Retention-hydrophobicity relationships for polyaromatic hydrocarbons and 4-hydroxybenzoic acid esters by micellar liquid chromatography data

A.P. Boichenko¹, L.P. Loginova¹, A.U. Kulikov^1,2, A.L. Iwashchenko^1,3,
М.М. Galat¹

¹ V.N. Karazin Kharkiv National University
4 Svobody sq., Kharkiv, 61077, Ukraine

² Scientific and Expert Pharmacopoeial Centre
33 Astronomicheskaya Str., Kharkiv, 61085, Ukraine

³ Testing Analytical Laboratory of Joint-Stock Company «Stoma»
3 Newton Str., Kharkiv, 61105, Ukraine

Summary: Owing to lack of generally accepted methodology, the retention-hydrophobicity relationships in liquid chromatography are constructed on the basis of physical-chemical models as well as by using of empirical equations. Number of equations increased terrifically for micellar liquid chromatography in consequence of increasing of factors influencing on selectivity and elution strength by comparison with reversed-phase liquid chromatography. However disembodied data do not allow recognizing clearly the advantages of one of the approaches.
In this work the quality of modeling of retention-hydrophobicity relationships was tested on the unified experimental data. It was observed that composition of mobile phase influence considerably on quality of retention-hydrophobicity relationships. As a result it is perspective to search unified method for estimation of hydrophobicity by micellar liquid chromatography.
Systematic investigation of influence of mobile phase composition on quality of relationships between k/logk and logK_ow for parabens (logK_ow from 1.96 to 3.57) leads to consequence of inadequacy of both models. Thus, it is inexpedient to use of relationship k – logK_ow because of absence of thermodynamic explanation even if it could provide more high correlation coefficients.
Parameters of Arunyanart and Cline-Love model (binding constants of analytes by micelles in mobile phase) are calculated with high uncertainty and as sequence could not provide high quality of modeling. Parameters of another physical-chemical model that based on quasi-chemical model of micelle formation have been used for derivation of new model for hydrophobicity estimation. However quality of new model could not be evaluated on the basis of available data.
At present time more universal and adequate is a methodology of hydrophobicity evaluation that based on the using of relationships between logk_mw and logK_ow, where logk_mw is obtained by extrapolation of logarithm of retention factor on zero concentrations of surfactant and organic modifier in micellar eluent.
It was demonstrated that the deviations from linearity for first members of homologous series or congeneric substances is nonrandom. Thus, it is appropriate using of micellar liquid chromatography for estimation of hydrophobicity of compounds with logK_ow not less than 3.

Keywords: partition constant; 1-octanol-water; retention-hydrophobicity; esters of 4-hydroxybenzoic acid; polyaromatic hydrocarbons.

 

Search of bioregulators with antioxidant action among S-derivatives of 4-merkaptoquinoline

L.A. Omelyanchik¹, V.I. Gencheva¹, D.M. Fedoryak², A.A. Brazhko¹, M.P. Zavgorodny¹, I.B. Labenskaya¹, M.N. Kornet<sup>1

1</sup> Zaporizhzhya National University
66 Zhukovsky Str., Zaporizhzhya, 63000, Ukraine

² Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine
1 Murmanska Str., Kyiv, 02094, Ukraine

Abstract: The article deals with the computer prognosis of feasible biological activity types among S-derivative 4-mercaptoquinolines and the synthesis of the respective compounds. These compounds are proved to have a wide range of biological effects. The dependence between the chemical structure of the compounds under study and their biological effect is stated.

Keywords: computer prognosis, virtual screening, S-derivative 4-mercaptoquinolines, antioxidative effect, «structure-effect» dependence.

The role of protein kinase CK2 in the regulation of oncogenesis, apoptosis and cellular stress response

G.P. Volynets, A.G. Golub, V.G. Bdzhola, S.M. Yarmoluk

Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv, 03143, Ukraine

Summary: Protein kinase CK2 is an ubiquitously expressed and pleiotropic protein kinase. CK2 is implicated in the regulation of several important cellular processes. CK2 is an important component in the network of integrated signaling pathways.
The main aim of review is a characterization of the role of CK2 in the regulation of neoplastic transformation, apoptosis and cellular stress response. CK2 takes part in oncogenesis аnd in progression of other pathological processes. Thus, CK2 is a potential target for developing of drugs, that can be used in medicine.

Keywords: protein kinase CK2, cell survival, oncogenesis, stress signaling pathway.

 

Synthesis of oligonucleotide 5’-conjugates with imidazophenazine intercalating agent

I.Ya Dubey¹, L.V. Dubey¹, D.M. Fedoryak², V.M. Zozulya³

¹ Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv, 03143, Ukraine

² Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine
1 Murmanska Str., Kyiv, 02094, Ukraine

³ B.I. Verkin Institute for Low Temperature Physics & Engineering, NAS of Ukraine, 47 Lenin ave., Kharkiv, 61103, Ukraine

Summary: New conjugate of the model 15-mer oligonucleotide (Tp)₁₄T with imidazo[4,5-b]phenazine intercalating agent was obtained. Reaction of N1-carboxyalkyl derivative of imidazophenazine with 5’-aminoalkyl-functionalized oligonucleotide in the presence of phosphonium coupling reagent BOP was used for the synthesis of modified oligothymidylate. Some spectral characteristics of the labeled oligomer were studied.

Keywords: oligonucleotide conjugates, intercalating agents, solid phase synthesis, functionalization, phosphonium reagents.

 

Facile synthesis of 2,3-phthaloylpyrocoline-1-carboxylic acid and its new derivatives

M.V. Stasevych, M.Yu. Plotnikov, M.O. Platonov, S.I. Sabat, R.Ya. Musyanovych, V.P. Novikov

Institute of Chemistry and Chemical Technology, National University «Lviv Polytechnic», 12 Bandera Str., Lviv, 79013, Ukraine


Summary: New amide and ester derivatives of 2,3-phthaloylpyrocoline-1-carboxylic acid were synthesized. The preparation of 2,3-phthaloylpyrocoline-1-carboxylic acid was improved. Obtained heterocycles are very important in organic synthesis for the search of new biologically active compounds with a wide spectrum of activity. Biological activity prediction using computer program PASS C&T was performed to indicate that newly synthesized compounds require further evaluation.

Keywords: 2,3-phthaloylpyrocoline-1-carboxylic acid.

Adenosine conformational possibilities: the DFT quantum mechanical investigation

R.O. Zhurakivsky¹, D.M. Hovorun²

¹ Taras Shevchenko National University
2 Glushkova Ave., Kyiv, 03127, Ukraine

² Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv, 03143, Ukraine

Summary: Comprehensive conformational analysis of adenosine, the canonical RNA nucleoside, is performed by means of density functional theory at MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) level. Main geometric, energetic and polar characteristics of all its 137 conformers are presented, as well as conformational equilibria in temperature interval 298.15-420 K. At T=298.15 K these are syn:anti=45.0%:55.0%; S:N=98.6%:1.4% and at T=420 K syn:anti= 34.9%:65.1%; S:E:N=93.3%:0.4%:6.3%. By quantum mechanical electron density topology analysis method (Bader’s Atoms-in-Molecules theory) as many as 20 types of intramolecular hydrogen bonds are established (their total number is 312) in all possible conformers of adenosine, namely these are C2’H...O5’, C2’H…N3, C3’H…N3, C3’H...HC8, C5’H1…N3, C5’H1…N9, C5’H1…C8, C5’H2…N3, C5’H2…N9, C5’H2…C8, C8H…O5’, O2’H...O3’, O2’H...N3, O3’H...O2’, O3’H...O5’, O5’H...O3’, O5’H…N3, O5’H…N9, O5’H...C8, and O5’H...HC8. Their conformational properties, geometric and electron topology characteristics are described.

Keywords: adenosine, conformational analysis, intramolecular hydrogen bonds, electron density topology analysis, DFT.

To the studies on (p-dimethylaminostyryl)pyridinium based homodimer to dsDNA binding mechanism

M.Yu. Losytskyy¹, N. Akbay², V.B. Kovalska¹, A.O. Balanda¹, A. Boutorine³ and S.M. Yarmoluk¹

¹ Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine
150 Zabolotny Str., Kyiv, 03143, Ukraine

² Hacettepe University, Department of Chemistry
06800, Ankara, Turkiye

³ Museum National d’Histoire Naturelle, RDDM, USM 0503, 43 rue Cuvier, Paris Cedex 05, F-75231 France; INSERM, U565, Paris, F-75231 France; CNRS, UMR 5153, Paris, F-75231 France

Summary: With the aim to study the interaction mode of (p-dimethylaminostyryl)pyridinium homodimer dye Dst-6 with dsDNA, the equilibrium constant of dye-dsDNA binding (K) and the number of dsDNA base pairs occupied with one bound dye molecule were estimated. Obtained data support the previously made suggestion about realization of groove-binding mechanism of dye-DNA interaction.

Keywords: styrylcyanine dye, DNA, fluorescence, groove-binding, binding constant.

Synthesis and structural study of N-substituted-1,7-dithia-4-azaspiro[4.4]nonan-3-one 7,7-dioxides

P.V. Shaitanov¹, S.S. Lukashov¹, O.V. Turov², S.M. Yarmoluk¹

¹ Institute of Molecular Biology and Genetics, NAS of Ukraine
150 Zabolotny Str., Kyiv, 03143, Ukraine

² Department of Chemestry, Taras Shevchenko National University
64 Volodymyrska Str., Kyiv, 01033, Ukraine

Summary: Reaction of 3-bromo-2,3-dihydrothiophene 1,1-dioxide with N-substituted-2-mercapto-N-R-acetamides in presence of KOH gave new derivatives of 1,7-dithia-4-azaspiro[4.4]nonane heterocyclic system. Structure of obtained derivatives was confirmed by methods of NМR-spectroscopy.

Keywords: 1,7-dithia-4-azaspiro[4.4]nonane, 4-R-1,7-dithia-4-azaspiro[4.4]nonan-3-one 7,7-dioxide, 3-bromo-2,3-dihydrothiophene 1,1-dioxide, 2-mercaptoacetamide, sulfolene, NMR.