E. V. Vasil'eva

Physicochemical Properties and Pharmacological Activity of Mn(II), Fe(II), Co(II), Cu(II), AND Zn(II) Gluconates

The well-known antitumor drugs suppress the immune system to different degrees [1]. It is therefore important to find substances possessing, in addition to antitumor activity, immunotropic properties. Of special interest in this respect are compounds of d-elements, an imbalance of which is known to accompany various pathological processes, including tumor growth [2 – 4]. The coordination compounds of these metals possess both immunomodulant properties [5 – 7] and cytotoxic activity [8 – 10]. It was reported that 3d-metal gluconates are effective correctors in some pathological states [11 – 14]. For this reason, we have synthesized gluconates of Mn, Fe, Co, Cu, and Zn (compounds I – V, respectively), determined some physicochemical properties of these compounds, and evaluated their cytotoxic and immunotropic activity. The compositions of gluconates I – V correspond to the general formula M(C6H11O7)2 2H2O, where M = Mn(II), Fe(II), Co(II), Cu(II), and Zn(II). The synthesized compounds were characterized by spectroscopic methods, thermogravimetric (TGA) and elemental analyses, and conductivity measurements in aqueous solutions. The IR absorption spectra of the synthesized compounds were analyzed in comparison to the spectra of the initial reagent, gluconic acid (VI), and the reference drug – calcium gluconate (VII). The IR spectra of metal gluconates display a strong absorption band at 1600 – 1588 cm – 1 and a medium-intensity band 1400 – 1420 cm – , corresponding to the antisymmetric and symmetric stretching vibrations of the carboxylate ion, respectively. In contrast, the spectrum of acid VI exhibits an absorption band at 1740 cm – , assigned to C=O of the COOH group. The formation of metal gluconates is always accompanied by almost complete vanishing of the absorption band at 1190 cm – 1 belonging to bending vibrations of the carboxy (C–O) group [15]. The absorption bands of bending vibrations of the secondary hydroxy groups OH, which are observed at 1220 – 1300 cm – 1 in the spectrum of calcium gluconate, shift to 1350 – 1400 cm – 1 in the spectra of compounds I – V. Significant differences between the IR spectra of gluconates and the spectra of gluconic acid and calcium gluconate are also observed for C–O of the secondary carboxy groups in the region of 1080 – 1135 cm – 1 and for their skeletal vibrations at 1000 – 1080 cm – 1 (Fig. 1). These distinctions indicate that these groups are involved in the formation of donor – acceptor groups with d-metal ions. Larsson [16] explained the observed character of absorption in this region by the formation of a chelate ring upon the complexation of d-elements with oxy acids. The results of C NMR measurements showed (Table 1) that this binding is mediated by the oxygen atom of a hydroxy group at the third carbon atom. This conclusion is confirmed by stereochemical considerations. Calculations by the AMPAK program using the AM-1 method, as well as the published data [17], indicate that the structure of molecule VI contains a fragment convenient for the formation of a six-member chelate cycle involving oxygen atoms of the carboxy group and the hydroxy group at the third carbon atom.

The Synthesis and Antiviral Activity of Glycyrrhizic Acid Conjugates with α-D-Glucosamine and Some Glycosylamines

Glycyrrhizic acid and its 30-methyl ester were conjugated with 2-amino-1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-glucopyranose, 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl amine, 2,3,4-tri-O-acetyl-α-L-arabinopyranosyl amine, 2-acetamido-2-deoxy-β-D-glucopyranosyl amine, and β-D-galactopyranosyl amine using N,N′-dicyclohexylcarbodiimide and its mixtures with N-hydroxybenzotriazole. Structures of the conjugates were confirmed by IR, UV, 1H, and 13C NMR spectroscopy. The glycoconjugate with the residues of 2-acetamido-2-deoxy-β-D-glucopyranosyl amine in the carbohydrate part of its molecule exhibited antiviral activity (ID50 4 μg/ml) toward the herpes simplex type 1 virus (HSV-1) in the VERO cell culture. Two compounds demonstrated anti-HIV-1 activity (50–70% inhibition of p24) in a culture of MT-4 cells at concentrations of 0.5–20 μg/ml.

Transformations of Glycyrrhizic Acid: XV. Synthesis of Triterpene Saponins with Monosaccharide Residues Attached through Ester Bonds

Triterpene saponins, glycoside analogues of glycyrrhizic acid with a modified carbohydrate chain containing monosaccharide residues attached through ester bonds, were synthesized. To this end, peracetylated glycyrrhizic acid or its 30-methyl ester were glycosylated by 2,3,4,6-tetra-O-acetyl-α-D-gluco- or -α-D-galactopyranosyl bromide in dichloroethane in the presence of Ag2CO3. Glycerrhetinic acid saponin with D-Galp residues exhibited a higher antiulcer activity than glycyrrhizic acid in rats at a dose of 25 mg/kg.

Extraction of Iridium(IV) from Hydrochloric Acid Solution with Bis(piperidinoethylthioethyl)-1-phenyl-1-ethanone

A bidentate organic compound containing nitrogen and sulfur donor atoms was tested as a reagent for extraction of iridium(IV) from aqueous solutions. The composition of the extractable Ir(IV) complex was determined by 1H NMR, UV, and IR spectroscopy and elemental analysis.

Synthesis and spectral properties of shielded 1,2-disubstituted imidazolines

Shielded 1,2-disubstituted imidazolines were synthesized by condensation of diethylenetriamine with 2-ethylhexanoic acid. UV, IR and1H and13C NMR spectral data were discussed. The effect was studied of α branching in an alkyl substituent at the 2 position of the imidazoline ring on the spectral parameters of the synthesized compounds.