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Molecules (Basel, Switzerland) Jun 2019The performance of 26 hybrid density functionals was tested against a tautomeric dataset (TautData), containing experimental information for the keto-enol tautomeric...
The performance of 26 hybrid density functionals was tested against a tautomeric dataset (TautData), containing experimental information for the keto-enol tautomeric equilibrium in 16 tautomeric azodyes and Schiff bases in cyclohexane, carbon tetrachloride and acetonitrile. The results have shown that MN12-SX, BHandH and M06-2X can be used to describe the tautomeric state of the core structures in the frame of ~0.5 kcal/mol error and correctly predict the tautomeric state in respect of dominating tautomeric form. Among them MN12-SX is the best performer, although it fails to describe the nonplanarity of some of the enol tautomers. The same experimental dataset was used to develop and test a special DFT functional (TautLYP) aimed at describing the tautomeric state in azo- and azomethyne compounds in solution when nonspecific solvents are used.
Topics: Algorithms; Azo Compounds; Coloring Agents; Models, Theoretical; Molecular Structure; Photochemical Processes; Spectrum Analysis; Stereoisomerism
PubMed: 31212924
DOI: 10.3390/molecules24122252 -
Chembiochem : a European Journal of... Aug 2022Azoreductases are potent biocatalysts for the cleavage of azo bonds. Various gene sequences coding for potential azoreductases are available in databases, but many of...
Azoreductases are potent biocatalysts for the cleavage of azo bonds. Various gene sequences coding for potential azoreductases are available in databases, but many of their gene products are still uncharacterized. To avoid the laborious heterologous expression in a host organism, we developed a screening approach involving cell-free protein synthesis (CFPS) combined with a colorimetric activity assay, which allows the parallel screening of putative azoreductases in a short time. First, we evaluated different CFPS systems and optimized the synthesis conditions of a model azoreductase. With the findings obtained, 10 azoreductases, half of them undescribed so far, were screened for their ability to degrade the azo dye methyl red. All novel enzymes catalyzed the degradation of methyl red and can therefore be referred to as azoreductases. In addition, all enzymes degraded the more complex and bulkier azo dye Brilliant Black and four of them also showed the ability to reduce p-benzoquinone. NADH was the preferred electron donor for the most enzymes, although the synthetic nicotinamide co-substrate analogue 1-benzyl-1,4-dihydronicotinamide (BNAH) was also accepted by all active azoreductases. This screening approach allows accelerated identification of potential biocatalysts for various applications.
Topics: Azo Compounds; Coloring Agents; Electrons; NADH, NADPH Oxidoreductases; Nitroreductases
PubMed: 35593146
DOI: 10.1002/cbic.202200121 -
Bioconjugate Chemistry Jan 2018Hyperbranched polyamidoamines (h-PAMAM) were prepared using a one-pot reaction to have similar molecular weight to third generation PAMAM (G3-PAMAM) dendrimers, and then...
Hyperbranched polyamidoamines (h-PAMAM) were prepared using a one-pot reaction to have similar molecular weight to third generation PAMAM (G3-PAMAM) dendrimers, and then functionalized with N-diazeniumdiolate nitric oxide (NO) donors. A wide range of NO storage capacities (∼1-2.50 μmol mg) and NO-release kinetics (t ∼30-80 min) were achieved by changing the extent of propylene oxide (PO) modification. The therapeutic potential of these materials was evaluated by studying their antibacterial activities and toxicity against common dental pathogens and human gingival fibroblast cells, respectively. Our results indicate that the combination of NO release and PO modification is necessary to yield h-PAMAM materials with efficient bactericidal action without eliciting unwarranted cytotoxicity. Of importance, NO-releasing PO-modified h-PAMAM polymers exhibited comparable biological properties (i.e., antibacterial action and cytotoxicity) to defect-free G3-PAMAM dendrimers, but at a substantially lower synthetic burden.
Topics: Anti-Bacterial Agents; Azo Compounds; Bacteria; Bacterial Infections; Cell Line; Dendrimers; Humans; Microbial Sensitivity Tests; Nitric Oxide Donors; Structure-Activity Relationship
PubMed: 29243926
DOI: 10.1021/acs.bioconjchem.7b00537 -
Chemical & Pharmaceutical Bulletin 2021The ability to control the reactions of highly active chemical species to enable straightforward synthesis of valuable compounds such as bioactive natural products and... (Review)
Review
The ability to control the reactions of highly active chemical species to enable straightforward synthesis of valuable compounds such as bioactive natural products and pharmaceuticals is a continuing challenge in synthetic organic chemistry. This review describes the development of a methodology using reactive metal-carbene species and its synthetic application in our laboratory. First, regioselective synthesis of γ-amino acid equivalents to take advantage of their metal-dependent reactivities and the mechanistic rationale are presented. Chemoselective and enantioselective dearomatization reactions of several arenes with silver-carbene are also discussed. In the second half of the review, we discuss a carbene-insertion reaction into an amide and urea C-N bond for the assembly of nitrogen-bridged cyclic molecules.
Topics: Azo Compounds; Catalysis; Metals, Heavy; Methane
PubMed: 34853283
DOI: 10.1248/cpb.c21-00757 -
Chemical & Pharmaceutical Bulletin 2020Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on...
Photopharmacology has attracted attention as an approach for the development of novel therapeutics because it allows regulation of the bioactivity of compounds based on their conformational change by photo-irradiation. Previously, we have reported several types of selective estrogen receptor (ER) modulators based on diphenylmethane skeleton. To develop novel photopharmacological reagents, we designed and synthesized a set of ER ligands based on azobenzene skeleton, which can switch its conformation following UV irradiation. Our results showed that after UV irradiation, the Z-form of the synthesized compound 9 interacted with ERα, with a K value of 2.5 µM, whereas the E-form of compound 9 did not bind ability to ERα at 10 µM.
Topics: Azo Compounds; Fluorescence Polarization; Humans; Ligands; Molecular Structure; Photochemical Processes; Receptors, Estrogen; Selective Estrogen Receptor Modulators; Stereoisomerism; Structure-Activity Relationship; Ultraviolet Rays
PubMed: 32238658
DOI: 10.1248/cpb.c19-01108 -
Molecules (Basel, Switzerland) Sep 2019Diazo compounds have proven to be a useful class of carbenes or metal carbenoids sources under thermal, photochemical, or metal-catalyzed conditions, which can... (Review)
Review
Diazo compounds have proven to be a useful class of carbenes or metal carbenoids sources under thermal, photochemical, or metal-catalyzed conditions, which can subsequently undergo a wide range of synthetically important transformations. Recently, asymmetric photocatalysis has provoked increasing research interests, and great advances have been made in this discipline towards the synthesis of optically enriched compounds. In this context, the past two decades have been the most productive period in the developments of enantioselective photochemical reactions of diazo compounds due to a better understanding of the reactivities of diazo compounds and the emergence of new catalytic modes, as well as easier access to and treatment of stabilized diazo compounds. This review highlights these impressive achievements according to the reaction type, and the general mechanisms and stereochemical inductions are briefly discussed as well.
Topics: Azo Compounds; Catalysis; Cycloaddition Reaction; Cyclopropanes; Photochemical Processes; Stereoisomerism
PubMed: 31480796
DOI: 10.3390/molecules24173191 -
International Journal of Molecular... Jun 2020Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of...
Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of linking units in the molecules such as amide-azo () and azo-azo (). The homologues of the same series contain different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxyl, carboxyl, chloro, nitro, and amino groups. All the intermediates and final compounds were characterized using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and Carbon, Hydrogen, and Nitrogen (CHN) elemental analysis. Liquid crystal properties for all compounds were determined using polarized optical microscope (POM). It was found that only intermediates with nitro and alkoxyl terminal chains showed a smectic A phase. All the final compounds with alkoxyl substituents are mesogenic with either smectic A or C phases. However, other intermediates and compounds were found to be non-mesogenic. The study on the fire retardancy of final compounds was determined using limiting oxygen index (LOI) method. The LOI value of pure polyester resin (22.53%) was increased up to 24.71% after treating with 1 wt% of hexachlorocyclotriphosphazene (HCCP). Moreover, all the compounds gave positive results on the LOI values and compound with the nitro terminal substituent showed the highest LOI value of 27.54%.
Topics: Amides; Azo Compounds; Flame Retardants; Liquid Crystals; Microscopy, Polarization; Molecular Structure; Nitriles; Oxygen; Phosphorus Compounds; Spectroscopy, Fourier Transform Infrared
PubMed: 32560033
DOI: 10.3390/ijms21124267 -
Angewandte Chemie (International Ed. in... Jan 2017The p300/CBP-associated factor (PCAF) and related GCN5 bromodomain-containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic...
The p300/CBP-associated factor (PCAF) and related GCN5 bromodomain-containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine-based L-45 (dubbed L-Moses) as the first potent, selective, and cell-active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)-(-)-norephedrine furnished L-45 in enantiopure form. L-45 was shown to disrupt PCAF-Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co-crystal structure of L-45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L-45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell-permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
Topics: Azo Compounds; Dose-Response Relationship, Drug; Drug Discovery; Hydralazine; Molecular Probes; Molecular Structure; Structure-Activity Relationship; p300-CBP Transcription Factors
PubMed: 27966810
DOI: 10.1002/anie.201610816 -
Angewandte Chemie (International Ed. in... Feb 2022Eg5 is a kinesin motor protein that is responsible for bipolar spindle formation and plays a crucial role during mitosis. Loss of Eg5 function leads to the formation of...
Eg5 is a kinesin motor protein that is responsible for bipolar spindle formation and plays a crucial role during mitosis. Loss of Eg5 function leads to the formation of monopolar spindles, followed by mitotic arrest, and subsequent cell death. Several cell-permeable small molecules have been reported to inhibit Eg5 and some have been evaluated as anticancer agents. We now describe the design, synthesis, and biological evaluation of photoswitchable variants with five different pharmacophores. Our lead compound Azo-EMD is a cell permeable azobenzene that inhibits Eg5 more potently in its light-induced cis form. This activity decreased the velocity of Eg5 in single-molecule assays, promoted formation of monopolar spindles, and led to mitotic arrest in a light dependent way.
Topics: Azo Compounds; Humans; Kinesins; Mitosis; Photochemical Processes; Spindle Apparatus
PubMed: 34958711
DOI: 10.1002/anie.202115846 -
Molecules (Basel, Switzerland) Aug 2010In this paper we present six select mesomorphic azo compounds distinguished by the presence of diverse substituents on a central benzene nucleus. All the synthesized...
In this paper we present six select mesomorphic azo compounds distinguished by the presence of diverse substituents on a central benzene nucleus. All the synthesized compounds exhibit enantiotropic mesophases. The mesomorphic properties of the substituted compounds were compared with those of the unsubstituted parent compound to evaluate the effect of the nature and position of the substituents on mesomorphism.
Topics: Azo Compounds; Entropy; Esters; Liquid Crystals; Phase Transition
PubMed: 20714316
DOI: 10.3390/molecules15085620