Rhodium-Catalyzed Direct Annulation of Aldehydes with Alkynes Leading to Indenones: Proceeding through <i>in Situ</i> Directing Group Formation and Removal

The Rh-catalyzed direct annulation of an aldehyde with an alkyne leading to indenone was achieved. The <i>in situ</i> temporal installation of acetylhydrazine enables the annulation of the <i>ortho</i> arene C–H bond with alkynes to form ketone hydrazone. Subsequently, the <i>in situ</i> directing group removal takes place since ketone hydrazone is more susceptible toward hydrolysis than aldehyde hydrazone. Notably, this procedure tolerates a series of functional groups, such as methoxyl, acetylamino, fluoro, trifluoromethyl, methoxycarbonyl, chloro, and bromo groups

Ring Fusion of Thiophene–Vinylene–Thiophene (TVT) Benefits Both Fullerene and Non-Fullerene Polymer Solar Cells

Conjugated polymers based on thiophene–vinylene–thiophene (TVT) and ethenylene fused TVT (ETVT) combined with alkylated dithienyl­benzothiadiazole (DTBT) were designed and synthesized to investigate the effect of ring fusion on the properties of TVT based photovoltaic polymers. It is found that ring fusion of the TVT segment significantly affects molecular architecture and optoelectronic properties of the polymer. Ring fusion can downshift the HOMO energy level and increase the absorption coefficient of the corresponding polymer. Combining with reduced energy loss, PETVTTBT shows superior photovoltaic performance to PTVTTBT, in both fullerene and non-fullerene polymer solar cells. Particularly, in ITIC based polymer solar cells, simultaneous enhancement in the <i>J</i>_SC, <i>V</i>_OC, and FF is demonstrated after ring fusion. As a result, PCE of PETVTTBT based solar cells increases drastically by 120% over that of PTVTTBT (3.69%), reaching 8.18%

Supplemental material for A method to eliminate unsprung adverse effect of in-wheel motor-driven vehicles

<p>Supplemental material for A method to eliminate unsprung adverse effect of in-wheel motor-driven vehicles by Shida Nie, Ye Zhuang, Fan Chen, Yong Wang and Shu Liu in Journal of Low Frequency Noise, Vibration and Active Control</p

Stable <i>S</i>‑Adenosylmethionine Analogue for Enzymatic Fluoromethylation

Fluorine is an important atom in medicinal chemistry and agrochemistry, and the fluoromethyl group, an isostere for various functional groups, can improve the metabolic stability and biological activity of compounds. However, enzymes that introduce fluorine and fluorine-containing groups are rare, and performing selective fluoromethylation remains a great challenge in organic chemistry. Biocatalytic fluoromethylation is severely limited by the instability of fluoro S-adenosylmethionine (SAM). Here, we designed and synthesized a stable fluoro SAM analogue, fluoro decarboxyl SAM (F-dcSAM). The F-dcSAM analogue is stable and can be accepted by many O-, S-, and N-methyltransferases, transferring fluoromethyl groups to their substrate. F-dcSAM and methyltransferases were applied to fluoromethylate various compounds, including several bioactive natural products, with high chemo- and regioselectivity. Kinetics studies showed that compared to SAM, F-dcSAM is an analogous or even better substrate for the methyltransferases NtCOMT and DnrK. We further showed that F-dcSAM can be readily prepared enzymatically by halide methyltransferase (HMT) from decarboxyl S-adenosyl-l-homocysteine (dcSAH) and CH2FI. The enzyme cascade reaction involving HMT and methyltransferases can transfer the CH2F group from CH2FI to substrates efficiently with multiple turnovers. Therefore, F-dcSAM can be directly used for enzymatic fluoromethylation or generated in situ through the coupled activities of HMT and methyltransferases. Our results suggest that F-dcSAM is a general abiological cofactor of methyltransferases for late-stage enzymatic fluoromethylation and facilitates the preparation of fluoro analogues of drug molecules. In addition, F-dcSAM is a stable nonaromatic sulfonium ion compound that serves as a fluoromethyl donor, which provides new opportunities for the development of novel CH2F reagents

Sequence Based Prediction of DNA-Binding Proteins Based on Hybrid Feature Selection Using Random Forest and Gaussian Naïve Bayes

<div><p>Developing an efficient method for determination of the DNA-binding proteins, due to their vital roles in gene regulation, is becoming highly desired since it would be invaluable to advance our understanding of protein functions. In this study, we proposed a new method for the prediction of the DNA-binding proteins, by performing the feature rank using random forest and the wrapper-based feature selection using forward best-first search strategy. The features comprise information from primary sequence, predicted secondary structure, predicted relative solvent accessibility, and position specific scoring matrix. The proposed method, called DBPPred, used Gaussian naïve Bayes as the underlying classifier since it outperformed five other classifiers, including decision tree, logistic regression, k-nearest neighbor, support vector machine with polynomial kernel, and support vector machine with radial basis function. As a result, the proposed DBPPred yields the highest average accuracy of 0.791 and average MCC of 0.583 according to the five-fold cross validation with ten runs on the training benchmark dataset PDB594. Subsequently, blind tests on the independent dataset PDB186 by the proposed model trained on the entire PDB594 dataset and by other five existing methods (including iDNA-Prot, DNA-Prot, DNAbinder, DNABIND and DBD-Threader) were performed, resulting in that the proposed DBPPred yielded the highest accuracy of 0.769, MCC of 0.538, and AUC of 0.790. The independent tests performed by the proposed DBPPred on completely a large non-DNA binding protein dataset and two RNA binding protein datasets also showed improved or comparable quality when compared with the relevant prediction methods. Moreover, we observed that majority of the selected features by the proposed method are statistically significantly different between the mean feature values of the DNA-binding and the non DNA-binding proteins. All of the experimental results indicate that the proposed DBPPred can be an alternative perspective predictor for large-scale determination of DNA-binding proteins.</p></div

Comparison of DBPPred with the existing methods based on independent blind tests on the same dataset PDB186.

<p>N/A means that the data are not available.</p

List of false positive rates of the proposed DBPPred and the existing iDNA-Prot, DNA-Prot, DNAbinder and DNABIND on datasets NDBP4025, RB174, RB256 and RB430.

<p>List of false positive rates of the proposed DBPPred and the existing iDNA-Prot, DNA-Prot, DNAbinder and DNABIND on datasets NDBP4025, RB174, RB256 and RB430.</p

ROC curves for the predictions of DNA-binding proteins on the PDB186 dataset.

<p>We compare the predictions of DBPPred with DNABIND and DNAbinder that provide real-value outputs.</p

Swollen Micelles for the Preparation of Gated, Squeezable, pH-Responsive Drug Carriers

Natural variations in pH levels of tissues in the body make it an attractive stimuli to trigger drug release from a delivery vehicle. A number of such carriers have been developed but achieving high drug loading combined with low leakage at physiological pH and tunable controlled release at the site of action is an ongoing challenge. Here we report a novel strategy for the synthesis of entirely hydrophilic stimuli-responsive nanocarriers with high passive loading efficiency of doxorubicin (DOX), which show good stability at pH 7 and rapid tunable drug release at intracellular pH. The particles (<i>D</i>_h = 120–150 nm), are prepared by cross-linking the core of swollen micelles of the triblock copolymer poly­[poly­(ethylene glycol) methyl ether methacrylate-<i>b</i>-<i>N</i>,<i>N</i>′-di(methylamino)ethyl methacrylate-<i>b</i>-<i>tert</i>-butyl methacrylate] (poly­(PEGMEM A)<i>-<i>b</i>-</i> PDMAEMA-<i>b</i>-P<i>t</i>BMA)). After subsequent deprotection of the <i>tert</i>-butyl groups a hydrophilic poly­(methacrylic acid) (PMAA) core is revealed. Due to the negative charge in the acidic core the particles absorb 100% of the DOX from solution at pH 7 at up to 50 wt % DOX/polymer, making them extremely simple to load. Unlike other systems, the DMAEMA “gating” shell ensures low drug leakage at pH 7, whereas physical shrinkage of the MAA core allows rapid release below pH 6. The particles deliver DOX with high efficiency to human pancreatic cancer AsPC-1 cell lines, even lowering the IC50 of DOX. As the particles are stable as a dry powder and can be loaded with any mixture of positively charged drugs without complex synthetic or purification steps, we propose they will find use in a range of delivery applications

Unexpected Role of <i>p</i>‑Toluenesulfonylmethyl Isocyanide as a Sulfonylating Agent in Reactions with α‑Bromocarbonyl Compounds

The reactions of <i>p</i>-toluenesulfonylmethyl isocyanide (TosMIC) with α-bromocarbonyl compounds leading efficiently to α-sulfonated ketones, esters, and amides were reported, in which an explicit new role of TosMIC as the sulfonylating agent was uncovered for the first time. Mechanistic study by control experiments and DFT calculations suggested that the reaction is initiated by Cu­(OTf)₂-catalyzed hydration of TosMIC to form a formamide intermediate, which undergoes facile C–S bond cleavage under the mediation of a Cs₂CO₃ additive