SYNTHESIS, CHARACTERIZATION, CYTOTOXIC, AND DNA-BINDING STUDIES OF SOME PLATINUM(II) COMPLEXES OF 1,2-DIAMINE AND ALPHA-DIIMINE WITH 2-PYRIDINECARBOXYLATE ANION

Seven new water-soluble cationic complexes of general formula [Pt(2-py c)(N-N)](+) (where N-N is 2NH(3), ethylenediamine (en), 1,2-diaminopro pane (1,2-dap), 1,3-diaminopropane (1,3-dap), (+/-) trans-1,2-diaminoc yclohaxane(dach), 2,2'-dipyridylamine (dpa) or 1,10-phenanthroline (ph en), and 2-pyridinecarboxylate anion) have been prepared. These comple xes have been characterized by conductance measurements, and by ultrav iolet-visible, infrared (IR), and H-1 nuclear magnetic resonance (NMR) spectroscopy. The COSY (correlated spectroscopy) spectra of [Pt(2-pyc )(dpa)](+) and [Pt(2-pys)(dpa)](+) further support the structures of t he above complexes with three nitrogen and one oxygen donor atoms in t he first coordination sphere of platinum(II) with 1,2-diamine or alpha -diimine and 2-pyridinecarboxylate anion behaving as bidentate ligands . One of the compounds, [Pt(2-pyc)(dpa)]Cl, also shows a birefringence property in water. These compounds inhibit the growth of P388 lymphoc ytic leukemia cells. [Pt(2-pyc)(dpa)](+) shows I.D.(50) value comparab le to cisplatin. However, six other complexes show higher I.D.(50) val ues than cisplatin. In addition, the inhibition studies also suggest t hat their target is DNA. Therefore, the interactions of four of the ab ove complexes with calf thymus DNA have been studied by ultraviolet an d fluorescence spectral methods. These studies suggest that [Pt(2-pyc) (NH3)(2)](+) and [Pt(2-pyc)(1,2-dap)(+) bind to DNA by noncovalent int eractions. On the other hand, [Pt(2-pyc)(dpa)](+) and [Pt(2-pyc)(phen) ](+) bind to DNA by covalent monofunctional binding. The latter two co mplexes have also been interacted with PUC19 DNA. The gel electrophore sis studies of these interactions suggest that these complexes bind to DNA, and this binding leads to a conformational change in DNA.