Ya. S. Glazkova

Synthesis and biological testing of tubuloclustin analogs containing alicyclic groups and 2-methoxyestradiol moiety

A number of analogs of tubuloclustin, N-[7-(2-adamantyloxy)-7-oxoheptanoyl]-N-deacetylcolchicine, were obtained. In these analogs, the colchicine moiety is formally replaced by the cyclohexane, adamantane, and 2-methoxyestradiol moieties (the steroid is attached through the hydroxy group at the C(17) atom). MTT assays revealed that the conjugates obtained are much less cytotoxic against A549 lung carcinoma cells than the lead compound.

Antiproliferative Activity of Tubuloclustin and its Steroid Analogs

Daily administration of tubuloclustin (1 mg/kg, 5 d, i.p.) to BDF1 mice with i.p. transplanted P388 leukemia extended statistically significantly by 45% their life spans compared with those of untreated controls (17 vs. 11.7 ± 3 d). The possibility in principle of preparing 2-methoxyestradiol analogs with a linker bonded through a steroid C6 ester was demonstrated. However, the resulting conjugates IIa and IIb were unstable with respect to a strong tendency for elimination from the C6–C7 bond. This may have been the reason for their low cytotoxicity in the MTT assay on A549 cell culture (IC50 > 10 μM). It was concluded that conjugates of higher stability must be synthesized as potential antitumor agents.

Synthesis and bioassay of benzimidazole conjugates with adamantane

The synthesis of 2-adamantyl-6-[(1H-benzimidazol-1-ylcarbonyl)amino]hexanoate and 2-adamantyl-7-(1H-benzimidazol-1-yl)-7-oxo-heptanoate, and the results of their cytotoxicity assay against human lung carcinoma cells A549 are presented in the paper. The impossibility of adding 5-(2-adamantyloxycarbonyl)pentyl isocyanate to nocodazole under various conditions was shown.

The structural state of iron in multicomponent aluminum iron borosilicate glass depending on their composition and synthesis conditions

The oxidation states and coordination environment of iron ions in borosilicate glass used for the immobilization of iron-containing radioactive waste are studied by the methods of Mössbauer and Fourier transform IR spectroscopies. In homogeneous glass, containing no more than 50 wt % of waste oxides, iron is present in the form of Fe3+ and Fe2+ ions in octahedral coordination with oxygen. The phase of a iron-containing spinel, in which iron atoms with an oxidation number of +3 in the magnetically ordered state surrounded tetrahedrally by oxygen atoms (Fe3+O4) and iron in the two- and trivalent states in the octahedral oxygen environment (Fe3+O6 + Fe2+O6) are present, is precipitated at higher waste concentrations. Both the Mössbauer and IR spectra of glass crystalline materials are combinations of the corresponding individual spectra. The quantitative ratio of the doubly- and triply-charged iron ions in samples depends on the synthesis conditions. The maximum fraction of iron in the glass phase (about 28%) and, at the same time, the maximum fraction of the Fe3+ ions (91.3%) are observed in the sample prepared in a crucible by heating in a laboratory furnace in the air environment and subsequent quenching on a metal sheet.

Oxidation state and coordination surrounding of iron and uranium in sodium aluminum iron phosphate glasses

The oxidation state of Fe and U and the coordination surrounding of Fe in uranium-containing sodium aluminum iron phosphate glasses were determined by analysis of the FeK and UL3 X-ray absorption nearedge structure (XANES), X-ray photoelectron spectroscopy (XPS), and Mössbauer spectroscopy on 57Fe nuclei. Uranium is present in the glasses in the form of U(V) and U(VI), and iron, in the form of Fe(III) and Fe(II), mainly in the distorted octahedral surrounding. The fraction of U in various oxidation states depends on the form of untroducing uranium (UO2 or UO3) and on the oxide concentration. With an increase in the UO3 concentration in glasses, the fraction of U(VI) increases and the fraction Fe(III) relative to Fe(II) decreases.

Oxidation state and local environment of iron and hydrolytic stability of multicomponent aluminum-iron-phosphate glasses for immobilization of high-level waste

The nuclear gamma resonance (Mössbauer effect) is used to determine the oxidation state and the coordination environment of iron ions in model glasses that simulate vitrified high-level waste. A major fraction of iron is present in the samples with relatively low contents of transition metal oxides as Fe(III) in the octahedral oxygen environment. When the content of transition metal oxides is high, iron is distributed between a glassy phase (10–15%) and a crystalline phase (85–90%). Iron in the first phase exists predominantly as Fe(III) in the octahedral environment, while in the second phase it is present as Fe(II) and Fe(III) ions as well in a form of octahedrally coordinated and participating ions in a “fast” electron exchange proceeding as mFe3+ + nFe2+ ↔ mFe2+ + nFe3+. The leach rate of Cs ions from boron-free glasses amounts to ~1 × 10–5 g/(cm2 day) and lower, and the value for Fe is three orders of magnitude lower. Upon annealing, both the rate and the degree of leaching increase by several times, while the boron-containing glasses exhibit lower hydrolytic durability. Both the rate and the degree of leaching of iron change insignificantly after annealing.

Molecular design and an attempt to synthesize a conjugate of 2-methoxyestradiol with adamantane

Based on molecular modeling data, 2-adamantyl 8-[(2-methoxyestra-1,3,5(10)-triene-3,17β-diol-6α-yl)amino]octanoate 2d is proposed as a structural analogue of highly cytotoxic N-(8-(adamant-2-yloxi)-8-oxooctanoyl)-N-deacetylcolchycine. Three-step synthesis of adamant-2-yl 8-aminooctanoate 5 is described. Reductive amination of 2-methoxy-6-oxo-17β-estradiol in weakly acidic medium in the presence of compound 5 and NaBH3CN or Na(OAc)3BH results in the product of elimination at the C6–C7 bond of steroid 7 rather than the formation of conjugate 2d.

Mössbauer study of the modulated magnetic structure of FeVO 4

Mössbauer spectroscopy is used to study the FeVO4 multiferroic, which undergoes two magnetic phase transitions at TN1 ≈ 22 K and TN2 ≈ 15 K. The first transition (TN1) is related to transformation from a paramagnetic state into a magnetically ordered state of a spin density wave, and the second transition (TN2) is associated with a change in the type of the spatial magnetic structure of the vanadate. The electric field gradient tensor at 57Fe nuclei is calculated to perform a crystal-chemical identification of the partial Mössbauer spectra corresponding to various crystallographic positions of Fe3+ cations. The spectra measured in the range TN2 < T < TN1 are analyzed on the assumption about amplitude modulation of the magnetic moments of iron atoms μFe. The results of model intersection of the spectra recorded at T < TN2 point to a high degree of anharmonicity of the helicoidal magnetic structure of the vanadate and to elliptic polarization of μFe. These features are characteristic of type-II multiferroics. The temperature dependences of the hyperfine interaction parameters of 57Fe nuclei that were obtained in this work are analyzed in terms of the Weiss molecular field model on the assumption of orbital contribution to the magnetic moments of iron cations.

Local crystal structure of multiferroic BiMnO3 studied by 57Fe probe Mössbauer spectroscopy

This paper presents a 57Fe probe Mössbauer spectroscopy study of a BiMn0.9657Fe0.04O3 manganite synthesized at high pressure (6 GPa). The BiMnO3 manganite possesses multiferroic properties and exhibits cooperative orbital ordering due to Jahn–Teller active Mn3+ ions. 57Fe Mössbauer spectra have been measured and analyzed in a wide temperature range, which includes the orbital ordering temperature of BiMnO3.