The Effect of Ring Nitrogen Atoms on the Homolytic Reactivity of Phenolic Compounds: Understanding the Radical-Scavenging Ability of 5-Pyrimidinols

Chemistry - A European Journal

Volumn 9, Issue 20, 2003, Pages 4997-5010

  Valgimigli, Luca ^a   Brigati, Giovanni ^a   Pedulli, Gian Franco ^a   DiLabio, Gino A ^c   Mastragostino, Marina ^a   Arbizzani, Catia ^a   Pratt, Derek A ^b  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b VANDERBILT UNIVERSITY   (United States)

^c NATIONAL RESEARCH COUNCIL CANADA   (Canada)

Author keywords

Antioxidants; Lipids; Phenols; Pyrimidinols; Radicals

Indexed keywords

ALCOHOLS; ANTIOXIDANTS; FREE RADICALS; REACTION KINETICS; SUBSTITUTION REACTIONS; SYNTHESIS (CHEMICAL);

HYDROGEN-ATOM DONORS;

AROMATIC COMPOUNDS;

2,4,6 TRIMETHYLPHENOL; 5 PYRIMIDINOL; ANTIOXIDANT; BUTYLCRESOL; HYDROGEN; NITROGEN; PEROXY RADICAL; PHENOL DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL COMPOSITION; DRUG SYNTHESIS; ENTHALPY; HYDROGEN BOND; HYPOTHESIS; KINETICS; OXIDATION; PHASE TRANSITION; REACTION ANALYSIS; THEORY; THERMAL ANALYSIS;

EID: 0142228953     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200304960     Document Type: Article

References (73)

1. a) L. J. Marnett, Carcinogenesis 2000, 21, 361-370;
2. b) A. Sevanian, F. Ursini, F. Free Radical Biol. Med. 2000, 29, 306-311;
3. c) D. Steinburg, S. Parhsarathy, T. E. Carew, J. C. Khoo, J. L. Witztum, N. Engl. J. Med. 1989, 320, 915-924;
4. d) G. M. Chisholm, D. Steinburg, Free Radical Biol. Med. 2000, 28, 1815-1826.
5. a) M. Lucarini, P. Pedrielli, G. F. Pedulli, S. Cabiddu, C. Fattuoni, J. Org. Chem. 1996, 61, 9259-9263;
6. b) M. Lucarini, G. F. Pedulli, M. Cipollone, J. Org. Chem. 1994, 59, 5063-5070 and references therein.
7. P. Franchi, M. Lucarini, G. F. Pedulli, L. Valgimigli, B. Lunelli, J. Am. Chem. Soc. 1999, 121, 507-514.
8. a) G. W. Burton, T. Doba, E. J. Gabe, L. Hughes, F. L. Lee, L. Prasad, K. U. Ingold, J. Am. Chem. Soc. 1985, 107, 7053-7065;
9. b) G. W. Burton, K. U. Ingold, Acc. Chem. Res. 1986, 19, 194-201.
10. J. S. Wright, E. R. Johnson, G. A. DiLabio, J. Am. Chem. Soc. 2001, 123, 1173-1183.
11. See for example: J. Alanko, A. Riutta, P. Holm, I. Mucha, H. Vapaatalo, T. Metsa-Ketela, Free. Radical Biol. Med. 1999, 26, 193-201; M. Manno, C. Ioannides, G. G. Gibson, Toxicol. Lett. 1985, 25, 121-130.
12. See for example: J. Alanko, A. Riutta, P. Holm, I. Mucha, H. Vapaatalo, T. Metsa-Ketela, Free. Radical Biol. Med. 1999, 26, 193-201; M. Manno, C. Ioannides, G. G. Gibson, Toxicol. Lett. 1985, 25, 121-130.
13. J. S. Wright, D. A. Pratt, G. A. DiLabio, T. P. Bender, K. U. Ingold, Cancer Detect. Prev. 1998, 22, 204.
14. M. C. Foti, E. R. Johnson, M. R. Vinqvist, J. S. Wright, L. R. C. Barclay, K. U. Ingold, J. Org. Chem. 2002, 67, 5190-5196.
15. D. A. Pratt, G. A. DiLabio, G. Brigati, G. F. Pedulli, L. Valgimigli, J. Am. Chem. Soc. 2001, 123, 4625-4626.
16. H. Bredereck, F. Effenberger, H. E. Schweizer, Chem. Ber. 1962, 95, 803-809.
17. A. Dornow, H. Hell, Chem. Ber. 1960, 93, 1998-2001.
18. P. C. Unangst, D. T. Connor, C. R. Kostlan, G. P. Shrum, S. R. Miller, G. Kanter, J. Heterocycl. Chem. 1995, 32, 1197-1200; D. T. Connor, C. R. Kostlan, US Pat. 5,177,079, January 5, 1993.
19. P. C. Unangst, D. T. Connor, C. R. Kostlan, G. P. Shrum, S. R. Miller, G. Kanter, J. Heterocycl. Chem. 1995, 32, 1197-1200; D. T. Connor, C. R. Kostlan, US Pat. 5,177,079, January 5, 1993.
20. F. J. Walker, J. L. LaMattina, US Pat. 4, 711, 888 December 8, 1987.
21. F. J. Walker, K. G. Kraus, J. Heterocycl. Chem. 1987, 24, 1485-1486; J. L. LaMattina, C. J. Mularski, Tetrahedron Lett. 1984, 25, 2957-2960.
22. F. J. Walker, K. G. Kraus, J. Heterocycl. Chem. 1987, 24, 1485-1486; J. L. LaMattina, C. J. Mularski, Tetrahedron Lett. 1984, 25, 2957-2960.
23. M. Lucarini, R Pedrielli, G. F. Pedulli, L. Valgimigli, D. Gigmes, P. Tordo, J. Am. Chem. Soc. 1999, 121, 11546-11553.
24. D. Griller, K. U. Ingold, Acc. Chem. Res. 1980, 13, 317-323.
25. M. Newcomb, Tetrahedron 1993, 49, 1151-1176.
26. C. Chatgilialoglu, K. U. Ingold, J. C. Scaiano, J. Am. Chem. Soc. 1981, 103, 7739-7742.
27. a) J. A. Franz, R. D. Barrows, D. M. Camaioni, J. Am. Chem. Soc. 1984,106, 3964-3967;
28. b) A. Burton, K. U. Ingold, J. C. Walton, J. Org. Chem. 1996, 61, 3778-3782.
29. -1 obtained by Fischer and co-workers (M. Weber, H. Fisher, J. Am. Chem. Soc. 1999, 121, 7381-7388), because when the same compound was calibrated with two different clocks, the older value provided a generally better agreement between the neophyl-based measurement and that obtained with 5-hexenyl or 2-methyl-2-(2-naphtyl)-1-propyl radical.
30. R. Leardini, M. Lucarini, G. E Pedulli, L. Valgimigli, J. Org. Chem. 1999, 64, 3726-3730.
31. When the neophyl or 2-methyl-2-(2-naphtyl)-1-propyl radicals were used as radical clocks, very small amounts of side products were observed. Thus, in addition to the expected tert-butylbenzene and isobutylbenzene, or 2-tert-butylnaphtalene and 2-isobutylnaphtalene, that represent the unrearranged and rearranged hydrocarbons of the neophyl and MNP radicals, we also observed 1-phenyl-2-methylpropene or 1-(2-naphtyl)-2-methylpropene as identified on the basis of their mass spectra. These hydrocarbons are know to originate from the disproportionation of the rearranged radical R′.[19b] and as such, the denominator in Equation (18) has been adjusted accordingly.
32. M. J. Kamlet, J.-L. M. Abboud, M. H. Abraham, R. W. Taft, J. Org. Chem. 1983, 48, 2877-2887.
33. The fls values used in the regression were 0.31, 0.45, and 0.55 for acetonitrile, ethyl acetate, and tert-butanol, respectively.
34. D. V. Avila, K. U. Ingold, J. Lusztyk, W. H. Green, D. R. Procopio, J. Am. Chem. Soc. 1995, 117, 2929-2930.
35. L. Valgimigli, J. T. Banks, K. U. Ingold, J. Lusztyk, J. Am. Chem. Soc. 1995, 117, 9966-9971.
36. C. Chatgilialoglu, S. Rossini, Bull. Soc. Chim. Fr. 1988, 298-300.
37. C. Chatgilialoglu, K. U. Ingold, J. Lusztyk, A. S. Narzan, J. C. Scaiano, Organometallics, 1983, 2, 1332-1335.
38. C. K. Ingold, F. R. Shaw, J. Chem. Soc. 1927, 2918-2926.
39. -1 and can therefore be neglected under our experimental conditions. One additional source of error in the competition kinetics relying on the measurement of the loss of starting material both for the compound under investigation and the reference compound arises from side reactions consuming one or both of the competing reactants. Since some of the measurements herein reported were performed with starting concentrations of pyrimidinol comparable to the concentration of radical initiator (di-tert-butylperoxide) and considering the relatively high absorbance of 5-pyrimidinols in the UV spectral region corresponding to the Hg-lamp emission (see Table 7) it is possible that direct photolysis of the pyrimidinol occurs to some extent which would be reflected in an overestimation of their rate of reaction with alkoxyl radicals. We thank a referee for pointing this out. However it should be noted that: 1) when benzene solutions of pyrimidinols 5c-f were irradiated directly in the cavity of an EPR spectrometer in the absence of any radical initiator, incident radiations 50-100 times more intense of those employed in the competition kinetics were necessary to observe EPR signals due to the corresponding aryloxyl radicals (presumably originated by photoionization followed by fast proton transfer), while no signal could be observed for pyrimidinols 5a,b; 2) kinetic measurement performed with different initial amounts of pyrimidinol (leading to a different extent of direct photolysis) afforded almost identical results; 3) kinetic measurements based on this competitive approach were performed under identical experimental conditions on α-tocopherol (for which direct photolysis is a known process and which has an ionization potential lower than all of the pyrimidinols) affording rate constants values very close to those, previously reported (ref. [26]), obtained by laser flash photolysis direct measurements. Direct photolysis of pyrimidinols was therefore judged to be of marginal importance under our experimental conditions.
40. J. A. Howard, in Free Radicals Vol. 2 (Ed.: J. K. Kochi), Wiley, New York, 1973, Chapter 12.
41. a) M. Cipollone, C. Di Palma, G. F. Pedulli, Appl. Magn. Res. 1992, 3, 99-106;
42. b) G. F. Pedulli, M. Lucarini, P. Pedrielli, M. Sagrini, M. Cipollone, Res. Chem. Intermed. 1996, 22, 1-14;
43. c) M. Lucarini, G. F. Pedulli, L. Valgimigli, J. Org. Chem. 1998, 63, 4497-4499.
44. V. M. Darley-Usmar, A. Hersey, L. G. Garland, Biochem. Pharm. 1989, 38, 1465-1469.
45. B. J. Lynch, P. L. Fast. M. Harris, D. G Truhlar, J. Phys. Chem. A 2000, 104, 4811-4815.
46. B. J. Lynch, D. G. Truhlar, J. Phys. Chem. A 2001, 105, 2936-2941.
47. See for instance: K. Vessman, M. Ekström, M. Berglund, C.-M. Andersson, L. Engman, J. Org. Chem., 1995, 60, 4461-4467; D. W. Brown, P. R. Graupner, M. Sainsbury, H. G. Shertzer, Tetrahedron, 1991, 47, 4383-4408.
48. See for instance: K. Vessman, M. Ekström, M. Berglund, C.-M. Andersson, L. Engman, J. Org. Chem., 1995, 60, 4461-4467; D. W. Brown, P. R. Graupner, M. Sainsbury, H. G. Shertzer, Tetrahedron, 1991, 47, 4383-4408.
49. Steric hindrance around the -OH moiety is known to play a major role in decreasing the reactivity of phenolic compounds toward hydrogen abstraction. See references [1]-[3].
50. C. Walling, Free Radicals in Solution, Wiley, New York, 1957; P. Khaushal, P. L. H. Mok, B. P. Roberts, J. Chem. Soc. Perkin Trans. 2, 1990, 1663-1670; F. Minisci, A. Citterio, Adv. Free Radical Chem. 1980, 6, 65-153; "Substituent Effects in Radical Chemistry": NATO ASI Ser. C 1986, 189, whole volume.
51. C. Walling, Free Radicals in Solution, Wiley, New York, 1957; P. Khaushal, P. L. H. Mok, B. P. Roberts, J. Chem. Soc. Perkin Trans. 2, 1990, 1663-1670; F. Minisci, A. Citterio, Adv. Free Radical Chem. 1980, 6, 65-153; "Substituent Effects in Radical Chemistry": NATO ASI Ser. C 1986, 189, whole volume.
52. C. Walling, Free Radicals in Solution, Wiley, New York, 1957; P. Khaushal, P. L. H. Mok, B. P. Roberts, J. Chem. Soc. Perkin Trans. 2, 1990, 1663-1670; F. Minisci, A. Citterio, Adv. Free Radical Chem. 1980, 6, 65-153; "Substituent Effects in Radical Chemistry": NATO ASI Ser. C 1986, 189, whole volume.
53. C. Walling, Free Radicals in Solution, Wiley, New York, 1957; P. Khaushal, P. L. H. Mok, B. P. Roberts, J. Chem. Soc. Perkin Trans. 2, 1990, 1663-1670; F. Minisci, A. Citterio, Adv. Free Radical Chem. 1980, 6, 65-153; "Substituent Effects in Radical Chemistry": NATO ASI Ser. C 1986, 189, whole volume.
54. 2O at 25°C; see: S. F. Mason, J. Chem. Soc. 1958, 674-685; A. E. Castro, P. Pavez, J. G. Santos, J. Org. Chem. 1999, 64, 2310-2313.
55. 2O at 25°C; see: S. F. Mason, J. Chem. Soc. 1958, 674-685; A. E. Castro, P. Pavez, J. G. Santos, J. Org. Chem. 1999, 64, 2310-2313.
56. The use of different radical clocks to time the hydrogen abstraction from the two substrates (5-hexenyl radical for phenol 4b[3] and neophyl radical for pyrimidinol 5d) is expected it give only a minor contribution (if any) to the observed difference in activation energy, since they give rise to the formation of C-H bonds or approximately equal BDE (about 98 kcalmol-1 by Benson's rule, see S. W. Benson, Thermochemical Kinetics, Wiley, New York, 1976) and contributing approximately the same "triplet repulsion" term (see A. A. Zavitsas, C. Chatgilialiglu, J. Am. Chem. Soc. 1995, 117, 10645-10654).
57. The use of different radical clocks to time the hydrogen abstraction from the two substrates (5-hexenyl radical for phenol 4b[3] and neophyl radical for pyrimidinol 5d) is expected it give only a minor contribution (if any) to the observed difference in activation energy, since they give rise to the formation of C-H bonds or approximately equal BDE (about 98 kcalmol-1 by Benson's rule, see S. W. Benson, Thermochemical Kinetics, Wiley, New York, 1976) and contributing approximately the same "triplet repulsion" term (see A. A. Zavitsas, C. Chatgilialiglu, J. Am. Chem. Soc. 1995, 117, 10645-10654).
58. F. J. Walker, US Pat. 5,001,136 March 19, 1991.
59. See for instance: J. A. Badway, M. L. Karnovsky, Ann. Rev. Biochem. 1980, 49, 695-726; B. Halliwell, Am. J. Med. 1991, 91, 145-225; M. Valgimigli, L. Valgimigli, D. Trere, S. Gaiani, G. F. Pedulli, L. Gramantieri, L. Bolondi, Free. Radical. Res. 2002, 36, 939-948.
60. See for instance: J. A. Badway, M. L. Karnovsky, Ann. Rev. Biochem. 1980, 49, 695-726; B. Halliwell, Am. J. Med. 1991, 91, 145-225; M. Valgimigli, L. Valgimigli, D. Trere, S. Gaiani, G. F. Pedulli, L. Gramantieri, L. Bolondi, Free. Radical. Res. 2002, 36, 939-948.
61. See for instance: J. A. Badway, M. L. Karnovsky, Ann. Rev. Biochem. 1980, 49, 695-726; B. Halliwell, Am. J. Med. 1991, 91, 145-225; M. Valgimigli, L. Valgimigli, D. Trere, S. Gaiani, G. F. Pedulli, L. Gramantieri, L. Bolondi, Free. Radical. Res. 2002, 36, 939-948.
62. A. H. Fainberg, S. Winstein, J. Am. Chem. Soc. 1956, 78, 2763-2767.
63. H. Bredereck, R. Gommpper, H. Herling, Chem. Ber. 1958, 91, 2832-2849.
64. C. W. Shoppee, D. Stevenson, J. Chem. Soc. Perkin Trans. 1, 1972, 3015-3020.
65. D. Barillier, Phosphorus Sulfur Relat. Elem 1978, 5, 251-254.
66. G. A. DiLabio, D. A. Pratt, A. D. LoFaro, J. S. Wright, J. Phys. Chem. A 1999, 103, 1653-1661.
67. a) G. A. DiLabio, D. A. Pratt, J. S. Wright, Chem. Phys. Lett. 1999, 311, 215-220;
68. b) G. A. DiLabio, D. A. Pratt, J. S. Wright, J. Org. Chem. 2000, 65, 2195-2203.
69. A. D. Becke, J. Chem. Phys. 1993, 98, 5648-5652; C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785-789.
70. A. D. Becke, J. Chem. Phys. 1993, 98, 5648-5652; C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785-789.
71. A. P. Scott, L. Radom, J. Phys. Chem. 1996, 100, 16502-16513.
72. P. Y. Alaya, H. B. Schlegel, J. Chem. Phys. 1997, 107, 375-384.
73. Gaussian 98 (Revision A.7), M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montgomery, 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, 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, C. Gonzalez, M. Challacombe, P. M. W. Gill, B. G. Johnson, W. Chen, M. W Wong, J. L. Andres, M. Head-Gordon, E. S. Replogle, J. A. Pople, Gaussian, Inc., Pittsburgh, PA, 1998.