cis-dichloro-palladium(II) complexes with diaminosuccinic acid and its diethyl ester: synthesis, molecular structure, and preliminary DNA-binding and antitumor studies.
The reactions of K2PdCl4 with meso-diaminosuccinic acid (H2dasa) in 0.1 M HCl or its diethyl ester dihydrochloride Et2dasa.2HCl in neutralized aqueous solution yield cis-[Pd(H2dasa)Cl2](I) and cis-[Pd(Et2dasa)Cl2](II), respectively. These products were characterized by elemental analysis, IR spectroscopy, and TG-DTA thermal analysis. The crystal of II is monoclinic, space group C2/c (a = 14.292(5), b = 14.636(5), c = 13.435(5) A, beta = 98.08(2) degrees, Z = 8, R = 0.041 and wR = 0.06). The Pd(II) atom exhibits a roughly square planar coordination with two Pd-N bonds (Et2dasa) (2.014(2) and 2.049(7) A) and two cis-imposed Pd-Cl bonds (2.294(2) and 2.303(2) A). Compound I reacts with 2,2'-bipyridine in neutral aqueous solution to give [Pd(2,2'-bipy)(dasa)].3H2O(III) in a process of cis-chloride substitution by 2,2'-bipy as a model N-heterocyclic chelating entity. The molecular and crystal structure of III is also reported. It was observed that both cis-dichloro-Pd(II) complexes having Pd(H2dasa) (acidic) and Pd-(Et2dasa)(esterified) chelate entities induce conformational changes in the covalent closed circular (ccc) form of pUC8 plasmid. Both compounds were assayed for antitumor activity in vitro against MDA-MB 468 and HL-60 human cancer cell lines. The results show that compounds I and II have values of ID50 lower than those of K2PdCl4, and also lower than those of diaminoacid ligands (meso-diaminosuccinic acid and meso-diaminosuccinate diethyl ester). Thus it is likely that the imposed cis-coordination of the chelating H2dasa or Et2dasa to the Pd(II) center increases the biological activity of these palladium(II) complexes.
Matilla
A
A
Department de Química Inorgánica, Facultad de Farmacia, Universidad de Granada, Spain.
Tercero
J M
JM
Dung
N H
NH
Viossat
B
B
Pérez
J M
JM
Alonso
C
C
Martín-Ramos
J D
JD
Niclós-Gutiérrez
J
J
D000599:Amino Acids, Diamino / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C090281:(2,2'-bipyridine)(diaminosuccinic acid)palladium(II); D000599:Amino Acids, Diamino; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C090283:dichloro(diaminosuccinate diethyl ester)palladium(II); C090282:dichloro(diaminosuccinic acid)palladium(II); D004247:DNA