cis-Dichloro(α,ω-diamino carboxylate ethyl ester)palladium(II) as Palladium(II) versus Platinum(II) Model Anticancer Drugs:  Synthesis, Solution Equilibria of Their Aqua, Hydroxo, and/or Chloro Species, and in Vitro/in Vivo DNA-Binding Properties

Abstract

cis-Dichloro(d,l-2,3-diaminopropionate ethyl ester)palladium(II), cis-[Pd(Etdap)Cl(2)] (I), and cis-dichloro(d,l-2,4-diaminobutyrate ethyl ester)palladium(II), cis-[Pd(Etdab)Cl(2)] (II), were synthesized and characterized by elemental analysis, IR spectroscopy, and TG-DTA thermal analysis. The equilibrium model and log beta(pqr) constants of hydrolytic species of I and II were also investigated by potentiometric methods (I = 0.15 M (NaClO(4)) and 37 degrees C). Aqueous solutions of cis-[Pd(Etdaa)(H(2)O)(2)](ClO(4))(2) (Etdaa = Etdap (III) or Etdab (IV)) were prepared by stoichiometric reaction of I or II with AgClO(4). Thus, log beta(pqr) of the corresponding cis-aquahydroxo (pqr = 1,0,-1) and di(&mgr;-hydroxo) (pqr = 2,0,-2) species were obtained from E(H(+)) data of alkalimetric titrations of solutions of III or IV. Such constants were then used as fixed values to obtain log beta(pqr)() of chloro-containing species (cis-dichloro (1,2,0), cis-chloroaqua (1,1,0), and cis-chlorohydroxo (1,1,-1)) from E(H(+)) and E(Cl(-)) data pairs simultaneously obtained by titration of solutions of III or IV with NaOH and NaCl. All log beta(pqr) were fitted by the SUPERQUAD program. Appropriate log beta(pqr)() sets give good simulations of experimental titration curves and several species distribution diagrams. In addition the interaction of I and/or II with DNA in vitro and in vivo was studied by various methods. UV spectral data and melting and renaturation curves indicate that both compounds destabilize the DNA helicoidal structure. Compound II disrupts in vivo the structure and transcription process of polytene chromosomes of Drosophila hydei.

Water-soluble platinum(II) complexes of diamine chelating ligands bearing amino-acid type substituents: the effect of the linked amino acid and the diamine chelate ring size on antitumor activity, and interactions with 5′-GMP and DNA

“…Platinum complexes PtCl 2 (dap-Metala), PtCl 2 (dabMetala), PtCl 2 (dap-phe) and PtCl 2 (dab-phe) were synthesized using equimolar ratios of K 2 PtCl 4 and diamine chelating ligands, following a method adapted from Inagaki et al [49] and Gonzalez et al [50] (Scheme 2). As free diamine chelating ligands were present as amine salts, a neutralization with NaHCO 3 was necessary prior to platination.…”

Synthesis, and characterization of ruthenium(II) polypyridyl complexes containing α-amino acids and its DNA binding behavior

“…It has been observed that the complexes [Ru(j 3 -L)(EPh 3 )Cl 2 ] (E = P, As; L = tpy and tptz) containing both the EPh 3 and polypyridyl ligands behave as good precursors and act as metallo-ligands in the syntheses of homo-/hetero-bimetallic complexes [17,18]. Also, these behave as inhibitors of Topo II and heme polymerase activity.…”

“…The synthesis of complexes containing a-amino acids has become increasingly important due to their significant role in biological fields [19,20]. The amino acids are known to bind metal ions as a bi-dentate N,O-donor ligand forming five membered chelate rings after dissociation of the acidic proton [17,18]. It is noteworthy that while the chemistry of many transition metal complexes containing amino acids has been studied in detail, the chemistry of ruthenium complexes has received only little attention [21,22].…”

Effects of Tris and Hepes buffers on the interaction of palladium–diaminopropane complexes with DNA

“…Recent advances in this area have focused on Pd(II) complexes with one N,N-diamino [17][18][19][20] or N,S-aminothioether [21][22][23] chelating ligand that impels cis-coordination with more labile ligands (containing two chlorine or nitrate moieties or one dicarboxylate moiety). In such cases, the chelating ligand prevents cis-trans isomerization around Pd(II) in spite of its greater lability (about 10 5 -fold) relative to its Pt(II) [13,17,24] analogs.…”