Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress, and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes GCLM, NQO1, and HO1 in human lung epithelial cells, while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using a mouse model. Our studies showed 2-trifluoromethyl-2′-methoxychalone (2b) to be a potent activator of Nrf2, both in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure–activity relationship and proposed a possible mechanism of Nrf2 activation.

H₂O/D₂O negative ion time-of-flight mass spectra from electron transfer processes at different collision energies with neutral potassium yield OH^-/OD^-, O^-, and H^-/D^-. The branching ratios show a relevant energy dependence with an important isotope effect in D₂O. Electronic state spectroscopy of water has been further investigated by recording potassium cation energy loss spectra in the forward scattering direction at an impact energy of 205 eV (lab frame), with quantum chemical calculations for the lowest-lying unoccupied molecular orbitals in the presence of a potassium atom supporting most of the experimental findings. The DO-D bond dissociation energy has been determined for the first time to be 5.41 ± 0.10 eV. The collision dynamics revealed the character of the singly excited (1b₂^-1) molecular orbital and doubly excited states in such K-H₂O and K-D₂O collisions.

We report novel data on ion-pair formation in hyperthermal (30–800 eV) neutral potassium collisions with neutral pyrimidine (Pyr, C₄H₄N₂) molecules. In this collision regime, negative ions formed by electron transfer from the alkali atom to the target molecule were time-of-flight mass analyzed and the fragmentation patterns and branching ratios have been obtained. The most abundant product anions have been assigned to CN⁻ and C₂H⁻ and the electron transfer mechanisms are comprehensively discussed. Particular importance is also given to the efficient loss of integrity of the pyrimidine ring in the presence of an extra electron, which is in contrast to dissociative electron attachment experiments yielding the dehydrogenated parent anion. Theoretical calculations were performed for pyrimidine in the presence of a potassium atom and provided a strong basis for the assignment of the lowest unoccupied molecular orbitals accessed in the collision process. In order to further our knowledge about the collision dynamics, potassium cation (K⁺) energy loss spectrum has been obtained and within this context, we also discuss the role of the accessible electronic states. A vertical electron affinity of (−5.69 ± 0.20) eV was obtained and may be assigned to a π3*(b₁) state that leads to CN⁻ formation.

Effective bond breaking in electron transfer from K collisions with C ₆ Cl ₆ .

In this contribution, we report a comprehensive study on the formation of hexachlorobenzene (C₆Cl₆) negative ions probed by low-energy electron interactions from 0 up to 12 eV in a gas-phase crossed beam experiment. The anionic yields as a function of the electron energy reveal a rich fragmentation pattern of the dissociative electron attachment process, yet the most intense ion has been assigned to the non-dissociated parent anion that survives long enough within the detection time window. Other less intense fragment anions have been assigned as Cl⁻, Cl₂ ⁻, C₆Cl₄ ⁻, and C₆Cl₅ ⁻. The experimental results are accompanied by quantum chemical calculations at various levels of accuracy, providing an insight into the electronic structure, thermochemical thresholds, electron affinities and structures of neutral and anionic molecular species. The electron attachment process induces a considerable geometry change in the temporary-negative ion relative to the neutral molecule, where the most intense fragment anion assigned to Cl⁻ can be formed solely through a curve crossing involving a π*/σ* coupling. The yield of chlorine anions shows a signature of vibrational excitation reminiscent of a Jahn–Teller distortion.