Diazine Derivatives Research Articles

The pattern of bifurcated hydrogen bonds in thiourea cocrystals with diazine derivatives: experimental and quantum theoretical studies.

Cocrystals of thiourea with pyrazine N-oxide as thiourea-pyrazine N-oxide (2/1), C4H4N2O·2CH4N2S, (I), and with phenazine as thiourea-phenazine (6/7), 7C12H8N2·6CH4N2S, (II), both crystallize in the monoclinic space group P21/c. In the crystalline state, molecules of both components are linked by N-H...N hydrogen bonds. In addition, there are R22(8) hydrogen-bond synthons between thiourea molecules in both crystal structures. Furthermore, bifurcated hydrogen bonds between the -NH groups in the thiourea molecule and the N and O atoms in the N-oxide ring [in (I)], as well as the N atom in the central phenazine ring [in (II)], play a significant role in both structures. This emerging motif was thoroughly examined using quantum chemistry methods.

Recent Advances in Design and Development of Diazole and Diazine Based Fungicides (2014-2023).

With fungal diseases posing a major threat to agricultural production, the application of fungicides to control related diseases is often considered necessary to ensure the world's food supply. The search for new bioactive agents has long been a priority in crop protection due to the continuous development of resistance against currently used types of active compounds. Heterocyclic compounds are an inseparable part of the core structures of numerous lead compounds, these rings constitute pharmacophores of a significant number of fungicides developed over the past decade by agrochemists. Among heterocycles, nitrogen-based compounds play an essential role. To date, diazole (imidazole and pyrazole) and diazine (pyrimidine, pyridazine, and pyrazine) derivatives make up an important series of synthetic fungicides. In recent years, many reports have been published on the design, synthesis, and study of the fungicidal activity of these scaffolds, but there was a lack of a comprehensive classified review on nitrogen-containing scaffolds. Regarding this issue, here we have reviewed the published articles on the fungicidal activity of the diazole and diazine families. In current review, we have classified the molecules synthesized so far based on the size of the ring.

Design, Synthesis, and Antiproliferative Activities of 1,3‐Disubstituted 2‐Thioxoimidazolidin‐4‐one Derivatives against HepG2 and MCF‐7 Cells

AbstractA series of 1,3‐disubstituted‐2‐thioxoimidazolidin‐4‐one and diazine derivatives were synthesized and confirmed through IR, NMR, and mass spectrometry. The in vitro cytotoxic activity of synthesized compounds against HePG2 and MCF‐7 cells were assessed by MTT assay. Furthermore, Aromatase, VEGFR‐2, B‐Raf, cell cycle, Annexin V, caspase‐3 and sulphatase expression by PCR, and β‐catenin expression by western blot were estimated. The results revealed that the synthesized compounds possess cytotoxic activity against HePG2 and MCF‐7 cell lines. Compound 11 (2,2′‐(1E,1′E)‐1,1′‐(hydrazine‐1,2‐diylidene) bis (ethan‐1‐yl‐1‐ylidene) bis (4‐(phenyldiazenyl) phenol) had greater cytotoxic activity than staurosporine (6.24 μg/mL), with IC50 of 2.55 μg/mL against HepG2 cells and (4.21 μg/mL) against MCF‐7 cells. Moreover, the inhibitory activity against aromatase was (0.156 μg/mL), (0.23 μg/mL) against VEGFR2, and (0.25 μg/mL) against B‐Raf. Also, this compound decreased DNA content of HepG2 cells in the S phase and the G2/M phase, and increased the apoptosis in Annexin measurement. By real‐time PCR, This compound up‐regulated the expression of caspase‐3 in HepG2 cells, reduced the expression of sulphatase gene in HepG2 cells, and reduced β‐catenin expression in HepG2 by western blot analysis. Consequently, the synthesized derivatives could be a promising scaffold for the development of potent anti‐cancer agents due to their apoptotic and anti‐inflammatory activities.

Virtual Screening and Multi-targets Investigation of Novel Diazine Derivatives as Potential Xanthine Oxidase Inhibitors Based on QSAR, Molecular Docking, ADMET Properties, Dynamics Simulation and Network Pharmacology.

Hyperuricemia is closely related to the occurrence of gout, hypertension, diabetes, hyperlipidemia, cardiovascular disease, kidney disease, metabolic syndrome, etc. However, xanthine oxidase inhibitors (XOIs) can fundamentally solve the problem of excessive uric acid. Compared to single-target drugs, multi-target drugs are not prone to adverse reactions and exert a synergistic effect. Therefore, the discovery of new multi-target XOIs and their mechanism of therapeutic hyperuricemia are important to overcome adverse effects and resistance to currently available drugs. The purpose of this paper is to obtain novel diazine derivatives as promising multi-target XOIs and discover the interaction mechanism for the better treatment of hyperuricemia. Novel multi-target XOIs diazine derivatives, and their interaction mechanism have been obtained through QSAR, molecular docking, dynamics simulation, and network pharmacology. In addition, ADMET properties and synthetic accessibility of novel XOIs have been considered using ADMETLAB 2.0 and SwissADME. 24 novel diazine derivatives as potential multi-target XOIs lead compounds have been found through virtual screening of the PubChem database. Moreover, the most notable top five compounds are worthy of further developing as multi-target XOIs drugs. XDH, TBK1, DGAT1, MYC, CDKN1A, PPARD, PDE6C, and EIF4E are recommended as relevant targets of therapeutic hyperuricemia. Through the combination of different methods, we have discovered five novel promising diazine derivatives as potential multi-target XOIs drugs. Meanwhile, eight targets have been found to be helpful in the research on therapeutic hyperuricemia. We expect this investigation will offer clear insights into the production of efficient XOIs drugs.

A combination of machine learning model and density functional theory method to predict corrosion inhibition performance of new diazine derivative compounds

This study proposes a novel approach that combines machine learning (ML) and density functional theory (DFT) methods to construct a quantitative structure-properties relationship (QSPR) model for diazine derivatives as anti-corrosion inhibitors. A dataset is constructed by combining three existing diazine isomer datasets to represent diazine compounds. Thirty-two different ML algorithms were implemented on the dataset, and the gradient boosting regressor (GBR) model was identified as the best predictive model for diazine and each isomer dataset based on the coefficient of determination (R2) and root mean square error (RMSE) metric values. This consistency was also observed when the GBR model was implemented on four other diazine derivatives, resulting in high corrosion inhibition efficiency (CIE) values ranging from 85.02 % to 94.99 %. The DFT calculations for these derivatives also showed strong adsorption energies ranging from − 4.41 to − 6.09 eV, in line with the CIE trend obtained from the ML prediction. This novel approach can provide insights into the properties of prospective organic corrosion inhibitors prior to experimental investigations, which could accelerate the development of new and effective organic corrosion inhibitors.

Site-Selective C-H Alkylation of Diazine N-Oxides Enabled by Phosphonium Ylides.

The synthesis of alkylated diazine derivatives is important for their practical utilization as pharmaceuticals and for other purposes. Herein, we describe the metal-free site-selective C-H alkylation of diazine N-oxides using phosphonium ylides that affords a variety of alkylated diazine derivatives with broad functional group tolerance. The utility of this method is showcased by the late-stage functionalization of a commercially available drug such as varenicline. Notably, the sequential C-H alkylation of pyrazine N-oxides for the total synthesis of a pyrazine-containing natural product, paenibacillin A, highlights the importance of this method.

SYNTHESIS OF SOME DIAZINE AND TRIAAZOLE DERIVATIVES FROM FURFURAL

The synthesis of heterocyclic compounds especially when their structure containing nitrogen ,oxygen and sulfur atoms are growing up due to their wide spread in nature ,many mechanistic pathways to reach the target with nearly negligible loss of their dose and there are numerous me thods to derivatives their structures There for the development in hetero cyclic synthesis will provide new metabolic pathways when these compounds have succeeded to be used as drug ,Moreover it was known for long time that about 95 % of cancer drugs are heterocyclic compounds .There are also many methods found in the literature for the synthesis of both triazoles and trdiazines from different routes In this investigation furfural was used as precursor for the synthesis of some new diazine and triazole derivatives (3-11).The synthesized compounds were characterized by IR ,and 1HNMR and are discussed.

Synthesis, Identification, Theoretical and Experimental Studies of Carbon Steel Corrosion Inhibition in Sea Water by Some New Diazine Derivatives linked to 5-Nitro Isatin Moiety

This research includes synthesis of new 5-Nitro isatin derivatives starting from 5-nitro-3-(imino acetohydrazide)-2-oxo indole (1) namely 5-nitro-3-[iminoaceto(tetra hydropyridazin-3,6-dione)-2-yl]-2-oxo indole (2); 5-nitro-3-[iminoaceto(hexahydrodiazepine-3,7-dione)-2-yl]-2-oxo indole (3); 5-nitro-3-[iminoaceto (1,2-dihydro pyridiazin-3,6-dione)-2-yl]-2-oxo indole (4); 5-nitro-3-[iminoaceto (8-nitro- 1,2-dihydrophtalazin-3,10-dione)-2-yl]-2-oxo indole (5) and 5-nitro-3-[iminoaceto (1,2-dihydrophtalazin-3,10-dione)-2-yl]-2-oxo indole (6). The derivatives were characterized using FTIR, 1HNMR, 13CNMR and C.H.N.S analysis with the measurement of some physical properties. Quantum mechanical method of the Density Functional Theory (DFT) of B3LYP with a level of 6-311++G (2d, 2p) were used to calculate the geometrical structure, physical properties and inhibition efficiency parameters, were at the equilibrium geometry in four media (vacuum, DMSO, EtOH and H2O). The theoretical results showed that compound (3) was the best corrosion inhibitor among the others. Finally, the corrosion inhibition, kinetics, and thermodynamics studies of the prepared compound (3) for carbon-steel in sea water had been conducted using the potentiodynamic polarization procedure, while the surface changes of the carbon steel were studied using SEM (Scanning Electron Microscopy) and AFM (Atomic Force Microscopy) techniques.

Luminescence Behavior of Protonated Methoxy-Substituted Diazine Derivatives: Toward White Light Emission

White light-emitting diodes (WOLEDs) are an efficient alternative to conventional lighting sources. Nevertheless, approaches to obtain WOLEDs still require complex processes that lead to high costs. In this sense, the use of a single emitting material that can take two forms of complementary emitting colors has emerged as a new strategy for the fabrication of WOLEDs. In this paper we describe the luminescent behavior upon protonation of a series of D-π-A push–pull molecules based on a methoxyphenyl or methoxynaphthyl donor unit and a diazine acceptor unit with different π-bridges. The effect of protonation on the emission properties depends on the nature of the diazine ring. The addition of trifluoroacetic acid (TFA) to pyrazine and quinoxaline derivatives led to quenching of the fluorescence whereas pyrimidine derivatives remained luminescent after protonation, which prompted a color change in the emission due to the appearance of a new red-shifted band in the spectra. These results were rationalized wit...

Synthesis and Evaluation Antibacterial Activity of Some New Substituted 5-Bromoisatin Containing Five, Six Heterocyclic Ring

This research includes the synthesis of some new different heterocyclic derivatives of 5-Bromoisatin. New sulfonylamide, diazine, oxazole, thiazole and 1,2,3-triazole derivatives of 5-Bromoisatin have been synthesized. The synthesis process started by the reaction of 5-Bromoisatin with different reagents to obtain schiff bases of 5-Bromoisatin intermediate compounds(1, 8, 19) by using glacial acetic acid as a catalyst in three routes. The first route, 5-Bromoisatin reacted with p-aminosulfonylchloride to product compound(1), then converted to sulfonyl amide derivatives(2-7) by the reaction of compound(1) with different substituted primary aromatic amine in absolute ethanol. The second route includes the reaction of 5-Bromoisatin reacted with ethyl glycinate to give 5-bromo-3-(Ethyl imino acetate)-2-oxo indole(8), which undergo react with hydrazine hydrate 80% to obtain hydrazine derivatives(9) that react with different acid anhydrides to obtain diazine derivatives(10-14). Also compound(8) reacts with urea and thiourea to give compounds(15,16) which undergo cyclization with p-bromophenacylbromide in absolute ethanol as a solvent to obtain oxazole (17) and thiazole (18), respectively. The third route included the reaction of 5-Bromoisatin with p-phenylenediamine in ethanol to obtain compound(19) which is converted to new substitutes 1,2,3-triazole derivatives(22,23) by diazotation of compound(19) and treating the resulted salt(20) with sodium azid, then acetylaceton or ethylacetoacetate, respectively. Newly synthesized compounds were identified by spectral methods. (FTIR, 1H-NMR, 13C-NMR) and measurements of some of its physical properties and also some specific reactions. Furthermore the effects of the synthesized compounds were studied on some strains of bacteria.

Synthesis and Evaluation Antibacterial Activity of Some New Substituted 5-Bromoisatin Containing Five, Six Heterocyclic Ring

This research includes the synthesis of some new different heterocyclic derivatives of 5-Bromoisatin. New sulfonylamide, diazine, oxazole, thiazole and 1,2,3-triazole derivatives of 5-Bromoisatin have been synthesized. The synthesis process started by the reaction of 5-Bromoisatin with different reagents to obtain schiff bases of 5-Bromoisatin intermediate compounds(1, 8, 19) by using glacial acetic acid as a catalyst in three routes. The first route, 5-Bromoisatin reacted with p-aminosulfonylchloride to product compound(1), then converted to sulfonyl amide derivatives(2-7) by the reaction of compound(1) with different substituted primary aromatic amine in absolute ethanol. The second route includes the reaction of 5-Bromoisatin reacted with ethyl glycinate to give 5-bromo-3-(Ethyl imino acetate)-2-oxo indole(8), which undergo react with hydrazine hydrate 80% to obtain hydrazine derivatives(9) that react with different acid anhydrides to obtain diazine derivatives(10-14). Also compound(8) reacts with urea and thiourea to give compounds(15,16) which undergo cyclization with p-bromophenacylbromide in absolute ethanol as a solvent to obtain oxazole (17) and thiazole (18), respectively. The third route included the reaction of 5-Bromoisatin with p-phenylenediamine in ethanol to obtain compound(19) which is converted to new substitutes 1,2,3-triazole derivatives(22,23) by diazotation of compound(19) and treating the resulted salt(20) with sodium azid, then acetylaceton or ethylacetoacetate, respectively. Newly synthesized compounds were identified by spectral methods. (FTIR, 1H-NMR, 13C-NMR) and measurements of some of its physical properties and also some specific reactions. Furthermore the effects of the synthesized compounds were studied on some strains of bacteria.

Inhibitive effect of azine and diazine derivatives on the corrosion of 316L SS in acidic media

The inhibiting effect of some azine and diazine derivatives on the corrosion of cyclic stressed 316L SS specimens in 3 M HCl in the presence of organic derivatives with concentrations (1×10-6 M - 11×10-6 M) at 30oC was studied using weight loss and galvanostatic polarization techniques. The inhibition of these derivatives on the uniform corrosion was evaluated by anodic and cathodic polarization curves of the electrode in the tested media. The examined derivatives exerted an inhibiting action towards corrosion. Polarization studies revealed that these derivatives behave as mixed inhibitors and inhibit corrosion by parallel adsorption on the specimen surface due to the presence of more than one active centre in the inhibitor molecule. The adsorption obeyed Temkin adsorption isotherm. The inhibitor efficiency increases with increasing the concentration of the inhibitor and decreases with increasing the value of the cyclic stress. Addition of I-, Br- and SCN- ions to the solution containing organic derivatives increases the inhibition efficiency of the system.

Recent Efforts for the Development of Antitubercular Drug Containing Diazine Ring

There has been considerable interest in the development of new molecule with antibacterial activities particularly against tuberclosis because mycobacterium species have developed resistant against currently used drugs, their toxic effect and long duration of therapy. The diazine (pyridazine, pyrimidine and piperazine) derivatives possess an important class of compound for new drugs research and development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their antitubercular activity. These observations have been guiding for the development of new molecules that possess potent antitubercular activity with minimum side effects or effective against MDR, XDR mycobacterium strains, and also in patient co-infected with HIV/AIDS.

In vitro and in silico studies of polycondensed diazine systems as anti-parasitic agents

Parasitic diseases caused by protozoarian agents are still relevant today more than ever. Recently, we synthesized several polycondensed diazine derivatives by means 1,3-dipolar cycloaddition reactions. A broad selection of these compounds were submitted to in vitro biological screening against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei, and Trypanosoma cruzi, resulting active at micromolar level. Induced Fit Docking/MM-GBSA studies were performed giving interesting indications about the probable mechanism of action of the most active compounds.

Synthesis and Antioxidant Evaluation of Some New 3‐Substituted Coumarins

3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3 via bromination of 1 to afford acetylbromide 2 followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of 3 with 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, 2-methyl-4H-benzo[d][1,3]oxazin-4-one, furo[3,4-b]pyrazine-5,7-dione or 2-methyl-5,6,7,8-tetrahydro-4H-benzothieno[2,3-d][1,3]oxazin-4-one afforded diazine derivatives 4-7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6-aminothiouracil, p-chlorobenzaldehyde and 3-acetylcoumarin. Moreover, refluxing of 6-aminothiouracil with one equivalent amount of 2 afforded the thiazolopyrimidine 9, while the pyrrolothiazolopyrimidine 10 was revealed when two equivalent amounts of 2 was used. Furthermore, treatment of enamine 11 with 2-aminobenzothiazole or 6-aminothiouracil afforded the pyrimidine derivatives 12 and 13, respectively. Transamination of enamine 11 with m-anisidine followed by cyclization of the resulting enaminone 14 gave the desired quinoline 15. Also, treatment of 11 with thiophenol in dioxane gave the mercapto derivative 16. Moreover, coupling of 11 with 4,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-3-yl-diazonium chloride, followed by complete cyclization of the resulting product afforded the pyridopyrazolothiazine 19 via the intermediate 18. Furthermore, the pyrazolopyrimidine 20 was revealed via a one pot condensation of 11, 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one and ammonium acetate. The thiadiazine derivatives 21-23 were obtained via treatment of 2 with the corresponding o-aminothiols. Desulphonation of 23 afforded the pyrazolotriazine 24. Finally, reaction of 2 with 2-hydroxybenzaldehyde gave benzofuran derivative 25. Representative compounds of the synthesized products were evaluated as antioxidant agents.

A facile synthesis of phenazine and quinoxaline (new 1,4-benzo diazine) derivatives using magnesium sulfate heptahydrate as a catalyst

Convenient and simple procedures for the synthesis of phenazine and quinoxaline derivatives were developed via a reaction of ophenylenediamines and 1,2-dicarbonyl compounds. In addition, the synthesis of two new derivatives of 1,4-benzo diazine derivatives and the catalytic activity of magnesium sulfate heptahydrate (MgSO4?7H2O) in the room temperature condensation of o-phenylenediamines and 1,2- dicarbonyl compounds in ethanol as solvent are reported. This method has many appealing attributes, such as excellent yields, short reactions times, and simple work-up procedures.

ChemInform Abstract: Integration of Layered Redox Proteins and Conductive Supports for Bioelectronic Applications

Integration of redox enzymes with an electrode support and formation of an electrical contact between the biocatalysts and the electrode is the fundamental subject of bioelectronics and optobioelectronics. This review addresses the recent advances and the scientific progress in electrically contacted, layered enzyme electrodes, and discusses the future applications of the systems in various bioelectronic devices, for example, amperometric biosensors, sensoric arrays, logic gates, and optical memories. This review presents the methods for the immobilization of redox enzymes on electrodes and discusses the covalent linkage of proteins, the use of supramolecular affinity complexes, and the reconstitution of apo-redox enzymes for the nanoengineering of electrodes with protein monolayers of electrodes with protein monolayers and multilayers. Electrical contact in the layered enzyme electrode is achieved by the application of diffusional electron mediators, such as ferrocene derivatives, ferricyanide, quinones, and bipyridinium salts. Covalent tethering of electron relay units to layered enzyme electrodes, the cross-linking of affinity complexes formed between redox proteins and electrodes functionalized with relay-cofactor units, or surface reconstitution of apo-enzymes on relay-cofactor-functionalized electrodes yield bioelectrocatalytic electrodes. The application of the functionalized electrodes as biosensor devices is addressed and further application of electrically wired enzymes as catalytic interfaces in biofuel cells is discussed. The organization of sensor arrays, self-calibrated biosensors, or gated bioelectronic devices requires the microstructuring of biomaterials on solid supports in the form of ordered micro-patterns. For example, light-sensitive layers composed of azides, benzophenone, or diazine derivatives associated with solid supports can be irradiated through masks to enable the patterned covalent linkage of biomaterials to surfaces. Alternatively, patterning of biomaterials can be accomplished by noncovalent interactions (such as in affinity complexes between avidin and a photolabeled biotin, or between an antibody and a photoisomerizable antigen layer) to provide a means of organizing protein microstructures on surfaces. The organization of patterned hydrophilic/hydrophobic domains on surfaces, by using photolithography, stamping, or micromachining methods, allows the selective patterning of surfaces by hydrophobic, noncovalent interactions. Photoactivated layered enzyme electrodes act as light-switchable optobioelectronic systems for the amperometric transduction of recorded photonic information. These systems can act as optical memories, biomolecular amplifiers, or logic gates. The photoswitchable enzyme electrodes are generated by the tethering of photoisomerizable groups to the protein, the reconstitution of apo-enzymes with semisynthetic photoisomerizable cofactor units, or the coupling of photoisomerizable electron relay units.

The Behavior of Phosphorus Reagents Towards Substituted Diazine and Hydrazine Derivatives

The reaction of dibenzoyldiazine with phosphorus ylides afforded the new 2-[(benzoylhydrazono)phenylalkyl]but-2-enedioic acid dialkylesters. Moreover, ethyl-2(triphenylphosphoranylidene)propionate reacts with dibenzoyldiazine to give the olefinic compound and triphenylphosphine oxide. On the other hand, oxovinylidene-triphenylphosphorane reacts with dibenzoyldiazine to give a new phosphorane adduct. Trialkyl phosphites react with dibenzoyldiazine to yield the dialkyl phosphonate products. The reaction of dibenzoylhydrazide with Wittig reagents gave rise to the new 3,7-diphenylpyrazolo[1,2-α]pyrazole-1,5-diones. Possible reaction mechanisms are considered, and the structural assignments are based on analytical and spectroscopic results.

SYNTHESIS OF FUSED AND SPIRO HETEROCYCLIC COMPOUNDS DERIVED FROM 3,5-PYRAZOLIDINEDIONE DERIVATIVES

The reaction of compound 1 with triethyl orthoformate afforded 2, which in turn reacted with CS2 and active methlyene compounds or malononitrile to give dithiolane and 4-malononitrile methylene derivatives 3,4, respectively. Treatment of compound 4 with active methylene compounds afforded spiro cyclopentene derivatives 5a-c. Compound 1 was reacted with bromomalononitrile or CS2 and halocompounds to afford furo-. thieno- and dithiolano-pyrazole derivatives 6–11, respectively. The reaction of compound 12 with phenacyl bromide or benzylidenemalononitrile furnished oxathiol-2-ylidene and pyridinethione derivatives 13,14, respectively. The dibromo derivative 16 was reacted with CS2 and active methylenes or malononitrile to obtain spiro dithietanes 17a-e and 4-dicyano-methlyene derivative 22, respectively. Compounds 17 underwent a cycloaddition reaction with thioglycolic acid, N-phenylbenzohydrazindoyl bromide, 2,5-dimethylfuran and 1-phenyl-3,5-pyrazolidinedi one to give cycloadducts 18–21, respectively. Treatment of > o-aminothiophenol or o-phenylenediamine with the dicyano compound 22 leads to the formation of spiro thiazepine or spiro diazine derivatives 23a,b . The arylidene derivatives 24 was reacted with S,S-acetals, N,S-acetals or ammonium dithiocarbamate to afford dithiane, oxazine or pyrazolodithiocarbamate derivatives 25–29, respectively. Chemoselective cyclization of compound 29 with H2SO4, NaOH or MeI gave compounds 30–32, respectively. Benzopyrano derivatives 34,36 were obtained through the reaction of compound 1 with a mixture of thiourea, triethyl orthoformate and ethyl cyanoacetate or with cyanoketene S,S diacetals, respectively.

Integration of Layered Redox Proteins and Conductive Supports for Bioelectronic Applications.

Integration of redox enzymes with an electrode support and formation of an electrical contact between the biocatalysts and the electrode is the fundamental subject of bioelectronics and optobioelectronics. This review addresses the recent advances and the scientific progress in electrically contacted, layered enzyme electrodes, and discusses the future applications of the systems in various bioelectronic devices, for example, amperometric biosensors, sensoric arrays, logic gates, and optical memories. This review presents the methods for the immobilization of redox enzymes on electrodes and discusses the covalent linkage of proteins, the use of supramolecular affinity complexes, and the reconstitution of apo-redox enzymes for the nanoengineering of electrodes with protein monolayers of electrodes with protein monolayers and multilayers. Electrical contact in the layered enzyme electrode is achieved by the application of diffusional electron mediators, such as ferrocene derivatives, ferricyanide, quinones, and bipyridinium salts. Covalent tethering of electron relay units to layered enzyme electrodes, the cross-linking of affinity complexes formed between redox proteins and electrodes functionalized with relay-cofactor units, or surface reconstitution of apo-enzymes on relay-cofactor-functionalized electrodes yield bioelectrocatalytic electrodes. The application of the functionalized electrodes as biosensor devices is addressed and further application of electrically "wired" enzymes as catalytic interfaces in biofuel cells is discussed. The organization of sensor arrays, self-calibrated biosensors, or gated bioelectronic devices requires the microstructuring of biomaterials on solid supports in the form of ordered micro-patterns. For example, light-sensitive layers composed of azides, benzophenone, or diazine derivatives associated with solid supports can be irradiated through masks to enable the patterned covalent linkage of biomaterials to surfaces. Alternatively, patterning of biomaterials can be accomplished by noncovalent interactions (such as in affinity complexes between avidin and a photolabeled biotin, or between an antibody and a photoisomerizable antigen layer) to provide a means of organizing protein microstructures on surfaces. The organization of patterned hydrophilic/hydrophobic domains on surfaces, by using photolithography, stamping, or micromachining methods, allows the selective patterning of surfaces by hydrophobic, noncovalent interactions. Photoactivated layered enzyme electrodes act as light-switchable optobioelectronic systems for the amperometric transduction of recorded photonic information. These systems can act as optical memories, biomolecular amplifiers, or logic gates. The photoswitchable enzyme electrodes are generated by the tethering of photoisomerizable groups to the protein, the reconstitution of apo-enzymes with semisynthetic photoisomerizable cofactor units, or the coupling of photoisomerizable electron relay units.