Synthesis of 29H,31H-phthalocyanine and chloro (29H,31H-phthalocyaninato) aluminum derivatives showed anti-cancer and anti-bacterial actions

Continuous administration of most chemotherapeutic drugs can induce different types of side effects. There has been growing interest in exploring an alternative approach to synthesizing compounds that are most effective and have fewer side effects. We synthesized 29H,31H-Phthalocyanine, and Chloro (29H,31H- phthalocyaninato) aluminum at low temperatures using lithium in the present study with diisopropylamide as the nucleophile. The physical characteristics of 29H,31H-Phthalocyanine, and Chloro (29H,31H- phthalocyaninato) aluminum were confirmed by FT-IR method, XRD, SEM, and the impact of these compounds on human colorectal carcinoma (HCT-116) and human cervical cells (HeLa) was examined. Treatment with 29H,31H-Phthalocyanine significantly decreased cancer cell growth and proliferation, as determined by MTT and DAPI staining analysis. In contrast, Chloro (29H,31H- phthalocyaninato) aluminum treatment did not show any inhibitory action on colon or cervical cancer cells. We also calculated the inhibitory concentration (IC50) of 29H,31H-Phthalocyanine, which was 30 µg/ml (HCT-116) and 33 µg/ml (HeLa cells). The antibacterial effectiveness of 29H,31H-Phthalocyanine, and chloro (29H,31H- phthalocyaninato) aluminum was studied using Enterococcus faecalis (E. faecalis). The CFU (colony frequency unit) assay confirmed significant activity against the test bacterium after treatment with 29H,31H-Phthalocyanine. However, no activity was seen upon treatment with chloro (29H,31H- phthalocyaninato) aluminum against E. faecalis.     

19F-detected dual-optimized inverted 1JCC 1,n-ADEQUATE

Modification of the recently reported ¹⁹F-detected 1,1-ADEQUATE experiment that incorporates dual-optimization to selectively invert a wide range of ¹J_CC correlations in a 1,n-ADEQUATE experiment is reported. Parameters for the dual-optimization segment of the pulse sequence were modified to accommodate the increased size of ¹J_CC homonuclear coupling constants of poly- and perfluorinated molecules relative to protonated molecules to allow broadband inversion of the ¹J_CC correlations. The observation and utility of isotope shifts are reported for the first time for 1,1- and 1,n-ADEQUATE correlations.     

Palladium-catalyzed vinylation of cyclohexenes using a directing-group strategy

Palladium-promoted vinylation of cyclohexenes via employment of a directing-group strategy to yield the coupled vinyl cyclohexenes with excellent regio- and stereoselectivity was studied. Typically, reaction of 2-(cyclohex-2-en-1-yl)-N-tosylacetamide ( 1a ) with (Z)-styryl bromides ( 2 ) gave cis-2-[(E)-styryl]cyclopent-3-en-1-yl-N-tosylacetamides in good to excellent yields. It is noticed that (Z)-styryl moiety was inverted into (E)-form in products. Unfortunately, (E)-styryl bromide substrates were not suitable for this reaction under the condition investigated. Further studies on norbornene system, we found that palladium-catalyzed reaction of endo-N-tosylbicyclo[2.2.1]hept-5-ene-2-carboxamide ( 6 ) with styryl bromides gave the Aza-Heck type products.     

环境响应性微胶囊及其在农业领域中应用的研究进展

在传统农业中,如何高效率地使用农药,提高其利用率,一直是一大难题。环境响应性微胶囊是一类在外界环境的刺激下,可以相适应地改变其表面结构的物质。这一类微胶囊具有智能、可控、精准、高效等特点。目前,这一项技术已经被广泛地应用于农业生产中。本文主要综述了环境中pH、温度、光以及磁场四大因素对响应性微胶囊的影响,并且简要介绍了该类微胶囊的制备技术、形成机理、主要材料以及在农业领域的应用。     

Mobility of Li+, Na+, and Cs+ cations in Nafion membrane,as studied by NMR techniques

The local mobility and diffusion of Li⁺, Na⁺, and Cs⁺ cations in Nafion 117 membrane were explored by ⁷Li, ²³Na, and ¹³³Cs spin relaxation and pulsed field gradient NMR techniques. It was shown that the macroscopic mass transfer of cations is controlled by ion motion near sulfonate groups. Lithium and sodium cations, whose hydrated energy is higher than the water hydrogen bond energy, are moving together with water molecules, but cesium cations possessing a low hydrated energy are jumping directly between the neighboring sulfonate groups.     

Sensitive Electrochemical Quantification of Proanthocyanidins in Grapevine (Vitis vinifera) by Utilizing Disposable Screen-printed Carbon Electrodes

This work presents quantification of proanthocyanidins (PAs) isolated from grapevine using disposable screen-printed carbon electrodes (SPCE). Procyanidin B2 (B2) used as a model to investigate the electrochemical characteristics of complicated PAs structures in Britton Robinson buffer solution using cyclic voltammetry and square wave voltammetry. B2 exhibits a well-defined reversible redox wave at +0.49 V vs. Ag/AgCl. Significantly, the B2 was determined over a linear concentration range of 3.45–34.6 μM with a detection limit of 2.07 μM. The SPCE was used to analyze PAs in grapevine samples, and the results were consistent with those obtained using Folin-Ciocalteu standard method.     

Enantioselective De Novo Synthesis of α,α-Diaryl Ketones from Alkynes

Chiral α,α-diaryl ketones are structural motifs commonly present in bioactive molecules, and they are also valuable building blocks in synthetic organic chemistry. However, catalytic asymmetric synthesis of α,α-diaryl ketones bearing a tertiary stereogenic center remains largely unsolved. Herein, we report a catalytic de novo enantioselective synthesis of α,α-diaryl ketones from simple alkynes via chiral phosphoric acid (CPA) catalysis. A broad range of enolizable α,α-diaryl ketones are prepared in good yields and with excellent enantioselectivities. The described protocol also serves as an efficient deuteration method for the preparation of enantiomerically enriched deuterated α,α-diaryl ketones. Using the methodology reported, bioactive molecules, including one of the best-selling anti-breast cancer drugs, tamoxifen, are readily synthesized.     

Palladium-Catalyzed Skeletal Rearrangement of Substituted 2-Silylaryl Triflates via 1,5-C−Pd/C−Si Bond Exchange

A palladium-catalyzed skeletal rearrangement of 2-(2-allylarylsilyl)aryl triflates has been developed to give highly fused tetrahydrophenanthrosilole derivatives via unprecedented 1,5-C−Pd/C−Si bond exchange. The reaction pathways can be switched toward 4-membered ring-forming C(sp²)−H alkylation by tuning the reaction conditions to give completely different products, fused dihydrodibenzosilepin derivatives, from the same starting materials. The inspection of the reaction conditions revealed the importance of carboxylates in promoting the C−Pd/C−Si bond exchange.     

In silico study of novel niclosamide derivatives,SARS-CoV-2 nonstructural proteins catalytic residue-targeting small molecules drug candidates

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated coronavirus disease 2019 (COVID-19) infection remains a global pandemic and health emergency with overwhelming social and economic impacts throughout the world. Therapeutics for COVID-19 are limited to only remdesivir; therefore, there is a need for combined, multidisciplinary efforts to develop new therapeutic molecules and explore the effectiveness of existing drugs against SARS-CoV-2. In the present study, we reported eight (SCOV-L-02, SCOV-L-09, SCOV-L-10, SCOV-L-11, SCOV-L-15, SCOV-L-18, SCOV-L-22, and SCOV-L-23) novel structurally related small-molecule derivatives of niclosamide (SCOV-L series) for their targeting potential against angiotensin-converting enzyme-2 (ACE2), type II transmembrane serine protease (TMPRSS2), and SARS-COV-2 nonstructural proteins (NSPs) including NSP5 (3CLpro), NSP3 (PLpro), and RdRp. Our correlation analysis suggested that ACE2 and TMPRSS2 modulate host immune response via regulation of immune-infiltrating cells at the site of tissue/organs entries. In addition, we identified some TMPRSS2 and ACE2 microRNAs target regulatory networks in SARS-CoV-2 infection and thus open up a new window for microRNAs-based therapy for the treatment of SARS-CoV-2 infection. Our in vitro study revealed that with the exception of SCOV-L-11 and SCOV-L-23 which were non-active, the SCOV-L series exhibited strict antiproliferative activities and non-cytotoxic effects against ACE2- and TMPRSS2-expressing cells. Our molecular docking for the analysis of receptor-ligand interactions revealed that SCOV-L series demonstrated high ligand binding efficacies (at higher levels than clinical drugs) against the ACE2, TMPRSS2, and SARS-COV-2 NSPs. SCOV-L-18, SCOV-L-15, and SCOV-L-09 were particularly found to exhibit strong binding affinities with three key SARS-CoV-2’s proteins: 3CLpro, PLpro, and RdRp. These compounds bind to the several catalytic residues of the proteins, and satisfied the criteria of drug-like candidates, having good adsorption, distribution, metabolism, excretion, and toxicity (ADMET) pharmacokinetic profile. Altogether, the present study suggests the therapeutic potential of SCOV-L series for preventing and managing SARs-COV-2 infection and are currently under detailed investigation in our lab.     

Is DFT Accurate Enough to Calculate Regioselectivity? The Case of 1,3-Dipolar Cycloaddition of Azide to Alkynes and Alkenes

The importance of regioselectivity in 1,3-dipolar cycloadditions (DCs) makes it surprising that no benchmarking study on this problem has appeared. We investigated whether DFT calculations are an accurate tool to predict the regioselectivity of uncatalyzed thermal azide 1,3-DCs. We considered the reaction between HN₃ and 12 dipolarophiles, comprising ethynes HC≡C−R and ethenes H₂C=CH−R (R=F, OH, NH₂, Me, CN, CHO), which cover a broad range of electron demand and conjugation ability. We established benchmark data by the W3X protocol [complete-basis-set-extrapolated CCSD(T)-F12 energy with T-(T) and (Q) corrections and MP2-calculated core/valence and relativistic effects] and showed that core/valence effects and high-order excitations are important for accurate regioselectivity. Regioselectivities calculated using an extensive set of density functional approximations (DFAs) were compared with benchmark data. Range-separated and meta-GGA hybrids gave the best results. Good treatment of self-interaction and electron exchange are the key features for accurate regioselectivity. Dispersion correction slightly improves agreement with W3X results. The best DFAs provide the isomeric TS energy difference with an expected error ≈0.7 mh and errors ≈2 mh can occur. The isomer yield provided by the best DFA has an expected error of ±5 %, though errors up to 20 % are not rare. At present, an accuracy of 1–2 % is unfeasible but it seems that we are not far from achieving this goal.