The effectiveness of targeted delivery of cisplatin conjugate with arabinogalactan to ascitic Ehrlich carcinoma in vivo using the target ligand, the AS42 aptamer, was studied in this work. Studies conducted on male ICR mice with ascitic Ehrlich carcinoma. Antitumor therapy was carried out with cisplatin and an arabinogalactan-platinum complex (AG-Pt) and an AG-Pt complex modified with aptamers to ascitic Ehrlich carcinoma cells. The toxicity of drugs was determined on the basis of biochemical parameters of blood in healthy mice after 5-fold administration. In our studies, cisplatin treatment of Ehrlich's ascitic carcinoma for 2 weeks led to the death of 6 out of 10 animals. The toxicity of the AG-Pt complex and the AG-Pt complex modified with the aptamer was not revealed. The number of tumor cells during therapy with cisplatin conjugates decreased by 10 times compared with the control. А new promising antitumor drug based on the standard drug cisplatin, which is more effective and less toxic, was presented in the work.

Cisplatin is an effective anticancer drug used to treat various types of cancer. The main disadvantage of the drug is its high toxicity. To reduce the toxic effect of cisplatin, we conjugated it with arabinogalactan, which is capable of forming soluble globules and bind poorly soluble pharmacological compounds by confining them inside spheroid globules. In this study, we compared the biological effect and mechanism of action of cisplatin and its complex with arabinogalactan (AG–Pt) on the growth of Ehrlich ascites carcinoma in vivo. It has been shown that the conjugates of arabinogalactan with cisplatin exerted a strong antitumor effect despite the fact that the dose of cisplatin in the composition of the conjugates was 10 times less than the standard dose. At the same time, the conjugates of arabinogalactan with cisplatin were virtually nontoxic. It has been established that the antitumor effect of cisplatin and its conjugates with arabinogalactan is due to the induction of apoptosis in tumor cells. It is assumed that a decrease in toxicity and an increase in the efficacy of cisplatin-arabinogalactan conjugates compared to pure cisplatin are associated with its more efficient accumulation in tumor cells.

Seven new phases containing hexachloroplatinate [PtCl6]2− and trans-1,2-dl-diammoniumcyclohexane 1,2-C6H10NH322+ ions were obtained by crystallization from solutions with minor variation of synthesis conditions. The compounds can be applied as precursors for the synthesis of effective anticancer drug tetraplatin ([PtC6H10(NH2)2Cl4]). The phase diversity was achieved by alterations including solvent acidity, crystallization rate, temperature, type of solvent, and the reagents ratio. The compounds were characterized by chemical and thermal analysis, IR, and 1H NMR spectroscopy. Crystal structures of the five compounds were determined by X-ray powder diffraction technique. The phases have ionic structures involving H2O, HCl molecules, or Cl− ions as supplementary species in the lattices. It helps to arrange some frames additionally interconnected by hydrogen bonds between ions and solvent molecules. It was suggested that crystal lattices adapted associated particles presented in solutions. It results in observed variety of the crystal structures. Besides the basic interest the obtained results are important for tetraplatin synthesis control.

The article presents the results of investigation of antitumor properties of platinum–arabinogalactan complex. We showed the ability of the complex to inhibit the growth of Ehrlich ascites tumor cells. It is found that the distribution of the platinum–arabinogalactan complex is not specific only for tumor cells in mice. The complex was found in all tissues and organs examined (ascites cells, embryonic cells, kidney, and liver). The mechanism of action of the arabinogalactan–platinum complex may be similar to cisplatin as the complex is able to accumulate in tumor cells.

A reaction of cis-diamminedichloroplatinum(II) with the natural polysaccharide arabinogalactan gave a product characterized by X-ray powder diffraction, IR spectroscopy, UV spectrophotometry, and thermogravimetry. It was demonstrated that cis-diamminedichloroplatinum(II) is bound to arabinogalactan by a linkage between its -C-O-C- bond and the hydrogen atom of the NH3 group of the starting complex. The product can suppress tumor growth with no toxic effect on the organism.

718 The complex trans 1,2 diaminocyclohexanetetra chloroplatinum(IV) (ormaplatin, tetraplatin) is a sec ond generation antitumor drug, which is similar in efficiency with respect to various tumors but less nephrotoxic than cis dichlorodiaminoplatinum(II) (cisplatin). It is also efficient against the human and murine tumor cells having the acquired resistance to cisplatin [1]. The preparation of this compound is based on the reactions(1) [2, 3] and (2) [1, 4] where 1,2 Dach is trans 1,2 d,l diaminocyclohexane):

The conditions inducing conversion of Magnus salt into diamminedichloroplatinum(II) isomers were studied. Syntheses of cis -diamminedichloroplatinum(II) and trans -diamminedichloroplatinum(II), which are used to prepare potassium or ammonium amminetrichloroplatinate(II), are described. The identity and structure of diamminedichloroplatinum(II) isomers were verified by elemental analysis, X-ray powder diffraction, and IR and UV spectroscopy. A workflow for preparing potassium or ammonium amminetrichloroplatinate(II) from diamminedichloroplatinum(II) isomers was developed. This workflow appreciably increases the product yield due to the return of unused Magnus salt to the main synthesis flow.

The influence of temperature gradients on the particle size and component composition of solid phases in heterogeneous systems of ammonium chloroplatinum(IV) and chlorhodium(III) complex salts was studied. A Benard cell was implemented as applied to not only homogeneous but also heterogeneous systems. Two contributions to the cocrystallization of rhodium with platinum are distinguishable and kinetically resolved: the formation of nonequilibrium solid solutions by ammonium chlorometalates and equilibrium Ostwald ripening. The elucidation of both factors helps in finding crystallization parameters for minimizing the rhodium contamination of platinum in refining practice.

A new method for the synthesis of [Pt2(NH3)4P2O7] is proposed. Its transformations in a hydrochloric acid medium are described.

The title compound, [PtCl2(C3H9N)(NH3)], was obtained from potassium tetrachloroplatinate(II) by a two-step route. Ab initio crystal structure determination was carried out using X-ray powder diffraction techniques. Patterson and Fourier syntheses were used for the atom locations and the Rietveld technique for the final structure refinement. The Pt coordination is close to planar, with Cl atoms in a cis orientation. Molecules are combined into groups of two molecules, with antiparallel PtN2Cl2 planes and a shortest Pt...Pt distance of 3.42 angstroms. The molecule groups are packed in a parquet motif into corrugated layers parallel to ab. The molecules in the layers are linked by H-N...Cl hydrogen bonds.

A comparison study of the bis(μ-oxalato)tetramminediplatinum(II) dimer [Pt 2 (NH 3 ) 4 (μ-C 2 O 4 ) 2 ] and the oxalatodiammineplatinum(II) chelate [Pt(NH 3 ) 2 C 2 O 4 ] is performed. The kinetics and mechanism of substitution of C 2 O 2– 4 for Cl – in aqueous chloride solutions are studied by photoelectronic spectroscopy, gravimetry, and chemical phase analysis within the 1.0–6.7 pH range at 75°C. The rate constants of substitution and the equilibrium constants for a two-step protonation for the dimeric and chelate complexes are calculated. Their solubility in 1 M KCl at 75°C; is determined. The unit cell parameters for [Pt 2 (NH 3 ) 4 (μ-C 2 O 4 ) 2 ] are determined: a = 3.858 Å, b = 10.704 Å, c = 6.795 Å, β = 94.35°. The IR spectra of [Pt(NH 3 ) 2 C 2 O 4 ], [Pt 2 (NH 3 ) 4 (μ-C 2 O 4 ) 2 ], and their deuterated analogs are studied.

Crystalline cis-Pt(NH3)(2)ClNO2 substances were isolated from the heterogeneous liquid-solid cis-[Pt(NH3)(2)Cl-2]-cis-[Pt(NH3)(2)(NO2)(2)]-H(2)Osystem. The phase and molecular compositions of the compounds obtained depended on the method of preparation and synthesis conditions. The compounds were studied by X-ray powder diffraction analysis and spectrophotometry. The crystals of the mixed-ligand cis-[Pt(NH3)(2)ClNO2] complex and a Cis-Pt(NH3)(2)Cl-0.98(NO2)(1.02) solid solution are monoclinic with the unit cell parameters a = 9.151(2), b = 8.802(4), c = 6.848(3) Angstrom, beta = 95.23(4)degrees and a = 9.218(3), b = 8.925(4), c = 6.703(3) Angstrom, beta = 97.12(3)degrees, respectively. The electronic absorption and X-ray diffraction data supported the conclusion that the crystalline cis-Pt(NH3)(2)ClNO2 substances are disordered solutions of three complexes [cis[Pt(NH3)(2)Cl-2], cis-[Pt(NH3)(2)ClNO2], and cis-[Pt(NH3)(2)(NO2)(2)]} in different proportions. Mutual transformations of these complexes occurring during the recrystallization were studied. When recrystallized under the conditions of interphase and liquid-phase equilibria, the individual mixed-ligand cis-[Pt(NH3)(2)ClNO2] complex undergoes ligand redistribution to give equilibrium cis-Pt(NH3)(2)Cl-0.98(NO2)(1.02) solid solution. The nonequilibrium bulk crystallization mainly results in the ordered crystal phase of the cis-[Pt(NH3)(2)ClNO2] complex.