Nanochemistry and biotechnology

In silico study of DNA binding interaction of сis-Palladium (II) 3-(2-pyridyl)-5-methyl-1,2,4-triazole in combination with C60 fullerene and evalution of their hemolytic activity in vitro.

Hurmach V.V.1, Grynyuk A.A.2, Prylutska S.V.1, Grynyuk I.I.1, 
Zakharchenko B.V. 1, Khomenko D.M.1, Nizhenkovska I.V.2, Kuznetsova O.V.2, PrylutskyyYu.I. 1, Scharff P.3,
1Taras Shevchenko National University of Kyiv, 64 Volodymyrska Str., Kyiv, 01601, Ukraine
E-mail: a_a_grinyuk@ukr.net
2 O.O.Bogomolets National Medical University, 13 T. Shevchenko boulevard, Kyiv, 01601, Ukraine
3Technical University of Ilmenau, 25 Weimarer Str., Ilmenau, 98693, Germany

Chemotherapeutic drugs such as cisplatin, doxorubicin, paclitaxel etc. kill cancer and normal cells and cause side effects in the organism. The creation of the new low toxic structural analogs of known anticancer drugs and modulation of their biological activity by nanostructures is important problem nowadays. 
In this regard, the promising compound is сis-Palladium(II) 3-(2-pyridyl)-5-methyl-1,2,4-triazole (cis-Pd(HL)Cl2). C60 fullerene nanostructure can be a modulator of biological action of palladium complex .
Тhe aim of the work was to predict biological activity of cis-Pd(HL)Cl2, to study interaction of DNA with cis-Pd(HL)Cl2 separately and in combination with C60 fullerene and to estimate their influence on erythrocytes hemolysis. 
Cis-Pd complex was synthesized and characterized using NMR and FTIR spectroscopy (the purity of compound was ≥98%). A highly stable water colloid solution of C60 fullerene (10-4 M, purity >99,5%, nanoparticle average size up to 50 nm) was synthesized at Technical University of Ilmenau (Germany). 
According to PASS program results, cis-Pd(HL)Cl2 can display antitumor effects. 
By using computer modeling it was shown that cis-Pd(HL)Cl2 could interact with C60 fullerene by Van der Waals forces, a complex form between 3-4 molecules of cis-Pd(HL)Cl2 and 1 molecules of C60. Compound cis-Pd(HL)Cl2 form stable complexes with DNA separately and in combination with C60 fullerene. 
Study of erythrocytes resistance to acidic hemolysis allows to elucidate the influence of pharmacological agent at the membrane level. Compound cis-Pd(HL) Cl2 in range concentration 1х10-6 – 1,5х10-5 М did not cause hemolytic effects. Erythrocytes hemolysis was observed in the presence 2x10-5 M cis-Pd (HL) Cl2, C60 fullerene prevented cis-Pd(HL)Cl2-induce hemolytic effect.
Thus, it is promising to create a new complex of cis-Pd (HL) Cl2 with C60 fullerene and study its antitumor properties in vitro and in vivo.