Ligands A feature an inward pointing NH function, able to engage in hydrogen bonding and amenable to being functionalized with amide and alkyl substituents. Ligands B comprise tricyclic aromatic backbones of different shape and electronic situation. The obtained heteroleptic coordination cages were investigated for their ability to bind phosphate diesters as guests. All‐atom molecular dynamics (MD) simulations in explicit solvent were conducted to understand the mechanistic relationships behind the experimentally determined guest affinities.Metallosupramolecular hosts of nanoscopic dimensions, which are able to serve as selective receptors and catalysts, are usually composed of only one type of organic ligand, restricting diversity in terms of cavity shape and functional group decoration. We report a series of heteroleptic [Pd 2A2B2] coordination cages was prepared by shape‐complementary assembly (SCA) from a modular set of ligands and screened for binding phosphate guests. All‐atom molecular dynamics simulations reveal that an endohedral hydrogen bond donor site is the decisive but not exclusive factor for binding phosphate diesters inside the cavity in a competitive solvent.A series of heteroleptic [Pd However, while corresponding assembly products often exhibit intriguing beauty concerning their highly symmetric shapes, e.g. following the Platonic or Archimedean solids, this can also restrict the versatility of the created voids and their equipment with chemical functionality.To gain more structural and functional diversity, we foster the development of assembly strategies aimed at the high‐yielding, non‐statistical synthesis of heteroleptic coordination cages composed of two or even more different ligands within one metallosupramolecular architecture.51, 522A2B2] coordination cages that self‐assemble from a library of shape complementary bis‐monodentate ligands A=1L4– and B=A–DL in a non‐statistical fashion 4](BF4)2 salt to a 1 : 1 mixture of solutions of one of ligands 1L4– with one of ligands A–DL in DMSO‐d6 and DMF‐d7 leads to the quantitative formation of the corresponding heteroleptic coordination cages of the type [Pd21L4–2A–DL2] after a few minutes at room temperature .The addition of 0.55 eq Pd21L2AL2] was confirmed by 1H NMR measurements, as downfield shifting of the signals of protons in close proximity to the nitrogen donors of both ligands was observed  Å. The carbazole planes of ligands 1L are almost coplanar with a N−N distance of 6.727(7) Å. Inspection of the structure reveals that the inner cavity can essentially be accessed from three directions, i.e. through the apertures between the neighboring unlike ligands . Furthermore, two encapsulated DMF molecules with their oxygen atom pointing towards the Pd centers were observed to be sandwiched between the carbazole moieties of ligands 1L in the crystal structure.For compound , containing ligand 2L instead of 1L, in which the carbazoles’ hydrogen bond donor functions are blocked by methyl substituents. Upon addition of 3G, a downfield shift of signals of the inner protons was still observed, though being much smaller compared to the situation with [Pd21L2AL2]. A much lower binding constant of K=77±3 M−1 was obtained accordingly, as the association should now be limited to overall weaker non‐covalent interactions between the cationic host and the phosphate, moreover in a very polar solvent environment. Titration of the other aromatic guests to cage [Pd21L2AL2] also showed binding to the host with comparable binding constants (Table S1). Remarkably, chiral guest 6G was also found to bind inside the host, giving rise to a slight guest‐to‐host chiral induction effect, as evidenced by CD spectral examination (Supporting Information). Furthermore, titration of aliphatic guests 1G and 4G indicated binding by shifting of the corresponding signals. Unfortunately, binding constants could not be determined due to a strong signal broadening after addition of more than 3 eq of guest. However, a guest competition experiment with cage [Pd21L2AL2] and 1 eq of diphenyl phosphate guest 3G as well as 1 eq of diethyl phosphate 4G clearly revealed that the aromatic guest is binding stronger than the aliphatic (Supporting Information). Clear indication for guest uptake was further obtained by trapped ion mobility spectrometry (TIMS), coupled to high‐resolution ESI‐TOF mass spectrometry, as the gas‐phase collisional cross sections (CCS) of the host–guest complexes did not change significantly compared to the free host. This is a strong indication for inside binding.To prove that guest binding is mainly driven by the formation of hydrogen bonds, the titration experiment was repeated with cage [Pd21L2AL2], carrying endohedral NH hydrogen bond donors, and [Pd22L2AL2], with these nitrogens methylated, all‐atom MD simulations in explicit DMSO solvent were performed (see Supporting Information). Multiple spontaneous binding and unbinding events of the 3G guest were observed during the extended MD simulation timescale of 50 μs, allowing to estimate the free energies of binding.−1 for cages [Pd21L2AL2] and [Pd22L2AL2], respectively. Thus, in line with the experimentally measured differences in the association constants (see above), the lack of the H‐bonding capability in 2L reduces binding affinity. To explain the surprisingly small free energy difference, the molecular interactions that govern the host–guest binding were characterized more closely. First, a contact analysis was performed, considering the likelihood of interactions between individual host features (e.g. the NH or NCH3 groups or the aromatic moieties of the ligands) and functionalities of the guest (i.e. the anionic phosphate and the phenyl groups). To that end, the chunks of the MD simulation trajectories were analyzed during which the guest was bound inside the cage cavity. Figure 21L2AL2], binding of the 3G guest is mediated by both, H‐bonds between the phosphate and the NH groups of the cage and, in addition, by nonpolar contacts between the 3G phenyl groups and the different chemical moieties of the cage . In the methylated [Pd22L2AL2] cage, the lack of the H‐bonding capability is partially compensated by an increase of nonpolar contacts, especially with AL  partially compensated by more favorable interactions between the guest and hydrophobic ligand AL in the methylated cage (Table S4). In addition, to investigate the selectivity of the cage towards guests of different size, we repeated the MD simulations also for guest 4G binding to cage [Pd22L2AL2] . As expected, binding of the smaller diethyl phosphate guest is much weaker than for 3G, with a binding free energy of about −1±1 kJ mol−1. Closer analyses of the interaction energies between [Pd22L2AL2] and 4G (Table S5) show that this smaller affinity can be attributed to a loss of favorable interactions of the guest with the extended aromatic surfaces of ligands 2L and AL. This result suggests that instead of the mere size of the guest, the nature of the phosphate substituents  plays an important role as well.To gain atomic‐level insights into the molecular interactions underlying the experimentally observed differences in guest binding by cages [Pd3G@Pd21L2AL2] and [5G@Pd21L2AL2] via slow vapor diffusion of Et2O into solutions of the host–guest compounds in DMF. Surprisingly, the phosphate esters were found to be not located inside the pocket of the host but interact with the Pd cations from the outer faces of the coordination cages in the densely packed solid state structures  and two DMF molecules , positioned in exactly the same locations as in the structure of the parental host shown in Figure In addition, we tried to obtain further insight from a solid‐state structure of the host–guest complex. We were able to obtain single crystals of , however, the binding constants decreased significantly. For example, a binding constant of K=98±1 M−1 was calculated for [3G@Pd21L2BL2] and constants for titration of 3G to the other cage derivatives containing ligands CL and DL are in a comparable, low range  in a modular, non‐statistical fashion. The uptake of different phosphate esters was quantified by NMR titrations and it was revealed by all‐atom MD simulations that strong binding is mainly driven by hydrogen bonding to the endohedral NH functions of ligands We herein show that the recently growing class of heteroleptic metallosupramolecular cagesThe 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.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.


Six different industrial amines are employed as co‐catalyst in millimolar concentrations to deliver a series of new reactive system. While such absorbents were so far believed to provide a CO2 reservoir and act as sacrificial proton source, we herein demonstrate that this role can be played by methanol, and that the adduct formed between CO2 and the amine can act as an effector or inhibitor toward the catalyst, thereby enhancing or reducing the production of formate. Pentamethyldiethylentriamine (PMDETA), identified as the best effector in our series, converts CO2 in wet methanolic solution into bisammonium bicarbonate. Computational studies revealed that this adduct is responsible for a barrierless transformation of CO2 to formate by the reduced form of the Mn catalyst covalently bonded to the electrode surface. As a consequence, selectivity can be switched on demand from CO to formate anion, and in the case of (PMDETA) an impressive TONHCOO− of 2.8×104 can be reached. This new valuable knowledge on an integrated capture and utilization system paves the way toward more efficient transformation of CO2 into liquid fuel.Carbon cloth electrode modified by covalently attaching a manganese organometallic catalyst is used as cathode for the electrochemical reduction of CO Carbon cloth electrodes were modified by attaching a manganese organometallic catalyst to the surface by covalent bonds. The system has been used for the electrochemical reduction of CO2 in presence of amines in methanol solution. The enhanced CO2 solubility and the use of pentamethyldiethylentriamine (PMDETA) induce change in chemical selectivity from CO to formate, with very high performances and high selectivity. Recent reports pointed out that an integrated approach, wherein the capture, utilization and storage technologies are designed to operate synergistically, may represent one of most effective options for viable and scalable GHG (Green House Gases) mitigation. ‐2,2’‐bipyridine) containing two acidic OH groups in proximity of the purported metal binding site for CO2 redox catalysis show enhanced catalytic activity towards HCOOH production.The latter is a true transformation, not a utilization but it raises the issue of the electron source needed to produce hydrogen, itself required for CO formate.17 In pa2 reduction integrated to its absorption remain scarce.2 with a Mn‐based soluble electrocatalyst, in the presence of amines .2 under the form of carbamates, but also to stabilize and promote the formation of the hydride catalytic intermediate (HMn), thereby favoring formate production instead of CO.) covalently bound to a Carbon Cloth (CC) surface. CC is a relatively cheap material of low electrical resistance and large surface area, widely exploited for the preparation of electrodes for low temperature fuel cells.Herein we investigate the role and impact of amines in millimolar concentration on the electroreduction of COMn/CC) was tested as a catalyst for CO2 electrochemical reduction in a three‐electrode cell with two gastight compartments, with methanol as a solvent. Its performance was studied in the presence of a panel of industrial amines (CO)3Br was anchored to a carbon cloth (CC) electrode surface via the formation of C−C bonds. The presence of the aniline moiety on the bipyridyl ligand enables the grafting of the complex onto carbon surfaces via the in situ formation of the corresponding diazonium salt. This method advantageously bypasses the isolation and purification of the diazonium reactive intermediate. Electrochemical reduction is performed to trigger C−C bond formation and N2 evolution. To assess the amount of electrocatalyst covalently bound on CC, a comparative ICP analysis was performed on the pristine CC starting material and on Mn/CC. A surface coverage Γ of 1.67×10−9 mol cmECSA−2 was obtained, in reasonable agreement with the previously reported value (1.4×10−9 mol cmECSA−2), determined via the indirect method of charge integration of the CV data collected from CC bonded nitroaniline.Mn/CC catalyst. The spectrum obtained from the catalyst sample before exhaustive electrolysis displays two peaks at 641.9 and 653.0 eV , which can be assigned to Mn(I) 2p3/2 and 2p1/2, respectively. This is in perfect agreement with previous studies on Mn(I) derivative that reported the two peaks at 641.8 and 653.0 eV.CC electrode was first tested for CO2 electroreduction using a three‐electrode cell with two gastight compartments filled with methanol, kept under a constant flow of CO2 (30 mL/min). An onset reduction potential of –1.35 V vs. Ag/AgCl was applied.The modified 2 reduction was performed with the Mn/CC modified electrode immersed into CO2‐saturated MeOH solution of each amine (1 mM) within the cathodic compartment. The different amines tested , Diethanolamine (DEA), Pentamethyldiethylentriamine (PMDETA), Triethylamine (TEA), Tetramethyletylendiamine (TMEDA) and 2‐tert‐butyltetramethylguanidine (TBG).With the exact same setup, CO2 capture , most of the captured CO2 is absorbed by physical dissolution (see Table 2)=1 atm, this gas has a solubility of 0.007 in MeOH,1H NMR for DEA, DETA and PMDETA, which cover the scope of primary to tertiary amines, bearing between one and three binding sites and either undergoing preferentially carbamation or carbonation (see Supporting Information section 4). As Gibb's free energy of carbonation is lower compared to carbamation, we herein used a 50‐fold excess of water with respect to the amine, which enables the former process to be as favored as the latter  act as substrates during electroreduction can eventually be ruled out, allowing us to focus on the potential role of these CO2‐amine derivatives in the very catalytic process. We have recently shown that industrial polyamines used for CO2 capture are powerful metal chelators which can effectively be employed for metal extraction in methanolic medium. In agreement with this previous study, we observed that 20 minutes of CO2 flow were required to fully pre‐load the amine solution and further enable the electrolysis to proceed properly. Any attempt to directly contact the unloaded diluted amine and the catalyst, systematically resulted in a detrimental effect on the reduction activity. In addition, DFT calculations also suggests that the real catalyst (i. e. the Mn pentacoordinate anion [Mn(bpy)(CO)3]−, −Mn, see Scheme 2 or MeOH (see Supporting Information section 4). After the preliminary CO2 saturation, Mn/CC was inserted in solution, continuously supplied with CO2 while the electrolysis was conducted with a set potential of −1.35 V vs. Ag/AgCl. Karl‐Fischer titrations were performed at the beginning and at the end of the process, confirming that a constant amount of H2O was present in the medium, around 0.96 mg/mL (i. e. 0.1 % w/w or 50 mM).At such low amine concentration 1 mM), at least three orders of magnitude lower than what is commonly used for CO mM, at lCO, TONH2 and corresponding FE values were obtained by sampling gases from the cell headspace every 5 minutes and by injecting them in a micro‐GC analyzer, while TONHCOO− and FEHCOO− were evaluated by quantitative 1H NMR analysis of the catholyte at the end of electrolysis.Table H2, TONCO and TONHCOO− values after 22 h of continuous CPE at −1.35 V for all amines , and the production of H2 and CO over time of a methanolic solution containing PMDETA.Figure Mn/CC catalyst only afforded CO (FECO=60 %) and H2 (FEH2=40 %) as CO2 reduction products when used in aqueous medium,CO=51 %, FeH2=20 % and FEHCOO−=26 % . The most striking results were obtained by the addition of PMDETA, which strongly shifted the selectivity of Mn/CC towards formate, with a remarkable FEHCOO− of 66 %. Noteworthy, while FEH2 of DETA, DEA and PMDETA are similar , FECO values of PMDETA is significantly lower (5 %). The main difference between the three amines is that PMDETA presents three tertiary amine functionalities, which orients CO2 capture exclusively toward carbonation (Eq. (2), Scheme TEA, TMEDA and TBG. These species respectively present one, two and three tertiary amine functionalities, which are conjugated into a guanidine pattern in the latter. Surprisingly, these additives did not induce an increase in the production of formate compared to the amine‐free reference system. In contrary, TMEDA displayed an unexpected detrimental effect on formate production, yielding TONCO values similar to those obtained in the absence of amine, and a noticeable increase in FEH2 and TONH2. TEA, TMEDA and TBG reached TONHCOO− values of 4040, 873 and 6563, and TONCO of 5735, 10073 and 6159, respectively. From this set, it appears that PMDETA was the most efficient catalytic additive, favoring the reduction of CO2 into formate in methanolic solutions with high TON and FE.Within the series tested, 3]− (−Mn) reacts in acetonitrile with the starting neutral complex [Mn(bpy)(CO)3Br] (Mn) producing directly the neutral dimer, a key intermediate in the electrochemical reduction of the Mn bipyridyl complexes. We hypothesized that in the present case, MeOH can transform [Mn(bpy)(CO)3]− into the corresponding hydride HMn(bpy)(CO)3, namely HMn, since the Mn catalyst is locked on the CC surface and it is unlikely to react with another Mn unit.Daasbjerg and coworkers3]− complex, and that the chemical reaction [Mn(bpy)(CO)3]−+CO2+MeOH→[HMn(bpy)(CO)3]+MeCO3− displays a favorable ΔG=−55.0 KJ/mol (see Supporting Information section 4).Selected DFT calculations, performed to explain the main trends and elucidate the underpinning mechanisms, clearly indicate that the proton of MeOH points towards the metal center of the pentacoordinated [Mn(bpy)(CO)3OD but with a fixed 50 mM D2O provided some clues about the species that may be present in the cathodic compartment and on their relative abundance (Supporting Information section 3). On average, amines can be loaded with around 0.3–0.4 equiv. of CO2 per nitrogen site at 500 mM. This loading does not vary substantially upon dilution with CO2‐saturated CD3OD containing 50 mM D2O, as attested by measurement of the protonation state  and by the absence of stripping. For amines bearing primary and secondary nucleophilic nitrogen binding sites such as DEA and DETA, dilution from 500 to 5 mM globally switches the CO2 fixation pathway, from carbamation to carbonation. At high alkalinity/amine concentration, methyl carbonate MeCO3− is observed as a carbonation side product. For PMDETA, a 1.05 : 1.00 HCO3−: amine molar ratio is obtained (see Supporting Information), which validates the formation of catalytic amounts of biprotonated PMDETA, named 2 c‐PMDETA , whereas the formate production in MeOH proceed via the hydride HMn and its reduced form −HMn. Table 2 to the −HMn radical anion. The adduct (−⋅⋅⋅CO2Mn‐H) produces the intermediate (2Mn⋅⋅⋅H‐CO−), which is 57.4 KJ/mol more stable than the (−⋅⋅⋅CO2Mn‐H) precursor, via the transition state −⋅⋅⋅CO2)TSTS is only 2.9 KJ/mol higher than the intermediate (2Mn⋅⋅⋅H‐CO−), (54.5 KJ/mol lower in energy with respect the starting (−⋅⋅⋅CO2Mn‐H) adduct). The final formate complex (−Mn⋅⋅⋅OCHO) is more stable than the starting species by 78.4 KJ/mol. Subsequent release of formate anion and electron transfer restores the starting radical anion catalyst −Mn. The mechanism leading to the coordination of CO2 to −Mn (and CO production) displays a similar energy barrier .By using 2 solutions  and/or by stabilizing key transition states. With the exception of TMEDA, all amines display a similar TONH2. This strongly suggests that the main source of protons in solution is MeOH rather than the ammonium moieties paired with carbamates or carbonates.[As mentioned earlier, adducts generated from diluted amine‐CO Figures  a‐f shourbonates.20TMEDA stands as an extreme case in the series, markedly favoring H2 over formate. The conversion of this α,β‐diamine into a bisammonium dication upon double carbonation is strongly disfavored, therefore its main adduct with CO2 combines a basic nitrogen moiety and an ammonium group . This quadrupolar species perfectly meets the requirements to activate a complementary quadrupolar species, such as CO2 . It also highlights the activating role of PMDETA, as CO2 binding is accompanied by its bending by 5°, which pre‐activates this substrate toward hydride addition , but the reaction with the reduced Mn hydride radical anion −HMn proceeds barrierless toward the production of formate, which is coordinated to Mn metal via the H atom .Additional DFT calculations confirm this interpretation. The divalent ammonium‐bicarbonate salt 2 capture adducts in significant amounts, which should respectively activate complementary dipoles or quadrupoles such as methanol or CO2 and enhance the production of H2 or formate, remains valid on the rest of the series. DETA stands in between the two extreme cases of PMDETA and TMEDA and moderately enhances the selectivity toward formate production. We recently reported that DETA‐CO2 is a compositionally complex system in methanolDETA‐based library of carbamates and carbonates  moderates the enhancing effect toward formate production. The other amines of the series behave as negative controls  and the diluent (proton source and CO2 reservoir). In silico DFT studies elucidated the entire mechanism of the process, which was confirmed to diverge on demand toward CO or formate production depending on the structure of the amine additive used. In particular, an unexpected barrierless conversion of CO2 to formate was observed in our operating conditions with PMDETA. A lock‐and‐key scenario emerges from this analysis to explain the role of CO2‐loaded amines in the activation of either dipolar (methanol) or quadrupolar (CO2) substrates towards the reaction with the Mn catalyst, enabling to tune the reaction toward H2 or formate production.To the best of our knowledge, this study proposes the first example of a covalently bound organometallic complex devoted to CO2 capture and conversion by electrochemical and chemical means. It clearly calls for further improvement, such as increasing the effective concentration of CO2 and facilitating the release of formate. Yet, it brings the proof of feasibility of amine‐assisted enhancement of electrochemical activity and selectivity, on a catalytic systems fulfilling several of the many requirements for potential industrial deployment.We believe that this study should stimulate many investigations on the synergies between CO2) were detected and quantified with an Agilent 490 μGC with two separate CP‐Molsieve 5 Å columns, equipped with a thermal conductivity detector. Columns were kept at 85 °C and at a pressure of 21 psi. CO and H2 were quantified using He and Ar as carrier gases, respectively. The gas inside the measurement cell was sampled for 30 s every 5 min to fill the μGC 10 μL sample loop, and eventually 400 nL were injected into the column. Ar, He, and CO2 pure gases (>99.9995 %) from Sapio have been used, and two different certified standard concentrations of CO and H2 in Ar matrix (Rivoira) for μGC calibration.2 were 1 ppmv and 0.5 ppmv, respectively. Formate was quantitatively detected by q1H NMR recorded on a JEOL ECP 400 FT NMR spectrometer (1H operating frequency 400 MHz) at 298 K using DMSO as an internal standard. 1H chemical shifts are reported relative to TMS (δ=0) and referenced against solvent residual peaks. All reagents and solvents were obtained from commercial sources at reagent‐grade purity and used as received. Diethylenetriamine (99 %), N,N,N’,N’‐Tetramethyl Ethylenediamine (∼99 %), N,N,N’,N’’,N’’‐Pentamethyldiethylenetriamine (99 %), Diethanolamine (≥98 %), Triethylamine (≥99.5 %), 2‐tert‐butyltetramethylguanidine (≥97 %) were purchased from Sigma‐Aldrich. CO2  and N2 (≥99.9 %) were obtained from Air Liquid. D2O  was purchased from Eurisotop.CV and CPE experiments were performed using an Amel 7050 potentiostat. Gaseous reduction products (CO and H6 0.1 M) as supporting electrolyte. TBAPF6  was recrystallized twice from hot ethanol and dried before use. A single compartment cell was used for CV measurements. The pristine carbon cloth, CC,  was cut in pieces of 3.4 cm2 and ultrasonically cleaned in 50 % wt 2‐propanol solution in Milliq water for 15’ and in pure Milliq water for additional 20’, then dried in an oven at 60 °C for one hour, in a similar manner as previously reported.CC was employed as working electrode, alongside a Pt counter electrode and an Ag/AgCl (KCl 3 M) as reference electrode. Under our experimental conditions, the reference ferrocene/ferrocenium (Fc/Fc+) redox is at E1/2=0.40 V (ΔEp=65 mV) vs. Ag/AgCl.Electrochemical measurements were conducted in methanol  with tetrabutylammonium hexafluorophosphate . TBAPF6  was dissolved in methanol (40 mL) in a three‐electrode cell with two gastight compartments under Ar. The gas flow was saturated with methanol vapors by a pre‐bubbler system in order to avoid evaporation in the cell.Functionalized Procedure with no addition of amines: the solution was saturated with a constant flow of CO2 . The electrolysis was started by setting a potential of −1.35 V vs. Ag/AgCl.Procedure with addition of amines: specific aliquots of the amines (1 mM) were added in the cathodic compartment. The solution was saturated with a constant flow of CO2  prior to insert Mn/CC electrode, in order to fully load the amine . The electrolysis was started by setting a potential of −1.35 V vs. Ag/AgCl.CPE was performed for 15–22 h during which the electrochemical cell was protected from light.The authors declare no conflict of interest.1As 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.


Serum‐glucocorticoid‐induced kinase‐1 (SGK1) regulates ion homeostasis and promotes survival under stress conditions. The expression of SGK1 is under transcriptional and post‐translational regulations that are frequently altered in cancer and immune disorders. We report that an N‐terminal amphipathic alpha‐helix determines SGK1 expression levels through two distinct mechanisms. It tethers SGK1 to intracellular organelles generating a large pool of membrane‐bound SGK1, which is differentially stabilized in lipid droplets (LD) in fed conditions or degraded in the endoplasmic reticulum by ER‐phagy in starvation. Association of the α‐helix to organelles does not depend on dedicated receptors or special phospholipids rather, it is intrinsic to its physicochemical properties and depends on the presence of bulky hydrophobic residues for attachment to LDs. The second mechanism is recruitment of protein‐chaperones that recognize the α‐helix as an unfolded protein promoting survival of the cytosolic SGK1 fraction. Together, the findings unveil an unexpected link between levels of energy storage and abundance of SGK1 and how changes in calorie intake could be used to modulate SGK1 expression, whereas the inhibition of molecular chaperones could serve as an additional enhancer in the treatment of malignancies and autoimmune disorders with high levels of SGK1 expression. It protects against numerous stress stimuliDriven by the frequently increased expression level of SGK1 in pathologies, particularly in cancer and T cell‐mediated disorders, we sought to identify post‐translational processes and interacting proteins that modulate the abundance of SGK1 in cells and in mouse tissues. We found two distinct processes operating alongside that either stabilize or promote degradation of SGK1. One relies on SGK1 association to intracellular organelle's membranes and the other recruits a large array of chaperones from different protein quality control machineries. These regulatory mechanisms could be targeted for therapeutic reduction of SGK1 levels in malignant cells and other pathological processes that exhibit increased SGK1 transcription.2Supplementary File 33.1The crystal structure of human SGK1 catalytic domain has been solved (PDB ID: 3HDM) but not that of the Nt that encodes a critical degron. Prediction of the secondary structure of a stretch of hydrophobic residues using PEP‐FOLD yields an α‐helix from residues R16 to R31 Figure . As the Next, we examined whether SGK1 associates to artificial lipid bilayers by incorporating recombinant SGK1 and ∆60SGK1 into artificial liposomes examined by floatation through a sucrose step gradient. Figure We next looked for association of SGK1 to cellular membranes using immunofluorescence microscopy. The endoplasmic reticulum (ER) was identified with calnexin, the Golgi apparatus with polypeptide N‐acetylgalactosaminyltransferase 2 (GALNT2) and mitochondria with Hsp60. SGK1 colocalized extensively with ER, some with the Golgi complex and was undetected in mitochondria Figure , showing3.2We have previously shown that SGK1 is ubiquitinated by the Ub‐conjugating UBC6 and UBC7 enzymes and the Ub ligase Hrd1 that are ER‐associated and lead to rapid SGK1 degradation.The LD‐mediated stabilization of SGK1 observed in cultured cells was confirmed in tissues of transgenic mice that express SGK‐3FL driven by the CAG promoter Figure . We used1/2 was 42 min  and lysosomal inhibitors (1t/2 40 ± 8 min) stabilizes it  decreased SGK1 expression by 50 ± 6% Figure . Starvatt Figure , suggestTo examine whether SGK1 localizes in autophagosomes, we used AD293 cells stably transfected with LC3 fused with GFP (GFP‐LC3). Starvation induced by removing serum and adding rapamycin for 4 h led to the redistribution of the green fluorescence signal from a diffuse pattern into puncta that grew to the size of large vesicles after treatment with the lysosomal inhibitor bafilomycin A1 (BAF), consistent with the vesicles being autophagosomes Figure . These cTo answer how SGK1 could end up in autophagosomes, we first examined whether SGK1 forms cytosolic insoluble aggregates captured by autophagosomes.These findings suggest that starvation‐induced ER‐phagy sends a fraction of SGK1 to autophagosomes for lysosomal degradation. The mechanism by which SGK1 ends in autophagosomes could be proximity to ER‐phagy receptors that is, SGK1 hitchhikes its way to autophagosomes or alternatively, autophagic membranes could also recognize directly SGK1 in the ER surface. We noticed three putative motifs (the first one conserved from frog to human) Figure  in the c3.5Thus far, we have shown that SGK1 associates to various intracellular organelles and SGK1 stability is organelle‐specific. However, the cytosolic fraction of SGK1 is also highly susceptible to degradation. To identify proteins that promote or protect SGK1 from degradation, we used crosslinking strategies in 293T expressing SGK1. First, we used disuccinimidyl suberate (DDS) Figure . Table 1Functional significance of SGK1 interactions with crosslinked chaperones was examined. Suppression of endogenous Hsp70 activity by the inhibitor Azur C destabilized SGK1 significantly reducing steady‐state abundance Figure . Hsp90/CSGTA and Bat3/Bag6 have been linked to the degradation of misfolded proteins; they form a complex together with UBL4A and TRC35 that specializes in preventing the aggregation of transmembrane segments of integral membrane proteins that are either mislocalized or retrotranslocated from the ER to the cytosol.4Tight control of intracellular protein levels is necessary to adjust cellular responses to rapidly changing external and internal stimuli in order to adapt to fluctuations in the environment. This requirement cannot be met only by transcriptional regulation but also requires modulation of the target protein half‐life. Unique among the AGC family of kinases, SGK1 is subject to fine‐tuning of its intracellular concentration by transcription and degradation, a precondition necessary to modulate the response of SGK1 and integrate it with the signals of overlapping kinases such as AKT1.The main protein degradation pathways in eukaryotes are the proteasome, lysosome and autophagosomes. Conventionally, the ubiquitin‐proteasome degradative system is primarily responsible for the turnover of short‐lived proteins whereas autophagy degrades the bulk of long‐lived cytosolic proteins though, these differences may blur as more proteins are examined. Here, we found two mechanisms that regulate SGK1 protein abundance; both of them stem from the amphipathicity of the Nt α‐helix. One involves association of SGK1 to intracellular organelles: ER, LDs and autophagosomes, the other recruits various types of chaperones, illustrated in Figure 1t/2 value is an underestimation of SGK1 survival in the LD compartment because only a fraction of the total SGK1 localizes to LD thus, in these organelles, SGK1 survival is expected to be longer than 42 min. These observations were confirmed in mice by demonstrating higher steady state abundance of SGK1 in adipose tissues than in lean tissues. Accordingly, SGK1 signalling would be expected to increase in metabolically active organs such as liver, muscle and fat where the content of LDs largely increases under physiological adaptations and metabolic diseases .Association to intracellular membranes is driven by the Nt α‐helix that hides hydrophobic residues into the lipid environment of membranes to protect SGK1 from degradation. The association does not require a protein receptor or special lipids; it depends entirely on the physical properties of the α‐helix demonstrated by SGK1 incorporation into artificial liposomes in vitro. However, large hydrophobic side chains are required for binding to LDs; if those residues are substituted with small hydrophobic side chains, SGK1 cannot attach to LDs, though association to other intracellular organelles remains intact. This result agrees with the notion that bulky hydrophobic side chains detect and bind membrane packing defects that are unique to the surface of LDs.SGK1 also integrates into autophagosomes but the effect on stability is by redirecting a fraction of SGK1 to lysosomes. The answer to the question of how SGK1 ends up in autophagosomes is likely provided by ER‐phagy that carries SGK1 with ER fragments engulfed by autophagosomes recognized by ER‐phagy receptors. Furthermore, a conserved GIM‐like motif in SGK1 associates with GABARAPL1 and weakly with GABARAPL2 suggesting that SGK1 could be directly recognized as cargo by autophagosomes. Although we did not investigate whether SGK1 plays a role in the life cycle or biology of autophagosomes, no changes in autophagy levels were observed when SGK1 was expressed in 293T or in mice adipocytes. This differs from a previous report where a constitutively active SGK1‐S422D reduced autophagy in muscles of a transgenic mouse,The other system that determines SGK1stability is the protein quality control that we found interactive also with the Nt of SGK1. This motif recruits a wide range of chaperones, foldases and holdases that recognize the α‐helix as an unfolded polypeptide or as a mislocalized transmembrane domain. These chaperones were identified by crosslinking conducted with two different chemical reagents and spacer lengths: both recovered the same types of chaperones associated with full length SGK1 but not with ∆60SGK1 highlighting that the recruiting motif is the amphipathic α‐helix. Hsp90 and CDC37—that form a functional complex—were the exception because CDC37 selectively recruits client kinases binding to the catalytic domain.How SGK1 may transition from chaperones to association with intracellular organelles and what are the consequences for SGK1 stability? The current findings are consistent with SGK1 recruiting chaperones early in its biogenesis, as the hydrophobic α‐helix is the first segment of the protein to emerge from ribosomes. The chaperones Hsp90, Bat3/SGTA and chaperonins are associated with ribosomes and engage with clients early during synthesis.The strict control of SGK1 abundance is frequently disrupted in pathological conditions such as in malignant cells where SGK1 expression is frequently increased, a property that extends to cells lines derived from malignant tumours as illustrated in the screening conducted here Figure .49, 5The authors confirm that there are no conflicts of interests.Madiha Javeed Ghani: Formal analysis (lead); Investigation (lead); Methodology ; Validation (lead); Visualization (lead); Writing – original draft ; Writing – review & editing (supporting). Wenxue Gu: Formal analysis (supporting); Investigation ; Methodology (supporting); Writing – original draft (supporting). Zhuyuan Chen: Formal analysis (supporting); Investigation (supporting); Methodology (supporting); Validation (supporting); Writing – original draft (supporting). Cecilia M Canessa: Conceptualization (lead); Formal analysis (supporting); Funding acquisition (lead); Project administration (lead); Supervision (lead); Writing – original draft ; Writing – review & editing .Figure S1Click here for additional data file.Figure S2Click here for additional data file.Figure S3Click here for additional data file.Figure S4Click here for additional data file.Table S1Click here for additional data file.Table S2Click here for additional data file.Table S3Click here for additional data file.Supplementary MaterialClick here for additional data file.


When homogeneously nucleated in solution, lead sulfochlorides form Pb3S2Cl2 nanocrystals. Conversely, the presence of CsPbCl3 triggers the formation of Pb4S3Cl2/CsPbCl3 epitaxial heterostructures. The phase selectivity is guaranteed by the continuity of the cationic subnetwork across the interface, a condition not met in a hypothetical Pb3S2Cl2/CsPbCl3 heterostructure. The perovskite domain is then etched, delivering phase-pure Pb4S3Cl2 nanocrystals that could not be synthesized directly.Colloidal chemistry grants access to a wealth of materials through simple and mild reactions. However, even few elements can combine in a variety of stoichiometries and structures, potentially resulting in impurities or even wrong products. Similar issues have been long addressed in organic chemistry by using reaction-directing groups, that are added to a substrate to promote a specific product and are later removed. Inspired by such approach, we demonstrate the use of CsPbCl 3S2Cl2 and Pb4S3Cl2.Phase-selective approaches, such using reaction-directing groups, are often seen in traditional organic chemistry and catalysis. Here authors use perovskite nanocrystals as disposable templates to drive the phase-selective synthesis of two colloidal nanomaterials, the lead sulfohalides Pb Nowadays, NCs are exploited in many different fields, as NCs-based products are steadily finding their way to commercial applications18. A colloidal approach to the synthesis of inorganic materials offers several advantages over more traditional solid-state chemistry techniques, such as milder reaction conditions, ease of tunability deriving from a wider choice of precursors, better processability of the products, and straightforward access to nanostructured materials. However, both this flexibility and the push toward materials combining a higher number of elements come at the cost of increased complexity. One example is the field of colloidal semiconductors, where lead-based NCs are among the most explored compounds due to the appealing optoelectronic properties demonstrated by lead halide perovskites in the UV-VIS and by lead chalcogenides in the IR spectral ranges19. There, the combination of as little as four elements  can yield NCs of a variety of phases: the binaries CsX, PbX2, and PbE22, the well-known cesium lead halides 24, and the still little explored lead chalcohalides (Pb4S3Br2 and Pb4S3I2)26. All these compounds are often obtained under similar reaction conditions, and can therefore compete during the synthesis, requiring a careful tuning of the synthetic protocols to achieve an impurity-free synthesis of the desired product.Since its early days27. This requires a multi-step rational design of the synthetic procedure, that is common for organic chemistry but is missing in the colloidal synthesis of NCs, as most procedures consist of a one-step reaction.This condition is not dissimilar from that of many organic chemistry reactions, where two molecules can react following different pathways and resulting in different products. Similar issues are often addressed by exploiting reaction-directing groups, that are moieties which are attached to one of the reagents in order to direct the reaction pathway toward the desired product, and are removed at a later stageaEbXc, and only four stable compositions are known in bulk 29, together with two recently reported high-pressure metastable phases 31. Our group pioneered the investigation of lead chalcohalides at the nanoscale, discovering two additional compounds (Pb4S3Br2 and a yet not identified Pb-S-Cl phase) in the form of NCs25. More recently, we found that Pb4S3Br2 can match epitaxially the CsPbX3 perovskite to form colloidal heterostructures, thus demonstrating a remarkable synthetic and structural compatibility26. Here we focus our attention on the lead sulfochlorides, demonstrating that the yet unknown Pb-S-Cl phase obtained through direct synthesis is Pb3S2Cl2, whose structure, here identified as monoclinic, is a distorted version of the cubic Pb3Se2Br2 prototype  the presence of a perovskite-like atomic plane26, and ii) the continuity of the cationic subnetwork across the chalcohalide/perovskite interface32. Such conditions are not met for Pb3S2Cl2, whose homogeneous nucleation is, therefore, less favorable than the heterogeneous nucleation of Pb4S3Cl2 templated by the CsPbCl3 perovskite.The reason why CsPbCl36, with the phase-selection capabilities ensured by the epitaxial templating, all in the liquid phase.Overall, our method effectively combines the concept of sacrificial substrates, such as the alkali halide single crystals used for the large-area synthesis of films and ultrathin materials25, but in our previous work the small size of the particles and the heavy PbS contamination prevented us from determining the composition and crystal structure, which had therefore remained unknown to date. To solve the structure in the present work, we prepared large-size NCs via a two-step procedure, consisting of nucleation and seeded growth  pattern could not be fitted based on the supposedly related Pb3Se2Br2 cubic prototype31, suggesting a different structure. Therefore, we exploited a combination of techniques to solve it. First, we performed a single-NC 3D Electron Diffraction (3D-ED)37 experiment to identify the unit cell parameters and a list of possible space groups  experiments respectively . Beyond this size the NCs became insoluble in the reaction medium, and the accretion process halted. The composition measured by SEM-EDX was Pb:S:Cl = 3.2:1.8:2.0, which is compatible with our previously advanced hypothesis of a Pbups Fig. . For somely Fig. .Cc space group 31, while 4E3X2 39. Indeed, in both structures Pb2+ is surrounded by eight anions, and S2− features a distorted octahedral coordination. Conversely, the coordination of the halide changes: in Pb3S2Cl2 the smaller Cl− ions share the same octahedral coordination as S2−, while the larger Br− and I− ions in Pb4S3X2 are surrounded by seven Pb2+ ions in a pentagonal bipyramidal configuration. The reason is likely that bulkier anions can accommodate an enlarged coordination environment. Interestingly, Pb3S2Cl2 is the only lead chalcohalide where Cl− is coordinated by an octahedron of Pb2+ ions. Such coordination has been recently proposed on the surface of PbS NCs synthesized in excess of PbCl2 to account for the formation of a Cl-rich shell that improves the optical properties43, suggesting that these NCs might be passivated by a layer of some lead sulfochloride compound. For further comparisons between the structures of Pb3S2Cl2 and Pb3S2X2 compounds see 4S3Br2 and Pb4S3I2 NCs and a comparison of PDF profiles by RootProf44.The solution was found in the monoclinic 4S3Br2 can grow epitaxially on lead halide perovskite domains26, suggesting that other isostructural compounds, i.e., Pb4S3I2 and a hypothetical Pb4S3Cl2, would do the same. Conversely, the Pb3S2Cl2 structure we hereby solved is remarkably different from that of the Pb4S3X2 compounds, to the point that the epitaxial compatibility with CsPbX3 would be lost. This prompted us to think that the synthesis of a sulfochloride/perovskite heterostructure would produce domains of the yet unknown compound Pb4S3Cl2 instead. Indeed, the Pb4S3X2/CsPbX3 match, regardless of the halide, is strictly structure specific. First, both the chalcohalide and the perovskite share a plane of Pb2+ ions arranged in a square grid, which serves as an interface between the two domains  showed that the heterostructures were composed of two highly crystalline domains jointed along a flat interface spanning across the entire nanoparticle Fig. . As expe4S3Cl2/CsPbCl3 interface, superimposed in Fig. 2+ cationic subnetwork through the quantitative analysis of HAADF-STEM images , remarking that the electronic properties of lead chalcohalides are not straightforwardly related to those of chemically similar compounds. A comparable absorption profile was found in the heterostructures spectrum, combined with the blunt absorption edge of the direct-gap CsPbCl3 domain  when the perovskite domain was involved in the heterojunction  and a band narrowing, further corroborating the strong similarities between the optoelectronic properties of these three systems. See Owing to the relaxation of the momentum conservation at the nanoscale, both the free-standing sulfochlorides and the heterostructures exhibited a broad PL peak at ∼1.8 eV  yielded Pb3S2Cl2 NCs, only the selective etching of the heterostructures perovskite domain allowed us to recover free-standing Pb4S3Cl2 NCs. This ultimately means that we could select the reaction product between two competing phases, a problem of great relevance in the synthesis of colloidal inorganic nanomaterials. Both the obtained lead sulfochlorides shared remarkably similar optoelectronic properties. This, combined with our previous observation on bromine- and iodine-based sulfohalides25, suggests that lead sulfohalide compounds are mostly stoichiometry- and structure-insensitive. Interestingly, the discovery of the Pb3S2Cl2 structure demonstrates that Cl− in lead chalcohalides can be coordinated by an octahedron of Pb2+ ions, differently from Br− and I−. This supports the recent observations of a PbClx-rich shell on the surface of PbS NCs synthesized using PbCl2 as a precursor, a condition that is remarkably similar to our synthetic protocol and might indeed lead to the formation of a lead sulfochloride surface layer43.In this work, we have exploited the epitaxial templating effect of CsPbCl27, and allowed us to design the phase-selective synthesis of two yet unknown materials (Pb3S2Cl2 and Pb4S3Cl2) based on structural considerations only. Such an approach to a deterministic synthesis of NCs may be extended to other phases with known or predictable epitaxial relations, taking advantage of the vast library of already reported nanomaterials as starting templates. For example, in the field of chalcohalides it might lead to yet unknown selenium- and tellurium-based materials, or even to compounds where the halide is replaced by pseudohalide ions . In conclusion, we envision that our phase-selective templating approach will open new routes for the colloidal syntheses of nanomaterials which are now hindered by an excessive activation energy for the homogeneous nucleation, or by the competitive formation of undesired phases.We remark that our use of perovskite NCs as disposable and phase-selective epitaxial templates parallels that of reaction-directing groups in traditional organic chemistry and catalysis2, 98%), lead(II) bromide , lead(II) iodide , lead(II) thiocyanate (Pb(SCN)2, 99.5%), lead(II) acetate trihydrate (Pb(OAc)2·3H2O, 99.99%), cesium(I) carbonate , dodecanethiol , and sulfur powder  were purchased from Sigma‐Aldrich. All reagents were used as received without any further purification.1-octadecene , oleic acid , oleylamine , lead(II) chloride (PbCl2. The resulting mixture was sonicated until the complete dissolution of the sulfur powder.0.064 g (2 mmol) of S powder were mixed with 10 mL of ODE (pre-degassed at 120 °C under vacuum for an hour) in a 20 mL glass vial inside a glove box filled with N2 (0.8 mmol) were solubilized at 120 °C in a mixture of 2 mL of OLA, 2 mL of OA and 20 mL of ODE in a 100 mL flask. The solution was then heated up to 170 °C, and 2 mL of the S-ODE stock solution, pre-heated at 150 °C, were swiftly injected. The NCs formed ∼10–30 s after the injection, as revealed by the color change of the solution from pale yellow to red. After 1 min, the reaction was quenched by cooling the flask with a room-temperature water bath. The NCs were recovered by adding 40 mL of ethyl acetate, followed by a centrifugation at 6000 rpm (∼2940 × g) for 5 min. The precipitate was discarded, and the supernatant was suspended in hexane or toluene. If needed, the sample could be washed multiple times by adding ethyl acetate and repeating the centrifugation. The maximum diameter for Pb3S2Cl2 NCs obtained by direct synthesis was 7–8 nm (see 0.21 g of PbCl3S2Cl2 NCs prepared as detailed above. A stock solution of reagents was prepared by dissolving 0.2966 g of PbCl2 (1.06 mmol) and 0.6898 g of Pb(SCN)2 (2.13 mmol) in a mixture of 4 mL of OLA, 4 mL of OA, and 40 mL of ODE in a 100 mL flask at 120 °C. During its preparation, the stock solution must not exceed this temperature to avoid the thermal decomposition of the thiocyanate, which would cause the nucleation of PbS NCs25. Once the two solids were completely solubilized, the stock solution was cooled to room temperature, filtered with a 0.2 μm PTFE syringe filter, and loaded on a syringe pump. Then, a crude Pb3S2Cl2 reaction mixture in ODE was obtained by following the procedure detailed in the previous paragraph up to before the addition of ethyl acetate. 12 ml of such solution were heated to 170 °C, and the stock solution of PbCl2 and Pb(SCN)2 was added dropwise at a controlled rate of 10 mL/h with the help of a syringe pump. Finally, the reaction mixture was washed with ethyl acetate as described in the previous paragraph, and the NCs were suspended in hexane. A last step of filtration performed with a 0.2 μm PTFE syringe filter allowed to remove any impurity of PbS that may have formed during the accretion process. The so-obtained Pb3S2Cl2 NCs measured 29.5 ± 2.0 nm on average, and were used to solve the structure of the material by a combination of 3D-ED, XRPD, and PDF experiments. See Larger NCs were obtained through a seeded growth approach, performed by using as starting seeds Pb4S3Br2 (and Pb4S3I2) were prepared following our previously published method25. In short, 0.2 mmol of PbBr2 (or PbI2) and 0.2 mmol of Pb(SCN)2 where dissolved in a mixture of 10 mL ODE and 250 μL of OLA and OA at 120 °C in a 25 mL three-necked flask. Then, the solution was quickly heated (∼20 °C/min) and started turning from light-yellow to bloody red above 150 °C while the NCs nucleated and grew. The reaction was quenched by cooling the flask in a water bath. The NCs were recovered by simple centrifugation or by ethyl-acetate assisted precipitation followed by centrifugation . The so-obtained Pb4S3Br2 and Pb4S3I2 NCs were used to refine the structure of both materials by XRPD and PDF experiments , OA  and ODE (17.5 mL) were loaded into a 50 mL 3-neck flask, dried for 1 h at 110 °C and then heated under N2 to 150 °C until the solution turned clear. The resulting mixture was transferred into a N2 filled glass vial, which was stored inside a glovebox for further use.The Cs-oleate precursor was prepared by increasing the concentration of oleic acid in comparison to our previously reported method2 powder , OA (5 mL), and OLA (5 mL) were mixed with ODE (30 mL) in a 100 mL three neck round bottom flask. The reaction mixture was dried/degassed under vacuum for 15 min at 110 °C. Then, the flask was filled with N2 and the temperature was raised to 150 °C. After complete dissolution of PbCl2 salt, the solution was cooled down to room temperature (25 °C) and transferred into a N2-filled glass vial.PbCl26. Briefly, Pb(OAc)2·3H2O powder  and OA (1.3 mL), were mixed with ODE (18.7 mL) in a 50 ml three neck round bottom flask. The reaction mixture was degassed under vacuum for 1 h at 110 °C and then heated under N2 to 150 °C until all Pb(OAc)2·3H2O reacted with OA. Thereafter, the solution was cooled down to room temperature (25 °C) and transferred into N2-filled glass vials.The lead oleate stock solution was prepared following our previously reported method3 nanoclusters were synthesized following a previously reported method26. Briefly, 4 mL of the above-mentioned PbCl2 stock solution were transferred into the N2 filled 20 ml glass vial. Thereafter, 0.25 mL of the Cs-oleate precursor were injected into the PbCl2 stock solution at 40 °C and the resulting mixture was kept under stirring for 20 min. After about 20 min, the mixture (turbid white) was centrifuged at 8000 rpm (∼3935 × g) for 5 min, the supernatant was discarded, and the precipitate was redispersed in 0.9 mL of degassed ODE.CsPbCl2. The vial was heated to 200 °C, and 100 μL of the above-mentioned Pb(OA)2 solution and 20 μL DDT (diluted in 200 μL predried ODE) were added into the reaction system. Then, the mixture of S (0.1 mL) and CsPbCl3 nanoclusters (0.9 mL) was rapidly injected into the reaction mixture. The reaction was allowed to proceed for 5 min and was subsequently quenched by immersing the vial in an ice and water bath. The crude solution was then centrifuged by adding methyl acetate (with volume ratio of 1 to 1) and the precipitate was redispersed in toluene. See 4.0 mL of degassed ODE were added to a 20 mL glass vial under N2 solution, separately prepared by dissolving PbCl2 salt (1 mmol) in ODE (15 mL) in the presence of oleic acid (2.5 mL) and oleylamine (2.5 mL), was added to the toluene dispersion containing the heterostructures, and the mixture was vortexed for 1 min. Then, the solution was centrifuged by adding methyl acetate and the precipitate was redispersed in hexane or toluene for further use. The role of this treatment is to reconstruct the surface of the CsPbCl3 perovskite domains after the antisolvent-assisted precipitation, and to ensure the long-term colloidal stability of the sample.A PbCl3, without S-ODE) was swiftly injected. The mixture was annealed for 5 min and subsequently cooled down by using an ice water bath. The resulting mixture was centrifuged at 8000 rpm (∼3935 × g) for 5 min, the supernatant was discarded, and the precipitate was dispersed in 4 mL of toluene.4.0 mL of ODE were added to a 20 mL glass vial under air and heated to 150 °C, then 1.0 mL of the above-mentioned seed cluster solution (CsPbCl1 mL of heterostructures dispersed in hexane (corresponding to one entire batch of heterostructures) was treated first with oleylamine (60 μL). Then, an equal volume ratio of dimethylformamide  was added to the heterostructures dispersion and the resulting mixture was vortexed for 30 s. After the complete phase separation of solvents (2–3 min), DMF was removed by using a syringe and pre-dried oleic acid (60 μL) was introduced in the hexane dispersion. Subsequently, the now etched NCs were centrifuged by adding methyl acetate (with 1 to 1 volume ratio) and were redispersed in toluene for further use. See Bright-field TEM images of the samples were acquired with a JEOL-1100 transmission electron microscope operating at an acceleration voltage of 100 kV. The samples were prepared by drop casting diluted solutions of NCs or heterostructures onto carbon film-coated 200 mesh copper grids for low-resolution TEM.θ:2θ scan mode on a Panalytical Empyrean diffractometer, equipped with a 1.8 kW Cu-Kα ceramic anode working at 45 kV–40 mA and a PIXcel3D detector. XRPD data were acquired on samples in the form of dry powders or drop-casted solutions; the measurements were carried out in air at room temperature using a zero-diffraction silicon substrate.Lab-grade XRPD analyses were performed in 48. The color code in the intensity map correlates with the total intensity scattered from each atomic column. The intensity is calculated by fitting a Gaussian function to each atomic column: the intensity value of a column equals the volume of its Gaussian peak.High-resolution HAADF-STEM images were acquired with a probe-corrected cubed Thermo Fisher Scientific Themis Z Microscope operating at 300 kV with a probe semi-convergence angle of 20.5 mrad. For a quantitative analysis of the HAADF-STEM image, the intensities of the individual atomic columns in a single heterostructure were analyzed by using the StatSTEM software6 source. Data were acquired in STEM mode after defocusing the beam to achieve a parallel illumination of the sample. A beam size of about 150 nm in diameter was obtained by inserting a 5 μm C2 condenser aperture. A mild illumination was adopted to avoid any alteration or amorphization of the sample, and to slow down the accumulation of organic contaminants. 3D-ED data were recorded with an ASI Timepix detector49, which is able to detect single electrons and deliver a pattern that is virtually background-free. The camera length was 180 mm, with a theoretical resolution limit of 0.75 Å.3D-ED data were collected on a Zeiss Libra TEM operating at 120 kV and equipped with a LaB3S2Cl2, Pb4S3Br2, and Pb4S3I2 were measured in both setups, optimized for PDF and XRPD measurements, respectively. Lanthanum hexaboride (LaB6) was measured as a standard material to calibrate the wavelength and the detector geometry, including the sample-to-detector distance. An empty capillary was measured for background estimation. Diffraction images were azimuthally integrated and converted into intensity profiles vs 2θ and vs momentum transfer 50. PDF profiles were calculated up to interatomic distances r of 50 Å from the Q profiles with the program PDFGetX351. The parameters for PDF calculation  were optimized on individual PDF profiles, to avoid large termination effects and preserve the signal to noise ratio. The Qmax values were 23.7 Å−1 for Pb3S2Cl2 and 22.0 Å−1 for Pb4S3Br2 and Pb4S3I2.Synchrotron diffraction data were collected at the 28ID-2 beamline of the National Synchrotron Light Source (NSLS-II) of the Brookhaven National Laboratory with an X-ray energy of 67.17 keV (0.1846 Å) and a 0.5 mm × 0.5 mm beam size. A Perkin Elmer XRD 1621 digital imaging detector (2048 × 2048 pixels and 200 × 200 µm pixel size) was mounted orthogonal to the beam path in two positions: 228 mm and 1365 mm downstream of the sample. Samples of Pb3S2Cl2 NCs structure was performed through a combination of 3D-ED, XRPD, and PDF analyses. 3D-ED52 was used to determine the starting unit cell parameters and a set of possible space groups. In the process, the software ADT3D53 was used. XRPD was exploited to select the most promising space groups for the structure solution, extract the integrated intensities of reflections and perform the ab-initio structure solution by Direct Methods. In the process, the software EXPO201438 was used. Both XRPD and DFT data were exploited to refine the structure of NCs, by alternating the refinement in the direct (PDF) and reciprocal (XRPD) spaces. To analyze the PDF profiles, the PDFGUI55 and DiffPy-CMI16 software packages were used. The same refinement strategy was applied to Pb4S3Br2 and Pb4S3I2 NCs, while the structure solution step was not needed because the starting structure was already known30. All the crystal structure illustrations shown in this work were produced by using the software VESTA56. Additional details are provided in the The solution and refinement of the PbAbsorbance and photoluminescence (PL) spectra of solution NCs and heterostructures were recorded on a Cary 500 spectrophotometer and Cary Eclipse spectrofluorometer, respectively. The spectra were measured in 10 × 10 mm quartz cuvettes. A wavelength of 350 nm was used for excitation during the collection of PL spectra. Regarding the extended spectroscopy: for PL and transient PL measurements, the samples were excited using a Laser-export Co. Ltd., frequency tripled, pulsed Nd:YAG laser at 3.49 eV (355 nm) and at 2.33 eV (532 nm) with 1 kHz repetition rate and detected respectively using an Hamamatsu Mini-Spectrometer and an Oriel Instrument Cornerstone 1/4 m monochromator coupled with a Hamamatsu UV–VIS photomultiplier tube. Cryogenic Measurements were performed in a liquid nitrogen-cooled Oxford Instruments Limited cryostat.3S2Cl2 phase, we compared by DFT calculations the stability of the monoclinic Pb3S2Cl2 structure that we solved with that of a hypothetic cubic Pb3S2Cl2 structure. We performed this investigation on the corresponding 2 × 2 × 2 supercells at the gamma point. In particular, we relaxed both atomic positions and cell parameters at the DFT level using the PBE exchange−correlation functional57, and a double-ζ basis set plus polarization functions (DZVP) on all atoms as implemented in the CP2K 8.1 package58. Scalar relativistic effects were incorporated as effective core potentials in the basis set. With this approach, we determined that the monoclinic Pb3S2Cl2 2 × 2 × 2 supercell is more stable than the prototypal cubic one by 164 kcal/mol.To assess the impact of the cubic symmetry breaking on the stability of Pb59, quantifies the orbital localization of a given molecular orbital and it is defined as:Both the structural relaxation and the electronic structure calculations of atomistic NCs models were carried out at the DFT/PBE/DZVP level of theory with CP2K. In order to identify any surface localized states that could trap charge carriers, we also computed the Inverse Participation Ratio (IPR) for chalcohalide and perovskite, both in the form of free-standing NCs and in the heterostructure. The IPR, as also demonstrated for other NCsPα,i represents the weight of molecular orbital i on a given atom α expanded in an atomic orbital basis. For finite systems, the IPR provides an estimate of the number of atoms that contribute to a given electronic state i. It can range from the inverse of the number of atoms in the system  to 1 in the case of states localized on single atoms. In other terms, IPR values very close to 0 identify delocalized states.Here, Supplementary InformationSupplementary Data 1


The oxide materials have high capacity but high intercalation potential, low first cycle efficiency, and unstable cycle. Here, based on the understanding of the K intercalation mechanism of vanadium oxides, a novel zero strain anode material with layered structure of dual‐ions (Na+/K+) is designed (NaK(VO3)2—V2O5). The introduction of Na/K ion contributed to the transmission and further stabilized the structure. It has an excellent rate performance , and its special K storage mechanism and zero‐strain characteristics are revealed for the first time by ex situ scanning electron microscope, X‐ray powder diffraction, X‐ray photoelectron spectroscopy, and other test methods. Considering the excellent performance endowed by these unique inherent properties, NaK(VO3)2—V2O5 shows great potential for commercial anode materials and may promote the innovation of KIB.Potassium‐ion batteries (KIB) have similar energy storage mechanism with lithium‐ion battery, but the potassium (K) resource is rich, which shows great potential for large‐scale energy storage system. Recently, the anode materials of KIB studied mainly include carbon materials, transition metal oxides, and alloy materials. The amorphous hard carbon shows the best comprehensive performance, but its intercalation potential is close to 0 V (versus K 3)2‐V2O5 with excellent crystallinity and interface has been achieved through the reconstruction of layer structure. The electrochemical performances and the kinetic properties of the anode are significantly improved due to the formation of 2D ion channels.The new heterojunction material of NaK(VO The potassium (K) ion battery (KIB) is also a promising technic, due to the low cost and abundance in nature. However, K has a larger radius and reach a lower electrochemical kinetics, thus, the experience in lithium/sodium‐ion battery could not directly be applied in the KIB. To implement highly efficient intercalation of K+, the best way is to use specifically designed zero‐strain material to prepare long‐life KIB.In response to the energy crisis and environmental pollution the renewable energy sources, such as wind, solar and hydrogen energy have attracted much attention as supplement to the fossil fuels1 Whil Compared with K+ conversion and alloy electrode materials, layered materials provide a wide 2D channel for reversible intercalation/de‐intercalation of cations, resulting in a relatively better cyclic stability of the lattice of layered materials without serious deformation.Typical layered materials have strong in‐plane chemical bonds and weak van der Waals interactions between adjacent layers, and large interlayer space and 2D channel width result in high ionic conductivity and strong charge transfer ability, which are often used for metal ion storage.5 Compα‐V2O5) is a typical layered cathode material for lithium‐ion battery, and the embedded cations are usually stored in the layers. Because of its high basal spacing, vanadium pentoxide could be applied as the cathode material in other alkali‐ion battery in theory. However, the intercalation and de‐intercalation of K+ between α‐V2O5 layers are difficult, due to the limitation of the unevenness and compact layer space. The insertion of metal ions has a positive effect on stabilizing the layered structure of V2O5. However, it may change the structure of V2O5 and reduce the specific capacity of V2O5‐based cathode. 2D structures with large active surface area can increase the contact area between electrode and electrolyte, providing a large number of active sites, and promoting ion transport, which may be an effective way to solve the problem. Making 2D V2O5 on a large scale remains a huge challenge. In addition, heating and annealing V2CTx (MXene) produces a layered array of V2O5. Compared with the original V2O5, the original lamellar structure is retained in the crystal structure, and the interlamellar space is increased in the microscale, theoretically providing a good storage site for K ions through 2D ion channels. It suggests that it is more cost‐effective to do the former  than the latter (in Nano structure). Pre‐intercalation can improve the inherent energy storage properties of layered materials, including increasing the interlayer distance, stabilizing the crystal phase, and enhancing the electrical conductivity. However, pre‐intercalation will sacrifice the active site and inevitably lose capacity. Therefore, optimizing pre‐insertion can provide as many active sites as possible while maintaining the layered structure.The orthorhombic vanadium pentoxide (e layers.7 Beca3)2‐V2O5 was introduced for anode in KIB. Which was synthesized by one‐step solid‐phase mixing NaK alloy with V2O5. NaK(VO3)2 2‐V2O5 is V5+.) material has a uniform large lamellar spacing structure (3.22 A) and better [−2 2 1] crystal structure. Through support of O—V—O with dual‐ion (Na+/K+) in between and could let the rapid storage and diffusion of K+ realized without the modification of other conductive substrates. In terms of crystalline structure, even if de‐intercalation of K+ between the layers, NaK(VO3)2 crystal remains stable by Na+. In the application of anode electrode of KIB, NaK(VO3)2‐V2O5 shows high specific capacity and ultra‐high rate performance. In addition, it is found that the material has no phase change during charge and discharge from the X‐ray powder diffraction (XRD) test, which proved that zero strain anode was obtained. The mechanism of K storage enhancement was discussed by electrochemical kinetic analysis. This work could provide a general method for making zero‐strain anode materials from vanadium‐based materials for the next generation of battery systems.Herein, a heterojunction layered material of NaK2 has dual‐ion, which could induce a strong bond between two adjacent O—V—O layers to form a stable structure. In addition, the more stable [−221] orientation of NaK(VO3)2 has a larger and uniform tunnel 2‐V2O5 could provide a promising technique for the further study on KIB.Layered Ve Figure 1a. In oracancies.11 Dur3)2‐V2O5 were investigated by scanning electron microscope (SEM) and transmission electron microscope (TEM) and XRD. SEM images show that the NaK(VO3)2‐V2O5 structure consists of many coarse‐faced nanosheets and is slightly different for the V2O5 2‐V2O5 has two Vanadium‐Based Oxides (NaK(VO3)2 : PDF#26‐1474 and V2O5: PDF#41‐1426) and is obviously lower than that in the literature, which is related to the increased disorder of crystal structure caused by some vacancies, it can further accelerate the rapid transfer of electrons in the charging and discharging process due to the V2O5 provide more space. X‐ray photoelectron spectroscopy (XPS) results confirmed that the electron cloud bias from electron‐rich —V═O‐ and —V—O—V‐ component to low binding energy field inducing the formation of built‐in electric field at the heterojunction interface 2 has been first studied by XPS analysis.Morphology and phase structure of the prepared NaK2‐V2O5 for KIB was further investigated. The aluminum foil is cheaper and lighter than copper foil, which can not only significantly reduce the price of the KIB, but also reduce the weight of the collector and solve the overdischarge problem. Such technology has been applied first in KIB and the battery model now looks like Figure 3)2‐V2O5 exhibits excellent K storage properties compare to V2O5, for example, the KIB based on NaK(VO3)2‐V2O5 maintained a high capacity of 208 mAh g−1 at 0.1 A g−1 while the V2O5 had a low capacity of 105 mAh g−1 after 300 cycles. It is worth noting that drastic fluctuation of the specific capacity and coulombic efficiency is due to repeated activation of NaK(VO3)2‐V2O5 anode. Although specific capacity and coulombic efficiency move up and down violently, specific capacity has been more reliable, typically falling from the peak of a cycle to its trough by only 18 mAh g−1. Moreover, the electrochemical properties of the two anode materials were studied by charge‐discharge curves at different cycles 2‐V2O5 is relatively flat. It is important that the inclined region is attributed to surface‐driven K+ storage behavior, and the quasi‐elevation region is attributed to K+ intercalation behavior, in line with expectations. In addition, the initial discharge capacity of the electrode is close to 1800 mAh g−1 with a small initial coulombic efficiency due to high electrolyte (3M KFSI) content and more decomposition in anode for stable SEI in Figure  To find out the voltage value of the redox‐active materials, the cyclic voltammetry (CV) test was performed. The results of the first three cycles of NaK(VO3)2‐V2O5 and V2O5 at 0.1 mV s−1 are shown in Figure  The peaks at 0.85 V correspond to the intercalation of K+ in the NaK(VO3)2‐V2O5, and peaks at 0.51 and 0.92 V are de‐intercalation of K+, which was in agreement with the charge–discharge curve.The electrochemical performance of NaK2‐V2O5 showed a good activation property much better cycling stability, and a receivable discharge capacity at high‐rate 2‐V2O5 are 264, 141, 264, 115, 96, 53, 47, and 37 mAh g−1, respectively, which are much higher than those of V2O5 without pre‐intercalation of Na+/K+ . It is important that dramatically increase during the initial cycles is due to KIB systems might become unstable during the high current density change. When back to 0.2 A g−1, the NaK(VO3)2‐V2O5‐based KIB maintained a capacity of 241 mAh g−1. The results suggested that through lattice regulation, better rate performance and more stable cycle performance were obtained of the KIB. The effect of dual‐ion intercalation in KIB has been investigated by the different rate on the charge and discharge processes. In Figure 3)2‐V2O5 has less capacity loss than V2O5, resulting in better efficiency. Thorough structural design of dual‐ion pre‐intercalation in the V2O5, obtained a rigid crystalline framework, and the zero‐strain anode with excellent performance was realized.In addition, the inset in Figure e Figure . At 0.2–y change.19 Whe2‐V2O5 and V2O5 for KIB are shown in Figure 2‐V2O5 is completely unchanged during the discharge and charge process, indicating that the crystal structure of NaK(VO3)2‐V2O5 has a rare zero strain characteristic. On the contrary, analyses were conducted on the raw data 2‐V2O5 has high stability and zero strain characteristics in the process of intercalation/de‐intercalation of K+, which is the fundamental internal reason for its super stable K storage performance. The XPS analysis of NaK(VO3)2‐V2O5 shows that SEI formed oxygen ions in O 2p is higher and rich in inorganic component, while O═V in material is thinner 2‐V2O5. The difference in valances state of O and V in Figure + embedded in V2O5 layered structure leads to structural damage, accompanied by the formation of the second phase, which will lead to capacity fading. Due to the stability of NaK(VO3)2‐V2O5 larger structure and no phase transition occur during the reversible deintercalation of K+, which will deliver excellent cyclic stability. Interestingly, the XPS results of different state of cycled anode of V2O5 also demonstrate that the curves have similar characters with raw material of NaK(VO3)2‐V2O5, so this is an irreversible process. Importantly, after analyzing the morphology changes before and after cycling 2‐V2O5 is slightly changed, it is obvious that there is no damage or pulverization of the material after charge and discharge, which proves that the material has excellent structural stability. The structures and properties of NaK(VO3)2‐V2O5 are analyzed and characterized by means of XRD, XPS, and SEM, the results indicating that the NaK(VO3)2‐V2O5 is zero‐strain structure.The battery was disassembled after 50 cycles, and the different status of XRD of NaK(VO3)r Figure , which d−1), Figure 3)2‐V2O5 is mainly controlled by capacitive and pseudocapacitance behavior . In addition, the results of CV test show that the peaks of NaK(VO3)2‐V2O5 at 0.51 to 0.53 V are significantly higher than those of V2O5, indicating that the heterogeneous interface promotes the intercalation and de‐ intercalation process of K+ and makes K+ more inclined stabilize the layered structure of O—V—O, which is related to the synergistic effect of controllable grain boundary of heterojunction. Figure v0.5 curves. This result can reveal the electrochemical kinetics of the two materials (the detail in Supporting Information). The diffusion coefficient of NaK(VO3)2‐V2O5 is 5.9 × 10−13 cm2 s−1 which is much higher than that of V2O5 (2.8 × 10−13 cm2 s−1). This further revealed that the dual‐ion pre‐intercalation with heterojunction interface can effectively reduce the charge transfer resistance and accelerate the migration of K+, thus obtaining superior rate performance. At 5 A g−1, the capacity of KIB based on NaK(VO3)2‐V2O5 remained 89 mAh g−1 after 2500 cycles. The charging and discharging curve is close to 100% from 500th to 2000th 2‐V2O5 is the best KIB material with the best rate and cycling performance so far.The relationship between the electrochemical property and the crystalline structure was further investigated by the CV test at different scan rates (0.2–1 mV scitance).20 In h Figure , even wh−1, and it is observed the specific capacity in the initial stage is very low and then it increases after several cycles. Due to an activation process, which could release the potential of NaK(VO3)2‐V2O5 to a greater extent with the large volume of K+, they all have an activation process in the rapid insertion/extraction. After the capacity increases to the maximum value and the attenuation decreases slowly with an acceptable specific capacity, indicating that the cycle stability is good. As for low current density (0.1 A g−1) at the beginning and the electrochemical reaction with NaK(VO3)2‐V2O5 with K+ insertion/extraction is sufficient, the high specific capacity can maintain in the initial.It is worth noting that the electrode is cycled under large current densities of 5 and 10 A g−1) and long cycle  of NaK(VO3)2‐V2O5. However, high‐concentration salt electrolytes are costly and KFSI‐based electrolytes corrode aluminum foil (current collector), compared to conventional low‐concentration electrolyte based on 3 M KFSI, which generally have the advantages of better chemical stability and lower cost. Besides, with a carbonate base of 1 M potassium hexafluoroarsenate (KPF6) in ethylene carbonate/diethyl carbonate (EC/DEC) and their performance tends to degrade significantly with cycles 2‐V2O5 in KIB. Furthermore, the XPS indicates that the 3 M KFSI in DME is rather stable in the cycle and similar to 3 M KFSI in DME. It is pointed out that F 1s spectrum showed two different fluorine species, S‐F (687 eV) and KF (684 eV), respectively, KF in KPF6 with low binding energy like cycled of V2O5 2‐V2O5 exhibits a record ultra‐fast and ultra‐stable K storage performance. Combined with XRD and XPS analysis, it is revealed that the crystal structure of NaK(VO3)2‐V2O5 has rare zero strain characteristics, and the thin and tough SEI formed in ether electrolyte is beneficial to the K storage, is conducive to better cycle and rate performance.Furthermore, Figure llector),22 com3+ is enhanced by the Pre‐intercalation of dual‐ions (Na+/K+) at the heterojunction interface of NaK(VO3)2‐V2O5, which is beneficial to the improvement of electrochemical performance of KIB. The crystalline engineering modification, abundant active sites are provided for the heterostructures with homogeneous and stable layered structure, ensuring a higher contribution of pseudo‐capacitance, fast rates of diffusion of K+, and accelerating the reaction kinetics. In addition, the regulation of morphology engineering, the interaction between vanadium oxide is strengthened by inorganic crystals modulated, and the overall structure of the electrode material is kept stable to the zero‐strain of K+ repeated insertion/extraction. NaK(VO3)2‐V2O5 has excellent performance due to its unique intrinsic properties, which is expected to become a commercial anode material and promote the innovation of KIB.The crystals engineering, the diffusion kinetics of KThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.