Redox Communication within Multinuclear Iron–Sulfur Complexes Related to Electronic Interplay in the Active Site of [FeFe]Hydrogenase

The one‐electron oxidations of a Fe₂ complex lead to the formation of a persistent metal‐stabilized thiyl radical Fe₂ species, mixed‐valent Fe₄, and Fe₈ complexes. The unpaired spin in the Fe₂ radical species delocalizes over the Fe₂ and the aromatic dithiolate, mostly on the terminal sulfur. The subsequent dimerization of the singly oxidized Fe₂ to the Fe₄ retains the partial thiyl radical character. For an analogue with less steric hindrance, the π–π stacking interaction between the dithiolato aromatic rings induces generation of the Fe₈, in which process electronic structures of the species are modulated through reducing the thiyl radical to the thiolate. Electronic reorganization repeats when the Fe₈ is converted to Fe₄. Electronic interplay in the complexes decreases the energy gap of frontier MOs and buffers electronic impacts upon redox events. Easier accessible redox potentials and increased stability of the species are facilitated. The results demonstrate that electronic versatility of the benzenedithiolate exerts pronounced influences on electronic and coordination structure of the metal complexes.     

Solid‐state 31P NMR investigation on the status of guanine nucleotides in paclitaxel‐stabilized microtubules

Microtubule dynamics is a target for many chemotherapeutic drugs. In order to understand the biochemical effects of paclitaxel on the GTPase activity of tubulin, the status of guanine nucleotides in microtubules was investigated by ³¹P cross‐polarization magic angle spinning (CPMAS) NMR. Microtubules were freshly prepared in vitro in the presence of paclitaxel and then lyophilized in sucrose buffer for solid‐state NMR experiments. A ³¹P CPMAS NMR spectrum with the SNR of 25 was successfully acquired from the lyophilized microtubule sample. The broadness of the ³¹P spectral lines in the spectrum indicates that the molecular environments around the guanine nucleotides inside tubulin may not be as crystalline as reported by many diffraction studies. Deconvolution of the spectrum into four spectral components was carried out in comparison with the ³¹P NMR spectra obtained from five control samples. The spectral analysis suggested that about 13% of the nucleotides were present as GTP and 37% as GDP in the β‐tubulin (E‐site) of the microtubules. It was found that most of the GDPs were present as GDP‐P_i complex in the microtubules, which seems to be one of the effects of paclitaxel binding. Copyright © 2015 John Wiley & Sons, Ltd.     

From single‐chain folding to polymer nanoparticles via intramolecular quadruple hydrogen‐bonding interaction

Single‐chain folding via intramolecular noncovalent interaction is regarded as a facile mimicry of biomacromolecules. Single‐chain folding and intramolecular crosslinking is also an effective method to prepare polymer nanoparticles. In this study, poly(methyl methacrylate‐co?2‐ureido‐5‐deazapterines functionalized ethylene methacrylate) (P(MMA‐co‐EMA‐DeAP)) is synthesized via free radical polymerization. The single‐chain folding of P(MMA‐co‐EMA‐DeAP) and the formation of the nanoparticles in diluted solution (concentration <0.005 mg/mL) are achieved via supramolecular interaction and intramolecular collapsing during the disruption‐reformation process of the hydrogen bonding triggered by water. The size and the morphology of the nanoparticles are characterized by dynamic light scattering, transmission electron microscope, and atomic force microscope. The results show that the size of the nanoparticles depends on the molecular weight of the polymer and the loading of 2‐ureido‐5‐deazapterines functionalized ethylene methacrylate (EMA‐DeAP) on the polymer backbone. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1832–1840     

Metabolic profiles of dioscin in rats revealed by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry

Dioscin (DIS), one of the most abundant bioactive steroidal saponins in Dioscorea sp., is used as a complementary medicine to treat coronary disease and angina pectoris in China. Although the pharmacological activities and pharmacokinetics of DIS have been well demonstrated, information regarding the final metabolic fates is very limited. This study investigated the in vivo metabolic profiles of DIS after oral administration by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry method. The structures of the metabolites were identified and tentatively characterized by means of comparing the molecular mass, retention time and fragmentation pattern of the analytes with those of the parent compound. A total of eight metabolites, including seven phase I and one phase II metabolites, were detected and tentatively identified for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. In addition, a possible metabolic pathway on the biotransformation of DIS in vivo was proposed. This study provides valuable and new information on the metabolism of DIS, which will be helpful for further understanding its mechanism of action. Copyright © 2015 John Wiley & Sons, Ltd.