Bulletin of the Korean Chemical Society最新文献

Tauopathy is characterized by the abnormal aggregation of tau proteins. In order to develop drugs for tauopathies, a variety of different therapeutic strategies have been investigated. Synapse loss is a hallmark of tauopathies and is reportedly related to cognitive impairment in Alzheimer's disease as well. Emerging evidence suggests that pathogenic tau species are linked to synaptic dysfunction and synapse loss in tauopathies. As such, a potential therapeutic approach to ameliorate synaptic dysfunction and counteract synaptic loss due to pathogenic tau holds promise. This review highlights the pathological links between tau pathology and synaptic integrity and current efforts to develop therapeutics rescuing synaptic dysfunction for tauopathies, which will help to understand the association between tau and synapses and develop disease-modifying drugs for tauopathies.

Mesoporous manganese dioxide (mMnO₂) was first synthesized for the loading of methotrexate (MTX), and then dopamine was in situ polymerized on the surface of the MTX-loaded mMnO₂ (mMnO₂-MTX) in an alkaline solution to encapsulate the drug in the mesopores of mMnO₂. Both low pH and glutathione (GSH) can result in the degradation of mMnO₂ and poly(dopamine) (PDA), and thus the delivery of MTX from the mMnO₂-MTX-PDA can be triggered by low pH and GSH. Near-infrared (NIR) light-responsive delivery of MTX can be achieved owing to the outstanding photothermal conversion capability of PDA; on the other hand, the mMnO₂-MTX-PDA can be utilized for photothermal therapy under the irradiation of NIR light due to the elevated temperature. The results of cytotoxicity test demonstrate that the pH, GSH, and NIR light tri-responsive drug-controlled delivery system has excellent biocompatibility, while exhibits pronounced growth inhibition against murine breast tumor cell line 4T1.

Preparation of highly enantioenriched six-membered 1,4-N,N- and N,O-heterocycles has been developed through [4 + 2] heteroannulation of α-bromoacetates with 1,4-binucleophiles. Two consecutive substitutions of highly diastereoenriched L-serinate-derived α-bromoacetates provide convenient access to a wide range of C-aryl/aliphatic substituted 1,4-N,N- and N,O-heterocycles with up to 99:1 er.

PEO-based polymer electrolytes are currently attracting widespread interest as the next-generation electrolytes for batteries that overcome the limitations of conventional liquid electrolytes. Despite this favorable feature, there are still several issues to be addressed for practical applications. In this context, this paper presents various strategies to overcome their intrinsic challenges in PEO-based solid-state polymer electrolyte. More details are available in the article by Jiyoung Lee and Byeong-Su Kim.

The confocal interpretation of organelle-selective fluorogenic chemosensors can be ambiguous because of inconsistency between the sensor localization and reaction site. To overcome this limitation, we implemented the photoactivation strategy which refers to light-controlled probe activation within cells at the desired time. In this study, we synthesized a photoactivatable dihydrofluorescein probe (1) and its cell-permeable derivative (3, acetoxymethyl ester of 1). We confirmed their reactivity to reactive oxygen species (ROS) and photoactivation in both solution and cells. The photoactivation of probe 3 facilitated temporal control between probe treatment and the occurrence of fluorogenic events. We conducted organelle colocalization studies and cellular ROS imaging, clearly showing that the probe primarily localized to early/late endosomes and reacted with intracellular ROS at these endosomes. These findings highlight the effectiveness of the photoactivation strategy for fluorogenic ROS probes in mitigating ambiguities associated with conventional fluorogenic ROS sensing approaches.

Stable N-heterocyclic carbenes (NHCs) have garnered significant attention in synthetic chemistry due to their versatile applications. In this study, we explored a novel mechanochemical method for the generation of free carbenes, which could be a good complement to traditional approaches that require strong bases or reductants. Ball milling of NHC–CS₂ adducts at room temperature successfully resulted in the quantitative formation of free carbenes that can be subsequently trapped by sulfur or selenium. Importantly, heating NHC–CS₂ adducts in solution phase did not lead to the successful generation of free carbenes, in agreement with the high activation energy required for NHC–CS₂ dissociation. These findings underscore the potential of ball milling as a robust and versatile approach for generating NHCs from stable NHC-small molecule adducts, and opens new avenues for developing mechanochemical strategies for generating valuable NHC-derived compounds.

A novel nonlinear optical cocrystal, KHC₂O₄·B(OH)₃, composed of infinite [HC₂O₄] and [B(OH)₃] chains, exhibits a remarkably high birefringence (0.164@1064 nm) in the short-wavelength ultraviolet region (254 nm). More details are available in the article by Yang Li, Jihyun Lee, Kang Min Ok.

In this study, the effectiveness of electrospun poly(ethylene glycol) (PEG) nanofibers as polymer electrolytes for dye-sensitized solar cells (DSSCs) is evaluated. Regular PEG nanofibers are electrospun at an applied voltage of 15 kV, using a polymer concentration of 13 wt% and tip-to-collector distance of 20 cm. Subsequently, the photovoltaic effect in DSSCs containing PEG-nanofiber electrolytes with different I₂ concentrations is analyzed. On reducing the concentration of I₂ in the PEG-nanofiber electrolyte, the short-circuit photocurrent density (Jsc) of the corresponding DSSC increases significantly. A high power-conversion efficiency of 5.93% is recorded (by a solar simulator under AM 1.5 illumination) for a PEG-nanofiber-based DSSC containing an I₂/tetrabuthylammonium iodide (TBAI) molar ratio of 0.25. Additionally, electrochemical impedance spectroscopy is used to analyze the charge-transfer resistance of the TiO₂/PEG-nanofiber electrolyte interface in the fabricated DSSCs; the electrolyte uptake, ionic conductivity, and charge-transfer resistance values are investigated as a function of the molar ratio of I₂/TBAI.

Development of dual inhibitors of pan-RAF/VEGFR2 is important for the treatment of K-Ras mutated colorectal cancer, which is one of the most common and lethal malignancies. Building upon our studies in dual inhibitors of pan-RAF/VEGFR2, we designed and synthesized new dual inhibitor candidates by installing a urea or guanidine moiety to the previously reported dual inhibitors in order to enhance both metabolic stability and solubility. Various 1-(5-((3-(9H-purin-6-yl)pyridin-2-yl)amino)-2-fluorophenyl)-3-phenylurea and 1-(5-((3-(9H-purin-6-yl)pyridin-2-yl)amino)-2-fluorophenyl)-3-phenylguanidine derivatives were synthesized, and their antiproliferative activities against LS513 cell (K-Ras^G12D) and VEGFR2 were evaluated. Among the tested compounds, 1-(5-((3-(9H-purin-6-yl)pyridin-2-yl)amino)-2-fluorophenyl)-3-(3-fluorophenyl)urea (7b) and 1-(5-((3-(9H-purin-6-yl)pyridin-2-yl)amino)-2-fluorophenyl)-3-(4-chloro-3-trifluoromethyl)phenyl)urea (7e) are the most potent dual inhibitors against LS513 (GI₅₀ = 0.1 and 0.06 μM, respectively) and VEGFR2 (IC₅₀ = 0.03 and 0.06 μM, respectively). The preclinical study with these compounds are currently underway.

The kinetics of nucleophilic substitution reactions involving 2,4-dinitrophenyl 5-substituted-2-thiophenecarboxylate were studied kinetically with 4-Z-C₆H₄O⁻/4-Z-C₆H₄OH, which facilitated the reactions, in 20 mol% DMSO(aq). The reactions followed second-order kinetics and exhibited β_acyl = −2.34 to −2.92, ρ(Y) = 2.71–3.39, β_nuc = 0.74–0.83, and |β_lg| = 0.40–0.57. Based on the interpretation of the results, we have concluded that the reaction follows an addition–elimination mechanism in which the first step is the rate-determining step (rds). The transition state structures for the 4-ZC₆H₄O⁻-promoted reactions remained nearly the same with a change in the leaving group from 4-nitrophenoxide to 2,4-dinitrophenoxide. The mechanism of the 4-ZC₆H₄O⁻-promoted reaction was similar to that of R₂NH-promoted reactions, except that the former proceeded with the 1st step being the rds and the latter proceeded with a change in the rds from the second to the first step with a stronger nucleophile.