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Abstract— We have developed an alternative method for the synthesis of an analog of natural retinal, which contains the p-fluorophenyl fragment instead of the trimethylcyclohexene ring. The proposed scheme for the synthesis of the target all-E-isomer of the target retinoid consists of using C5-phosphonate that contains the terminal nitrile group under Horner–Emmons reaction conditions. It has been shown that this scheme is more efficient and provides a higher total yield of the target product than the previously described variant. The procedure has been developed for the preparation of an analog of microbial proteorhodopsin ESRh from Exiguobacterium sibiricum, which contains a modified chromophore. It has been found that, as in the case of bacterioopsin from Halobacterium salinarum, the replacement of the trimethylcyclohexene ring in the natural chromophore by the p-fluorophenyl fragment does not prevent the formation of the artificial pigment F-Phe-ESRh from proteorhodopsin ESRh, which preserves the cycle of photochemical reactions. Certain differences have been found between the properties of native recombinant ESRh and its analog F-Phe-ESRh including a shift in the absorption maximum to the short-wavelength region, the formation of M intermediate at lower pH values, the presence of “long-lived M,” and a general slowdown in the photocycle. The reduced stability of the resulting proteorhodopsin analog F-Phe-ESRh to prolonged exposure to visible light has been also demonstrated.

The state and the prospects of implementation of major investment projects combined into the Eastern Gas Program have been analyzed. The terms of realization, the state of resources and the state of gas transportation system under the projects forming part of them are considered. It is shown that only one (Sakhalin) of four gas production centers foreseen in the program has an adequate infrastructure; the unifed gas transportation system has not been established, and the gas processing industry has received insuffcient development. It has been determined that the capacity of the pipeline makes up 70% of the total production volume and this is the factor limiting the development of the gas production and processing industry in the regions. The reasons for a change of the terms and conditions of the development of the projects of the Eastern Gas Program have been investigated. It is shown that the discrepancy in key goals and the actual state of gas industry in the eastern regions of the country is explained by the changing situation in the key gas markets, which determines the fnal economic effciency of the projects, the lack of the solution to long-term demand problems and stable sources of fnancing. The prospects of the development of the projects of the Gas Program and the risks of implementation for the Russian side have also been investigated. The article describes a dependence of the implementation of separate projects on the possibility of signing effcient international contracts with the countries of the Asia-Pacifc region and on the success of the strategy of formation of new export goods niches based on the in-depth processing of hydrocarbon raw materials. The consequences of creating the full-scale gas industry in Eastern Russia have been analyzed. It has been determined that the projects within the Program with a focus on the formation of the national export income have been implemented. It is shown that the projects within the Program do not ensure an accelerated development of the Eastern regions of the country because of the lack linkages between the projects and other branches of regional economy. Furthermore, the regions do not accumulate fnancial resources from the project implementation.

Guidelines and principles for the development of new labels and probes for bionanophotonics, methods for their preparation, and labeling procedures for various targets are briefly discussed.

The effects of chromophoric group structures on the functional properties of bacteriorhodopsin (BR) and proteorhodopsin from E. sibiricum (ESRh) were compared. ESRh retinal binding site was found as preserving the similar stereo- and spatial restrictions on the chromophore structure during the retinal protein reconstitution process (except for C25-analog AR8). It was revealed that the structure peculiarities of the chromophore analog molecules affect the optical parameters of ESRh and BR pigment families in similar ways.

A series of 5-substituted 3-pyridylisoxazoles were synthesized using [3+2] cycloaddition of nitrile oxides to alkynes with variation of substituents at position 5 of the isoxazole ring without additional synthetic stages and with retention of 2-pyridyl-, 3-pyridyl, and 4-pyridyl substituents at position 3 of the isoxazole ring. Substituted pyridylisoxazoles are the potential antiaggregatory agents showing in vitro activity in the concentration range from 1•10−6 mol L−1 to 1•10−4 mol L−1 toward the human platelet rich blood plasma with arachidonic acid being used as the inductor of aggregation. These compounds do not act as cyclooxygenase or thromboxane synthase inhibitors, nor as thrombin inhibitors.

A number of photochromic markers, viz., spirobenzopyrans containing one or two active carboxy groups attached directly or through a spacer, as well as their model derivatives, were synthesized. The obtained compounds were characterized by instrumental methods of analysis. Spectrokinetic methods were used to study the behavior of the spirobenzopyran markers and the model derivatives in solutions in EtOH and toluene.

The absorption spectra and decay kinetics of the ground and triplet states of merocyanine (MC) form of spiropyran vinylogs have been investigated by nanosecond laser flash photolysis techniques in toluene and ethanol. The 3 MC decays to the ground state MC either by quenching with O 2 or due to the intersystem crossing. Relative quantum yield of both 3 MC and MC drastically decreases when the terminal polar group is separated from the indoline moiety by the C C-linker. In the presence of the C C-linker the replacement of terminal CN by CHO has no effect. The yield of 3 MC and corresponding MC in ethanol is 5 times smaller than that in toluene solution.

A method for synthesizing a photochromic ligand and using it as a structural element in a new nanodimensional hybrid construction in which CdSe quantum dots are covalently bonded to a spiropyran molecule has been proposed. Such a hybrid construction makes it possible to reversibly control the system fluorescence using a change in spiropyran ligand structure induced by light with different wavelengths (a reversible conversion from a colorless closed form into a colored merocyanine form). The possibilities for using this type of hybrid material for photocontrollable devices in nanophotonics are discussed.

Spectral-kinetic properties of intermediates of spiropyran retinal analogs (SRA), which molecules contain spiropyran and retinoid (with different polyenic chain length and aldehyde terminal group) fragments, have been investigated by nanosecond laser flash photolysis techniques using excitation wavelengths 337 and 380–450 nm in toluene. Relative quantum yields of different SRA intermediates formation relative to those of model compounds, namely triplet excited state and merocyanine form generated upon pyran cycle cleavage have been measured. It has been found that merocyanine form does not form upon photolysis of SRA with polyenic chain length of 5 and 9 using excitation wavelengths of 380–450 nm, the triplet state of retinoid fragment is observed exclusively. The yield of merocyanine (MC) form is the largest one upon SRA photolysis with excitation wavelength of 337 nm for 6′-formylsubstituted spiropyran (it exceeds that of unsubstituted analog in 8 times and forms mainly from the triplet state). The yields of MC for SRA with polyenic chain length of 3, 5 and 9 carbon atoms are 5–10 times smaller than that for unsubstituted spiropyran.

The model peptide synthesis from mixtures of amino acids was carried out under the thermal cycling and isothermal modes. The compositions of the obtained mixtures of products and the primary amino acid sequence of the synthesized peptides were determined by Fourier transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry in combination with high-performance liquid chromatography with the application of de novo sequencing of the synthesized products. The processes of abiogenous synthesis of peptides were shown to occur under relatively mild temperature conditions and give a substantially less number of peptides as compared with the possible statistical set. The evolution of the system takes place in the process of the synthesis in solid phase with the disappearance of a series of the most unstable peptides. The selection process with the formation of complementary peptides takes place in peptide synthesis under the thermal cyclic mode.

In the present review, we summarize our recent studies on the synthesis and spectral–kinetic parameters of photochromic retinals based on spiropyrans, diarylethenes, and a fulgimide and the use of these compounds for the preparation of artificial analogs of natural bacteriorhodopsin.

Two bioisosteric analogs, 5-phenyl-3-(3-pyridyl)isoxazole and 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole, were synthesized so as to compare their antiaggregatory activities, to determine a pharmacologically active fragment in molecules of this type, and to explore the mechanisms of action of potential antiag-gregatory compounds belonging to the class of 3,5-substituted isoxazoles. Antiaggregatory activities of these compounds were studied in vitro using three aggregation inducers, such as arachidonic acid, adenosine diphosphate, and adrenaline. It was shown that 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole and 5-phenyl-3-(3-pyridyl)isoxazole completely suppressed platelet aggregation induced by arachidonic acid and the second wave of platelet aggregation induced by adrenaline or adenosine diphosphate. The antiaggregatory activity of substituted isoxasole was 1.1–1.5 times higher than that of substituted oxadiazole. In contrast to the isoxazole analog, 5-phenyl-3-(3-pyridyl)-1,2,4-oxadiazole in concentrations of 300–400 μM partially suppressed the first wave of aggregation induced by adenosine diphosphate. It was demonstrated that both compounds were not thrombin inhibitors in vitro at concentrations up to 250 μM. Thus, introduction of a nitrogen atom into the C4-position of the isoxazole ring changes the molecule properties. It suggests that the pharmacophoric fragment of the molecule should be the whole isoxazole or 1,2,4-oxadiazole ring but not a part of the ring as was supposed previously.

Four new retinal analogs on basis of nitro-substituted indoline spiropyran were prepared and the spectral kinetic study of their photochromic properties was carried out. Specific influence of nature and length of polyenic substituents on spectral characteristics of spiropyran forms, efficiency of photochromic transformations and photodegradation was established.

New dihetarylethenic retinal analogs were synthesized, and their photochromic behavior was studied. The relationship between the compound structures and their spectral and kinetic parameters was determined due to the comparative spectral-kinetic studies of synthesized dihetarylethenes. It was shown, that all synthesized compounds possess expressed photochromic properties and the thermal irreversibility. The best kinetic characteristics for the photocyclization process as well as a low photodegradation were measured for short-chain nitrile.

The synthesis of retinal analogue series that contain a spyropyran moiety instead of a trimethylcyclohexene ring was proposed. The process of the retinal analogue interaction with bacterioopsin from apomembranes of Halobacterium salinarum and the spectral properties of the newly formed pigments were studied. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru.

Spectral properties of new crowned spiropyrans and their cationic complexes are described.

The spectral properties of new crowned retinal analogs and their bacteriorhodopsin complexes are described.

A new 5,10,15,20-tetrasubstituted porphyrin containing four 6’-nitro-1,3,3-trimethylspiro(indolino-2,2’-2H-chromene) substituents and its complexes with Zn2+ and Cu2+ ions were prepared and characterized by physicochemical methods of analysis.

An effective synthetic approach to the preparation of a new crown-ether vinylogs involving the Horner–Emmons olefination of carbonyl precursors with the use of C2- and C5-phosphonates was proposed. The effects of the conjugation chain length and the nature of the terminal polar functions in the phosphonate reagent on the yield and process stereoselectivity were discussed.

A method of simultaneous one-stage synthesis of three retinal derivatives (5,6-dioxo-5,6-seco-, 5,6-dihydro-5,6-epoxy-, and 4-oxoretinal) was proposed, with the yield of the first derivative being ∼50%. These compounds are useful tools for studying the antitumor activity of retinoids, the reconstituted bacteriorhodopsin analogues with changed parameters of photocycle, and the reactivity of retinal derivatives in the processes of oxidation by molecular oxygen.

A method for synthesis of retinal analogs labeled with electron-density groups is suggested. The interaction of these polyene compounds with bacterioopsin in apomembrane of Halobacterium salinarum was tested. A retinal analog containing a crown-ether receptor group is able to interact readily with bacterioopsin giving rise to rapid formation of a pigment with absorption maximum at 460 nm. This pigment is capable of undergoing cyclic photoconversion. The crown-bacteriorhodopsin photocycle is extremely slow and its quantum efficiency is very low (∼3% of that in native bacteriorhodopsin). This photocycle includes an M-like intermediate with a differential absorption maximum at 380 nm. A retinal analog in which the β-ionone ring is replaced by ferrocene moiety forms a stable chromoprotein with the main absorption band at 483 nm and a shoulder near 590-610 nm.

Glacial-relict species of the genus Mysis (opossum shrimps) inhabiting both fresh-water lakes and brackish sea waters in northern Europe show a consistent lake/sea dichotomy in eye spectral sensitivity. The absorbance peak (λmax) recorded by microspectrophotometry in isolated rhabdoms is invariably 20-30 nm red-shifted in "lake" compared with "sea" populations. The dichotomy holds across species, major opsin lineages and light environments. Chromophore exchange from A1 to A2 (retinal → 3,4-didehydroretinal) is a well-known mechanism for red-shifting visual pigments depending on environmental conditions or stages of life history, present not only in fishes and amphibians, but in some crustaceans as well. We tested the hypothesis that the lake/sea dichotomy in Mysis is due to the use of different chromophores, focussing on two populations of M. relicta from, respectively, a Finnish lake and the Baltic Sea. They are genetically very similar, having been separated for less than 10 kyr, and their rhabdoms show a typical lake/sea difference in λmax (554 nm vs. 529 nm). Gene sequencing has revealed no differences translating into amino acid substitutions in the transmembrane parts of their opsins. We determined the chromophore identity (A1 or A2) in the eyes of these two populations by HPLC, using as standards pure chromophores A1 and A2 as well as extracts from bovine (A1) and goldfish (A2) retinas. We found that the visual-pigment chromophore in both populations is A1 exclusively. Thus the spectral difference between these two populations of M. relicta is not due to the use of different chromophores. We argue that this conclusion is likely to hold for all populations of M. relicta as well as its European sibling species.

The photochemical properties of various bacteriorhodopsin analogs in water suspensions and PVA films have been studied and their promise for technological purposes (especially as a basis for colour-imaging and -recognition devices) is shown.

Two new photochromic labels of spiro[chromene-2,2’-indole] series supplied with 5-positioned maleimide moieties suitable for labelling macromolecules with sulfhydryl groups were synthesized.

A method of simultaneous one-stage synthesis of three retinal derivatives (5,6-dioxo-5,6-seco-, 5,6-dihydro-5,6-epoxy-, and 4-oxoretinal) was proposed, with the yield of the first derivative being approximately 50%. These compounds are useful tools for studying the antitumor activity of retinoids, the reconstituted bacteriorhodopsin analogues with changed parameters of photocycle, and the reactivity of retinal derivatives in the processes of oxidation by molecular oxygen. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 6; see also http://www.maik.ru.

The phenomenon of supercooperativity in platelet aggregation is manifested by the occurence of clear-cut thresholds in dose—response relationships; in such cases the Hill coefficient has unusually high values. Approximation, by the Hill equation, of the relationship of the rate of arachidonate-induced platelet aggregation to the concentrations of either the inducer or inhibitors such as substituted pyridyl isoxazoles (synthesized by us), indomethacin, and pinane thromboxane A 2 , demonstrated that the Hill coefficients ranged from 30 to 100. 3-(3-Pyridyl)-5-phenylisoxazole, which exhibited maximal anti-aggregatory activity among the synthesized compounds, inhibited neither cyclooxygenase nor thromboxane synthase. The compounds affected the signal transduction pathway at/or posterior to the stage of thromboxane A 2 reception.

A number of substituted pyridylisoxazoles and their 4,5-dihydro analogs were synthesized by 1,3-dipolar cycloaddition of substituted nitrile oxides to either alkenes or alkynes. The synthesized compounds inhibit arachidonic acid-induced aggregation of human thrombocytes at concentrations of 10(-6) to 10(-3) M. Due to low toxicity, these compounds can be regarded as potential antithrombosis medicines.

We described two synthetic routes for preparation of new crown ether derivatives of polyenals, containing variable length of the conjugation chain.

Relationships of the chromophore structure and photochemical behaviour of bacteriorhodopsin analogs in solution and their possible technical applications were discussed.