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We designed and synthesized a series of derivatives containing the right-side DFGH-ring structure of physalin-type natural products, decorated with a hydrophobic substituent. The synthetic scheme utilizes a highly efficient, one-pot protocol for simultaneous construction of the GH-ring system, promoted by HF/pyridine. Among the compounds synthesized, 5d inhibited TNF-α-stimulated NF-κB activation with similar potency to physalin B.State-to-state dynamics of the benchmark hydrogen exchange reaction H + H2 (v = 0-4, j = 0-3) → H2 (v’, j’) + H is investigated with the aid of the real wave packet approach of Gray and Balint-Kurti (J. Chem. Phys. 1998, 108, 950-962) and electronic ground BKMP2 potential energy surface of Boothroyd et al. (J. Chem. Phys. 1996, 104, 7139-7152). Initial state-selected and product state-resolved reaction probabilities, integral cross section, and product diatom vibrational and rotational level populations at a few collision energies are reported to elucidate the energy disposal mechanism. State-specific thermal rate constants are also calculated and compared with the available literature results. Coriolis coupling terms of the nuclear Hamiltonian are included, and calculations are parallelized over the helicity quantum number, Ω’. Attempts are made, in particular, to study the effect of reagent vibrational and rotational excitations on the dynamical attributes. It is found that the calculations become computationally expensive with reagent vibrational and rotational excitation. Reagent vibrational excitation is found to enhance the reactivity and has significant impact on the energy disposal to the vibrational and rotational degrees of freedom of the product. The interplay of reagent translational and vibrational energy on the product vibrational distribution unfolds an important aspect of the energy disposal mechanism. The effect of reagent rotation on the state-to-state dynamics is found not to be very significant, and the weak effect turns out to be specific to v’.Gas phase spectroscopy is a powerful tool for examining fundamental chemical structures and properties free from solvent molecules. We developed a gas-phase resonance Raman spectroscopy combined with IR-laser ablation of a droplet beam, which allowed us to elucidate local structures around chromophores in gas-phase proteins and DNAs. To demonstrate the potential of this approach, we applied this method to myoglobin, one of the heme proteins, and elucidated its structures in the gas phase and in aqueous solution. The experimental spectra are compared with calculated spectra of stable heme structures for the structural determination. These results show the oxidation/spin states of the Fe atom in myoglobin in the gas phase and were compared with the aqueous solution from the obtained resonant Raman spectra. The present method gives an important tool to investigate the gas-phase structure of large biomolecules.Ion identity and concentration influence the solubility of macromolecules. To date, substantial effort has been focused on obtaining a molecular level understanding of specific effects for anions. By contrast, the role of cations has received significantly less attention and the underlying mechanisms by which cations interact with macromolecules remain more elusive. To address this issue, the solubility of poly(N-isopropylacrylamide), a thermoresponsive polymer with an amide moiety on its side chain, was studied in aqueous solutions with a series of nine different cation chloride salts as a function of salt concentration. Phase transition temperature measurements were correlated to molecular dynamics simulations. The results showed that although all cations were on average depleted from the macromolecule/water interface, more strongly hydrated cations were able to locally accumulate around the amide oxygen. These weakly favorable interactions helped to partially offset the salting-out effect. Moreover, the cations approached the interface together with chloride counterions in solvent-shared ion pairs. Because ion pairing was concentration-dependent, the mitigation of the dominant salting-out effect became greater as the salt concentration was increased. Weakly hydrated cations showed less propensity for ion pairing and weaker affinity for the amide oxygen. As such, there was substantially less mitigation of the net salting-out effect for these ions, even at high salt concentrations.The field of bioactive lipids is ever expanding with discoveries of novel lipid molecules that promote human health. Adopting a lipidomic-assisted approach, two new families of previously unrecognized saturated hydroxy fatty acids (SHFAs), namely, hydroxystearic and hydroxypalmitic acids, consisting of isomers with the hydroxyl group at different positions, were identified in milk. Among the various regio-isomers synthesized, those carrying the hydroxyl at the 7- and 9-positions presented growth inhibitory activities against various human cancer cell lines, including A549, Caco-2, and SF268 cells. In addition, 7- and 9-hydroxystearic acids were able to suppress β-cell apoptosis induced by proinflammatory cytokines, increasing the possibility that they can be beneficial in countering autoimmune diseases, such as type 1 diabetes. Rutin 7-(R)-Hydroxystearic acid exhibited the highest potency both in cell growth inhibition and in suppressing β-cell death. We propose that such naturally occurring SHFAs may play a role in the promotion and protection of human health.Brasilane-type sesquiterpenes have been known for a long time, but their biosynthetic pathways and mechanisms remain elusive. Recently, two groups independently characterized a Trichoderma terpene cyclase that produces trichobrasilenol, a brasilane-type sesquiterpene, and a plausible biosynthetic pathway was proposed based on isotopic labeling experiments. In the proposed mechanism, the characteristic brasilane-type 5/6 bicyclic skeleton is synthesized from a 5/7/3 tricyclic intermediate via a complicated concerted reaction, including six chemical events of C-C σ bond metathesis and rearrangements, ring-contraction, π bond formation, and regioselective hydroxylation. However, our density functional theory (DFT) calculations do not support this mechanism. On the basis of DFT calculations, we propose a new pathway for trichobrasilenol biosynthesis, involving a multistep carbocation cascade in which cyclopropylcarbinyl cations in equilibrium with homoallyl cations play a pivotal role. This pathway and mechanism is in good agreement with previous biosynthetic studies on brasilane-type compounds and related terpenoids, including isotope-labeling experiments and byproducts analysis.