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QSAR of benzene derivatives: comparison of classical descriptors, quantum theoretic parameters and flip regression, exemplified by phenylalkylamine hallucinogens

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Abstract

A physical model of electronic effects in the QSAR of benzene derivatives, together with a regression technique for finding predictive equations, is presented. The model is simple, based on the quantum theoretic description of the benzene molecule, and accounts for the variance in activity of hallucinogenic phenylalkylamines as well as a classical description in terms of electronic (atomic charge, orbital energy), hydrophobic (Hansch π) and steric (substituent volume) terms. The new model involves the energies of four π-like near frontier orbitals and the orientations of their nodes. It is less affected by colinearity than the classical approach. This model more than any other illustrates the essential wave mechanical nature of the interaction of a drug with its receptor, as the π-like orbitals involved are standing waves of probability of finding an electron in a given location in the field of the atomic nuclei, and have no classical counterpart.

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References

  1. Clare, B.W., J. Med. Chem., 33 (1990) 687.

    Google Scholar 

  2. Shulgin, A., Shulgin, A., PIHKAL: A Chemical Love Story; Transform Press: Box 13675 Berkeley, California, 1991.

    Google Scholar 

  3. Clare, B.W., J. Med. Chem., 41 (1998) 3845.

    Google Scholar 

  4. a.) Clare, B.W., THEOCHEM507 (2000) 157, b.) Clare, B.W., THEOCHEM 535 (2001) 301.

    Google Scholar 

  5. Pople, J.A., Beveridge, D.L., Approximate Molecular Orbital Theory; McGraw Hill: New York, 1970.

    Google Scholar 

  6. Dewar, M.J.S., Zoebisch, E.G., Healy, E.F., Stewart, J.J.P., J. Amer. Chem. Soc. 107 (1985) 3902.

    Google Scholar 

  7. Parr, R. G., Yang, W., Density-functional theory of atoms and molecules, Oxford Univ. Press: Oxford, 1989.

    Google Scholar 

  8. Parr, R.G., Pearson, R.G., J. Am. Chem. Soc., 105 (1983) 7512.

    Google Scholar 

  9. Mracec, M., Muresan, S., Mracec, M., Simon, Z., Naray-Szabo, G., Quant. Struct.-Act. Relat., 16 (1997) 459.

    Google Scholar 

  10. Mracec, M., Mracec, M., Kurunczi, L., Nusser, T., Simon, Z., Naray-Szabo, G., THEOCHEM, 367 (1996) 139.

    Google Scholar 

  11. Barfknecht, C.F., Nichols, D.E., J. Med. Chem., 18 (1975) 208.

    Google Scholar 

  12. Gupta, S.K., Bindal, M.C., Singh, P., Arzneim. Forsch., 32 (1982) 1223.

    Google Scholar 

  13. Domelsmith, L.N., Eaton, T.A., Houk, K.N., Anderson, G.M. III., Glennon, R.A., Shulgin, A.T., Castagnoli, N., Kollman, P.A., J. Med. Chem., 24 (1981) 1414.

    Google Scholar 

  14. Mracec, M., Mracec, M., Ann. West Univ. Timisoara, ser. chem., 6 (1997) 15.

  15. Mracec, M., Mracec, M., Muresan, S., Bologa, C., Kurunczi, L., Simon, Z., Ann.West Univ. Timisoara, ser. chem., 5 (1996) 125.

    Google Scholar 

  16. PCMODEL V. 5.0, Available from Serena Software, Box 3076 Bloomington IN 47402-3076 U.S.A.

  17. Hyperchem v. 6.0, Available from Hypercube, Inc. 1115 NW 4th Street, Gainesville, Florida 32601-4256 U.S.A.

  18. Stewart, J.J.P., Q.C.P.E. Bull., 10 (1990) 86.

    Google Scholar 

  19. MOLDEN, written by G. Schaftenaar, CAOS/CAMM Center Nijmegen, Toernooiveld, Nijmegen, The Netherlands.

  20. Gaussian 98, Revision A.9, M. J. Frisch, G. W. Trucks, H.B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomery, Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J. M. Millam, A. D. Daniels, K.N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J.B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M.W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E. S. Replogle, and J. A. Pople, Gaussian, Inc., Pittsburgh PA, 1998.

    Google Scholar 

  21. File Gaussang.zip from the site http://www.chem.uwa.edu.au/ research/bclare/

  22. Becke, A.D., Phys. Rev., A38 (1988) 3098.

    Google Scholar 

  23. Lee, C., Yang, W., Parr, R.G., Phys. Rev. B37 (1988) 785.

    Google Scholar 

  24. Hehre, W.J., Radom, L., Schleyer, P. v.R., Pople, J.A., Ab Initio Molecular Orbital Theory, John Wiley & Sons: New York, 1986.

    Google Scholar 

  25. Klamt, A., Schüürman, G., J. Chem. Soc. Perkin Trans 2, (1993) 799. 633

    Google Scholar 

  26. Besler, B.H., Merz, K.M., Kollman, P.A., J. Comp. Chem., 11 (1990) 431.

    Google Scholar 

  27. ClogP for Windows, ver 1.0.0. Available from BioByte Corp. 201 West 4th St., Suite 204, Claremont CA 91711, U.S.A.

  28. file martha.zip from the site http://www.chem.uwa.edu.au/ research/bclare/

  29. Metropolis, N., Rosenbluth, A.W., Rosenbluth, M.N., Teller, A., Teller, E., J. Chem. Phys., 21 (1953) 1087.

    Google Scholar 

  30. Press, W.H., Teukolsky, S.A, Vetterling, W.T., Flannery, B.P., Numerical Recipes in Fortran, Second Edition; Cambridge: 1992, pp. 436-448.

  31. Hansch, C., Maloney, P.P., Fujita, T., Muir, R., Nature (London), 194 (1962) 178.

    Google Scholar 

  32. Free, S.M., Wilson, J.W., J. Med. Chem., 7 (1964) 395.

    Google Scholar 

  33. Furnival, G. M., Wilson R.W., Technometrics, 16 (1974) 499.

    Google Scholar 

  34. BMDP Dynamic, Release 7. Available from SPSS Inc., Headquarters, 233 S. Wacker Drive, 11th Floor, Chicago. Illinois 60606.

  35. Daniel, C., Wood, F. S., Fitting Equations to Data;Wiley: New York, 1971.

    Google Scholar 

  36. Chatterjee, S., Price, B., Regression Analysis by Example; 1st Ed, Wiley: New York, 1977; pp. 199-200.

    Google Scholar 

  37. Forsythe, G.E., J. Soc. Indust. Appl. Math., 5 (1957) 74.

    Google Scholar 

  38. Johnson, K.J., Numerical Methods in Chemistry. Dekker; NewYork: 1980, pp. 262-273.

    Google Scholar 

  39. Clare, B.W., Supuran, C.T., Unpublished observations.

  40. Supuran, C.T., Clare, B.W., SAR and QSAR in Environmental Research, 12 (2001) 17.

    Google Scholar 

  41. Supuran, C.T., Scozzafava, A., Briganti, F., Clare, B.W., J. Med. Chem., 43 (2000) 1793.

    Google Scholar 

  42. Karelson, K. Molecular Descriptors in QSAR/QSPR, Wiley-Interscience, New York, 2000.

    Google Scholar 

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  1. Department of Chemistry, The University of Western Australia, 35 Stirling Highway, Crawley, W.A, 6009, Australia

    Brian W. Clare

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  1. Brian W. Clare
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Clare, B.W. QSAR of benzene derivatives: comparison of classical descriptors, quantum theoretic parameters and flip regression, exemplified by phenylalkylamine hallucinogens. J Comput Aided Mol Des 16, 611–633 (2002). https://doi.org/10.1023/A:1021966231380

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