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The recently described crystalline cyclic (alkyl)(amino)carbene with a 1,1'‐ferrocenylene (fc) backbone fc(CPh2−C−NMes) (A, Mes=mesityl) is highly reactive due to its particularly pronounced ambiphilicity and is thermally not stable in solution due to an intramolecular insertion of the divalent carbon atom into a methyl C−H bond of the Mes substituent. The closely related congener fc(CPh2−C−N‐p‐C6H4‐tBu) (1) cannot undergo such an insertion reaction. Nevertheless, 1 is too short‐lived for isolation due to a rapid 1,2‐shift of a phenyl group, furnishing the isomeric cyclic enamine fc[C(Ph)=C(Ph)−N‐p‐C6H4‐tBu] (1') in a specific decomposition process unprecedented for CAACs. Trapping of 1 was possible with carbon monoxide, elemental selenium and with [CuBr(SMe2)], respectively affording the aminoketene 1=C=O, the selenoamide 1=Se and the homoleptic CuI complex [Cu(1)2][CuBr2]. 1 is an even stronger ambiphile than A according to NMR spectroscopic data. Similar to A, 1 does not react with H2, because the experimentally observed intramolecular process is kinetically more favourable according to DFT results. [ABSTRACT FROM AUTHOR]

Background and Aims: Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the intrahepatic (iCCA) or extrahepatic (eCCA) bile ducts with poor prognosis and limited treatment options. Prior evidence highlighted a significant contribution of the non‐canonical NF‐κB signalling pathway in initiation and aggressiveness of different tumour types. Lymphotoxin‐β (LTβ) stimulates the NF‐κB‐inducing kinase (NIK), resulting in the activation of the transcription factor RelB. However, the functional contribution of the non‐canonical NF‐κB signalling pathway via the LTβ/NIK/RelB axis in CCA carcinogenesis and progression has not been established. Methods: Human CCA‐derived cell lines and organoids were examined to determine the expression of NF‐κB pathway components upon activation or inhibition. Proliferation and cell death were analysed using real‐time impedance measurement and flow cytometry. Immunoblot, qRT‐PCR, RNA sequencing and in situ hybridization were employed to analyse gene and protein expression. Four in vivo models of iCCA were used to probe the activation and regulation of the non‐canonical NF‐κB pathway. Results: Exposure to LTα1/β2 activates the LTβ/NIK/RelB axis and promotes proliferation in CCA. Inhibition of NIK with the small molecule inhibitor B022 efficiently suppresses RelB expression in patient‐derived CCA organoids and nuclear co‐translocation of RelB and p52 stimulated by LTα1/β2 in CCA cell lines. In murine CCA, RelB expression is significantly increased and LTβ is the predominant ligand of the non‐canonical NF‐κB signalling pathway. Conclusions: Our study confirms that the non‐canonical NF‐κB axis LTβ/NIK/RelB drives cholangiocarcinogenesis and represents a candidate therapeutic target. [ABSTRACT FROM AUTHOR]

The 1,1'-diaminoferrocene derivatives [Fe(η5- C5H4-NHAd)2] (Ad = 2-adamantyl) and [Fe(η5-C5H4- NHtBu)2] were investigated in terms of their suitability for the synthesis of N-heterocyclic tetrylenes of the type [{Fe(η5-C5H4)NR)2}E] (E = Ge, Sn). The synthesis of these target compounds was easily achieved with R = tBu, but failed with R = Ad. In the latter case, the stannylene was not sufficiently stable for isolation and decomposed to the aminoiminoferrocene derivative [Fe(η5-C5H4-NHAd) (η5-C5H4-N = Ad')] (Ad' = adamant-2-ylidene). Attempts to synthesise [{Fe(η5-C5H4-NAd)2}Ge] afforded intractable material, from which the unusual compound [μ2-{Fe(η5-C5H4-NAd)2}Ge2(μ3-O)(GeCl2)] was obtained by serendipity. It contains GeO, stabilised by adduct formation with GeCl2 and the target germylene. [Fe(η5-C5H4-NHtBu)2], [Fe(η5-C5H4-NHAd)2], [Fe(η5-C5H4-NHAd)(η5-C5H4-N = Ad')], [μ2-{Fe(η5-C5H4-NAd)2}Ge2(μ3-O)(GeCl2)] and [{Fe(η5-C5H4- NtBu)2}E] (E = Ge, Sn) were structurally characterised by single-crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]