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The reaction of 1,3,5-[([.sup.i][Pr.sub.2]]PO).sub.3][C.sub.6]H3 with [Co.sub.2][(CO).sub.8] leads to the isolation of a POCOP-type mononuclear pincer complex {[K.sup.P],[K.sup.C],[K.sup.P]-2,4,6-[([.sup.i][Pr.sub.2]]PO).sub.3]C6[H.sub.2]}Co[(CO).sub.2] [(1) or a tetranuclear species {[K.sup.P]-{[K.sup.P],[K.sup.C],[K.sup.P]-2,4,6-[([.sup.i][Pr.sub.2]]PO).sub.3][C.sub.6][H.sub.2]}Co[(CO).sub.2]}.sub.2][Co.sub.2][(CO).sub.6] (2), depending on the ligand to cobalt ratio employed. The latter compound can be an impurity during the synthesis of {2,6-[([.sup.i][Pr.sub.2]]PO).sub.2]-4-[Me.sub.2]N-[C.sub.6][H.sub.2]}Co[(CO).sub.2], when the ligand precursor 5-(dimethylamino)resorcinol is contaminated with phloroglucinol due to incomplete monoamination. Similarly, the reaction of 1,3,5-[( [.sup.i][Pr.sub.2]]PO).sub.3]C6H3 with [NiCl.sub.2] in the presence of 4-dimethylaminopyridine provides {[K.sup.P],[K.sup.C],[K.sup.P]-2,4,6-[([.sup.i][Pr.sub.2]]PO).sub.3][C.sub.6][H.sub.2]}NiCl (3) bearing an appended phosphinite group. Structures 1-3 have been studied by X-ray crystallography. Key words: phosphinite, pincer complexes, C-H activation, appended functionality, catalyst immobilization. La reaction du 1,3,5-[([.sup.i][Pr.sub.2]PO).sub.3][C.sub.6][H.sub.3] avec le [Co.sub.2][(CO).sub.8] permet d'isoler le complexe de ligand pince mononucleaire de type POCOP{[K.sup.P],[K.sup.C],[K.sup.P]-2,4,6-[([.sup.i][Pr.sub.2]PO)3[C.sub.6][H.sub.2]}Co(CO).sub.2] [(1)oul'especetetranucleaire[{[K.sup.P]-{[K.sup.P],[K.sup.C],[K.sup.P]-2,4,6-([.sup.i][Pr.sub.2]PO)3[C.sub.6][H.sub.2]}Co(CO).sub.2]}.sub.2][Co.sub.2][(CO).sub.6](2), selon le rapport ligand-cobalt utilise. Cette derniere espece peut etre une impurete issue de la synthese du {2,6-[([.sup.i][Pr.sub.2]]PO).sub.2]-4-[Me.sub.2]N-[C.sub.6][H.sub.2]}Co[(CO).sub.2], lorsque le precurseur de ligand 5-(dimethylamino)resorcinol est contamine par du phloroglucinol en raison d'une monoamination incomplete. De maniere similaire, la reaction du 1,3,5-[([.sup.i][Pr.sub.2]PO).sub.3][C.sub.6][H.sub.3] avec le [NiCl.sub.2] en presence de 4-dimethylaminopyridine produit le {[K.sup.P],[K.sup.C],[K.sup.P]-2,4,6-([.sup.i][Pr.sub.2]PO)3[C.sub.6][H.sub.2]}NiCl (3) portant un groupe phosphinite attache. Nous avons etudie les structures 1-3 par radiocristallographie. [Traduit par la Redaction] Mots-cles : phosphinite, complexes de ligands pinces, activation de liaison C-H, groupe fonctionnel attache, immobilisation du catalyseur., Introduction Diphosphinite-derived POCOP-type pincer complexes have been studied extensively as homogeneous catalysts for a wide variety of organic transformations (.1-11) To facilitate catalyst-product separation and catalyst recycling, (12), (13) Lewis [...]

Targeting ferroptosis has attracted exponential attention to eradicate cancer cells with high iron‐dependent growth. Increasing the level of intracellular labile iron pool via small molecules and iron‐containing nanomaterials is an effective approach to induce ferroptosis but often faces insufficient efficacy due to the fast drug metabolism and toxicity issues on normal tissues. Therefore, developing a long‐acting and selective approach to regulate ferroptosis is highly demanded in cancer treatment. Herein, a lysosome‐targeted magnetic nanotorquer (T7‐MNT) is proposed as the mechanical tool to dynamically induce the endogenous Fe2+ pool outbreak for ferroptosis of breast cancer. T7‐MNTs target lysosomes via the transferrin receptor‐mediated endocytosis in breast cancer cells. Under the programmed rotating magnetic field, T7‐MNTs generate torques to trigger endogenous Fe2+ release by disrupting the lysosomal membrane. This magneto‐mechanical manipulation can induce oxidative damage and antioxidant defense imbalance to boost frequency‐ and time‐dependent lipid peroxidization. Importantly, in vivo studies show that T7‐MNTs can efficiently trigger ferroptosis under the magnetic field and play as a long‐acting physical inducer to boost ferrotherapy efficacy in combination with RSL3. It is anticipated that this dynamic targeted strategy can be coupled with current ferroptosis inducers to achieve enhanced efficacy and inspire the design of mechanical‐based ferroptosis inducers for cancer treatment. [ABSTRACT FROM AUTHOR]

Lysosomes play a central role in biochemical signal transduction and oxidative stress in cells. Inducing lysosome membrane penetration (LMP) to cause lysosomal‐dependent cell death (LCD) in tumor cells is an effective strategy for cancer therapy. Chemical drugs can destroy the stability of lysosomes by neutralizing protons within the lysosomes or enhancing the fragility of the lysosomal membranes. However, there remain several unsolved problems of traditional drugs in LMP induction due to insufficient lysosomal targeting, fast metabolism, and toxicity in normal cells. With the development of nanotechnology, magnetic nanoparticles have been demonstrated to target lysosomes naturally, providing a versatile tool for lysosomal modulation. Combined with excellent tissue penetration and spatiotemporal manipulability of magnetic fields, magnetic modulation of lysosomes progresses rapidly in inducing LMP and LCD for cancer therapy. This review comprehensively discussed the strategies of magnetic modulation of lysosomes for cancer therapy. The intrinsic mechanisms of LMP‐induced LCD were first introduced. Then, the modulation of lysosomes by diverse physical outputs of magnetic fields was emphatically discussed. Looking forward, this review will shed the light on the prospect of magnetic modulation of lysosomes, inspiring future research of magnetic modulation strategy in cancer therapy. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseNanotechnology Approaches to Biology > Nanoscale Systems in Biology [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Limited data exist on the characteristics of atypical epidermal growth factor receptor (EGFR) mutations in early-stage lung cancer. Our goal was to elucidate the associations with outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical EGFR mutations. METHODS Eligible patients between 2014 and 2019 were retrospectively identified and grouped into exon20 insertion mutations and major atypical mutations, which included G719X, L861Q and S768I. Disease-free survival (DFS) was evaluated in the entire cohort and stratified by radiologic characteristics. Recurrence patterns were investigated and compared between groups. A competing risk model was used to estimate the cumulative incidence of recurrence. RESULTS A total of 710 patients were finally included. Among them, 289 (40.7%) patients had exon 20 insertion mutations and 421 (59.3%) patients had major atypical mutations. There was no significant difference regarding DFS (P  = 0.142) between groups in the entire cohort. The interaction between mutation subtype and the presence of ground-glass opacities was significant (hazard ratio 2.00, 95% confidence interval 1.59–2.51, P  < 0.001), indicating DFS between exon 20 insertion mutations and major atypical mutations may be different among subsolid and solid tumours. Survival analysis consistently revealed no significant difference in subsolid tumours (P  = 0.680), but favourable DFS of exon 20 insertion mutations in solid tumours (P  = 0.037). Furthermore, patients with exon 20 insertion mutations had a lower risk of developing bone metastases did those with radiologic solid tumours (Gray's test, P  = 0.012). CONCLUSIONS Exon 20 insertion mutations were correlated with favourable DFS and lower incidence of bone metastases in radiologic solid lung adenocarcinomas harbouring atypical EGFR mutations. [ABSTRACT FROM AUTHOR]