A new dirhenium(III) complex cis-[Re2(GABA)2Cl5(H2O)]Cl.2H2O with zwitterionic gamma-aminobutyrate ligands was prepared and characterized by spectral methods and crystallography. The structure of the compound is comprised of dinuclear complex cations (Re-Re 2.2437(3) A) involving cis-oriented double carboxylate bridges, four equatorial chloride ions and two weakly bonded aqua and chloride ligands in the axial positions at two rhenium centers (Re-O 2.363(3), Re-Cl 2.6735(12) A). Antitumor properties of the complex were studied in the model of tumor growth with the use of Wistar rats inoculated by tumor carcinoma Guerink cells. The introduction of the compound in dosage according to the scheme of antioxidant therapy, inhibited the tumor growth by ca. 60% and led to stabilization of red blood cells in the tumor-bearing organisms. The combined introduction of the compound and cisplatin had a significant impact on the tumor growth and the disappearance of the tumors in most of the animals.
Liposomes loaded with the rhenium compound (bis-dimethylsulfoxido-cis-tetrachlorodi-μ-pivalatodirhenium(III) (cis-Re2((CH3)3CCOO)2Cl4.2DMSO, I) and cisplatin in the molar ratio of 4:1 as well as those loaded only with I were synthesized and characterized by scanning electron microscopy, transmission electron microscopy, dynamic light scattering and electronic absorption spectroscopy. The relative stability of liposomes loaded with I is reflected by a minimal change in the electronic absorption spectra over a period of 8 days whereas the stability of those loaded with both drugs is lower, which we ascribe to the formation of new Re-Pt species inside the liposomes. Furthermore, the investigations of the co-encapsulation effects on the anticancer activity of the Re-Pt system were undertaken. Importantly, the co-encapsulated liposomes exhibit synergistic or additive anticancer activities in vivo, e.g. introduction of these liposomes into tumor-bearing rats demonstrated their antianemic, nephro- and hepato-protecting effects. These liposomes, which are active in cancer treatment, protect the dirhenium compounds from hydrolysis and preserve the biological properties of the Re-Pt hybrid. This study reveals the importance of combined therapy in nanotechnology and medicine.
In the view of developing a synthetic route for the controlled insertion of distinct organometallic moieties into peptide nucleic acid (PNA) oligomers, a proof-of-principle study of the chemoselective insertion of three different organometallics into a building block containing both a PNA backbone and an alkyne side-chain is presented in this study.
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