The Application of Hückel and Extended Hückel Molecular Orbital Calculations to Biochemical Problems

  • W. Brock Neely

Abstract

Professor A. Szent-Györgyi, in writing of his research [1], said, “...my relations to the various sciences were very promiscuous and made me remain an amateur scientist but a professional poacher”. A similar feeling arises from the complexity of the subject of structure activity analysis which requires the application of knowledge from all fields. In this endeavor, one quickly develops the ability to take the results and observations of other people in an effort to determine what is necessary for a chemical to be an active drug. The process leads to generalizations which, hopefully, will allow the design of better chemicals for specific end uses. One of the first generalizations discovered is that in this sort of study you cannot allow yourself the luxury of becoming too engrossed in any one discipline — you must maintain a proper perspective and attempt to keep all parameters in balance.

Keywords

Phenol Styrene Reso Cholinesterase Phenoxy 

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References

  1. [1]
    Szent-Györgi, A., p. 64 in Current Aspects of Biochemical Energetics, Academic Press, New York, (1966).Google Scholar
  2. [2]
    Pullman B. and Pullman A., Quantum Biochemistry, Wiley (Interscience), New York, (1963).Google Scholar
  3. [3]
    Streitweiser, A., Jr., Molecular Orbital Theory for Organic Chemists, Wiley, New York, (1961).Google Scholar
  4. [4]
    Neely, W. B., Unger, I., Blair, E. H., Nyquist, R. A., Biochemistry 3, 1477, (1964PubMedCrossRefGoogle Scholar
  5. [4a]
    Neely, W. B., Mol. Pharmacol., 1, 137, (1965).PubMedGoogle Scholar
  6. [5]
    Neely, W. B., White, H. C., Rudzik, A., J. Pharm. Sci. 57, 1176, (1968).PubMedCrossRefGoogle Scholar
  7. [6]
    Fujita, T., Iwasa, J., Hansch, C., J. Am. Chem. Soc., 86, 5175, (1964).CrossRefGoogle Scholar
  8. [7]
    Hoffmann, R., J. Chem. Phys., 39, 1397, (1963).CrossRefGoogle Scholar
  9. [8]
    Allen, L. C. and Russell, J. D., J. Chem. Phys., 46, 1029, (1967).CrossRefGoogle Scholar
  10. [9]
    Kier, L. B., Mol. Pharmacol., 3, 487, (1967).PubMedGoogle Scholar
  11. [10]
    Jellinek, F., Acta. Cryst., 10, 277, (1957).CrossRefGoogle Scholar
  12. [11]
    Chiou, C. Y., Long, J. P., Cannon, J. G., Armstrong, P. D., J. Pharmacol. Exp. Therap., 166, 243, (1969).Google Scholar
  13. [12]
    Reeves, R. E., Advan. Carbohydrate Chem., 6, 197, (1951).Google Scholar
  14. [13]
    Neely, W. B., J. Med. Chem., 12, 16, (1969).PubMedCrossRefGoogle Scholar
  15. [14]
    Eliel, E. L., Allinger, N. L., Angyal, S. J., Morrison, G. A., Conformational Analysis, Interscience, New York, (1965).Google Scholar
  16. [15]
    Rao, V. S. R., Sundararajan, P. R., Ramakishnan, C., Ramachandran, G. N., p. 721, in Conformation of Biopolymers, 2, (G. N. Ramachandran, Ed.), Academic Press, New York, (1967).Google Scholar
  17. [16]
    DeDatta, S. K., Bantilan, R. T., Park, J. K., Nature, 221, 64, (1969).CrossRefGoogle Scholar
  18. [17]
    Johnson, F., Chem. Rev., 68, 375, (1968).CrossRefGoogle Scholar
  19. [18]
    Overberger, C. G. and Tanner, D., J. Am. Chem. Soc., 77, 369, (1955).CrossRefGoogle Scholar
  20. [19]
    Fukui, K, Yonezawa, T., Shingu, H., J. Chem. Phys., 20, 722, (1952).CrossRefGoogle Scholar
  21. [20]
    Hoffmann, R. and Imamura, A., Biopolymers, 7, 207, (1969).CrossRefGoogle Scholar
  22. [21]
    Boer, F. P., Newton, M. D., Lipscomb, W. N., Biopolymers, 52, 890, (1964).Google Scholar
  23. [22]
    Newton, M. D., Boer, F. P., Palke, W. E., Lipscomb, W. N., Proc. Natl. Acad. Sci. U.S., 52, 890, (1964).CrossRefGoogle Scholar
  24. [23]
    Newton, M. D., Boer, F. P., Lipscomb, W. N., J. Am. Chem. Soc., 88, 2353, (1966)CrossRefGoogle Scholar
  25. [23a]
    Boer, F. P., Newton, M. D., Lipscomb, W. N., J. Am. Chem. Soc., 88, 2361, (1966)CrossRefGoogle Scholar
  26. [23b]
    Newton, M. D., Boer, F. P., Lipscomb, W. N., J. Am. Chem. Soc., 88, 2367, (1966)CrossRefGoogle Scholar
  27. [23c]
    Palke, W. E., Lipscomb, W. N., J. Am. Chem. Soc., 88, 2384, (1966).CrossRefGoogle Scholar
  28. [24]
    Boer, F. P. and Lipscomb, W. N., J. Chem. Phys., 50, 989, (1969).CrossRefGoogle Scholar
  29. [25]
    Cammarata, A., J. Med. Chem., 11, 1111, (1968).PubMedCrossRefGoogle Scholar
  30. [26]
    Klopman, G. and Hudson, R. F., Theoret. Chem. Acta, 8, 165, (1967).CrossRefGoogle Scholar
  31. [27]
    Klopman, G., J. Am. Chem. Soc., 90, 223, (1968).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1970

Authors and Affiliations

  • W. Brock Neely
    • 1
  1. 1.Biochemical Research LaboratoryThe Dow Chemical CompanyMidlandUSA

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