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Several 1-azulenyl vinyl crown ethers were synthesized starting from (1-azulenylmethyl) triphenylphosphonium iodide and 4-formylbenzo-crown ethers in the Wittig reaction conditions. The reaction worked in fair conditions and the obtained mixtures of geometric isomers were separated using column chromatography. The isomers were identified using 1H-NMR spectra and the mass spectra were recorded using ESI. The UV-vis spectra showed bathochromic effect in Z isomer compared with the E one.

Some considerations regarding the mechanism of arsa-Wittig condensation have been supplemented with the synthesis of compounds substituted with the nitro to phenyl and various alkyl groups to the azulene moiety. For several unknown meta-substituted 1-styrylazulenes Wittig synthesis was used. The obtained products were completely characterized. A look at the behavior of the products in NMR and UV-Vis spectrometry was taken.

This paper comes as a continuation of our efforts to prepare vinylazulenes, moving our attention to the seven-membered azulene cycle. Several azulenic substrates were tested in order to study the possibility of preparation of poly(thiophenevinyl)azulenes, needed for the generation of dendrimeric structures. The compounds containing methyls in positions 4,6 and 8 could be condensed with 2- and 3- thiophenecarbaldehyde in tBuOK/THF yielding mono-, bis- and tris- condensed products in function of molar ratio of reagents, catalyst, solvent. The reaction works in thermodynamic control, preferring 6-position instead of 4(8)-position, which generates less stable alkenes (steric hindrance) and has a trans stereochemistry. Usually mixtures of products are obtained if more condensation position are present, even if a large aldehyde excess is used. In forcing conditions, the intermediate alcohols suffer an Oppenauer hydride transfer to the excess aldehyde, generating undesired ketones. For condensation of a methyl group situated on the five-membered cycle it must be activated by substitution with +PPh3 followed by a Wittig condensation.

The tetrazole-5-diazonium salt, obtained by diazotizing 5-aminotetrazole in strong acid solution, was coupled with azulenes in the presence of pyridine to produce 5-(azulen-1-yldiazenyl)tetrazoles in good yields. The tetrazole moiety was monoalkylated in 1- and in 2- position using dimethyl sulfate for methylation and benzyl bromide for benzylation. The excess of alkylating agent generated in small amount tetrazole dialkylated salts. The synthesized compounds were characterized and some of their properties have been investigated, such as optical, magnetical and electrical.

Alzheimer�s is a progresive neurodegenerative disease that interferes with human cognitive ability, memory and behavior. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes are major therapeutic routes for the treatment of Alzheimer disease. In the study, nevel bis-polymethylenquinoline-bis-carboxamides (3a-f) and bis-polymethylenquinoline-bis-carboxylic acids (5a-b) having as precursor benzidine, were obtained in good yields by Pfitzinger condensation reactions of bis-isatines with corresponding cyclanones. The compounds were characterized by elemental analysis, FT-IR, NMR and mass spectrometry. Furthermore, the compounds were subjected to molecular docking dynamics simulations to ascertain their potentials as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Molecular docking simulations showed varied binding activities towards the two binding sites of acetylcholinesterase: 4EY7 and 1OCD, and human butyrylcholinesterase: 1P0I. Compounds 3e and 5b demostrated strong binding affinities with 1P0I, 1OCD and 4EY7 biotargets similar to the binding modes of donepezil and tacrine (co-crystallized inhibitors of acetylcholinesterase) and butyrate (co-crystallized inhibitors of butyrylcholinesterase).

As a continuation of research on 1-vinylazulenes synthesis, on their physico–chemical properties as well as on their use as colorimetric and electrochemical materials for the detection of heavy metals ions, new compounds, 4-(azulen-1-ylmethylene)-2-phenyloxazol-5(4H)-ones, are reported. The exceptional structure of azulene moiety with symmetrical electron distribution only with respect to the x-axis gives some special chemical and physical properties to compounds in which it is inserted. Various azulene-1-carbaldehydes and hippuric acids are condensed with good yields in Erlenmeyer—Plöchl reaction conditions. The obtained 1-vinylzulenes were characterized and their UV-Vis and NMR spectra were briefly discussed.

The differential scanning calorimetric (DSC) - thermogravimetry (TG) techniques have been employed in order to investigate the thermal behavior of two amino acids, namely: L- proline and 4-hydroxy- L -proline gamma irradiated. The results were compared with similar ones for the same non-irradiated compounds. The samples were irradiated at room temperature with gamma radiations using a 137Cs source. The exposure doses ranged between 0.63 kGy‐ 10 kGy. The phase transition points (melting) and decomposition processes occurring by heating were put in evidence from DSC thermograms in the temperature range between ambient to 500 °C. The effects of gamma rays on thermal parameters and their variation as a function of dose were analyzed. The measurements have shown that after L -proline and 4-hydroxy- L -proline irradiation, the values of the melting/decomposition temperatures, enthalpies, heat capacities, weight loss and purity decrease. The GC-MS technique was used to identify the yields of the molecular products of the irradiation, and Fourier transformed infrared (FTIR) method to highlight the functional groups and hydrogen bonds and their modification related to irradiation.

In this work, we present a simple, two-stage method for the preparation of new and efficient antimicrobial hybrid systems, based on isoniazid and pyrazine-2-carbohydrazide tuberculostatic agents covalently linked to graphene oxide. In the first step, the carboxyl groups of graphene oxide are activated by transforming them into the corresponding acid chloride groups, which, in the second step, will react with the amino groups of the two drugs. Pyrazine-2-carbohydrazide was obtained from pyrazinoic acid and hydrazine hydrate and was confirmed by nuclear magnetic resonance spectroscopy. The materials have been characterized by elemental analysis, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Their antimicrobial activity was tested on mycobacterial (Mycobacterium terrae), as well as on Gram-negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), Gram-positive bacteria (Staphylococcus aureus ATCC 6538, Staphylococcus aureus ATCC 25923) and fungal (Candida albicans ATCC 10231), in planktonic and biofilm growth state. The biocompatibility of the tested compounds was assessed in vitro by live-dead fluorescence staining and flow cytometry. The results of this study have shown that the functionalization of graphene oxide with isoniazid and pyrazine-2-carbohydrazide both enhanced the anti-mycobacterial activity of the respective drugs and extended their antimicrobial spectrum towards other microbial strains, in planktonic and biofilm growth state, showing a promising potential for mitigating the impact of antimicrobial resistance and the deleterious effects of microbial biofilms. At the active tuberculostatic concentrations, the tested compounds exhibit very low cytotoxicity and do not interfere with the cellular cycle of Hep-2 cells. The flow cytometry and live/dead fluorescence staining proved that the tested compounds exhibit a microbicidal effect through induction of cellular lesions, consecutive to membrane depolarization.

A series of nine dual molecular probes containing dansyl and TEMPO groups with fluorescent and paramagnetic properties, respectively, linked by linear alkyl chains were synthesized and characterized. The series of probes bearing only the dansyl moiety was also obtained. The photophysical properties of the probes were investigated in aqueous solution and the results evidenced the quenching effect of the nitroxide group on the fluorescence quantum yield of the dansyl moiety. Host–guest interactions of these dual molecular probes with β-cyclodextrin were investigated simultaneously by electron paramagnetic resonance (EPR) and fluorescence spectroscopies. The analysis of both EPR and fluorescence data evidenced the formation of complexes with preferential inclusion of the dansyl group in the cyclodextrin cavity and 1 : 1 stoichiometry. The association constants for the inclusion complexes were of the 102 M−1 order of magnitude. Diffusion experiments of the probes in natural and functionalised alginate gels bearing adamantane and/or cyclodextrin units have shown the suitability of these compounds to describe interactions in complex and non-uniform systems in which host–guest interactions play an important role.

Bis-dansyl fluorescent probes bearing aliphatic diamine linkers of increasing length (2DA1.n, n = 2, 4, 6, 8, 10, 12) were synthesized, and their emissive characteristics in solvents and in cyclodextrin solutions were discussed. Dual emission from locally excited (LE) and intramolecular charge transfer (CT) excited states was observed. The LE/CT relative magnitude is sensitive to solvent polarity and linker length. In water, the CT or LE state is favoured for short chain or long chain probes, respectively. The LE/CT relative magnitude also depends on the CD type: 2-hydroxypropyl-β-CD favours the CT state, while β- and γ-CD stabilise the LE state.

A new synthesized molecular receptor, 2,2'-(ethane-1,2-diylbis((2-(azulen-2-ylamino)-2-oxoethyl)azanediyl))diacetic acid (L) has been used as building block for the development of new colorimetric and electrochemical sensors for metal ions complexation. The monomer L shows a high selectivity towards mercury ions among other cations, as highlighted by naked eye and UV–Vis spectra. The oxidative electropolymerization of L on glassy carbon electrodes lead to complexing polyL coated electrodes. They have been characterized by electrochemical techniques, their surface morphology and topography being evaluated by scanning electron microscopy and atomic force microscopy. These new modified electrodes show the ability to complex metal ions using chemical preconcentration-anodic stripping voltammetry technique.

Metal ion complexing modified electrodes were obtained by oxidative electropolymerization of 1 H -pyrrole-1-hexanoic acid (monomer L ) on glassy carbon disks with very good reproducibility in the elaboration process. Poly L films were characterized by scanning electron microscopy, atomic force microscopy, electrochemical techniques, and their hydrophilic character was evaluated by contact angle measurements. Using chemical preconcentration-anodic stripping technique at optimized parameters (pH, open circuit preconcentration time, reduction potential and time) linear calibration curves with ranges from 3 × 10 −11 M to 8 × 10 −8 M, and from 5 × 10 −11 M to 7 × 10 −8 M were obtained for Pb(II) ions using two thickness of poly L films. Their corresponding detection limits (S/N = 3) were 20pM and 30pM, respectively. These limits are favorable in comparison with other modified electrodes developed for Pb(II) detection. Poly L modified electrodes were used for electroanalysis of Pb(II) ion in tap waters, and the results were validated by GF-AAS method. Also, the modified electrodes presented very good stability over time.

The synthesis of pyrylium and pyridinium salts and pyridines with azulene-1-yl moieties in position 4 and two 2-heteroarylvinyl groups in positions 2 and 6 was accomplished. The pyrylium salts were obtained starting from pyranones and pyridines could be prepared from these salts by treating them with ammonium acetate. The general procedures for the synthesis of pyridinium salts, which occur with good results in less delocalized electronic systems, do not take place when applied to the above obtained pyrylium salts. Therefore, as starting material 4-(azulen-1-yl)-1-(n-butyl)-2,6-dimethylpyridinium perchlorate was used, which was condensed with heteroarylcarboxaldehydes. These compounds were completely characterized and some of their spectra were discussed. Their interaction with some metal ions was revealed, observing an affinity better than in the case of simple azulenepyridines. In the last part of the paper are presented redox potentials for several pyrylium salts and pyridines in comparison with those of the nonvinylogated derivatives.

Finding new, biocompatible matrices that allow us to model the generation of free radicals is of utmost importance for balancing the harmful and beneficial effects of the latter. In this respect, we report here the simultaneous encapsulation of the radical source and the antioxidant agent in a polyethylene glycol/β-cyclodextrin (PEG/β-CD) covalent gel network. We used electron paramagnetic resonance spectroscopy to evaluate the scavenging action of plant extracts (purple loosestrife, comfrey, milfoil, horsetail, thyme, carob, green coffee) embedded in PEG/β-CD gels. Free radicals were generated in situ by UV irradiation of riboflavin co-embedded in the gels. Prior to this, the extracts were characterized in what concerns their antioxidant activity, and their major polyphenolic constituents were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. Purple loosestrife showed the highest antioxidant capacity, followed by comfrey and milfoil. Using the 5,5-dimethyl-1-pyrroline N-oxide spin trap, we have demonstrated that the gel-embedded extracts effectively scavenge the reactive carbon-centered free radicals generated in gel. The PEG/β-CD gels have been shown to be a valuable alternative matrix for the encapsulation of plant active principles having antioxidant activity. Moreover, co-encapsulation of the radical source transforms these gels into a controlled environment in which free radical processes can be tailored.

The synthesis and electrochemical characterization of a new azulene-thiourea like complexing monomer namely, (2E)-2-(azulen-1-ylmethylidene) hydrazinecarbothioamide (L) is reported. The electropolymerization of L in acetonitrile on glassy carbon electrodes, put in evidence by EQCM and ferrocene redox assay probe, led to the immobilization of the complexing monomer on the electrode surface. The polyL modified electrodes were electrochemically characterized and their morphology was evaluated using scanning electron microscopy. The complexing abilities of L and polyL towards heavy metal ions were highlighted.

Several vinylazulenes containing heterocyclic units were prepared using Knoevenagel condensation. The condensation took place between electron rich 1-azulenecarbaldehyde derivatives and their vinylogues with heterocycles. The catalysts were chosen in order to catalyze the reaction without giving side reactions, such as heterocycle decomposition or formylazulene decarbonylation. Several NMR signals were briefly discussed. The optical properties of the colored substances were evidenced as a function of their structure. The pH-dependence of the chromophores was evidenced for two compounds; as well as their active solvatochromism. Their electrochemical properties were evaluated from the redox potentials and correlated to their structure.

Several vinylazulenes containing metalophilic groups were prepared as potential host molecules in ligands for metal ion detectors. The azulene-1-carbaldehyde derivatives were condensed with methylene active compounds in the presence of piperidine. The reaction is influenced by both the nature of the methylene activating groups and by the presence of the alkyl groups on the 4-,6- or 8- position of the azulene moiety. Some unusual reagents, as nitroacetate were condensed with imines activated by acetic anhydride. Several autocondensation azulenic products were evidenced in the presence of weak activated methylenes. Considerations regarding S1 and S2 absorption bands of the azulene compounds were revealed and correlated with frontier molecular orbitals. At the same time, the prepared ligands redox potentials were investigated by differential pulse voltammetry (DPV).

The synthesis of a series of thiosemicarbazone ligands bearing azido groups, which were further immobilized on the surface of phenylethynyl-functionalized glassy carbon (GC) electrodes through a Cu(I)-catalyzed "click" reaction is reported. The modified electrodes presented a remarkable selectivity towards Hg(II) among other metal ions. Under optimized conditions and using the accumulation at open circuit-anodic stripping technique, detection limits below nanomolar level were obtained for Hg(II). Further, we demonstrated that GC electrodes "clicked" with thiosemicarbazone ligands can be used successfully for the analysis of Hg(II) ions from water samples. Moreover, the modified electrodes showed a very good reproducibility, stability over time and reusability, and can therefore be employed as sensitive and selective sensors for Hg(II) ion analysis in environmental samples.

Low-molecular-weight organic gelators generate physical gels by the formation of three-dimensional fibrous network structures as a response to various physicochemical stimuli such as heat, light, ultrasound and chemical environments. Dibenzylidene sorbitol (DBS) represents a typical compound able to generate gels because of some prerequisite structural features: the presence of functional groups to form intermolecular hydrogen bonds and of aromatic groups to be involved in π–π interactions, or chirality. Herein, we present the synthesis of three derivatives of DBS-bearing carboxy groups attached to phenyl rings and the corresponding spin-labelled compounds. We studied the formation of physical gels resulting from self-assembly of DBS derivatives with the aim of highlighting the influence of the position of the carboxy group on the gel properties. These types of compounds can form gels in polar solvents (such as water, DMSO) by either temperature treatment or variation of the pH. In this study, the systems were investigated by rheological measurements, SEM analysis and EPR measurements. The results showed that the introduction of carboxy groups into the structure of DBS generates weaker gels compared with the parent gelator, DBS. The spin probes used in this study (spin-labelled DBS derivatives and 5-doxyl stearic acid) demonstrated that assembly of gelator molecules is a highly selective process. The two-component feature of EPR spectra of spin probes in gels is proof that EPR spectroscopy is sensitive to the non-homogeneity of these systems.

The determination of pH values at the equivalence (isosbestic) point from the electronic spectra of several azulen-1-yl-thiazol-2-yl diazenes allowed the obtaining of their pK a values. All the studied compounds are very weak bases. The pK a values were correlated with the diazenes structure. The values for oxidation and reduction peak potentials are obtained from DPV curves. A good correlation was found between the calculated values for molecular orbitals energies and the experimental recorded data for the redox processes.

An efficient two-step method was developed for the synthesis of 1,2-di(azulen-1-yl)ethenes 15-17, having the double bond included in a five-membered carbocyclic or heterocyclic ring. The method involves preparation of the appropriate diketone precursors through Vilsmeier-Haack or Friedel-Crafts reactions, followed by their McMurry cyclization. Alkenes 16 and 17 were quantitatively converted into the corresponding dehydro derivatives 24 and 25, respectively, by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The electrochemical properties of compounds 15-17, 24 and 25 were examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), and the relationship between their structure and electrochemical behavior was established.

Azo dyes with either one or two identical or different azulen-1-yl moieties attached to the structure -N2-C6H4-N2-C6H4-N2- were prepared, the phenylene ring being either 1,3-1′,3′ or 1,4-1′,4′ disubstituted. The syntheses were accomplished in good yields via mono or bis diazotization of the corresponding anilines followed by the coupling with unsubstituted or alkyl substituted azulenes in acetic/acetate medium. The recorded electronic spectra of the synthesized compounds were analyzed and were compared with those of related compounds. The isosbestic points resulting from protonation of the azo compounds enabled pKa values to be determined. From these pKa values it is apparent that all studied compounds are very weak bases. The high solvatochromic property of the compounds with para,para-substituted phenylene groups reflects the hyperpolarizability of these compounds.

Pyranylium perchlorates with azulen-1-yl moiety in 4-position and thiophen-2-yl or furan-2-yl in 2 and 6-positions were obtained by the substitution of 4-chloro corresponding salts with azulenes. The pyranylium salts are used as starting materials for the synthesis of pyridine and pyridinium salts. The products were characterized and for pyridines pKa was spectroscopically determined. Several attempts were made for pyridine complexation with metal cations as Hg2+ or Ag+. J. Heterocyclic Chem., (2011).

3- and 4-[(Azulen-1-yl)-azo]-azo-benzenes were obtained in good yields using the buffered coupling reaction between several alkyl-substituted azulenes and diazotized phenylazo-phenylamines in dichloroacetic acid. The coupling products were characterized and the recorded electronic spectra are discussed. The isosbestic points obtained by protonation enabled the determination of their p K a values.

The rosemary extract was encapsulated in polyethylene or in covalently-based network gels. The covalent gels were obtained by the reaction of isocyanate end-capped polyethylene glycol (PEG) with β-cyclodextrin or glycerol. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to evaluate the antioxidant activity (AA) of rosemary extract entrapped in polymeric structures and in ethanol or water solutions. The AA of the rosemary extract was determined using a DPPH radical for samples prepared in ethanol, and a water-soluble derivative, the sulphonated DPPH radical (DPPH-SO3Na), for the rosemary extract in water. Formulation of the rosemary extract in polymeric gels ensures a rapid release which determines the AA values similar to those in solution.

Pyranylium perchlorates with azulen-1-yl moiety in 4-position and thiophen-2-yl or furan-2-yl in 2 and 6-positions were obtained by the substitution of 4-chloro corresponding salts with azulenes. The pyranylium salts are used as starting materials for the synthesis of pyridine and pyridinium salts. The products were characterized and for pyridines pKa was spectroscopically determined. Several attempts were made for pyridine complexation with metal cations as Hg2+ or Ag+. J. Heterocyclic Chem., (2011).

(Azulen-1-yl)carboxylic acids 3-substituted by 2-(thiazol-2- or 3-yl)-ethenyl groups and their esters were synthesized starting either from the corresponding 1-azulenyl-2-thiazolyl-ethenes, 3, or from methyl 3-formyl-azulen-1-yl carboxylate, 7. The ethenes 3 were phosgenated in an electrophylic reaction followed by the reaction with water or alcohol. The aldehyde 7 was transformed in Schiff base which was reacted with corresponding thienylacetic acid to generate the ester 6b. The products characterization and considerations about the obtained compounds structure are reported.

An easy and efficient solvent-free synthesis of 1-(azulen-1-yl)-2-aryl- and heteroarylethenes is described. The reaction was performed simply by melting solid mixtures of azulenic Schiff bases and arylacetic acids, the crude products being purified by column chromatography. Limitations of the method were established by study of a large range of aryl and heteroarylacetic acids and also by examination of various azulenic Schiff bases. The same reaction was observed with other active methylene compounds, such as malonic acid and its derivatives or 1,3-diketones. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

(E)-2-(Azulen-1-yldiazenyl)-1,3,4-thiadiazoles, unsubstituted or substituted either at azulen-1-yl moiety or at 5-position of thiadiazole ring were synthesized. Among the acids used as diazotization medium, dichloroacetic acid was the best choice. In several cases the by-products such as thioether 9 were isolated along with the normal coupling derivatives. The generated products were characterized and their MS and UV-vis spectra discussed. A computational study on (E)-2-(azulen-1-yldiazenyl)-1,3,4-thiadiazoles was undertaken based on density functional theory (DFT) to determine frontier orbital energies and other physical properties. The absorption maxima and the basicity of the new compounds are close to those of the corresponding diazenes containing thiazole, previously described. They have brick color in neutral medium and violet in strong acidic solutions. The redox potentials were also determined remarking the influence of the substituents on these potentials.

Dioxane-4,6-diones with (azulen-1-yl)methylene attached to position 5 were obtained by condensation of azulene-1-carbaldehydes with Meldrum's acid. The reaction was performed either neat or in absolute ethanol using a base as a catalyst. The involvement of the generated C=C bond either in electrophilic or radical reactions appears to be restricted. The advanced molecular polarization of the obtained products can account for the low reactivity of this bond. With the electrophilic reagents only the 3-position of azulenyl moiety was substituted. The azulene acylation with acetylsalicyloyl chloride occurred with rearrangement of the acyl chloride and, the formed products are 4H-1,3-benzodioxin-4-ones where azulen-1-yl moiety occupies the position 2 of the heterocyclic system.

3,3′-Disubstituted 1,1′-biazulene derivatives were obtained in good yields starting from thedimers* of azulene-1-azo aromatic compounds and from the corresponding Schiff bases coupled at 3 positions.