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Mechanism and kinetics of the hydroxyl and hydroperoxyl radical scavenging activity of N-acetylcysteine amide

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Abstract

The ·OH and ·OOH radical scavenging activity of N-acetylcysteine amide (NACA) has been studied using density functional theory, specifically the M05-2X functional. All possible reaction sites have been considered, and the branching ratios have been estimated. The efficiency of different mechanisms of reaction has been evaluated, and it has been concluded that NACA reacts exclusively by hydrogen atom transfer (HAT). The overall reactivity of NACA toward OH radicals is proposed to be diffusion-controlled in both non-polar and polar media. The values of the overall rate coefficients are 3.80 × 109 and 1.36 × 109 L mol−1 s−1 for benzene and aqueous solutions, respectively. The reactivity of NACA toward ·OOH, on the other hand, is much lower but still higher than those of melatonin and caffeine. HAT from the –SH site is proposed to be the channel accounting for most of the radical scavenging activity of NACA in aqueous solution. In non-polar environments, two channels of reaction were found to similarly contribute to the overall reactivity of NACA toward OH radicals. They are those corresponding to hydrogen atom transfer from –CH2 and –SH sites.

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References

  1. Grinberg L, Fibach E, Amer J, Atlas D (2005) Free Radic Biol Med 38:136

    Article  CAS  Google Scholar 

  2. Penugonda S, Mare S, Goldstein G, Banks WA, Ercal N (2005) Brain Res 1056:132

    Article  CAS  Google Scholar 

  3. Price TO, Uras F, Banks WA, Ercal N (2006) Exp Neurol 201:193

    Article  CAS  Google Scholar 

  4. Wu W, Abraham L, Ogony J, Matthews R, Goldstein G, Ercal N (2008) Life Sci 82:1122

    Article  CAS  Google Scholar 

  5. Zhang X, Banerjee A, Banks WA, Ercal N (2009) Brain Res 1275:87

    Article  CAS  Google Scholar 

  6. Banerjee A, Zhang X, Manda KR, Banks WA, Ercal N (2010) Free Radic Biol Med 48:1388

    Article  CAS  Google Scholar 

  7. Sayre LM, Perry G, Smith MA (2008) Chem Res Toxicol 21:172

    Article  Google Scholar 

  8. Lin MT, Beal MF (2006) Nature 443:787

    Article  CAS  Google Scholar 

  9. Reddy PH (2006) J Neurochem 96:1

    Article  CAS  Google Scholar 

  10. Schoeneich C (2005) Biochim Biophys Acta 1703:111

    CAS  Google Scholar 

  11. Giasson BI, Ischiropoulos H, Lee VMY, Trojanowski JQ (2002) Free Radic Biol Med 32:1264

    Article  CAS  Google Scholar 

  12. Aksenov MY, Aksenov MV, Butterfield DA, Geddes JW, Markesbery WR (2001) Neuroscience 163:373

    Article  Google Scholar 

  13. Perry G, Raina AK, Nunomura A, Wataya T, Sayre LM, Smith MA (2000) Free Radic Biol Med 28:831

    Article  CAS  Google Scholar 

  14. Berlett BS, Stadtman ER (1997) J Biol Chem 272:20313

    Article  CAS  Google Scholar 

  15. Penugonda S, Mare S, Lutz P, Banks WA, Ercal N (2006) Toxicol Appl Pharm 216:197

    Article  CAS  Google Scholar 

  16. Offen D, Gilgun-Sherki Y, Barhum Y, Benhar M, Grinberg L, Reich R, Melamed E, Atlas D (2004) J Neurochem 89:1241

    Article  CAS  Google Scholar 

  17. Scott LE, Orvig C (2009) Chem Rev 109:4885

    Article  CAS  Google Scholar 

  18. Zhao Y, Schultz NE, Truhlar DG (2006) J Chem Theory Comput 2:364

    Article  Google Scholar 

  19. Zavala-Oseguera C, Alvarez-Idaboy JR, Merino G, Galano A (2009) J Phys Chem A 113:13913

    Article  CAS  Google Scholar 

  20. Velez E, Quijano J, Notario R, Pabón E, Murillo J, Leal J, Zapata E, Alarcón G (2009) J Phys Org Chem 22:971

    Article  CAS  Google Scholar 

  21. Vega-Rodriguez A, Alvarez-Idaboy JR (2009) Phys Chem Chem Phys 11:7649

    Article  CAS  Google Scholar 

  22. Galano A, Alvarez-Idaboy JR (2009) Org Lett 11:5114

    Article  CAS  Google Scholar 

  23. Black G, Simmie JM (2010) J Comput Chem 31:1236

    CAS  Google Scholar 

  24. Furuncuoglu T, Ugur I, Degirmenci I, Aviyente V (2010) Macromolecules 43:1823

    Article  CAS  Google Scholar 

  25. Galano A, Macías-Ruvalcaba NA, Campos ONM, Pedraza-Chaverri J (2010) J Phys Chem B 114:6625

    Article  CAS  Google Scholar 

  26. Gao T, Andino JM, Alvarez-Idaboy JR (2010) Phys Chem Chem Phys 12:9830

    Article  CAS  Google Scholar 

  27. Iuga C, Alvarez-Idaboy J R, Vivier-Bunge A (2011) J Phys Chem A (in press). doi:10.1021/jp201517p

  28. Galano A (2011) Phys Chem Chem Phys 13:7147

    Google Scholar 

  29. Pérez-González A, Galano A (2011) J Phys Chem B 115:1306

    Article  Google Scholar 

  30. Leon-Carmona JR, Galano A (2011) J Phys Chem B 115:4538

    Article  CAS  Google Scholar 

  31. Gaussian 09, Revision A.02, Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam NJ, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian Inc., Wallingford

  32. Marenich AV, Cramer CJ, Truhlar DG (2009) J Phys Chem B 113:6378

    Article  CAS  Google Scholar 

  33. Ashcroft RG, Coster HGL, Smith JR (1981) Biochim Biophys Acta 643:191

    Article  CAS  Google Scholar 

  34. Naumann R, Jonczyk A, Kopp R, van Esch J, Ringsdorf H, Knoll W, Graber P (1995) Angew Chem Int Ed Engl 34:2056

    Article  CAS  Google Scholar 

  35. Raguse B, Braach-Maksvytis V, Cornell BA, King LG, Osman PDJ, Pace RJ, Wieczorek L (1998) Langmuir 14:648

    Article  CAS  Google Scholar 

  36. de Heer MI, Mulder P, Korth H–G, Ingold KU, Lusztyk J (2000) J Am Chem Soc 122:2355

    Article  Google Scholar 

  37. Pratt DA, Mills JH, Porter NA (2003) J Am Chem Soc 125:5801

    Article  CAS  Google Scholar 

  38. Gregor W, Grabner G, Adelwohrer C, Rosenau T, Gille L (2005) J Org Chem 70:3472

    Article  CAS  Google Scholar 

  39. Leopoldini M, Marino T, Russo N, Toscano M (2004) J Phys Chem A 108:4916

    Article  CAS  Google Scholar 

  40. Nenadis N, Sigalas MP (2008) J Phys Chem A 112:12196

    Article  CAS  Google Scholar 

  41. Martinez A, Rodriguez-Girones MA, Barbosa A, Costas M (2008) J Phys Chem A 112:9037

    Article  CAS  Google Scholar 

  42. Okuno Y (1997) Chem Eur J 3:210

    Article  Google Scholar 

  43. Benson SW (1982) The foundations of chemical kinetics. Krieger, Malabar

    Google Scholar 

  44. Ardura D, Lopez R, Sordo TL (2005) J Phys Chem B 109:23618

    Article  CAS  Google Scholar 

  45. Alvarez-Idaboy JR, Reyes L, Cruz J (2006) Org Lett 8:1763

    Article  CAS  Google Scholar 

  46. Alvarez-Idaboy JR, Reyes L, Mora-Diez N (2007) Org Biomol Chem 5:3682

    Article  CAS  Google Scholar 

  47. Galano A (2007) J Phys Chem A 111:1677

    Article  CAS  Google Scholar 

  48. Galano A (2008) J Phys Chem C 112:8922

    Article  CAS  Google Scholar 

  49. Galano A, Cruz-Torres A (2008) Org Biomol Chem 6:732

    Article  CAS  Google Scholar 

  50. Galano A, Francisco-Márquez M (2008) Chem Phys 345:87

    Article  CAS  Google Scholar 

  51. Mora-Diez N, Keller S, Alvarez-Idaboy JR (2009) Org Biomol Chem 7:3682

    Article  CAS  Google Scholar 

  52. Eyring H (1935) J Chem Phys 3:107

    Article  CAS  Google Scholar 

  53. Evans MG, Polanyi M (1935) Trans Faraday Soc 31:875

    Article  CAS  Google Scholar 

  54. Truhlar DG, Hase WL, Hynes JT (1983) J Phys Chem 87:2664

    Article  CAS  Google Scholar 

  55. Eckart C (1930) Phys Rev 35:1303

    Article  CAS  Google Scholar 

  56. Collins FC, Kimball GE (1949) J Colloid Sci 4:425

    Article  CAS  Google Scholar 

  57. Smoluchowski M (1917) Z Phys Chem 92:129

    Google Scholar 

  58. Truhlar DG (1985) J Chem Ed 62:104

    Article  CAS  Google Scholar 

  59. Einstein A (1905) Ann Phys Leipzig 17:549

    Article  CAS  Google Scholar 

  60. Stokes GG (1903) Mathematical and physical papers. Cambridge University Press, Cambridge

    Google Scholar 

  61. Galano A, Alvarez-Diduk R, Ramirez-Silva MT, Alarcon-Angeles G, Rojas-Hernandez A (2009) Chem Phys 363:13

    Article  CAS  Google Scholar 

  62. Chiodo SG, Leopoldini M, Russo N, Toscano M (2010) Phys Chem Chem Phys 12:7662

    Article  CAS  Google Scholar 

  63. Leopoldini M, Rondinelli F, Russo N, Toscano M (2010) J Agric Food Chem 58:8862

    Article  CAS  Google Scholar 

  64. Leopoldini M, Russo N, Toscano M (2011) Food Chem 125:288

    Article  CAS  Google Scholar 

  65. Pryor WA (1988) Free Radic Biol Med 4:219

    Article  CAS  Google Scholar 

  66. Draganic IG, Draganic ZD (1971) The radiation chemistry of water. Academic Press, New York

    Google Scholar 

  67. Sies H (1985) Oxygen stress. Academic Press, London

    Google Scholar 

  68. Simic MG, Taylor KA, Ward JF, von Sonntag C (1991) Oxygen radicals in biology and medicine. Plenum Press, New York

    Google Scholar 

  69. Davies KJA (1991) Oxidative damage and repair: chemical, biological and medical aspects. Pergamon Press, New York

    Google Scholar 

  70. Sies H (1991) Oxygen stress-oxidants and anti-oxidants. Academic Press, London

    Google Scholar 

  71. Stadtman ER (1993) Annu Rev Biochem 62:797

    Article  CAS  Google Scholar 

  72. Von Sonntag C (1987) The chemical basis of radiation biology. Taylor and Francis, London

    Google Scholar 

  73. Marnett LJ (1987) Carcinogenesis 8:1365

    Article  CAS  Google Scholar 

  74. Pryor WA (1986) Annu Rev Physiol 48:657

    Article  CAS  Google Scholar 

  75. Koopmans T (1933) Physica 1:104

    Article  CAS  Google Scholar 

  76. Linderberg J, Öhrn Y (2004) Propagators in quantum chemistry, 2nd edn. Wiley-Interscience, Hoboken

    Book  Google Scholar 

  77. von Niessen W, Schirmer J, Cederbaum LS (1984) Comput Phys Rep 1:57

    Article  Google Scholar 

  78. Herman MF, Freed KF, Yeager DL (1981) Adv Chem Phys 48:1

    Article  CAS  Google Scholar 

  79. Ortiz JV (1999) Adv Quantum Chem 35:33

    Article  CAS  Google Scholar 

  80. Zakrzewski VG, Ortiz JV (1994) Int J Quantum Chem 28:23

    Article  CAS  Google Scholar 

  81. Zakrzewski VG, Ortiz JV (1995) Int J Quantum Chem 53:583

    Article  CAS  Google Scholar 

  82. Zakrzewski VG, Ortiz JV, Nichols JA, Heryadi D, Yeager DL, Golab JT (1996) Int J Quantum Chem 60:29

    Article  Google Scholar 

  83. Ortiz JV (1996) J Chem Phys 104:7599

    Article  CAS  Google Scholar 

  84. Ferreira AM, Seabra G, Dolgounitcheva O, Zakrzewski VG, Ortiz JV (2001) In: J Cioslowski (ed) Quantum-mechanical prediction of thermochemical data, vol 131. Kluwer, Dordrecht

  85. Zakjevskii VV, King SJ, Dolgounitcheva O, Zakrzewski VG, Ortiz JV (2006) J Am Chem Soc 128:13350

    Article  CAS  Google Scholar 

  86. Zakjevskii VV, Dolgounitcheva O, Zakrzewski VG, Ortiz JV (2007) Int J Quantum Chem 107:2266

    Article  CAS  Google Scholar 

  87. Flores-Moreno R, Ortiz JV (2009) J Chem Phys 131:124110

    Article  Google Scholar 

  88. Mayer JM (2004) Annu Rev Phys Chem 55:363

    Article  CAS  Google Scholar 

  89. Mayer JM, Hrovat DA, Thomas JL, Borden WT (2002) J Am Chem Soc 124:11142

    Article  CAS  Google Scholar 

  90. Young D (2001) Computational chemistry: a practical guide for applying techniques to real world problems. Wiley, New York, pp 227–228

    Google Scholar 

  91. Allodi MA, Kirschner KN, Shields GC (2008) J Phys Chem A 112:7064

    Article  CAS  Google Scholar 

  92. Galano A, Francisco-Márquez M (2009) J Phys Chem B 113:16077

    Article  CAS  Google Scholar 

  93. Galano A, Francisco-Márquez M (2009) J Phys Chem B 113:11338

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The author thanks Laboratorio de Visualización y Cómputo Paralelo at UAM—Iztapalapa for the access to its computer facilities.

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  1. Departamento de Química, División de Ciencias Básicas e Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, Av San Rafael Atlixco No.186, Col., 09340, Vicentina, DF, México

    Annia Galano

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Electronic supplementary material: The online version of this article contains supplementary material: the spin-squared values for all the open-shell species, before and after annihilation of the first spin contaminant; as well as their percent errors with respect to the expected value (PDF 59 kb)

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Galano, A. Mechanism and kinetics of the hydroxyl and hydroperoxyl radical scavenging activity of N-acetylcysteine amide. Theor Chem Acc 130, 51–60 (2011). https://doi.org/10.1007/s00214-011-0958-0

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