Research findings show that NH4+ (oxygen ligand) and CH3COO– (hydrogenligand) with preferential adsorption on the Zn electrode surface can not only hinder Zn anode directly contact with active H2O, but also regulate the pH value of the electrolyte, thus suppressing the parasitic reactions. Additionally, the formed SEI is mainly consisted of Zn5(CO3)2(OH)6 with a high Zn2+ transference number, which could achieve a dendrite‐free Zn anode by homogenizing Zn deposition. Consequently, the Zn||Zn symmetric batteries with CH3COONH4‐based electrolyte can operate steadily at an ultrahigh current density of 40 mA cm–2 with a cumulative capacity of 6880 mAh cm–2, especially stable cycling at −10 °C. The assembled Zn||MnO2 full cell and Zn||activated carbon capacitor also deliver prominent electrochemical reversibility. This work provides unique understanding of designing multi‐functional electrolyte additive and promotes a long lifespan at ultrahigh current density for AZIBs.Aqueous Zn‐ion batteries (AZIBs) have been recognized as promising energy storage devices due to their high theoretical energy density and cost‐effectiveness. However, side reactions and Zn dendrite generation during cycling limit their practical application. Herein, ammonium acetate (CH 3COONH4 electrolyte additive for dendrite‐free embraced extraordinary rate‐performance and high reversibility with a cumulative capacity of 6880 mAh cm–2 at an ultrahigh current density of 40 mA cm–2, superior to other Zn anode. The Zn||Zn symmetrical cells with attractive cycling performance stabilize over 900 h at a low temperature of −10 °C.Zn metal anode enabled by CH In the recent years, rechargeable aqueous zinc ion batteries (AZIBs) have lately drawn intensive attentions, mainly owing to their rich resources, cost‐effectiveness, environmental robustness, and high‐safety. Furthermore, the zinc metal possesses a higher theoretical capacity density (5855 mAh cm–3) and low redox potential (−0.763 V vs standard hydrogen electrode). Unfortunately, the problem of interfacial parasitic reactions, corrosion, and formation of zinc dendrite during the Zn plating/stripping process have hindered their commercialized application, which leads to poor utilization, lower Coulombic efficiency (CE), and short cycling lifespans of zinc metal anodes. Therefore, designing dendritic‐free and stable Zn anodes for AZIBs is a pressing task.Lithium‐ion batteries (LIBs) have taken the leading position as rechargeable and environmentally benign energy storage equipment according to the lack of memory effects and high energy densities.3, 4 Among them, electrolyte optimization comprises high concentration electrolytes, quasi/solid‐state electrolytes, and electrolyte additives. Therefore, the electrolyte additives with the advantages of simplicity, high efficiency, and low‐cost are regarded as one of the most promising ways to stabilize Zn anodes. To date, a series of studies have been researched on the development of electrolyte additives. For instance, Wang et al. have proved that the decomposition of H2O was eliminated by the preferential solvation of dimethyl sulfoxide (DMSO) with Zn2+ and the strong interaction of H2O‐DMSO. In addition, Chen's group adopted a saccharin additive into the electrolyte to reduce the proportion of H2O in the electrical double layer through the characteristic adsorption of saccharin anions on the zinc anode, thus inhibiting the side reaction of the electrode‐electrolyte interface. Other electrolyte additives such as glucose, ethylenediaminetetraacetic acid tetrasodium salt, glycerol, 1‐ethyl‐3‐methylimidazolium chloride, ethyl ether, and lithium chloride, were also studied, and the progress of many efforts was obvious. However, attention is still limited to the pH of the electrolyte, which plays a crucial role in restricting side reactions and improving interface stability during cycling, especially at high current densities.Several modification strategies have been proposed to build durable and high‐performance Zn anodes, including surface/interface adjustment and construction, electrode/host structure design, electrolyte optimization, and separator modification.20 Amo For instance, AZIBs and Zn‐ion‐based capacitors that maintain stable performance under the subzero temperatures are urgently needed. The aqueous electrolytes will freeze at low temperature (<0 °C), which not only decreases the migration rate of Zn2+, but also causes a sharp fluctuation in pH at the interface within the Zn electrode/aqueous electrolyte. As a result, the overpotential is high, CE is poor, and the cycling life is limited. Therefore, it is vital to maintain the pH value of the electrolyte in a timely manner when operating at subzero temperatures, and less attention has been paid to these issues.Recently, the demand for commercial energy storage applications operated in extreme weather or low‐temperature conditions has risen.36 For3COONH4), is initially introduced in aqueous ZnSO4 electrolyte to restrain H2 evolution and maintain the pH value of the electrolyte . Moreover, the ZnSO4: CH3COONH4 electrolyte effectively improves the electrochemical performance of Zn‐based electrochemical energy storage devices based on MnO2 and activated carbon (AC) cathodes.Herein, a trifunctional electrolyte additive, ammonium acetate  and the corrosion current decreasing by 0.252 mA cm–2 compared with that in the ZnSO4 electrolyte , which is superior to most of the previous reports  tests further confirmed that there was a significant reduction in the roughness of the cycled Zn anode surface in the presence of additives  characterization was utilized to probe the inhibitory effect of the additives on dendrite growth, as presented in s Figure . In cont2 Figure . The mors Figure . Optical4: CH3COONH4 electrolytes exhibited more pronounced C 1s  and N 1s signals  belonging to CH3COO– and NH4+, respectively, partially adsorbed on the surface of Zn foil. Nevertheless, the N 1s spectrum of the zinc anode in the ZnSO4 electrolyte surface shows no significant diffraction peaks, and the peak density of C═O is extremely weak. To corroborate the mechanism of the protective barrier on the Zn anode surface, the absorption energies of H2O, NH4+, and CH3COO– on Zn (0001) were calculated through density functional theory (DFT). Figure4+ and CH3COO– on Zn (0001) are much lower than that of H2O, demonstrating that NH4+ and CH3COO– are adsorbed on the Zn metal surface to form an ion protective layer during cycling, which effectively blocks the direct contact of water molecules with the zinc electrode.In addition, the solid electrolyte interphases (SEI) formation of Zn anodes in the modified electrolyte was also explored. As depicted in Figure 4: CH3COONH4 electrolyte was carried out, it was found that the SEI layer with a thickness of about 2 µm was formed on the anode surface after cycling  to Zn metal (≈1021.7 eV), further verifying that the formation of the protective SEI layer on the Zn anode, which is consistent with the characterization results of SEM‐EDS. In Figure 5(CO3)2(OH)6 component was produced on the surface of Zn anode after cycling in ZnSO4: CH3COONH4 electrolyte 2(OH)6 (Equation 5(CO3)2(OH)6:To investigate the detailed component of the SEI layer, scanning electron microscope ‐ energy dispersive spectroscopy (SEM‐EDS) characterization for the cycled Zn anode in ZnSOtZn2+) of the SEI formed in the modified electrolyte was larger than that in the ZnSO4 electrolyte  of the Zn2+ de‐solvation in different interfaces was obtained by fitting the corresponding Nyquist plots of Zn symmetric cells with different kinds of electrolyte from 298.15 to 323.15 K  in ZnSO4: CH3COONH4 electrolyte increased by 14.2 mV at the first cycle compared with ZnSO4 electrolyte 2(OH)6 plays a significant role in the inhibition of dendrite formation.The Zn‐ion transference number 6·5H2O was generated on the interface of the zinc anode. In sharp contrast, the diffraction peak intensity of Zn4SO4(OH)6·5H2O on the contact face of the zinc electrode after cycling in the modified electrolyte can almost negligibly, suggesting that the SEI formed can evidently ameliorate the thermodynamic steadiness of Zn, which could be propitious to enhance the long‐term cycle performance of AZIBs, particularly at ultrahigh current density (40 mAh cm–2). Compared to the use of ZnSO4 bare electrolyte, the cells in the electrolyte with additives exhibited a stable resistance of ≈250 Ω with the extension of standing time. The phenomenon further demonstrated that the SEI protective layer could effectively alleviate the adverse chemical side reaction of interface within the Zn anode and the ZnSO4: CH3COONH4 electrolyte, to ensure excellent interface stability , mainly because NH4+ and CH3COO– could balance the concentration of OH– and H+ in the electrolyte. HER inevitably occurs during charging and discharging, which leads to corrosion of the Zn anode and a local rise in the pH value. As observed, the pH value of the electrolyte without CH3COONH4 additive increased from 4.29 to 4.85 after 150 min of cycling at a current density of 5 mA cm–2, while the pH of the electrolyte with the CHCOONH4 held steady, implying that the pH buffered CH3COONH4 can remain the pH value of the electrolyte by combining CHCOO– and NH4+ with the H+ and OH– in the electrolyte respectively, which is capable of achieving secondary protection for the zinc electrode to suppress the electrochemical side reactions during the charge and discharge process. The pH evolution of the two electrolytes after cycled at a higher current density of 20 mA cm–2 was also monitored . More surprisingly, Zn||Zn symmetric cell work steadily for 900 h under harsh conditions at −10 °C, the Zn||AC capacitor with excellent cycling performance stabilizes over 10000 cycles at low temperature of −10 °C. Finally, this novel electrolyte additive provides a reference for the development of AZIBs with a wide temperature range in the future.In summary, we have discovered that by utilizing CH44 electrolytes were prepared by dissolving ZnSO4·7H2O in deionized water at room temperature and the ZnSO4: CH3COONH4 electrolytes were prepared by adding 20 mM ammonium acetate (CH3COONH4) into the 2 M ZnSO4 electrolytes. The MnO2/carbon cloth cathode was prepared by the electrodeposition method according to the previous research. Typically, the electrodeposition was conducted in a solution consisting of 0.1 M Mn(CH3COO)2·4H2O and 0.1 M Na2SO4 at 1.0 V for 300 s. More details of the material characterization and computational methods were provided in the Supporting Information.The ZnSOresearch.37 Typ4 and ZnSO4: CH3COONH4) each with 50 µL were dropped into the coin cell with a piece of glass fiber as a separator. The full cells were fabricated by using Zn plate, MnO2 cathode, and two different electrolytes (ZnSO4 with 0.2 M MnSO4 or ZnSO4: CH3COONH4 with 0.2 M MnSO4) and glass fiber. The galvanostatic cycling tests was tested in the voltage range of 0.8–1.8 V (vs Zn2+/Zn).The symmetric cells were assembled by using two pieces of Zn foils as two electrodes in CR2032‐type cell. Two different electrolytes (ZnSOThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.Supplemental Video 1Click here for additional data file.


In the originally published version of this paper, an incorrect definition forthe term “MAP7” was introduced during the production process. The correctdefinition for MAP7 is “microtubule-associated protein 7,” which nowappears with the article online.The production team apologizes for the error.


However, the efficacy of the biological effect of the different isomers and the impact on humans are unknown. Our study assessed carboxylative efficacy of trans and cis MK7 and compared it with other vitamin K isomers, evaluating both the expression of residues of carboxylated Gla‐protein by western blot analysis and using a cell‐free system to determine the GGCX activity by HPLC. Trans MK7H2 showed a higher ability to carboxylate the 70 KDa GLA‐protein, previously inhibited in vitro by warfarin treatment. However, cis MK7 also induced a carboxylation activity albeit of a small extent. The data were confirmed chromatographically, in which a slight carboxylative activity of cis MK7H2 was demonstrated, comparable with both K1H2 and oxidized trans MK7 but less than trans MK7H2. For the first time, a difference of biological activity between cis and trans configuration of menaquinone‐7 has been reported.Carboxylative enzymes are involved in many pathways and their regulation plays a crucial role in many of these pathways. In particular, γ‐glutamylcarboxylase (GGCX) converts glutamate residues (Glu) into γ‐carboxyglutamate (Gla) of the vitamin K‐dependent proteins (VKDPs) activating them. VKDPs include at least 17 proteins involved in processes such as blood coagulation, blood vessels calcification, and bone mineralization. VKDPs are activated by the reduced form of vitamin K, naturally occurring as vitamin K1 (phylloquinone) and K2 . Among these, MK7 is the most efficient in terms of bioavailability and biological effect. Similarly to other  GGCXγ‐glutamylcarboxylaseGlaγ‐carboxyglutamateGluGlutamateK1H2Reduced phylloquinoneMK4H2Reduced menaquinone‐4MK7H2Reduced menaquinone‐7MKsMenaquinonesnHDFsneonatal Human Dermal FibroblastsTRLstriglyceride rich lipoproteinsVKDPsvitamin K‐dependent proteinsVKORC1vitamin K 2,3‐epoxide reductase complex subunit 11Bacillus subtilis natto.Vitamin K represents a group of fat‐soluble compounds sharing a common chemical structure, 2‐methyl‐1,4‐naphthoquinone, and differ in length and in the saturation degree of the side chain.The main function of all types of vitamin K is to activate proteins that serve important roles in blood clotting, heart, and bone health. In particular, the reduced form of vitamin K is a cofactor for γ‐glutamylcarboxylase (GGCX), an enzyme catalyzing the reaction of post‐translational carboxylation of glutamate (Glu) residues into γ‐carboxyglutamate (Gla) of the vitamin K‐dependent proteins (VKDPs) activating them. All the VKDPs must be carboxylated to become active and the most well‐known include coagulation factors II, VII, IX, X, prothrombin, proteins C, S, Z, and the bone‐related proteins .As a result of the carboxylation, vitamin K is transformed to an epoxide which is reduced back by the vitamin K 2,3‐epoxide reductase complex subunit 1 (VKORC1).However, vitamin K1 and K2 exhibit different chemical characteristics leading to a difference in absorption and tissue distribution, therefore affecting the biological function. In fact, after the transportation of all vitamin K in the liver by triglyceride‐rich lipoproteins (TRLs), K1 is retained and rapidly excreted while K2 is transported in circulation by LDL to extrahepatic tissues such as bone and vasculature. Therefore, vitamin K2 has a better absorption profile in comparison with K1, although it varies between isoforms.In addition, the role of MK7 in bone health has been highlighted by several studies showing how natto consumption reduces the incidence of hip fractures in women in Japantrans K vitamers, whereas by chemical synthesis both isomeric forms (cis and trans) are produced in a variable proportion dependent from the method of synthesis used. Moreover, the industrial production includes a purification phase of the post‐reaction mixture and, depending on the method and on the efficiency, the final preparation may contain both forms.cis isomers at different locations in the isoprenoid chain of MK7.The production of K vitamers, including MK7, can occur by natural fermentation or by chemical synthesis. Chemical synthesis is a more economical method. The fermentation is carried out by highly specific enzymes and produces all cis/trans isomers is very important taking into consideration the biological properties of the vitamin preparations, because the impact on humans is unknown. Moreover, some studies demonstrated that the cis isomer of the vitamin K1 is inactive or exhibits merely 1% of the biological activity of the trans forms and is present in supplemented food, in particular in infant formulas.cis isomer compared with the trans of this menaquinone. In this context, the present study aims to compare the carboxylative efficacy of both cis and trans MK7 isomeric forms.The presence of different forms of vitamin K2, including 2cis and trans isomeric forms of MK7  and cis (≥95%) MK7 were kindly provided by Gnosis‐Lesaffre , while MK4, K1, and warfarin were purchased from Sigma‐Aldrich.The carboxylative efficacy of 7 Figure  has been2.12.Primary culture of neonatal Human Dermal Fibroblasts (nHDFs), purchased from Lonza Group Ltd., were maintained in Minimum Essential Medium (MEM) supplemented with 10% fetal bovine serum (Carlo Erba reagents) penicillin (100 U/ml), streptomycin (100 μg/ml), and L‐glutamine (2 mM), at 37°C under controlled humidified atmosphere containing 5% COtrans MK7 , to find the lowest concentration effective in carboxylation restoring. Subsequently, MK7 isomers were compared by treating nHDFs for 24 h with 1 and 10 μM of cis or trans MK7 in combination with warfarin (200 μM).For all experiments, confluent cells at the passages 11–14 were treated and incomplete medium was used to avoid the interference of serum K vitamins. After the verification of the warfarin treatment condition efficient on Gla‐protein inhibition (200 μM for 24 h), cells were incubated for 24 h in the presence of warfarin 200 μM and different concentrations of Treated cells were scraped in cold PBS, centrifuged (1000 g for 5 min at 4°C) and lysed in RIPA buffer  and added to a protease inhibitor cocktail.2.2Protein concentration was quantified using a BCA protein assay kit (ThermoFisher Scientific) and 35 μg of denaturated proteins were resolved on 10% SDS–PAGE and then transferred onto polyvinylidene fluoride membrane. The membranes were blocked in Tris‐buffered saline with 0.2% (v/v) Tween 20 (TBS‐T) containing 5% (w/v) nonfat dry milk, and then exposed to the primary antibody anti‐γ‐carboxyglutamyl (Gla) residues  or anti‐β‐actin  for 2 h at room temperature. After washing in TBS‐T, the membranes were incubated with the secondary antibody anti‐mouse IgG, HRP‐linked  for 1 h at room temperature. Protein bands were acquired by C‐DiGit Blot Scanner (LI‐COR Biosciences) using SuperSignal West Dura ECL (ThermoFisher Scientific) and quantified by densitometry using the ImageJ software. β‐Actin was used as a reference control.2.3cis and trans MK7 forms to promote γ‐glutamyl carboxylase activity was evaluated chromatographically by using an hexapeptide (FLEFLK) conjugated with fluorescein marker (FITC) containing only one carboxylation site as reported by the method previously described.cis and trans MK7 isomers were chemically reduced by incubation in a mixture of 20 mM DTT, 50 mM NaCl, and 2 mM Tris at 37°C for 24 h in the dark and added to a microsomal fraction extracted from the livers of five mice fed for 4 weeks with a low vitamin K diet  containing GGCX and to a FLEFLK‐FITC fluorescent peptide. HPLC analysis with fluorescence detection optimized for FITC (494 nm excitation and 521 nm emissions) enabled the carboxylated and the undercarboxylated forms to be discriminated. The efficacy of each vitamin K reduction was measured by reversed‐phase HPLC by separation on a C12 Max RP  against isocratic methanol and detection at 246 nm, as described earlier.The ability of 2.4p value of ≤0.05 was considered statistically significant and reported as: *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001.All experiments were performed at least in triplicate. Data are presented as the mean ± standard deviation. Statistical analyses were conducted using GraphPad Prism version 8.4.2. Comparisons among groups were analyzed using one‐way ANOVA followed by Tukey's multiple comparisons test for GGCX activity and using unpaired T test for GLA‐protein content. A 3Efficacy in promoting carboxylation by different forms of vitamin K could be evaluated in a cellular model by blocking the recycling of vitamin K already contained in the cells as this could mask the results. This is possible using vitamin K antagonists, such as warfarin, which inhibit the enzyme vitamin K epoxide reductase.trans MK7 able to counteract the warfarin effect, four different concentrations  of this vitamin were tested. Figure trans MK7 was not enough to restore the carboxylation of the 70 kDa GLA‐protein inhibited by 200 μM warfarin. It was partially restored by adding 1 μM of exogenous trans MK7 and was totally rescued in the presence of 10 μM trans MK7, while further GLA‐protein increment did not occur with higher MK7 concentration  residues of a single unknown protein band of approximately 70 kDa  conjugated with fluorescein. When its carboxylation site is carboxylated, its retention time changes and can be revealed by HPLC.Since only the reduced form of vitamin K acts as a cofactor of the carboxylases and is responsible for the activation of the vitamin K‐dependent proteins, to compare the carboxylative activity of different vitamin K isomers, they were chemically reduced before the addition to the microsomal fraction containing GGCX and FLEFLK‐FITC fluorescent peptide. Therefore, the carboxylative efficacy is dependent on the amount of reduced forms of vitamin K isomers used and reported in Table 2 and MK7H2 promoted the highest carboxylative activity reaching values, expressed as a percentage of GGCX activity with respect to K1H2, of 168 ± 22% and 166 ± 48%, respectively. However, MK4 along with K1 had the highest stability in their quinol form, being predominantly present in the reduced form . Conversely, carboxylative activity of trans MK7 is attributable to only 44% of its reduced form. Finally, cis MK7H2 showed a comparable GGCX activity to both oxidized trans MK7 and K1H2 , significantly lower compared with trans MK7H2 (p ≤ 0.01).As shown in Figure 4cis and trans, resulting in a non‐linear and linear molecular structure, respectively. The double bond arrangement determining the molecular shape affects the interaction with subcellular structures such as GGCX and, consequently, the biological activity.Vitamin K can exist as geometric isomers, trans configuration of vitamin K1cis and trans phylloquinone in different tissues of vitamin K deficiency‐induced rats following intracardiac injection of both isomers.cis isomer of vitamin K1 in liver decreased much slower in comparison with the trans one. Moreover, the cis isomer was associated with the mitochondrial fraction, while the trans configuration with the endoplasmic reticulum fraction.It was demonstrated that only the In this context, the present study aimed to compare the vitamin MK7 isomers efficacy in promoting carboxylation, evaluating both the expression of residues of carboxylated Gla‐protein by western blot analysis and using a cell‐free system to determine the vitamin K‐dependent gamma‐glutamyl carboxylase (GGCX) activity by HPLC.trans MK7 showed a higher ability to carboxylate the 70 KDa GLA‐protein, previously inhibited by warfarin, compared with cis isomer independently from the concentration used. However, cis MK7 co‐supplemented with warfarin was found to induce a carboxylative activity albeit of small extension. This could be due to the real capacity of this isomeric form to interact with vitamin K‐dependent gamma‐glutamyl carboxylase. Alternatively, since vitamin K is recycled, the possible presence of residual trans form could be enough to activate the carboxylation.cis MK7H2, comparable with both K1H2 and oxidized trans MK7, has been showed. The latter is inactive as it must be reduced to act as a cofactor, but probably still retains some type of carboxylative activity although to a lower extension.2 and trans MK7H2 showed a similar and the highest carboxylative capacity, the amount of reduced trans MK7 (44%), the active form, was lower compared with MK4H2 (100%).Firstly, carboxylation deficit was created by treating the fibroblasts with warfarin, which in the cellular model and under the experimental conditions blocked the carboxylation of a single protein band corresponding to about 70 kDa, which was analyzed in relation to different forms of MK7. In this cellular model, cis/trans in the composition could have affected the carboxylative activity of the menaquinones.In this regard, Buitenhuis et al.Cis isomers of MK7 are formed during the chemical synthesis of this vitamin.cis isomers at different locations in the isoprenoid chain of MK7.cis isomers could be remarkably high, both leading to increased instability and lower biological effect.cis and trans forms of MK7. Due to the identification of a high content of the cis/trans MK7 isomers in reference to all trans MK7 in some dietary supplements,cis/trans forms of MK7 is needed.Therefore, the supplements can contain both the cis isomers have lower biological effects, the isomeric composition must be taken into consideration for the supplement formulation and its efficacy.Since the vitamin K supplementation is essential to reach the recommended daily intake in certain conditions such as during developmental stages, CVD, and osteopenia, and, considering that the cis and trans configuration of menaquinone‐7 has been reported. In particular, the trans isomeric form showed higher carboxylative capacity compared with the cis one. However, this latter was not completely ineffective. This could be as a consequence of a conserved capacity of interaction with enzymes even if to a lower extension and/or of the presence of trans residual contaminant traces.In conclusion, for the first time a difference of biological activity between No conflict of interest to declare.


CK2 is a ubiquitous protein kinase with an anti-apoptotic role and is found to be overexpressed in multiple cancer types. To this end, the inhibition of CK2 is of great interest with regard to the development of novel anti-cancer therapeutics. ATP-site inhibition of CK2 is possible; however, this typically results in poor selectivity due to the highly conserved nature of the catalytic site amongst kinases. An alternative methodology for the modulation of CK2 activity is through allosteric inhibition. The recently identified αD site represents a promising binding site for allosteric inhibition of CK2α. The work presented herein describes the development of a series of CK2α allosteric inhibitors through iterative cycles of X-ray crystallography and enzymatic assays, in addition to both fragment growing and fragment merging design strategies. The lead fragment developed, fragment 8, exhibits a high ligand efficiency, displays no drop off in activity between enzymatic and cellular assays, and successfully engages CK2α in cells. Furthermore, X-ray crystallographic analysis provided indications towards a novel mechanism of allosteric inhibition through αD site binding. Fragments described in this paper therefore represent promising starting points for the development of highly selective allosteric CK2 inhibitors. Development of a novel CK2α inhibitor from a fragment-based screen with a proposed novel mechanism of action. The role of CK2α is to recruit substrates and to control the intracellular localisation of the kinase.2 CK2 has been found to be overexpressed in numerous cancer cells, and many of its roles in cancer, such as modulation of cell proliferation and cell death, are attributable to its activity in the nucleus.3 There are no known mutations in CK2α implicated in cancer, in line with its constitutively active role, and rather than an oncoprotein, it is considered a facilitator that enhances tumorigenesis.4CK2 is a pleiotropic, constitutively active Ser/Thr kinase with one of the largest sets of target proteins of eukaryotic protein kinases.5 As a pro-survival kinase, overexpression of CK2α appears to both facilitate the growth of tumour cells and provide a mechanism for the cells to avoid apoptosis. Therefore, cells rely on CK2α's activity to survive, becoming addicted to its non-oncogenic activity which is typically enhanced by increasing CK2α expression. This is particularly true for cells that are challenged with chemotherapeutic agents and the most promising uses for CK2α inhibitors stem from these observations.6One of the key roles of CK2α is to promote anti-apoptotic pathways through activation of the NF-κB and Wnt signalling pathways.7–9 Indeed, inhibition of CK2α has been demonstrated to help overcome resistance to specific chemotherapeutic agents. For example, imatinib-resistant CML cells were shown to become sensitive to the drug again when co-administered with CK2α inhibitors.10–13Drug resistance is a serious problem for cancer therapies, and agents that can reverse or prevent the emergence of drug resistance are desperately needed. By suppressing survival signals, CK2α inhibition shows great potential as a combination therapy agent that could be used with tumour-specific agents to both augment their efficacy and minimise the development of resistance, or even reverse it.14There are also examples of tumours where CK2α could be effective as a monotherapy target. For example, glioblastomas, irrespective of their stage or p53 status, have been shown to be particularly vulnerable to CK2α inhibition. Glioblastomas are traditionally hard-to-treat cancers, highly malignant and with poor prognosis and thus novel treatments for these tumours is of great importance. On the contrary, non-cancerous glial cells appear to be unaffected by CK2α inhibition suggesting that selectivity for cancer cell death could be achieved with CK2-inhibiting therapies.15–17 Despite its limited selectivity, CX-4945 is well-tolerated, suggesting that inhibition of CK2α activity is a viable therapeutic target, notwithstanding the ubiquitous roles of CK2 in cells.18 However, promiscuous inhibitors are likely to have more serious side effects if used therapeutically and thus it is desirable to have more selective kinase inhibitors to probe the true potential of CK2α inhibition in the clinic.ATP competitive inhibitors of CK2α have been extensively studied, but they tend to suffer from relatively poor kinase specificity, as exemplified by the clinical candidate CX-4945.6,19,20 This pocket provides an exciting opportunity for the development of more specific CK2α inhibitors with novel mechanisms of action. We initially utilised this new pocket to develop a proof-of-concept molecule by growing a fragment hit from the αD pocket into the ATP site by linking it to a low-affinity active site “warhead”. The resulting molecule (CAM4066) is a nanomolar CK2α inhibitor with better selectivity than any other previously described CK2α inhibitor and inhibits the growth of several cancer cell lines.6,19A promising strategy for the development of more selective CK2α inhibitors is to target binding pockets outside of the conserved ATP binding site. Previously, we have used a fragment-based approach to discover a new, cryptic pocket located next to the ATP site, termed the αD site.In this work, using a fragment-based approach, we discovered novel molecules that could inhibit the activity of CK2α through binding in the αD pocket. The work described herein showcases how CK2 inhibition can be achieved without relying on interactions with the highly conserved ATP binding site and, therefore, paves the way towards the development of highly selective CK2α inhibitors.6 The elaboration of fragment 1 into the inhibitor CAM4066 has been reported previously.6,19The original fragment screens that led to the discovery of the αD pocket identified five fragments which bound in the αD pocket .6 The elX-ray crystallography showed that fragments 2, 4 and 5 bound in both the αD site and ATP site and so were of limited use for probing the αD site . FragmenTo this end, a virtual secondary screen was conducted whereby a series of commercially available and in-house analogues of 3 were docked using glide and the promising compounds from this virtual screen were tested against CK2α. This was performed initially as a crystallographic screen, after which any compounds that bound solely in the αD site were followed up by the kinase activity assay. From this process, three more fragments were discovered to bind only in the αD pocket  whilst also exhibiting promising ligand efficiencies of 0.44 and 0.47, respectively (50 = 86 ± 24 μM) which again led to a promising ligand efficiency of 0.44  and maintained high ligand efficiencies (≥0.50). The bromine of fragment 8 was also systematically varied with a range of common substituents  as determined by the phosphorylation assay and similar binding affinities as determined by ITC  μM of 8 .As expected, the binding of fragment 8 was largely inhibited by the αD-binder, indicating that fragment 8 does indeed bind in the αD site .vice versa, which is likely if 8 and its analogues affect CK2α through an allosteric mechanism. Further study would be needed to explain this observation.The result from the experiment with CX4945 was less clear. In the presence of CX4945, the binding of fragment 8 was significantly reduced . This coThe crystal structures of all the key fragments studied herein clearly showed that these compounds bound to CK2α in the αD pocket and appear to inhibit the enzyme through allostery. The crystal structures yield several clues as to the possible mechanism of the allosteric inhibition.1)et al. to be a crucial residue: when Asn118 was deleted, CK2α was no longer active.22 Asn118 is replaced upon its movement by a conserved water which sits at the mouth of the αD site where it interacts with the backbone carbonyls of Thr119 and Ile164.Firstly, ATP binding may be altered by changes in the hinge region caused by the movement of the αD loop. Specifically, the movement of the hinge region causes Asn118 to rotate out from the mouth of the αD pocket into a position where it participates in a water bridge to ATP. Asn118 has previously been shown by Srinivasan 2)6,23 When ATP or its analogues are bound, the loop normally adopts an open conformation, but when the ATP site is empty, or occupied by a compound not interacting with the hinge region in the same way as ATP, the loop adopts a closed conformation. From this it can be inferred that when ATP leaves the ATP site, the loop will then adopt the closed conformation; the transition to the closed conformation may be important for causing ADP to leave the ATP site. However, when the αD site is occupied by the fragments presented herein, this transition cannot occur, possibly stalling the phosphorylation mechanism.A second possible mechanism of inhibition could be the blocking of the transition between the open and closed form. As has been discussed previously, the αD loop is uniquely flexible in CK2α and has been observed in multiple conformations, most commonly the open and closed forms in crystallography.19 This could be attributed to a number of different factors. Firstly, many of the previous fragments bound very weakly so inhibition would not be observable in the assay. Secondly, in the structures of many of these previous fragments (e.g. PDB entry 5CS6) the αD loop is displaced and enters a more disordered open conformation. On the contrary, when the allosteric fragments bind, the αD loop is locked in a more rigid, ordered conformation which is also reflected in lower B-factors for this loop . Furthermore, fragment 8 also showed promising inhibition of cell growth through inhibition of phosphorylation by CK2α (GI50 = 88 ± 7 μM). This fragment-sized tool molecule, alongside its derivatives, confirmed that the αD site can be successfully exploited to achieve inhibition of CK2. Although 8 is unlikely to display high kinase selectivity due to its small size, it opens the potential for further development to identify a selective tool compound for CK2. The binding site was confirmed in solution by ligand-based NMR and the crystal structures of the various fragments bound gave several indications as to the mechanism of allosteric inhibition, but more detailed analyses are needed to eliminate any orthosteric effect on the ATP site by 8. These molecules and the information we have presented herein represent a promising starting point for future development and structure-based design of allosteric CK2α inhibitors which operate by a novel mechanism of action.We have presented five diverse fragments bound in the αD site. One of these fragments (3) bound solely in the αD site and showed weak inhibition of the kinase activity of CK2α. This weakly binding fragment was optimised into a higher affinity molecule, fragment 8, that bound solely in the αD site and showed clear inhibition of CK2α (ICThere are no conflicts to declare.MD-013-D2MD00161F-s001


The –COO−–Bi3+ ionic bond construction was conductive to enhance the interface affinity between BiVO4 and MIL–101–NH2. Due to the highly efficient light capture and sufficient electron traps induced by oxygen vacancies and the formation of a heterostructure, the improved separation and transportation rates of charge carriers are realized. In addition, the MIL–101–NH2/BiVO4 composite is favorable for Cr(VI) photocatalytic removal (91.2%). Moreover, FNBV–3 (Fe/Bi = 0.25) also exhibited an excellent reusability after five cycles.In this study, a flower–like BiVO At present, several available methods have been proposed to remedy the pollution, including catalytic reduction, chemical precipitation, membrane–based separation, and absorption [Heavy metal ions have increasingly attracted attention in wastewater pollutants . Among tsorption . Very resorption . To datesorption ,6,7.4 has proven to be one of the classical photocatalysts with non–toxicity, a good stability, and a suitable band gap [4 needs to surmount the low surface and displays a poor performance in photogenerated electron–hole pairs separation. Against that, regulating the properties of a photocatalytic system via optimizing the morphologies or structure of the photocatalyst has become a promising research topic. In a general way, the addition of surfactants, a high temperature, or a template are commonly applied for morphological modifications. The CTAB–assisted synthesis of the BiVO4 micro–tube by Ying et al. [4 sheet with the addition of surfactant PEG–1000 under 140 °C, which was nearly twice  as capable of photocatalytically removing MO as irregular BiVO4. Both of their exception activities can be attributed to the active sites enhancement, corresponding to the greater surface area [2 an ideal catalytic candidate for wastewater purification. MIL–101–NH2 exhibited great promise in photocatalytic activity because of the Fe–O cluster which can cause direct excitation and induce an electron transfer [2 to be utilized in photocatalysis. Huang et al. [2O5/NH2–MIL–101 (Fe) composite, which can perform well a photocatalytic degradation toward the removal of TC . Immobilizing CrPd nanoparticles over MIL–101–NH2, Cr0.4Pd0.6/MIL–101–NH2 was employed in the generation of hydrogen from formic acid at 323 K (2009 mol H2 mol Pd−1h−1) and was much more superior than the vast majority of noble metal catalysts reported [2 is still limited in its actual application due to the expensive cost. BiVOband gap ,9,10. Hog et al.  showed ag et al.  producedace area . There cice 86%, 0 min as ace area . Comparetransfer . Additiotransfer . All theg et al.  studied  88.3%, 1 min. Imm4 and MIL–101–NH2, we have surprisingly obtained the flower–like MIL–101–NH2/BiVO4 composite without surfactants. The three–dimensional structure facilitates the improved absorption of visible light. Otherwise, the preparation was facile and free of surfactants. In this hybrid, the stability of the composite promoted through the new connection was constituted as –COO−–Bi3+ bond. The separation of photogenerated electron–hole pairs are fostered with the construction of the built–in electric field and it enhances the photocatalysis under a visible illumination. In this work, the characterization of MIL–101–NH2/BiVO4 was proposed and the appropriate experimental condition of the photocatalytic reduction of Cr(VI) was optimized.Herein, by combining the advantages between BiVO2/BiVO4 composite was achieved and the product is yellowish–brown in color. The pre–prepared addition of MIL–101–NH2 drove the self–assembly of BiVO4 into a flower–like structure through a facile hydrothermal method. Additionally, FNBV–3 was chosen for the materials’ characterization, outlined below, based on its impressive performance in the photocatalytic reduction of Cr(VI).Following the method illustrated in 4 particles have a sphere–like structure. The pristine MIL–101–NH2 was well–organized octahedral in shape with a 100 nm diameter  is approximated compared to the nominal amount. As revealed in 2 (34.8%) and BiVO4 (65.2%) component in FNBV–3 was assessed by TG curve analysis. The BET specific surface area promotion is demonstrated in 2.SEM studies were utilized to lay bare the morphology and microstructure of the as–prepared samples . It can diameter . As discn FNBV–7 . Microcoi et al. . In addi2ATA linkers in FNBV–3. Contrasted with the corresponding peaks of pure FN, C=O shifted towards the positive side, which may be due to the charge density promotion over C=O after the protonation of FN [7/2 and Bi 4f5/2, a consensus among the previous theory, were resolved into 159.0 and 164.4 eV, which represented the characteristic of the Bi3+ state. The opposite shifted compared with the pristine over bismuth and C=O, suggesting there is an electrovalent bonding force between Bi3+ and –COO− [3/2 and Fe 2p1/2, with satellite peaks being located at 716.7 and 730.6 eV  [n = 3–7. The low content and high distribution of FN may lead to FNBV–1 and FNBV–2 being undetectable. Accordingly, the successful complexation of FN and BV was thus suggested, and oxygen vacancies show a negligible influence on the hybrids of MIL–101–NH2 and BiVO4.XRD patterns a were de–101–NH2 . Confirm83–1699) ,28. More−1 and 1630 cm−1 in all the spectra is assigned to the presence of absorbed H2O molecules. For FN, the characteristic absorption of 528 cm−1 is associated with Fe–O. Furthermore, peaks at 1257 cm−1 and 2900 cm−1 are attributed to C–N and –NH2 in the linker of the framework [−1 took place in the BV spectrum in respect of the V–O stretching vibration peak and confirmed the observation of monoclinic scheelite BiVO4, which was synthesized from XRD [2 and BiVO4 was distinctly proved. Thereby, the introduction of oxygen vacancies cannot destroy their chemical structure’s stability. The slight red shift of the V–O bond in FNBV–n accounts for a length increase and the Raman spectra were utilized to prove it [as(V–O) shifted towards the lower wavelength region with MIL–101–NH2. This further supports that the V–O bond length of BiVO4 increased corresponding to the empirical relation below [To determine the constitution of the functional group, FT–IR patterns were conducted in prove it ,32. As son below : υ = 2132Cr2O7 solution. Before it was exposed to an illumination, a dark adsorption in 1 h was set for the adsorption and desorption equilibrium achievement. The blank examination was operating as well, assuring that the spontaneously Cr(VI) depoisonous under irradiation without catalysts, and a direct reaction with Cr(VI) in the absence of light as well. −1). It is clear that the elimination capacity was increased after BV coupled with FN and that the enhancement of the photocatalytic activity was consistent with DRS. Such an enhancement may be related to the factual accessible active site. For FNBV–n (n = 1–3) could be bound up with the high separation of photogenerated carriers while overloading may block the transfer [12 for PFO and R22 for PSO), which alluded to the fitness of the models with the relative data obtained. The highest value of κ1 was obtained from FNBV–3, which was about 20–fold compared to that of BV. Moreover, the synergistic factor sκ (Equation (4)) for FNBV–3 is applied for quantitatively appraised the synergistic effect [0 (mg·L−1) is the initial concentration of the Cr(VI) solution and C (mg·L−1) is that at time t; κ1 (h−1) is the rate of reduction given as the slope in PFO while PSO is the rate constant for κ2 (L·h·mg−1); and κ, κBV, and κFN are the fitted reaction rate constants of FNBV–3, BV, and FN, respectively.The Cr(VI) PCR over different materials was performed on the Ktransfer . Meanwhitransfer . Among ctransfer ,37. In atransfer  as a coec effect . The val−1). The effect of the initial concentration study was unveiled in ZPC) pointed to ca. 3.1. This can explain why FNBV–3 performed best when adopted as pH = 2 with the electrostatic attraction effect between FNBV–3 and Cr2O72− or HCrO4− (the dominating species of Cr(VI) in an acidic aqueous dispersion) [+ surroundings are a great help in the detoxification of Cr(VI) as well. The photocatalytic activity of FNBV–3 under the optimal condition was compared to other BiVO4–based catalysts reported with a different morphology in previous literatures, as tabulated in It is noteworthy to mention that the reaction system’s pH value was considered to be a crucial parameter in the reduction of Cr(VI) . Figure persion) . The abu3+ in the reaction solution was negligible. Such can be presumed as the as–prepared sample was a perfect match with the recyclability and stability in real photocatalysis. Thus, MIL–101–NH2/BiVO4 composite can serve as an appropriate photocatalyst to solve the pollution of heavy ions Cr(VI) in water.According to g, eV) of the samples. As demonstrated in 4–based hybrids, interpreting the substantially boosted photocatalytic reduction [g evaluation in UV–vis DRS was measured to access the optical absorption quality and band gap energy , Ethylenediaminetetraacetic acid disodium , p–benzoquinone , and tertiary butanol  were selected to consume the electronics (e−), holes (h+), superoxide anion radicals (·O2−), and hydroxyl radicals (·OH), respectively. This weakened the removal rate with the trapping of AgNO3, deducing that e− led a predomination in the photocatalytic process, while the capture of O2− or ·OH could also contribute to the drop. The influence caused by the TBA should be ascribed to the equilibrium transmitting to Cr(VI) [− [On the basis of previous research papers, PCR was processed with the contribution of multitudinous reactive substances. To identify the major active specie responsible for the Cr(VI) reduction over FNBV–3, control experiments with a few scavengers are executed in o Cr(VI) ,47. On tr(VI) [− . 2 and BiVO4 was followed by the conventional separation of photogenerated electron–hole pairs. The O2− and ·OH could not form, which conflicted with the quenching test, as the band was located at the position which was either more positive or negative than E(O2/O2−) and E(H2O/·OH) [2 and VB of BiVO4, so that FNBV–3 could generate O2− and ·OH under irradiation.In light of the estimated band structure, a conceivable mechanism for the improvement of the photoreduction manifestation in FNBV–3 is suggest in H2O/·OH) ,50,51. T2/BiVO4 composite facilitated in the adsorption by a large specific surface area and the charge effect on the surface. Then, the involved photolysis after being exposed to visible light is documented in Equations (6)–(13). Based upon the aforementioned results, the direct Z–scheme heterojunction was confirmed and illustrated in From the analysis above, in this paper we raised a plausible mechanism for the removal of Cr(VI). Before irradiation, the MIL–101–NHThe chemical reagents used were all commercially available without further purification and the corresponding specific information is outlined in the 2 powder was prepared via a modified facile solvothermal method, as has been previously documented in the literature, and was denoted as FN [2/BiVO4 composites with varying molar ratios were synthesized through a hydrothermal method and the preparation process was illustrated in 3)3·5H2O and 0.02 mmol of FN were ultrasonically dispersed into 40 mL of DI. Subsequently, 0.3 mmol of Na3VO4·12H2O was added slowly stirred for 30 min. The above mixture was kept under 373 K for 24 h in a 100 mL Teflon–lined autoclave. After centrifugation and washing, the powder was collected. The obtained powder was placed in a vacuum oven and kept dry at 333K overnight. The final sample was nominated as FNBV–3. Likewise, FNBV–n (n = 1–7) composites were created with a different molar ratio of Fe to Bi . For comparison, the pristine BiVO4 was yielded under the same manner as outlined above, with the absence of MIL–101–NH2, and was referred to as BV.The MIL–101–NHed as FN ,53. The 4 performed as has been documented.Scanning electron microscope (SEM) images (JSM–7600F) were used to obtain the morphology and structure of the product. Meanwhile, the energy–dispersive X–ray spectroscopy (EDS) of the composite was recorded on INCA X–Act, Oxford Instruments. The gas adsorption isotherm and specific surface area were deduced on the basis of Brunauer Emmett Teller (BET) methods (BSD–PM2). Moreover, XRD patterns were conducted by an Ultima IV equipped with Cu Kα radiation, and the crystal data and phase structure were analyzed. The chemical states and the composition of the elements on the surface can be detected through X–ray photoelectron spectroscopy (XPS) (AXIS UltraDLD). VERTEX 80v, referring to a KBr disk, was employed to document the Fourier transform infrared spectroscopy (FT–IR). The UV–vis absorption spectra were acquired on a UV–2802 spectrometer. The UV–vis diffuse reflection spectra (UV–vis DRS) of the specimens were acquired by using UV–2600 with BaSO−2). Before illumination, the as–prepared product was added into Cr(VI) solution  and was stirred in the dark for 1 h until it reached an adsorption–desorption equilibrium. During the process, the reaction samples (each in 3 mL) were filtered (0.22 μm syringe filter) at each interval of time and the filtrate concentrations were monitored by the purple complex absorbance at 540 nm, according to the 1,5–diphenylcarbazide colorimetric (DPC) method [0 − Ct)/C0 × 100%, where η refers to the removal ability and C0 and Ct represents the solution concentration before and after the experiment. The photocatalytic reduction (PCR) activity on Cr(VI) under visible light was systematically investigated at room temperature. The catalytic reaction was performed through a Xe lamp equipped with a 420 nm cut–off filter  method . Data weVB and ECB correspond to the VB and CB edge position, respectively; X is the electronegativity of the semiconductor; Eg relates to the band–gap energy; and Ee represents the energy of free electrons vs. hydrogen (4.5 eV). In the report, the above equations (Equations (14)–(16)) were the value of VB and CB from BiVO4. Based on the band gap of MIL–101–NH2 and BiVO4, the mechanism which refers to the MIL–101–NH2/BiVO4 composite efficiently and photocatalytically reducing Cr(VI) is exhibited in A necessity is obtaining the band structure of the semiconductor to fully investigate the separation behavior of the heterostructures. The potential of the value band (VB) and conduction band (CB) component were estimated by the empirical formulas ,54:EVB =2/BiVO4 composites with varying molar ratios of Fe/Bi were successfully prepared and characterized, with the existence of oxygen vacancies and the newly formed interaction between –COO− in MIL–101–NH2 and Bi3+ in BiVO4. The as–synthesized materials were evaluated by the reduction of the hexavalent chromium under a visible–light illumination. Fe/Bi = 0.25 (FNBV–3) was selected for the optical molar ratio according to its photocatalytic performance . It could be reasonable to infer that the modification of BiVO4 with MIL–101–NH2 enhanced the light–harvesting ability and accelerated the migration of the photogenerated carrier, contributing to the prominent photocatalytic activity. Moreover, the material also bared an outstanding stability and recyclability. This study announced the feasible utilization in detoxifying Cr(VI) under the co–effect of a light irradiation and MIL–101–NH2/BiVO4 composite. With this work, we hope to share some insight and reflect on the recent photocatalytic practices.In summary, flower–like MIL–101–NH


The germanone has a rather high thermal stability in arene solvent, and no detectable change was observed at 80 °C for at least one week. However, high thermal stability of [IPrN]2Ge=O does not prevent its reactivity toward small molecules. Structural analysis and initial reactivity studies revealed the highly polarized nature of the terminal Ge=O bond. Besides, the addition of phenylacetylene, as well as O‐atom transfer with 2,6‐dimethylphenyl isocyanide make it a mimic of nucleophilic transition‐metal oxides. Mechanism for O‐atom transfer reaction was investigated via DFT calculations, which revealed that the reaction proceeds via a [2+2] cycloaddition intermediate.A rare three‐coordinate germanone [IPrN] A rare three‐coordinate germanone: bis(imino)germanone [IPrN]2Ge=O imidazolin‐2‐imino) was successfully isolated. Initial reactivity studies combined with experimental and computational bonding analysis revealed highly polarized nature of the terminal Ge=O bond. Moreover, transition metal oxide‐like reactivity has been observed for the addition of phenylacetylene, as well as O‐atom transfer with 2,6‐dimethylphenyl isocyanide. Specifically germanones (R2Ge=O), were long thought to be elusive and unstable intermediates,pπ‐pπ overlap between oxygen and electropositive germanium atoms, that results in weak and polarized Ge−O bonds.2Ge=X with a terminal heavier group 16 element ,I was described by Driess in 2009  results in a distorted tetrahedral geometry around the electron‐deficient germanium center. 2 2 were2. We found that the Wiberg Bond Index  indicates partial double bond character for Ge=O (1.30). Natural Population Analysis showed a positive Ge center  and a negatively charged O center (−1.02), whereas Natural Bond Orbital analysis shows only one Ge−O bond (Table S2). Analyzing the molecular orbitals  shows that the HOMO is mainly located on the π‐system of the IPrN groups, while the LUMO is associated with the π‐system of the phenyl rings of 2. HOMO−3 and LUMO+9 are the orbitals that are directly associated with the Ge=O π‐bonding , which depict an O‐dominated π‐orbital and a Ge‐dominated π*‐orbital, respectively. Interestingly, HOMO−3 and LUMO+9 indicate very little coupling to the N atoms of the IPrN groups, which also suggests that Ge=O can be described as a double bond although the zwitterionic resonance structure 2’  calculations were performed to understand the electronic structure of 2 is reflected by the following reactivity study (Scheme 2 shows reactivity toward pinacolborane (HBpin), bromotrimethylsilane (TMSBr) and phenylsilane (PhSiH3), with polarized B−H, Si−Br or Si−H single bonds, to immediately afford the corresponding 1,2‐adducts 3, 4 and 5 at room temperature. The 1H NMR signal of the Ge−H bond in 3 appears at 5.04 ppm, which is similar to that in 5 (4.78 ppm).The polarized Ge=O bond of y Scheme  and 4. T3 reaction product of III (Eind2Ge(H)OSiH2Ph; Ge−H: 7.94 ppm), the Ge−H signal in 5 is significantly upfield shifted, which could be attributed to the strongly π‐electron donating NHI ligands. In consequence, full conversion of 2 to 5 was observed after 30 min, whereas III was reacted for one day with PhSiH3 until completion of the reaction could be confirmed.Compared to the analog PhSiH2 reacted with the C=O bond of benzaldehyde (PhCHO), to smoothly furnish the cyclic product 6. The formation of the four‐membered heterocycle in 6 was confirmed by 1H/13C HSQC and HMBC NMR spectroscopy, revealing a singlet at 99.7 ppm for the ring carbon atom, and a singlet at 5.10 ppm for the ring proton.Moreover, 3 to 6 can be attributed to the highly polarized Geδ+−Oδ− bond, it has been the scope to test the reactivity of 2 towards other small molecules. Treatment of 2 with H2 and NH3 showed no conversion and reaction with CO2 formed an unidentified product mixture. Upon exposure towards MeOH, germanone 2 was directly converted into the imine IPrNH as a result of high proton affinity of the imidazolin‐2‐iminato ligand. However, the reaction of 2 with a terminal alkyne  at room temperature resulted in direct conversion to the hydroxoacetylide complex 7 in good yield . This reactivity is reminiscent of pyridine‐stabilized Ti(IV) oxo complex Cp*2(pyridine)Ti=O (Cp*=η5‐C5Me5) reported by Bergman and coworkers.Since the formation of products i=O Cp*=η5‐C5Me5 r2 with 0.5 equivalent of 2,6‐dimethylphenyl isocyanide (CNXyl) led to a mixture of the [2+2] cycloaddition product 8 (50 % NMR yield) and the O‐atom transfer product 1  at room temperature, which immediately resulted in the desired compound 8 in nearly quantitative yield.More interestingly, reaction of 2 with CNXyl . We found that the [2+2] cycloaddition product 9 is an energetically favored intermediate , while the dissociation and formal O‐atom transfer leads to 10 , which can react with another molecule of 2 to provide the thermodynamically stable product 8 . We note that the calculated high barriers  are in general agreement with the observed very slow reaction at room temperature and reaction mechanism can explain the observed mixture of products (1+8). We also studied other possible pathways but all attempts to locate the direct coordination of CNXyl to Ge and a GeOC three membered ring intermediate with an exocyclic=NXyl unit were not successful. Additionally, we found a direct O‐atom transfer mechanism, but it was less favorable than the cycloaddition pathway .Computational analysis using DFT was carried out to understand the reactivity of η2‐DHF)(BDI)Re=O, ‐2,4‐dimethyl‐β‐diketiminate) with isocyanides, R−NC  was described in 2018.2 acted not only as a heavy ketone, but also as a mimic of nucleophilic transition metal oxides (TMO). In fact, the O‐atom transfer reaction with isocyanides is prototypical for TMO.For comparison, the reactivity of a rhenium(III) terminal oxo complex, η2‐DHFBDIη2‐DHF even at elevated temperatures.To clarify the reaction mechanism of O‐atom transfer by aiming at the isolation of isocyanide complexes similar to known silicon derivatives,2 with a trigonal planar geometry. Thanks to the efficient stabilization by two bulky and strongly π‐donating NHI substituents, germanone 2 is remarkable stable in arene solvent for at least one week. High stability makes it easier to handle and allows us to investigate its reactivity towards various molecules. The addition reactions of 2 with pinacolborane (HBpin), bromotrimethylsilane (TMSBr), phenylsilane (PhSiH3), and benzaldehyde (PhCHO) demonstrated polarized Geδ+−Oδ− reactivity. In addition, the conversion of phenylacetylene (PhCCH), as well as the O‐atom transfer reaction with 2,6‐dimethylphenyl isocyanide (CNXyl) displayed its transition metal oxide‐like behavior. This similarity may provide new opportunities for main group metal mediated catalytic applications in the future.In summary, we have achieved the synthesis and isolation of bis(imino)germanone The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.Supporting InformationClick here for additional data file.


Under magnetic excitation, the ICNPs generate locally confined hot spots, selectively activating the Cu2Cr2O5 surface while the global temperature remains low (≈80 °C). The catalyst selectively hydrogenates a scope of benzylic and non‐benzylic ketones under mild conditions , while ICNPs@Cu2Cr2O5 or Cu2Cr2O5 are inactive when the same global temperature is adjusted by conventional heating. A flow reactor is presented that allows the use of magnetic induction for continuous‐flow hydrogenation at elevated pressure. The excellent catalytic properties of ICNPs@Cu2Cr2O5 for the hydrogenation of biomass‐derived furfuralacetone are conserved for at least 17 h on stream, demonstrating for the first time the application of a magnetically heated catalyst to a continuously operated hydrogenation reaction in the liquid phase.Copper chromite is decorated with iron carbide nanoparticles, producing a magnetically activatable multifunctional catalytic system. This system (ICNPs@Cu A commercial heterogeneous catalyst is decorated with iron carbide nanoparticles to produce a multifunctional catalytic system with magnetic heating capabilities. Under magnetic induction, local hot spots are generated at the catalyst surface, unlocking continuous‐flow hydrogenation of aromatic ketones under mild conditions. This approach is versatile and potentially transferrable to a wide range of heterogeneous catalysts and transformations. The approach is still associated with severe challenges and limitations, including for example tedious catalyst synthesis procedures, fast deactivation/agglomeration during catalysis, and inapplicability under continuous flow conditions.5, 6 A2Cr2O5, Figure In this context, we report the preparation, characterization, and continuous‐flow application of a multifunctional catalytic system composed of ICNPs‐decorated copper chromite  of average size 14 nm were prepared according to a procedure previously developed by some of us.2 (see Supplementary Information for details). In a second step, ICNPs were dispersed in THF and the colloidal solution obtained was added to Cu2Cr2O5 (targeted loading: 12 wt % ICNPs=> ca. 9 wt % Fe). The resulting mixture was sonicated under argon at r.t., leading to a black precipitate and a clear supernatant after 5 min. At the end of this impregnation step, the precipitate was dried under vacuum, giving a magnetic black powder. Finally, the resulting material was treated using magnetic induction  for 1 h, thereby “anchoring” the ICNPs to the Cu2Cr2O5 surface. Without such treatment, ICNPs leaching and poor catalytic performance were observed, as discussed later.Iron carbide nanoparticles  and magnetic properties (SM=140 emu g−1), respectively . In addition, measurements of specific absorption rates (SARs) by calorimetry evidenced the very high heating power of ICNPs under magnetic induction . These characterization data of ICNPs are consistent with the results described in a prior publication.2Cr2O5 by scanning electron microscopy with energy dispersive X‐ray spectroscopy (SEM‐EDX) evidenced evenly distributed ICNPs over the Cu2Cr2O5 surface , powder X‐ray diffraction (XRD) and vibrating sample magnetometer (VSM) provided information about the NPs size (13.7 +/− 1.0 nm), crystallinity , well in agreement with the theoretical value. Characterization of ICNPs@Cu2Cr2O5 by powder XRD gave characteristic patterns for Cu2Cr2O5 for both its unreduced and reduced state , in accordance with literature.2Cr2O5, presumably due to peak overlapping of the characteristic regions with those of Cu2Cr2O5 , as well as to a relatively low loading of ICNPs.The Fe loading of ICNPs@Cu2Cr2O5 were first investigated for the hydrogenation of furfuralacetone (FFA) as model substrate. This choice was motivated by the multiple hydrogenation steps of FFA . Then, either the furan ring is hydrogenated first, giving the saturated ketone 4‐(tetrahydro‐2‐furanyl)‐2‐butanone (1 b) through route a), or the ketone is hydrogenated first, giving the unsaturated alcohol α‐methyl‐2‐furanpropanol (1 c) through route b). Finally, 1 b and 1 c are hydrogenated to form the completely saturated tetrahydro‐α‐methyl‐2‐furanpropanol (1 d). Cu2Cr2O5 is known to selectively reduce ketones without hydrogenating aromatic rings,[1 c without further hydrogenation of the furan ring.The first step of the reaction network consists in the hydrogenation of the C=C bond to give 4‐(2‐furanyl)‐2‐butanone  was dissolved in heptane (0.5 mL) and reacted in the presence of the catalyst (30.0 mg) under H2 (3 bar) and magnetic induction  for 2 h. For comparison, the results obtained from reactions performed with classical heating under the same global temperature are also given .The catalytic performance of ICNPs@Curs Table . In typi1 a was observed (Entry 1). Increasing the amplitude of the magnetic field to 64 mT and above lead to the full conversion of the substrate and to the production of 1 c in 91 % to >99 % yield. Thus, the activation by magnetic induction of ICNPs was found to be efficient to activate the Cu2Cr2O5 hydrogenation catalyst in solution. Interestingly, similar reactions conducted with classical heating at the same global temperature of 40 and 80 °C gave no conversion at all (Table 1 a in poor yield (33 %). Full conversion to product 1 c could only be observed when raising the temperature to 120 °C.At low field strength, the conversion was incomplete, and only C=C hydrogenation leading to product 2Cr2O5. Comparable catalytic results were reached if the reactions with classical heating were performed with pure Cu2Cr2O5, demonstrating that Cu2Cr2O5 itself is the active catalyst. Along the same line, using only magnetically activated ICNPs without Cu2Cr2O5 did not lead to any furfuralacetone conversion (Table S3). Attempts to use a lower loading of ICNPs on Cu2Cr2O5 (5 wt %) under optimized conditions  led to very low conversions, presumably due to an insufficient heating of the catalyst (Table S4). On the other hand, increasing the loading of ICNPs to 20 wt % resulted only in a slight increase in the yield of 1 c (95 % instead of 91 %). A loading of 12 wt % was thus conserved for the rest of the study.This confirms that under magnetic induction local hot spots allow the reaction to proceed at temperatures significantly higher than the observable global temperature of the reactor. It should be noted that the decoration with ICNPs did not have a significant impact on the intrinsic catalytic performance of Cu2Cr2O5 under magnetic heating at 64 mT   and C=O (kC=O=0.18 mol L h−1) hydrogenation are very close, outlining the excellent ketone reduction activity of the ICNPs@Cu2Cr2O5 catalyst. Interestingly, stopping and re‐starting the alternating current magnetic field regularly during the recording of a time profile lead to the perfectly concomitant stop or re‐start of the catalyst activity , which is ca. 40 °C higher than the global temperature measured during the experiments under magnetic induction. In sharp contrast with the use of magnetic induction, conventional heating did not allow quickly stopping and re‐starting the reaction by switching ON and OFF the power supply due to much longer heating and cooling times .To get further insight into the kinetics of the reaction, time profiles were recorded for the hydrogenation of furfuralacetone using ICNPs@Cu) Figure . The resy Figure . This ou2Cr2O5 catalyst under magnetic induction was explored for a scope of aromatic ketones . Interestingly, 2‐acetonaphtone (9) and benzophenone (10) were partially hydrodeoxygenated under standard conditions, suggesting that the ICNPs@Cu2Cr2O5 catalyst is active for C−O bond cleavage.The versatility of the ICNPs@CuThese results are in contrast to what was observed using Ru@ICNPs catalysts, where benzylic ketones with electron donating substituents were hydrodeoxygenated to aromatic alkanes while substrates with electron withdrawing groups resulted in lower conversions.2Cr2O5 at 64 mT and at 120–150 °C, selective hydrogenation of benzylic ketones is favored under magnetic induction while conventional heating leads to hydrodeoxygenation. This may suggest an influence of the heating mode on the reactivity of the ICNPs@Cu2Cr2O5 catalyst.In comparison, no ketone reduction activity was observed when performing the hydrogenation of non‐benzylic and benzylic ketones with classical heating at the same global temperature of 80 °C (Table S4). In the case of non‐benzylic ketones, comparable product yields could be obtained only when raising the temperature to 150 °C. Applying high temperatures (120 °C or 150 °C) with benzylic ketones led to the full hydrodeoxygenation of the substrates (Table S5). Interestingly, despite fairly comparable ketone hydrogenation activities of ICNPs@Cu2Cr2O5 catalyst was studied using furfuralacetone (1) as substrate. For this, the reaction conditions were selected to have a mixture of products 2 and 4, allowing to probe any change in performance. The catalyst could be reused at least 10 times with fairly constant activity and selectivity . The slight decrease of selectivity through the cycles is presumably due to the loss of small quantities of catalyst during the washing step applied between each cycle. SEM and SEM‐EDX characterization after 10 cycles showed no significant change of the catalyst surface. ICNPs are still evenly distributed over the Cu2Cr2O5 surface , presumably due to ICNPs detaching from the Cu2Cr2O5 surface during the reaction and workup. The performances and stability of the ICNPs@Cu2Cr2O5 catalyst were further investigated under continuous flow conditions using furfuralacetone (1) as substrate.The possibility to recycle the ICNPs@Cue Figure –g and one Figure . Element1, 0.05 mol L−1 in heptane, flow rate 0.1 g min−1, 0.15 mL min−1) is mixed into a flowing stream of H2  resulting in a well‐mixed gas/liquid reactant phase entering the reaction zone. The resulting mixture flows through a high pressure HPCL glass column used as a tube reactor which contains a catalyst bed of 500 mg ICNPs@Cu2Cr2O5  and is subjected to the AC magnetic field. The system pressure is set to 5 bar and controlled by a back pressure regulator. At the output of the reactor, an online GC‐FID is installed to analyze the products in real‐time. A detailed description is provided in the Supplementary Information, Figure S8–9. After a rapid screening of the magnetic field amplitude (Table S7), the reaction conditions were fixed to 0μHmax=42 mT, with a substrate flow of 0.1 g min−1  a gas flow of 0.001 g min−1 (2.47 mL min−1) and a pressure of 5 bar, WHSV=0.1 h−1. This gave complete conversion of the substrate and product 1c in 88 % yield, corresponding to a H2 conversion of 3 %. A large excess of H2 (similar to the batch experiments) was used to avoid a significant gradient of the partial H2 pressure along the reactor bed. Under these conditions, a temperature of ca. 110 °C was measured by an infrared camera at the surface of the reactor. Raising the magnetic field amplitude above 42 mT lead to an increase of the global temperature (ca. 125 °C) but to a slight decrease of the catalytic activity (75 % of 1c), presumably due to the local boiling of the solvent limiting the access of the substrate to the active sites. For comparison purposes, an analogous continuous flow experiment was performed using conventional heating at 120 °C instead of magnetic induction, by replacing the coil by a trace heater. Strikingly, no conversion of 1 was observed under these conditions, highlighting the advantage of using magnetic induction to perform a reaction locally at a temperature higher than the observable temperature measured at the surface of the reactor. The stability of the ICNPs@Cu2Cr2O5 catalyst under continuous flow conditions was studied for 17 h on stream under standard conditions  were maintained at all time during the 17 h continuous flow reaction, without any sign of deactivation. This confirms and further demonstrates the remarkable and unprecedented stability and practicability of the ICNPs@Cu2Cr2O5 catalyst that was already glimpsed through the batch recycling experiments.The development of a continuous flow set‐up able to accommodate our catalytic system  and its operating conditions  is particularly challenging and has not been achieved until now. Figure s Figure . Excelle2Cr2O5 with magnetic iron carbide nanoparticles (ICNPs) of high heating power using a straightforward synthetic procedure. The resulting ICNPs@Cu2Cr2O5 multifunctional catalyst was applied to the hydrogenation of aromatic ketones to aromatic alcohols activated by magnetic induction. The reaction proceeded smoothly under mild conditions  without any additional heating thanks to the creation of local hot spots by the magnetically activated ICNPs on the Cu2Cr2O5 surface. Notably, the catalyst (decorated or not) is completely inactive under identical conditions applying conventional thermal heating. A scope of benzylic and non‐benzylic ketones was readily hydrogenated to the corresponding aromatic alcohols in excellent yields and selectivities. Recycling and long‐term experiments conducted under batch (10 cycles) and continuous flow conditions (17 h on stream) demonstrated effective reusability and high long‐term stability of the ICNPs@Cu2Cr2O5 catalyst. A continuous‐flow reactor for liquid‐phase reactions with pressurized gases was designed and built to tackle the challenges associated with the use of an alternating current magnetic field. To the best of our knowledge, this is the first report of a continuously operated liquid‐phase hydrogenation reaction catalyzed by a magnetically activated heterogeneous catalyst.In conclusion, we report the decoration of commercial Cu2Cr2O5 catalyst for the hydrogenation of aromatic ketones, the presented strategy to design, synthesize, and apply multifunctional catalytic systems with magnetic heating capabilities should be transferrable readily to a wide range of heterogeneous catalysts and transformations. The study demonstrates the possibility to modify even standard heterogeneous catalysts with novel physical properties  in a simple and versatile manner. The presented methodology will enable a much broader exploration of the potential of magnetic induction in catalysis and may thus pave the way toward practical application of this innovative tool.Exemplified here with the ICNPs@CuThe authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.Supporting InformationClick here for additional data file.


The ordered binding of equal numbers of terephthalate and fumarate ditopic carboxylate linkers at the trigonal antiprismatic Zr6 core creates close‐packed layers of fumarate‐connected clusters that are connected along the single remaining threefold axis by terephthalates. This well‐defined linker arrangement retains the three‐dimensional porosity of the Zr cluster‐based UiO family while creating two distinct windows within the channels that define two distinct guest diffusion paths. The ordered material is accessed by a restricted combination of composition and process parameters that were identified by high‐throughput synthesis.We report a metal‐organic framework where an ordered array of two linkers with differing length and geometry connect [Zr fcu net produces a zirconium‐based MOF Zr6(BDC)3(Fum)3 with two distinct windows and multiple guest diffusion pathways. This phase is formed by single‐step synthesis in a narrow region of the available chemical space, and its identification required a large set of synthetic experiments that were facilitated by automated high‐throughput methods.The ordered arrangement of terephthalate and fumarate linkers over the  Metal‐organic frameworks, MOFs, are crystalline and porous materials composed of metal‐based nodes and organic linkers.Automated high‐throughput (HT) methods for materials synthesis and analysis are powerful tools for the systematic exploration of multiparameter chemical systems.6O4(OH)4]12+ cluster unit have received considerable attention not only for their high chemical stability but also for their three‐dimensional porosity, structural diversityfcu) topology is based on an octahedral Zr6 core whose 12 edges are bridged by ditopic carboxylate linkers to form the extended structure: the four μ3‐O2− and four μ3‐OH− ligands are located alternately above each triangular face of the core. The positions of the twelve carboxylate linkers around the inorganic cluster define a cuboctahedron. UiO‐66 has been the prototype for the development of several mixed‐linker MOFs. Cubic structures of randomly distributed linkers with the same lengths are produced either by single‐step synthetic protocolsbcu topology where only eight of the twelve edges of the Zr6 octahedron are bridged by linkers. A subsequent synthetic step then introduces four linkers onto the remaining edges.fcu Zr MOF with ordered multiple linkers obtained from a single‐step synthesis, or of any such material with a linker ratio distinct from 2:1 or a structural arrangement of linkers different from 8 plus 4. The aim of this study is single‐step self‐assembly of an ordered array of two linkers that is not subject to these constraints.Zirconium carboxylate MOFs built from the [Zr2/terephthalic acid/fumaric acid/formic acid in DMF. The material is based on the underlying fcu topology where the [Zr6O4(OH)4]12+ clusters are connected by six terephthalate and six fumarate linkers. This ordered arrangement of the two distinct linkers produces trigonally distorted tetrahedral and octahedral cages which share two types of windows that are differentiated by the linkers that describe them. This is the first fcu Zr MOF with two windows and reflects the opportunity to control three‐dimensional MOF porosity precisely through multiple linker chemistry.We present a new 12‐c Zr MOF with equal content of ordered terephthalate and fumarate linkers. This material was prepared in a single‐step synthesis and discovered by high‐throughput exploration of the chemical space defined by the reagents ZrOClfcu topology MOFs, UiO‐66 and MOF‐801The ditopic linkers terephthalate and fumarate were selected for the exploration of mixed‐linker Zr MOF synthesis as they both form 12‐c 2⋅8 H2O as the metal source because it forms the stable solutions essential for automated dispensing. We then selected the reaction conditions to be explored for the robotic high‐throughput synthesis of Zr‐based MOF with mixed terephthalate (T) and fumarate (F) linkers by evaluating reported conditions from the literature where ZrOCl2⋅8 H2O was used , were chosen to be the same for all reactions as they have been used extensively in synthesis of both UiO‐66 and MOF‐801. The time and temperature of reaction were fixed at 48 hours and 120 °C, respectively, to provide sufficient duration and high enough temperature to favour formation of a new phase without encountering problems due to DMF volatility. In order to exploit the liquid‐handling robot used to prepare reaction mixtures, we selected conditions that enabled the use of stock solutions of the reaction components. The implicit necessity for these solutions to be stable at room temperature throughout the duration of the automated sample preparation, which required up to 2 hours to complete, imposed a limit on the concentration of the ZrOCl2⋅8 H2O stock solution used of 0.0225 M, because of its solubility in DMF. The volume of this stock solution added to each reaction mixture was also fixed, giving each 10 mL‐scale reaction mixture the same ZrOCl2⋅8 H2O concentration of 38 mg/10 mL. The combinatorial parameters explored in the high‐throughput syntheses were thus limited to the ratio between the two linkers, (T:F), and their total amount relative to the quantity of Zr, Zr:(T+F), as well as the amount of formic acid (FA:Zr). These three parameters were expected to have the largest influence on the chemistry and potential formation of a new phase.The synthesis of UiO‐662 and total amount of linker Zr:(T+F)=0.25:0.75, 0.5:0.5, and 0.66:0.33 , and were run under the same condition (120 °C for 48 hours).We adopted a grid search and used automated dispensing of reaction mixtures by liquid‐handling robots to accelerate the exploration of the space. The chemical space was sub‐divided to span a broad range of compositions, covered by a set of 45 points (Table S2), in the first, broad iteration of the exploration of new phases. The two linkers were introduced in mixtures of five different compositions, T:F=1:0, 0.75:0.25, 0.5:0.5, 0.25:0.75 and 0:1, at each of three molar ratios between ZrOCl3 Figure . Formic 1H NMR analysis on the digested solids , where the molar ratio T:F is higher than the nominal value, for example a solid synthesised with T:F=1:1 contains T:F=1:0.64 (Table S8).After the completion of the reactions, the samples were classified by visual inspection. Only 11 out of 45 3(Fum)3 crystallizes in R3‾(space group no. 148), a=b=12.69646(7) Å, c=37.9733(4) Å, V=5301.20(8) Å3. The space group assignment was based on the observed systematic absences. Structure solution was carried out using synchrotron PXRD data collected at beamline I11  Å) through a combined Monte Carlo/Simulated Annealing approach with TOPAS‐Academic V5, followed by Rietveld refinement . During refinement, the occupancies of the linkers were fixed at the values determined by 1H NMR analysis of the activated material , while the occupancies of MeOH molecules located in the pores were obtained from refinement.As observed in the first batch, in the second batch there were distinct regions where the reactions yielded no solid product, which were the mixtures with low linker and high modulator content, and regions where solid product was formed. PXRD patterns of the solid products Figures  and S13 6(BDC)3(Fum)3 is a 12‐c framework of [Zr6O4(OH)4]12+ clusters connected by six terephthalates and six fumarates in the fcu topology 3(Fum)3 3(Fum)3, 1767 Å3, lies in between those of UiO‐66 (2231 Å3) and MOF‐801 (1418 Å3). In contrast to MOF‐801, where the zigzag shape of the fumarates causes the alternating tilting of the Zr clusters about the unit cell vectors 3(Fum)3 adopt the same orientations  and 2.363(4) Å. The terephthalates are essentially symmetric bridges, with Zr–OTerephthalate bond lengths 2.148(2) and 2.079(4) Å.The lower rhombohedral symmetry of Zr3 Figure  compared6 Figure  is assoc Figures  and S18.s Figure , the clus Figure , resultiab plane of the rhombohedral structure, which are connected by the terephthalates . These distorted tetrahedral and octahedral cages are connected by two types of triangular windows, one fully composed of fumarates, 3F, 3(Fum)3 has two distinct types of window between the cages 3(Fum)3 is expressed in the different distances between opposing windows of the same type in the octahedral cage, measured through the cage centre. This distance between 3F windows is 12.650(2) Å and between 2T1F windows is 10.555(3) Å .Zr clusters and fumarates thus form close‐packed hexagonal layers, describing the s Figure  in the t, Figure  and one , Figure . In conts Figure . The deg6(BDC)3(Fum)3 define two types of possible diffusion pathways for guest molecules. In the path parallel to the Zr fumarate layers, the guest passes through the 2T1F window only 3(Fum)3 was performed on a sample prepared from synthesis that involves ZrCl4 as starting material because this affords the product at higher yield, 83 %, than the ZrOCl2‐based synthesis, 15 %. . The phase purity of this sample was confirmed with PXRD . The organic components of Zr6(BDC)3(Fum)3 were analysed by 1H NMR after digestion of the sample in NaOD/D2O. The MeOH‐exchanged sample displays molar ratios T:F:MeOH:FA=1:0.92:3.4:0.2 . The deviation from the equimolar composition between the two linkers and the presence of formates in this sample are indicative of missing linker defects in the Zr6(BDC)3(Fum)3 structure. It is well known that modulated synthesis of Zr MOFs promotes the formation of defects,−/MeOH as terminal ligands on the defect sites of UiO‐66.6(BDC)3(Fum)3, the MeOH exchanged sample was activated under high vacuum at 60 °C to remove non‐coordinating MeOH from the pores before digestion and 1H NMR analysis , while the structure of the material is preserved . The molar ratio T:F:MeOH:FA=1:0.92:0.6:0.2 is used to derive the formula of the activated material as Zr6O4(OH)4(BDC)2.77(Fum)2.55(MeO)0.83(MeOH)0.83‐ (Formate)0.55, in which 0.68 linkers, or 11.3 % of the 6 linkers in the idealised composition, are missing, with their sites in each cluster occupied by formate and pairs of MeO−/MeOH ligands. These missing linkers have an effect on the porous properties of the material, as they generate extra accessible space and decrease the density of the framework. Zr6(BDC)3(Fum)3 exhibits a type I N2 adsorption desorption isotherm .Compositional and porous characterisation of Zr6(BDC)3(Fum)3 lie between the respective values of MOF‐801 (690 m2 g−1/ 0.27 cm3 g−1) and UiO‐66 (1290 m2 g−1/0.49 cm3 g−1).fcu net controls the global porous properties, surface area and pore volume, as well as the local ones, the size and the shape of the individual cages and windows. This approach offers additional tuning capabilities for the porous properties of a high symmetry net through the precise locally‐ and long‐range ordered definition of intermediate surface areas created from distinct pore shapes. The well‐established isoreticular expansion or contraction of a single linker MOF offer large changes in surface area and pore size that preserve the shape and number of cages and windows,The experimental BET surface area and pore volume of Zr2, terephthalic acid, fumaric acid and formic acid was explored to identify new MOF by high‐throughput experimental screening. The two‐linker ordered MOF, Zr6(BDC)3(Fum)3, was the only new phase discovered and it is formed in a narrow region of this space, in contrast to the linker‐disordered cubic material formed by the same two linkers. The identification of the linker‐ordered system by single‐step self‐assembly then required the screening at fine compositional resolution that is enabled by the high‐throughput approach. Although each linker individually affords an important, well‐studied member of the key fcu net Zr‐based MOF family, both with one pore window and a single guest diffusion path, Zr6(BDC)3(Fum)3 is not a simple intermediate between these structures. Rather, its structure is generated by ordered linker decoration of the fcu net that breaks the symmetry to introduce anisotropy into the three‐dimensional porosity, which is now characterised by two distinct diffusion paths. The ordering of terephthalate and fumarate binding to the [Zr6O4(OH)4]12+ cluster creates two windows of different shape that describe the distorted octahedral and tetrahedral cages defining these paths. This ordering precisely defines the porosity locally to each cage and is distinct from the locally heterogeneous tuning offered by disordered multiple linker MOF average structures. The resulting simultaneous tuning of pore size and shape, which affords interval pore volume between the parents, differs from isoreticular expansion in that it tunes within a defined range of extra‐framework space. Multiple linker ordered decoration of canonical single linker MOF topologies can harness the resulting combinatorial and chemical diversity of linker sets to generate new porous materials families where the size and shape of the internal space can be precisely modified for optimal guest interaction.The chemical space defined by ZrOCl1H NMR and TGA measurements. It also contains additional figures, tables and notes. Deposition Numbers 2089846 contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service www.ccdc.cam.ac.uk/structures. The datasets supporting the findings of this study are available from the University of Liverpool and can be found at https://datacat.liverpool.ac.uk/id/eprint/1460.The Supporting information file contains detailed experimental procedures and results from PXRD, The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.Supporting InformationClick here for additional data file.


Triplet‐triplet annihilation (TTA) is a spin‐allowed conversion of two triplet states into one singlet excited state, which provides an efficient route to generate a photon of higher frequency than the incident light. Multiple energy transfer steps between absorbing (sensitizer) and emitting (annihilator) molecular species are involved in the TTA based photon upconversion process. TTA compounds have recently been studied for solar energy applications, even though the maximum upconversion efficiency of 50 % is yet to be achieved. With the aid of quantum calculations and based on a few key requirements, several design principles have been established to develop the well‐functioning annihilators. However, a complete molecular level understanding of triplet fusion dynamics is still missing. In this work, we have employed multi‐reference electronic structure methods along with quantum dynamics to obtain a detailed and fundamental understanding of TTA mechanism in naphthalene. Our results suggest that the TTA process in naphthalene is mediated by conical intersections. In addition, we have explored the triplet fusion dynamics under the influence of strong light‐matter coupling and found an increase of the TTA based upconversion efficiency. Triplet‐triplet annihilation (TTA) of naphthalene has been investigated by using multi‐reference methods along with quantum dynamics simulations. The study involves obtaining the mechanistic details of the process and understand the time evolution of nuclear wavepacket on the computed potential energy surfaces. The results suggest that the TTA is mediated by conical intersections (CIs). It is also demonstrated that the strong light‐matter interaction increases the efficiency of TTA based photon upconversion. The population then transfers to the T1 state of the annihilator molecule via Dexter triplet‐triplet energy transfer (TET). The T1 states of two annihilator molecules fuse together to form the S1 state, which produces the high energy photon, hν2 as a result of the fluorescence emission.ab initio and TD‐DFT computed singlet‐triplet energy gaps., which includes all 1/S0 CI has been computed at the SA2‐CASSCF level of theory. For the monomer calculations, SA3‐CASSCF  reference wave function with an active space of CAS(6/6) has been used. The MOLPRO‐2020 quantum chemistry program package has been used for all electronic structure calculations. state are π5, π2*, π6 and π1*, among which the first two orbitals are localized on one monomer and the last two are on the other monomer. The triplet‐triplet state wavefunction has also been found to be a superposition of multiple determinants. One of the leading configuration is shown in Figure π5 and π2*have down spin, and the electrons of π6 and π1*have up spin. The two lowest singlet excited states ([S1S0] and [S0S1]) of naphthalene dimer are degenerate at the S0‐crossed geometry , we could optimize the dimerized product (S0‐dimer) on the ground state without imposing any geometrical constraints. Three primary differences have been observed between the S0‐dimer and S0‐crossed structures: 1) the dimer is structurally more symmetric and the monomers are perfectly stacked. 2) The intermolecular distance, rCC reduces to 1.65 Å due to the formation of two sigma bonds between the monomers. 3) The newly formed sigma bonds change the hybridization of the corresponding carbon atoms from sp2 to sp3. Consequently, the β (butterfly bending) angle reduces from 180° to 133.5°, which results in a bent at the sp3 carbon atoms  geometry with the reduced constraint value of rCC=3 Å. A minimum energy structure has been optimized for the first excited state (S1‐min), which exhibits similar geometrical changes as S0‐dimer but to a lesser extent resulting the reduction in rCC to 2.39 Å and β to 154.2°. In addition to the discussed stationary points, we also have optimized a conical intersection between ground and the first excited state, denoted as S1/S0 CI. Among the obtained critical points, the S1/S0 CI has been found to be the most asymmetric structure with respect to S1‐min (or S0‐dimer). This CI allows the molecule on the first excited state to decay to the ground state non‐radiatively. Similar type of CI was observed in the case of butadiene dimerization process.We have optimized the relevant critical points on the PESs of the naphthalene dimer. The equilibrium geometry corresponding to the reactant complex of the dimer has been obtained by performing the constrained optimization with a constraint intermolecular distance r around  Å, we co1T1] state has been scrutinized by connecting the above‐discussed critical points of naphthalene dimer. Starting from the reactant complex (S0‐crossed), a relaxation pathway toward S0‐dimer has been constructed by performing three sets of geometry interpolations: one from S0‐crossed to S0‐eclipsed, two between S0‐eclipsed and S1‐min, and three from S1‐min to S0‐dimer. Subsequently, at these interpolated geometries, the CASSCF energies have been calculated for the four lowest electronic states. The corresponding potential energy curves are depicted in Figure 1T1] state of naphthalene intersects with both the [S1S0] and [S0S1] states along the dimerization pathway. These crossings will be referred to as CI10 and CI01, respectively, in the rest of the paper. The path also exhibits an avoided crossing between ground and first excited state in the vicinity of S1‐min. CI10 and CI01 are accessible for the S0‐crossed geometry on the [T1T1] state through a barrierless pathway  state, hence will be referred to as the TTA based upconversion process. A curve crossing between singlet and [T1T1] states was also revealed in a singlet fission and TTA study of ethylene dimer model by using ab initio and DFT calculations.The fate of the molecule after reaching the  state population transfers significantly to the lower electronic states via CI10 seam point along the Q2 mode. Taken together, the fast and slow decay time scales corresponding to the population dynamics of [T1T1] state can be attributed to the wave packet evolution along Q2 and Q1 modes, respectively.The PESs have been represented by a two‐dimensional grid with 256 points along 1S0] and [S0S1] state can access two pathways, upconversion (at the FC geometry) or the pericyclic minimum region, to proceed. Based on the branching ratio calculations by using Eq. 9, the probability of the population reaching the upconversion region has been estimated to be more than 35 % by the end of the simulation timescale  used to perform the polaritonic non‐adiabatic dynamics simulations. The coupling strength, which depends on the molecular transition dipole moment and the cavity field strength, has been varied to estimate the cavity effects on the TTA process. The electronic structure calculations on naphthalene reveal that the magnitude of transition dipole moments between ground and first singlet excited state to be relatively small (≈0.05 au). However, experimental studies commonly use acene derivatives such as TIPS‐naphthalene or TIPS‐anthracene instead of the parent molecules, and they have stronger transition dipole moments and consequent small fluorescence lifetimes. state decay rate increases significantly by increasing the cavity coupling strength. Interestingly, the rise of the population in the [S0S1] state decreases with an increase in the coupling strength, whereas the time evolution curve for [S1S0] state is unchanged. This suggests that the [T1T1] state population directly transfers to the |S0S0,1state, which increases with the increase in field strength  whereas the latter channel forms the excimer minimum. The fluorescence emission from the singlet exciton state produces the photon higher in energy than the incident light and this explains the photon upconversion due to the TTA process. The second channel forming the pericyclic minimum reduces the upconversion efficiency by non‐radiatively decaying to the ground state via an avoided crossing with the ground state or S1/S0 CI  should be addressed to the authors.Supporting InformationClick here for additional data file.