메뉴 건너뛰기




Volumn 14, Issue 28, 2008, Pages 8640-8651

A simple and efficient strategy to enhance the antioxidant activities of amino-substituted glutathione peroxidase mimics

Author keywords

Antioxidant activity; GPx mimics; Noncovalent interactions; Selenium; Selenoenzymes

Indexed keywords

AMINATION;

EID: 53849112342     PISSN: 09476539     EISSN: 15213765     Source Type: Journal    
DOI: 10.1002/chem.200800963     Document Type: Article
Times cited : (112)

References (85)
  • 7
    • 0042314356 scopus 로고    scopus 로고
    • Angew. Chem. Int. Ed. 2003, 42, 4742-4758;
    • (2003) Angew. Chem. Int. Ed , vol.42 , pp. 4742-4758
  • 10
    • 0000751243 scopus 로고
    • b) H. Sies, Angew. Chem. 1986, 98, 1061-1075:
    • (1986) Angew. Chem , vol.98 , pp. 1061-1075
    • Sies, H.1
  • 22
    • 0001329534 scopus 로고    scopus 로고
    • d) T. Wirth, Molecules, 1998, 3, 164-166;
    • (1998) Molecules , vol.3 , pp. 164-166
    • Wirth, T.1
  • 26
    • 4544323685 scopus 로고    scopus 로고
    • Angew. Chem. Int. Ed. 2004, 43, 4513-4515;
    • (2004) Angew. Chem. Int. Ed , vol.43 , pp. 4513-4515
  • 33
    • 4544308709 scopus 로고    scopus 로고
    • Angew. Chem. Int. Ed. 2004, 43, 1268-1270;
    • (2004) Angew. Chem. Int. Ed , vol.43 , pp. 1268-1270
  • 38
    • 0029787936 scopus 로고    scopus 로고
    • For more details on Se⋯X (X = O, N. F, Cl, Br, I. etc.) interactions, see a) M. Iwaoka, S. Tomoda, J. Am. Chem. Soc. 1996, 118, 8077-8084;
    • For more details on Se⋯X (X = O, N. F, Cl, Br, I. etc.) interactions, see a) M. Iwaoka, S. Tomoda, J. Am. Chem. Soc. 1996, 118, 8077-8084;
  • 52
    • 0000855362 scopus 로고
    • a) T. Wirth, Angew. Chem. 1995, 107, 1872-1873:
    • (1995) Angew. Chem , vol.107 , pp. 1872-1873
    • Wirth, T.1
  • 59
    • 0024473554 scopus 로고    scopus 로고
    • It has been reported that the introduclion of a nitro group at the position ortho to the selenium in ebselen can enhance the GPx activity, mainly through electronic effects (ref, 10a, Further theoretical investigations suggested that the increase in the catalytic activity observed upon introduction of an additional group at the position ortho to the selenium in ebselen may arise from steric factors and not from an electronic effect (ref, 10b, Recently, the introduction of methoxy substituents at the positions para to selenium has been shown to enhance the GPx-like activities of aromatic cyclic seleninate esters (ref, 10c, However, the effects of the additional substituents on the stabilities and reactivities of various catalytically active intermediates are not clear; a) M.J. Parnham, J. Biederman, C. Bittner, N. Dereu, S. Leyck, H. Wetzig, Agents Actions 1989, 27, 306-308;
    • It has been reported that the introduclion of a nitro group at the position ortho to the selenium in ebselen can enhance the GPx activity, mainly through electronic effects (ref. [10a]). Further theoretical investigations suggested that the increase in the catalytic activity observed upon introduction of an additional group at the position ortho to the selenium in ebselen may arise from steric factors and not from an electronic effect (ref. [10b]). Recently, the introduction of methoxy substituents at the positions para to selenium has been shown to enhance the GPx-like activities of aromatic cyclic seleninate esters (ref. [10c]). However, the effects of the additional substituents on the stabilities and reactivities of various catalytically active intermediates are not clear; a) M.J. Parnham, J. Biederman, C. Bittner, N. Dereu, S. Leyck, H. Wetzig, Agents Actions 1989, 27, 306-308;
  • 63
    • 53849086120 scopus 로고    scopus 로고
    • E. D. Glendening, J. E. Reed, J. E. Carpenter, F. Weinhold, Natural Bond Orbital NBO, Version 3.1
    • b) E. D. Glendening, J. E. Reed, J. E. Carpenter, F. Weinhold, Natural Bond Orbital (NBO), Version 3.1.
  • 64
    • 53849132310 scopus 로고    scopus 로고
    • This may lead to an enhancement in the catalytic activity
    • The coordination of the nitrogen to selenium can also be suppressed by using a less nucleophilic tertiary amide group instead of a tertiary amine, G. Mugesh, K. P. Bhabak, unpublished results
    • The coordination of the nitrogen to selenium can also be suppressed by using a less nucleophilic tertiary amide group instead of a tertiary amine. This may lead to an enhancement in the catalytic activity. However, diselenides possessing tertiary amide substituents were found to be inactive due to their extremely poor reactivity toward PhSH. G. Mugesh, K. P. Bhabak, unpublished results.
    • However, diselenides possessing tertiary amide substituents were found to be inactive due to their extremely poor reactivity toward PhSH
  • 65
    • 53849087093 scopus 로고    scopus 로고
    • Although electron-donating substituents such as the methoxy group are expected to increase the positive charge on selenium, the higher stability of the methoxy-substituted zwilterion relative to the unsubslituted compound is probably due to an increase in the basicity of the tertiary amino group. Therefore, the amino groups in compounds 26, 28, and 30 are better bases than the amino substituents in compounds 25, 27, and 29
    • Although electron-donating substituents such as the methoxy group are expected to increase the positive charge on selenium, the higher stability of the methoxy-substituted zwilterion relative to the unsubslituted compound is probably due to an increase in the basicity of the tertiary amino group. Therefore, the amino groups in compounds 26, 28, and 30 are better bases than the amino substituents in compounds 25, 27, and 29.
  • 66
    • 53849120166 scopus 로고    scopus 로고
    • The identification of selenenic and seleninic acids is based on literature data and a number of control experiments. Treatment of the diselenides with H2O2 (5 equiv) produced the selenenic and seleninic acids in the cases of 4, 20, and 21, and only the selenenic acids in the case of 22-24. Treatment of selenols 25-30 with H2O2 produced identical signals in the 77Se NMR. This precludes the possibility of the formation of any thiol esters in the reactions. The reactions of the oxidized species with PhSH are also helpful for assignation of the signals for the selenenic acid and seleninic acid intermediates. While the selenenic acids 38, 40, and 42 required only one equivalent of PhSH each to produce the corresponding selenenyl sulfides quantitatively, higher concentrations of PhSH were required for complete conversions of the oxidized compounds derived from 4, 20, and 21 into the
    • 77Se NMR. This precludes the possibility of the formation of any thiol esters in the reactions. The reactions of the oxidized species with PhSH are also helpful for assignation of the signals for the selenenic acid and seleninic acid intermediates. While the selenenic acids 38, 40, and 42 required only one equivalent of PhSH each to produce the corresponding selenenyl sulfides quantitatively, higher concentrations of PhSH were required for complete conversions of the oxidized compounds derived from 4, 20, and 21 into the corresponding selenenyl sulfides. As an example, the signal due to the selenenic acid 37 disappeared completely upon addition of one equivalent of PhSH to a mixture containing selenenic acid 37 and seleninic acid 43. The addition of an excess amount of PhSH to the mixture converted both 37 and 43 into the selenenyl sulfide 31.
  • 67
    • 53849083034 scopus 로고    scopus 로고
    • It should be noted that selenenic acids are generally quite unstable and may not survive in solution for long times. They tend to disproportionate in solution to give the corresponding seleninic acids and diselenides (3RSeOH→RSeO2H+RSeSeR+H2O, However, no such disproportionation was observed in the cases of selenenic acids 38, 40, and 42, which were stable enough to be detected by 77Se NMR spectroscopy. This is due to the presence of the methoxy substituents, which protect the selenium moieties from overoxidalion. For structurally characterized stable selenenic acids, see: a) T. Saiki. K. Goto, R. Okazaki. Angew. Chem. 1997, 109, 2320-2322;
    • 77Se NMR spectroscopy. This is due to the presence of the methoxy substituents, which protect the selenium moieties from overoxidalion. For structurally characterized stable selenenic acids, see: a) T. Saiki. K. Goto, R. Okazaki. Angew. Chem. 1997, 109, 2320-2322;
  • 78
    • 53849109882 scopus 로고    scopus 로고
    • Gaussian 98, 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, A. G. Baboul, 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. Johnson, W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E. J. Replogle, A. J. Pople, Gaussian, Inc, Pittsburgh, PA. 1998
    • Gaussian 98, 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, A. G. Baboul, 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. Johnson, W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E. J. Replogle, A. J. Pople, Gaussian, Inc., Pittsburgh, PA. 1998.
  • 83


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.