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Synthesis 2005(20): 3555-3564  
DOI: 10.1055/s-2005-918442
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and in vitro Enzyme Hydrolysis of Trioxadiaza- and Tetraoxadiaza-Crown Ether-Based Complexing Agents with Disposable Ester Pendant Arms

Tímea Iványi, István Lázár*
University of Debrecen, Department of Inorganic and Analytical Chemistry, Egyetem tér 1, Debrecen 4032, Hungary
Fax: +36(52)489667; e-Mail: lazar@delfin.unideb.hu;
Further Information

Publication History

Received 23 February 2005
Publication Date:
27 October 2005 (online)

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Abstract

New disposable ester derivatives of the complexing agents N,N′-bis(carboxymethyl)piperazine, -homopiperazine, -1,7-diaza-15-crown-5 and -1,10-diaza-18-crown-6 were synthesized with a variety of synthetic methods and fully characterized. Hydrolytic properties of the pendant arms were studied under different pH conditions as well as in the presence and absence of porcine liver esterase enzyme and approximate hydrolysis half lives were determined by 1H NMR technique. In vitro studies on pig liver cell homogenates and living thin chicken liver slices proved that the selected double ester 4b can penetrate liver tissues spontaneously, liberate the free complexing agent N,N′-bis(carboxymethyl)-18-ane-N2O4 (ODDA) inside the cells and are potentially capable of removing lead and other toxic metal ions from the liver.

Key words

crown compounds - complexes - esters - enzymes - hydrolyses

    References

  • 2a Selypes A. Bánfalvi S. Bokros F. Győry E. Takács S. Bull. Environm. Contamin. Toxicol.  1997,  58:  408 
    Google Scholar
  • 2b

    Schweizer, K. Hungary still counting cost of pollution legacy, http://www.planetark.com/dailynewsstory.cfm/newsid/12588/newsDate/1-Oct-2001/story.htm.
  • 3 Lakatos Gy. Fleit E. Mészáros I. Toxicology Lett.  2003,  140-141:  333 
    CrossrefGoogle Scholar
  • 4a Domingo JL. Reprod. Toxicol.  1998,  12:  499 
    CrossrefGoogle Scholar
  • 4b

    http://www.pdrhealth.com/content/natural_medicine/chapters/200120.shtml.
    Crossref
  • 5 Aposhian HV. Maiorino RM. Gonzalez-Ramirez D. Zuniga-Charles M. Xu Z. Hurlbut KM. Junco-Munoz P. Dart RC. Aposhian MM. Toxicology  1995,  97:  23 
    CrossrefGoogle Scholar
  • 6 Ma D. Lu F. Overstreet T. Milenic DE. Brechbiel MW. Nucl. Med. Biol.  2002,  29:  91 
    CrossrefGoogle Scholar
  • 7a Brücher E. Győri B. Emri J. Solymosi P. Sztanyik LB. Varga L. J. Chem. Soc., Chem. Commun.  1993,  574 
    CrossrefGoogle Scholar
  • 7b Brücher E. Győri B. Emri J. Jakab S. Kovács Z. Solymosi P. Tóth I. J. Chem. Soc., Dalton Trans.  1995,  3353 
    CrossrefGoogle Scholar
  • 8 Varga L, Törőcsik M, Brücher E, Emri J, Győri B, Sztanyik BL, Juhász IL, and Király Ö. inventors; Hungarian Patent  209389.  Chem. Abstr. , 115, 35724
  • 9 Varga LP. Sztanyik LB. Rónai E. Bodó K. Brücher E. Győri B. Emri J. Kovács Z. Int. J. Radiat. Biol.  1994,  66:  399 
    CrossrefGoogle Scholar
  • 10 Emri J, Győri B, Brücher E, Sztanyik LB, Varga L, Király Ö, and Kanyár B. inventors; PCT Int. Appl.  WO 9110655.  Chem. Abstr. , 115, 183388
  • 11a Kulstad S. Malmsten LA. Acta Chem. Scand.  1979,  B33:  469 
    CrossrefGoogle Scholar
  • 11b Gatto VJ. Arnold KA. Viscariello AM. Miller SR. Morgan CR. Gokel GW. J. Org. Chem.  1986,  51:  5373 
    CrossrefGoogle Scholar
  • 11c White BD. Arnold KA. Gokel GW. Tetrahedron Lett.  1987,  28:  1749 
    CrossrefGoogle Scholar
  • 11d Tsukube H. Adachi H. Morosawa S. J. Chem. Soc., Perkin Trans. 1  1989,  89 
    CrossrefGoogle Scholar
  • 11e White BD. Mallen J. Arnold KA. Fronczek FR. Gandour RD. Gehrig LMB. Gokel GW. J. Org. Chem.  1989,  54:  937 
    CrossrefGoogle Scholar
  • 12 Chang AC. Rowland ME. Inorg. Chem.  1983,  22:  3866 
    CrossrefGoogle Scholar
  • 13a Ariens EJ. Drug Design   Academic Press; New York: 1971. 
    CrossrefGoogle Scholar
  • 13b Rautio J. Nevalainen T. Taipale H. Vepsäläinen J. Gynther J. Lainen K. Järvinen T. Eur. J. Pharm. Sci.  2000,  11:  157 
    CrossrefGoogle Scholar
  • 13c Kozak A. inventors; US Patent 6 077  837.  ; Chem. Abstr. , 133, 63944
    Crossref
  • 14a Mahfouz NM. Aboul-Fadl T. Diab AK. Eur. J. Med. Chem.  1998,  33:  675 
    CrossrefGoogle Scholar
  • 14b Ferretti A. Knijn E. Iorio E. Pulciani S. Giambenedetti M. Molinari A. Meschini S. Stingaro A. Calcabrini A. Freitas I. Strom R. Arancia G. Podo F. Biochim. Biophys. Acta  1999,  1438:  329 
    CrossrefGoogle Scholar
  • 14c Changani KK. Fuller BJ. Bryant DJ. Bell JD. Ala-Korpela M. Taylor-Robinson SD. Moore DP. Davidson BR. J. Hepatology  1997,  26:  336 
    CrossrefGoogle Scholar
  • 14d Grivet J.-P. Delort A.-M. Porais J.-C. Biochimie  2003,  85:  823 
    CrossrefGoogle Scholar
  • 15a Catsch A. Federation Proc., Suppl. 10, Part II  1961,  20:  206 
    Google Scholar
  • 15b Miller SC, and Bruenger FW. inventors; US Patent  5403862.  ; Chem. Abstr.
  • 16 Fischer E. Speier A. Ber. Dtsch. Chem. Ges.  1895,  28:  3252 
    Google Scholar
  • 17 Butler CL. Renfrew AG. Clapp M. J. Am. Chem. Soc.  1938,  60:  1472 
    CrossrefGoogle Scholar
  • 18 Pedersen DS. Rosenbohm C. Synthesis  2001,  2431 
    Article in Thieme ConnectGoogle Scholar
  • 19 Lerche-Langrand C. Toutain HJ. Toxicology  2000,  153:  221 
    CrossrefGoogle Scholar
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LEAD Action News Vol. 3, No. 3 Winter 1995; Adulteration of Paprika in Hungary http://www.zip.com.au/˜djrat/lanv3n3/lanv3n3-6.html.