Hydrazone Unit Research Articles

Copper Incorporated Covalent Organic Framework as a Heterogeneous Catalyst for CuAAC Reaction

AbstractCovalent organic frameworks (COFs) incorporating metal are attractive alternatives for metal‐catalyzed organic transformations. For effective metal incorporation in COF a favorable ligand environment is required. Pyridine and hydrazone units can provide effective binding sites for transition metals. The major challenge in synthesizing hydrazone‐linked COFs is the inherent flexibility of the linker, causing differences in lengths and orientations during solvothermal synthesis. We demonstrate that incorporation of enol form in the framework facilitates non‐covalent interactions such as hydrogen bonding, reduces degrees of freedom and enhances rigidity. Here, we synthesized TFP‐PyHz COF utilizing 2,4,6‐trihydroxybenzene‐1,3,5‐tricarbaldehyde (TFP) and pyridine‐2,6‐dicarbohydrazide. Enol form in the framework was confirmed by comparing the IR and 13C solid‐state NMR spectra of TFP‐PyHz with its model compound. The presence of this enol form also facilitates the incorporation of Cu2+ through post‐modification as confirmed by IR and XPS analysis of postmodified Cu‐TFP‐PyHz. The copper‐incorporated material Cu‐TFP‐PyHz is utilized as a heterogeneous catalyst for copper‐catalyzed click reactions, enabling the synthesis of 1,4‐triazoles.

Novel Imidazole‐based Hydrazonoyl Cyanides and Amidrazones Containing N(N,O)‐Heterocycles: Selective Synthesis, Reaction Mechanisms and Preliminary Anticancer Evaluation

AbstractTwo series of novel hybrid heterocyclic compounds that combine the imidazole ring with bioactive piperidine, morpholine or piperazine heterosystems, through a hydrazone unit, were easily obtained by two competitive pathways. Starting from 5‐amino‐4‐cyanoformimidoyl imidazoles and 1‐aminopiperidine, 4‐aminomorpholine or 1‐amino‐4‐methylpiperazine under mild acidic media led to the selective synthesis of 5‐aminoimidazole 4‐carboxamidrazones, whereas the corresponding 4‐hydrazonoyl cyanide derivatives were obtained under stronger acidic conditions. These highly functionalized imidazoles provide convenient synthetic precursors to a vast array of heterocycles with potential pharmaceutical applications. The reaction mechanisms were elucidated on the basis of experimental assays and in silico calculations. The compounds were screened against colorectal cancer HCT116‐p53 wt cell line, and significant IC50 values of 3.69 μM and 4.83 μM were obtained.

Fluorescent Biomass-Based Platform for Detection of ClO- in Cells and Water-Soluble Systems.

The generation and presence of excessive hypochlorous acid derivative ionic form (ClO-) could cause various diseases, such as arteriosclerosis, DNA damage, and cardiovascular illness. It is a critical need to develop a highly sensitive sensor for reliable detection of ClO- in cells and water-soluble systems. In this work, a hydroxyl group has been introduced into the compound 2-amino-3-(((E)-4-(2-(2-(2-hydroxyethoxy)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)benzylidene)amino)maleonitrile (NDC) to increase its solubility in water, at the same time, the hydrazone unit was designed as a specific recognition group for the "off-on" fluorescence probe of ClO-. The probe NDC presents high selectivity, sensitivity, anti-interference, and low detection limit (67 nM) for ClO-. The recognition mechanism that ClO- breaks the C=N bond and forms the fluorescent compound 4-(2-(2-(2-hydroxyethoxy)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)benzaldehyde (ND-3) has been confirmed by time-of-flight mass spectrometry. The probe NDC presents a good performance in the actual test of water samples and can be designed as the test papers for the quick and convenient detection of ClO- range from 0 to 1 μM. Moreover, the practical application was demonstrated by the successful imaging of endogenous and exogenous ClO- in HeLa cells. Our fluorescent biomass-based platform opens vast possibilities for repeatability, sensitivity, and selectivity detection of ClO- in cells and water-soluble systems.

Synthesis of nimbolide and its analogues and their application as poly(ADP-ribose) polymerase-1 trapping inducers.

Nimbolide, a ring seco-C limonoid natural product, was recently found to inhibit the poly(ADP)-ribosylation (PARylation)-dependent ubiquitin E3 ligase RNF114. In doing so, it induces the 'supertrapping' of both PARylated PARP1 and PAR-dependent DNA-repair factors. PARP1 inhibitors have reshaped the treatment of cancer patients with germline BRCA1/2 mutations partly through the PARP1 trapping mechanism. To this end, modular access to nimbolide analogues represents an opportunity to develop cancer therapeutics with enhanced PARP1 trapping capability. Here we report a convergent synthesis of nimbolide through a late-stage coupling strategy. Through a sulfonyl hydrazone-mediated etherification and a radical cyclization, this strategy uses a pharmacophore-containing building block and diversifiable hydrazone units to enable the modular synthesis of nimbolide and its analogues. The broad generality of our synthetic strategy allowed access to a variety of analogues with their preliminary cellular cytotoxicity and PARP1 trapping activity reported.

New Amino Acid-Based Thiosemicarbazones and Hydrazones: Synthesis and Evaluation as Fluorimetric Chemosensors in Aqueous Mixtures.

Bearing in mind the interest in the development and application of amino acids/peptides as bioinspired systems for sensing, a series of new phenylalanine derivatives bearing thiosemicarbazone and hydrazone units at the side chain were synthesised and evaluated as fluorimetric chemosensors for ions. Thiosemicarbazone and hydrazone moieties were chosen because they are considered both proton-donor and proton-acceptor, which is an interesting feature in the design of chemosensors. The obtained compounds were tested for the recognition of organic and inorganic anions (such as AcO-, F-, Cl-, Br-, I-, ClO4-, CN-, NO3-, BzO-, OH-, H2PO4- and HSO4-) and of alkaline, alkaline-earth, and transition metal cations, (such as Na+, K+, Cs+, Ag+, Cu+, Cu2+, Ca2+, Cd2+, Co2+, Pb2+, Pd2+, Ni2+, Hg2+, Zn2+, Fe2+, Fe3+ and Cr3+) in acetonitrile and its aqueous mixtures in varying ratios via spectrofluorimetric titrations. The results indicate that there is a strong interaction via the donor N, O and S atoms at the side chain of the various phenylalanines, with higher sensitivity for Cu2+, Fe3+ and F- in a 1:2 ligand-ion stoichiometry. The photophysical and metal ion-sensing properties of these phenylalanines suggest that they might be suitable for incorporation into peptide chemosensory frameworks.

Study of the separation ability differences of three covalent organic frameworks as coated materials in capillary electrochromatography

Covalent organic frameworks (COFs) have great potential applications in chromatographic separation. So it is crucial to understand the relationship between the separation ability of COFs and their structures. Here we report a strategy to evaluate the separation ability of three 2D COFs and explore the relationship between separation ability and their molecular structures. The three 2D COFs (COF-LZU1, COF-42 and COF-LZU8) have one same building unit 1,3,5-triformylbenzene, while varied from the conjugated linking units and functional side-chains. They were used to construct coated capillary column for capillary electrochromatographic separation of same groups of phthalates. They exhibited different separation efficiencies. COF-42 and COF-LZU8 coated capillary columns provided good signal resolutions and high column efficiencies with high theoretical plate numbers. It is demonstrated that COFs with hydrazone unit and longer side-chains provided higher selectivity and resolutions for the phthalates separation. Molecular simulations and DFT calculations were further proceeded to explore the deep reason why the three COFs coated CEC displayed different separation ability based on the host−guest interactions on molecular level. This work highlights a new opportunity to select or design functional COFs and improve their efficiency in chromatographic separation based on host−guest chemistry.

Novel C-3-(N-alkyl-aryl)-aminomethyl rifamycin SV derivatives exhibit activity against rifampicin-resistant Mycobacterium tuberculosis RpoBS522L strain and display a different binding mode at the RNAP β-subunit site compared to rifampicin.

Antimicrobial resistance is a main concern in tuberculosis treatment and is often associated with the emergence of Mycobacterium tuberculosis strains resistant to rifampicin (RIF), which is one of the cornerstones of tuberculosis chemotherapy. In this study, aminoalkyl-aromatic ring tails were appended to the C3 position of rifamycin core to assess the role of C3 substitutions to the anti-mycobacterial activity of the rifamycin antibiotics. The typical hydrazone unit of RIF was replaced by an amino-alkyl linkage to connect the aromatic ring tails with the rifamycin naphthoquinone core. Eight novel C3-(N-alkyl-aryl)-aminoalkyl analogues of rifamycin SV were synthesised and screened invitro against wild-type HR37Rv and "hypervirulent" HN-878 strains, and a panel of rifampicin-resistant M.tuberculosis clinical isolates carrying mutations at the 522, 531 and 455 positions of the rpoB gene (RpoBS522L, RpoBS531L and RpoBH455D strains). The analogues exhibited anti-tubercular activity against H37Rv and HN-878 at submicromolar or nanomolar concentrations, and against clinical H37Rv isolates bearing the S522L mutations at low micromolar concentration. Benzylamine moiety-including analogue 8 was as active as rifampicin against HN-878 with a MIC90 value of 0.02μM, whereas 14 and 15, which included tryptamine and para-methyl-sulfonylbenzylamine C3-substituents, respectively, showed higher anti-tubercular activity (MIC90=3μM) compared to rifampicin against the S522L mutated H37Rv strain. Detailed in silico analysis of different RNAP molecular systems predicted a distinct, possibly novel, binding mode for the new rifamycin analogues. These were found to occupy a different space in the binding pockets of both wild type and mutated RNAP proteins compared to that of rifampicin. Moreover, the molecular modelling experiments investigated the ability of the novel analogues aromatic tails to establish key interactions at the RNAP binding site. These interesting findings might pave the way for generating rifamycin analogues that can overcome anti-microbial resistance in M.tuberculosis.

Design, synthesis and biological evaluation of novel 3-phenylpropanamide derivatives with acyl hydrazone units

In this study, a series of 3-phenylpropanamide derivatives with acyl hydrazone units were synthesized and characterized by 1H NMR, 13C NMR and HR MS. And the structure of compound III33 was confirmed by X-ray single crystal. The bioassay results showed that, compounds III8, III17, III22, and III34 showed excellent inhibition on Xanthomonas oryzae pv. pryzae (Xoo) with EC50 values of 7.1, 8.8, 9.5, and 4.7 μg/mL in vitro. The EC50 values of compounds III12, III14 and III33 against Ralstonia solanacearum (Rs) were 7.6, 7.6 and 7.9 μg/mL, respectively, all lower than the values of thiadiazol copper (TC) was 66.8 μg/mL and bismerthiazol (BT) was 72.4 μg/mL. Compounds III12, III14, III33, and III34 exhibited excellent antibacterial activity of more than 80% against Xanthomonas axonopodis pv. citri (Xac) in vitro. Besides, compounds III8 (51.4%) and III34 (52.1%) were highly effective against Xoo in vivo, outperforming TC (49.5%) and BT (47.8%). Compounds III8 (29.8%) and III34 (24.6%) were close to TC (41.7%) and BT (47.8%) in terms of protective efficacy against Xoo in vivo. Meanwhile, some of title compounds also displayed inhibitory effects against phytopathogenic fungi. In a word, this study illustrated that the structures combined with phenylpropane amide derivatives of the acyl hydrazone units could be used as potential antibacterial reagents in the future.

A new diarylethene based chemosensor for colorimetric recognition of arginine and fluorescent detection of Cu2+

A novel diarylethene derivative with a benzothiazolinone hydrazone unit was synthesized as a new chemical sensor, the photochemical properties and ion selectivity were studied. It not only acted as a colorimetric sensor for detecting arginine in the ring-closed isomer, but also served as a fluorescence sensor for detecting Cu2+ in the ring-open isomer. When various metal ions were added to the sensor solution respectively, only Cu2+ resulted in an obvious quenching of fluorescence, and the fluorescence color changes from yellow to black. What's more, upon the addition of arginine, the color of the ring-closed isomer's solution changed from purple to blue, which was attributed to the proton transfer from ring-closed isomer to arginine, it can be proved by 1H NMR spectrum. Furthermore, the chemosensor could also be made into test papers for detecting Cu2+ in actual water samples.

Multifunctional behavior of bis-acylhydrazone: Real-time detection of moisture in organic solvents, halochromism and aggregation induced emission

A versatile novel indenopyrazine/indenoquinoxaline appended acylhydrazones (1 and 2) have been designed and synthesized successfully. Compounds 1 and 2 are designed such that, it comprises of acylhydrazone, which is responsible for moisture detection via deprotonation of the original molecule, pyrazine, pyridine and hydrazone unit which is responsible for halochromism via protonation and deprotonation, further the integrated twisted molecular structure results in the aggregation-induced emission features. Successive treatment of Fˉ and moisture to compound 1 and 2 produce reversible colorimetric responses that are easily visualized by the naked eye. Further, the corresponding mechanism was effectively confirmed by 1H NMR spectral analysis. The inherent halochromic features of appended unique pyrazine and pyridine core in compounds 1 and 2 were studied by the sequential addition of trifluoroacetic acid (TFA) and triethylamine (TEA) which is authenticated by reversible colorimetric changes as well as absorption spectral studies. Compound 1 adopts a twisted scissor-like structure and due to multiple weak interactions results in an interesting supramolecular network. Furthermore, both compound 1 and 2 exhibits the aggregation-induced emission features in DMF/water mixture, which was expansively confirmed through DLS particle analysis and TEM images. The integration of three distinct features into a single molecule are scarce.

Synthesis and structural characterization of dinuclear Zinc(II) and Europium(III) complexes based on a bis-hydrazone ligand

A C2-symmetrical N,O-Schiff base ligand containing two hydrazone units has been synthesized and structurally characterized. The solid state structure as determined by single-crystal X-ray diffraction analysis reveals the presence of both intramolecular and intermolecular hydrogen bonds which lead to the formation of a C1-symmetrical conformation as well as a novel one-dimensional (1-D) helical hydrogen-bonded network. The reactions of this bis-hydrazone ligand with zinc(II) and europium (III) salts under appropriate conditions resulted in dinuclear mono-ligand zinc and tri-ligand europium complexes, respectively. The complexes were characterized by NMR spectroscopies, mass spectrometry and elemental analysis. The zinc complex has been further structurally determined by X-ray crystallography. In its solid state structure, the ligand is doubly deprotonated incorporating two zinc(II) cores that are bridged with both phenol-O group and acetate counterions. The solution electronic absorption and emission properties were characterized for both the ligand and zinc complex.

Modulating the selectivity of a colorimetric sensor based on a Schiff base-functionalized diarylethene towards anions by judicious choice of solvent

A novel diarylethene derivative with a 9-fluorenone hydrazone unit has been synthesized, which showed multi-responsive for light, acid-base and anions. Its sensing properties were well studied by colorimetric and spectroscopic method, and the selectivity could be modulated through judicious choice of solvent. It can simultaneously colorimetric sensing of carbonate ion in methanol with the detection limit of 1.25 × 10−6 mol L-1 and cyanide ion in tetrahydrofuran with the detection of 2.85 × 10−7 mol L−1, respectively. The different sensing mechanism for carbonate ion and cyanide ion was confirmed by UV–vis and 1H-NMR characterization techniques. Moreover, the compound can be used detect carbonate ion and cyanide ion in natural water sample with a high accuracy.

Methyl 4-{N′-[(1E)-1-(pyrazin-2-yl)ethylidene]hydrazinecarbonyl}benzoate

The title Schiff base, C15H14N4O3, was synthesized by the condensation reaction between caprylic hydrazide and 2-acetylpyrazine. There are two independent pseudo-enantiomeric molecules, A and B, in the asymmetric unit that differ mainly in the orientation of the hydrazone units. For example, the dihedral angles between the benzene and pyrazine rings are 20.836 (13) (A) and 15.701 (14)° (B). The molecular packing features N—H...O hydrogen bonds that lead to a twisted supramolecular chain along the b-axis direction. The presence of C—H...O interactions consolidates the chains into a three-dimensional architecture. The studied sample was a two-component twin.

Discovery of Unprecedented Hydrazine-Forming Machinery in Bacteria.

Recent studies described several different routes that facilitate nitrogen-nitrogen bond formation in natural product biosynthesis. We report herein the identification of unprecedented machinery for hydrazine formation involved in the biosynthesis of s56-p1, a dipeptide natural product with a unique hydrazone unit. The gene cassette comprising this machinery is widespread across several bacterial phyla, highlighting the overlooked potential of bacteria to synthesize hydrazine.

A colorimetric and fluorescent chemosensor for selective detection of Cu2+ based on a new diarylethene with a benzophenone hydrazone unit.

A new photochromic diarylethene based on benzophenone hydrazone has been synthesized. Its photochromic and fluorescent properties changed upon alternating irradiation with UV/Vis light and adding Cu2+ /EDTA in methanol, which showed that the diarylethene could be served as a colorimetric and fluorescent chemosensor for selective detection of Cu2+ based on internal charge transfer processes. The colorimetric and turn-off fluorescent selective detection of Cu2+ was attributed to the 2:1 complex of the diarylethene and Cu2+ . The binding constant (Ka) was 1.53×104 L mol-1 and the limit of detection of the diarylethene for Cu2+ was calculated to be 1.45×10-6 mol L-1 . In addition, the metal-responsive photochromic behavior of diarylethene was applied successfully to the construction of a molecular logic circuit.

Genome Mining of Amino Group Carrier Protein-Mediated Machinery: Discovery and Biosynthetic Characterization of a Natural Product with Unique Hydrazone Unit.

We recently revealed that a Streptomyces strain possesses the gene encoding amino group carrier protein (AmCP). AmCP is involved in the biosynthesis of a previously unidentified nonproteinogenic amino acid, (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), which is a core compound for the synthesis of the dipeptide-containing novel natural product vazabitide A. We used polymerase chain reaction (PCR) screening to investigate the diversity of the biosynthetic machinery that uses AmCP; the results revealed that genes encoding AmCP are widely distributed among actinomycetes. The heterologous expression of the AmCP-containing gene cluster from Streptomyces sp. SoC090715LN-17 led to the discovery of s56-p1, a novel natural product. The structure of s56-p1 was determined by spectroscopic analysis; the results revealed that s56-p1 has a putative DADH-derived molecule as the core and also possesses a unique hydrazone unit that is rarely observed in natural products. Our results pave the way for investigations of unexploited AmCP-mediated biosynthesis routes among actinomycetes and of the biosynthetic mechanism of the unique hydrazone unit.

A new dual-channel ratiometric fluorescent chemodosimeter for Cu2+ and its imaging in living cells

A new BODIPY derivative bearing hydrazone and hydrazide moieties was developed as an efficient dual-channel ratiometric fluorescence chemodosimeter 1 for Cu2+ in neutral aqueous medium via Cu2+-mediated hydrolysis of CN bond in hydrazone unit. Confocal microscopy experiments have demonstrated that chemodosimeter 1 could also be used in live cells for the fast detection of Cu2+.

ChemInform Abstract: Controlled Folding, Motional, and Constitutional Dynamic Processes of Polyheterocyclic Molecular Strands

AbstractReview: [84 refs.

Controlled Folding, Motional, and Constitutional Dynamic Processes of Polyheterocyclic Molecular Strands.

General design principles have been developed for the control of the structural features of polyheterocyclic strands and their effector-modulated shape changes. Induced defined molecular motions permit designed enforcement of helical as well as linear molecular shapes. The ability of such molecular strands to bind metal cations allows the generation of coiling/uncoiling processes between helically folded and extended linear states. Large molecular motions are produced on coordination of metal ions, which may be made reversible by competition with an ancillary complexing agent and fueled by sequential acid/base neutralization energy. The introduction of hydrazone units into the strands confers upon them constitutional dynamics, whereby interconversion between different strand compositions is achieved through component exchange. These features have relevance for nanomechanical devices. We present a morphological and functional analysis of such systems developed in our laboratories.

Synthesis and structural characterization of zinc(II) and cobalt(II) complexes based on multidentate hydrazone ligands

Two multidentate Schiff base ligands containing a hydrazone unit have been synthesized and investigated for zinc(II) and cobalt(II) coordination chemistry. The reactions of the 4-pyridyl derived hydrazone ligand HL1 with zinc(II) or cobalt(II) salts gave three mononuclear complexes that were structurally characterized by X-ray diffraction analysis. The results revealed that the ligand could adopt different coordination modes when various counter anions were employed. While in the case that zinc dichloride was used as a metal salt a neutral mononuclear mono-ligand complex was formed, the deprotonation of hydrazone occurred when zinc(II) or cobalt(II) nitrate were present and two new isostructural mononuclear bis-ligand complexes were isolated. Modification of the hydrazone ligand with oxygen donors was found to have a significant impact on the ligand reactivity, and a similar reaction of H2L2 with cobalt(II) nitrate gave a protonated product of H2L2 without the incorporation of cobalt(II), which features a one-dimensional hydrogen-bonded network in the solid state.