Synthesis of 1,3-diarylsubstituted indazoles utilizing a Suzuki cross-coupling/deprotection/N-arylation sequence

Herein we report a general synthesis of 1,3-diarylsubstituted indazoles utilizing a two-step Suzuki cross-coupling/deprotection/N-arylation sequence. This procedure proceeds in excellent overall yield starting from the 3-iodo-N-Boc indazole derivative allowing for rapid access to these compounds.     

Disposable highly ordered pyrolytic graphite-like electrodes: Tailoring the electrochemical reactivity of screen printed electrodes

We demonstrate that the electron transfer properties of disposable screen printed electrodes can be readily tailored via the introduction of a polymeric formulation into the ink used to fabricate these electrochemical platforms. This approach allows the role of the binder on the underpinning electrochemical properties to be explored and allows the electrochemical reactivity of the screen printed electrodes to be tailored from that of edge plane to basal plane of highly ordered pyrolytic graphite.     

Role of 2‐oxo and 2‐thioxo modifications on the proton affinity of histidine and fragmentation reactions of protonated histidine

A combination of electrospray ionisation (ESI), multistage and high‐resolution mass spectrometry experiments was used to compare the gas‐phase chemistry of the amino acids histidine (1), 2‐oxo‐histidine (2), and 2‐thioxo‐histidine (3). Collision‐induced dissociation (CID) of all three different proton‐bound heterodimers of these amino acids led to the relative gas‐phase proton affinity order of: histidine >2‐thioxo‐histidine >2‐oxo‐histidine. Density functional theory (DFT) calculations confirm this order, with the lower proton affinities of the oxidised histidine derivatives arising from their ability to adopt the more stable keto/thioketo tautomeric forms. All protonated amino acids predominately fragment via the combined loss of H₂O and CO to yield a₁ ions. Protonated 2 and 3 also undergo other small molecule losses including NH₃ and the imine HN=CHCO₂H. The observed differences in the fragmentation pathways are rationalised through DFT calculations, which reveal that while modification of histidine via the introduction of the oxygen atom in 2 or the sulfur atom in 3 does not affect the barriers against the loss of H₂O+CO, barriers against the losses of NH₃ and HN=CHCO₂H are lowered relative to protonated histidine. Copyright © 2010 John Wiley & Sons, Ltd.     

Temperature dependence of the reaction C2H (C2D) + O2 between 295 and 700 K

The rate coefficients for the reactions of C₂H and C₂D with O₂ have been measured in the temperature range 295 K T 700 K. Both reactions show a slightly negative temperature dependence in this temperature range, with k_C2H+O2 = (3.15 ± 0.04) × 10⁻¹¹ (T/295 K)^{−(0.16 ± 0.02)} cm³ molecule⁻¹ s⁻¹. The kinetic isotope effect is k_C2H/k_C2D = 1.04 ± 0.03 and is constant with temperature to within experimental error. The temperature dependence and the C₂H + O₂ kinetic isotope effect are consistent with a capture-limited metathesis reaction, and suggest that formation of the initial HCCOO adduct is rate-limiting.     

Measurement of the rate coefficient of the reaction CH+O2 → products in the temperature range 2200 to 2600 K

The rate coefficient of the reaction CH+O₂ → products was determined by measuring CH-radical concentration profiles in shock-heated 100–150 ppm ethane/1000 ppm O₂ mixtures in Ar using cw, narrow-linewidth laser absorption at 431.131 nm. Comparing the measured CH concentration profiles to ones calculated using a detailed kinetics model, yielded the following average value for the rate coefficient independent of temperature over the range 2200–2600 K: The experimental conditions were chosen such that the calculated profiles were sensitive mainly to the reactions CH+O₂ → products and CH₃+M → CH+H₂+M. For the methyl decomposition reaction channel, the following rate-coefficient expression provided the best fit of the measured CH profiles: Additionally, the rate coefficient of the reaction CH₂+H→CH+ H₂ was determined indirectly in the same system: © 1997 John Wiley & Sons, Inc.     

Effects of Curcumin Analogues DMC and EF24 in Combination with the Cytokine TRAIL against Kidney Cancer

The natural compound curcumin has been shown to have therapeutic potential against a wide range of diseases such as cancer. Curcumin reduces cell viability of renal cell carcinoma (RCC) cells when combined with TNF-related apoptosis-inducing ligand (TRAIL), a cytokine that specifically targets cancer cells, by helping overcome TRAIL resistance. However, the therapeutic effects of curcumin are limited by its low bioavailability. Similar compounds to curcumin with higher bioavailability, such as demethoxycurcumin (DMC) and 3,5-bis(2-fluorobenzylidene)-4-piperidone (EF24), can potentially have similar anticancer effects and show a similar synergy with TRAIL, thus reducing RCC viability. This study aims to show the effects of DMC and EF24 in combination with TRAIL at reducing ACHN cell viability and ACHN cell migration. It also shows the changes in death receptor 4 (DR4) expression after treatment with these compounds individually and in combination with TRAIL, which can play a role in their mechanism of action.     

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.