The role of in situ generated fluorinated sulfur intermediates, formed through the interaction of the electrophilic fluorine source Selectfluor with sulfur-containing reagents, in the chemoselective transformations of benzhydrols was investigated from a mechanistic perspective. The 1,2-dimethyldisulfide-Selectfluor combination enabled the selective self-etherification of benzhydrols, and this transformation was shown to proceed via benzhydrol-centered reactive intermediates activated by fluorinated sulfur species. Upon increasing the reaction temperature and 1,2-dimethyldisulfide was replaced with carbon disulfide, the reaction pathway was altered, leading to the selective oxidation of benzhydrols to the corresponding benzophenones. Under the same conditions, when nitromethane was employed as the solvent, Ritter-type amidation was achieved via the solvolytic activation of the benzhydrols. Based on control experiments and the effects of reaction parameters, plausible mechanisms for these condition-dependent chemoselective transformations are proposed and discussed.

Interfacial chemistry of molecular baskets remains poorly understood despite their promise for supramolecular applications of detection and sequestration of toxic molecules including those of illicit drugs, organophosphorus compounds, and anticancer agents. We present a fundamental investigation of the interfacial behavior of three amphiphilic supramolecular baskets (ASB 4, 8, and 12), having increasingly longer yet linear alkyl chains at the top of their bowl-shaped cavity. The studies were completed at the air-water interface to elucidate surface activity, interfacial stability, self-assembly, and monolayer organization that drive inverted monolayer formation, in which the molecular arms orient toward the aqueous phase in a configuration opposite to that typically observed for lipids. Herein, surface pressure-area isotherms of ASB 4, 8, 12, deposited on a water surface, were performed in tandem with nonequilibrium relaxation experiments to quantify surface activity, thermodynamic stability, and monolayer compressibility of the baskets' monolayer assembly. Brewster angle microscopy enabled direct visualization of morphological evolution, aggregation, and packing at the interface. We show that systematic extension of the hydrocarbon arms, from four to 12 methylene groups, progressively modifies intermolecular packing, drives distinct two-dimensional aggregation pathways, and increases number densities at the air-water interface. Atomistic molecular dynamics simulations corroborate many of these experimentally observed trends and provide mechanistic detail on the cooperative roles of basket topology and interfacial concentration in regulating the hydration structure and dynamics within the cavities generated by surface-adsorbing baskets, consistent with observed variations in surface activity and packing. Our results establish how the topology of these unique supramolecules and their concentration govern interfacial organization and offer a rational framework for designing amphiphiles with predictable behavior at soft interfaces.

Benzophenone-3 (BP3) is an organic pollutant widely detected in soil and aquatic environments. The aims of this study were to isolate a bacterium which is capable of degrading BP3 and converting it into non-toxic products, and to design a non-sterile culture process which may be applied to the real biological treatment systems for the bioremediation of BP3. Klebsiella huaxiensis W2 (GenBank accession number: PQ143284) isolated from a wastewater treatment system was found to have high potency to degrade BP3. This bacterium degraded BP3 into two byproducts: phenol, 2,4-bis-(1,1-dimethylethyl) and benzyl benzoate. Oxygenases (P450 monooxygenases, dioxygenases etc.) were predicted to be effective in BP3 degradation. BP3-degradation products did not cause a toxicity on fibroblast cell line. Optimizing inoculum size, that is, inoculating the high size (1–2

Correction for ‘Molecular bowls for inclusion complexation of toxic anticancer drug methotrexate’ by Pratik Karmakar et al. , Chem. Sci. , 2024, 15 , 10155–10163, https://doi.org/10.1039/D3SC05627A.

We describe the preparation, assembly, recognition characteristics, and bioactivity of dendritic basket 6 12− . This novel cavitand has a deep aromatic pocket with three ( S )-glutamic acid dendrons at the rim to amplify water solubility and prevent self-association. 1 H NMR spectroscopy, calorimetry (ITC), and mass spectrometry (ESI-MS) measurements validate the formation of an inclusion complex between 6 12− and anticancer drug methotrexate (MTX 2− ) in water ( K d =9.2 μM). To identify the docking pose, a comparison of computed (DFT and MM) and experimental 1 H NMR chemical shifts suggests that MTX 2− folds inside 6 12− (π⋅⋅⋅π), forming HBs with the peptidic dendrons while anchoring (C−H⋅⋅⋅π) to the aromatic pocket through its N-methyl group. In consequence, 6 12− selectively binds MTX 2− in competition with structurally similar folic acid and leucovorin (reversal poisoning agent). While the host is biocompatible (HEK293; IC 50 >150 μM) and produces inclusion complex [MTX⊂ 6 ] 14− in cell media, it experiences limitation in pharmacokinetic sequestration of MTX 2− as dihydrofolate reductase's affinity to the drug is suggested to prevail over that of 6 12− . Nonetheless, considering the basket's biocompatibility, tunability, and chemoselectivity, it stands as the leading candidate in the pursuit of an effective abiotic antidote for methotrexate poisoning.

Herein, we describe a metal‐free methodology using Selectfluor with disulfane, for the deoxygenation of N‐heterocyclic N‐oxides (33 examples). This effective, robust, and simple methodology enables the synthesis of various deoxygenated analogues from a wide range of N‐heterocyclic N‐oxide cores at room temperature in short reaction times with quantitative yields.

We describe the preparation and study of novel cavitands, molecular bowls 16+ and 26+, as good binders of the anticancer drug methotrexate (MTX). Molecular bowls are comprised of a curved tribenzotriquinacene (TBTQ) core conjugated to three macrocyclic pyridinium units at the top. The cavitands are easily accessible via two synthetic steps from hexabromo-tribenzotriquinacene in 25% yield. As amphiphilic molecules, bowls 16+ and 26+ self-associate in water by the nucleation-to-aggregation pathway (NMR). The bowls are preorganized, having a semi-rigid framework comprising a fixed bottom with a wobbling pyridinium rim (VT NMR and MD). Further studies, both experimental (NMR) and computational (DFT and MCMM), suggested that a folded MTX occupies the cavity of bowls wherein it forms pi-pi, C-H-pi, and ion pairing intermolecular contacts but also undergoes desolvation to give stable binary complexes (mu M) in water. Moreover, a computational protocol is introduced to identify docking pose(s) of MTX inside molecular bowls from NMR shielding data. Both molecular bowls have shown in vitro biocompatibility with liver and kidney cell lines (MTS assay). As bowl 26+ is the strongest binder of MTX reported to date, we envision it as an excellent candidate for further studies on the way toward developing an antidote capable of removing MTX from overdosed cancer patients. We describe synthesis, conformational dynamics and assembly characteristics of novel and tribenzotriquinacene-based hosts in water. These biocompatible molecules form stable inclusion complexes with toxic and anticancer drug methotrexate.

Protocols have been developed that allow easy access to 4-alkynylquinazolines under transition-metal-free conditions. The ring opening reaction of 4-(benzofuran-2-yl)quinazolines obtained from the arylation of quinazolines with benzofuran is the first way to achieve 4-alkynylquinazolines. Direct alkynylation of quinazolines with terminal alkynes in the presence of n-BuLi and iodine or with alkynyl Grignard reagents is another strategy. Desilylation of 4-((trimethylsilyl)ethynyl)quinazolines obtained by direct alkynation is the third approach to give 4-alkynylquinazolines. It has also been shown that the protocols are applicable for scale-up synthesis.

Abstract Transition-metal-free arylation reactions have attracted considerable attention for economic and environmental reasons over the past 40 years. In recent years, much effort has been made to develop efficient transition-metal-free approaches for the arylation of heteroarenes. Covering the literature from 2015 to early 2021, this review aims to provide a thorough overview of the synthetic and mechanistic aspects of these atom-economical and environmentally benign reactions. 1 Introduction 2 Arylation of Pre-functionalized Heteroarenes 2.1 Arylation of Heteroaryl Halides 2.2 Decarboxylative Arylation of Heteroarenes 3 Direct C–H Arylation of Heteroarenes 3.1 C(sp2)–H Arylation 3.2 C(sp3)–H Arylation 4 N-Arylation of Heteroarenes 5 Summary and Outlook

The transition metal-free coupling reactions of unactivated diazanaphthalenes were studied using only lithium tetramethylpiperidine (LiTMP) reagent. Symmetrical and nonsymmetrical bis-diazanaphthalenes were synthesized in moderate to high yield by homo- and cross-coupling of related monomers. In addition, the single-step synthesis of diquinoxalino [2,3-a: 2', 3'c] phenazine and 2,2': 3', 2 '' - terquinoxaline using the appropriate equivalent amount of LiTMP was performed. The products were characterized by means of NMR spectroscopy and HRMS spectrometry.

The transition metal‐free coupling reactions of unactivated diazanaphthalenes were studied using only lithium tetramethylpiperidine (LiTMP) reagent. Symmetrical and nonsymmetrical bis‐diazanaphthalenes were synthesized in moderate to high yield by homo‐ and cross‐coupling of related monomers. In addition, the single‐step synthesis of diquinoxalino [2,3‐a: 2', 3'c] phenazine and 2,2': 3', 2″ ‐ terquinoxaline using the appropriate equivalent amount of LiTMP was performed. The products were characterized by means of NMR spectroscopy and HRMS spectrometry.

A concise method for the construction of heteroaryl-fused phenazines was developed via PIFA-BF3·Et2O-mediated oxidative coupling of di-heteroarylated quinoxalines for the first time. Synthesis of mono- and di-heteroarylation of quinoxaline was performed effectively using only LiTMP reagent under transition metal-free conditions and without the use of halogen-containing starting compounds. In addition, nonsymmetrical di-heteroarylated quinoxalines were synthesized through reheteroarylation of mono-heteroarylated quinoxalines in the same way. Oxidation of the saturated compounds formed after heteroarylation was easily accomplished with iodine. The UV–vis absorption and fluorescence features of some compounds were examined.

The synthesis of brominated quinoxaline derivatives starting from several kinds of quinoxaline by different bromination strategies was studied. First the synthesis of some brominated quinoxalines was accomplished along with the development of an alternative and effective synthesis of some known compounds. A new, clean, and effective synthetic method for selective reduction of quinoxaline to 1,2,3,4-tetrahydroquinoxaline was also developed. The products obtained were characterized by means of NMR spectroscopy, elemental analyses, and mass spectrometry.