esters of dibasic acids and the solvolysis of the intermediate anhydrides, J. Am. Chem. Soc 82, 5858–5865 (1960).CrossRefGoogle Scholar
  25. 25.
    J. M. Karle and I. L. Karle, Correlation of reaction rate acceleration with rotational restriction. Crystal-structure analysis of compounds with a trialkyl lock, J. Am. Chem. Soc 94, 9182–9189 (1972).CrossRefGoogle Scholar
  26. 26.
    C. Danforth, A. W. Nicholson, J. C. James, and G. M. Loudon, Steric acceleration of lactonization reactions: an analysis of “stereopopulation control,” J. Am. Chem. Soc. 98, 4275–4281 (1976).CrossRefGoogle Scholar
  27. 27.
    J. L. Fry and R. C. Badger, Evidence for a remote secondary kinetic deuterium isotope effect arising from a sterically congested ground state, J. Am. Chem. Soc 97, 6276–6277 (1975).CrossRefGoogle Scholar
  28. 28.
    R. E. Winans and C. F. Wilcox, A comparison of stereopopulation control with conventional steric effects in lactonization of hydrocoumarinic acids, J. Am. Chem. Soc 98, 4281–4285 (1976).CrossRefGoogle Scholar
  29. 29.
    R. Hershfield and G. L. Schmir, Lactonization of ring-substituted coumarinic acids. Structural effects on the partitioning of tetrahedral intermediates in esterification, J. Am. Chem. Soc. 95, 7359–7369 (1973); Lactonization of coumarinic acids. Kinetic evidence for three species of the tetrahedral intermediate, J. Am. Chem. Soc 95, 8032–8040 (1973).CrossRefGoogle Scholar
  30. 30.
    D. E. Koshland, Jr., K. W. Carraway, G. A. Dafforn, J. D. Gass, and D. R. Storm, The importance of orientation factors in enzymatic reactions, Cold Spring Harbor Symp. Quant. Biol 36 13–20 (1971).Google Scholar
  31. 31.
    D. E. Koshland, Jr., The catalytic power of enzymes, Proc. Robert A. Welch Found. Cont. Chem. Res 15, 53–91 (1972).Google Scholar
  32. 32.
    G. A. Dafforn and D. E. Koshland, Jr., The sensitivity of intramolecular reactions to the orientation of reacting atoms, Bioorg. Chem 1, 129–139 (1971).CrossRefGoogle Scholar
  33. 33.
    A. Dafforn and D. E. Koshland, Jr., Theoretical aspects of orbital steering, Proc. Nat. Acad. Sci. USA 68, 2463–2467 (1971).PubMedCrossRefGoogle Scholar
  34. 34.
    D. R. Storm and D. E. Koshland, Jr., An indication of the magnitude of orientation factors in esterification, J. Am. Chem. Soc 94, 5805–5814 (1972).CrossRefGoogle Scholar
  35. 35.
    D. R. Storm and D. E. Koshland, Jr., Effect of small changes in orientation on reaction rate J. Am. Chem. Soc. 94, 5815–5825 (1972).CrossRefGoogle Scholar
  36. 36.
    R. M. Moriarity and T. Adams, A criticism of the use of certain bridged bicyclic hydroxycarboxylic acids as model compounds for the concept of orbital steering, J. Am. Chem. Soc 95, 4070–4071 (1973).CrossRefGoogle Scholar
  37. 37.
    T. Adams and R. M. Moriarity, Acid-catalyzed lactonization of exo-and endo-bicyclo[2.2.2] oct-5-ene-carboxylic acids. Structural clarifications, J. Am. Chem. Soc 95, 4071–4073 (1973).CrossRefGoogle Scholar
  38. 38.
    D. R. Storm, R. Tjian, and D. E. Koshland, Jr., Rate acceleration by alteration in the orientation of reacting atoms. Comparisons of lactonizations in bicyclo[2,2,2] and bicyclo[2,2,1] ring structures, Chem. Commun. 1971, 854–855.Google Scholar
  39. 39.
    B. Capon, Orbital steering: An unnecessary concept, J. Chem. Soc. B 1971, 1207.Google Scholar
  40. 40.
    D. F. DeTar, Calculation of steric effects in reactions, J. Am. Chem. Soc. 96, 1254–1255 (1974); Quantitative predictions of steric acceleration, J. Am. Chem. Soc 96, 1255–1256 (1974).CrossRefGoogle Scholar
  41. 41.
    T. C. Bruice, A. Brown, and D. O. Harris, On the concept of orbital steering in catalytic reactions, Proc. Nat. Acad. Sci. USA 68, 658–661 (1971).PubMedCrossRefGoogle Scholar
  42. 42.
    C. E. Kim and L. L. Ingraham, The question of orbital steering in the reaction, H2O + CH2O, Biochim. Biophys. Acta 297, 220–228 (1970).CrossRefGoogle Scholar
  43. 43.
    R. Hershfield and G. L. Sehmir, Mechanism of acid-catalyzed thiolactonization. Kinetic evidence for tetrahedral intermediates, J. Am. Chem. Soc 94, 6788–6793 (1972).CrossRefGoogle Scholar
  44. 44.
    G. N. J. Port and W. G. Richards, Orbital steering and the catalytic power enzymes, Nature (London) 231, 321–322 (1971).CrossRefGoogle Scholar
  45. 45.
    D. G. Hoare, Significance of molecular alignment and orbital steering in mechanisms for enzymatic catalysis, Nature (London) 236, 437 (1972).CrossRefGoogle Scholar
  46. 46.
    H. Umeyama, A. Imamura, C. Nagata, and M. Hanano, Molecular orbital study on the enzymic reaction mechanism of a-chymotrypsin, J. Theor. Biol 41, 485–502 (1973).PubMedCrossRefGoogle Scholar
  47. 47.
    T. C. Bruice, Views on approximation, orbital steering, and enzymatic and model reactions, Cold Spring Harbor Symp. Quant. Biol. 36 21–27 (1971).CrossRefGoogle Scholar
  48. 48.
    M. I. Page, Entropie rate accelerations and orbital steering, Biochem. Biophys. Res. Commun 49, 940–944 (1972).PubMedCrossRefGoogle Scholar
  49. 49.
    A. Dafforn and D. E. Koshland, Jr., Proximity, entropy, and orbital steering. Biochem. Biophys. Res. Commun. 52, 779–785 (1973).CrossRefGoogle Scholar
  50. 50.
    W. P. Jencks and M. I. Page, “Orbital steering,” entropy, and rate accelerations, Biochem. Biophys. Res. Commun. 57, 887–892 (1974).CrossRefGoogle Scholar
  51. 51.
    T. C. Bruice and S. J. Benkovic, Bioorganic Mechanisms, Vol. 1, Benjamin, Reading, Mass. (1966).Google Scholar
  52. 52.
    T. C. Bruice and U. K. Pandit, Intramolecular models depicting the kinetic importance of “fit” in enzymatic catalysis, Proc. Nat. Acad. Sci. USA 46, 402–404 (1960).PubMedCrossRefGoogle Scholar
  53. 53.
    C. DeLisi and D. M. Crothers, The contribution of proximity and orientation to catalytic reaction rates, Biopolymers 12, 1689–1704 (1973).CrossRefGoogle Scholar
  54. 54.
    A. J. Kirby and A. R. Fersht, Intramolecular catalysis, Prog. Bioorg. Chem 1. 1–82 (1971).CrossRefGoogle Scholar
  55. 55.
    B. Capon, Intramolecular catalysis, Essays Chem. 3. 127–156 (1972).Google Scholar
  56. 56.
    M. L. Bender, Mechanisms of Homogeneous Catalysis from Protons to Proteins,WileyInterscience, New York (1971), Chap. 9.Google Scholar
  57. 57.
    R. D. Gandour and R. L. Schowen, Intramolecular catalysis in medicinal chemistry, Annu. Rep. Med. Chem 7, 279–288 (1972).CrossRefGoogle Scholar
  58. 58.
    B. Capon, in: Proton-Transfer Reactions ( E. F. Caldin and V. Gold, eds.), pp. 339–384, Chapman & Hall, London (1975).Google Scholar
  59. 59.
    M. Balakrishnan, G. V. Rao, and N. Venkatassubramian, Neighboring group participation in ester hydrolysis, J. Sci. Ind. Res 33, 641–651 (1974).Google Scholar
  60. 60.
    S. S. Minor and R. L. Schowen, One proton solvation bridge in intramolecular catalysis of ester hydrolysis, J. Am. Chem. Soc 95, 2279–2281 (1973).CrossRefGoogle Scholar
  61. 61.
    A. R. Fersht and A. J. Kirby, The hydrolysis of aspirin. Intramolecular general base catalysis of ester hydrolysis, J. Am. Chem. Soc 89, 4857–4863 (1967).PubMedCrossRefGoogle Scholar
  62. 62.
    A. R. Fersht and A. J. Kirby, Structure and mechanism in intramolecular catalysis. The hydrolysis of substituted aspirins, J. Am. Chem. Soc 89, 4853–4857 (1967).PubMedCrossRefGoogle Scholar
  63. 63.
    R. D. Gandour, C. Olomon, and M. Sneller, unpublished results.Google Scholar
  64. 64.
    John L. Hogg, Transition state structures for catalysis by serine hydrolases and for related organic reactions, Ph.D. thesis, University of Kansas, Lawrence (1974).Google Scholar
  65. 65.
    H. B. Bürgi, J. M. Kehn, and G. Wipff, An ab initio study of nucleophilic addition to a carbonyl group, J. Am. Chem. Soc. 96, 1956–1957 (1974).CrossRefGoogle Scholar
  66. 66.
    H. Umeyama, A molecular orbital study on the solvolysis of aspirin derivatives and acyl-achymotrypsin, Chem. Pharm. Bull 22, 2518–2529 (1974).PubMedCrossRefGoogle Scholar
  67. 67.
    E. R. Garrett, The kinetics of solvolysis of acyl esters of salicylic acid, J. Am. Chem. Soc 79, 3401–3408 (1957).CrossRefGoogle Scholar
  68. 68.
    G. V. Rao, Solvent effects on intramolecular catalysis, Indian J. Chem 13, 608–609 (1975).Google Scholar
  69. 69.
    A. J. Kirby and G. J. Lloyd, Intramolecular general base catalysis of intramolecular nucleophilic catalysis of ester hydrolysis, J. Chem. Soc. Perkin Trans. 2 1974, 637–642.Google Scholar
  70. 70.
    A. J. Kirby and G. T. Lloyd, Structure and efficiency in intramolecular and enzymic catalysis: Intramolecular general base catalysis. Hydrolysis of monoaryl malonates, J. Chem. Soc. Perkin Trans. 2 1976, 1753–1761.Google Scholar
  71. 71.
    R. D. Gandour, Structural requirements for intramolecular proton transfers, Tetrahedron Lett. 1974, 295–299.Google Scholar
  72. 72.
    V. Gold, D. G. Oakenfull, and T. Riley, The acetate-catalyzed hydrolysis of aryl acetates, J. Chem. Soc. B 1968, 515–519.Google Scholar
  73. 73.
    M. F. Aldersley, A. J. Kirby, and P. W. Lancaster, Intramolecular displacement of alkoxide ions by the ionized carboxy group: Hydrolysis of alkyl hydrogen dialkylmaleates, J. Chem. Soc. Perkin Trans 2 1974, 1504–1510.Google Scholar
  74. 74.
    T. C. Bruice and A. Turner, Solvation and approximation. Solvent effects on the bimolecular and intramolecular nucleophilic attack of carboxyl anion on phenyl esters, J. Am. Chem. Soc 92, 3422–3428 (1970).CrossRefGoogle Scholar
  75. 75.
    E. Gaetjens and H. Morawetz, Intramolecular carboxylate attack on ester groups. The hydrolysis of substituted phenyl acid succinates and phenyl acid glutarates, J. Am. Chem. Soc 82, 5328–5335 (1960).CrossRefGoogle Scholar
  76. 76.
    J. W. Thanassi and T. C. Bruice, Neighboring carboxyl group participation in the hydrolysis of monoesters of phthalic acid. The dependence of mechanisms on leaving group tendencies, J. Am. Chem. Soc 88, 747–752 (1966).PubMedCrossRefGoogle Scholar
  77. 77.
    W. P. Jencks, F. Barley, R. Barnett, and M. Gilchrist, The free energy of hydrolysis of acetic anhydride, J. Am. Chem. Soc 88, 4464 4467 (1966).Google Scholar
  78. 78.
    T. Higuchi, L. Eberson, and J. D. McRae, Acid anhydride—free acid equilibria in water in some substituted succinic acid systems and their interaction with aniline, J. Am. Chem. Soc 89, 3001–3004 (1967).CrossRefGoogle Scholar
  79. 79.
    M. J. Haddadin, T. Higuchi, and V. Stella, Solvolytic reactions of cylic anhydrides in anhydrons acetic acid, J. Pharm. Sci 64, 1759 (1975).PubMedCrossRefGoogle Scholar
  80. 80.
    M. D. Hawkins, Hydrolysis of phthalic and 3,6-dimethylphthalic anhydrides, J. Chem. Soc. Perkin Trans. 2 1975, 282–284.Google Scholar
  81. 81.
    L. Eberson and H. Welinder, Studies on cyclic anhydrides. III. Equilibrium constants for the acid—anhydride equilibrium in aqueous solutions of certain vicinal diacids, J. Am. Chem. Soc 93, 5821–5826 (1971).CrossRefGoogle Scholar
  82. 82.
    J. Gerstein and W. P. Jencks, Equilibria and rates for acetyl transfer among substituted phenyl acetates, acetylimidazole, O-acylhydroxamic acids and thiol esters, J. Am. Chem. Soc 86, 4655–4663 (1964).CrossRefGoogle Scholar
  83. 83.
    R. Fuchs and E. S. Lewis, in Techniques of Chemistry (E. S. Lewis, ed.), Vol. 6, p. 812, Wiley, New York (1974).Google Scholar
  84. 84.
    L. Pauling, The Nature of the Chemical Bond, 3rd ed., Cornell University Press, Ithaca, N.Y. (1960), p. 239.Google Scholar
  85. 85.
    R. D. Gandour, V. J. Stella, M. Coyne, R. L. Schowen, and E. A. Icaza, Secondary isotope effects in intramolecular catalysis. Mono-p-bromophenyl succinate hydrolysisJ. Org. Chem. 43, in press.Google Scholar
  86. 86.
    J. R. Murdoch, Rate-equilibria relationships and proton-transfer reactions, J. Am. Chem. Soc 94, 4410–4418 (1972).CrossRefGoogle Scholar
  87. 87.
    L. Eberson and L. A. Svensson, Studies on catechol esters. Part III. Hydrolysis of Ohydroxylphenyl acid succinates; competing intramolecular nucleophilic and general hase catalysis, Acta Chem. Scand 26, 2631–2641 (1972).PubMedCrossRefGoogle Scholar
  88. 88.
    D. C. Best, G. M. Underwood, and C. A. Kingsbury, On conformation—reactivity correlations, J. Org. Chem 40, 1984–1987 (1975).CrossRefGoogle Scholar
  89. 89.
    S. Scheiner, W. N. Lipscomb, and D. A. Kleier, Molecular orbital studies of enzyme activity. 2. Nucleophilic attack on carbonyl systems with comments on orbital steering, J. Am. Chem. Soc 98, 4770–4777 (1976).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • Richard D. Gandour
    • 1
  1. 1.Department of ChemistryLouisiana State UniversityBaton RougeUSA

Personalised recommendations