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In the last decade, pyridoxine derivatives were widely used for the synthesis of molecules with important biological and physical properties. However, rational synthesis of the compounds with desirable biochemical or physical properties often requires information about their spatial structure and conformational mobility. NMR spectroscopy is a powerful tool for conformational analysis of biologically important samples, such as pyridoxine derivatives, in solution. This paper is devoted to a review of the results obtained by our group over the last 5 years on the NMR study of nine newly synthesized pyridoxine derivatives in acetone solution. It was shown that studied compounds are involved into several conformational exchange processes. The activation energies of all observed conformational exchange processes were calculated.

Pyridoxine derivatives, 3-hydroxy-2-methylpyridine-4- and -5-carbohydrazides, were synthesized according to optimized known procedures, and a method for the synthesis of 5-(hydroxymethyl)-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-6-carbohydrazide was developed. The hydroxymethyl groups in positions 5 and 6 of 2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine showed different reactivities, and only the 6-hydroxymethyl group was selectively oxidized to aldehyde under mild conditions. The lactone ring in 5,6-dihydrofuro[3,4-b]pyridin-7(5H)-one was found to be stable to nucleophiles. The synthesized hydrazides showed no antimycobacterial activity.

The search for new antibacterial and antiseptic drugs is an urgent problem due to the resistance of microorganisms to existing drugs. In this work, for the first time, the design of antibacterial and bactericidal agents based on quaternary ammonium compounds on thiacalixarene macrocyclic platform was proposed and implemented. A series of tetrasubstituted quaternary ammonium salts with different nature and length of the substituent (-N+(CH3)2R, R = CH2Ph, CnH2n+1, n = 1, 4, 8, 10) based on p-tert-butylthiacalix[4]arene in cone and 1,3-alternate conformations was obtained with excellent yields. The obtained compounds have a high antibacterial effect against Gram-positive (S. aureus, S. epidermidis, B. subtilis) bacteria comparable with commercial antiseptics chlorhexidine, miramistin and benzalkonium chloride. It was found that quaternary ammonium derivatives of thiacalix[4]arene in 1,3-alternate conformation more effectively inhibit the growth of the tested bacterial strains in comparison with compounds in cone conformation. Cytotoxicity studies on human skin fibroblast (HSF) cells demonstrated that all compounds were less toxic compared to reference drugs. The different type of interaction of the studied compounds with model DPPC lipid membranes explains different antibacterial activity and cytotoxicity of compounds. The compounds in cone conformation are adsorbed on the DPPC vesicles membrane surface, while the incorporation of lipophilic alkyl fragments of macrocycles in 1,3-alternate conformation into the membrane leads to “clumping” of DPPC vesicles. It was shown the saving of antibacterial activity of thiacalixarene derivatives in 1,3-alternate conformation on Gram-positive clinical strains. The obtained results allow viewing the described thiacalixarene based quaternary ammonium compounds as promising molecules in the development of the new antibacterial agents.

The conformational properties of three pyridoxine derivatives were studied by 1 H dynamic NMR spectroscopy. Conformational exchange caused by a rotation of 2-nytrophenyl group around one single C-C bond, of 2,4-dinitrophenyl substituent around two single C-O bonds, and twist-twist transformations of the seven-membered ketal cycle was observed by NMR experiments at low temperatures. Meanwhile, the conformational exchange of the acetal ring remains fast in the NMR timescale even at 198 K. The energy barriers for all observed conformational exchange processes were determined by the lineshape analysis of dynamic NMR spectra. The activation barriers of the 2-nitrophenyl group rotation were almost the same for all studied compounds, about 40-41 kJ/mol. The energy barriers of the conformational exchange processes of the 2,4-nitrophenyl group and the ketal cycle increased significantly up to 10 kJ/mol in comparison with previously studied compounds with similar structure. Copyright © 2016 John Wiley & Sons, Ltd.

An approach to the synthesis of epoxides based on 6-hydroxymethylpyridoxine acetals was developed. The epoxides obtained were involved in the ring opening reactions by nitrogen-, oxygen-, and sulfur-containing nucleophiles. Cytotoxicity and antiadrenergic properties of some synthesized compounds were studied on the models in situ and in vivo.

Methods for the synthesis of quaternary phosphonium salts based on 3-hydroxypyridine and 4-deoxypyridoxine were developed. Some of obtained compounds possess high antibacterial and antitumor activity in vitro.

A convenient method for the synthesis of pyridoxine alkenyl derivatives by the Wittig reaction of [(2,8-dimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methyl]triphenylphosphonium chloride with aldehydes was suggested. Some of the compounds obtained exhibit antitumor activity in vitro.

A series of pyridoxine derivatives was investigated by (1) H and 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR. The free energies of activation for the pyridyl-oxygen rotation of the 2,4-dinitrophenyl ether of the seven-membered acetals of pyridoxine were measured by dynamic NMR. A conformational exchange between the chair and twist forms of the seven-membered acetal ring was confirmed by dynamic NMR and STO3G computations.

A novel organic compound 9-(2,4-dinitrophenyloxy)-3,3,8-trimethyl-1,5-dihydro-[1,3]dioxepino[5,6-c]pyridine (DNPAP) has been synthesized and a nonlinear optical (NLO) crystal has been grown by slow evaporation method. Compound was subjected to different characterization analyses in order to find out its suitability for optoelectronic applications. Single crystal and powder X-ray diffraction analyses show that DNPAP crystallizes in the orthorhombic space group Pca21. The range of optical absorption was ascertained by recording UV–Vis spectrum. The second harmonic generation (SHG) test has shown that DNPAP possesses 6.4-times higher NLO efficiency compared to KDP.

Synthetic approaches to three cyclic 2,4,5,6-tetrakis(hydroxymethyl)pyridin-3-ol acetonides were developed. Among seven possible mono- and diketals, six-membered cyclic ketal incorporating the hydroxymethyl group in the 4-position turned out to be the most thermodynamically favorable. The experimental data were consistent with the results of quantum-chemical calculations of the Gibbs energies of formation of different acetonides. The structure of the isolated compounds was studied by X-ray diffraction.

By oxidation of (Z)-4,7-dihydro-1,3-dithiepines with meta-chloroperbenzoic acid the corresponding 4,7-dihydro-1λ4,3-dithiepine 1-oxides were synthesized in ∼85% yield. A complete assignment of signals in the 1H and 13C NMR spectra of the compounds obtained was established. According to XRD analysis the seven-membered heterocycles crystallized in conformations chair or boat. The calculations by DFT method in the B3LYP/6-31G(d,p) version showed the possibility of conformational equilibrium of these forms in the gas phase.

X-ray data for both title molecules display a chair conformation with exo location of cyclopropane moiety and axial or equatorial sulfinyl group. Dynamic 1H and 13C NMR spectroscopy at −95 °С exhibit conformational homogeneity for the first diastereomer and two component chair – twist-boat equilibrium (2:3) for the latter.

Spiro[cyclohexane-1,4′-[3,5]dioxabicyclo[5.1.0]octanes] were synthesized, and their conformational behavior was studied by dynamic 13C NMR spectroscopy. Anancomeric displacement of conformational equilibrium toward two nonequivalent twist conformers with close energies was revealed. The relative Gibbs energies ΔG o and enthalpies of formation ΔH o of twist and chair-like conformers with endo and exo orientation of the three-membered ring of structurally related formaldehyde and acetone acetals were calculated in terms of the density functional theory at the B3LYP/6-31G(d,p) level. Like spiro-cyclohexane analogs, they were shown to have a non-chair conformation.

According to the data of single crystal X-ray diffraction analysis and computational methods, the seven-membered rings of acylated pyridoxine acetonides have C2 symmetry. Two stereochemical transformations in solutions, enantiotopomerization of P-, M-conformations with spiral chirality of twist-boat forms and diastereotopomerization of structures that differ in the configuration of the phenolic oxygen substituents, were revealed by dynamic 1H NMR spectroscopy.

X-ray, 1H NMR and IR spectroscopy methods have been applied to a series of heterobicyclo[5.1.0]octanes. Endo epoxide and exo thiirane based on 2-tert-butyl-2-oxo-1,3,2-dioxaphosphepine exhibit chair form in a crystal state. Strong predominance of the chair conformation takes place in solution also as for similar bicyclic acetals produced from 2-tert-butyl-1,3-dioxacyclohept-5-ene. 3,5-Dioxa-8-thiabicyclo[5.1.0] octane bearing no a bulky substituent was found to exist as a mixture of stereoisomers in solution.

IR spectroscopy and ab initio calculations have been applied to the title compounds. Bicyclic acetals were found to exist as mixture of chair and twist-boat conformations, a parent epoxide being in ternary equilibrium. X-ray data on 4-methyl (exo) derivative display a twist-boat form.

Conformationally heterogeneous 2-substituted 1,3-dithiacyclohept-5-enes (R = Ph, Me, t-Bu), which exist in solution as chair and boat conformers, react with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate with high exo-diastereoselectivity: only the chair conformer is involved. The steric structure of 4-methyl-3,5-dithia-9,10-diazabicyclo[5.4.0]undeca-7,10-diene was determined by X-ray analysis. Its crystal packing and supramolecular structure were also analyzed.

3-Substituted 1H,5H-naphtho[1,8-ef][1,3]dithiocines (R = H, Me, Ph, t-Bu) were oxidized with m-chloroperoxybenzoic acid to the corresponding 2-oxides having trans configuration (R ≠ H). According to the 1H and 13C NMR data (including NOESY experiments), the disubstituted compounds at room temperature exist in a boat conformation with equatorial orientation of the substituent on C3 and oxygen atom on S2. The compound with no substituent on C3 gives rise to a mixture of boat conformers with axial and equatorial sulfoxide oxygen atoms at a ratio of 83:17.

4-R-3,5-Dioxabicyclo[5.1.0]octanes were prepared in good yields by reduction of the corresponding 8,8-dichloro derivatives in a system Li-t-BuOH. According to the data of dynamic 1H and 13CNMR spectroscopy involving experiments in the NOESY mode the formal (R = H) at −93°C in (CD3)2CO exists in nearly equally occupied chair forms with endo- and exo-oriented three-membered ring. The like structure were found in the diastereomeric 4-Me(t-Bu)-analogs. The characteristic feature of 13C NMR spectra consists in considerable difference in the chemical shifts of the C8 atoms (Δδ∼16–17 ppm). The data on epimerization of diastereomers and calculations along AM1 procedure suggest for formal a three-component equilibrium including a twist-form.

X-ray structure investigation of the title compounds displays a chair form with equatorial alkyl substituent. 1 H NMR and PM3 semiempirical calculations have been also applied and the effect of the planar fragment on the chair–twist-boat equilibrium has been observed.

According to dynamic 13C NMR spectroscopy trans-2-R-(R=Ph, Me, Et, Pri)-5,6-benzocycloheptene-1-oxides at −60 °C in CDCl3 exist as an equilibrium mixture of the chair and boat forms with the substituents in the equatorial position. Unsubstituted (R=H) compound has in addition a boat form with an axial sulfinyl group, whereas for But derivative conformational equilibrium is anancomerically shifted to the boat structure. X-ray study of trans-2-isopropyl-1,3-dithia-5,6-benzocycloheptene-1,3-dioxide displays a chair form with equatorial alkyl substituent and axial-equatorial SO-moieties.

Dichloro- and dibromocyclopropanation of 2-substituted 1,3-dioxacyclohept-5-enes according to Makosza resulted in formation of the corresponding 4-substituted 8,8-dichloro(dibromo)-3,5-dioxabicyclo[5.1.0]octanes in good yields. Ultrasonic activation of the process considerably shortened the reaction time. According to the 13C NMR spectra, the chair-twist equilibrium is essentially displaced toward the chair conformer for the exo isomers and toward the twist conformer for the endo structures. Similar results were obtained by AM1 semiempirical calculations which indicated that the CCl···O interaction largely determines the conformational equilibrium. The state of the diastereoisomer epimerization equilibrium depends on the size of the substituent at the acetal carbon atom.

X-ray structure investigation of fused seven-membered acetals based on vitamin B6 and 3,4-bis(hydroximethyl)furan have been performed. Molecules adopt chair conformations with equatorial position of substituents at acetal carbons; the geometry of acetal cycles resembles that of related seven-membered phthalylacetals. Stereochemistry of the tetracyclic adduct of furan-containing acetal with maleic anhydride was also investigated. The product exhibits endo–exo configuration with appreciably distorted seven-membered chair-like conformation.

According to semiempirical AM1 calculations, the stability of the boat and twist forms of 2-R-1,3- dioxacyclohept-5-enes depends on the size of substituents at the acetal carbon atom. The twist form gives diastereomeric H complexes with chloroform and methanol of the cis and trans structure, containing monocentered hydrogen bonds, whereas the chair conformation preferably forms complexes with a two-centered hydrogen bond. Based on theoretical data (θO H, ΔH, geometry of complexes), the specific features of H complexes of the conformers in electrophilic addition and cycloaddition were revealed. Considerable preferableness of the exo attack of the diastereotopic double bond in the H complex having the chair form is due to the steric accessibility of the exo side, whereas in the complexes of the twist form the facial selectivity is appreciably lower.

Principles for establishing the nature of solvation effects in stereoisomeric equilibria have been formulated. Using 1H NMR spectroscopy, the equilibrium constants have been determined in 12 solvents for the endo and exo isomers of 1,9,10,11,12,12-hexachloro-4,6-dioxatricyclo[7.2.1.02,8]dodec-10-ene which is characterized by a high barrier to stereoisomeric transformations. The results of correlation analysis have shown that solvation of the conformers with dissimilar orientations of the hexachloronorbornene fragment with respect to the chair-like acetal moiety is determined by the polarity and proton-acceptor properties of the medium. Comparison with the data on solvent effect on the equilibrium between 2-isopropyl-5-methoxy-1,3-dioxane epimers suggests that the formation of H-complexes is controlled by electronic and conformational factors.

The oxidation of 3-R-1,5-dihydro-2,4-benzothiepines with m-chloroperbenzoic acid occurs in a highly diastereoselective fashion. The resulting trans-sulfoxides at -60°C in CDCl3 exist as an equilibrium mixture of the chair and boat forms with the substituents in the equatorial position. The fraction of the boat conformation increases in the series R = Ph, Me, t-Bu.

The kinetics of electrophilic addition reaction of bromine to a multiple bond in a series of con-formationally unhomogenous 2-substituted 1'3-dioxa-5-cycloheptenes was studied. We found that the com-pounds with trans structure are formed. The partial reaction rate constant for chair, twist forms, thereaction susceptibility parameters to the substituent electronic effect at the C2atom are obtained. Relativereactivity of the alternative steric structures is defined by the specific solvation of the substrate. The result obtained are compared with those achieved without accounting for conformational term.

(Z)-But-2-ene-1,4-dithiol was found to undergo isomerization into the E isomer. Condensation of (Z)- and (E)-but-2-ene-1,4-dithiols with acetaldehyde gave isomeric fourteen-membered bis-dithioacetals whose structure was determined by X-ray analysis.

The composite silver and gold nanoparticles (AgNPs and AuNPs) coated with nonionic amphiphilic block copolymers (Pluronics L121, F68, or F127) are prepared by their adsorption under critical micelle concentrations. It is found that Pluronics bind to the surface of metal NPs as a very thin film by the hydrophobic association through polypropylene oxide) block of the copolymers. The modification increases the colloidal stability of NPs with increasing hydrophilic-lipopltilic balance of Pluronics in the order of L121, F127, and F68. In order to investigate the potentials of polymer coated noble metal NPs as surface-enhanced Raman spectroscopy (SERS) probes, fluorescent dyes and doxorubicin are used as model compounds. IL is found that Pluronic component promotes the adsorption of these compounds on the composite NPs resulting in a considerable increase of Raman signal. This effect is attributed to increased concentration of the analyte molecules on the composite surface due to the hydrophobic and charge-charge interactions between the analytes and the Pluronic coat, and the stabilization of NPs by poly(ethylene oxide) blocks. The copolymer coated AgNPs show higher SERS activity than the counterparts prepared with AuNPs. Among the prepared composites, the AgNPs modified with Pluronic F127 containing extended poly(propylene oxide) and poly(ethylene oxide) blocks exhibit maximal Raman activity using rhodamine 6G (Rh6G) with a EF of 9.04 x 10(6). The results show that the developed Pluronic-based SERS probes can be used for sensitive and selective analysis of organic analytes.

3,5-Dioxabicyclo[5.1.0]octane-8-carbaldehyde was synthesized in three steps, including initial stereoselective exo-cyclopropanation of 1,3-dioxacyclohept-5-ene with ethyl diazoacetate. The subsequent phosphorylation according to Abramov and Kabachnik-Fields gave the corresponding α-hydroxy(acetoxy)- and α-aminocyclopropylmethylphosphonates with protected hydroxymethyl moieties at the three-membered ring.

The computer controlled multistage synthesis of fine-grained photographic emulsions is described. Scanning electron microscopy was used to investigate the shape and size (10 – 1500 nm) distribution of silver halide crystals in the emulsion. The influence of stirrers in the chemical reactor and also surfactant addition on the emulsion quality was revealed. In the result of the investigation a new method for obtaining of high quality photosensitive materials based on the tabular multicoated silver halide crystals was proposed.

The kinetics of hydroperoxide ROOH (R=H, t−Bu, Ph(CH3)2C) reduction by copper(I) O,O-dialkyldithiophosphates has been studied using the UV-spectrophotometric method. Rate constants for the redox reactions have been determined and some suggestions concerning their mechanisms have been made.