Nikolay E. Polyakov

Water Soluble Complexes of Carotenoids with Arabinogalactan

We present the first example of water soluble complexes of carotenoids. The stability and reactivity of carotenoids in the complexes with natural polysaccharide arabinogalactan were investigated by different physicochemical techniques: optical absorption, HPLC, and pulsed EPR spectroscopy. Compared to pure carotenoids, polysaccharide complexes of carotenoids showed enhanced photostability by a factor of 10 in water solutions. A significant decrease by a factor of 20 in the reactivity toward metal ions (Fe(3+)) and reactive oxygen species in solution was detected. On the other hand, the yield and stability of carotenoid radical cations photoproduced on titanium dioxide (TiO(2)) were greatly increased. EPR measurements demonstrated efficient charge separation on complex-modified TiO(2) nanoparticles (7 nm). Canthaxanthin radical cations are stable for approximately 10 days at room temperature in this system. The results are important for a variety of carotenoid applications, in the design of artificial light-harvesting, photoredox, and catalytic devices.

Free Radical Formation in Novel Carotenoid Metal Ion Complexes of Astaxanthin

The carotenoid astaxanthin forms novel metal ion complexes with Ca(2+), Zn(2+), and Fe(2+). MS and NMR measurements indicate that the two oxygen atoms on the terminal cyclohexene ring of astaxanthin chelate the metal to form 1:1 complexes with Ca(2+) and Zn(2+) at low salt concentrations <0.2 mM. The stability constants of these complexes increased by a factor of 85 upon changing the solvent from acetonitrile to ethanol for Ca(2+) and by a factor of 7 for Zn(2+) as a consequence of acetonitrile being a part of the complex. Optical studies showed that at high concentrations (>0.2 mM) of salt, 2:1 metal/astaxanthin complexes were formed in ethanol. In the presence of Ca(2+) and Zn(2+), salts the lifetime of the radical cation and dication formed electrochemically decreased relative to those formed from the uncomplexed carotenoid. DFT calculations showed that the deprotonation of the radical cation at the carbon C3 position resulted in the lowest energy neutral radical, while proton loss at the C5, C9, or C13 methyl groups was less favorable. Pulsed EPR measurements were carried out on UV-produced radicals of astaxanthin supported on silica-alumina, MCM-41, or Ti-MCM-41. The pulsed EPR measurements detected the radical cation and neutral radicals formed by proton loss at 77 K from the C3, C5, C9, and C13 methyl groups and a radical anion formed by deprotonation of the neutral radical at C3. There was more than an order of magnitude increase in the concentration of radicals on Ti-MCM-41 relative to MCM-41, and the radical cation concentration exceeded that of the neutral radicals.

Photochemical and Optical Properties of Water-Soluble Xanthophyll Antioxidants: Aggregation vs Complexation

Xanthophyll carotenoids can self-assemble in aqueous solution to form J- and H-type aggregates. This feature significantly changes the photophysical and optical properties of these carotenoids, and has an impact on solar energy conversion and light induced oxidative damage. In this study we have applied EPR and optical absorption spectroscopy to investigate how complexation can affect the aggregation ability of the xanthophyll carotenoids zeaxanthin, lutein, and astaxanthin, their photostability, and antioxidant activity. It was shown that complexation with the polysaccharide arabinogalactan (AG) polymer matrix and the triterpene glycoside glycyrrhizin (GA) dimer reduced the aggregation rate but did not inhibit aggregation completely. Moreover, these complexants form inclusion complexes with both monomer and H-aggregates of carotenoids. H-aggregates of carotenoids exhibit higher photostability in aqueous solutions as compared with monomers, but much lower antioxidant activity. It was found that complexation increases the photostability of both monomers and the aggregates of xanthophyll carotenoids. Also their ability to trap hydroperoxyl radicals increases in the presence of GA as the GA forms a donutlike dimer in which the hydrophobic polyene chain of the xanthophylls and their H-aggregates lies protected within the donut hole, permitting the hydrophilic ends to be exposed to the surroundings.

Complex of Calcium Receptor Blocker Nifedipine with Glycyrrhizic Acid

Physicochemical methods were used to explore the regularities of complexing between the calcium channel blocker nifedipine (NF) and pharmaceutically acceptable complex-forming glycyrrhizic acid (GA) in view of the discovered influence of GA on the therapeutic activity of NF. 1H NMR (including relaxation measurements) and UV-vis spectra have produced illustrative evidence that NF forms stable complexes with GA within a wide concentration range, from 0.05 to 5 mM. At low GA concentrations, below 0.5 mM, NF forms an inclusion complex where each NF molecule is bound by two molecules of GA. Computer simulations of the NMR experimental data have shown that, in aqueous solution, the stability constant of this complex, K, is about 10(5) M(-1). At higher concentrations, GA forms large micelle-like aggregates which increase the water solubility of NF. Quenching of chemically induced dynamic nuclear polarization effects in the photoinduced interaction of the NF-GA complex with tyrosine suggests that complex formation with GA completely blocks the single electron-transfer step between NF and the amino acid. This, arguably, could explain the increased therapeutic activity of GA complexes, since GA might protect the drug molecule from the reaction with amino acid residues of the receptor binding site.

Enhancement of the Photocatalytic Activity of TiO2 Nanoparticles by Water-Soluble Complexes of Carotenoids †

Photoirradiation of TiO(2) nanoparticles by visible light in the presence of the water-soluble natural polysaccharide arabinogalactan complexes of the hydrocarbon carotenoid β-carotene leads to enhanced yield of the reactive hydroxyl (OH) radicals. The electron paramagnetic resonance (EPR) spin-trapping technique using α-phenyl-N-tert-butyl nitrone (PBN) as the spin-trap has been applied to detect this intermediate by trapping the methyl and methoxy radicals generated upon reaction of the hydroxyl radical with dimethylsulfoxide (DMSO). The free radicals formed in this system proceed via oxygen reduction and not via the reaction of holes on the TiO(2) surface. As compared with pure carotenoids, carotenoid-arabinogalactan complexes exhibit an enhanced quantum yield of free radicals and stability toward photodegradation. The observed enhancement of the photocatalytic efficiency for carotenoid complexes, as measured by the quantum yield of the desired spin adducts, arises specifically from the decrease in the rate constant for the back electron transfer to the carotenoid radical cation. These results are important for a variety of TiO(2) applications, namely, in photodynamic therapy, and in the design of artificial light-harvesting, photoredox, and catalytic devices.

Solubilization and stabilization of macular carotenoids by water soluble oligosaccharides and polysaccharides

Xanthophyll carotenoids zeaxanthin and lutein play a special role in the prevention and treatment of visual diseases. These carotenoids are not produced by the human body and must be consumed in the diet. On the other hand, extremely low water solubility of these carotenoids and their instability restrict their practical application as components of food or medicinal formulations. Preparation of supramolecular complexes of zeaxanthin and lutein with glycyrrhizic acid, its disodium salt and the natural polysaccharide arabinogalactan allows one to minimize the aforementioned disadvantages when carotenoids are used in food processing as well as for production of therapeutic formulations with enhanced solubility and stability. In the present study, the formation of supramolecular complexes was investigated by NMR relaxation, surface plasmon resonance (SPR) and optical absorption techniques. The complexes increase carotenoid solubility more than 1000-fold. The kinetics of carotenoid decay in reactions with ozone molecules, hydroperoxyl radicals and metal ions were measured in water and organic solutions, and significant increases in oxidation stability of lutein and zeaxanthin in arabinogalactan and glycyrrhizin complexes were detected.

Polysaccharide arabinogalactan from larch Larix sibirica as carrier for molecules of salicylic and acetylsalicylic acid: preparation, physicochemical and pharmacological study

Abstract Inclusion complexes of salicylic acid (SA) and acetylsalicylic acid (aspirin, ASA) with polysaccharide arabinogalactan (AG) from larch wood Larix sibirica and Larix gmelinii were synthesized using mechanochemical technology. In the present study, we have investigated physicochemical properties of the synthesized complexes in solid state and in aqueous solutions as well as their anti-aggregation and ulcerogenic activity. The evidence of the complexes formation was obtained by nuclear magnetic resonance (NMR) relaxation technique. It was shown that in aqueous solution the molecules of SA and ASA are in fast exchange between the complex with AG macromolecules and solution. The stability constant of aspirin complex was calculated. It was shown that mechanochemically synthesized complexes are more stable when compared to the complex obtained by mixing solutions of the components. Complexes of ASA show two-fold increase of anti-platelet effect. It allows to reduce the dose of the antithrombotic drug and its ulcerogenic activity. These results substantiate the possibility to design new preparations on the basis of ASA with increased activity and safety.

The mechanisms of the oxidation of NADH analogues 1. Photochemical oxidation of N-unsubstituted 1,4-dihydropyridines by various acceptors

Abstract The reactivity of different active centers has been studied during the photo-oxidation of N -unsubstituted 1,4- dihydropyridines (1,4-DHPs) by various electron acceptors. The participation of that or another reactive center (NH, (C-4)H, (C-3)CO group) in the reaction has been observed, depending on the type of process, 1,4- DHP structure, medium polarity and related properties. In the case of photo-initiated interaction with electron acceptors, the elementary mechanism of the process includes the sequential stages of electron, proton and hydrogen atom transfer (e − , H + , H . ) if the electron acceptors are quinones which are able to form charge transfer complexes with the initial 1,4-DHP. When acceptors of another type are used, the primary act of the photo-oxidation process is the abstraction of hydrogen atoms from the C-4 position of the 1,4-DHP, and the oxidation takes place as the two-stage (H . , H . ) process.

The mechanisms of the oxidation of NADH analogues 2. N-Methyl-substituted 1,4-dihydropyridines

Abstract The mechanism of the photoinitiated oxidation of N -methyl-substituted 1,4-dihydropyridines (1,4-DHPs) by quinones was studied in acetonitrile. Electron transfer with the formation of a radical ion pair (radical cation of 1,4-DHP and radical anion of acceptor) forms the initial stage of the process. Abstraction of a hydrogen atom from the 1,4-DHP radical cation in the bulk leads to the formation of the main product of photo-oxidation — pyridinium cation. Traces of water in the reaction mixture and the pH exert a significant influence on the photo-oxidation of N -substituted 1,4-DHPs.

Influence of glycyrrhizin on permeability and elasticity of cell membrane: perspectives for drugs delivery.

Abstract Glycyrrhizin or glycyrrhizic acid (GA) – triterpene glycoside extracted from licorice root – has been intensively studied over the past decade and is considered to be a potential drug delivery system. Glycyrrhizin was found to enhance the therapeutic effect of various drugs; however the detailed mechanism of these effects is still unknown and attracts the attention of researchers. In this work, we have made an attempt to clarify the mechanism of Glycyrrhizin activity on molecular and cellular level. The influence of GA on the functional properties of biomembranes was investigated via NMR spectroscopy and atomic force microscopy (AFM) using human erythrocytes as a model system. GA was shown to increase the permeability (about 60%) and to decrease elasticity modulus of cell membranes (by an order of magnitude) even in micromolar concentrations. Changes on the erythrocyte surface were also detected by AFM. These results could provide a new insight on the mechanism of bioavailability enhancement of some drugs in the presence of glycyrrhizin, as well as the mechanism of its own biological activity. The role of cholesterol–glycyrrhizin binding in the observed effects is also discussed.