Iron-catalyzed δ-selective conjugate addition of methyl and cyclopropyl Grignard reagents to α,β,γ,δ-unsaturated esters and amides

Iron-catalyzed δ-selective conjugate addition of methyl and cyclopropyl Grignard reagents to α,β,γ,δ-unsaturated esters and amides took place in good yields to give products exclusively with cis-β,γ-olefinic bond.     

Alkyne-Tagged Apigenin,a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads

A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC₅₀ of 2.36 ± 0.22, and 10.55 ± 3.37 µM, respectively, while the cytotoxicities were similar to the original apigenin at the CC₅₀ of 70.34 ± 11.79, and 82.82 ± 11.68 µM, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.     

Vacuum fusion determination of oxygen in gadolinium,terbium metal and iron-terbium alloy

The extraction conditions for the accurate determination of oxygen in gadolinium, terbium and iron-terbium alloy using vacuum fusion analysis were studied. The influence of the gettering effect, the analyzing temperature and the weight ratio of the bath metal to the sample were investigated. Oxygen values of gadolinium and terbium were measured by the graphite crucible, the graphite capsule, the tin bath, the iron-tin bath and the platinum-tin bath techniques in the temperature range of 1500–2100 °C using vacuum fusion analysis. These oxygen values were compared with those obtained by inert gas fusion analysis. In inert gas fusion analysis, the samples were analyzed with iron and tin in a tin capsule, and the samples with platinum in a tin capsule were analyzed in a graphite capsule enclosing with carbon powder. Oxygen values of both metal samples in the graphite capsule at 2000 °C, with an iron-tin bath at 1850 °C and a platinum-tin bath at 2000 °C in vacuum fusion analysis, were respectively in good agreement within their errors; the oxygen values of gadolinium were also in good agreement with that from inert gas fusion analysis in the iron-tin bath, but those of terbium were not in agreement. This agreement for gadolinium guarantees the reliability of the conditions for the accurate determination, and the difference of oxygen values for terbium suggests a need for further consideration on the conditions of the inert gas fusion analysis.     

Rational principles for modulating fluorescence properties of fluorescein

Rational design strategies based on practical fluorescence modulation mechanisms would enable us to rapidly develop novel fluorescence probes for target molecules. Here, we present a practical and general principle for modulating the fluorescence properties of fluorescein. We hypothesized that (a) the fluorescein molecule can be divided into two moieties, i.e., the xanthene moiety as a fluorophore and the benzene moiety as a fluorescence-controlling moiety, even though there is no obvious linker structure between them, and (b) the fluorescence properties can be modulated via a photoinduced electron transfer (PeT) process from the excited fluorophore to a reducible benzene moiety (donor-excited PeT; d-PeT). To evaluate the relationship between the reduction potential of the benzene moiety and the fluorescence properties, we designed and synthesized various derivatives in which the reduction potential of the benzene moiety was fine tuned by introducing electron-withdrawing groups onto the benzene moiety. Our results clearly show that the fluorescence properties of fluorescein derivatives were indeed finely modulated depending upon the reduction potential of the benzene moiety. This information provides a basis for a practical strategy for rational design of novel functional fluorescence probes.     

A novel fluorescent probe for zinc ion based on boron dipyrromethene (BODIPY) chromophore

ZnAB has the combined structure of N,N-bis(2-pyridylmethyl)ethylenediamine as a specific chelater for Zn(2+) and 1,3,5,7-tetramethyl-8-phenyl-boron dipyrromethene as a fluorophore. Complexation of ZnAB with Zn(2+) produces a remarkable enhancement of fluorescence intensity. ZnAB has the advantages of less sensitivity to solvent polarity and pH than fluorescein-based Zn(2+) probes. Furthermore, it is not influenced by other cations, such as Na(+), K(+), Ca(2+), and Mg(2+), which exist at high concentrations under physiological conditions, even at 2.5 mM. The results show that ZnAB is a Zn(2+) probe suitable for biological applications.     

Hybrid QM/MM studies on energetics of malonaldehyde in condensed phase

Energetics of eight enol isomers of a malonaldehyde (MA) at the ground state in CCl₄ solvent environment have been investigated using a hybrid quantum mechanical (QM)/molecular mechanics (MM) method. It is found that relative energies of the isomers slightly change due to interactions between MA and surrounding atoms. In an isolated environment all eight isomers have stable planar structure. On the other hand, most of the isomers have nonplanar structure in CCl₄ whose interactions with the solute molecules are, however, weak. Mainly, structural changes are found in the H? O? C?C dihedral angle ?_{H? O? C?C}, i.e., a hydrogen atom that is connected directly with an oxygen atom, is located at a nonplanar position, and other atoms remain almost planar. Vertical excitation energies of low‐lying excited states at the resultant optimized structure of each isomer are evaluated. The vertical excitation energies in CCl₄ are almost the same as those in the isolated environment, but some changes were found in the triplet excitation states. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

Theoretical study of the mechanism of hydrogenation of side-on coordinated dinitrogen activated by Zr binuclear complexes ([(eta5-C5Me4H)2Zr]2(mu2,eta2,eta2-N2))

The reaction mechanism of the reduction of dinitrogen coordinated side-on to a binuclear Zr complex, [(eta(5)-C(5)Me(4)H)(2)Zr](2)(mu(2),eta(2),eta(2)-N(2)) (T1), was investigated theoretically using a model complex, [(eta(5)-C(5)H(5))(2)Zr](2)(mu(2),eta(2),eta(2)-N(2)) (A1), employing density functional theory calculations. The effectiveness of A1 in describing T1 was confirmed by comparing the structures, distributions of charge, and frontier molecular orbitals. Our calculations showed that A1 has a twisted structure, resembling that of T1, which results in similar properties. The calculations for A1 and its derivatives on H(2) addition clearly explain the reaction mechanism and the reaction path that T1 follows, as well as the experimentally required reaction conditions. The immediate reaction of the first and second H(2) additions produces [(eta(5)-C(5)Me(4)H)(2)ZrH](2)(mu(2),eta(2),eta(2)-N(2)H(2)) (T2), and this is explained by the barrier heights of the reaction, which were calculated to be 20.4 and 10.9 kcal/mol, respectively. The latter barrier was below that of A1 + 2H(2). Complex T2 may be the initial complex for further H(2) addition under proper conditions, or it could lose one H(2) molecule followed by H migration from the Zr site to the N site. Both reactions are expected to occur, because of the closeness of the barrier heights (25.1 and 36.5 kcal/mol, respectively). Gentle warming is required for further H(2) additions, which can be understood from the energetics as well. The high reactivity of T1 with H(2) has been discussed by the comparison of the calculation of A1 and another complex with different ligands, presenting an interesting indication on the effects of the ligands. These theoretical results and discussion explaining the experiment should provide insight into the nature of the hydrogenation mechanism.     

Highly efficient and photostable photosensitizer based on BODIPY chromophore

Photosensitizers are reagents that produce reactive oxygen species upon light illumination and are commonly used to study oxidative stress or for photodynamic therapy. There are many available photosensitizers, but most have limitations, such as low photostability, structural instability, or a limited usable range of solvent conditions. Here, we describe a novel photosensitizer scaffold (2I-BDP) based on the unique characteristics of the BODIPY chromophore (i.e., high extinction coefficient, high photostability, and insensitivity to solvent environment). 2I-BDP shows stronger near-infrared singlet oxygen luminescence emission and higher photostability than the well-known photosensitizer, Rose Bengal. Unlike other photosensitizers, this scaffold is widely applicable under various conditions, including lipophilic and aqueous environments. HeLa cells loaded with 2I-BDP could be photosensitized by light illumination, demonstrating that 2I-BDP is potentially useful as a reagent for cell photosensitization, oxidative stress studies, or PDT.     

Ag+ selection by aza‐18‐crown‐6 ethers N‐Substituted on heterocyclic aromatics

Substitution on the nitrogen atom, where necessary by high‐pressure S_NAr reactions, of aza‐18‐crown‐6 ethers linked to heterocyclic aromatics has extended the number of potential host compounds for Ag⁺. The complexation of Ag⁺ by the new compounds has been evaluated by liquid membrane ion transport and ion extraction experiments. The nature of the binding sites of these new host compounds for Ag⁺ has been assessed, in DMF/D₂O (4/1), by ¹³C nmr titration experiments with AgClO₄.     

A novel,cell-permeable,fluorescent probe for ratiometric imaging of zinc ion

Zn(2+) plays important roles in various biological systems; as a result, the development of tools that can visualize chelatable Zn(2+) has attracted much attention recently. We report here newly synthesized fluorescent sensors for Zn(2+), ZnAF-Rs, whose excitation maximum is shifted by Zn(2+) under physiological conditions. Thus, these sensors enable ratiometric imaging, which is a technique to reduce artifacts by minimizing the influence of extraneous factors on the fluorescence of a probe. Ratiometric measurement can provide precise data, and some probes allow quantitative detection. ZnAF-Rs are the first ratiometric fluorescent sensors for Zn(2+) that enable quantitative analysis under physiological conditions. ZnAF-Rs also possess suitable K(d) for applications, and high selectivity against other biologically relevant cations, especially Ca(2+). Using these probes, changes of intracellular Zn(2+) concentration in cultured cells were monitored successfully. We believe that these probes will be extremely useful in studies on the biological functions of Zn(2+).