Accounts of Chemical Research
DOI: 10.1021/acs.accounts.3c00395
[ASAP] Identification of Chemical and Structural Characteristics of Acrylic Paint Layer Using Terahertz Metasurfaces
Analytical Chemistry
DOI: 10.1021/acs.analchem.3c02727
Synthesis, theoretical, in silico and in vitro biological evaluation studies of new thiosemicarbazones as acetylcholinesterase and carbonic anhydrases inhibitors
Eleven new thiosemicarbazone derivatives (1-11) were designed from nine different biologically and pharmacologically important isothiocyanate derivatives containing functional groups such as fluorine, chlorine, methoxy, methyl, and nitro at various positions of the phenyl ring, in addition to the benzyl unit in the molecular skeletal structure. First, their substituted-thiosemicarbazide derivatives were synthesized from the treatment of isothiocyanate with hydrazine to synthesize the designed compounds. Through a one-step easy synthesis and an eco-friendly process, the designed compounds were synthesized with yields of up to 95% from the treatment of the thiosemicarbazides with aldehyde derivatives having methoxy and hydroxyl groups. The structures of the synthesized molecules were elucidated with elemental analysis and FT–IR, 1H NMR, and 13C NMR spectroscopic methods. The electronic and spectroscopic properties of the compounds were determined by the DFT calculations performed at the B3LYP/6-311++G(2d,2p) level of theory, and the experimental findings were supported. They exhibited a highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (KI values are in the range of 23.54±4.34 to 185.90±26.16 nM, 103.90±23.49 to 325.90 ±77.99 nM, and 86.15±18.58 to 287.70±43.09 nM for AChE, hCA I, and hCA II, respectively). Furthermore, molecular docking simulations were performed to explain each enzyme-ligand complex's interaction.
Phosphine‐catalyzed [4+3] annulation reaction of indole derivatives with MBH carbonates: A facile access to indole‐1,2‐fused 1,4‐diazepinones and azepines
Comprehensive Summary
A phosphine-catalyzed [4+3] annulation between dinucleophilic indole derivatives and Morita−Baylis−Hillman (MBH) carbonates was discovered by using the N1 and N4′/C4′ nucleophilicities of the indole precursors, in which indoles act as four atom synthons. This protocol provides an efficient and facile access to indole-1,2-fused 1,4-diazepinones and azepines in good to high yields in one step, which illustrates potential synthetic utilities in drug discovery.
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DBU Promoted Deformylative/Dehalogenative Difunctionalization to Access β‐Bromovinyl Aldehydes Derived from Tetralones
Metal-free deformylative/dehalogenative carbonylation, Michael addition of β-bromovinyl aldehydes for the synthesis of δ-oxo esters and vinyl ethers have been reported. Nucleophilic and organo-catalytic behaviour of DBU is explored and the regeneration of the parent starting material from the vinyl ether is also highlighted.
Abstract
Herein we have disclosed metal-free 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU)-catalyzed protocol for the deformylative/dehalogenative carbonylation and Michael addition of β-bromovinyl aldehydes with acrylates and carbonylation followed by etherification with benzyl bromides to synthesize δ-oxo esters and vinyl ethers respectively in good yields under an open atmosphere with broad substrate scope. Regeneration of starting material from vinyl ethers, organo-catalytic and nucleophilic behavior of DBU is also discussed.
An Indolin‐3‐imine Photobase and pH Sensitive Fluorophore
Touching base: The photobasicity and pH sensitivity of a fluorescent indolin-3-imine derivative is described. The fluorophore can deprotonate and sense weakly acidic protic solvents – a process enhanced by excited state proton transfer. Cell imaging experiments revealed that indolin-3-imine is a potential scaffold for fluorescence cell microscopy.
Abstract
This work presents the pH sensing ability of a fluorescent indolin-3-imine derivative. Protonation of the weakly basic imine (pK a=8.3 of its conjugate acid) results in a significant red-shift of the absorption band. The fluorophore acts as a photobase, with a basicity increase of approximately 6 units upon photoexcitation. This behavior promotes excited state proton transfer from weak acids such as protic solvents. The characteristics of the fluorophore enable sensing of water fractions in organic solvents and differentiation between methanol, ethanol, and longer chain alcohols. Initial cell studies indicated the future potential of indolin-3-imines as fluorophores for bioimaging applications.
Solvatochromic Properties of (Iso)quinolylpyrrole‐Boron Difluoride Complexes Bearing N,N‐Diphenylanilinyl Group and Its Regio‐Effect
Asymmetric boron complexes composed of (iso)quinolyl-pyrrole ligands possessing triphenylamine unit on the (iso)quinoline or pyrrole moieties were systematically prepared. Their optical properties were investigated in various organic solvents, and they showed solvatochromic properties, which were influenced by the π-structure of the ligands and the position of the electron-donor group. The degrees of changes in the emission-color drastically changed for regioisomeric chromophores 1 and 2. In this study, the solvatochromic properties of the compounds were investigated and described using both experimental and computational results.
Development and Crosslinking Properties of Psoralen‐Conjugated Triplex‐Forming Oligonucleotides as Antigene Tools Targeting Genome DNA
We conducted a close investigation of psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs). The triangular relationships between structural differences, photo-crosslinking efficiencies, and biological activities were examined. This research suggested that the photo-crosslinking of Ps-TFO did not reach a plateau under cell irradiation conditions, highlighting the need to develop new psoralen derivatives that are more reactive under cell irradiation conditions.
Abstract
Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been utilized for genome editing and anti-gene experiments for over thirty years. However, the research on Ps-TFOs employing artificial nucleotides is still limited, and their photo-crosslinking properties have not been thoroughly investigated in relation to biological activities. In this study, we extensively examined the photo-crosslinking properties of Ps-TFOs to provide fundamental insights for future Ps-TFO design. We developed novel Ps-TFOs containing 2′-O,4′-C-methylene-bridged nucleic acids (Ps-LNA-mixmer) and investigated their photo-crosslinking properties using stable cell lines that express firefly luciferase constitutively to evaluate the anti-gene activities of Ps-LNA-mixmer. As a result, Ps-LNA-mixmer successfully demonstrated suppression activity, and we presented the first-ever correlation between photo-crosslinking properties and their activities. Our findings also indicate that the photo-crosslinking process is insufficient under cell irradiation conditions (365 nm, 2 mW/cm2, 60 min). Therefore, our results highlight the need to develop new psoralen derivatives that are more reactive under cell irradiation conditions.
Small Molecules Targeting Human UDP‐GlcNAc 2‐Epimerase
Uridine diphosphate N-acetylglucosamine 2-epimerase (GNE) is a key enzyme in the sialic acid biosynthesis pathway. Sialic acids are primarily terminal carbohydrates on glycans and play fundamental roles in health and disease. In search of effective GNE inhibitors not based on a carbohydrate scaffold, we performed a high-throughput screening campaign of 68,640 drug-like small molecules against recombinant GNE using a UDP detection assay. We validated nine of the primary actives with an orthogonal real-time NMR assay and verified their IC50 values in the low micromolar to nanomolar range manually. Stability and solubility studies revealed three compounds for further evaluation. Thermal shift assays, analytical size exclusion and interferometric scattering microscopy demonstrated that the GNE inhibitors acted on the oligomeric state of the protein. Finally, hydrogen-deuterium exchange mass spectrometry (HDX-MS) revealed which sections of GNE were shifted upon the addition of the inhibitors. In summary, we have identified three small molecules as GNE inhibitors with high potency in vitro, which serve as promising candidates to modulate sialic acid biosynthesis in more complex systems
Chemical Composition and Evaluation of Antibacterial, Antibiofilm and Mutagenic Potentials of a Propolis Sample from the Atlantic Forest of Midwest Brazil
Sixteen triterpenoids with various skeletal types, five phenylpropanoid derivatives, and two flavonoids were isolated from a propolis sample produced by Apis mellifera collected in the Atlantic Forest of Midwest Brazil. Among these compounds, six triterpenes, namely 3β,20R-dihydroxylanost-24-en-3-yl-palmitate, (23E)-25-methoxycycloartan-23-en-3-one, 24-methylenecycloartenone, epi-lupeol, epi-a-amyrin, and epi-β-amyrin are being reported for the first time in propolis, while cycloartenone, (E)-cinnamyl benzoate, and (E)-cinnamyl cinnamate are new findings in Brazilian propolis. The presence of cycloartane- and lanostane-type triterpenoids, the latter being a class of compounds of restricted distribution in propolis worldwide, has not been reported in propolis from Midwest Brazil until now. The ethyl acetate phase obtained from the ethanol extract was effective in preventing biofilm formation by Staphylococcus aureus, with an inhibition rate of about 96% at 0.5 mg.mL-1, and with quercetin isolated as one of its active constituents. In contrast, the hexane phase exhibited notable antibacterial activity against Pseudomonas aeruginosa, inhibiting bacterial growth by 92% at 0.5 mg.mL-1; however, none of the triterpenoids isolated from this phase proved active against this pathogen. The ethanol extract was neither toxic nor mutagenic at the concentrations tested, as determined by the in vivo SMART assay on Drosophila melanogaster, even under conditions of high metabolic activation.