Orthogonal or simultaneous use of disulfide and hydrazone exchange in dynamic covalent chemistry in aqueous solution

Hydrazone and disulfide exchange have been combined in a single system, but can be addressed independently: by adjusting the pH of the solution from acidic to mildly basic it is possible to switch from exclusively hydrazone exchange to exclusively disulfide exchange, while at intermediate pH both reactions occur simultaneously.     

Synthesis of insulin fragments with disulfide bridges between intact chains A20-B19

The synthesis of six insulin fragments is described, in which various sequences of the two chains are linked by the disulfide bridge between A²⁰ and B¹⁹. The fragments in question are: A^20–21–B^19–21, A^20–21–B^18–21, A^20–21–B^17–21, A^19–21–B^19–21, A^16–21–B^18–21 and A^20–21–B^12–21. In order to build up the simpler fragments the disulfide bridge was established by oxidation with iodine of two S-trityl cysteine peptides in which the carboxyl and amino groups were protected by the t-butyl and t-butyloxycarbonyl residue. From the mixture obtained the unsymmetrical cystine peptide was separated in all cases from the two symmetrical ones by counter-current distribution. In the synthesis of the more complex fragments advantageous use was made of smaller unsymmetrical fragments prepared as above but having one amino group protected by the N-trityl residue. After selective elimination of this group it was possible to lengthen the peptide chain at this position. The free peptides were obtained by removal of the protecting groups with strong acids, in particular concentrated hydrochloric acid. While in this deprotecting step the disulfide bond was stable, conditions are discussed under which disproportionation was observed. None of the six synthetic insulin fragments showed activity in stimulating rat adipose tissue to convert ¹⁴C-labelled glucose to CO₂ in vitro.     

Tandem carbon-carbon bond-forming radical addition-cyclization reaction of oxime ether and hydrazone

The novel tandem radical addition-cyclization of oxime ethers and hydrazones intramolecularly connected with the alpha,beta-unsaturated carbonyl group is described. The radical reaction of oxime ethers 1, 2, and 4 connected with acryloyl and methacryloyl moieties proceeded smoothly to give the heterocycles via a tandem C-C bond-forming process. The tandem reaction of hydrazone 5 took place in the presence of Zn(OTf)(2) as a Lewis acid to give the trans-cyclic product 17 without the formation of the cis-isomer. The diastereoselective radical addition-cyclization reaction of chiral oxime ether 19 was also studied. The tandem reaction of 19 proceeded smoothly even in aqueous media, providing the novel method for asymmetric synthesis of gamma-butyrolactones and beta-amino acid derivatives.     

A remarkably flexible and selective receptor for Ba2+ amplified from a hydrazone dynamic combinatorial library

A new [2+2] tetra-hydrazone macrocyclic receptor was significantly amplified in a dynamic combinatorial library upon templation with alkaline earth metal ions. After optimisation the product could be isolated in 95% yield and its interaction with ions was investigated by NMR and UV-Vis spectroscopy.     

Studies on isoxazole and pyrazole formation by the reaction of trifluoromethyl-substituted anilines with oxime and hydrazone dianions

5-(2-Aminophenyl)isoxazoles are obtained in good yields by the reaction of 2-(trifluoromethyl)aniline with dilithio derivatives of oximes of acetone, 3-pentanone, propiophenone, and cyclohexanone. An analogous synthesis of a substituted isoxazole from 4-(trifluoromethyl)aniline and 3-pentanone oxime and the synthesis of a substituted pyrazole from 2-(trifluoromethyl)aniline and 3-pentanone hydrazone are less efficient.     

Prediction of beta-sheet topology and disulfide bridges in polypeptides

An ab initio method has been developed to predict beta architectures in polypeptides. The approach predicts the topology of beta-sheets and disulfide bridges through a novel superstructure-based mathematical framework originally established for chemical process synthesis problems. Two types of superstructure are introduced, both of which emanate from the principle that hydrophobic interactions drive the formation of a beta-structure. The mathematical formulation of the problem results in a set of integer linear programming (ILP) problems that can be solved to global optimality to identify the optimal beta-configuration. These (ILP) models can also predict a ranked ordered list of the best, second-best, third-best, etc., topologies of beta-sheets and disulfide bridges. The approach is shown to perform very well for several benchmark polypeptide systems, as well as polypeptides exhibiting challenging nonsequential beta-sheet topologies folds (56 to 187 amino acids).     

Synthesis,characterization, DNA binding,DNA cleavage,antioxidant and in vitro cytotoxicity studies of ruthenium(II) complexes containing hydrazone ligands

The synthesis, spectral characterization, and biological studies of ruthenium(II) hydrazone complexes [RuCl(CO)(PPh₃)₂L] (where L = hydrazone ligands) have been carried out. The hydrazones are monobasic bidentate ligands with O and N as the donors and are preferably found in the enol form in all the complexes. The molecular structure of the ligands HL¹, HL²_, and HL³ were determined by single-crystal X-ray diffraction. The DNA binding studies of the ligands and complexes were carried out by absorption spectroscopic and viscosity measurements. The results revealed that the ligands and complexes bind to DNA via intercalation. The DNA cleavage activity of the complexes, evaluated by gel electrophoresis assay, revealed that the complexes are good DNA cleaving agents. The antioxidant properties of the complexes were evaluated against DPPH, OH, and NO radicals, which showed that the complexes have strong radical-scavenging. Further, the in vitro cytotoxic effect of the complexes examined on HeLa and MCF-7 cancer cell lines showed that the complexes exhibited significant anticancer activity.     

Synthesis,crystal structure,DNA interaction and anticancer evaluation of pyruvic acid derived hydrazone and its transition metal complexes

A novel tridentate chelating ligand, Ethyl 2‐(2‐(2‐chlorobenzoyl)hydrazono)propanoate and its late transition metal complexes were synthesized, characterized and evaluated for anticancer behavior. The structures were elucidated with the help of elemental analyses, spectral (vibrational, electronic, NMR and mass) and thermo‐gravimetric techniques. Single crystal X‐ray crystallographic studies of the ligand suggest an orthorhombic lattice structure with Pna21 space group. The interaction of ligand and complexes with DNA (CT‐DNA) has been extensively studied using absorption, emission, viscosity and thermal denaturation studies with E. coli DNA. The DNA cleavage ability of ligand and metal complexes was tested using plasmid pBR322 DNA by gel electrophoresis method. The ligand and its copper complex have been evaluated for their in vitro anticancer activity against human cancer cells of different origin such as KB (Oral), A431 (Skin), Mia‐Pa‐Ca (Pancreases), K‐549 (Lung), K‐562 (Leukemia), MCF‐7 (Breast) and VERO by MTT assay and the apoptosis assay was carried out with acridine orange/ethidium bromide (AO/EB) staining method. The studies suggest that ligand and copper complex exhibit significant cytotoxic activity on KB, MCF‐7, A‐431, Mia‐Pa‐Ca‐2 an d A‐549 cell lines compared to K‐562 and VERO cell lines.     

Synthesis and insecticidal activity of anthranilic diamides with hydrazone substructure

A series of anthranilic diamides with a hydrazone substructure was synthesised and characterised using ¹HNMR, ¹³C NMR, IR and elemental analyses. The in vitro insecticidal activity of all the compounds was tested against Plutella xylostella. The results showed the synthesised compounds to possess good insecticidal activity. The LC₅₀ values of compounds VIIg, VIIl, VIIm, VIIn exhibited excellent insecticidal activities, with the LC₅₀ affording 7.92 mg L^?1, 12.01 mg L^?1, 0.62 mg L^?1 and 10.71 mg L^?1, respectively. These may prove to be useful as potential insecticidal agents.     

Synthesis, structures, and properties of 15-oxoisosteviol thiosemicarbazone and oxime

New nitrogen-containing derivatives of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) containing oxo, hydroxyimine, and thiosemicarbazone groups were synthesized. Isosteviol 15-oxo-16-thiosemicarbazone forms a 1: 1 complex with Cu^II and inhibits the growth of Mycobacterium tuberculosis (H37R_V, in vitro) at the minimum inhibitory concentration of 20 μg mL^?1.     

Synthesis,spectroscopic investigation and biological activity of metal complexes with ONO trifunctionalalized hydrazone ligand

Mn^II, Fe^III, Co^II, Ni^II, Cu^II, Zn^II, La^III, Ru^III, Hf^IV, Zr^IV and U^VI complexes of 4-methylphenylamino acetoacetylacetone hydrazone have been synthesized and characterized by elementals analyses, i.r., u.v.–vis. spectra, magnetic moments, conductances, thermal analyses (d.t.a and t.g.a) and e.s.r measurements. The i.r. data show that, the ligand behaves as a neutral bidentate type (10), (13) and neutral tridentate type (4), (11), (12) and (21) monobasic bidentate type (7) or monobasic tridentate type (2), (3), (5), (6), (8), (14), (15), (16), (18), (19), (20) and (22) or dibasic tridentate type (5), (9) and (17) towards the metal ion. Molar conductances in DMF solution indicate that, the complexes are non-electrolytes. The e.s.r spectra of solid complexes (8) and (10) show axial type spectra with , d(x²-y²) ground state with significant covalent bond character. However, complex (12), shows an isotropic type, indicating a octahedral manganese(II) complex. Antibacterial and antifungal tests of the ligand and some of its metal complexes are also carried out and it has been observed that, the complexes are more potent bactericides and fungicides than the ligand.     

Design,synthesis, and bioactivity evaluation of novel thiochromanone derivatives containing an oxime or oxime ether moiety

In this study, using botanical active component thiochromanone as the lead compound, a series of novel thiochromanone derivatives containing an oxime or oxime ether moiety were designed and synthesized. The half-maximal effective concentration (EC₅₀) values of compound 4a against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicolaby (Xoc), and Xanthomonas axonopodis pv. citri (Xac) were 6, 10, and 15 μg/ml, respectively, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, compound 4a also revealed better antifungal activity against Botrytis cinerea, with the EC₅₀ value of 18 μg/ml, than that of Carbendazim. To the best of our knowledge, this is the first report on the antibacterial and antifungal activities of this series of novel thiochromanone derivatives containing an oxime or oxime ether moiety.     

Synthesis of DNA with phenanthridinium as an artificial DNA base

A phenanthridinium-containing DNA building block was synthesized as an ethidium nucleoside analogue starting from 3,8-diamino-6-phenyl-phenanthridine. Using this building block, oligonucleotides bearing the phenanthridinium moiety as an artificial DNA base were prepared via automated solid-phase phosphoramidite chemistry. The modified phenanthridinium-containing DNA duplexes were characterized by UV/vis absorption spectroscopy (including the melting behavior), CD spectroscopy, and steady-state fluorescence spectroscopy. These experiments reveal the expected similarity of the synthetic phenanthridinium moiety with noncovalently bound ethidium. More importantly, the results show clearly that the artificial phenanthridinium base is intercalated within the DNA base stack. The counterbase as part of the complementary strand seems to have only a minor influence on the intercalation properties of the phenanthridinium moiety.     

Morpholine hydrazone scaffold: Synthesis,anticancer activity and docking studies

In this paper, synthesis and anticancer activities of morpholine hydrazones scaffold(1-17) thoroughly studied. Small series of morpholine hydrazones synthesized by treating 5-morpholinothiophene-2-carbaldehyde with different aryl hydrazides to form morpholine hydrazones scaffold(1-17). The in vitro anticancer potential of all these compounds was checked against human cancer cell lines like Hep G2(human hepatocellular liver carcinoma) and MCF-7(human breast adenocarcinoma). Analogs 13 had similar substantial cytotoxic effects towards Hep G2 with IC_(50) value 6.31±1.03μmmol/L when compared with the standard Doxorubicin(IC_(50)value 6.00±0.80μmmol/L); while compounds 5,8 and 9 showed potent cytotoxicity against MCF-7 with IC_(50) value 7.08±0.42μmmol/L, 1.26±0.34μmmol/L and11.22±0.22μmmol/L respectively when compared with the standard Tamoxifen(IC_(50)= 11.00±0.40μmol/L). Molecular docking studies also performed to understand the binding interaction.     

Synthesis and antituberculosis activity of derivatives of the diterpenoid isosteviol with azine,hydrazide, and hydrazone moieties

Derivatives of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with azine, hydrazone, and hydrazide moieties were synthesized. They exhibited high tuberculostatic activity in vitro against the strain Mycobacterium tuberculosis H₃₇R_V (minimum inhibiting concentration in the range 6.3–1.7 μg/mL).     

二茂铁双酰腙化合物的合成及电化学性质

以二茂铁双酰肼为原料,合成出两个二茂铁基酰腙类物质,通过元素分析、IR、1H NMR等分析手段确定了化合物的组成;电化学研究表明,化合物a在高电位区有两个不可逆氧化峰,应是酰腙活性基团被氧化的结果,通过量化计算,得到了化合物a的稳定结构。     

Synthesis, characterization, structures, and catalytic property of oxovanadium(V) complexes with hydrazone ligands

The reaction of [VO(Acac)₂] with 4-methyl-N′-[(2-hydroxy-1-naphthyl)methylidene]benzohydrazide (H₂L¹) and 4-methyl-N′-[1-(2-hydroxynaphthyl)ethyiidene]benzohydrazide (H₂L²), respectively, in methanol, affords two new oxovanadium(V) complexes [VO(OMe)L¹]₂ (I) and [VO(OMe)L²] (II). Both complexes have been characterized by elemental analysis, IR, and single crystal X-ray diffraction methods. Complex I is a methoxide-bridged dinuclear oxovanadium(V) compound, while complex II is a mononuclear oxovanadium(V) compound. The dinegative hydrazone ligands coordinate to the metal atoms through phenolate, imine, and deprotonated amide donor atoms. The geometry around vanadium atom in I is a distorted VNO₅ octahedron, while that in II is a VNO₄ square pyramid. Both complexes have effective catalytic property for the sulfoxidation reaction.     

Conformations and vibrational properties of disulfide bridges: Potential energy distribution in the model system diethyl disulfide

Disulfide bridges are important structural elements in proteins. It is well-known that the position of the characteristic disulfide band at ca. 500 cm⁻¹ in the vibrational spectra varies with the conformation around the disulfide unit. In our computational study on the model system diethyl disulfide, both wavenumber and normal mode composition are analyzed simultaneously as a function of conformation. For the disulfide band, a negative correlation between the calculated vibrational wavenumber and the SS stretching contribution is detected. This trend in the normal mode composition provides an explanation for experimentally observed wavenumber shifts of the disulfide band.     

含卤素原子酰腙化合物的合成、表征及与CT-DNA的相互作用

以4-羟基苯乙酸甲酯、水合肼为原料合成4-羟基苯乙酰肼,再与卤代苯甲醛(X=F、Cl、Br)反应,获得3种含有卤素原子的新型酰腙化合物4-氟苯甲醛-4-羟基苯乙酰腙(Ⅰ)、4-氯苯甲醛-4-羟基苯乙酰腙(Ⅱ)和4-溴苯甲醛-4-羟基苯乙酰腙(Ⅲ),并培养得到上述化合物的单晶。通过元素分析和X-射线单晶衍射对它们进行了表征。结果表明,它们均属三斜晶系,P1空间点群,分子之间通过氢键相互作用,交错排列堆积。利用热重分析研究了它们的热稳定性,并分别计算了它们热分解过程的表观活化能(Ea),结果显示它们的热稳定性都较高。采用紫外光谱研究了它们与ct-DNA的相互作用,发现它们均是以插入模式与ct-DNA作用。通过微量热实验研究了化合物与ct-DNA相互作用过程的热效应(ΔH),化合物Ⅰ、Ⅱ和Ⅲ的ΔH分别为1.87、2.86和5.54 k J·mol-1,说明它们与ct-DNA相互作用的大小为:ⅢⅡⅠ。