Svetlana V. Blokhina

Synthesis, biological activity, distribution and membrane permeability of novel spiro-thiazines as potent neuroprotectors

New spiro-derivatives of 1,3-thiazine - potential neuroprotectors have been synthesized. It has been determined that the obtained compounds are biologically active and capable of blocking the glutamate-induced calcium ion uptake into synaptosomes of rat brain cortex. The inhibitory activity of the test substances was shown to depend on the chemical nature and structure of the substituents bound with an exocyclic nitrogen atom. Non-polar alkyl and polar radicals with halogen, oxygen and nitrogen atoms were used as substituents. It is typical of the active spiro-thiazines to have alkyl substituents in ortho- and para-position of the benzene ring. Among the investigated spiro-thiazines it is the derivatives with ethyl- and isopropyl-groups in the aril part of the molecules that are the lead-compounds with a high inhibitory ability. We measured the distribution coefficients of the substances in octanol/buffer and hexane/buffer systems and made conclusions about the ability of the investigated drug-like compounds to penetrate the biological membranes. By using the parabolic model we derived a quadratic equation that allowed us to evaluate quantitatively the inhibitory activity of spiro-thiazines with hydrophobic substituents based on lipophilicity data. We also studied the permeability through the phospholipidic membrane and introduced a correlation equation describing the dependence of the investigated spiro-thiazines activity on the descriptors characterizing the donor-acceptor properties.

Thermodynamic properties and selectivity of substituted liquid-crystal formylazobenzenes as stationary phases for gas chromatography

The retention of xylene, cresol, methylanisole, and lutidine isomers was studied by gas chromatography using the stationary phases based on mesomorphic 4-butyloxy-4′-formylazobenzene and 4-(3-hydroxypropyloxy)-4′-formylazobenzene. A thermodynamic interpretation of the structural selectivity of the nematic phase of the mesogens was proposed.

Liquid-crystalline polypropyleneimine dendrimer as a stationary phase for gas chromatography

The adsorption properties of a stationary phase for gas chromatography based on a Chromaton N-AW diatomite support modified with a 2K2S16 mesomorphic polypropyleneimine dendrimer are studied. Using the Rohrschneider constants, the studied stationary phase is classified as low polar. It is shown that the new stationary phase is suitable for the separation of both isomers and mixtures of organic substances bearing various functional groups up to a temperature of 150°C.

Solubility, lipophilicity and membrane permeability of some fluoroquinolone antimicrobials.

Aqueous solubility and distribution of ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin antimicrobials drugs in octanol/buffer system has been measured by the isothermal saturation method using buffer solutions pH2.0 and 7.4 in the temperature range of 293.15-313.15K. Thermophysical characteristics for the compounds have been determined by the DSC method. It has been established that the solubility of levofloxacin in these buffers is higher than that of the other fluoroquinolones. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor-acceptor capacity of the molecules on drugs solubility has been studied. According to the lipophilicity parameter fluoroquinolones are ranged in the following order: enrofloxacin>levofloxacin>ciprofloxacin>norfloxacin. The thermodynamic solubility and distribution functions of the studied compounds have been obtained. The permeability coefficients of the substances through an artificial phospholipid membrane were determined. The drugs with a lower aqueous solubility were estimated to have higher distribution coefficients and membrane permeability.

Polymorphs and solvates of felodipine: analysis of crystal structures and thermodynamic aspects of sublimation and solubility processes

Single crystals of the crystallosolvates [felodipine + N-methylformamide] and [Fel + DMF] with 1 : 1 stoichiometry were grown, and their structures were solved by X-ray diffraction methods. The crystal structures were analyzed together with the already published felodipine forms I and II, and crystallosolvate [Fel + formamide]. The temperature dependence of saturated vapor pressure for polymorphic form I was obtained and thermodynamic characteristics of sublimation process with crystal lattice energy estimation were calculated. The fusion processes of solvatomorphs were investigated and their thermophysical parameters were determined. The differences in crystal lattice energy of the three crystallosolvates and those of the unsolvated forms were obtained by solution calorimetry technique. The impact of the “guest”/solvent molecules on the crystal lattice energy of the crystallosolvates was analyzed. The dissolution kinetics of felodipine form I, [Fel + FA], [Fel + N-Me-FA] and [Fel + DMF] in water was investigated. The solution calorimetric and solubility experiments were used to obtain the thermodynamic characteristics of phase transitions (crystallosolvate → unsolvated phase).

Thermodynamics of solution in liquid crystalline poly(propyleneimine) dendrimers by inverse gas chromatography

Thermodynamic characteristics of infinitely diluted solutions of n-alkanes and n-alcohols in the columnar and isotropic phases of poly(propyleneimine) dendrimers, generations 1-3 (G1-G3), have been investigated by inverse gas chromatography (IGC). Effects of the dendrimer structure, the chemical nature and molecular size of the non-mesogenes on the ability to get dissolved in the liquid crystalline phases are discussed. The compatibility of the low-molecular compounds with the anisotropic phases is stated to increase with generation G.

Mesomorphism of thermotropic poly(propyleneimine) dendrimers and phase equilibria in systems on their basis

The thermotropic mesomorphism of poly(propyleneimine) dendrimers of first, second, and third generations has been studied by the methods of polarization thermomicroscopy and DSC. Phase diagrams for the binary systems of dendrimers with n-amyloxy-n′-cyanobiphenyl calamite liquid crystal and hexa(pentyloxy)triphenylene discotic liquid crystal have been constructed. Measurements have been carried out over the entire concentration range at temperatures corresponding to the stable states of nematic, columnar, and isotropic phases. The effects of the chemical nature and shape of linear and cyclic mesogen molecules on the manifestation of mesomorphism in LC dendrimers are considered.

Thermodynamic parameters for the dissolution of n-alkanes and n-alkanols in a liquid-crystalline polypropylenimine dendrimer: A gas-chromatographic study

Thermodynamic parameters for the dissolution of n-alkanes (C7-C11) and n-alcohols (C5-C9) under infinite dilution in the columnar and isotropic phases of a polypropylenimine dendrimer have been determined by inverse gas chromatography. Thermodynamic functions have been investigated as a function of the phase state of a mesogen, the length of alkyl chains of sorbates, and temperature. For the dissolution of low-molecular-mass organic compounds, a higher endothermic effect corresponds to a larger entropy factor with its positive deviation from ideality. The dominant effect of the entropy constituent of the Gibbs energy on the dissolution of sorbates in a high-molecular-mass LC solvent has been revealed. The Rohrschneider constants have been estimated for the stationary phase based on the dendrimer. The experimental data indicate the low polarity of the sorbent that is close to those of phenyl-containing siloxane phases.

Chromatographic properties of fullerene modified with liquid crystal p,p'-azoxyphenetol

Stationary phases for gas chromatography based on liquid crystal p,p′-azoxyphenetol applied onto Chromaton N-AW bearing a layer of C60 fullerene were studied. The thermodynamic properties of the adsorption of n-alkanes and n-alcohols on the mesogen surface were studied at low occupancies. Test mixtures of structural isomers of substituted benzene and polycyclic aromatic hydrocarbons were analyzed in a wide temperature range from 100 to 240°C.

On the Nature of Interaction Between Fullerene and Aniline

Abstract Interaction between fullerene C60 and N,N‐dialkyl‐substituted anilines was studied by gas–liquid chromatography (GLC) and titration calorimetry. The GLC study was performed at 140–200°C in the poly(tetramethylbenzene) solvent with ultra‐high solubility of C60. No interaction of the C60–aniline type was registered under such conditions. Calorimetric titration performed at 25°C in a non‐aromatic solvent confirmed the lack of complex formation. Minute exoeffect registered is explained by suppressing of the rotation motion of the C60 molecules accompanied by energy dissipation for the aniline environment.