Book of Abstracts - Ruhr-Universität Bochum

P-78
ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
In Vitro Interactions of Rhenium(III) Compounds with Phospholipids and
Nucleic Bases Derivatives
a Dina Y. Yegorova, b Nataliia I. Shtemenko, a Alexander V. Shtemenko
a Department of Inorganic Chemistry, Ukrainian State Chemical Technological University,
Gagarin Ave. 8, Dnipropetrovs’k 49005, Ukraine. E-mail: shtemenko@ukr.net, b Department
of Biophysics and Biochemistry, Dnipropetrovs’k National University, 72 Gagarin avenue,
Dnipropetrovs’k 49010, Ukraine
In our previous investigations it was shown that rhenium(III) complexes had antitumor, antihemolytic
and red blood cells stabilizing properties. 1 The important component of the integral biological activity
of any substance is its ability to cross the cell membrane and to react with nuclear bases. Investigations
of the interaction between rhenium(III) cluster complexes and phospholipids as one of the main
components of a cell membrane and nuclear bases is of great importance as may help to understand
the mechanism of their action and to find further synthetic directions.
In this work the experiments were accomplished with cluster rhenium(III) compounds with common
formulas: [Bu4N]2×[Re2Cl8], cis-[Re2(CH3COO)2Cl4]×2H2O, trans-Re2(C2H5COO)2Cl4 ,
Re2(RCOO)3Cl3, Re2(RCOO)4Cl2, where R - CH3, C2H5, i-C3H7, C10H15; with phospholipids:
phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and nuclear bases derivatives: 9methyladenin
and 9-methylguanin. The electronic absorbtion spectra of mixtures of the substances
were studied.
According to the obtained spectra the strongest interaction was found with phosphatidylholine among
other main phospholipids of cells membrane. It was shown that the mechanism of interaction
depended on the structural type of cluster rhenium(III) complexes. In the case of tetra-μ-carboxylates
bridged equatorial carboxylic groups were replaced by phosphate groups of phosphatidylholine with
following formation of monodentate derivatives. During interaction of phosphatidylholine with cistetrachlorodi-μ-carboxylates
of dirhenium(III) replacement of terminal chlorides by
phosphatidylholine ligands with formation of monodentate derivatives with the change of the
previous structural type was shown. The same interactions were shown to be realized during formation
of nanoliposomes of cluster rhenium(III) compounds and phosphatidylholine.
Hydrolytic process of the complex rhenium(III) compounds was shown to take place in water
solutions, that’s why nanoliposomal forms of rhenium(III) complex compounds were obtained from
phosphatidylholine to prolong their therapeutic effect. It was shown that the coordination of phosphate
groups of phosphatidylholine to the cluster centre (unit) of Re2 6+ provided prevention of hydrolytic
process and increased the stability of these compounds.
Bidentate coordination of the 9 MeA to equatorial position of the cluster Re2 6+ centre through N1/N6
atoms of the nucleic base heterocidic ring was shown. Another type of coordination was shown for
Guanine derivative: 9MeG coordinated by monodentate mode to axial position of the Re2 6+ centre only
through N1 atom of the heterocidic ring. The mechanism of interaction between nucleic bases and
rhenium(III) compounds was different in comparison with the same for platinides that explained the
effectiveness of the Rhenium – Platinum antitumor system in the earlier experiments in vivo.
References
1. (a) N. Shtemenko, P. Collery, A. Shtemenko, Anticancer Res. 2007, 27, 2487-2492. (b) A.
Shtemenko, P. Collery, N. Shtemenko, K. Domasevitch, E. Zabitskaya, A. Golichenko, Dalton Trans.
2009, 5132-5136.
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