Halogenated Flavonoid Derivatives Display Antiangiogenic Activity

Antiangiogenic agents attenuate tumours’ growth and metastases and are therefore beneficial as an adjuvant or standalone cancer regimen. Drugs with dual antiproliferative and antiangiogenic activities can achieve anticancer efficacy and overcome acquired resistance. In this study, synthetic flavones (5a,b) with reported anticancer activity, and derivatives (4b and 6a), exhibited significant inhibition of endothelial cell tube formation (40–55%, 12 h) at 1 µM, which is comparable to sunitinib (50% inhibition at 1 µM, 48 h). Flavones (4b, 5a,b and 6a) also showed 25–37% reduction in HUVECs migration at 10 µM. In a Western blotting assay, 5a and 5b subdued VEGFR2 phosphorylation by 37% and 57%, respectively, suggesting that VEGFR2 may be their main antiangiogenic target. 5b displayed the best docking fit with VEGFR2 in an in silico study, followed by 5a, emphasizing the importance of the 7-hydroxyl group accompanied by a 4−C=S for activity. Conversely, derivatives with a 4-carbonyl moiety fitted poorly into the target’s binding pocket, suggesting that their antiangiogenic activity depends on a different target. This study provides valuable insight into the Structure Activity Relationships (SAR) and modes of action of halogenated flavones with VEGFR2 and highlights their therapeutic potential as antiangiogenic/anticancer lead compounds.     

Time-dependent infrared emission following photodissociation of nitromethane and chloropicrin

Nitromethane (CH(3)NO(2)) and its chlorinated analogue, chloropicrin (CCl(3)NO(2)), were photolyzed at 193, 248, and 266 nm, and the products were observed by time-dependent Fourier transform infrared emission spectroscopy. At 193 and 248 nm, the primary photodissociation pathway for nitromethane was cleavage of the C-N bond to produce CH(3) + NO(2)(A (2)B(2)). At 266 nm, weak emission was observed following photodissociation of nitromethane, but an infrared spectrum could not be obtained. The photodissociation of chloropicrin at 193 nm produced the analogous product channel CCl(3) + NO(2)(A (2)B(2)) in addition to several other product channels. At 248 and 266 nm, only CCl(3) + NO(2)(A (2)B(2)) was observed. The production of phosgene (CCl(2)O) from chloropicrin photodissociation was not observed in this study.     

Energy-resolved photoionization of alkylperoxy radicals and the stability of their cations

The photoionization of alkylperoxy radicals has been investigated using a newly developed experimental apparatus that combines the tunability of the vacuum ultraviolet radiation of the Advanced Light Source at Lawrence Berkeley National Laboratory with time-resolved mass spectrometry. Methylperoxy (CH(3)OO) and ethylperoxy (C(2)H(5)OO) radicals are produced by the reaction of pulsed, photolytically produced alkyl radicals with molecular oxygen, and the mass spectrum of the reacting mixture is monitored in time by using synchrotron-photoionization with a double-focusing mass spectrometer. The kinetics of product formation is used to confirm the origins and assignments of ionized species. The photoionization efficiency curve for CH(3)OO has been measured, and an adiabatic ionization energy of (10.33 +/- 0.05) eV was determined with the aid of Franck-Condon spectral simulations, including ionization to the lowest triplet and singlet cation states. Using the appearance energy of CH(3)(+) from CH(3)OO, an enthalpy of formation for CH(3)OO of Delta(f) (CH(3)OO) = (22.4 +/- 5) kJ mol(-1) is derived. The enthalpy of formation of CH(3)OO(+) is derived as Delta(f) = (1019 +/- 7) kJ mol(-1) and the CH(3)(+)-OO bond energy as (CH(3)(+) - O(2)) = (80 +/- 7) kJ mol(-1). The C(2)H(5)OO(+) signal is not detectable; however, the time profile of the ethyl cation signal suggests its formation from dissociative ionization of C(2)H(5)OO. Electronic structure calculations suggest that hyperconjugation reduces the stability of the ethylperoxy cation, making the C(2)H(5)OO(+) ground state only slightly bound with respect to the ground-state products, C(2)H(5)(+) and O(2). The value of the measured appearance energy of C(2)H(5)(+) is consistent with dissociative ionization of C(2)H(5)OO via the Franck-Condon favored ionization to the ? (1)A' state of C(2)H(5)OO(+).     

First-order metal-insulator transitions in manganites: are they universal?

Conductivity data for La(2-2x)Sr(1+2xMn2O7 (x = 0.6) show a first-order transition from an orbital- or charge-ordered insulator to a metal as the temperature falls below approximately 160 K. The change in conductivity is 100 times larger than that seen previously in any single-phase manganite in zero field. The metallic low-temperature state is similar to x = 0.58, but x = 0.58 shows no evidence of orbital or charge order. This result supports a conclusion that strongly coupled magnetic-conductive transitions are first order.     

QCD vacuum as a disordered medium: a simplified model for the QCD dirac operator

We model the QCD Dirac operator as a power-law random banded matrix (RBM) with the appropriate chiral symmetry. Our motivation is the form of the Dirac operator in a basis of instantonic zero modes with a corresponding gauge background of instantons. We compare the spectral correlations of this model to those of an instanton liquid model (ILM) and find agreement well beyond the Thouless energy. In the bulk of the spectrum the dimensionless Thouless energy of the RBM scales with the square root of system size in agreement with the ILM and chiral perturbation theory. Near the origin the scaling in the RBM remains the same as in the bulk which agrees with chiral perturbation theory but not with the ILM. Finally we discuss how this RBM should be modified in order to describe the spectral correlations of the QCD Dirac operator at the finite temperature chiral restoration transition.     

Orbital and Spin Chains in ZnV2O4

Our powder inelastic neutron scattering data indicate that ZnV2O4 is a system of spin chains that are three-dimensionally tangled in the cubic phase above 50 K due to randomly occupied t(2g) orbitals of V3+ (3d(2)) ions. Below 50 K in the tetragonal phase, the chains become straight due to antiferro-orbital ordering. This is evidenced by the characteristic wave vector dependence of the magnetic structure factor that changes from symmetric to asymmetric at the cubic-to-tetragonal transition.     

Crystal field in the CeAl3 heavy-fermion compound

An analysis of inelastic neutron scattering in the CeAl₃ heavy fermion compound is presented. Using single-crystal magnetic-susceptibility and inelastic neutron scattering data, an unambiguous solution for the set of parameters of the electric crystal field Hamiltonian is obtained: B ₂ ⁰ = (5.8 ± 0.2) × 10^?2 meV and B ₄ ⁰ = (2.3 ± 0.1) × 10^?2 meV. The energy level scheme for the ground-state multiplet of the Ce³⁺ ion in CeAl₃ consists of the ground level Γ₉?±3/2〉 and two doublets Γ₈?±5/2〉 and Γ₇?±1/2〉 having close energies of ～6.3 meV at a temperature of 20 K. As follows from comparing the crystal-field parameters in the RAl₃ series (R = Ce, Pr, Nd), the fact that the parameters A ₂ ⁰ 〈r ²〉 and A ₄ ⁰ 〈r ⁴〉 in CeAl₃ differ significantly in value from the respective parameters in PrAl₃ and NdAl₃ cannot be explained in terms of the lattice constants of these isostructural compounds being different but rather is due to the enhanced hybridization of the localized 4f electrons of cerium with conduction electrons.     

Localized excitation in the hybridization gap in YbAl3

The intermediate valence compound YbAl3 exhibits a broad magnetic excitation in the inelastic neutron scattering spectrum with characteristic energy E1 approximately 50 meV, equal to the Kondo energy (T(K) approximately 600-700 K). In the low temperature (T < T(coh) approximately 40 K) Fermi liquid state, however, a new peak in the scattering occurs at E2 approximately 33 meV, which lies in the hybridization gap that exists in this compound. We report inelastic neutron scattering results for a single-crystal sample. The scattering at energies near E1 qualitatively has the momentum (Q) dependence expected for interband scattering across the indirect gap. The scattering near E2 has a very different Q dependence: it is a weak function of Q over a large fraction of the Brillouin zone and is smallest near (1/2,1/2, 1/2). A possibility is that the peak at E2 arises from a spatially localized excitation in the hybridization gap.