Bis(indenyl)zirconium(IV) complexes of monofunctional bidentate salicylidimines

A series of (C₉H₇)₂Zr(SB)Cl complexes whereSB ^– is the anion of bidentateSchiff base derived from salicylaldehyde and 4-substituted anilines, viz. salicylidene-4-ansidine, salicylidene-4-phenetidine, salicylidene-4-chloroaniline, salicylidene-4-bromoaniline, salicylidene-4-iodoaniline and salicylidene-4-nitroaniline, have been synthesized by the reaction of bis(indenyl)zirconium(IV) dichloride andSchiff base (SBH) in 1:1 molar ratio in refluxingTHF in the presence of triethylamine. The new derivatives have been characterized on the basis of their elemental analyses, conductance measurements and spectral (IR,¹H-NMR, UV-VIS) studies.

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Bis(indenyl)zirkonium(IV)-Komplexe monofunktioneller zweizähniger Salicylidimine

Zusammenfassung Es wurde eine Reihe von (C₉H₇)₂Zr(SB)Cl-Komplexen synthetisiert, wobeiSB ^– für das Anion einer zweizähnigenSchiff-Base steht. DieSchiff-Basen sind von Salicylaldehyd und 4-substituierten Anilinen hergeleitet: Salicyliden-4-anisidin,-4-phenetidin, -4-Cl-, -4-Br-, -4-I-anilin und -4-Nitroanilin. Die Synthese erfolgte über die Reaktion von Bis(indenyl)zirkonium(IV)-dichlorid mit derSchiff-Base (SBH) in einem molaren Verhältnis von 1:1 am Rückfluß in Gegenwart von Triethylamin undTHF als Lösungsmittel. Zur Charakterisierung der neuen Derivate wurden Elementaranalysen, Leitfähigkeitsmessungen und spektroskopische Daten (IR,¹H-NMR, UV-VIS) herangezogen.

     

Selective functionalization of ferrocenyl compounds using a novel solvent free synthetic method for the preparation of bioactive unsymmetrical ferrocenyl derivatives

A novel solvent free synthetic method has been designed by using rice husk ash (RHA) as solid support for the selective functionalization of ferrocenyl derivatives and described the synthesis of a 1,1′‐unsymmetrically bi‐functionalized ferrocenyl compounds for their biological evaluation. Single crystal X‐ray structural evaluation showed some interesting intra‐molecular hydrogen bonding interactions across the chains of the ferrocenyl molecule, while DFT calculation revealed the significance of the orientation between the two cyclopentadienyl rings for the hydrogen bonding interaction. Redox and antibacterial properties have been studied to understand the electronic and biological effect of different hydrazone system and their potential for future application.     

Mono- and bisphenoxy derivatives of bis(indenyl) titanium(IV)

A series of (C₉H₇)₂Ti(OAr)Cl and (C₉H₇)₂Ti(OAr)₂ complexes whereAr=C₆H₅,p-ClC₆H₄, α-C₁₀H₇ or β-C₁₀H₇, have been synthesised by the reaction of bis(indenyl) titanium(IV) dichloride with an appropriate phenol in a 1:1 and 1:2 molar ratio in refluxing benzene in the presence of triethylamine. The new derivatives have been characterized on the basis of their elemental analyses, conductance measurements and spectral (IR,¹H-NMR and electronic) studies.     

A new asymmetric synthesis of (+)-12b-epidevinylantirhine

We report a new asymmetric synthesis of the indole alkaloid derivative (+)-12b-epidevinylantirhine through stereoselective cyclization of a tethered indole nucleus onto an N-acyliminium ion intermediate, generated from a readily available non-racemic bicyclic lactam building block, and subsequent template modification through a highly diastereoselective conjugate addition protocol. In addition, we present the first X-ray crystal structure of this indole target.     

Transition metal chemistry of oxime containing ligands,VII

Complexes of pyridine-2-aldoxime (Hpox) with iron(II) and chromium(III) of type, [Fe(Hpox)₂ X ₂] (X=Cl, Br, I or NCS); [Cr(Hpox)₃]Cl₃·3 H₂O; [Cr(Hpox)₂ X ₂]ClO₄ (X=F, Cl or Br) and [Cr(Hpox)₂(H₂O)₂]Br₃·H₂O were prepared and characterized by analytical X-ray powder diffraction, magnetism, vibrational (conventional and far-infrared) and electronic spectroscopy techniques. X-ray and electronic spectral data indicate that all the complexes except [Cr(Hpox)₃]Cl₃·3 H₂O havetrans-pseudo-octahedral microsymmetry around the metal ion. Infrared spectral data indicate that the ligand, Hpox, behaves like a neutral ligand and coordinates to the metal ion through pyridine nitrogen atom and oxime nitrogen atom in all these complexes. The magnetic susceptibilities of chromium(III) complexes, measured over a temperature range 300–78 K, are independent of temperature whereas the magnetic moments of iron(II) complexes over a temperature range 300–20 K are dependent of temperature. The observed temperature dependence of magnetic moments of iron(II) complexes was used to evaluate the magnitude of orbital reduction factor,k, the low-symmetry distortion parameter, , and the extent of reduction in spin-orbital coupling, . In all these iron(II) complexes the magnetic results indicate the presence of an orbitally non-degenerate,⁵B_2g, ground state. Magnetically unperturbed and perturbedMössbauer spectra of iron(II) complexes at various temperatures have also been reported. Magnetically perturbedMössbauer spectra of iron(II) complexes at 4.2 K in an axial field of 60kGauss indicate that the principal component of electric field gradient tensor is positive and consistent with⁵B_2g ground electronic state in a tetragonal (D _4h) local site symmetry.

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Übergangsmetallkomplexe mit Oxim-enthaltenden Liganden, VII. Elektronische und strukturelle Eigenschaften vonFe(II)-undCr(III)-Komplexen mit Pyridin-2-aldoxim

Zusammenfassung Es wurden Komplexe von Pyridin-2-aldoxim (Hpox) mit Fe(II) und Cr(III) vom Typ [Fe(Hpox)₂ X ₂] (X=Cl, Br, I, NCS), [Cr(Hpox)₃]Cl₃·3 H₂O, [Cr(Hpox)₂ X ₂]ClO₄ (X=F, Cl, Br) und [Cr(Hpox)₂(H₂O)₂]Br₃·H₂O hergestellt. Charakterisierung und Diskussion von Geometrie und Bindungsverhalten in den Komplexen erfolgte auf Grund von analytischen Daten, Röntgen-Pulveraufnahmen, Elektronenanregungsspektroskopie, Infrarotspektroskopie, magnetischen Messungen undMössbauer-Spektroskopie.

     

Generation of statin drug metabolites through electrochemical and enzymatic oxidations

The generation of key drug metabolites for the purpose of their complete structural characterization, toxicity testing, as well as to serve as standards for quantitative studies, is a critical step in the pharmaceutical discovery and development cycle. Here, we utilized electrochemistry/mass spectrometry for the detection and subsequent generation of six phase I metabolites of simvastatin and lovastatin. Both simvastatin and lovastatin are widely used for the treatment of hypercholesterolemia. There are known drug–drug interaction issues of statin therapy, and it has been suggested that the oxidative metabolites may contribute to the cholesterol-lowering effect of both statins. Of the known phase I metabolites of simvastatin and lovastatin, none are commercially available, and chemical means for the synthesis of a very few of them have been previously reported. Here, we report that electrochemical oxidation of less than 1 mg each of simvastatin and lovastatin led to the generation of three oxidative metabolites of each parent to allow complete nuclear magnetic resonance characterization of all six metabolites. The yields obtained by the electrochemical approach were also compared with incubation of parent drug with commercially available bacterial mutant CYP102A1 enzymes, and it was found that the electrochemical approach gave higher yields than the enzymatic oxidations for the generation of most of the observed oxidative metabolites in this study.

Mild Oxidation of Thiofunctional Polymers to Cytocompatible and Stimuli‐Sensitive Hydrogels and Nanogels

Nanogels consist of three dimensionally cross‐linked hydrophilic polymer chains and can thus be easily modified through functionalization of the polymeric building blocks, for example to yield stimuli‐sensitive materials. For drug transport and intracellular release, redox‐sensitive systems are especially of interest, as the intracellular space is reductive. In this study, parameters that allow preparation of nanogels with tunable size between 150 and 350 nm are systematically evaluated and identified. Most importantly, a new and mild oxidation catalyst, alloxan, is introduced for the preparation of the nanogels. This broadens the range of possible payloads to more‐sensitive molecules. Particle stability, degradation in cytosolic conditions, and cytocompatibility in concentrations up to 10 mg · mL^?1 are demonstrated.

     

Click synthesis of N1-(β-D-ribofuranosyl)-C4-(coumarin-4″-yl)-1,2,3-triazoles

A series of eight N¹-(β-D-ribofuranosyl)-C⁴-(coumarin-4′′-yl)-1,2,3-triazoles have been synthesized by Cu(I)-catalyzed click reaction of 1-azido-1-deoxy-2,3,5-tri-O-benzoyl-β-D-ribofuranose with differently substituted 4-ethynylcoumarins followed by debenzoylation of the resulted N¹-(2′,3′,5′-tri-O-benzoyl-β-D-ribofuranosyl)-C⁴-(coumarin-4″-yl)-1,2,3-triazoles in 71 to 89% overall yields. The structures of all the synthesized compounds were established on the basis of their spectral data analysis that was further confirmed by X-ray data analysis of one of the model benzoylated compounds, i.e. N¹-(2′,3′,5′-tri-O-benzoyl-β-D-ribofuranosyl)-C⁴-(7″-isopropoxycoumarin-4″-yl)-1,2,3-triazole.     

Peptide Cysteine Thiols Act as Photostabilizer of Avobenzone through Stabilizing the Transition State of Keto-Enol Tautomerization

Photostabilizers have been used to impart stability to an FDA-approved chemical UV-A filter avobenzone against the UV-A radiations and sunlight. The thiol group of glutathione plays a critical role in imparting the photostabilization activity of glutathione on avobenzone. The current report aims to evaluate the photostabilization activity of multiple thiols containing cysteine peptides on avobenzone. Cysteine-tripeptide and cysteine-pentapeptide were chemically synthesized and characterized using mass spectrometry. Synthetic peptides were assessed for their photostabilization activity on the enolic-form of the avobenzone under natural sunlight using UV spectroscopy in both protic and aprotic solvents. Unlike glutathione, which has pronounced activity in protic solvents, cysteine-pentapeptide exhibits similar photoprotection activity in both protic and aprotic solvents. Computational calculations using DFT suggest that peptide cysteine thiols may assist in the reversal of the photoketonization process of avobenzone thereby exhibiting the photoprotection activity to the enolic-form of avobenzone. Peptide cysteine thiols lower the activation energy barrier of keto-to-enol tautomerization of avobenzone by 30 kcal mol⁻¹ by assisting the proton shuttle through a six-membered transition state. The current report emphasizes the applications of peptide thiols in cosmetics and may help in the development of peptides as aesthetic medicines.     

DNA Nanogels To Snare Carcinogens: A Bioinspired Generic Approach with High Efficiency

Polycyclic aromatic hydrocarbons (PAHs) are combustion‐related pollutants and are ubiquitous in the environment, including in sources of drinking water. Upon contact with DNA, stable PAH–DNA adducts form rapidly as the first step towards their toxic effects. In this work, we prepared hydrophilic DNA nanogels to exploit this generic complexation process as a biomimetic scavenging method. This approach relies on interaction between PAHs and the complete network that constitutes the water‐swollen nanogels, and is not restricted to interfacial adsorption. Up to 720 μg of PAH per gram of DNA nanogel are taken up, meaning that 1 mg of DNA nanogel is sufficient to purify a liter of water containing the critical PAH concentration for cancer risk (600 ng L^?1). As a result of short diffusion pathways, PAH uptake is rapid, reaching 50 % loading after 15 minutes. Beyond PAHs, DNA nanogels may be useful for the generic detoxification of water containing genotoxins, since most known molecules that strongly associate with DNA are mutagenic.