cis-Dichloro(alpha,omega-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.
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.
González
M. L.
ML
Departamento de Química Inorgánica, Facultad de Farmacia, Universidad de Granada, E-18071 Granada, Spain, Instituto de Parasitología y Biomedicina "López-Neyra" (CSIC), Granada, Spain, and Centro de Biología Molecular "Severo Ochoa" (CSIC), Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
Tercero
J. M.
JM
Matilla
A.
A
Niclós-Gutiérrez
J.
J
Fernández
M. T.
MT
López
M. C.
MC
Alonso
C.
C
González
S.
S