Novel iron complexes bearing N6-substituted adenosine derivatives: synthesis, magnetic, 57Fe Mössbauer, DFT, and in vitro cytotoxicity studies.
Iron complexes (1-7) involving N6-benzyladenosine derivatives of the predominant composition [Fe(L(n))Cl(3)].H(2)O {where L(1)=N6-(2-fluorobenzyl)adenosine (1), L(2)=N6-(4-fluorobenzyl)adenosine (2), L(3)=N6-(2-trifluoromethylbenzyl)adenosine (3), L(4)=N6-(3-trifluoromethylbenzyl)adenosine (4), L(5)=N6-(4-trifluoromethylbenzyl)adenosine (5), L(6)=N6-(4-trifluoromethoxybenzyl)adenosine (6), and L(7)=N6-(4-chlorobenzyl)adenosine (7)} have been synthesized. The compounds have been characterized by elemental analysis, variable-temperature and in-field 57Fe Mössbauer, ES+ MS, FTIR, 1H and 13C NMR spectroscopies, magnetochemical and conductivity measurements, thermal (TGA/DSC/DTA) analyses, and DFT calculations. It has been found that the organic molecule is coordinated to iron via N7 atom of the appropriate adenosine derivative and the products are represented by mixtures of complexes with various iron oxidation (Fe(III)/Fe(II)) and spin states (S=5/2, 4/2, 3/2, 2/2) and geometries (tetrahedral or trigonal bipyramidal). It is caused by the fact that partial redox processes proceed during the reactions due to the presence of a ribose moiety, which is oxidized to the corresponding 5'-ribotic acid, and simultaneously, a portion of Fe(III) cations is reduced to Fe(II) ones. Moreover, a significant effect of crystal water molecules on stereochemistry, and hence, on magnetic and spectral properties of the prepared complexes has been found. The compounds have been tested for their in vitro cytotoxicity against the following human cancer cell lines: malignant melanoma (G-361), osteogenic sarcoma (HOS), chronic myelogenous leukemia (K-562), and breast adenocarcinoma (MCF-7). The most important results have been obtained for complex 2 with IC(50) values 8-16 microM against HOS, K-562, and MCF-7 cell lines, and for complex 6 with IC(50) value 4 microM against MCF-7 cell line.
Trávnícek
Zdenek
Z
Department of Inorganic Chemistry, Faculty of Science, Palacký University, Krízkovského 10, CZ-77147 Olomouc, Czech Republic. zdenek.travnicek@upol.cz
Mikulík
Jirí
J
Cajan
Michal
M
Zboril
Radek
R
Popa
Igor
I
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D000465:Algorithms; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007501:Iron / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D015204:Spectroscopy, Mossbauer
D009942:Organometallic Compounds; D007501:Iron; D000241:Adenosine