Kamila Neplechová

A comparison of DNA binding profiles of dinuclear platinum compounds with polyamine linkers and the trinuclear platinum phase II clinical agent BBR3464

Abstract. The DNA binding profiles of three bis Pt(II) polyamine-linked compounds, [{trans-PtCl(NH3)2}2{µ-spermine-N1,N12}]4+, [{trans-PtCl(NH3)2}2{µ-spermidine-N1,N8}]3+, and [{trans-PtCl(NH3)2}2{µ-BOC-spermidine}]2+, were compared with that of a novel trinuclear phase II clinical agent, [{trans-PtCl(NH3)2}2{µ-trans-Pt(NH3)2(H2N(CH2)6NH2)2}]4+. All of the compounds bind preferentially in a bifunctional manner, according to unwinding of supercoiled DNA circles. The kinetics of binding of these compounds corresponds to their relative charge (2+ to 4+). The preference for the formation of interstrand crosslinks, however, does not follow a charge-based pattern. By studying the results of DNA polymerase extension products on a DNA template modified by the compounds, and by incorporating the complementary method of RNA transcription mapping, it was possible to determine the nucleotide bases that are preferred sites of binding. The stop sites due to platinum adducts were determined, and some preliminary observations concerning the range and type of crosslinks were established. It can be concluded that dinuclear Pt compounds are similar to their trinuclear counterpart, and that charge differences do not contribute solely to the variances between the compounds.

Reaction of Triselenium Heptoxide with Pyridine – Novel DA-complex 4Py· Se2O5

Se3O7 reacts with an excess of pyridine (Py) and forms the donor-acceptor (DA) complexes Py · SeO2 and 4Py · Se2O5. The latter compound was characterised by elemental analysis, Raman spectroscopy, thermal analysis and X-ray crystallography: orthorhombic system, space group Pbca with a = 17.133(5) A, b = 11.585(6) A c = 22.461(6) A, calculated density 1.652 g.cm−3, Z = 8, reflections collected, 2569, final R value 0.0442. This is the first compound in which tetravalent selenium atom is co-ordinated by three nitrogen atoms.

Unusual DNA binding properties of chelate ring-opening platinum complexes

Bis(aminophosphine) platinum complexes were studied from the point of view of their DNA binding. They were found to show a different binding manner from that of cisplatin.