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Conformational sensitivity of polyether macrocycles to electrostatic potential: Partial atomic charges, molecular mechanics, and conformational prediction

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Abstract

Molecular recognition (whether by enzymes, the immune system, or chelating ligands) depends critically on molecular conformation. Molecular mechanics predicts energetically favorable molecular conformations by locating low energy conformations using an empirical fit of molecular potential energy as a function of internal coordinates. Molecular mechanics analysis of 18-crown-6 demonstrates that the nonbonded term (primarily the electrostatic part) is the largest contributor to the conformational energy. Nevertheless, common methods of treating the electrostatic interaction for 18-crown-6 yield inconsistent values for conformational energies partly because partial charges assigned to each atom can change with conformation due to through-space inductive effects which are not considered in most molecular mechanics programs. Similar findings from several other groups are reviewed to support our conclusions. We argue for care and caution in predicting conformational preferences of molecules with two or more highly polar atoms. We also discuss the desirability of using an empirical method of partial charge determination such as the charge equilibration algorithm of Rappé and Goddard (or a suitable generalization which includes polarization) as a method of including these effects in molecular mechanics and molecular dynamics calculations.

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References

  1. C. J. Pedersen:J. Am. Chem. Soc. 89, 7017 (1967).

    Google Scholar 

  2. J. J. Christensen, D. J. Eatough and R. M. Izatt:Chem. Rev. 74, 351 (1974).

    Google Scholar 

  3. R. D. Hancock and A. E. Martell:Chem. Rev. 89, 1875 (1989).

    Google Scholar 

  4. M. Dobler, J. D. Dunitz, and P. Seiler:Acta. Crystallogr. B30, 2741 (1974); P. Seiler, M. Dobler, and J. D. Dunitz:Acta Crystallogr. B30, 2744 (1974); M. Dobler and R. P. Phizackerley:Acta Crystallogr. B30, 2746 (1974);B30, 2748 (1974).

    Google Scholar 

  5. G. Michaux and J. Riesse:J. Am. Chem. Soc. 104, 6895 (1982).

    Google Scholar 

  6. G. W. Gokel, D. M. Goli, C. Minganti, and L. Echegoyen:J. Am. Chem. Soc. 105, 6786 (1983).

    Google Scholar 

  7. R. D. Hancock:Acc. Chem. Res. 23, 253 (1990).

    Google Scholar 

  8. R. M. Izatt, J. S. Bradshaw, S. A. Nielsen, J. D. Lamb, and J. J. Christensen:Chem. Rev. 85, 271 (1985).

    Google Scholar 

  9. R. M. Izatt, K. Pawlak, J. S. Bradshaw, and R. L. Bruening:Chem. Rev. 91, 1721 (1991).

    Google Scholar 

  10. R. D. Hancock:J. Chem. Ed. 69, 615 (1992).

    Google Scholar 

  11. T. Yamabe, K. Hori, K. Akagi and K. Fukui:Tetrahedron 35, 1065 (1979).

    Google Scholar 

  12. M. J. Bovill, D. J. Chadwick, and I. O. Sutherland:J. Chem. Soc. Perkin Trans. II, 1529 (1980).

    Google Scholar 

  13. J. Leszczyński, A. Nowek, and W. Wojciechowski:J. Mol. Struct. (Theochem) 85, 211 (1981).

    Google Scholar 

  14. G. Wipff, P. Weiner, and P. Kollman:J. Am. Chem. Soc. 104, 3249 (1982).

    Google Scholar 

  15. K. Hori, H. Yamada, and T. Yamabe:Tetrahedron 39, 67 (1983).

    Google Scholar 

  16. B. M. Rode and S. V. Hannongbua:Inorg. Chim. Acta 96, 91 (1985).

    Google Scholar 

  17. J. W. H. M. Uiterwijk, S. Harkema and D. Feil:J. Chem. Soc. Perkin Trans II, 721 (1987).

    Google Scholar 

  18. E. D. Glendening, D. Feller, and M. A. Thompson:J. Am. Chem. Soc. 116, 10657 (1994).

    Google Scholar 

  19. L. von Szentpály and I. L. Shamovsky:J. Mol. Struct. (Theochem) 305, 249 (1994).

    Google Scholar 

  20. Y. L. Ha and A. K. Chakraborty:J. Phys. Chem. 96, 6410 (1992).

    Google Scholar 

  21. H. Bruning and D. Feil:J. Comput. Chem. 12, 1 (1991).

    Google Scholar 

  22. J. van Eerden, S. Harkema, and D. Feil:J. Phys. Chem. 92, 5076 (1988).

    Google Scholar 

  23. P. D. J. Grootenhuis and P. A. Kollman:J. Am. Chem. Soc. 111, 2152 (1989).

    Google Scholar 

  24. G. Ranghino, S. Romano, J. M. Lehn, and G. Wipff:J. Am. Chem. Soc. 107, 7873 (1985).

    Google Scholar 

  25. T. P. Straatsma and J. A. McCammon:J. Chem. Phys. 91, 3631 (1989).

    Google Scholar 

  26. Y. Sun and P. A. Kollman:J. Chem. Phys. 97, 5108 (1992).

    Google Scholar 

  27. M. Billeter, A. E. Howard, I. D. Kuntz, and P. A. Kollman:J. Am. Chem. Soc. 110, 8385 (1988).

    Google Scholar 

  28. A. E. Howard, U. C. Singh, M. Billeter, and P. A. Kollman:J. Am. Chem. Soc. 110, 6984 (1988).

    Google Scholar 

  29. J. R. Damewood, Jr., W. P. Anderson, and J. J. Urban:J. Comput. Chem. 9, 111 (1988).

    Google Scholar 

  30. W. L. Hase, M. C. Richou, and S. L. Mondro:J. Phys. Chem. 93, 539 (1989).

    Google Scholar 

  31. B. P. Hay, J. R. Rustad, and C. J. Hostetler:J. Am. Chem. Soc. 115, 11158 (1993); B. P. Hay and J. R. Rustad:J. Am. Chem. Soc. 116, 6316 (1994).

    Google Scholar 

  32. F. T. H. Leuwerink, S. Harkema, W. J. Briels, and D. Feil:J. Comput. Chem. 14, 899 (1993).

    Google Scholar 

  33. U. Burkert and N. L. Allinger:Molecular Mechanics, ACS Monograph Series Vol. 177 (American Chemical Society, Washington, D. C., 1982).

    Google Scholar 

  34. P. K. Weiner and P. A. Kollman:J. Comput. Chem. 2, 281 (1981); S. J. Weiner, P. A. Kollman, D. A. Case, U. C. Singh, C. Ghio, G. Alagona, S. Profeta, Jr., and P. Weiner:J. Am. Chem. Soc. 106, 765 (1984).

    Google Scholar 

  35. S. L. Price and A. J. Stone:J. Chem. Soc. Faraday Trans. 88, 1755 (1992).

    Google Scholar 

  36. J. H. Krieger: ‘Computer-Aided Molecular Design Teeming with Change’,Chem. Eng. News, April 14, 1994, pp. 31–40.

  37. See, for example the way AMBER ([34]) sometimes scales 1–4 electrostatic interactions.

  38. S. Tsuzuki and K. Tanabe:J. Chem. Soc. Perkin Trans. 2, 181 (1991).

    Google Scholar 

  39. S. Tsuzuki, T. Uchimaru, K. Tanabe, and T. Hirano:J. Phys. Chem. 97, 1346 (1993).

    Google Scholar 

  40. G. D. Smith, R. L. Jaffe, and D. Y. Yoon:J. Phys. Chem. 97, 12752 (1993).

    Google Scholar 

  41. A. J. Kirby and N. H. Williams: inThe Anomeric Effect and Associated Stereoelectronic Effects, ACS Symposium Series No. 539, G. R. J. Thatcher, Ed. (American Chemical Society, Washington, D.C., 1993), p. 55.

    Google Scholar 

  42. S. Dasgupta, K. A. Smith, and W. A. Goddard, III:J. Phys. Chem. 97, 10891 (1993).

    Google Scholar 

  43. P. I. Nagy, W. J. Dunn III, G. Alagona, and C. Ghio:J. Am. Chem. Soc. 113, 6719 (1991).

    Google Scholar 

  44. B. H. Besler, K. M. Merz Jr., and P. A. Kollman:J. Comput. Chem. 11, 431 (1990).

    Google Scholar 

  45. M. Orozco and F. J. Luque:J. Comput. Chem. 11, 909 (1990).

    Google Scholar 

  46. G. G. Ferenczy, C. A. Reynolds, and W. G. Richards:J. Comput. Chem. 11, 159 (1990).

    Google Scholar 

  47. A. K. Rappé and W. A. Goddard, III:J. Phys. Chem. 95, 3358 (1991).

    Google Scholar 

  48. J. Gasteiger and M. Marsili:Tetrahedron 36, 3219 (1980).

    Google Scholar 

  49. G. Del Re, G. Pepe, D. Laporte, C. Minichino, and B. Serres:Prog. Clin. Biol. Res. 172B, 115 (1985).

    Google Scholar 

  50. J. Mullay:J. Comput. Chem. 9, 399 (1988).

    Google Scholar 

  51. R. J. Abraham, G. H. Grant, I. S. Haworth, and P. E. Smith:J. Comput.-Aided Mol. Design 5, 21 (1991).

    Google Scholar 

  52. L. von Szentpály:J. Mol. Struct. (Theochem) 233, 71 (1991).

    Google Scholar 

  53. P. Politzer, J. E. Huheey, J. S. Murray, and M. Grodzicki:J. Mol. Struct. (Theochem) 259, 99 (1992).

    Google Scholar 

  54. J. M. Park, K. T. No, M. S. Jhon, and H. A. Scheraga:J. Comput. Chem. 14, 1482 (1993).

    Google Scholar 

  55. W. van Gunsteren and H. Berendsen:Angew. Chem. Int. Ed. Engl. 29, 992 (1990).

    Google Scholar 

  56. D. A. Greenberg, C. D. Barry, and B. R. Marshall:J. Am. Chem. Soc. 100, 13 (1978).

    Google Scholar 

  57. H. Zhang, I. H. Chu, S. Leming, and D. V. Dearden:J. Am. Chem. Soc. 113, 7415 (1991).

    Google Scholar 

  58. I. H. Chu, H. Zhang, and D. V. Dearden:J. Am. Chem. Soc. 115, 115 (1993).

    Google Scholar 

  59. S. Maleknia and J. Brodbelt:J. Am. Chem. Soc. 114, 4295 (1992).

    Google Scholar 

  60. S. Maleknia and J. Brodbelt:J. Am. Chem. Soc. 115, 2837 (1993).

    Google Scholar 

  61. Y. Sun and P. A. Kollman:J. Comput. Chem. 13, 33 (1992).

    Google Scholar 

  62. S. L. Mayo, B. D. Olafson, and W. A. Goddard III:J. Phys. Chem. 94, 8897 (1990).

    Google Scholar 

  63. A. K. Rappé, C. J. Casewit, K. S. Colwell, W. A. Goddard, III, and W. M. Skiff:J. Am. Chem. Soc. 114, 10024 (1992).

    Google Scholar 

  64. R. S. Mulliken:J. Chem. Phys. 36, 3428 (1962); I. N. Levine:Quantum Chemistry, 4th edition (Prentice Hall, Englewood Cliffs, N.J., 1991), pp. 475–478.

    Google Scholar 

  65. A. E. Reed, R. B. Weinstock, and F. Weinhold:J. Chem. Phys. 83, 735 (1985).

    Google Scholar 

  66. U. C. Singh and P. A. Kollman:J. Comput. Chem. 5, 129 (1984).

    Google Scholar 

  67. P. A. Kollman and K. M. Merz, Jr.:Acc. Chem. Res. 23, 246 (1990).

    Google Scholar 

  68. P. Cieplak and P. Kollman:J. Comput. Chem. 12, 1232 (1991).

    Google Scholar 

  69. C. M. Breneman and K. B. Wiberg:J. Comput. Chem. 11, 361 (1990).

    Google Scholar 

  70. D. E. Williams:Biopolymers 29, 1367 (1990).

    Google Scholar 

  71. M. N. Bellido and J. A. C. Rullmann:J. Comput. Chem. 10, 479 (1989).

    Google Scholar 

  72. W. L. Jorgensen and J. Gao:J. Am. Chem. Soc. 110, 4212 (1988).

    Google Scholar 

  73. C. A. Reynolds, J. W. Essex, and W. G. Richards:Chem. Phys. Lett. 199, 257 (1992); J. W. Essex, C. A. Reynolds and W. G. Richards:J. Am. Chem. Soc. 114, 3634 (1992).

    Google Scholar 

  74. C. A. Reynolds, J. W. Essex, and W. G. Richards:J. Am. Chem. Soc. 114, 9075 (1992).

    Google Scholar 

  75. C. H. Faerman and S. L. Price:J. Am. Chem. Soc. 112, 4915 (1990).

    Google Scholar 

  76. S. L. Price, C. H. Faerman, and C. W. Murray:J. Comput. Chem. 12, 1187 (1991).

    Google Scholar 

  77. C. Chipot, J. G. Angyan, B. Maigret, and H. A. Scheraga:J. Phys. Chem. 97, 9797 (1993).

    Google Scholar 

  78. J. J. Urban and G. R. Famini:J. Comput. Chem. 14, 353 (1993).

    Google Scholar 

  79. T. R. Stouch and D. E. Williams:J. Comput. Chem. 13, 622 (1992).

    Google Scholar 

  80. S. Dasgupta, K. A. Smith, and W. A. Goddard, III:J. Phys. Chem. 97, 10891 (1993).

    Google Scholar 

  81. W. D. Cornell, P. Cieplak, C. I. Bayly and P. A. Kollman:J. Am. Chem. Soc. 115, 9620 (1993).

    Google Scholar 

  82. F. Colonna and E. M. Evleth:Chem. Phys. Lett. 212, 665 (1993).

    Google Scholar 

  83. L. E. Chirlian and M. M. Francl:J. Comput. Chem. 8, 894 (1987).

    Google Scholar 

  84. C. L. Bayly, P. Cieplak, W. D. Cornell, and P. A. Kollman:J. Phys. Chem. 97, 10269 (1993).

    Google Scholar 

  85. U. Sternberg, F. T. Koch, and M. Mollhoff:J. Comput. Chem. 15, 524 (1994).

    Google Scholar 

  86. Z. Su:J. Comput. Chem. 14, 1036 (1993).

    Google Scholar 

  87. J. Rodriguez, F. Manaut, and F. Sanz:J. Comput. Chem. 14, 922 (1993).

    Google Scholar 

  88. C. Aleman, F. J. Luque, and M. Orozco:J. Comput. Chem. 14, 799 (1993).

    Google Scholar 

  89. K. B. Wiberg and R. P. Rablen:J. Comput. Chem. 14, 1504 (1993).

    Google Scholar 

  90. D. E. Williams: inReviews in Computational Chemistry, Vol. 2, K. B. Lipkowitz and D. B. Boyd, Eds. (VCH publishers, New York, 1991), p. 216.

    Google Scholar 

  91. T. R. Stouch and D. E. Williams:J. Comput. Chem. 14, 858 (1993).

    Google Scholar 

  92. B. T. Thole:Chem. Phys. 59, 341 (1981).

    Google Scholar 

  93. T. P. Lybrand and P. A. Kollman:J. Chem. Phys. 83, 2923 (1985).

    Google Scholar 

  94. J. Caldwell, L. X. Dang, and P. A. Kollman:J. Am. Chem. Soc. 112, 9144 (1990).

    Google Scholar 

  95. L. X. Dang, J. E. Rice, J. Caldwell, and P. A. Kollman:J. Am. Chem. Soc. 113, 2481 (1991).

    Google Scholar 

  96. L. Perera and M. L. Berkowitz:J. Chem. Phys. 95, 1954 (1991).

    Google Scholar 

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  1. Department of Chemistry, Brigham Young University, 84602, Provo, Utah, USA

    Randall B. Shirts & Lloyd D. Stolworthy

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  1. Randall B. Shirts
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Shirts, R.B., Stolworthy, L.D. Conformational sensitivity of polyether macrocycles to electrostatic potential: Partial atomic charges, molecular mechanics, and conformational prediction. J Incl Phenom Macrocycl Chem 20, 297–321 (1994). https://doi.org/10.1007/BF00708876

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