Complete Charge Regulation by a Redox Enzyme Upon Single Electron Transfer

The degree by which metalloproteins partially regulate net charge (Z) upon electron transfer (ET) was recently measured for the first time using “protein charge ladders” of azurin, cytochrome c, and myoglobin [Angew. Chem. Int. Ed. 2018 , 57(19), 5364–5368; Angew. Chem. 2018 , 130, 5462–5466 ]. Here, we show that Cu, Zn superoxide dismutase (SOD1) is unique among proteins in its ability to resist changes in net charge upon single ET (e.g., ΔZ_ET(SOD1)=0.05±0.08 per electron, compared to ΔZ_ET(Cyt‐c)=1.19±0.02). This total regulation of net charge by SOD1 is attributed to the protonation of the bridging histidine upon copper reduction, yielding redox centers that are isoelectric at both copper oxidation states. Charge regulation by SOD1 would prevent long range coulombic perturbations to residue pK_a’s upon ET at copper, allowing SOD1’s “electrostatic loop” to attract superoxide with equal affinity (at both redox states of copper) during diffusion‐limited reduction and oxidation of superoxide.     

Extracellular matrix alterations in low‐grade lung adenocarcinoma compared with normal lung tissue by imaging mass spectrometry

Lung adenocarcinoma (LUAD) is the second most common cancer, affecting both men and women. Fibrosis is a hallmark of LUAD occurring throughout progression with excess production of extracellular matrix (ECM) components that lead to metastatic cell processes. Understanding the ECM cues that drive LUAD progression has been limited due to a lack of tools that can access and report on ECM components within the complex tumor microenvironment. Here, we test whether low‐grade LUAD can be distinguished from normal lung tissue using a novel ECM imaging mass spectrometry (ECM IMS) approach. ECM IMS analysis of a tissue microarray with 20 low‐grade LUAD tissues and 20 normal lung samples from 10 patients revealed 25 peptides that could discriminate between normal and low‐grade LUAD using area under the receiver‐operating curve (AUC) ≥0.7, P value ≤.001. Principal component analysis demonstrated that 62.4% of the variance could be explained by sample origin from normal or low‐grade tumor tissue. Additional work performed on a wedge resection with moderately differentiated LUAD demonstrated that the ECM IMS analytical approach could distinguish LUAD spectral features from spectral features of normal adjacent lung tissue. Conventional liquid chromatography with tandem mass spectrometry (LC‐MS/MS) proteomics demonstrated that specific sites of hydroxylation of proline (HYP) were a main collagen post translational modification that was readily detected in LUAD. A distinct peptide from collagen 3A1 modified by HYP was increased 3.5 fold in low‐grade LUAD compared with normal lung tissue (AUC 0.914, P value <.001). This suggests that regulation of collagen proline hydroxylation could be an important process during early LUAD fibrotic deposition. ECM IMS is a useful tool that may be used to define fibrotic deposition in low‐grade LUAD.     

Part I: The Development of the Catalytic Wittig Reaction

We have developed the first catalytic (in phosphane) Wittig reaction (CWR). The utilization of an organosilane was pivotal for success as it allowed for the chemoselective reduction of a phosphane oxide. Protocol optimization evaluated the phosphane oxide precatalyst structure, loading, organosilane, temperature, solvent, and base. These studies demonstrated that to maintain viable catalytic performance it was necessary to employ cyclic phosphane oxide precatalysts of type 1 . Initial substrate studies utilized sodium carbonate as a base, and further experimentation identified N,N‐diisopropylethylamine (DIPEA) as a soluble alternative. The use of DIPEA improved the ease of use, broadened the substrate scope, and decreased the precatalyst loading. The optimized protocols were compatible with alkyl, aryl, and heterocyclic (furyl, indolyl, pyridyl, pyrrolyl, and thienyl) aldehydes to produce both di‐ and trisubstituted olefins in moderate‐to‐high yields (60–96 %) by using a precatalyst loading of 4–10 mol %. Kinetic E/Z selectivity was generally 66:34; complete E selectivity for disubstituted α,β‐unsaturated products was achieved through a phosphane‐mediated isomerization event. The CWR was applied to the synthesis of 54 , a known precursor to the anti‐Alzheimer drug donepezil hydrochloride, on a multigram scale (12.2 g, 74 % yield). In addition, to our knowledge, the described CWR is the only transition‐/heavy‐metal‐free catalytic olefination process, excluding proton‐catalyzed elimination reactions.     

p-Laplacian problems with jumping nonlinearities

We consider the p-Laplacian boundary value problem

(1)     

A general synthetic method for MPO(4) (M = Co, Fe, Mn) frameworks using deep-eutectic solvents

A general approach was developed to synthesize a series of cobalt, manganese, and iron phosphate frameworks in deep-eutectic solvents through tuning important reaction parameters including temperature, time, and addition of water.     

Electrochemical studies of verdazyl radicals

The redox properties of verdazyl radicals are presented using cyclic voltammetry techniques. These radicals can be reversibly reduced as well as oxidized. Electron-donating and -withdrawing substituents have significant effects on the oxidation and reduction potentials as well as the cell potential (E(cell) = | E(ox) degrees - E(red) degrees |) for these radicals; a correlation between the electron spin distribution and redox properties is developed.     

The first example of enamine-Lewis acid cooperative bifunctional catalysis: application to the asymmetric aldol reaction

(-)-Sparteine directed lithiation of N-Boc-pyrrolidine, alkylation with chloromethylboronate pinacol ester and acid-based deprotection provides homoboroproline HX salt in 94% ee, which is then an efficient enamine-type pyrrolidine catalyst in an asymmetric aldol reaction when neutralised and especially when esterified in situ with a tartrate ester, for example, providing 90% ee of the aldol adduct derived from acetone and p-nitrobenzaldehyde.     

细胞内的拥挤环境有助于提高蛋白工作效率

生物酶必须在细胞内拥挤环境下行使功能。最新的研究表明,生物酶或许利用这种复杂环境而更加高效的工作。驱动蛋白是一类可以沿着微管定向输运物质的马达蛋白,当施加某种扰动时可以加快驱动蛋白的运动。实验与模拟结果同时表明,许多蛋白在嘈杂环境中的工作效率比在安静环境中的更高。     

Estimates of radiation over clouds and dust aerosols: Optimized number of terms in phase function expansion

The bulk-scattering properties of dust aerosols and clouds are computed for the community radiative transfer model (CRTM) that is a flagship effort of the Joint Center for Satellite Data Assimilation (JCSDA). The delta-fit method is employed to truncate the forward peaks of the scattering phase functions and to compute the Legendre expansion coefficients for re-constructing the truncated phase function. Use of more terms in the expansion gives more accurate re-construction of the phase function, but the issue remains as to how many terms are necessary for different applications. To explore this issue further, the bidirectional reflectances associated with dust aerosols, water clouds, and ice clouds are simulated with various numbers of Legendre expansion terms. To have relative numerical errors smaller than 5%, the present analyses indicate that, in the visible spectrum, 16 Legendre polynomials should be used for dust aerosols, while 32 Legendre expansion terms should be used for both water and ice clouds. In the infrared spectrum, the brightness temperatures at the top of the atmosphere are computed by using the scattering properties of dust aerosols, water clouds and ice clouds. Although small differences of brightness temperatures compared with the counterparts computed with 4, 8, 128 expansion terms are observed at large viewing angles for each layer, it is shown that 4 terms of Legendre polynomials are sufficient in the radiative transfer computation at infrared wavelengths for practical applications.