The ferrocenyl groups are linked by C—H⋯π(ring) interactions.The unsubstituted cyclopentadienyl ring is rotationally disordered while the other Cp ring and its substituent are close to coplanar. In the crystal, the molecules pack in ‘bilayers’ parallel to the  5H5)(C18H13ClN)], is nearly coplanar with the phenyl-1-(4-chlorophenyl)methanimine substituent, with dihedral angles between the planes of the phenylene ring and the Cp and 4-(chlorophenyl)methanimine units of 7.87 (19) and 9.23 (10)°, respectively. The unsubstituted cyclopentadienyl ring is rotationally disordered, the occupancy ratio for the two orientations refined to a 0.666 (7)/0.334 (7) ratio. In the crystal, the molecules pack in ‘bilayers’ parallel to the ab plane with the ferrocenyl groups on the outer faces and the substituents directed towards the regions between them. The ferrocenyl groups are linked by C—H⋯π(ring) interactions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (46.1%), H⋯C/C⋯ H (35.4%) and H⋯Cl/Cl⋯H (13.8%) interactions. Thus C—H⋯π(ring) and van der Waals interactions are the dominant interactions in the crystal packing.The substituted cyclopentadienyl ring in the title molecule, [Fe(C They are, however, rotated along their long axis with respect to each other, and despite their nearly coplanar nature that predestines them for π-stacking interactions, no such interactions are observed in the solid state. Indeed, directional interactions are sparse in the structure of the title compound. Ferrocenyl groups are tied together by C—H⋯π interactions, facilitated by neighboring ferrocene units within each layer being roughly 90° rotated against each other. Cp-H atoms thus point towards the π-system of neighboring Cp rings. The shortest C—H⋯π interactions are between H5 and H7 towards the C atoms C7 and C10 of the substituted Cp ring at −x + y + z , and between H3 and H10 towards C atoms C4 and C3 at −x + y − z . The shortest C—H centroid interaction is for C7—H7⋯Cg2 . Also present is a C22—H22⋯Cg5 interaction  and a weak C4—H4⋯Cl1 hydrogen bond , C⋯N/N⋯C  and Cl⋯Cl contacts  have only 0.5%, 0.2% and 0.1% contributions.In order to visualize the intermolecular interactions in the crystal of the title compound, a Hirshfeld surface (HS) analysis  found three closely related, ferrocene-substituted Schiff base compounds:  . In a 250 mL round-bottom flask, 1.0 mmol of 4-ferrocenyl aniline in 15 mL of dried methanol was mixed with an equimolar amount of 4-chlorophenyl aldehyde in 15 mL of dried methanol. The mixture was agitated under reflux, the progress of the reaction was monitored by TLC, and the desired product was formed within 6 h. The solvent was removed under vacuum and the solid that was obtained was recrystallized from methanol (yield: 87%) to yield brown crystals, m.p. 210 K. 1H NMR  δ 4.08 ; 4.36  ; 4.68 ; 7.20 ; 7.48 ; 7.53 ; 7.88  ; 8.52 . 13C NMR  δ 66.42 ; 69.05 ; 69,64 ; 84.80 ; 121.10 ; 126.76 ; 129.09 ; 129.87 ; 134.92 ; 137.20 ; 137.72 ; 149.21  ; 157.62 .4-Ferrocenyl aniline was synthesized according to a reported procedure (Hu I/σ(I) > 15 and chosen from the full data set with CELL_NOW  with a second component (14%) rotated 180° about the b axis. To eliminate possible bias, the raw data were processed as triclinic using the multi-component version of SAINT . The data were corrected for absorption using TWINABS . ADPs of equivalent major and minor disordered C atoms were constrained to be identical. The occupancy ratio for the two orientations refined to a 0.666 (7)/0.334 (7) ratio.H atoms attached to carbon were placed in calculated positions (C—H = 0.95–1.00 Å). All were included as riding contributions with isotropic displacement parameters 1.2–1.5 times those of the parent atoms. The unsubstituted cyclopentadienyl ring is rotationally disordered over two sets of sites with the two components refined as rigid pentagons  I, global. DOI: 10.1107/S2056989021008033/zl5016Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989021008033/zl5016Isup3.cdxSupporting information file. DOI: 2101472CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Scientific Reports 10.1038/s41598-021-85236-z, published online 02 April 2021Correction to: P values.The original version of this Article contained an error in the legend of Figure 4, where the minus sign was missing in the A) Densities of Alpha  for low-stimulus and high-stimulus groups shows 1.23 × difference in means with P < 2.9E04 (K–S test). (B) Densities for Ea  shows 4.8 × difference in means with P < 3.9E05 (K–S test). (C) Densities for CV_Alpha shows 3.5 × difference in means with P < 5.8E04 (K–S test). (D) Densities for Theta/Beta ratio shows 1.13 × difference in means . (E) Densities for Complexity shows 1.17 × difference in means with P < 7.5E05 (K–S test). (F) Average power spectrums of low- and high- stimulus groups. Error bars: average spatial variability across individuals.”“Differences between low-stimulus and high-stimulus groups. (now reads:A) Densities of Alpha  for low-stimulus and high-stimulus groups shows 1.23 × difference in means with P < 2.9E-04 (K–S test). (B) Densities for Ea  shows 4.8 × difference in means with P < 3.9E-05 (K–S test). (C) Densities for CV_Alpha shows 3.5 × difference in means with P < 5.8E-04 (K–S test). (D) Densities for Theta/Beta ratio shows 1.13 × difference in means . (E) Densities for Complexity shows 1.17 × difference in means with P < 7.5E-05 (K–S test). (F) Average power spectrums of low- and high- stimulus groups. Error bars: average spatial variability across individuals.”“Differences between low-stimulus and high-stimulus groups. (The original Article has been corrected.


An unusual and labile spirocyclic tetrahedral intermediate (72+) is observed in CO2‐pressurized (0.5–2.0 bar) solutions of cation 4+ at low temperatures, as demonstrated by variable‐temperature NMR studies, which were confirmed crystallographically. In addition, cations 3+ and 4+ actively bind carbonyls, nitriles and acetylenes by 1,3‐dipolar cycloaddition, as shown by selected examples.Electrophilic fluorophosphonium triflates bearing pyridyl ( Extending the FLP library: Electrophilic fluorophosphonium triflates bearing pyridyl or imidazolyl substituents act as intramolecular N/P frustrated Lewis pairs that are capable of small molecule activation, that is, reversible CO2 sequestration and binding of carbonyls, nitriles and acetylenes. The corresponding 31P and 19F NMR spectra of the solution containing 3[OTf] reveal no interaction or reaction at ambient temperature indicated by the resonances for cation 3+ (δ(31P)=54.8 ppm, δ(19F)=−114.0 ppm, 1JPF=996 Hz) in the spectra. However, a VT NMR investigation disclosed the reversible and temperature‐dependent binding of CO2 by 3[OTf] , a small high field shifted doublet resonance at δ(31P)=−55.5 ppm , which is well in the region for a penta‐coordinate phosphorus atom, thus, indicating the formation of the CO2 adduct 5[OTf]. The corresponding resonance in the 19F NMR spectrum is detected as a downfield shifted doublet resonance at δ(19F)=−30.0 ppm. When the temperature is further decreased to 213 K the integral ratio of 5[OTf] increases to 41 : 59. The carbon atom of the bound CO2 is observed as a doublet resonance at δ(13C)=141.8 ppm (2JPC=3 Hz). Further decrease of the temperature to 193 K leads to the separation of a colorless precipitate, suggesting that 5[OTf] exhibits a reduced solubility in CD2Cl2 at low temperature. Accordingly, gradually increase to RT leads to the dissolution of 5[OTf] and its disappearance in the NMR spectrum. This process is reversible without decomposition of 3[OTf]. We investigate this interaction of 3[OTf] with CO2 theoretically with two different models  than model 3+‐2CO_B (−18.4 kJ/mol). Moreover, the calculated 31P NMR chemical shift change (Δδ=δ(3+‐2CO_A)−δ(3+)) for model 3+‐2CO_A (Δδ(31P)=−124 ppm) is in the range of the experimental result (Δδ(31P)=−110.7 ppm), while the calculated Δδ(31P) for model 3+‐2CO_B is only shifted by −17 ppm which is not observed in the respective 31P NMR spectrum. Thus, the CO2 activation is proposed to proceed via the P and pyridyl N atoms, affording 5[OTf] in the configuration of model 3+‐2CO_A. As the DFT calculation reveals a slightly improved CO2 binding energy (−23.0 kJ/mol) for 4[OTf], we also investigated the reactivity of 4[OTf] towards CO2  at ambient temperature results in the immediate formation of a colorless solid. However, the solid re‐dissolves immediately after releasing the pressure and all our separation attempts ended up with the recovery of 4[OTf]. We therefore monitored the reaction of 4[OTf] with CO2 (1.5 bar) by NMR spectroscopy in degassed CD3NO2. The 31P NMR spectrum at ambient temperature shows signals of two different adducts at δ(31P)=−60.0 ppm  and δ(31P)=−61.5 ppm  besides the signal of 4[OTf] (δ(31P)=55.2 ppm, δ(19F)=−111.5 ppm, 1JPF=1045 Hz, Figure 19F spectrum are detected at δ(19F)=−8.1 ppm (1JFP=737 Hz) and δ(19F)=−16.9 ppm (1JFP=740 Hz), respectively. Interestingly, the 13C NMR spectrum displays two signals for the bound CO2 moiety at δ(13C)=139.9 ppm (2JPC=7 Hz) as a doublet resonance and at δ(13C)=105.5 ppm (2JPC=8 Hz) as a triplet resonance suggesting a coupling to two phosphorus atoms.13 This strongly indicates the formation of a 1 : 1 FLP‐CO2 adduct 6[OTf] (δ(31P)=−61.5 ppm, δ(19F)=−16.9 ppm, 1JPF=740 Hz) and a 2 : 1 FLP‐CO2 adduct 7[OTf]2 (δ(31P)=−60.0 ppm, δ(19F)=−8.1 ppm, 1JPF=737 Hz). The 31P NMR chemical shift change of 6[OTf] (Δδ=δ(6+)−δ(4+), −116.7 ppm) is well in the range of calculated model 4+‐2CO_A (Δδ(31P)=−108 ppm). Decreasing the temperature stepwise to 243 K, the integral ratio of 7[OTf]2 gradually increases to 66 %, while the integral ratio of 6[OTf] increases to 28 %. Variable‐temperature NMR studies at 0.5 or 2.0 bar CO2 pressure did not show significant difference on the integral ratio of 6[OTf] and 7[OTf]2. Although the calculated electrophilicities are similar for 3[OTf]  and 4[OTf] ,2 with 3[OTf]. This suggests that a certain nucleophilicity of the Lewis basic site is crucial for the formation of the 2 : 1 FLP‐CO2 adduct 7[OTf]2.The 6+ and 72+ by vapor diffusion of CH2Cl2 into a CH3NO2 solution of 4[OTf] under CO2 atmosphere (0.5 bar) at −30 °C  and aluminum (VII) complexes °. One oxygen is bound by the Lewis acidic P atom with a P1−O1 bond length of 1.773(5) Å and the carbon atom is stabilized by the Lewis basic N atom to give a N1−C1 bond length of 1.442(10) Å. The C1−O1 (1.307(8) Å) and C1=O2 (1.206(10) Å) bonds in the CO2 fragment are comparable to other FLP‐CO2 adducts . (+9 a/+9 b: δ(31P)=−49.3/−65.0 ppm, δ(19F)=3.0/19.9 ppm, 1JPF=738/702 Hz, 71 and 95 % isolated yield) are indicated by multinuclear NMR spectroscopy =101.8/96.7 ppm, 2JCP=9/11 Hz) are significantly shifted to higher field compared to the free acetone (δ(13C)=207 ppm).9 a,b[OTf] are shifted to lower field (9 a+/9 b+: δ(13C)=151.0/150.2 ppm, 2JCP=18/19 Hz). Interestingly, when compounds 9 a, b[OTf] are reacted with acetone at room temperature, the formation of 8 a, b[OTf] under release of CH3CN is observed after a reaction time of 1 h  at room temperature for 4 h, the formation of 10 a, b and 11 a, b[OTf]2 is observed, while 12 a, b[OTf] are cleanly formed by fluoride abstraction from 10 a, b to 11 a, b2+ after reacting at 80 °C overnight or at ambient temperature for 2 weeks  is more Lewis acidic than 3+ , thus, low reaction tendency from 11 a, b+ to 12 a, b+ seems to be influenced by solvent effects, which significantly decrease the Lewis acidity compared to the gas phase calculations.2 are found as singlet resonances in the 1P NMR spectra at δ(31P)=6.9 and −15.0 ppm, while 12 a, b[OTf] are observed as doublet resonances in the 31P and 19F NMR spectra (12 a+/12 b+: δ(31P)=−88.8/−98.8 ppm, δ(19F)=34.0/25.2 ppm, 1JPF=707/718 Hz, Table 11 a[OTf]212 b[OTf] (66 %) as pure products for full characterization.When s Scheme , iii–v. 8 a, b[OTf], 9 a, b[OTf] and 12 b[OTf] are confirmed by X‐ray analysis of suitable single crystals which were obtained by slow vapor diffusion of n‐pentane into saturated CH2Cl2 solutions at −30 °C  and the fluorine atoms occupy the axial position. The P−F bonds (1.637(2) −1.673(13) Å) are elongated compared to those of the starting materials 3+ and 4+, but comparable to those in difluorophosphoranes 3PF2: 1.638(2) Å).8 a+/8 b+: 1.695(2)/1.695(3) Å) are significantly shorter compared to the acetonitrile adducts (9 a+/9 b+: 1.777(2)/1.788(2) Å) while the C−N bonds are around 0.15 Å longer (8 a+/8 b+: 1.495(4) Å/1.411(5) Å, 9 a+/9 b+: 1.250(3)/1.272(3) Å, Table The molecular structures of compounds C Figure . All obt8 a+/8 b+: 1.495(4)/1.411(5) Å and the C−N distances of the nitrile moiety (9 a+/9 b+: 1.250(3)/1.272(3) Å) are typical for C−O single bonds and C=N double bonds, respectively.12 b+ shows that the pyridyl moiety is in the axial position, opposite to the fluorine atom , 2061971 (for 2[OTf]), 2061972 (for 3[OTf] ⋅ C6H5F), 2061973 (for 6[OTf] ⋅ 7[OTf]2 ⋅ CH3NO2), 2061974 (for 8 a[OTf] ⋅ CH2Cl2), 2061975 (for 8 b[OTf] ⋅ CH2Cl2), 2061976 (for 9 a[OTf] ⋅ (CH2Cl2)2 ⋅ CH3CN), 2061977 (for 9 b[OTf]), 2061978 (for 13), 2061979 (for 12b[OTf]), and 2061980 (for 14)2061970  or imidazolyl (4[OTf]) substituents, thus an additional Lewis basic site, represent a new type of intramolecular FLP that reacts with small molecules in a cooperative manner. The cyclizations of 3[OTf] and 4[OTf] with the 1,2‐dipolar compounds acetone, acetonitrile and acetylenes gave rise to the formation of the corresponding heterocyclic compounds, thus illustrating the cooperative reactivity of the new FLP derivatives. This is additionally demonstrated by the reversible formation of adducts with CO2 (5+ and 6+) at low temperature, which was investigated by variable‐temperature NMR studies and X‐ray analysis. Surprisingly, the bifunctional phosphonium cation 4+ forms an adduct with CO2 (72+) comprising one molecule of CO2 and two molecules of 4+, resulting in a spirocyclic geometry at the central carbon atom, which is hitherto unreported for an N/P FLP system. These novel bifunctional phosphonium cations extend the diverse library of FLP systems, and the reversible CO2 adduct formation might provide new applications for in FLP chemistry, which we are currently investigating.In summary, electrophilic fluorophosphonium compounds bearing pyridyl  should be addressed to the authors.Supporting InformationClick here for additional data file.


In the crystal, chains parallel to the c axis are generated by intermolecular N—H⋯O hydrogen bonds with the chains assembled into a three-dimensional network structure by intermolecular C—H⋯O hydrogen bonds and C—H⋯π(ring) interactions. The molecule of (II), C22H21N3O, differs from (I) only in the substituent at the hydrazide N atom where a phenylmethylene moiety for (II) is present instead of a furanmethylene moiety for (I). Hence, molecules of (I) and (II) show similarities in their molecular and crystal structures. The conformation of the central portion of the molecule of (II) is also therefore partially determined by an intramolecular N—H⋯O hydrogen bond and intermolecular N—H⋯O hydrogen bonds form chains parallel to the c axis. Likewise, the chains are connected into a three-dimensional network by C—H⋯O hydrogen bonds and C—H⋯π(ring) interactions.The conformation about the central benzene ring in the molecule of (I), C These cs Table 1.c-axis direction n Table 2, which ak Table 2.et al., 2016N′-methylidenebenzohydrazide skeleton: N′-[(4-chlorophenyl)methylidene]-2-[amino]benzohydrazide ethylidene]-2-[amino]benzohydrazide benzohydrazide benzohydrazide -2-[amino]-N′-(2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-ylidene)benzohydrazide °. These rings make dihedral angles of 47.79 (8) and 69.24 (9)°, respectively, with the central benzene ring. In the crystal structure of VEDBAK, molecules are linked into a three-dimensional supramolecular network by N—H⋯O, C—H⋯O hydrogen bonds and weak C—H⋯π interactions.In the crystal structure of LEBSET, molecules are linked into a three-dimensional supramolecular network by N—H⋯N, N—H⋯O, C—H⋯O hydrogen bonds and weak C—H⋯π interactions.A and B) having differing conformations that mainly concern the dihedral angles between the hydroxyphenyl and dimethylphenyl rings relative to the central phenylene ring, with values of 30.16 (6) and 58.60 (6)° in molecule A and of 13.42 (7) and 60.31 (7)° in molecule B. With the exception of the dimethylphenyl substituent, the conformations of the rest of each molecule are largely determined by intramolecular O—H⋯N and N—H⋯O hydrogen bonds. In the crystal structure, N—H⋯O hydrogen bonds link the molecules into chains extending parallel to the a axis where the types of molecules alternate in an ⋯A⋯B⋯A⋯B⋯ fashion.The asymmetric unit of DABREG consists of two molecules (S(6) ring motif. In the crystal structure of LEGHAI, molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds to the same acceptor atom, forming sheets lying parallel to the bc plane. The crystal packing also features C—H⋯π interactions.In LEGHAI, the central benzene ring makes dihedral angles of 45.36 (9) and 55.33 (9)° with the thiophene ring and the dimethyl-substituted benzene ring, respectively. The dihedral angle between the thiophene ring and dimethyl-substituted benzene ring is 83.60 (9)°. The thiophene ring and the benzene ring are twisted from the mean plane of the C(=O)—N—N=C bridge [maximum deviation = 0.0860 (13) Å], with dihedral angles of 23.86 (9) and 24.77 (8)°, respectively. An intramolecular N—H⋯O hydrogen bond generates an S(6) ring motif in the molecule, and a short intramolecular contact (H⋯H = 1.88 Å) is also observed. In the crystal structure of LEGHIQ, molecules are linked by pairs of N—H⋯N hydrogen bonds into inversion dimers. The crystal packing also features C—H⋯π interactions.In LEGHIQ, the dihedral angle between the benzene rings is 58.05 (9)°. The non-H atoms of the hydrazide group lie in a common plane (r.m.s. deviation = 0.0006 Å) and are close to co-planar with their attached benzene ring [dihedral angle = 8.02 (9)°]. An intramolecular N—H⋯O hydrogen bond generates an via N—H⋯O and weak C—H⋯O hydrogen bonds, forming chains along the a-axis direction. In each molecule, there is an intramolecular N—H⋯O hydrogen bond.The asymmetric unit of the compound YAXJUE comprises two molecules. The dihedral angles between the benzene rings in the two molecules are 59.7 (2) and 61.27 (18)°. The cyclohexene rings adopt sofa and half-chair conformations. In the crystal structure of YAXJUE, molecules are connected Synthesis of (I) A mixture of 1 mmol of 2-furaldehyde (96 mg) and 1 mmol of 2-[amino]benzohydrazide (255 mg) in 20 ml of ethanol was refluxed and monitored by TLC until completion. The reaction mixture was cooled to room temperature when the solid product was obtained. The crude product was filtered off, dried and recrystallized from ethanol to afford crystals suitable for X-ray diffraction. M.p. 479–483 K.Synthesis of (II) In a solution of 20 ml of ethanol, a mixture of 106 mg (1 mmol) of benzaldehyde (106 mg) and 255 mg (1 mmol) of 2-[amino]benzohydrazide was refluxed for 4 h. The solid product was obtained after the reaction mixture was cooled to room temperature. The crude product was filtered off, dried and recrystallized from ethanol to afford crystals suitable for X-ray diffraction. M.p. 466–469 K.Crystal data, data collection and structure refinement details are summarized in Table 310.1107/S2056989021001353/wm5599sup1.cifCrystal structure: contains datablock(s) global, I, II. DOI: 10.1107/S2056989021001353/wm5599Isup2.hklStructure factors: contains datablock(s) I. DOI: 10.1107/S2056989021001353/wm5599IIsup3.hklStructure factors: contains datablock(s) II. DOI: Click here for additional data file.10.1107/S2056989021001353/wm5599Isup4.cmlSupporting information file. DOI: Click here for additional data file.10.1107/S2056989021001353/wm5599IIsup5.cmlSupporting information file. DOI: 2061393, 2061392CCDC references:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


The -2,2′-{[bis[(azaniumylylidene)methanylylidene]}bis(6-methoxyphenolate) ligand, obtained from o-vanillin and -(−)-1,2-diphenylethylenediamine, exhibits a slightly distorted planar arrangement of the four coordinated O atoms. In the crystal, the complex shows intramolecular N—H⋯O hydrogen bonds and weak intermolecular C—H⋯O hydrogen bonds. The Hirshfeld surface analysis indicates that the most important contributions to the packing are from H⋯H (33.5%), O⋯H (34.1%) and C⋯H (21.7%) contacts.In the title complex, [Sm(NO The bond lengths between the metal center and the nitrate oxygen atoms range from 2.475 (5) to 2.633 (5) Å, showing more flexibility than those of the Schiff base ligand. In the Schiff base ligand, the imine moieties are protonated to form iminium cations, but the C=N bond lengths remain close to those of normal imine bonds at 1.287 (8) and 1.30 (1) Å.et al., 2013Intramolecular hydrogen bonds occur between the iminium protons and the phenolic oxygen atoms, with lengths of 1.71–1.89 Å Table 1. The bonet al., 2009et al., 2004CrystalExplorer17.5 -3-(methoxy)phenyl]methaniminiumato})tris(nitrato)samarium -{μ-}bis[6-(methoxy)phenolato]]}trinitratoeuropium(III)nickel(II) -(−)-1,2-Diphenylethylenediamine  and o-vanillin  were dissolved in ethanol (30 mL) and the resulting mixture was stirred at 313 K for 1 h to afford a yellow solution. To this solution, samarium nitrate hexahydrate  was added and it was stirred at 313 K for 2 h. A yellow precipitate appeared immediately. The precipitate was filtered and washed with ethanol and hexane. The title compound  was obtained as a yellow solid. IR  : 1624 (C=N double bond). Fluorescence bands in methanol solution were observed at 562 (4G5/2 → 6H5/2), 597 (4G5/2 → 6H7/2) and 644 (4G5/2 → 6H 9/2) nm. Single crystals suitable for X-ray diffraction were obtained by recrystallization from methanol and diethyl ether  solution.(1Uiso(H) = 1.2Ueq(C) or 1.5Ueq(C-methyl). SIMU, ISOR and AFIX 66 commands were used for C55, C56, C57, C58, C59, C60 to suppress temperature anisotropy and restrain bond lengths to appropriate values.Crystal data, data collection and structure refinement details are summarized in Table 210.1107/S2056989021004424/tx2039sup1.cifCrystal structure: contains datablock(s) 1R, I. DOI: 10.1107/S2056989021004424/tx2039Isup2.hklStructure factors: contains datablock(s) I. DOI: 2080014CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Scientific Reports 10.1038/s41598-020-72306-x, published online 17 September 2020Correction to: The original version of this Article contained an error.The p value stated in the text for differences in fasting blood sugar, between non-overweight and obese groups, was incorrect. The text,“There was no statistically significant difference in the level of ALT (98.9 ± 34.6 vs. 96.3 ± 24.1 p = 0.76), serum vitamin B12 (559 ± 417.1 vs. 433 ± 185.4 p = 0.18), fasting blood sugar  or the serum homocysteine levels (13.2 ± 4.0 vs. 14.04 + 1.80 p = 0.49) between the non-overweight and obese groups.”now reads,“There was no statistically significant difference in the level of ALT (98.9 ± 34.6 vs. 96.3 ± 24.1 p = 0.76), serum vitamin B12 (559 ± 417.1 vs. 433 ± 185.4 p = 0.18) or the serum homocysteine levels (13.2 ± 4.0 vs. 14.04 + 1.80 p = 0.49) between the non-overweight and obese groups. Though the fasting blood sugar  was significantly different, there was only one patient whose fasting blood sugar placed them within range of a diabetes mellitus diagnosis .”This has been corrected in the PDF and HTML versions of the Article.


Thereby, each signal alone only induces a moderate production of pro‐inflammatory cytokines and lipid mediators (LMs). However, MCs, which simultaneously sense (co‐sensing) IL‐33 and ATP, display an enhanced and prolonged activation of the TAK1‐IKK2‐NF‐κB signalling pathway. This resulted in a massive production of pro‐inflammatory cytokines such as IL‐2, IL‐4, IL‐6 and GM‐CSF as well as of arachidonic acid‐derived cyclooxygenase (COX)‐mediated pro‐inflammatory prostaglandins (PGs) and thromboxanes (TXs), hallmarks of strong MC activation. Collectively, these data show that co‐sensing of ATP and IL‐33 results in hyperactivation of MCs, which resembles to MC activation induced by IgE‐mediated crosslinking of the FcεRI. Therefore, the IL‐33/IL‐33R and/or the ATP/P2X7 signalling axis are attractive targets for therapeutical intervention of diseases associated with the loss of integrity of cellular barriers such as allergic and infectious respiratory reactions.IL‐33 and ATP are alarmins, which are released upon damage of cellular barriers or are actively secreted upon cell stress. Due to high‐density expression of the IL‐33 receptor T1/ST2 (IL‐33R), and the ATP receptor P2X7, mast cells (MCs) are one of the first highly sensitive sentinels recognizing released IL‐33 or ATP in damaged peripheral tissues. Whereas IL‐33 induces the MyD88‐dependent activation of the TAK1‐IKK2‐NF‐κB signalling, ATP induces the Ca Co‐sensing of ATP and IL‐33 triggers hyperactivation of mast cells resulting in an amplified production of pro‐inflammatory cytokines and eicosanoids. Imagewas created with BioRender.com. After centrifugation, cells were recovered in KREBS‐HEPES buffer supplemented with 1 mM CaCl2 and diluted to a final density of 1 × 106 cells/ml. Cells were transferred onto black 96‐well microplates PS F‐bottom (Greiner bio‐one), and the signal was monitored by a NOVOstar microplate reader (BMG Labtechnologies GmbH) at 37°C : emission at 510 nm, excitation at 340 nm (Ca2+‐bound Fura‐2) and 380 nm (free Fura‐2). By subsequent cell lysis with triton X‐100, the maximal fluorescence signals were determined, followed by chelating Ca2+ with 20 mM EDTA to assess the minimal fluorescence.To determine the effect of ATP (Sigma) and/ or IL‐33 (50 ng/ml) (PeproTech) on the intracellular Ca3). BMMCs were treated with anti‐CD16/CD32 and rat‐IgG (Jackson) to prevent non‐specific binding of the staining antibodies. BMMCs were stained with PE‐anti‐CD117 or APC‐anti‐CD117, FITC‐anti‐FcεRI or PE‐CD107α . MC/9‐NFAT and MC/9‐NF‐κB MC lines were stained with PE‐anti‐CD117. All cells were analysed with a LSR II flow cytometer (BD). Data were analysed with FlowJo 10 .BMMCs were harvested and washed with PBA  (PeproTech) and/or ATP (500 µM) (Sigma). Lysis of the cells was performed with lysis buffer , and the protein concentration was determined . Boiled samples (treated with 6 × Laemmli buffer) were separated on 10% sodium dodecyl sulphate (SDS)‐Laemmli gels. Gels were transferred onto nitrocellulose membranes (biostep) by electroblotting. After blocking (with dry milk), membranes were incubated with either anti‐pT180/pY182‐p38, anti‐pS177/181‐IKK2, anti‐p184/187‐pTAK1, anti‐pT202/pY204‐ERK1/2, anti‐pS32‐IκBα, and anti‐pS536‐p65 or the respective anti‐total antibodies (non‐phosphorylated proteins) . Washed membranes (TBS/0·1% Tween) were incubated with HRP‐conjugated secondary anti‐rabbit‐Ig, or anti‐mouse‐Ig or anti‐goat‐Ig (SeraCare). Detection was performed with ECL reagent (Pierce).Washed BMMCs were seeded in IL‐3‐free media at a density of 106 cells/ml) were seeded in IL‐3‐free media. After 1 h, cells were pre‐treated with the inhibitors cyclosporine (4 µg/ml) , the Ca2+ chelator BAPTA‐AM (5 µM) (Ca2+ chel.) for Ca2+ depletion, U0126 (10 µM)  , the selective P2X7 inhibitor, A438079 (50 µM)  (Sigma) or skepinone‐L (1 µM) (Cayman)  or vehicle for 30 min. Afterwards, BMMCs were stimulated with IL‐33 (50 ng/ml) (PeproTech) or ATP (500 µM) (Sigma) or both in combination for 24 h. Supernatants were transferred to ice‐cold methanol containing deuterium‐labelled internal standards  for the quantification of LM and sample recovery. Sample preparation was performed as recently shown recently reported [2O was added . Samples were subjected to solid‐phase extraction using Sep‐Pak® Vac 6cc 500 mg/6 ml C18 (Waters). After washing with H2O and n‐hexane, LM were eluted with methyl formate. Samples were dried using an evaporation system (TurboVap LV) and resuspended in methanol‐water  for UPLC‐MS‐MS automated injections. LM profiling was analysed with an Acquity™ UPLC system (Waters) and a QTRAP 5500 mass spectrometer (ABSciex) equipped with a TurboV™ Source and electrospray ionization. LM was eluted using an ACQUITY UPLC® BEH C18 column  at 50°C with a flow rate of 0·3 ml/min and a mobile phase consisting of methanol‐water‐acetic acid of 42:58:0·01 (v/v/v) that was ramped to 86:14:0·01 (v/v/v) over 12.5 min and then to 98:2:0·01 (v/v/v) for 3 min [BMMCs (1 × 10reported . In brieor 3 min . The QTr6 cells/ml) were seeded in IL‐3‐ and serum‐free media. After 1 h, cells were pre‐treated with the inhibitors cyclosporine A (4 µg/ml) , the Ca2+ chelator BAPTA‐AM (5 µM) (Ca2+ chel.) for Ca2+ depletion, U0126 (10 µM)   or skepinone‐L (1 µM) (Cayman)  or vehicle for 30 min. Afterwards, BMMCs were stimulated with IL‐33 (50 ng/ml) (PeproTech) or ATP (500 µM) (Sigma) or both in combination for 24 h. Supernatants were transferred to pre‐coated ELISA plates and the competitive LTC4 ELISA was performed as described in the instructions (Cayman).BMMCs . Statistics were performed with IBM SPSS Statistics version 20.0 .All experiments were performed at least with three biological replicates. One biological replicate always is the bone marrow culture from at least 2 mice. Western blots intensities were determined with the ImageJ software (Fiji). The phospho‐specific Western blots were normalized to the total protein blots. The control (unstimulated sample) of wt BMMCs was set as 1. For analysis of CaThe authors declare no competing financial interests.P.M.J., N.A., M.G., O.W. and A. D. performed and analysed experiments, wrote and edited the manuscript; P.W., F.W., U.J. and C.K.: performed and analysed experiments, edited the manuscript; T.K. and E.S. provided material and edited the manuscript; S.D. developed the concept, designed the research, performed most of the experiments, analysed data, drafted, wrote and edited the paper.Fig S1Click here for additional data file.Fig S2Click here for additional data file.Fig S3Click here for additional data file.Fig S4Click here for additional data file.Fig S5Click here for additional data file.Fig S6Click here for additional data file.Fig S7Click here for additional data file.Fig S8Click here for additional data file.Fig S9Click here for additional data file.


C—Br⋯π and C=O⋯π interactions stabilize the molecular packing, resulting in a three-dimensional network.In the crystal, N—H⋯O hydrogen bonds link the molecules into dimers with an  20H16BrN3O2, was determined using an inversion twin. Its asymmetric unit comprises two crystallographically independent molecules (A and B) being the stereoisomers. Both molecules are linked by pairs of N—H⋯O hydrogen bonds, forming a dimer with an R22(16) ring motif. The dimers are connected by further N—H⋯O and N—H⋯N hydrogen bonds, forming chains along the c-axis direction·C—Br⋯π interactions between these chains contribute to the stabilization of the molecular packing. Hirshfeld surface analysis showed that the most important contributions to the crystal packing are from H⋯H, C⋯H/H⋯C, O⋯H/H⋯O, Br⋯H/H⋯Br and N⋯H/H⋯N interactions.The crystal structure of the title compound, C In molecule A, the phenyl (C7–C12) and bromophenyl (C14–C19) rings form dihedral angles of 64.0 (4) and 86.3 (4)°, respectively, with the mean plane of the central dihydropyridine ring. In molecule B, the corresponding dihedral angles are 77.2 (4) and 83.9 (4)°. The acetyl groups in both molecules are almost planar  and they make the dihedral angles of 89.5 (5) and 87.7 (5)° with the mean planes of the dihydropyridine rings in these molecules.The title compound crystallizes in the monoclinic space group it Fig. 1. These mB⋯O21 and N26—H26A⋯O1 hydrogen bonds  Å, C21=O21⋯Cg2 = 110.8 (6)°, O1⋯Cg5 = 3.748 (8) Å, C1=O1⋯Cg5 = 125.1 (6)°, where Cg2 and Cg5 are the centroids of the C7–C12 phenyl ring in molecule A and the C27–C32 phenyl ring in molecule B, respectively]. The dimers are connected by N—H⋯O and N—H⋯N hydrogen bonds with an c-axis direction (Table 1Cg6v = 3.407 (4) Å, C17—Br1⋯Cg6v = 145.2 (3)°; symmetry code (v) −1 + x, 1 − y, −z; Cg6 is the centroid of the C34–C39 ring]. Together with the other intermolecular contacts given in Table 2Strong N6—H6ds Fig. 1 link moln Table 1 and 5 ▸.A and B, CrystalExplorer17  indicate regions of N—H⋯O interactions. The N—H⋯N and C—H⋯N interactions , the molecular conformation of the title compound is stabilized by an intramolecular O—H⋯O hydrogen bond, forming an S(6) ring motif. In the crystal, molecules are linked by intermolecular N—H⋯N and C—H⋯N hydrogen bonds, and N—H⋯π and C—H⋯π interactions, forming a three-dimensional network.In OZAKOS (space group: PPi.e. R32(8)] is formed involving the sulfonate group, the pyrimidinium cation and the water molecule. Both salts form a supramolecular homosynthon [In both the related salts, JEBREQ (space group: P21/n) and SETWOE (space group: P21/c), adopt nearly planar structures. The crystal structure of SETWUK is stabilized by intermolecular C—H⋯F and C—H⋯π interactions. The C—H⋯F bond generates a linear chain with a C(14) motif. The crystal structure of SETWOE is stabilized by intermolecular C—H⋯O and C—H⋯π interactions. The C—H⋯O hydrogen bonds generate rings with 22R(14) and 22R(20) motifs. In addition, in SETWOE and SETWUK, intramolecular O—H⋯O interactions are found, which generate an S(6) graph-set motif. No significant aryl–aryl or π–π interactions exist in these structures. All this bears some resemblance to the title compound.The polysubstituted pyridines, SETWUK (space group: To a solution of 2-(4-bromobenzylidene)malononitrile  and acetoacetanilide  in methanol (25 mL), piperidine (2–3 drops) was added and the mixture was stirred at room temperature for 48 h. Then 15 mL of methanol were removed by rotary evaporation from the reaction mixture, which was left overnight. The precipitated crystals were separated by filtration and recrystallized from ethanol/water (1:1) solution .1H NMR : 2.29 ; 4.15 ; 4.34 ; 5.98 ; 7.12–7.35 ; 7.40 ; 7.61 .13C NMR : 27.86 (CH3—C=O), 37.94 (CH—Ar), 57.24 (=Cquat), 62.41 (CH—C=O), 117.21 (CN), 121.25 (Br-Car), 127.67 (CHar), 128.19 (2CHar), 129.58 (2CHar), 130.15 (2CHar), 130.74 (2CHar), 136.98 (Car), 140.37 (Car), 154.14 (=Cquat), 166.20 (N—C=O), 202.55 (C=O).Uiso(H) = 1.2Ueq or 1.5Ueq(C-methyl).Crystal data, data collection and structure refinement details are summarized in Table 410.1107/S2056989022001232/yk2165sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2056989022001232/yk2165Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989022001232/yk2165Isup3.cmlSupporting information file. DOI: 2149629CCDC reference:  crystallographicinformation; 3D view; checkCIF reportAdditional supporting information:


The crystal structures of two triclinic polymorphs of a new tetrakis-substituted pyrazine carboxylic acid, 3,3′,3′′,3′′′-[)tetrakis(sulfanediyl)]tetrapropionic acid, are reported, together with the crystal structures of two potassium-organic frameworks. 20H28N2O8S4, (4L1H), have been obtained, 4L1_AH and 4L1_BH. Each structure crystallized with half a molecule in the asymmetric unit of a triclinic P4L1_BH were of poor quality, but the X-ray diffraction analysis does show the change in conformation of the –CH2—S—CH2—CH2– side chains compared to those in polymorph 4L1_AH. In the crystal of 4L1_AH, molecules are linked by two pairs of O—H⋯O hydrogen bonds, enclosing R22(8) ring motifs forming layers parallel to plane (100), which are linked by C—H⋯O hydrogen bonds to form a supramolecular framework. In the crystal of 4L1_BH, molecules are also linked by two pairs of O—H⋯O hydrogen bonds enclosing R22(8) ring motifs, however here, chains are formed propagating in the [001] direction and stacking up the a-axis. Reaction of 4L1H with Hg(NO3)2 in the presence of a potassium acetate buffer did not produce the expected binuclear complex, instead crystals of a potassium–organic framework were obtained, poly[sulfanyl]methyl}pyrazin-2-yl)methyl]sulfanyl}propanoato)potassium], [K(C20H27N2O8S4)]n (3L1KH). The organic mono-anion possesses inversion symmetry with the pyrazine ring being located about an inversion center. A carboxy H atom is disordered by symmetry and the charge is compensated for by a potassium ion. A similar reaction with Zn(NO3)2 resulted in the formation of crystals of a dipotassium-organic framework, poly[sulfanyl]methyl}pyrazine-2,5-diyl)bis(methylene)]bis(sulfanediyl)}dipropionato)dipotassium], [K2(C20H26N2O8S4)]n (2H2L1K). Here, the organic di-anion possesses inversion symmetry with the pyrazine ring being located about an inversion center. Two symmetry-related acid groups are deprotonated and the charges are compensated for by two potassium ions.Two polymorphs of the title tetrakis-substituted pyrazine carboxylic acid, 3,3′,3′′,3′′′-{}tetrapropionic acid, C The first is pyrazine-2,3,5,6-tetracarboxylic acid (pztca), which was originally synthesized by Wolff at the end of the 19th century , which was first synthesized by Jiang et al. )tetrakis(sulfanediyl)]tetrapropionic acid , for which two nickel(II) binuclear complexes, I and II, were synthesized , crystallized with half a molecule in the asymmetric unit )tetrakis(sulfanediyl)]tetrapropionic acid  of the centrosymmetric molecule being positionally disordered . The difference in the two polymorphs is essentially in the orientation of the –CH2—S—CH2—CH2—C– side arms, as shown in Fig. 5a and b. Selected torsion angles are given in Table 1In an attempt to form a co-crystal, equimolar amounts of _B Fig. 4. It crysed Fig. 4b. The d4L1H with Hg(NO3)2 in the presence a 1 M potassium acetate buffer led to the formation of colourless crystals that proved to be a potassium–organic framework (3L1KH); see Fig. 6+ ion is linked to the O atoms of the acid groups and has a coordination number of eight (KO8) and a distorted dodecahedral geometry . The K⋯O bond lengths vary between 2.682 (2) and 3.069 (3) Å (Table 2−) distances: 2.6823 (2) and 2.828 (2) Å compared to 3.056 (3) and 3.069 (3) Å, respectively.Reaction of ry Fig. 7a. The KÅ Table 2. Intere4L1H with Zn(NO3)2 in the presence of a 1 M potassium acetate buffer led to the formation of colourless crystals that proved to be a dipotassium–organic framework (2H2L1K); see Fig. 8+ ions are linked to the O atoms of the acid groups and both K+ ions have a coordination number of six (KO6) and have edge-sharing bipyramidal geometries. The K+ ions are bridged by atoms O1 and O3, forming chains propagating along the b-axis direction . The K⋯O bond lengths vary between 2.6682 (12) and 2.8099 (14) Å (Table 3−) bond lengths is much less significant  of the organic anion are similar, and similar to that in 4L1_BH , while the conformation of the second (involving atom S2) differs significantly  through white to blue . The Hirshfeld surfaces (HS) of 4L1_AH, and 4L1_BH mapped over dnorm are given in Fig. 13a and b concern the O—H⋯O hydrogen bonds in the crystal structures of both compounds.The Hirshfeld surfaces are colour-mapped with the normalized contact distance, 4L1_AH, and 4L1_BH are shown in Fig. 14The percentage contributions of inter-atomic contacts to the HS for both compounds are compared in Table 94L1_AH, and 4L1_BH, respectively. These are followed by C⋯H/H⋯H contacts at, respectively, 4.5 and 4.9%. The N⋯H/H⋯N contacts contribute, respectively, 3.0 and 2.5%.The third most important contribution to the HS is from the S⋯H/H⋯S contacts at 13.4 and 16.1%, for 4L1_AH, and 4L1_BH, are given in Fig. 15Etot) are also included there; see Tan et al. , the dispersion forces (Edis) and the total energy diagrams (Etot), are shown in Fig. 16et al., 2017et al., 2019−1 within a radius of 6 Å of a central reference molecule. It can be seen that for both polymorphs the major contribution to the intermolecular interactions is from electrostatic potential forces (Eele), reflecting the presence of the classical O—H⋯O hydrogen bonds.A comparison of the energy frameworks calculated for et al., 2016viz. 2,3,5,6-pyrazinetetracarboxylic acid (pztca) and 2,3,5,6-tetrakis(4-carboxyphenyl)pyrazine (pztba). Ligand pztba has been shown to be extremely successful in forming metal–organic frameworks potassium] . The asymmetric unit consists of half a mono-deprotonated ligand molecule located about an inversion center, and half a potassium ion. The carboxy H atom is disordered by symmetry, similar to the situation in the structure of 3L1KH. Here the K⋯O bond lengths vary from 2.7951 (11) to 2.8668 (13) Å. The K+ cation has a coordination number of 8 (KO8) and a distorted dodecahedral geometry as in 3L1KH .Potassium salts of carboxylic acids are relatively common. A search for potassium salts of purely organic carboxylic acids and excluding hydrates, yielded over 200 hits. The potassium salt of L1 Fig. 7a and 11pzdca; Fig. 12-3-carboxypyrazine-2-carboxylato)-diaquapotassium], has been reported -hexaaquabis(6-carboxypyridine-2-carboxylato-O)dipotassium potassium] , with the K⋯O bonds lengths varying from 2.8197 (14) to 3.0449 (15) Å. The K+ ion has a coordination number of seven (KO6N) and has an edge-sharing pentagonal antiprism geometry, forming chains . This structure can be compared to that of 2H2L1K where the two independent K+ ions, each with a coordination number of six (KO6), have edge-sharing bipyramidal geometries, also forming chains .The structure of MUMPIW is that of a potassium-organic framework Fig. 17b, with s Fig. 17b. This ns Fig. 7b and 12et al., 1994The synthesis and crystal structure of the reagent tetra-2,3,5,6-bromomethyl-pyrazine (TBr) have been reported (Ferigo 4L1):Synthesis of 3,3′,3′′,3′′′-{tetrakis(sulfanediyl)}tetrapropionic acid  that X-ray diffraction analysis indicated to be triclinic polymorph 4L1_AH.Mercaptopropionic acid  was dissolved in 50 ml THF. A minimum amount of water (a few ml) was added to dissolve 1.4166 g  of NaOH. The volume of the mixture was increased to 100 ml by adding THF and the reaction was stirred under reflux for 1 h. Then TBr  dissolved in 50 ml THF was added dropwise using an addition funnel. The mixture was stirred under reflux for 6 h. After drying under vacuum, the residue was dissolved in 50 ml of deionized water, and HCl puriss. was added dropwise until a clearly acid pH was obtained. This mixture was stirred at room temperature for 1–2 h. The yellow precipitate that formed was filtered off and washed with a minimum amount of water and then CHCl4L1H in methanol gave colourless crystals of rather poor quality. However, X-ray diffraction analysis indicated that a second triclinic .1H NMR , δ(ppm): 4.03 , 2.78  = 7.0, H3), 2.62  = 7.0, H4).13C NMR , δ(ppm): 174.54 , 150.12 , 34.29 , 33.64 , 26.65 .20H28N2O8S4, Mw = 552.71 g mol−1: Calculated: C 43.46, H 5.11, N 5.07%. Found: C 43.40, H 5.17, N 4.87%.Elemental Analysis for Cm/z: 591.04 [M + K]+; 575.06 [M + Na]+; 553.08 [M + H]+; 471.07; 449.09.ESI–MS, −1) ν: 2926(s), 2666(m), 2590(s), 1693(s), 1429(s), 1406(s), 1340(m), 1270(s), 1200(s), 1163(m), 1134(s), 1107(m), 1055(w), 918(s), 658(m), 489(m).IR :Synthesis of poly[sulfanyl]methyl}pyrazin-2-yl)methyl]sulfanyl}propanoate)potassium] (KH3)2  and 4L1H  were mixed together in 20 ml of a 1 M potassium acetate buffer. The mixture was left at 323 K under stirring and nitrogen conditions for 1 h. The mixture was then filtered and left to evaporate in air for six weeks. Colourless plate-like crystals were obtained, which were shown to be a potassium–organic framework.Hg(NO−1) ν: 3422(m), 2922(m), 1713(m), 1580(s), 1399(s), 1247(m), 1190(m), 1152(m), 1114(m), 811(m), 787(m).IR :Synthesis of poly[sulfanyl]methyl}pyrazine-2,5-diyl)bis(methylene)]bis(sulfanediyl)}dipropionato)dipotassium] (K3)2  and 4L1H  were mixed together in 20 ml of a 1M potassium acetate buffer. The mixture was left at 323 K under stirring and nitrogen for 1 h. The mixture was then filtered and left to evaporate in air for 6 weeks. Colourless plate-like crystals were obtained, which proved to be a dipotassium-organic framework.Zn(NO−1) ν: 3401(m), 1579(s), 1401(s), 1303(m).IR . They were therefore included in calculated positions assuming the formation of carboxylic acid dimers; O—H = 0.82 Å and refined as riding with Uiso(H) = 1.5Ueq(O).For + salt of pyrazine tetracarboxylic acid  = 1.2Ueq(C).For all four compounds, the C-bound H atoms were included in calculated positions and treated as riding on their parent C atom with C—H = 0.97 Å and 4L1_AH and 4L1_BH, the alert _diffrn_reflns_point_group_measured_fraction_full value  below minimum (0.95) was given. For 4L1_AH it involves 131 random reflections out of a total of 2180, viz. 6.0%, while for 4L1_BH it involves 158 random reflections out of a total of 2184, viz. 7.2%.For 4L1_AH, 4L1_BH and 2H2L1K the multiplicity of reflections was 2 or less and so an empirical absorption correction was applied.For 10.1107/S2056989021003479/pk2656sup1.cifCrystal structure: contains datablock(s) H4L1A, H4L1B, KH3L1, K2H2L1, Global. DOI: 10.1107/S2056989021003479/pk2656H4L1Asup2.hklStructure factors: contains datablock(s) H4L1A. DOI: 10.1107/S2056989021003479/pk2656H4L1Bsup3.hklStructure factors: contains datablock(s) H4L1B. DOI: 10.1107/S2056989021003479/pk2656KH3L1sup4.hklStructure factors: contains datablock(s) KH3L1. DOI: 10.1107/S2056989021003479/pk2656K2H2L1sup5.hklStructure factors: contains datablock(s) K2H2L1. DOI: Click here for additional data file.10.1107/S2056989021003479/pk2656H4L1Asup6.cmlSupporting information file. DOI: Click here for additional data file.10.1107/S2056989021003479/pk2656H4L1Bsup7.cmlSupporting information file. DOI: Click here for additional data file.10.1107/S2056989021003479/pk2656KH3L1sup8.cmlSupporting information file. DOI: Click here for additional data file.10.1107/S2056989021003479/pk2656K2H2L1sup9.cmlSupporting information file. DOI: 2074770, 2074769, 2074768, 2074767CCDC references:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


The two molecules A and B are involved in intermolecular C—H⋯O and C—H⋯N hydrogen bonds.The title compound, C 9H7NO2S crystallizes with two independent molecules (A and B) in the asymmetric unit with Z = 8. Both molecules are almost planar with a dihedral angle between the isoxazole and thiophen rings of 3.67 (2)° in molecule A and 10.00 (1) ° in molecule B. The packing of molecules A and B is of an ABAB⋯ type along the b-axis direction, the configuration about the C=C bond is Z. In the crystal, the presence of C—H⋯O, C—H⋯ N and π–π interactions [centroid–centroid distances of 3.701 (2) and 3.766 (2) Å] link the molecules into a three-dimensional architecture. An analysis of Hirshfeld surfaces shows the importance of C—H⋯O and C—H⋯N hydrogen bonds in the packing mechanism of the crystalline structure.The title compound, C In the present study, we report on the synthesis, molecular and crystal structure together with a Hirshfeld surface analysis of the title isoxazole derivative.Isoxazolones show some interesting biological properties. They are inhibitors of the factorization of tumor necrosis alpha (TNF-α) (Laughlin A and B) in the asymmetric unit. The molecular structure adopts a Z-configuration about the C=C [1.354 (3) Å in molecule A and 1.357 (3) Å in molecule B] double bonds. The molecular structure of the title compound is shown in Fig. 1. It crysA) and C11—C12—C13 (molecule B) differing by 0.8 (2)°. Also, a slight difference of 0.3 (2)° is observed between the angles C2—C5—C6 and C11—C14—C15. In molecule A, the angle between the normal of the molecular plane (O2A/N1A/C1A–C3A) and the normal of the (S1A/C6A–C9A) plane is 3.67 (2)°. An important difference is observed in molecule B, where the angle between the normal of the molecular plane (O3B/N2B/C10B–C12B) and the normal of the (S2B/C15B–C18B) plane is 10.00 (1)°. In the molecular skeleton, the angle between the mean planes of the molecules A and B is 4.09 (1)°. Each of the two methyl groups, C4 and C13, has a C—H bond lying in the mean plane of the molecular skeleton, and they are oriented toward the thiophene group.The bond lengths in the two molecules are practically equal, while there are slight differences in bond angles; with for example C2—C3—C4  Å and Cg3⋯Cg4ii = 3.766 (2) Å where Cg1, Cg2, Cg3 and Cg4 are the centroids of the O2A/N1A/C1A–C3A, S2B/C15B–C18B, S1A/C6A–C9A and O3B/N2B/C10B–C12B rings, respectively; symmetry codes: (i) −x, y, z; (ii) −x, y, z]. The two molecules A and B are involved in intermolecular C—H⋯O and C—H⋯N hydrogen bonds . The H⋯H contacts, accounting for about 35.4% of the Hirshfeld surface  represent the largest contribution and are seen in the fingerprint plot as a pair of shorts pikes at de + di = 2.2 Å; comparing this to van der Waals radius, we find the difference between them is about 1 Å, which means it is a very powerful interaction. H⋯O/O⋯H contacts  make a contribution of 28.7%, with a distinctive peak in the fingerprint plot at de + di = 2.4 Å; the van der Waals radius sum for this interaction is about 2.7 Å.The Hirshfeld surface analysis . Although the H⋯N /N⋯H interactions have a notable contribution of 12% to the Hirshfeld surface , their interatomic distances (de + di = 2.4 Å) are less than their van der Waals radius (2.7 Å), which means that it is a very strong interaction in this structure. The presence of π–π stacking reflects the presence of C⋯C contacts , which account for 7.9% of the Hirshfeld surface with de + di = 3.4 Å; the van der Waals radius is 3.4 Å, so we can confirm the presence of π–π stacking. Two further views of the Hirshfeld surface are shown in Fig. 5The pair of short peaks at ce Fig. 4e, theirts Fig. 4f, whichet al., 2016Z)-4-(thiophen-2-ylmethylidene)isoxazol-5(4H)-one unit gave five hits: 4-(2-hydroxybenzylidene)-3-methylisoxazol-5(4H)-one -one -4-benzylidene-3-methylisoxazol-5(4H)-one -one -4-(4-hydroxybenzylidene)-3-methylisoxazol-5(4H)-one , 10.00 (1), 0.86 (9), 7.02 (8), 2.65 (16), 4.55 (15), 6.50 (1), 7.98 (8) and 3.18 (8)°, respectively.The asymmetric unit of the title compound contains two crystallographically independent molecules, as found for ERIXIN and WOYPIL while in AJESAK, MBYIOZ01 and VIDSAF, there is only one molecule per asymmetric unit. The configuration about the C=C bond is via C—H⋯O hydrogen bonds, forming ABAB chains along the [10A and B is of an ABAB⋯ type along the [100] direction. In our compound, the cohesion of the crystal is ensured by interactions of the type C—H⋯O, C—H⋯π and π–π [intercentroid distances of 3.701 (2) and 3.766 (2) Å compared with 3.811 (2) and 3.889 (2) Å in ERIXIN and 3.767 (2) and 3.867 (2) Å in WOYPIL].In the crystal of WOYPIL, the individual molecules are linked 5H4OS, 1 mmol), hydroxylamine hydrochloride , ethyl acetoacetate  and K2CO3 (5 mol%) were mixed in a 25 mL flask equipped with a magnetic stirrer. The mixture was refluxed in 5 mL of water for 3h (followed by TLC). When the reaction was judged to be finished, the mixture was gradually poured into ice-cold water. Stirring was maintained for a few minutes and the obtained solid was filtered and purified by crystallization from ethanol (yield 72%).Thiophene-2-carbaldehyde (CUiso(H) = 1.2–1.5Ueq(C).Crystal data, data collection and structure refinement details for the title compound are summarized in Table 210.1107/S2056989021002632/zn2002sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2056989021002632/zn2002Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989021002632/zn2002Isup3.cmlSupporting information file. DOI: 2069004CCDC reference:  crystallographic information; 3D view; checkCIF reportAdditional supporting information:


Broussonetia kazinoki, on vascular endothelial growth factor‐A (VEGF‐A)–stimulated endothelial cell responses in vitro and microvessel sprouting ex vivo. Treatment with broussonin A or B suppressed VEGF‐A‐stimulated endothelial cell proliferation by regulating the expression of cell cycle–related proteins and the phosphorylation status of retinoblastoma protein. In addition, treatment with broussonin A or B abrogated VEGF‐A‐stimulated angiogenic responses including endothelial cell migration, invasion, tube formation and microvessel formation from rat aortic rings. These anti‐angiogenic activities of broussonin A and B were mediated through inactivation of VEGF‐A‐stimulated downstream signalling pathways, localization of vascular endothelial‐cadherin at cell‐cell contacts, and down‐regulation of integrin β1 and integrin‐liked kinase. Furthermore, treatment with broussonin A or B inhibited proliferation and invasion of non–small cell lung cancer and ovarian cancer cells. Taken together, our findings suggest the pharmacological potential of broussonin A and B in the regulation of angiogenesis, cancer cell growth and progression.In the present study, we demonstrate the regulatory effects and mechanism of broussonin A and B, diphenylpropane derivatives isolated from  Vascular endothelial growth factor (VEGF) has long been appreciated as a key therapeutic target for the treatment of diseases associated with pathological angiogenesis.These complex dynamics of VEGF‐mediated signalling networks may partially explain the limitation of anti‐VEGF/VEGFR therapy in the clinic. Therefore, in‐depth investigations of integrative signalling pathways within the tumour microenvironment may provide crucial therapeutic targets and strategies for improving clinical outcomes.Broussonetia kazinoki (B. kazinoki) Siebold (Moraceae), a deciduous shrub distributed in Eastern Asia including Korea, China and Japan, has been traditionally used as a folk medicine for the treatment of amblyopia, inflammation and oedema as well as a raw material for making high‐quality paper in Korea. The extract and bioactive components isolated from B. kazinoki have been reported to possess various pharmacological properties including myogenic, anti‐allergic, anti‐inflammatory, anti‐diabetic and anti‐tumour activities.B. kazinoki or marmesin, a furanocoumarin component isolated from B. kazinoki, negatively modulates VEGF‐A‐induced angiogenic responses by inactivation of VEGF‐A/VEGFR‐2‐mediated signalling network.B. kazinoki, B. papyrifera and Anemarrhena asphodeloides (A. asphodeloides), has been reported to possess antiviral, anti‐inflammatory, anti‐adipogenic and oestrogenic properties.B. kazinoki and A. asphodeloides has been known to exert anti‐adipogenic and neurotrophic activities.B. kazinoki on endothelial cell and cancer cell responses.Broussonin A (2‐[3‐(4‐hydroxyphenyl)propyl]‐5‐methoxyphenol), a diphenylpropane derivative isolated from several plants including 22.1® BulletKit media and used between passages 4 and 6 for all experiments, according to the manufacturer's instructions (Lonza). Human non–small cell lung cancer (A549 and H1299) and ovarian cancer (SKOV‐3) cells from the American Type Culture Collection  were cultured in 10% foetal bovine serum‐Dulbecco's modified Eagle's medium .Human umbilical vein endothelial cells (HUVECs) from Lonza  were grown in EGM‐22.2B. kazinoki. High‐performance liquid chromatography (HPLC) analysis was performed on an Agilent 1200 series  using Kromasil® C18 column   with a stepwise gradient elution of methanol‐0.05% trifluoroacetic acid in water (20%–100% methanol) at a flow rate of 1 mL/min. The purity of broussonin A and B by HPLC analysis was >98%. 1H‐ and 13C‐nuclear magnetic resonance (NMR) spectra of broussonin A and B were recorded on a Bruker Ascend 700 MHz NMR spectrometer . Broussonin A: 1H‐NMR  7.00 , 6.92 , δ 6.69 , 6.36 , 6.34 , 3.72 , 2.53 , 1.81 ; 13C‐NMR  δ 158.9 (C‐4’), 155.6 (C‐2’), 154.8 (C‐4'’), 133.5 (C‐1'’), 129.7 (C‐6’), 128.9 , 121.0 (C‐1’), 114.6 , 104.0 (C‐5’), 100.9 (C‐3’), 54.1 (OCH3), 34.5 (C‐3), 32.1 (C‐2), 28.9 (C‐1); ESI(electrospray ionization)‐MS (mass spectrometry) (positive mode) m/z 259 [M + H]+. Broussonin B: 1H‐NMR  6.98 , 6.88 , δ 6.69 , 6.39 , 6.30 , 3.74 , 2.50 , 1.77 ; 13C‐NMR  δ 158.9 (C‐2’), 156.9 (C‐4’), 155.4 (C‐4'’), 134.1 (C‐1'’), 130.4 (C‐6’), 129.5 , 122.0 (C‐1’), 115.2 , 106.7 (C‐5’), 98.9 (C‐3’), 54.8 (OCH3), 35.1 (C‐3), 32.8 (C‐2), 29.5 (C‐1); ESI‐MS (positive mode) m/z 259 [M + H]+. The structures of broussonin A and B are presented in Figure Broussonin A and B were isolated in an ethyl acetate fraction partitioned from the ethanolic extract of 2.3S6K (T421/S424), anti‐phospho‐Akt (S473), anti‐phospho‐ERK (T202/Y204), anti‐phospho‐p38MAPK (T180/Y182), anti‐phospho‐pRb (S780) and anti‐phospho‐pRb (S807/S811) ; anti‐phospho‐tyrosine ; anti‐VEGFR‐2, anti‐vascular endothelial (VE)‐cadherin, anti‐integrin β1, anti‐ILK, anti‐p70S6K, anti‐Akt, anti‐ERK, anti‐p38MAPK, anti‐Cdk2, anti‐Cdk4, anti‐cyclin D, anti‐cyclin E, anti‐actin antibodies and mouse and rabbit IgG‐horseradish peroxidase conjugates ; Alexa Fluor 488–conjugated goat anti‐mouse IgG .The following agents were obtained from commercial sources: vascular endothelial growth factor‐A 165 ; anti‐phospho‐VEGFR‐2 (Y951) ; anti‐phospho‐p702.45 cells/well, SPL Life Sciences, Gyeonggi‐do, Republic of Korea) were serum‐starved for 14 h in endothelial cell basal medium‐2  and pretreated with broussonin A or B (0.1–10 µM) for 30 min, followed by VEGF‐A (10 ng/mL) stimulation for 24 h. In some experiments, human non–small cell lung cancer (A549 and H1299) and ovarian cancer (SKOV‐3) cells, plated on 6‐well plates (5 × 104 cells/well), were serum‐starved for 24 h in basal DMEM and pretreated with broussonin A or B (10 µM) for 30 min, followed by 10% FBS stimulation for 24 h. Cell proliferation and viability were determined as described previously.HUVECs, plated on 6‐well plates .Quiescent HUVECs were pretreated with broussonin A or B (10 µM) for 30 min, followed by VEGF‐A (10 ng/mL) stimulation for 24 h. Cells were fixed with ice‐cold 70% ethanol, stained with Muse™ cell cycle reagent, and then analysed by a Muse2.6TM Total RNA Purification kit . RNA purity and concentration were determined using a NanoDropTM 2000 spectrophotometer . One microgram of RNA was used as template for RT‐mediated PCR using 1st Strand cDNA Synthesis kit . Primer sets for integrin β1 were forward 5’‐GAAGGGTTGCCCTCCAGA‐3’ and reverse 5’‐GCTTGAGCTTCTCTGCTGTT‐3’; and the primer sets for glyceraldehydes‐3‐phosphate dehydrogenase (GAPDH) were forward 5’‐GAAGGTGAAGGTCGGAGTC‐3’ and reverse 5’‐GAAGATGGTGATGGGATTTC‐3’.Total RNA was isolated using PureHelix2.7Quiescent HUVECs were pretreated with broussonin A or B (10 µM) for 30 min, followed by VEGF‐A (10 ng/mL) stimulation for the indicated time points. Cells were lysed by incubation in 50 mM Tris‐HCl (pH 7.4), 1% Triton X‐100, 150 mM NaCl, 0.5 μg/mL leupeptin, 1 μg/mL pepstatin A, 10 μg/mL aprotinin, 100 μg/mL 4‐(2‐aminoethyl)benzenesulfonyl fluoride, 1 mM EDTA, 1 mM sodium orthovanadate, 25 mM sodium fluoride, 80 mM β‐glycerophosphate and 10% glycerol for 30 min at 4°C. Cell lysates were subjected to immunoprecipitation and Western blot as previously described.2.8A single wound was created in the centre of confluent HUVEC monolayer by a sterile pipette tip. After serum starvation for 2 h, cells were pretreated with broussonin A or B (0.1–10 µM) for 30 min, followed by VEGF‐A (10 ng/mL) stimulation for 16 h. Following fixation with methanol, cells were stained with 0.04% Giemsa solution . The migration of cells across a wound field gap was quantified as previously described.2.9® (BD Biosciences)‐coated transwell inserts   were serum‐starved for 2 h and pretreated with broussonin A or B (1–10 μM) for 30 min, followed by VEGF‐A (10 ng/mL) or 10% FBS stimulation for 16 h. After fixation with methanol, invasive cells were stained with 0.04% Giemsa solution and quantified from six different fields using x200 objective magnification.Transwell invasion assay was performed as previously described.2.10Quiescent HUVECs, plated on gelatin‐coated coverslips in 12‐well plates, were pretreated with broussonin A or B (10 µM) for 30 min, followed by VEGF‐A (10 ng/mL) stimulation for 30 min. Briefly, cells were fixed with 3.7% paraformaldehyde, permeabilized with 0.1% Triton X‐100, blocked with 5% BSA‐PBS, and incubated with anti‐VE‐cadherin antibody. Images were observed using a Carl Zeiss Microscope (Axio Imager.M2) and AxioVision Rel. 4.8 software .2.114 cells/mL) were plated on Matrigel®‐coated 24‐well plates and pretreated with broussonin A or B (1–10 µM) for 30 min, followed by VEGF‐A (10 ng/mL) for 6 h. Formation of capillary‐like structures was examined using an Olympus CKX41 inverted microscope (CAchN 10/0.25php objective) and ToupTek Toupview software .After serum starvation for 2 h, cells (4 × 102.12® were pretreated with broussonin A or B (10 µM) for 30 min, followed by VEGF‐A (500 ng/mL) for 3 days and then incubated with fresh broussonin A or B plus VEGF‐A every other day, and photographed on the 7th day using x40 objective magnification.Eight‐ to nine‐week‐old male Sprague Dawley rats (250 ± 10 g) were purchased from RaonBio Inc. . The animal experiments were conducted in accordance with the institutional guidelines. The experimental procedures were approved by the Institutional Animal Care and Use Committee at Dankook University . Thoracic aortic ring segments embedded in Matrigel2.13t test and was based on at least three different experiments. The results were considered to be statistically significant when p < .05.Statistical analysis was performed using Student's 33.11 cell cycle arrest, which is well correlated with suppression of cell proliferation ‐cadherin from β‐catenin and plakoglobin and modulates angiogenic responses such as endothelial permeability, invasion, proliferation and tube formation.3.4S6K), Akt, extracellular signal‐regulated kinase (ERK) and p38 mitogen‐activated protein kinase (p38MAPK).S6K, Akt, ERK and p38MAPK, as compared with untreated controls , a key kinase in integrin downstream signalling pathways, which are closely associated with angiogenesis and tumour progression Figure .39, 43.5Based on inhibitory effects of broussonin A and B on angiogenic responses, we next examined the ability of broussonin A and B to regulate proliferation and invasion in NSCLC p53 wild‐type A549 and p53‐deficient H1299 cells as well as ovarian cancer p53‐deficient SKOV‐3 cells Figure . Treatme4S6K and p38MAPK, redistribution of VE‐cadherin to cell‐cell contacts, and down‐regulation of integrin β1 and ILK. In addition, both broussonin A and B exert anti‐proliferative and anti‐invasive activities against NSCLC and ovarian cancer cells. Our findings demonstrate the pharmacological potential of broussonin A and B in the regulation of pathological angiogenic responses associated with cancer growth and progression.In the current study, we report that both broussonin A and B negatively regulate VEGF‐A‐induced in vitro endothelial cell responses including proliferation, migration, invasion and capillary‐like structure formation as well as ex vivo angiogenesis. The mechanism of these anti‐angiogenic effects involves inactivation of VEGF‐A/VEGFR‐2 downstream signalling pathways such as ERK, Akt, p70Integrins, transmembrane receptors that facilitate cell‐extracellular matrix and cell‐cell interactions, mediate a wide range of cellular responses including adhesion, migration, proliferation, invasion and angiogenesis associated with tumour growth and progression.Cell adhesion, migration and invasion are tightly controlled by the changes in the expression of adhesion molecules such as integrins and cadherins and/or activity of matrix metalloproteinases.In addition to anti‐angiogenic activity, both broussonin A and B have anti‐proliferative and anti‐invasive activities against NSCLC and ovarian cancer cells concomitant with suppression of integrin β1 expression, independently of p53 levels. In conclusion, our results provide significant insights into the regulatory roles and therapeutic efficacy of broussonin A and B in angiogenesis and cancer progression and warrant preclinical evaluation and development as a promising therapeutic agent for the treatment of a wide range of angiogenesis‐related diseases including cancer.The authors declare that there are no conflicts of interest.Jae Hyeon Kim: Conceptualization ; Investigation (lead); Methodology (lead); Validation ; Visualization ; Writing – original draft ; Writing – review & editing . Sunho Kim: Data curation ; Formal analysis ; Investigation . Surim Han: Data curation ; Formal analysis ; Investigation . Eun‐Kyung Ahn: Conceptualization (supporting); Data curation ; Investigation (supporting). Young‐Rak Cho: Conceptualization (supporting); Data curation ; Investigation (supporting). Wonsik Jeong: Data curation ; Investigation (supporting). Sung Joon Kim: Data curation (supporting); Investigation (supporting). Gyu‐Un Bae: Conceptualization (supporting); Resources (supporting). Joa Sub Oh: Conceptualization (supporting); Resources (supporting). Dong‐Wan Seo: Conceptualization (lead); Data curation ; Funding acquisition (lead); Resources (lead); Supervision (lead); Writing – original draft (lead); Writing – review & editing (lead).Supplementary MaterialClick here for additional data file.


Three intramolecular hydrogen bonds are observed in the title compound. In the crystal, molecules are connected by C—H⋯Cl and N—H⋯O hydrogen bonds. 18H15ClN3O+·Cl−·2H2O, three intramolecular hydrogen bonds are observed, N—H⋯O, O—H⋯Cl and O—H⋯O. In the crystal, molecules are connected by C—H⋯Cl and N—H⋯O hydrogen bonds. Strong C—H⋯Cl, N—H⋯O, O—H⋯Cl and O—H⋯O hydrogen-bonding interactions are implied by the Hirshfeld surface analysis, which indicate that H⋯H contacts make the largest contribution to the overall crystal packing at 33.0%.In the title compound, C For example, their biological activity and antimicrobial properties have been researched extensively (Neumann Database survey section). Three intramolecular hydrogen bonds are observed, N2—H2C⋯O2, O2—H2A⋯Cl2 and O2—H2B⋯O3  between the pyridazine rings [centroid–centroid distance = 3.4902 (12) Å], and also between the pyridine and benzene rings [3.7293 (13) and 3.8488 (13) Å], forming sheets.The water molecules and chloride anions are located in channels between the organic cations and are connected by O—H⋯O and O—H⋯Cl hydrogen bonds Table 1 into chant Fig. 2b betweeConQuest version 2021.3.0; Groom et al., 2016H)pyridazinone -one -one  on the Hirshfeld surface imply strong hydrogen-bonding interactions of types C—H⋯Cl, N—H⋯O, O—H⋯Cl and O—H⋯O. In the shape-index map , the π–π interactions are indicated by the red and blue triangles. Fig. 4c and Fig. 4d show di and de surfaces and Fig. 4e and 4f the curvedness and fragment path surfaces. Fig. 5a shows the overall two-dimensional fingerprint plot. The fingerprint plot delineated into H⋯H contacts  has a point with the tip at de + di = 2.05 Å. The pair of wings in the fingerprint plot defined into H⋯C/C⋯H contacts (19.3 percent contribution to the HS), Fig.5c, has a pair of thin edges at de + di ∼2.99 Å while the pair of wings for the H⋯Cl/Cl⋯H contacts  are seen as two spikes with the points at de + di = 2.97 Å and de + di = 2.41 Å. The fingerprint plot for H⋯O/O⋯H contacts  has two spikes with the tips at de + di = 2.11 Å and de + di = 1.83 Å. As seen in Fig. 5f the C⋯C contacts (7.4%) have an arrow-shaped distribution of points with tips at de + di = 3.37 Å. The contributions of the N⋯H/H⋯N contacts to the Hirshfeld surface (5.8%) are less important . Fig. 6To investigate the effect of the molecular interactions on the crystal packing, the Hirshfeld surface Fig. 3 and fingap Fig. 4b, the πnt Fig. 5g. Fig. et al., 2019E)-6-(4-chlorostyryl)-4,5-dihydropyridazin-3(2H)-one  and nicotinaldehyde  in 30 ml of ethanol, sodium ethanoate  was added. The mixture was refluxed for 3 h. The reaction mixture was cooled, diluted with cold water and acidified with concentrated hydrochloric acid. The precipitate was filtered, washed with water, dried and recrystallized from ethanol. White single crystals were obtained by slow evaporation at room temperature, yield 86%; m.p. 453 K; FT–IR (KBr): ν 3322 (NH), 1651 (C=O), 1584 cm−1 (C=N); 1H NMR  δ 13.20  , 8.98 , 8.83 , 8.57 , 8.05  8.02 , 7.65 , 7.45 , 7.36 , 7.08 , 4.09 ppm ; 13C NMR  δ 160.43, 145.98, 143.89, 141.87, 140.05, 139.25, 137.97, 134.90, 132.84,130.85, 128.82, 128.62, 128.54, 126.80, 125.08, 32.33 ppm. ESI-MS: m/z = 324.08 [M+H]+.The title compound was synthesized according to a previously published procedure (Daoui Uiso(H) = 1.2 Ueq.Crystal data, data collection and structure refinement details are summarized in Table 210.1107/S2056989022003346/jq2014sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2056989022003346/jq2014Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989022003346/jq2014Isup3.cmlSupporting information file. DOI: 2161716CCDC reference:  crystallographicinformation; 3D view; checkCIF reportAdditional supporting information:


In the crystal, the molecules are linked by C—H⋯N interactions along the a-axis direction, forming a C(6) chain. The molecules are further connected by C—Cl⋯π interactions and face-to-face π–π stacking interactions, forming ribbons along the a-axis direction. Hirshfeld surface analysis indicates that the greatest contributions to the crystal packing are from Cl⋯H/H⋯Cl (35.1%), H⋯H (10.6%), C⋯C (9.7%), Cl⋯Cl (9.4%) and C⋯H/H⋯C (9.2%) interactions.In the title compound, C The secondary important H⋯H and C⋯C interactions contribute 10.6%  and 9.7% , respectively, to the Hirshfeld surface. The remaining contributions for the title compound are from Cl⋯Cl, C⋯H/H⋯C, Cl⋯F/F⋯Cl, Cl⋯C/C⋯Cl, F⋯H/H⋯F, N⋯H/H⋯N, N⋯N and F⋯C/ C⋯F contacts, which are less than 9.7% and have a negligible effect on the packing. The percentage contributions of all interactions are listed in Table 3The overall two-dimensional fingerprint plot and those delineated into Cl⋯H/H⋯Cl, H⋯H, C⋯C, Cl⋯Cl and C⋯H/H⋯C contacts in the title molecule are illustrated in Fig. 76% Fig. 7c and 9.7% Fig. 7d, respeet al., 2016E)-1--2-phenyldiazene unit resulted in 28 hits. Nine compounds are closely related to the title compound, viz. LEQXOX  and 60.31 (14)°, respectively. In I, C—H⋯N and short Cl⋯Cl contacts are observed and in II, C—H⋯N and C—H⋯O hydrogen bonds and short C—Cl⋯O contacts occur. In III, the benzene rings form a dihedral angle of 63.29 (8)° and the molecules are linked by C—H⋯O hydrogen bonds into zigzag chains running along the c-axis direction. The crystal packing also features C—Cl⋯π, C—F⋯π and N—O⋯π interactions. In IV, the benzene rings make a dihedral angle of 56.13 (13)°. Molecules are stacked in columns along the a-axis direction via weak C—H⋯Cl hydrogen bonds and face-to-face π–π stacking interactions. The crystal packing is further consolidated by short Cl⋯Cl contacts. In V and VI, the aromatic rings form dihedral angles of 60.9 (2) and 64.1 (2)°, respectively. In the crystals, molecules are linked through weak X⋯Cl contacts (X = Cl for V and Br for VI), C—H⋯Cl and C—Cl⋯π interactions into sheets parallel to the ab plane. Additional van der Waals interactions consolidate the three-dimensional packing. In VII, the dihedral angle between the two aromatic rings is 64.12 (14)°. The crystal structure is stabilized by a short C—H⋯Cl contact, C—Cl⋯π and van der Waals interactions. In VIII, the benzene rings subtend a dihedral angle of 77.07 (10)°. In the crystal, molecules are associated into inversion dimers via short Cl⋯Cl contacts [3.3763 (9) Å]. In IX, the asymmetric unit comprises two similar molecules, in which the dihedral angles between the two aromatic rings are 70.1 (3) and 73.2 (2)°. The crystal structure features short C—H⋯Cl and C—H⋯O contacts and C—H⋯π and van der Waals interactions.In the crystals of et al., 2018E)-1--2-(4-fluorobenzylidene)hydrazine , tetramethylethylenediamine (TMEDA) , CuCl  and CCl4 . After 1–3 h , the reaction mixture was poured into ∼0.01 M solution of HCl , and extracted with dichloromethane (3 × 20 mL). The combined organic phase was washed with water (3 × 50 mL) and brine (30 mL), dried over anhydrous Na2SO4 and concentrated using a vacuum rotary evaporator. The residue was purified by column chromatography on silica gel using appropriate mixtures of hexane and dichloromethane (3/1–1/1). Crystals suitable for X-ray analysis were obtained by slow evaporation of an ethanol solution. Colourless solid (44%); m.p. 345 K. Analysis calculated for C14H7Cl4FN2 (M = 364.02): C 46.19, H 1.94, N 7.70; found: C 46.11, H 1.98, N 7.67%. 1H NMR  δ 7.31–7.83 . 13C NMR  δ 114.89, 115.12, 115.41, 115.74, 115.97, 118.33, 127.73, 128.08, 128.67, 129.17, 130.48, 132.04, 132.15 and 136.83. ESI–MS: m/z: 365.11 [M + H]+.The title dye was synthesized according to the reported method  = 1.2Ueq(C). Five outliers Crystal data, data collection and structure refinement details are summarized in Table 410.1107/S2056989021010756/vm2255sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2056989021010756/vm2255Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989021010756/vm2255Isup3.cmlSupporting information file. DOI: 2116300CCDC reference:  crystallographicinformation; 3D view; checkCIF reportAdditional supporting information:


Each Tb atom is coordinated by two cyclopentadienyl ligands in an η 5H5)2(C14H12NO2)], was synthesized from tris(cyclopentadienyl)(tetrahydrofuran)terbium and 2-{[(2-methoxyphenyl)imino]methyl}phenol. Each Tb atom is coordinated by two cyclopentadienyl ligands in an η5-coordination mode and by one N and two O atoms of the organic ligand in a tridentate κ3O,N,O′-mode.The air- and moisture-sensitive title compound, [Tb(C Such a combination of ligands provides an extremely broad structural diversity for cyclopentadienyl derivatives (2-{[(2-methoxyphenyl)imino]methyl}phenolato)terbium, which is a product of the partial protonation of the tris(cyclopentadienyl)terbium complex with 2-{[(2-methoxyphenyl)imino]methyl}phenol . Assuming that each cyclopentadienyl ligand donates three electron pairs, the terbium atom may be considered to be ennea-coordinated. Both cyclopentadienyl ligands are nearly symmetrically η5-coordinated to the Tb3+ cation. Thus, the Cp(centroid)—Tb distances [2.4207 (11) Å for the C1–C5 Cp ring and 2.4062 (10) Å for the C6–C10 Cp ring] are almost equal to the Cp(plane)—Tb distances [2.4196 (11) Å for C1–C5 Cp ring and 2.4054 (10) for C6–C10 Cp ring], and the CCp—Tb bond lengths are similar within each ring (Table 1Cp—Tb distance to the C1–C5 ring is longer by 0.011 Å than to the second Cp ligand. Such a slight asymmetry is caused by the presence of the tridentate asymmetric 2-{[(2-methoxyphenyl)imino]methyl}phenolate (L−) ligand. Atoms of the ligand are situated in two planes formed by the following sets of atoms: O1, C11–C16, N1, C24 (r.m.s. deviation = 0.0167 Å) and O2, C17–C23, N1 (r.m.s. deviation = 0.0333 Å). The dihedral angle between these planes of 44.58 (5)° indicates a perceptible loss of conjugation between two parts of the ligand due to the tridentate κ3N,O,O′-coordination mode. The bond redistribution within the ligand (see table in the supporting information) and the Tb—O and Tb—N bond distances 2Ln(O2NC14H12)]  were previously synthesized in low yields  or protonated (LH) derivatives have been poorly studied, whereas the structures of complexes bearing their closest analogs – doubly charged 2-{[(2-oxidophenyl)imino]methyl}phenolate and its various derivatives – have been studied moderately. This is, likely, due to the higher stability of the latter complexes, which is presumably caused, in short, by a higher degree of the optimization of electrostatic interactions 3(thf) was obtained according to a literature procedure 3(thf)  in 15 ml of THF. The reaction mixture was stirred for 24 h. The solution was concentrated under vacuum to a volume of ca 8–10 ml, and hexane (10 ml) was carefully layered on top of the resulting solution to initiate crystallization. Crystals obtained after several days were dried under dynamic vacuum for 1 h, yielding 0.315 g . The terbium content was determined by direct complexometric titration with the disodium salt of EDTA, using xylenol orange indicator imino]methyl}phenol  in 5 ml of THF was added slowly to a solution of Tb = 1.5Ueq(C) for methyl group and Uiso(H) = 1.2Ueq(C) for others.Crystal data, data collection and structure refinement details are summarized in Table 210.1107/S2056989021013025/yk2162sup1.cifCrystal structure: contains datablock(s) I. DOI: 10.1107/S2056989021013025/yk2162Isup2.hklStructure factors: contains datablock(s) I. DOI: Click here for additional data file.10.1107/S2056989021013025/yk2162Isup3.cdxSupporting information file. DOI: 2127087CCDC reference:  crystallographicinformation; 3D view; checkCIF reportAdditional supporting information:


Starting from this ligand monomeric [M(4‐BzhH2BoxCH)] (M=Na (7), K (18)) and dimeric [{M(4‐BzhH2BoxCH)}2] (M=K (28), Rb (9), Cs (10)) alkali metal complexes were synthesised by deprotonation. Abstraction of the potassium ion of 8 by reaction with 18‐crown‐6 resulted in the solvent separated ion pair [{(THF)2K@(18‐crown‐6)}{bis(4‐benzhydryl‐benzoxazol‐2‐yl)methanide}] (11), including the energetically favoured monoanionic ‐(4‐BzhH2BoxCH) ligand. Further reaction of 4−BzhH2BoxCH2 with three equivalents KH and two equivalents 18‐crown‐6 yielded polymeric [{(THF)2K@(18‐crown‐6)}{K@(18‐crown‐6)K(4‐BzhBoxCH)}]n (n→∞) (12) containing a trianionic ligand. The neutral ligand and herein reported alkali complexes were characterised by single X‐ray analyses identifying the latter as a promising precursor for low‐valent main group complexes.A novel sterically demanding bis(4‐benzhydryl‐benzoxazol‐2‐yl)methane ligand  4−BzhH2BoxCH2)Bis(4‐benzhydryl‐benzoxazol‐2‐yl)methane ( provides a versatile platform for monomeric ligands in [M(4‐BzhH2BoxCH)]  and dimeric [{M(4‐BzhH2BoxCH)}2]  alkali metal complexes. Even more remarkable the reaction of 4−BzhH2BoxCH2 with three equivalents KH and two equivalents 18‐crown‐6 yields polymeric [{(THF)2K@(18‐crown‐6)}{K@(18‐crown‐6)K(4‐BzhH2BoxCH)}]n (n→∞), containing a trianionic ligand. While the monoanions only provide N,N‐chelation like NacNac the latter trianion potentially provides C,N,N,C‐chelation and should be another promising ligand platform. N,N’‐ligands like β‐diketiminatesDippNacNac . These findings initiated research into other ligand platforms, which mimic the coordination abilities of the ubiquitous NacNac ligand, in particular the κ2‐N,N‐coordination of the two imine nitrogen atoms to a metal ion to form six‐membered metallaheterocycles. Starting from the bis(2‐pyridyl)methane ligand and its isoelectronically N,3N2M, M=cationic metal fragment) is maintained. In recent years the focus has been on symmetrical bis(benzoxazole‐2‐yl)methanides I to IV in Scheme 3‐linker unit ethylbisimidate dihydrochloride derived from malonic acid.n‐butyllithium or potassium hydride.X2Al(−I)]X=Cl, I). Despite of the steric demand provided by iPr‐ or tBu‐residues at C4‐position close to the coordination pocket in III or IV, mimicking the bulkiness provided by NacNac ligands, low‐oxidation or low‐valent Group 2 or 13 elements could so far not be synthesised. Therefore, we decided to introduce bulkier benzhydryl groups at the ligand scaffold inspired by compounds containing 2,6‐dibenzhydrylphenyl residues e. g. [:MH(L)]M=Ge or Sn, (L)=‐N(Ar)(SiiPr3), Ar=4‐iPr‐C6H2Bzh2) or [M(ArN)2CN=CtBu2]Ar=4‐tBu‐C6H2Bzh2). In the following paragraph, the six‐step synthesis of bis(4‐benzhydryl‐benzoxazol‐2‐yl)methane  and its behaviour in alkali metal coordination are discussed.Over the last decades, monoanionic bidentate 6, 4‐BzhH2BoxCH2), 2‐amino‐3‐benzhydrylphenol was first synthesised according to the synthetic protocols of Quaranta et al.1–5 see Supporting Information). Thereafter, two equivalents of 2‐amino‐3‐benzhydrylphenol and one equivalent of ethyl cyanoacetimidate hydrochloride C3‐linker unit were reacted by cyclocondensation reaction.) (7), starting material 6 and neat sodium metal were vigorously stirred until all metal was consumed (5 d). After all volatiles had been removed under reduced pressure, 7 was isolated as a white powder in excellent yields (98 %). Crystals suitable for single crystal XRD experiments were grown from a saturated toluene solution at −28 °C. Donor‐free 7 crystallises in the monoclinic space group P21/n with one molecule in the asymmetric unit ] (7) exhibits a distorted κ2‐N,N’‐coordination of the sodium ion by the imine ring nitrogen atoms. A negligible dislocation of the cation from the C3N2‐plane of 0.117(2) Å and a minor butterfly folding angle of 4.82(6)° between the two benzoxazol‐2‐yl moieties is observed (Table 7 (Na1−N1 2.3392(16) Å; Na1−N2 2.3456(15) Å) are similar to the Na1−N1 2.358(6) Å bond of the six‐membered sodium β‐diketiminate complex [(THF)2NaL]3)C(Ph)}2CH) but are slightly shorter than neutral five‐membered TMEDA based [[{Na{N(SiMe3)(Dipp)}(TMEDA)}2] (Na1−N2 2.4726(17) Å; Na1−N3 2.461(2) Å)iPrNC(NAr)(HNiPr)}(THF)]2  (Na1−N1 2.453(1) Å, Na1−N2 2.558(2) Å).+ ion π‐arene, interactions are formed to one phenyl group of the benzhydryl groups each.Ar distances ranging from 2.8305(18) (Cortho) to 3.0414(18) Å (Cipso) indicate a dihaptic arene coordination.1H NMR spectra of 6 and deprotonated species 7 show a significant deshielding in toluene and simultaneous downfield shift of the methanide bridge from δ(−H2C−)=3.85 ppm to δ(−HC−)=5.38 ppm whereas benzylic protons experience a significant upfield shift from δ(−HCPh2)=6.41 ppm to 5.27 ppm. Furthermore, arene protons (Ph and NCOC6H3) are slightly upfield shifted in sodium complex 7 compared to ligand 6. Elemental analysis and mass spectrometry  confirmed the synthesis of bulk [Na(4‐BzhH2BoxCH)] (7).6 with potassium hydride (Scheme 4‐BzhH2BoxCH)]n with n=1 (18) and 2 (28), (YLD: 89 %). Colourless crystals were grown from a saturated toluene solution at −30 °C after 1 d. Single crystal XRD experiments revealed a monomeric as well as a dimeric species in the solid state. Monomeric [(toluene)K(4‐BzhH2BoxCH)] crystallises in the triclinic space group P1‾with one molecule and half a toluene molecule in the asymmetric unit  Å is present. Due to the larger radius of potassium, longer K−N (K1−N1 2.7768(18) Å; K1−N2 2.6982(18) Å) and a less acute N1−K1−N2 of 70.73(5)° are observed. This is accompanied by an increasing butterfly folding angle to 5.54(8)°. Furthermore, potassium phenyl carbon distances suggest that the cation is η2‐(K1−C30 3.467(2) Å, K1−C31 3.224(2) Å) and η3‐coordinated (K1−C23 3.314(2) Å, K1−C27 3.503(2) Å, K1−C28 3.236(2) Å) by one phenyl residue of each benzhydryl group (A search in the CCDC version 5.41 (Aug. 2020)η6‐coordinated ones provided a range of short contacts between K and Cortho of 2.77 to 3.76 Å).  (K−H 2.64(4) to 3.37(3) Å, K−H‐C 117.8 to 120.7°)Ar)2] [M{N(SiMe3)2}3]  .9 and 10 also display interactions of metal ions and methanide bridges, but due to the increased residual electron density for the heavier homologues the determination of the freely refined hydrogen atom positions is not that reliable. Rising effective ionic radii,The second species derived from 0) YLD: 7 % comple0) YLD: 7 % comple0) YLD: 7 % compleZ,Z)‐ and ‐(4‐BzhH2BoxCH) (28: 2.775(2) to 3.015(2) Å; 9: 2.905(5) to 3.063(4) Å; 10: 3.033(3) to 3.285(3) Å), more acute average N−M−N angles  as well as a growing dislocation of the metal from the C3N2 plane (28: 1.877(4) to 2.282(3) Å; 9: 2.036(7) to 2.303(7) Å; 10: 2.302(5) to 2.430(5) Å) as well as from the −HC2N unit (28: 0.85(5) to 2.18(3) Å; 9: 0.699(13) to 2.196(9) Å; 10: 1.16(8) to 2.60(5) Å). Interestingly, the detected butterfly folding angles in both isomers ‐(4‐BzhH2BoxCH)≈23°; ‐(4‐BzhH2BoxCH)≈16°) are negligibly affected while coordinating the alkali metal ions. Additionally, all alkali metal complexes 28–10 were studied by 1H and 13C{1H} NMR spectroscopy in [D8]THF. Recorded 1H NMR spectra show a distinctive pattern of chemical shifts arising from the C2v symmetry of monoanionic bis(benzoxazol‐2‐yl)methanide scaffold and the benzylic bound protons, whereas phenylic protons of the benzhydryl groups could not be clearly assigned due to their peak overlap. Deprotonation of 6 results in an accumulation of electron density in the benzene periphery of both benzoxazol‐2‐yl moieties that again entails a general shielding of corresponding protons and an upfield shift. Concerning the 1H NMR shifts for the C−H bridging position, a minute but continuous decline along K (4.66 ppm)>Rb (4.65 ppm)>Cs (4.64 ppm) complexes is noticed. The opposite is found for para positioned protons  and benzylic protons. These protons exhibit a small but noticeable downfield shift =6.33 ppm to 6.43 ppm; δ=6.03 ppm to 6.17 ppm) which is in tune with the negative charge being restored in the phenylic benzhydryl groups yielding a growing metal arene interaction. Remaining benzoxazol‐2‐yl protons in ortho‐ and meta‐position shifts  do not seem to be influenced by varying alkali cations. Although 1H NMR spectra of 8–10 ([D8]THF) and sodium complex 7 ([D8]toluene) were measured in different solvents, benzylic protons  display a remarkable change of the average chemical shifts (▵δ=0.82 ppm). The 87Rb NMR spectrum of 9 from THF solution shows two singlets. Most probably [{Rb(4‐BzhH2BoxCH)}2] rearranges to give a THF‐solvated rubidium cation [Rb(THF)n] (δ=−1.69 ppm) and a bis(4‐benzhydryl‐benzoxazol‐2‐yl)methanide} based anion [Rb(4‐BzhH2BoxCH)2]− (δ=−254.69 ppm). The 133Cs NMR spectrum of 10 displays only one signal at δ=−31.12 ppm. Additionally, elemental analysis and mass spectrometry  confirmed the synthesis of heavier alkali complexes 8–10.These features Table  cause riZ,Z)‐ and ‐isomers of complex 8–10 and based on former gained knowledge of sterically less demanding bis(benzoxazol‐2‐yl)methanide potassium complexes+ [4‐BzhH2BoxCH]− (11) was isolated as a reddish solid in excellent yields (95 %). Crystals suitable for single XRD experiments were grown by vapour diffusion of pentane to a saturated THF solution of 11 at ambient temperature after 3 d. The colourless crystals in the triclinic space group P1‾contain one bis(4‐benzhydryl‐benzoxazol‐2‐yl)methanide anion and two halve (THF)2K(18‐crown‐6)} cations in the asymmetric unit K(18‐crown‐6)] . (11) was confirmed by mass spectrometry  and elemental analysis.On the basis of reported 2K(18‐crown‐6)}{K2(4‐BzhBoxCH)}]n (n→∞) 12 as very sensitive dark purple crystals by storing THF solutions at −30 °C. The crystal selection and mounting was challenging due to the dark colour and high sensitivity of compound 12. Thus, a moderate single crystal XRD data set could be collected after many attempts. Furthermore, the synthesis of 12 was improved by using ligand 6 and the exact stoichiometric quantities (4‐BzhH2BoxCH2:KH:18‐crown‐6=1 : 3 : 2) . Obtained THF solution was cooled to −30 °C for crystallisation. Complex 12 crystallises in the monoclinic space group P2/n with half a formula unit in the asymmetric unit  Å, C5−K2 3.245(8) Å) to the aryl moieties of two adjacent ‐trianions and also coordinated by an equatorial crown ether molecule. The η2‐coordination provides the link in the polymeric structure. Finally, a third potassium ion in the coordination pocket is surrounded by two nitrogen atoms in κ2‐fashion (N−K1 2.686(3) Å) and a phenyl ring of each benzhydryl moiety in asymmetrically η6‐fashion (CPh−K1: 2.930(3) Å to 3.291(3) Å), respectively. Determined nitrogen potassium distances and the perfect planarity of the ligand scaffold with the potassium ion in the plane of the trianion are in good agreement with the unsolvated κ2‐N,N‐[K(DippNacNac)]ipso‐atoms are basically shortened (1.426(4) to 1.478(4) Å) compared to HCbzh−Cipso of complexes 6–11 (1.508(8) Å to 1.538(6) Å) because of the deprotonation of the two benzylic positions (Cbzh) (benzhydryl group). The two anionic C9‐atoms are essentially in plane with the bound Cipso‐atoms  similar to previously studied potassium trityl complexes [KCPh3(THF)(PMDTA)],3(PMDTA)]3(L)]n .2‐hybridised carbon atoms (for details see Supporting Information), while the steric constraints prevent the phenyl rings from being coplanar leading to a propeller‐like arrangement. Within this arrangement, angles φ of the phenyl groups with respect to C2−C10−C16 plane (C3‐plane) are φ=32.38(17)° (C10 to C15), and 49.68(10)° (C1 to C6), whereas the smallest angle and shortest bond (C9−C16 1.426(4) Å) involves the phenyl system to which the cation is coordinated. These parameters correspond to an increased π‐electron‐delocalisation that is correlated with the overlap of the C3‐plane (C2−C10−C16) and coordinating phenyl ring (C16 to C21) which is dependent on cos(φ)2 functionφ=17.7°,≈90 %). Further direct analyses of 12 were challenging due to its low solubility in most solvents . To find further evidence for the synthesis of trifold deprotonated anion (4‐BzhBoxCH), suspensions of the dark red precipitate (12) were once again protonated (excess≈20 eq. H2O or D2O) in small scale (NMR experiment). These 1H and 2D NMR experiments (for details see Supporting Information), as well as mass spectrometry , confirmed the previous synthesis of 12.Since Brown or Buncel and Menon ascertained that triphenylmethane is deprotonated in THF by potassium hydride when DMFwn‐6)}{K2‐BzhBoxCH6 (4−BzhH2BoxCH2) comprising benzhydryl groups at both C4‐positions (ortho imine positions) in spatial proximity to the coordination pocket was presented. To get a better knowledge of its properties and find a possible precursor complex for subsequent salt metathesis reactions, 6 was deprotonated with alkali metal bases. Obtained products were analysed by NMR spectroscopy, mass spectrometry as well as single crystal XRD experiments. Crystals grown from toluene solutions unveiled monomeric [M(4‐BzhH2BoxCH)] (M=Na (7), K (18)) and dimeric [{M(4‐BzhH2BoxCH)}2] (M=K (28), Rb (9), Cs (10)) species in solid state. Latter alkali metal complexes display distorted κ2‐N,N‐coordinated ‐ and an ‐(4‐BzhH2BoxCH) configurational isomers, which display various polyhaptic metal arene interactions. Furthermore, potassium ion sequestration of 8 by 18‐crown‐6 resulted in [{(THF)2K(18‐crown‐6)}(4‐BzhH2BoxCH)] (11) a solvent separated ion pair containing energetically favoured monoanionic ‐(4‐BzhH2BoxCH) ligand. Additionally, reaction of 4‐BzhH2BoxCH2 with three equivalents KH and two equivalents 18‐crown‐6 yielded polymeric [{(THF)2K@(18‐crown‐6)}{K@(18‐crown‐6)K(4‐BzhBoxCH)}]n (n→∞) (12) featuring a remarkable trianionic ligand. The single crystal X‐ray diffraction experiment of 12 revealed one of the potassium ions to be η2‐coordinated by the benzoxazol‐2‐yl scaffold of two adjacent ‐ligands plus a crown ether molecule. A second potassium ion is surrounded by two nitrogen atoms in κ2‐fashion as well as one phenyl ring of each benzhydryl moiety in a symmetrically η6‐fashion, respectively. Future work with regard to the mono‐ (4‐BzhH2BoxCH) and trianionic (4‐BzhBoxCH) ligand will focus on the coordination of other metal, i. e. those from Group 13 or lanthanides. The benzhydryl groups attached to the benzoxazol‐2‐yl scaffold seem to exhibit similar qualities to the triphenylmethane, which is able to stabilise carbanionic, radical or carbonium ionic species owing to the extensive π‐delocalisation. With this in mind, future research might focus on the synthesis of 4‐BzhH2BoxCH2 based radical and carbonium ion compounds.Within this work, the six‐step synthesis and characterisation of a novel bulky bis(benzoxazol‐2‐yl)methane ligand d6, thf‐ d8, toluene‐ d8).[45] Deuterated benzene and toluene were dried over K (65 °C), THF was pre‐dried with LiAlH4 and stored over activated molecular sieve (3 Å) and stored in an argon dry box. Elemental analyses  were performed on a Vario EL3 at the Mikroanalytische Labor, Institut für Anorganische Chemie, University of Göttingen. LIFDI‐MS spectra were measured on a Jeol AccuTOF spectrometer and ESI (HR‐MS) measurements were performed on Bruker maXis spectrometer. All pKa measurements in acetonitrile were carried out as in reference [13]. Shock‐cooled crystals were selected from a Schlenk flask under argon atmosphere using the X‐TEMP2 device.6, 18, 9, 10, 11) or Ag‐  IμS microfocus source.6 a 3λ correction was applied.2 using the full‐matrix least‐squares methods of SHELXL6),2031908 (for 7), 2031909 (for 81), 2031910 (for 82), 2031911 (for 9), 2031912 (for 10), 2031913 (for 11), and 2031914 (for 12)Deposition Numbers 2031907  and 2D  NMR spectroscopic data were recorded on a Bruker Ascend 500 MHz, 400 MHz, and Avance 300 MHz spectrometer and referenced to the deuterated solvent  should be addressed to the authors.SupplementaryClick here for additional data file.