Nickel-Catalyzed 1,2-Diarylation of Alkenyl Carboxylates: A Gateway to 1,2,3-Trifunctionalized Building Blocks

A nickel-catalyzed conjunctive cross-coupling of alkenyl carboxylic acids, aryl iodides, and aryl/alkenyl boronic esters is reported. The reaction delivers the desired 1,2-diarylated and 1,2-arylalkenylated products with excellent regiocontrol. To demonstrate the synthetic utility of the method, a representative product is prepared on gram scale and then diversified to eight 1,2,3-trifunctionalized building blocks using two-electron and one-electron logic. Using this method, three routes toward bioactive molecules are improved in terms of yield and/or step count. This method represents the first example of catalytic 1,2-diarylation of an alkene directed by a native carboxylate group.     

一个关于肿瘤治疗的自由边界问题的数学分析

§1Introduction Avarietyofpartialdifferentialequationmodelsfortumorgrowthortherapyhave beendevelopedinthelastthreedecades[see2,3,16-18,21-26].Mostofthosemodelsare informoffreeboundaryproblems,andareverydiversified.Rigorousmathematical analysisofsuchfreeboundaryproblemshasdrawngreatinterest,andmanyinteresting resultshavebeenestablished[4-15].Inthispaperwedealwithamathematicalmodeldescribingtumorchemotherapy.In thismodelthetumorisviewedasdenselypacked,radially-symmetricsphereofradiusR(t)contain…     

Data assimilation and pollution forecasting in Burgers' equation with model error function

This article presents a correction method for a better resolution of the problem of estimating and predicting pollution, governed by Burgers' equations. The originality of the method consists in the introduction of an error function into the system's equations of state to model uncertainty in the model. The initial conditions and diffusion coefficients, present in the equations for pollution and concentration, and also those in the model error equations, are estimated by solving a data assimilation problem. The efficiency of the correction method is compared with that produced by the traditional method without introduction of an error function.Three test cases are presented in this study in order to compare the performances of the proposed methods. In the first two tests, the reference is the analytical solution and the last test is formulated as part of the “twin experiment”.The numerical results obtained confirm the important role of the model error equation for improving the prediction capability of the system, in terms of both accuracy and speed of convergence.     

Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC₅₀ values of 3.4–37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC₅₀ value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (−7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.     

Energy Storage by Poly(<Emphasis Type="Italic">o</Emphasis>-anisidine) Matrix During Oxidative Hydrolysis

The chromaticity of poly(o-anisidine) (POAN) doped with different acids (HA), HA-doped POAN, has been studied by the spectrophotometric technique and the results were substantiated by molecular mechanics (MM+) calculations. The observed absorbance decrease (λ around 720 nm, dark green coloration) with increasing concentration of the inorganic oxidizing agent (KMnO₄) can be attributed to the oxidative hydrolysis mechanism. The oxidative hydrolysis constant (K _h) is highly dependent on the strength of the acid used. The HClO₄-doped POAN matrix has the ability to store about 128.878 kJ⋅g⁻¹ chromogenic energy (CE) at the wavelength 720 nm in a condensed lightweight form. MM+ calculations suggest that the potential energy (PE) in kJ⋅mol⁻¹ of the optimum molecular geometric (OMG) structure of the HClO₄-doped POAN matrix is at least two (2.052) times more stable than the OMG of the base form (POAN-EB) of the POAN matrix. Kinetic parameters of the oxidative hydrolysis reaction of the HA-doped POAN matrix were deduced from absorbance variations with time. The results of computer-oriented kinetic analysis indicate that the rate-controlling step for HA-doped POAN oxidative hydrolysis is governed by the Ginstling-Bronshein equation that represents three-dimensional diffusion (D4). Activation parameters for the oxidative hydrolysis of the HClO₄-doped POAN matrix were computed and discussed.     

Guanidine-based task-specific ionic liquids as catalysts for aza-Michael addition under solvent-free conditions

An efficient and facile protocol for aza-Michael addition of aliphatic and aromatic amines to electron-deficit alkenes using [TMG][Lac] as catalyst under solvent-free conditions was established.     

Freeze-drying for the stabilisation of shellfish toxins in mussel tissue (<Emphasis Type="Italic">Mytilus edulis</Emphasis>) reference materials

Two samples of mussels (Mytilus edulis) were collected from the southwest of Ireland. One sample contained domoic acid, the other sample contained okadaic acid, dinophysistoxin-2 and azaspiracid-1, -2 and -3. Wet and freeze-dried reference materials were prepared from each of the two samples to test for differences in homogeneity, stability and extractability of the analytes in either condition. Wet materials were homogenised, aliquoted and hermetically sealed under argon and subsequently frozen at −80 °C. Dry materials were similarly homogenised but frozen in flat cakes prior to freeze-drying. After grinding, sieving and further homogenisation, the resulting powder was aliquoted and hermetically sealed. Domoic acid materials were characterised using HPLC–UV, while LC–MS was used for the determination of lipophilic toxins. The extractabilities of all phycotoxins studied were comparable for wet and freeze-dried materials once a sonication step had been carried out for reconstitution of the freeze-dried materials prior to extraction. Homogeneity was assessed through replicate analysis of the phycotoxins (n = 10), and was found to be similar for wet and freeze-dried materials, for both hydrophilic and lipophilic toxins. Water contents were determined for both wet and freeze-dried materials, and particle size was determined for the freeze-dried materials. Stability was evaluated isochronously over eight months at four temperatures (−20, +4, +20 and +40 °C). The freeze-dried material containing domoic acid was stable over the whole duration at all temperatures, while in the wet material domoic acid degraded to some extent at all temperatures except −20 °C. In freeze-dried and wet materials containing lipophilic toxins, okadaic acid, dinophysistoxin-2, azaspiracid-1 and azaspiracid-2 were stable over the whole duration at all conditions, while concentrations of azaspiracid-3 changed significantly in both materials at some storage temperatures. Figure Aliquots of freeze-dried and wet mussel tissue reference materials containing the various shellfish toxins examined in the study