Evgeniy V. Rumyantsev

Spectroscopic Studies of the Supramolecular Interactions Between Uracil and 5-Hydroxy-6-Methyluracil with Bovine Serum Albumin and its Bilirubin Complex

Using fluorescence and absorption spectroscopy the interaction of bovine serum albumin and its bilirubin complex with uracil and 5-hydroxy-6-methyluracil in phosphate buffer at pH 7.4 was investigated. The parameters of forming intermolecular complexes (binding constants, quenching rate constants, the radius of the quenching sphere and etc.) were determined. The interaction between serum albumin and uracils is carried out by the static quenching of protein fluorescence and has predominantly hydrophobic character. Using synchronous fluorescence spectroscopy the influence of uracil and 5-hydroxy-6-methyluracil on the conformational changes of the protein molecule was studied. Uracils effectively binds to bilirubin-albumin complex compared to free protein, which is caused by the interaction with tetrapyrrolic pigment in macromolecular complex. Molecular docking calculations also being presented.

Magnetic silica hybrids modified with guanidine containing co-polymers for drug delivery applications

Guanidine containing co-polymers grafted onto silica nanoparticles to form core-shell structure were prepared by sol-gel method in the presence of γ-Fe2O3 nanoparticles. The morphological features for uncoated and coated silica particles have been characterized with scanning electron microscopy. The results show that the polymer coated silicas exhibit spherical morphology with rough polymeric surface covered by γ-Fe2O3 nanoparticles. The grafting amount of guanidine containing co-polymers evaluated by thermogravimetric analysis was in the range from 17 to 30%. Then, the drug loading properties and cumulative release of silica hybrids modified with guanidine containing co-polymers were evaluated using molsidomine as a model drug. It was shown that after polymer grafting the loading content of molsidomine could reach up to 3.42±0.21 and 2.34±0.14mg/g respectively. The maximum drug release of molsidomine is achieved at pH1.6 (approximately 71-75% release at 37°C), whereas at pH7.4 drug release is lower (50.4-59.6% release at 37°C). These results have an important implication that our magneto-controlled silica hybrids modified with guanidine containing co-polymers are promising as drug carriers with controlled behaviour under influence of magnetic field.

Sol-gel synthesis of highly effective catalyst based on cobalt tetrasulfophthalocyanine complex and silicon oxide

New hybrid materials based on silicon oxide and water soluble cobalt phthalocyanine complex were synthesized and characterized. It was shown that synthesized material exhibit pronounced catalytic activity in the R–SH type of organic compounds oxidation reaction in comparison with the individual macroheterocycle. The influence of the synthetic route of the hybrid material preparation on its catalytic efficiency was determined.

Recent Advances of Individual BODIPY and BODIPY-Based Functional Materials in Medical Diagnostics and Treatment

BACKGROUND The group of fluorophores on boron dipyrrin platform (4,4- difluoro-4-bora3a,4a-diaza-s-indacene, also known as BODIPY) has attracted much attention in the field of molecular sensorics, including sensing of biomolecules and bioprocesses. Structural diversity of existing BODIPY with ample opportunities of directed modification of compounds makes this class of fluorophores attractive for medical and biological purposes. The recent progress in the design and functionalization of BODIPY allows using them for modification of drug micro- and nanocarriers in order to improve their therapeutic effect in cancer treatment. At the same time, integration of BODIPY into drug carriers provides the possibility of in vitro and in vivo real time imaging of used drug carriers. The high fluorescent intensity and low toxicity of BODIPY granted for conjugation with different biomolecules. RESULTS The present review focuses on the recent advances for application of individual BODIPY in medical diagnostics, antimicrobial activity, as well as establishing the role of BODIPY in labeling of biomolecules (e.g. proteins, hormones and DNA). Also the review highlights the potential of BODIPY in functionalization of drug micro- and nanocarriers in order to achieve better therapeutic efficiency compared with non-modified materials. The advantages derived from the use of BODIPY for preparation and modification of drug carriers are critically evaluated and potential for future challenges, especially concerning the design of innovative multi-functional BODIPY-based nanocarriers, is discussed in detail using representative examples from literature. CONCLUSION Our objective was to show that BODIPY are powerful tools for bioimaging, labeling of biomolecules and construction of new multifunctional drug carriers.

Fluorescent Properties of 8-phenylBODIPY in Ethanol – Ethylene Glycol Mixed Solutions

Fluorescent characteristics of two BODIPY dyes in solutions were investigated under the viscosity variations. Investigated dyes differ in the nature of 8-substituent of ligand molecule. Viscosity variation was achieved by changing of solvent composition in the binary system ethanol - ethylene glycol and solvent temperature. 8-Phenyl substituted BODIPY is found to exhibit properties of molecular rotor, i.e. its fluorescent characteristics are highly dependent on the viscosity or rigidity of the microenvironment. Increased temperature leads to a linear decrease of fluorescence parameters unlike the solvent composition variation where fluorescence change is nonlinear. The highest specific change in the fluorescence was observed in pure ethanol. Change in the nonradiative decay rate constant values with the increasing of viscosity indicates that the analyzed phenyl substituted complex is a true molecular rotor. Investigated 8-phenylBODIPY could be recommended as promising viscosity sensor in different organic media.

Analysis of solvation and structural contributions in spectral characteristics of dipyrrin Zn(II) complexes

Photophysical characteristics of several alkylated dipyrrin Zn(II) complexes in organic solvents were analyzed. Relations between spectral properties of complexes and physical-chemical parameters of solvents were determined with the use of linear regression analysis method. Each solvent parameter contribution in investigated spectral characteristics was estimated. Spectral properties of complexes under study depend on the specific interactions of zinc with the solvent molecules by specific axial coordination. Increasing of alkyl substitution lead to the bathochromic shifts in spectra due to the positive induction effect of alkyl groups.

Spectral and Photophysical Properties of Zinc(II) Complexes with Alkylsubstituted Derivatives of Dipyrrolylmethene and Their Resistance to Protolytic Dissociation and Photochemical Destruction

The spectral and photophysical properties of zinc(II) complexes with alkylsubstituted derivatives of dipyrrolylmethene, along with the kinetics of their protolytic dissociation and photochemical degradation in organic solvents of different natures, are studied by means of electronic absorption and fluorescence spectroscopy. It is found that protic solvents have the strongest effect on absorption spectra, while electron donors affect fluorescence spectra due to differences in the mechanisms of solvation for the ground and excited states of molecules. It is shown that the reaction product of the protolytic dissociation of complexes in benzene solutions of acetic acid is a protonated form of ligand. The observable and genuine rate constants of dissociation reactions are determined and activation parameters are calculated. A kinetic model of the process is proposed, and the regularities of the effect the nature of ligand has on the kinetics of dissociation are established. The photochemical degradation of compounds proceeds on monopyrrole products, the photolysis rate falls as the a degree of alkylation increases, and the nature of the substituent in the β-position of the ligand’s pyrrole ring has a greater effect on the stability of a compound.

Fluorescent Properties of BODIPY Sensors Based on Photoinduced Electron Transfer.

Two boron-dipyrrin (BODIPY) based dyes with dimethylaminophenyl and carboxyphenyl substituents in 8-position of dipyrrin ligand have been synthesized and characterized. Photophysical and spectral properties of the obtained compounds have been investigated in water-ethanol mixture and water-cyclohexane system with variation of pH values. The equilibria constants of the compounds were identified by classical methods of acid-base titration. BODIPY bearing dimethylaminophenyl and carboxyphenyl subunits show deprotonation/protonation dependent fluorescence off/on-switching. The change of the emission could be mechanistically explained by a PET (photoinduced electron transfer) from the 8-substituent to the fluorophore. The present study demonstrates that BODIPY-based fluorescent sensors can be used to measure the pH in the range of 2–13 extending the scope of BODIPY dyes available as pH-indicators. Investigated compounds demonstrate weak dye-dye interaction allowing their cooperative usage as indicators.

Kinetics of oxidation of bilirubin and its protein complex by hydrogen peroxide in aqueous solutions

A comparative study of oxidation reactions of bilirubin and its complex with albumin was carried out in aqueous solutions under the action of hydrogen peroxide and molecular oxygen at different pH values. Free radical oxidation of the pigment in both free and bound forms at pH 7.4 was shown not to lead to the formation of biliverdin, but to be associated with the decomposition of the tetrapyrrole chromophore into monopyrrolic products. The effective and true rate constants of the reactions under study were determined. It was assumed that one possible mechanism of the oxidation reaction is associated with the interaction of peroxyl radicals and protons of the NH groups of bilirubin molecules at the limiting stage with the formation of a highly reactive radical intermediate. The binding of bilirubin with albumin was found to result in a considerable reduction in the rate of the oxidation reaction associated with the kinetic manifestation of the protein protection effect. It was found that the autoxidation of bilirubin by molecular oxygen with the formation of biliverdin at the intermediate stage can be observed with an increase in the pH of solutions.

Effect of π-Extended Substituents on Photophysical Properties of BODIPY Dyes in Solutions.

Four boron-dipyrrine (BODIPY) based dyes with π-extended substituents in 8-position of dipyrrin ligand have been synthesized and characterized. Photophysical properties of the obtained compounds have been investigated in different individual solvents. Deposits of solvent polarity and viscosity were evaluated. BODIPY with 8-biphenyl substituent was found to be the fluorescent molecular rotor in contrast to more extended substituents. The complex nature of solvent-solute interactions leads to the poor applicability of standard multiparameter approaches to BODIPY solvatochromic properties. Fluorescence intensity was found to increase in case of solvent polarity growth, it is not typical for BODIPY. Taking that into account the BODIPY with π-extended substituents could be used for fluorescence viscosity measurements, and as the fluorescent media polarity indicators in analytical chemistry and biochemistry.