Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH11043
RESEARCH FRONT
Contents Vol 64(7)

Theoretical Investigations into the Role of Aryl Nitrenium Ions’ Stability on Their Mutagenic Potential

Eun J. Kim A , Anna M. Matuszek A , Bo Yu A and Jóhannes Reynisson A B
+ Author Affiliations
- Author Affiliations

A School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.

B Corresponding author. Email: j.reynisson@auckland.ac.nz

Australian Journal of Chemistry 64(7) 910-915 https://doi.org/10.1071/CH11043
Submitted: 25 January 2011  Accepted: 27 May 2011   Published: 19 July 2011

Abstract

By using Mulliken and Natural Bond Orbital (NBO) methods based on the density functional theory (DFT), partial charges of exocyclic nitrogen atoms were calculated for nitrenium ions formed from 201 known drugs and 50 Ames positive (mutagenic) compounds containing aryl amine and nitro moieties. The statistical difference of the partial charges was analysed based on the hypothesis that the mutagens have a more negative charge on their exocyclic nitrogen atom resulting in stable nitrenium ions, and thus a longer lifetime to react selectively with DNA; whereas known drugs are not in general mutagenic and therefore have a relatively more positive partial charge. The nitrenium ions with 1° amine parent compounds did not show a statistical difference between drugs and mutagens based on the Mulliken charges. A slight difference was observed in the NBO data where the drugs have more negative partial charge on their exocyclic nitrogen atoms compared with the mutagens. Interestingly, nitrenium ions with aryl nitro drugs as their parent compounds have more negative charge on the exocyclic nitrogen compared with the other drug classes. Aryl nitro drugs are relatively scarce and are often linked to genotoxicity, which fits with the hypotheses proposed. These results indicate that other physical properties besides the stability of the nitrenium ions are important to determine the mutagenic potential of aryl amine and nitro containing compounds.


References

[1]  D. W. Later, R. A. Pelroy, D. L. Stewart, T. McFall, G. M. Booth, M. L. Lee, M. Tedjamulia, R. N. Castle, Environ. Mutagen. 1984, 6, 497.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXls1Ght70%3D&md5=9f59c3e95b57c4eef9f42040522b3d2eCAS |

[2]  F. F. Kadlubar, F. A. Beland, Polycyclic Hydrocarbons and Carcinogenesis (Ed. R. G. Harvey) 1985, pp. 341–370 (American Chemical Society: Washington, D.C.)

[3]  F. F. Kadlubar, J. A. Miller, E. C. Miller, Cancer Res. 1977, 37, 805.
         | 1:CAS:528:DyaE2sXhs1KiurY%3D&md5=93e3776655c821010b303a0cef98ed52CAS |

[4]  J. C. Sinclair, J. Sandy, R. Delgoda, E. Sim, M. E. M. Noble, Nat. Struct. Biol. 2000, 7, 560.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXkslKntbY%3D&md5=469e85313a08f16861c0d273c654c1c7CAS |

[5]  P. D. Josephy, J. Summerscales, L. S. DeBruin, C. Schlaeger, J. Ho, Biol. Chem. 2002, 383, 977.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xnt1emtLk%3D&md5=0c360c929784db550f26c8627f0c95deCAS |

[6]  V. M. Arlt, M. Stiborova, C. J. Henderson, M. R. Osborne, C. A. Bieler, E. Frei, V. Martinek, B. Spoko, R. Wolf, H. H. Schmeiser, D. H. Phillips, Cancer Res. 2005, 65, 2644.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjtVeqsLw%3D&md5=e743d9d240811b02efcd0b93daa0abcaCAS |

[7]  C. C. Carroll, D. Warnakulasuriyarachchi, M. R. Nokhbeh, I. B. Lambert, Mutat. Res. 2002, 501, 79.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XisV2lu7c%3D&md5=91ffcdf6b66682cc675969593cc654b1CAS |

[8]  P. Boffetta, F. Nyberg, Br. Med. Bull. 2003, 68, 71.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVKru7g%3D&md5=f7c8e8bc83bdb4f31c019741029b9067CAS |

[9]  P. Vineis, F. Forastiere, G. Hoek, M. Lipsett, Int. J. Cancer 2004, 111, 647.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXmvVentbg%3D&md5=3bb63d5fb4bc688b458871c8ffe23e1dCAS |

[10]  V. M. Arlt, Mutagenesis 2005, 20, 399.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtlagur7L&md5=2b7c5afe5c387e46e7750db2b170a8d6CAS |

[11]  V. M. Arlt, H. Glatt, G. Gamboa da Costa, J. Reynisson, T. Takamura-Enya, D. H. Phillips, Toxicol. Sci. 2007, 98, 445.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXosFGjtbw%3D&md5=8fba20401851c8dfb8a4520ff39ff66bCAS |

[12]  M. Novak, S. Rajagopal, Chem. Res. Toxicol. 2002, 15, 1495.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xos1eisb0%3D&md5=fadec147f5ea8fc9aaa2e96d26674bfeCAS |

[13]  T. Nguyen, M. Novak, J. Org. Chem. 2007, 72, 4698.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmtVKmu7o%3D&md5=95f4ed797cdd418cea890a179536d6bbCAS |

[14]  E. Baciocchi, Acta Chem. Scand. 1990, 44, 645.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXlslWitrc%3D&md5=79da52c1849f677eb1c4f4efad2f9a49CAS |

[15]  G. L. Borosky, Chem. Res. Toxicol. 2007, 20, 171.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVensb0%3D&md5=46e2693d845f457a8d07769de9f5499dCAS |

[16]  G. L. Borosky, J. Mol. Graph. Model. 2008, 27, 459.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtlyks7vI&md5=3ae9027845acb741ef4bb396dc2e3476CAS |

[17]  J. Reynisson, M. Stiborová, V. Martínek, G. Gamboa da Costa, D. H. Phillips, V. M. Arlt, Environ. Mol. Mutagen. 2008, 49, 659.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtlWiurnJ&md5=49cee3656b7818262205ca1361a23620CAS |

[18]  J. Bentzien, E. R. Hickey, R. A. Kemper, M. L. Brewer, J. D. Dyekjær, S. P. East, M. Whittaker, J. Chem. Inf. Model. 2010, 50, 274.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlvFWgug%3D%3D&md5=29fb8023f3da222d8ca57f184389f387CAS |

[19]  M. Stiborová, V. Martínek, M. Svobodová, J. Šístková, Z. Dvořák, J. Š. Ulrichová, V. Simánek, E. Frei, H. H. Schmeiser, D. H. Phillips, V. M. Arlt, Chem. Res. Toxicol. 2010, 23, 1192.
         | Crossref | GoogleScholarGoogle Scholar |

[20]  P. Axerio-Cilies, I. P. Castañeda, A. Mirza, J. Reynisson, Eur. J. Med. Chem. 2009, 44, 1128.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXisVOms7g%3D&md5=aa27fdd5423b5bdf00bbed02698c18fcCAS |

[21]  R. Bade, H.-F. Chan, J. Reynisson, Eur. J. Med. Chem. 2010, 45, 5646.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsVGitrbF&md5=3ab81f7afb28af4731a62bbef7bd4995CAS |

[22]  L. Ioakimidis, L. Thoukydidis, S. Naeem, A. Mirza, J. Reynisson, QSAR Comb. Sci. 2008, 27, 445.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmtVWgsbo%3D&md5=1afedfabffaa69cca4a436c1505a833fCAS |

[23]  R. D. Snyder, Environ. Mol. Mutagen. 2009, 50, 435.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXos1ejs7w%3D&md5=bcc4b3c8ea6ae27f7f2eb9605e92758aCAS |

[24]  D. S. Wishart, C. Knox, A. C. Guo, S. Shrivastava, M. Hassanali, P. Stothard, Z. Chang, J. Woolsey, Nuc. Acid. Res. 2006, 34, D668.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XisFOrsw%3D%3D&md5=ca07c7884bc73ecc98750290483999b6CAS |

[25]  D. S. Wishart, C. Knox, A. C. Guo, D. Cheng, S. Shrivastava, D. Tzur, B. Gautam, M. Hassanali, Nuc. Acid. Res. 2008, 36, D901.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVSrs7Y%3D&md5=180476e3dfadb38629e9e870d021511cCAS |

[26]  M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09, Revision A.02. 2009 (Gaussian, Inc.: Wallingford, CT).

[27]  A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXisVWgtrw%3D&md5=ee5af041032bb2825357f4a4a02b5705CAS |

[28]  A. D. Becke, Phys. Rev. A 1988, 38, 3098.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXmtlOhsLo%3D&md5=b1c2dd99cfdac822ac37b382786fa037CAS |

[29]  C. Lee, W. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXktFWrtbw%3D&md5=a29e371e59c32e711fd8b4e5fd53e9a8CAS |

[30]  P. C. Hariharan, J. A. Pople, Theor. Chim. Acta 1973, 28, 213.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE3sXhtFGnsL4%3D&md5=7033e38d7e5762ee40e3580588ab082bCAS |

[31]  M. W. Wong, Chem. Phys. Lett. 1996, 256, 391.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XksFWlsbg%3D&md5=b1e3a67f0e4b813aea858efef5bd847cCAS |

[32]  A. E. Reed, L. A. Curtiss, F. Weinhold, Chem. Rev. 1988, 88, 899.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXmtlOitbw%3D&md5=eaaccf5f075c21e9fca9db4be606b508CAS |

[33]  R. S. Mulliken, J. Chem. Phys. 1962, 36, 3428.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF38Xks1KrtL8%3D&md5=3e1569a18e37834adefab69005214091CAS |

[34]  A. Masunov, J. J. Dannenberg, R. H. Contreras, J. Phys. Chem. A 2001, 105, 4737.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXislSqu74%3D&md5=10f266a73e7032da68a82215d42c570aCAS |

[35]  R. J. Barlow, Statistics A Guide to the Use of Statistical Methods in the Physical Sciences 1989 (John Wiley & Sons: Chicester).

[36]  D. Kirkland, M. Aardema, L. Henderson, L. Müller, Mutat. Res. 2005, 584, 1.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlsl2rur8%3D&md5=d7b29229ee492a3710febeb9e8d011baCAS |

[37]  T. Okazaki, K. K. Laali, B. Zajc, M. K. Lakshman, S. Kumar, W. M. Baird, W.-M. Dashwood, Org. Biomol. Chem. 2003, 1, 1509.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXkvFSns7s%3D&md5=0003d9b27e76ca12ec74c13d20f6984bCAS |

[38]  T. Okazaki, K. K. Laali, Org. Biomol. Chem. 2003, 1, 3078.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXms12gsLs%3D&md5=1120ae1711cee56a161cb8cd106bada5CAS |

[39]  J. Reynisson, G. Balakrishnan, R. Wilbrandt, N. Harrit, J. Mol. Struct. 2000, 520, 63.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXhsFensrY%3D&md5=b16343d30878dfe0b8091902eb9eeb3bCAS |

[40]  K. K. Laali, T. Okazaki, S. Kumar, S. E. Galembeck, J. Org. Chem. 2001, 66, 780.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjvFaiuw%3D%3D&md5=2ddb821bac06ea238f6e15e757a28730CAS |

[41]  T. Okazaki, K. K. Laali, J. Org. Chem. 2004, 69, 510.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhtVWitL3J&md5=ff05ee63a4d4bc53a38a7b6e8a230576CAS |

[42]  P. Cysewski, J. Mol. Struct. THEOCHEM 2005, 714, 29.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmtlSitw%3D%3D&md5=d37736dadc3cea7db0063fbbf752cc12CAS |

[43]  A. Mirza, R. Desai, J. Reynisson, Eur. J. Med. Chem. 2009, 44, 5006.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVCksLnJ&md5=5e0a5ef2ba0cecfaea6c74142ff02e3bCAS |

[44]  J. McCann, E. Choi, E. Yamasaki, B. N. Ames, Proc. Natl. Acad. Sci. USA 1975, 72, 5135.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE28XosFegtg%3D%3D&md5=02b483b4329919f723c0a81bea40f982CAS |

[45]  The Carcinogenic Potency Database (CPDB) http://potency.berkeley.edu/.

[46]  A. Thayer, C&EN. 2010, Sep.27, 16.