The L-type calcium channel blockers, Hantzsch 1,4-dihydropyridines, are not peroxyl radical-trapping, chain-breaking antioxidants

Chemical Research in Toxicology

Volumn 19, Issue 1, 2006, Pages 79-85

  Mulder, Peter ^a   Litwinienko, Grzegorz ^b   Lin, Shuqiong ^c   MacLean, Patricia D ^d   Barclay, L R C ^d   Ingold, K U ^c  

^a LEIDEN UNIVERSITY   (Netherlands)

^b UNIVERSITY OF WARSAW   (Poland)

^c NATIONAL RESEARCH COUNCIL CANADA   (Canada)

^d MOUNT ALLISON UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

1,1 DIPHENYL 2 PICRYLHYDRAZYL; 1,4 DIHYDROPYRIDINE; 5,6 DIHYDROAZACITIDINE; 6 HYDROXY 2,2,5,7,8 PENTAMETHYLCHROMAN; ACRIDAN; ACRIDINE DERIVATIVE; ANTIOXIDANT; CALCIUM CHANNEL BLOCKING AGENT; CALCIUM CHANNEL L TYPE; CALCIUM CHANNEL L TYPE BLOCKING AGENT; CHAIN BREAKING ANTIOXIDANT; CUMENE; DIBENZO 1,4 DIHYDROPYRIDINE DERIVATIVE; DIHYDROPYRIDINE DERIVATIVE; LACIDIPINE; N DEUTERIO 5,6 DIHYDROAZACITIDINE; N METHYL 5,6 DIHYDROAZACITIDINE; N METHYL 9,10 DIHYDROACRIDINE; NICARDIPINE; PEROXY RADICAL; PROBUCOL; STYRENE; TROLOX C; UNCLASSIFIED DRUG;

ANTIOXIDANT ACTIVITY; ARTICLE; CALCIUM BINDING; CARBON HYDROGEN BOND DISSOCIATION ENTHALPY; DISSOCIATION; ENTHALPY; HYDROGEN BOND; NONHUMAN; REACTION ANALYSIS; REACTION OPTIMIZATION;

ACRIDINES; ANTIOXIDANTS; BENZENE DERIVATIVES; BIPHENYL COMPOUNDS; CALCIUM CHANNEL BLOCKERS; CALCIUM CHANNELS, L-TYPE; CHROMANS; DIHYDROPYRIDINES; FREE RADICALS; HYDRAZINES; KINETICS; NIFEDIPINE; NIMODIPINE; OXIDATION-REDUCTION; PEROXIDES; STYRENE;

EID: 31844441727     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx0502591     Document Type: Article

References (74)

1. Godfraind, T. (1987) Classification of calcium antagonists. Am. J. Cardiol. 59, 11B-23B.
2. McCord, J. M. (1985) Oxygen-derived free radicals in postischemic tissue injury. N. Engl. J. Med. 312, 159-163.
3. Cantoni, O., Sestili, P., Cattabeni, F., Bellomo, G., Pou, S., Cohen, M., and Cerutti, P. (1989) Calcium chelator Quin 2 prevents hydrogen-peroxide- induced DNA breakage and cytotoxicity. Eur. J. Biochem. 182, 209-212.
4. (a) Mak, I. T., and Weglicki, W. B. (1990) Comparative antioxidant activities of propranolol, nifedipine, verapamil, and diltiazem against sarcolemmal membrane lipid peroxidation. Circ. Res. 66, 1449-1452.
5. (b) Mason, R. P., Mak, I. T., Trumbore, M. W., and Mason, P. E. (1999) Antioxidant properties of calcium antagonists related to membrane biophysical interactions. Am. J. Cardiol. 84, 161-221.
6. (c) Diaz-Araya, G., Godoy, L., Naranjo, L., Squella, J. A., Letelier, M. E., and Núñez-Vergara, L. J. (1998) Antioxidant effects of 1,4-dihydropyridine and nitroso aryl derivatives on the Fe+3/ascorbate- stimulated lipid peroxidation in rat brain slices. Gen. Pharmacol. 31, 385-391.
7. Aruoma, O. I., Smith, C, Cecchini, R., Evans, P. J., and Halliwell, B. (1991) Free radical scavenging and inhibition of lipid peroxidation by beta-blockers and by agents that interfere with calcium metabolism. A physiologically significant process? Biochem. Pharmocol. 42, 735-743.
8. (a) Lupo, E., Locher, R., Weisser, B., and Velter, W. (1994) In vitro antioxidant activity of calcium antagonists against LDL oxidation compared with alpha-tocopherol. Biochem. Biophys. Rex. Commun. 203, 1803-1808.
9. (b) Napoli, C, Chiariello, M., Palumbo, G., and Ambrosio, G. (1996) Calcium-channel blockers inhibit human low-density lipoprotein oxidation by oxygen radicals. Cardiovasc. Drugs Ther. 10, 417-424.
10. (c) Sobal, G., Menzel, E. J., and Sinzinger, H. (2001) Calcium antagonists as inhibitors of in vitro low-density lipoprotein oxidation and glycation. Biochem. Pharmacol. 61, 373-379.
11. Velena, A., Zilbers, J., and Dubers, G. (1999) Derivatives of 1,4-dihydropyridines as modulators of ascorbate-induced lipid peroxidation and high-amplitude swelling of mitochondria, caused by ascorbate, sodium linoleate and sodium pyrophosphate. Cell Biochem. Fund. 17, 237-252.
12. (a) Mak, I. T., Boheme, P., and Weglicki, W. B. (1992) Antioxidant effects of calcium channel blockers against free radical injury in endothelial cells. Correlation of protection with preservation of glutathione levels. Circ. Res. 70, 1099-1103.
13. (b) Mak, I. T., Boheme, P., and Weglicki, W. B. (1995) Protective effects of calcium channel blockers against free radical-impaired endothelial cell proliferation. Biochem. Pharmacol. 50, 1531-1534.
14. (a) Ingold, K. U. (1961) Inhibition of the autoxidation of organic substances in the liquid phase. Chem. Rev. 61, 563-589.
15. (b) Antunes, F., Barclay, L. R. C., Ingold, K. U., King, M., Norris, J. Q., Scaiano, J. C., and Xi, F. (1999) On the antioxidant activity of melatonin. Free Radical Biol. Med. 26, 117- 128. For further discussions of antioxidant mechanisms,
16. see also (c) Fowler, G., Daroszewska, M., and Ingold, K. U. (2003) Melatonin does not "directly scavenge hydrogen peroxide": Demise of another myth. Free Radical Biol. Med. 34, 77-83.
17. Mojumdar, S. C., Becker, D. A., DiLabio, G. A., Ley, J. J., Barclay, L. R. C., and Ingold, K. U. (2004) Kinetic studies on stilbazulenyl-bis-nitrone (STAZN), a nonphenolic chain-breaking antioxidant in solution, micelles, and lipid membranes. J. Org. Chem. 69, 2929-2936.
18. Mulder, P., Korth, H.-G., and Ingold, K. U. (2005) Why quantum chemical calculations must be used with caution to indicate 'a promising lead antioxidant'. Helv. Chim. Acta 88, 370-374.
19. (a) Van Amsterdam, F. T. M., Roveri, A., Maiorino, M., Ratti, E., and Ursini, F. (1992) Lacidipine: A dihydropyridine calcium antagonist with antioxidant activity. Free Radical Biol. Med. 12, 183-187.
20. See also (b) Toniolo, R., DiNarda, F., Bontempelli, G., and Ursini, F. (2000) An electroanalytical investigation on the redox properties of lacidipine supporting its anti-oxidant effect. Bioelectrochemistrt 51. 193-200.
21. López-Alarcón, C., Navarrete, P., Camargo, C., Squella, J. A., and Núñez-Vergara, L. J. (2003) Reactivity of 1,4-dihydropyridines toward alkyl, alkylperoxyl radicals, and ABTS radical cation. Chem. Res. Toxicol. 16, 208-215.
22. Bors, W., Crista, M., and Saran, M. (1984) Inhibition of the bleaching of the carotenoid crocin a rapid test for quantifying antioxidant activity. Biochim. Biophys. Acta 796, 312-319.
23. Paul, T., Young, M. J., Hill, I. E., and Ingold, K. U. (2000) Strand cleavage of supercoiled DNA by water-soluble peroxyl radicals. The overlooked importance of peroxyl radical charge. Biochemistry 39, 4129-4135.
24. Bedard, L., Young, M. J., Hall, D., Paul, T., and Ingold, K. U. (2001) Quantitative studies on the peroxidation of human low-density lipoprotein initiated by Superoxide and by charged and neutral alkylperoxyl radicals. J. Am. Chem. Soc. 123, 12439-12448.
25. Sanchez, C., Shane, R. A., Paul, T., and Ingold, K. U. (2003) Oxidative damage to a supercoiled DNA by water soluble peroxyl radicals characterized with DNA repair enzymes. Chem. Res. Toxicol. 16, 1118-1123 and references therein.
26. Barclay, L. R. C. (1988) The cooperative antioxidant role of glutathione with lipid-soluble and water-soluble antioxidants during peroxidation of liposomes initiated in the aqueous phase and in the lipid phase. J. Biol. Chem. 263, 16138-16142.
27. Barclay, L. R. C., Locke, S. J., MacNeil, J. M., VanKessel, J., Burton, G. W., and Ingold, K. U. (1984) Autoxidation of micelles and model membranes. Quantitative kinetic measurements can be made by using either water-soluble or lipid-soluble initiators with water-soluble or lipid-soluble chain-breaking antioxidants. J. Am. Chem. Soc. 106, 2479-2481.
28. See. for example, (a) Boozer, C. E., Hammond, G. S., Hamilton, C. E., and Sen, J. N. (1955) Air oxidation of hydrocarbons. II. The stoichiometry and fate of inhibitors in benzene and chlorobenzene. J. Am. Chem. Soc. 77, 3233-3237.
29. (b) Horswill, E. C., Howard, J. A., and Ingold, K. U. (1966) The oxidation of phenols. III The stoichiometries for the oxidation of some substituted phenols with peroxy radicals. Can. J. Chem. 44, 985-991.
30. Burton, G. W., and Ingold, K. U. (1981) Autoxidation of biological molecules. I. Antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro. J. Am. Chem. Soc. 103, 6472-6477.
31. (a) Núñez-Vergara, L. J., López-Alarcón, C., Navarreta-Encina, P. A., Atria, A. M., Camargo, C., and Squella, J. A. (2003) Electrochemical and EPR characterization of 1,4-dihydropyridines. Reactivity towards alkyl radicals. Free Radical Res. 37, 109-120.
32. (b) López-Alarcón, C., Spieski, H., Squella, J. A., Olea-Azar, C., Camargo, C., and Núñez-Vergara, L. J. (2004) Reactivity of 1,4-dihydropyridines toward SIN-1-derived peroxynitrite. Pharm. Res. 21, 1750-1757.
33. (c) Yáñez, C., López-Alarcón, C., Camargo, C., Valenzuela, V., Sugelaa, J. A., and Núñez-Vergara, L. J. (2004) Structural effects on the reactivity 1,4-dihydropyridines with alkylperoxyl radicals and ABTS radical cation. Bioorg. Med. Chem. 12, 2459-2468.
34. Howard, J. A., and Ingold, K. U. (1962) The inhibited autoxidation of styrene. Part I. The deuterium isotope effect for inhibition by 2,6-di-tert-butyl-4-methylphenol. Can. J. Chem. 40, 1851-1864.
35. See, e.g., rets 9b.d and 19c. (a) Landolt-Bornstein (1984) New Series: Radical Reaction Rates in Liquids. Vol. 13d, Springer-Verlag, Berlin.
36. (b) Landolt-Bornstein (1997) New Series: Radical Reaction Rales in Liquids, Vol. 18D2, Springer-Verlag, Berlin.
37. Valgimigli, L., Banks, J. T., Ingold, K. U., and Lusztyk, J. (1995) Kinetic solvent effects on hydroxylic hydrogen atom abstractions are independent of the nature of the abstracting radical. Two extreme tests using vitamin E and phenol. J. Am. Chem. Soc. 117, 9966-9971.
38. Valgimigli, L., Banks, J. T., Lusztyk, J., and Ingold, K. U. (1999) Solvent effects on the antioxidant activity of vitamin E. J. Org. Chem. 64, 3381-3383.
39. .) in alcohols. J. Org. Chem. 68, 3433-3438.
40. (b) Litwinienko, G., and Ingold, K. U. (2004) Abnormal solvent effects on hydrogen atom abstraction. 2. Resolution of the curcumin antioxidant controversy. The role of sequential proton loss electron transfer. J. Org. Chem. 69, 5888-5896.
41. Litwinienko, G., and Ingold, K, U. (2005) Abnormal solvent effects on hydrogen atom abstraction. 3. Novel kinetics in sequential proton loss electron transfer (SPLET) chemistry, J. Org. Chem. 70, 8982-8990.
42. Mulder, P., Korth, H.-G., Litwinienko, G., DiLabio, G. A., Barclay, L. R. C., and Ingold, K. U. (2005) Hydrogen atom transfer involving C-H, N-H and O-H bonds. Experment and theory. Manuscript in preparation.
43. Howard, J. A., and Ingold, K. U. (1965) Absolute rate constants for hydrocarbon autoxidation, I. Styrene. Can. J. Chem. 43, 2729-2736.
44. Howard, J. A. (1997). In Peroxyl Radicals (Alfassi, Z. B., Ed.) Chapter 10, John Wiley, Chichester. United Kingdom.
45. Burton, G. W., Doha, T., Gabe, E. J., Hughes, L., Lee, F. L., Prasad, L., and Ingold, K. U. (1985) Autoxidation of biological molecules. 4. Maximizing the antioxidant activity of phenols. J. Am. Chem. Soc. 107, 7053-7065.
46. (a) Pratt, D. A., DiLabio, G. A., Brigati, G., Pedulli, G. F., and Valgimigli, L. (2001) 5-Pyrimidinols: Novel chain-breaking antioxidants more effective than phenols. J. Am. Chem. Soc. 123, 4625-4626.
47. (b) Wijtmans, M., Pratt, D. A., Valgimigli, L., DiLabio, G. A., Pedulli, G. F., and Porter, N. A. (2003) 6-Amino-3-pyridinols: Towards diffusion-controlled chain-breaking antioxidants. Angew. Chem., Int. Ed. 42, 4370-4373.
48. (c) Wijtmans, M., Pratt, D. A., Brinkhorst, J., Serwa, R., Valgimigli, L., Pedulli, G. F., and Porter, N. A. (2004) Synthesis and reactivity of some 6-substituted-2,4-dimethyl-3-pyridinols, a novel class of chain-breaking antioxidants. J. Org. Chem. 69, 9215-9223.
49. (d) Barclay, L. R. C., Vinqvist, M. R., Mukai, K., Itoh, S., and Morimoto, H. (1993) Chain-breaking phenolic antioxidants: Steric and electronic effects in polyalkylchromanols, toeopherol analogues, hydroquinones, and superior antioxidants of the polyalkylbenzochromanol and naphthofuran class. J. Org. Chem. 58, 7416-7420.
50. Howard, J. A., and Ingold, K. U. (1967) Absolute rate constants for hydrocarbon autoxidation. VI. Alkyl aromatic and olefinic hydrocarbons. Can. J. Chem. 45, 793-802.
51. Abraham, M. H., Grellier, P. L., Prior, D. V., Duce, P. P., Morris, J. J., and Taylor, P. J. (1989) Hydrogen bonding. Part 7. A scale of solute hydrogen-bond acidity based on log K values for complexation in tetrachloromethane. J. Chem. Soc., Perkins Trans. 2, 699-711.
52. Bordwell, F. G., Zhang, X.-M., and Cheng, J.-P. (1993) Bond dissociation energies of the N-H bonds in anilines and the corresponding radical anions. Equilibrium acidities of aniline radical cations. J. Org. Chem. 58, 6410-6416.
53. Cheng, J.-P., Lu, Y., Zhu, X.-Q., Sun, Y., Bi, F., and He, J.-Q. (2000) Heterolytic and homolytic N-H bond dissociation energies of 4-substituted Hantzsch 2,6-dimethyl-1,4-dihydropyridines and the effect of one-electron transfer on the N-H bond activation. J. Org. Chem. 65, 3853-3857.
54. Snelgrove, D. W., Lusztyk, J., Banks, J. T., Mulder, P., and Ingold. K. U. (2001) Kinetic solvent effects on hydrogen-atom abstractions: Reliable, quantitative predictions via a single empirical equation. J. Am. Chem. Soc. 123, 469-477.
55. Abraham, M. H., Grellier, P. L., Prior, D. V., Morris, J. J., and Taylor, P. J. (1990) Hydrogen bonding. Part 10. A scale of solute hydrogen-bond basicity using log K values for complexation in tetrachloromethane. J. Chem. Soc., Perkin Trans. 2, 521-529.
56. Pratt, D. A., DiLabio, G. A., Mulder, P., and Ingold, K. U. (2004) Bond strengths in toluene, anilines and phenols. Acc. Chem. Res. 37, 334-340.
57. Mayer, J. M. (2004) Proton-coupled electron transfer: A reaction chemist's view. Annu. Rev. Phys. Chem. 55, 363-390.
58. (a) Zavitsas, A. A. (1972) Activation energy requirements in hydrogen abstractions. Quantitative description of the causes in terms of bond energies and infrared frequencies. J. Am. Chem. Soc. 94, 2779-2789.
59. See also Zavitsas, A. A., and Chatgilialoglu, C. (1995) Energies of activation. The paradigm of hydrogen abstractions by radicals, J. Am. Chem. Soc. 117, 10645-10654.
60. 3): A valence bond modeling". J. Phys. Chem. A 106, 5041-5042.
61. 3): A valence bond modeling". J. Phys. Chem. A 106, 5043-5045.
62. See, for example, (a) Mayer, J. M., Hrovat, D. A., Thomas, J. L., and Borden, W. T. (2002) Proton-coupled electron transfer versus hydrogen atom transfer in benzyl/toluene, methoxyl/methanol, and phenoxyl/ phenol self-exchange reactions. J. Am. Chem. Soc. 124, 11142- 11147.
63. (b) Rhile, I. J., and Mayer, J. M. (2004) One-electron oxidation of a hydrogen-bonded phenol occurs by concerted proton-coupled electron transfer. J. Am. Chem. Soc. 126, 12718-12719.
64. Baciocchi, E., Gerini, M. F., and Lanzalunga, O. (2004) Reactivity of phthalimide N-oxyl radical (PINO) toward the phenolic O-H bond. A kinetic study. J. Org. Chem. 69, 8963-8966.
65. DiLabio, G. A., and Ingold, K. U. (2005) A theoretical study of the iminoxyl/oxime self-exchange reaction. A five-center, cyclic proton-coupled electron transfer. J. Am. Chem. Soc. 127, 6693-6699.
66. (a) Russell, G. A. (1956) The rates of oxidation of aralkyl hydrocarbons. Polar effects in free radical reactions. J. Am. Chem. Soc. 78, 1047-1054.
67. (b) Hendry, D. G., and Russell, G. A. (1964) Retarding effects of polyarylmethanes in autoxidation reactions. J. Am. Chem. Soc. 86, 2371-2374.
68. (c) Howard, J. A., and Ingold, K. U. (1968) Absolute rate constants for hydrocarbon oxidation. XI. The reactions of tertiary peroxy radicals. Can. J. Chem. 46, 2655-2660.
69. Burton, G. W., and Ingold, K. U. (1984) Beta-carotene: An unusual type of lipid antioxidant. Science 224, 569-573.
70. (e) Scaiano, J. C., Martin, A., Yap, G. P. A., and Ingold, K. U. (2000) A carbon-centered radical unreactive toward oxygen: Unusual radical stabilization by a lactone ring. Org. Lett. 2, 899-901.
71. (f) Bejan, E. V., Font-Sanchis, E., and Scaiano, J. C. (2001) Lactone-derived carbon-centered radicals: Formation and reactivity with oxygen. Org. Lett. 3, 4059-4062.
72. (g) Aliaga, C., Stuart, D. R., Aspee, A., and Scaiano, J. C. (2005) Solvent effects on hydrogen abstraction reactions from lactones with antioxidant properties. Org. Lett. 7, 3665-3668.
73. Manring, L. E., and Peters, K. S. (1983) Picosecond observation of kinetic vs thermodynamic hydrogen atom transfer. J. Am. Chem. Soc. 105, 5708-5709.
74. Wayner, D. D. M., and Burton, G. W. (1989) The measurement of radical-trapping antioxidants and antioxidant activity in blood plasma. Handbook of Antioxidants in Biomedicine. Vol. 3. pp 223-232, CRC Press, Boca Raton, FL.