Ternary Copper(II) Complexes in Solution Formed With 8-Aza Derivatives of the Antiviral Nucleotide Analogue 9-[2-(Phosphonomethoxy)Ethyl]adenine (PMEA)

The stability constants of the mixed-ligand complexes formed between Cu(Arm)2+, where Arm = 2,2′-bipyridine (Bpy) or 1,10-phenanthroline (Phen), and the dianions of 9-[2-(phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA) and 8-[2-(phosphonomethoxy)ethyl]8-azaadenine (8,8aPMEA) (both also abbreviated as PA2-) were determined by potentiometric pH titrations in aqueous solution (25 °C; I = 0.1 M, NaNO3). All four ternary Cu(Arm)(PA) complexes are considerably more stable than corresponding Cu(Arm)(R-PO3) species, where R-PO3 2- represents a phosph(on)ate ligand with a group R that is unable to participate in any kind of interaction within the complexes. The increased stability is attributed to intramolecular stack formation in the Cu(Arm)(PA) complexes and also to the formation of 5-membered chelates involving the ether oxygen present in the -CH2-O-CH2-PO3 2- residue of the azaPMEAs. A quantitative analysis of the intramolecular equilibria involving three structurally different Cu(Arm)(PA) species is carried out. For example, about 5% of the Cu(Bpy)(8,8aPMEA) system exist with the metal ion solely coordinated to the phosphonate group, 14% as a 5-membered chelate involving the -CH2-O-CH-2-PO3 2- residue, and 81% with an intramolecular stack between the 8-azapurine moiety and the aromatic rings of Bpy. The results for the other systems are similar though with Phen a formation degree of about 90% for the intramolecular stack is reached. The existence of the stacked species is also proven by spectrophotometric measurements. In addition, the Cu(Arm)(PA) complexes may be protonated, leading to Cu(Arm)(H;PA)+ species for which it is concluded that the proton is located at the phosphonate group and that the complexes are mainly formed by a stacking adduct between Cu(Arm)2+ and H(PA)-. Conclusions regarding the biological properties of these azaPMEAs are shortly indicated

Isolation, characterization and antitumour properties of the 1,2-propylenediaminetetraacetate-trans-diaqua-copper(II)

A trans-diaquacomplex formed by copper(II) sulphate and the sequestering polyamminopolycarboxylic ligand 1,2-propylenediaminetetraacetic acid (PDTA) has been isolated and characterized by chemical analysis, titrimetry, FT-IR and electronic spectroscopy, Potentiometric and electronic measurements identified the ligand as tetradentate, two nitrogen and two oxygen atoms being bonded to the Cu(II) in planar positions. This octahedral monomeric soluble compound, is an unusual example of a copper (II) substance showing significant in vitro antitumour activity against the human ovarian tumour cells TG (ID50 = 2.29 μM at 48 h) and important in vivo antitumour activity against solid Sarcoma 180 with complete regression of the tumour at a dose of 12.5 mg/Kg body weight

Biological activity and redistribution of nucleolar proteins of two different cell lines treated with cis-dichloro-1,2-propylenediamine-N,N,N',N'-tetraacetato ruthenium (III) (RAP)

The interaction of a newly synthesized antitumor complex cis-dichloro-1,2-propylenediamine-N,N,N',N'-tetraacetato ruthenium (III) (RAP) with DNA was investigated in vitro through a number of techniques including comet assay, immunoprecipitation, and immunolocalization of certain nucleolar proteins (the upstream binding factor (UBF) and fibrillarin) involved in DNA transcription, rRNA processing, and ribosomal assembly. The results showed that RAP binds to the DNA of two cell lines (H4 and Hs-683) causing a delay in cell proliferation rate leading to a number of cellular modifications. These modifications include DNA-damage assessed by the single cell gel electrophoresis method (comet assay) and variation in the expression of nucleolar proteins; UBF was more abundant in RAP treated cells, this was explained by the high affinity of this protein to DNA modified by RAP. On the other hand, fibrillarin was found in less quantities in RAP treated cells which was explained by a de-regulation of the ribosomal machinery caused by RA