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 1 H 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-N2 O4 (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 1 LEAD Action News Vol. 3, No. 3 Winter 1995 ; Adulteration of Paprika in Hungary http://www.zip.com.au/˜djrat/lanv3n3/lanv3n3-6.html.
2a
Selypes A.
Bánfalvi S.
Bokros F.
Győry E.
Takács S.
Bull. Environm. Contamin. Toxicol.
1997,
58:
408
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
4a
Domingo JL.
Reprod. Toxicol.
1998,
12:
499
4b http://www.pdrhealth.com/content/natural_medicine/chapters/200120.shtml.
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
6
Ma D.
Lu F.
Overstreet T.
Milenic DE.
Brechbiel MW.
Nucl. Med. Biol.
2002,
29:
91
7a
Brücher E.
Győri B.
Emri J.
Solymosi P.
Sztanyik LB.
Varga L.
J. Chem. Soc., Chem. Commun.
1993,
574
7b
Brücher E.
Győri B.
Emri J.
Jakab S.
Kovács Z.
Solymosi P.
Tóth I.
J. Chem. Soc., Dalton Trans.
1995,
3353
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
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
11b
Gatto VJ.
Arnold KA.
Viscariello AM.
Miller SR.
Morgan CR.
Gokel GW.
J. Org. Chem.
1986,
51:
5373
11c
White BD.
Arnold KA.
Gokel GW.
Tetrahedron Lett.
1987,
28:
1749
11d
Tsukube H.
Adachi H.
Morosawa S.
J. Chem. Soc., Perkin Trans. 1
1989,
89
11e
White BD.
Mallen J.
Arnold KA.
Fronczek FR.
Gandour RD.
Gehrig LMB.
Gokel GW.
J. Org. Chem.
1989,
54:
937
12
Chang AC.
Rowland ME.
Inorg. Chem.
1983,
22:
3866
13a
Ariens EJ.
Drug Design
Academic Press;
New York:
1971.
13b
Rautio J.
Nevalainen T.
Taipale H.
Vepsäläinen J.
Gynther J.
Lainen K.
Järvinen T.
Eur. J. Pharm. Sci.
2000,
11:
157
13c Kozak A. inventors; US Patent 6 077 837.
; Chem. Abstr. , 133, 63944
14a
Mahfouz NM.
Aboul-Fadl T.
Diab AK.
Eur. J. Med. Chem.
1998,
33:
675
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
14c
Changani KK.
Fuller BJ.
Bryant DJ.
Bell JD.
Ala-Korpela M.
Taylor-Robinson SD.
Moore DP.
Davidson BR.
J. Hepatology
1997,
26:
336
14d
Grivet J.-P.
Delort A.-M.
Porais J.-C.
Biochimie
2003,
85:
823
15a
Catsch A.
Federation Proc., Suppl. 10, Part II
1961,
20:
206
15b Miller SC, and Bruenger FW. inventors; US Patent 5403862.
; Chem. Abstr.
16
Fischer E.
Speier A.
Ber. Dtsch. Chem. Ges.
1895,
28:
3252
17
Butler CL.
Renfrew AG.
Clapp M.
J. Am. Chem. Soc.
1938,
60:
1472
18
Pedersen DS.
Rosenbohm C.
Synthesis
2001,
2431
19
Lerche-Langrand C.
Toutain HJ.
Toxicology
2000,
153:
221