Type 1 diabetes (T1D) is an immune‐mediated illness, with selective destruction of β‐cells occurring in genetically predisposed persons.Serologic markers such as antibodies to islet cells and glutamic acid decarboxylase‐65 are typically present prior to clinical presentation of disease and lend themselves to measurement, contributing to T1D by presenting islet antigens, including insulin, leading to activation of T cells causing autoimmune destruction of pancreatic beta cells.The gut microbiome has been studied in a number of areas in medicine. Of interest, microbial fermentation of nondigestible carbohydrates can lead to production of several short chain fatty acids, including acetate, which is then taken up by pancreatic lymph nodes, where it appears to decrease autoreactive T cells as well as proinflammatory cytokines such as interleukin‐21, and butyrate, which increases regulatory T‐cell numbers,An entirely different treatment of T1D has addressed antiapoptotic/pro‐proliferative agents. Paired box gene 4 (PAX4) is a transcription factor involved in differentiation of the endoderm‐derived endocrine pancreas, which appears to be reactivated to promote islet cell growth in response to immune destruction. Individuals homozygous for the PAX4 C allele have reduced PAX4 function in comparison to those heterozygous for PAX4 A and PAX4 C, or to PAX4 A homozygotes. In several population studies, approximately three quarters of persons with T1D expressed PAX4 C/C, whereas this genotype was present in approximately one third of controls. The PAX4 C/C genotype was present in only 11% of a small group of persons positive for markers of islet autoimmunity who did not develop T1D over a long period of observation.Thioredoxins are antioxidant and anti‐inflammatory proteins present in all organisms, with thioredoxin‐interacting protein present in β‐cells blocking the action of thioredoxin, leading to activation of the inflammasome and playing roles in β‐cell glucotoxicity and apoptosis. The calcium channel blocker verapamil is another small molecule antihypertensive agent that has been found to reduce β‐cell cytoplasmic levels of ionized calcium, in turn inhibiting thioredoxin‐interacting protein. In a study of 24 persons with new‐onset T1D treated with verapamil, preservation of C‐peptide, reduction in insulin dosage requirement, and reduction in levels of the β‐cell autoantigen chromogranin A at 1 yearA potentially related approach to increasing β‐cell proliferation involves inhibition of dual specificity tyrosine‐regulated kinase 1A (DYRK1A), which blocks β‐cell proliferation caused by calcium entering the β‐cell via voltage‐dependent calcium channels.Thus, it appears that a number of lines of investigation suggest approaches that may prove of benefit in the treatment of early T1D. It is intriguing to speculate that some of these agents may be effective in combination, with, for example, both verapamil and harmine altering cytoplasmic ionized calcium levels or with combination of a pro‐proliferative agent one reducing β‐cell autoimmunity. We look forward to the results of ongoing clinical trials.


L(tta)2]CH3COO ‐1,2‐ cyclohexanediamine and tta=2‐thenoyltrifluoroacetonate) shows good CPL in organic solvents, because the tta ligands efficiently sensitize Yb NIR luminescence and the readily prepared chiral ligand L endows the complex with the necessary dissymmetry. PLGA nanoparticles incorporate the complex and protect the metal ion from the intrusion of solvent molecules, while ensuring biocompatibility, water solubility and stability to the complex. Hydrophilic NIR‐CPL optical probes can find applications in the field of NIR‐CPL bio‐assays.We report the first example of very efficient NIR Circularly Polarized Luminescence (CPL) (around 970 nm) in water, obtained thanks to the combined use of a chiral Yb complex and of poly lactic‐co‐glycolic acid (PLGA) nanoparticles. [Yb Unprecedented NIR CPL activity in water from a hydrophobic chiral Yb(III) complex embedded in PLGA nanoparticles was observed Current applications of circularly polarized luminescence (CPL) in bioimaging would greatly benefit from its extension and consolidation in the near‐infrared (NIR) region, where tissues, skin, blood and water are quite transparent and scattering is also relatively low. The 1000–1400 nm range is sometimes called the second biological window and it is emerging as a very attractive region for biological imaging. CPL in this region benefits from the specificity, selectivity and sensitivity, which are typical of the chiroptical counterpart of emission spectroscopy, in the context of biological applications, like, for example microscopy and bioassays.Complexes of NIR emitting lanthanide ions like Yb(III), having small size and metal‐centred emission properties, may provide good candidates, thanks to the 1 μm emission band of Yb(III), associated with its low toxicity and to the well‐known chemistry developed for using other lanthanides in biomedicine.Moreover, in addition to biomedical applications, Yb‐centred NIR‐CPL may lend itself to several other technological fields, where vis‐CPL allied to Eu or Tb have already demonstrated a positive impact.2F5/2→2F7/2 emission transition, around 980 nm, is characterized by a high value of the rotational strengthantenna effect).NIR‐CPL activity is indeed expected in the case of chiral Yb(III)‐based complexes in which the spin allowed 2F5/2 excited state lifetime to only few μsL(tta)2(H2O)]CF3SO3 complex, where L stand for N, N’‐bis(2‐pyridylmethylidene)‐1,2‐ cyclohexanediamine, respectively L(tta)2]CH3COO complex. With respect to the free [YbL(tta)2]CH3COO molecule dissolved in dichloromethane (DCM), the water stable nanoparticles loaded with the complex possess a similar Yb(III) luminescence efficiency, while the CPL activity appears almost doubled. In other words, to the best of our knowledge, [YbL(tta)2]CH3COO represents the first case of a chiral Yb(III) complex embedded in PLGA nanoparticles (NPs) stable in water and exhibiting efficient NIR emission with a good degree of polarization. In detail, this paper deals with the characterization and chiroptical investigation in solid state, organic solution (DCM) and in water dispersible PLGA nanoparticles of the ([YbL(tta)2]CH3COO complex.Unfortunately, its sizeable CPL activity in dichloromethane solution (gL(tta)2]CH3COO) of the synthesized complex is in agreement with the elemental analysis results , which together with the TGA‐DSC analysis  and ESI mass spectrometry  rule out the presence of water molecules either in the inner or outer coordination spheres of the metal ion, in the powdered sample. In fact, up to 150 °C, no significant weight loss (<0.7 %) as well as no endothermic peak are observed . On the contrary, a significant weight loss (around 55 %), related to the thermal decomposition of the organic matter, is detected in the 200–600 °C range. Lastly, an endothermic event is recorded at temperature >600 °C due to the shift from N2 to air resulting in the complete combustion of the material. At 700 °C, almost 20 % of the original mass is recovered in agreement with the residual presence of the only Yb2O3. For both the enantiomers, Yb(III) ion efficiently emits light in the NIR spectral region, upon excitation around 365–380 nm, in correspondence with the diketonate‐centred singlet‐singlet π‐π* enolic transition of tta. Typical Yb(III) emission  ionThe excitation spectra present other two maxima peaking at 310 and 450 nm. While the former band is associated to the 2F5/2 excited state.The decay profile of the emission Figure  presentsAs underlined in the introduction and in agreement with the results obtained from the other experimental techniques, a lifetime value around 10 μs is compatible with the absence of water molecules (and other high energy oscillators) in the metal ion environment (inner and outer coordination sphere).The emission spectrum recorded in a 0.44 mM DCM solution  are similar to that recorded in the solid state. The rise time constant is 1.4 μs and the lifetime of the excited state is 15.1 μs and 12.3 μs, for the S,S and R,R enantiomers, respectively. The values of the lifetimes are comparable with that recorded in the solid state (12.3 μs). This indicates that the nature of the emitting complex is the same as that in the solid state and sensitization mechanism still involves the triplet state of the tta ligand.First of all, the two higher energy components are narrower and better resolved than in Figure L(tta)2]A; A=nitrate or triflate anion) suggests the presence in DCM solution of a couple of interconverting isomers possessing C1 symmetry and differing by the relative orientation of the two tta ligands; in both cases the counterion is bound to the metal ion.C2 symmetry . This demonstrates that the NMR spectra are in all cases averages due to fast equilibria between the isomers, a situation that prevents any quantitative analysis of the paramagnetic shifts. Furthermore, the results reported in that paperL(tta)2(H2O)]CF3SO3 complex can completely loose the CPL activity once its surroundings move from the DCM solvent to the PLGA polymer. Similar effect of solvation on the CPL activity of coordinatively saturated chiral Eu(III) complexes has been recently reported by D. Parker et al.Since, it has been shown that Y(III) complexes may serve as suitable computational models for the Ln(III) analogues, a detailed structural study performed by some of us on the Y(III)‐based counterpart ([YL(tta)2]⋅CH3COO molecule stable in aqueous solution, we prepared a nanoformulation in which this complex is embedded in PLGA by means of a modified nanoprecipitation method at 20 °C.As for the strategy to make the  ⋅ CH3COO embedded in the NPs show again a NIR CPL mirror image . In the case of the Yb(III)‐based complex, and contrary to the Eu(III) counterpart, the effect of the PLGA moiety on the environment of the metal ion is such that it improves the CPL efficiency of the complex.Interestingly, the two enantiomers of ⋅CH3COO molecule, on the CPL activity of Ln(III)‐based complexes. Despite several studies focused on CPL from nanoparticles and nanoassemblies of a different nature (pure organic and inorganic or hybrid organic–inorganic nanocomposites)In conclusion, we have demonstrated that the good emission properties of Yb(III)‐based hydrophobic complexes can be preserved also in water upon encapsulation of the emitting complex into PLGA nanoparticles. Such a supramolecular architecture is capable of: i) ensuring water solubility and stability to the Yb(III) complex, which normally is neither soluble nor stable in water; ii) ensuring biocompatibility to the system and iii) protecting the metal ion from the intrusion of water molecules, which are detrimental to the Ln(III) luminescence efficiency. It should also be noted that the CPL activity of the complexes in the NIR domain region is not only retained but significantly increased. This result confirms what we recently discovered on the unexpected role of achiral entities such as counterion, solvent molecule and, in the present case, the PLGA polymer surrounding the CH3COO ‐1,2 ‐cyclohexanediamine)Synthesis of the chiral complexes  of Htta (2‐Thenoyltrifluoroacetyl‐acetone) have been dissolved in a methanol (3 mL) solution containing 84.7 mg (1506.8 mmol) of KOH. The clear solution was slowly added to a methanol solution (7 mL) of the enantiopure ligand L [200.4 mg (684.9 mmol)] and Yb(CH3COO)3 [289.2 mg (684.9 mmol)]. The final mixture was stirred for 30 minutes at room temperature and then the solvent was removed under reduced pressure. The desired product was obtained in a good yield as yellowish powder upon extraction in dichloromethane (5 mL) followed by solvent removal in vacuo.L(tta)2]⋅CH3COO: Yield ca. 80 % for both enantiomers.+); 804.13(100 %), 805.13 (90 %), 803.13 (55 %) ([YbL(tta)(CH3COO)2+H]+); 315.19 (100 %) : 220.97 (100 %) [tta]−Elemental Anal. Calc. for C2]⋅CH3COO loaded PLGA nanoparticlesPreparation of [YbL(tta): 2 mg of PLGA and 1 mg of the complex were mixed in acetonitrile. Then, the solution was diluted 60 times with an aqueous solution of glycine (pH 9) and the precipitation of a colloidal substance (the nanoparticles) was observed. The nanoparticles were washed twice with a small amount of water, centrifuged for 30–40 minutes (11000 rpm) and then resuspended in 1 mL of water. This colloidal solution is used for the spectroscopic measurements.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.


VI fluorides have recently received enormous attention because of their potential as chemical biology probes, as a result of their reactivity in a simple, modular, and efficient manner. Whereas the synthesis and application of the level 1 fluorination at SVI atoms (sulfonyl and sulfonimidoyl fluorides) have been widely studied and reviewed, the synthetic strategies towards higher levels of fluorination (levels 2 to 5) are somewhat more limited. This Minireview evaluates and summarizes the progress in the synthesis of highly fluorinated aryl‐SVI compounds at all levels, discussing synthetic strategies, reactivity, the advantages and disadvantages of the synthetic procedures, the proposed mechanisms, and the potential upcoming opportunities.(Hetero)arylsulfur compounds where the S atom is in the oxidation state VI represent a large percentage of the molecular functionalities present in organic chemistry. More specifically, (hetero)aryl‐S The number of methods that exploit the synthesis of (hetero)arylsulfur(VI) fluorides is steadily growing due to their potential in organic synthesis. This Minireview covers the synthesis of arylsulfur(VI) fluorides from levels 2 to 5 of fluorination, the substrate scope, mechanisms, and the further applicability of these fluorinated compounds. Indeed, compounds of this class have recently been re‐evaluated, as they have shown interesting properties and applications in various fields of expertise.VI compounds, with untapped reactivity and applications. Moving up the pyramid, one can find aryltetrafluoro‐λ6‐sulfanyl chlorides and aryltetrafluoro‐λ6‐sulfanes, with various synthetic procedures reported in the literature for their preparation. In particular, aryltetrafluoro‐λ6‐sulfanyl chlorides have been widely studied and applied as precursors for pentafluoro(aryl)‐λ6‐sulfane (Ar−SF5) and deoxyfluorinating agents.6‐sulfanylarenes (Ar−SF5), which recently gained the attention of the chemistry community because of the unique properties of the SF5 group in material science and medicinal chemistry fields.5 group is sterically highly demanding, thus it can be considered as an isostere of the tert‐butyl (tBu) and the trifluoromethyl (CF3) groups.[B(C6F5)4], fluorosulfoxonium cations 24–27 could be isolated and characterized by NMR spectroscopy and single‐crystal XRD. Experimental analysis (Gutmann–Beckett method) and theoretical calculations (DFT) confirmed the high Lewis acidity of fluorosulfoxonium cations 24–27. Finally, compound 25 was demonstrated to be highly active in Friedel–Crafts‐type reactions with 1,1‐diphenylethene  can react with trimethylsilylamines28 and 29  is not synthetically viable and, therefore, alternative synthetic routes were required. In 1980, Ruppert showed that aryl‐SVI oxytrifluorides 31 could be obtained by direct fluorine addition to sulfinic fluorides 30 using F2 at very low reaction temperatures.19F NMR spectroscopy confirmed the finding through the presence of an AX2 pattern, which is in agreement with a trigonal bipyramidal geometry of an S atom with two fluorine atoms occupying the axial positions   to the corresponding ArSOF3 using easy‐to‐handle reagents and mild reaction conditions. Such compounds exhibit extremely high reactivity and rapidly evolve into their corresponding arylsulfonyl fluoride analogues (ArSO2F) upon exposure to trace amounts of H2O. The high sensitivity of the compounds made all efforts to isolate them unsuccessful. However, the high electrophilicity of ArSOF3 was turned into an advantage, and a wide range of primary aryl‐ and alkylamines were engaged in good yields, thus delivering highly coveted arylsulfonimidoyl fluorides.An advance in the area arrived in 2020, when Wang and Cornella developed a new method for the synthesis of ArSOFs Scheme .[28] T4VI chlorotetrafluorides (Ar−SF4Cl) has been widely studied due to their potential subsequent applications. Ar−SF4Cl compounds are not only the most commonly utilized precursors to access level 5 (see Section 5), but also widely applied as deoxy‐ and desulfafluorinating agents ,6‐sulfanyl chlorides 44 do not react with C−O and C−S bonds; however, upon activation with a reductant such as pyridine, ArSF345 is generated in situ and acts as a highly effective reagent for the deoxyfluorination of alcohols, aldehydes, ketones, carboxylic acids, and sulfur compounds (Scheme The synthesis of aryl‐Ss Scheme .[29] Ts Scheme .VI tetrafluorides were observed in crude mixtures from reactions between organosulfur(II) compounds and anhydrous hydrogen fluoride under electrolytic conditions.4Cl compounds, by using Cl2 or ClF as oxidants  required the presence of a large excess of CF3OF. Based on 19F NMR spectroscopy results, it was proposed that after an initial oxidation to the corresponding diaryl‐S(IV) difluoride 57, cationic intermediate 58 forms, which eventually leads to 56 upon warming.It was in 1973 when Denney et al. developed a method for the synthesis of diaryl‐St Scheme .[39] W4Cl arrived in 1997 when Janzen and co‐workers reported the oxidation of aryldisulfides with XeF2 in the presence of [Et4N][Cl] (Scheme 2 favored the formation of the trans isomer (method A), whereas lower amounts of oxidant favored the cis isomer (method B). Regardless of the method employed, analytically pure stereoisomers could not be obtained.A breakthrough in the synthesis of Ar−SF] Scheme .[40] A3 species are formed. At this point, two pathways can be envisaged. As already reported by Janzen and Ou, wVI chlorotetrafluorides with excellent trans stereoselectivity  to the S atom decreased the yield considerably (79–81), with the corresponding heteroaryl‐SF3 compounds afforded as side products in almost all cases.Inspired by the procedure developed by Umemoto et al., Kanishchev and Dolbier and co‐workers synthesized a wide range of 2‐pyridyl‐Sy Scheme .[43] H4Cl  on the pyridine moiety (87–89) led to the undesired heteroaryl‐SF3 being obtained. The authors hypothesized that the presence of an electron‐withdrawing group (EWG) such as fluorine would decrease the nucleophilicity of the N atom in the pyridine ring and, hence, stabilize the SF4Cl group.Shibata and co‐workers expanded this reactivity to 3‐ and 4‐pyridyl‐SFl Scheme .[44] T4Cl that avoided the use of hazardous, gaseous oxidizing agents (e.g. F2 and Cl2). The method featured the easy‐to‐handle solid trichloroisocyanuric acid (TCCA), potassium fluoride (KF), and catalytic amounts of trifluoroacetic acid (TFA). This simple synthetic method permitted the synthesis of a wide range of aryl‐ and heteroaryl‐SF4Cl compounds in good yields aryl‐SFl Scheme .[46] H4Cl has recently been reported by Wang and Cornella  starting materials.Another improvement in the synthesis or aryl‐ and heteroaryl‐SFa Scheme .[28] I3 Scheme  and leve4Cl  together with undesired compounds such as ArSO2F and ArSOF.Recently, Pascali and co‐workers reported a strategy to obtain aryltetrafluoro‐λ6‐sulfanyl chlorides have attracted great attention as precursors of (hetero)aryl‐SF5 and as deoxyfluorinating agents.4Cl compounds have also been utilized in the synthesis of alkynyl‐ and alkenyl‐aryltetrafluoro‐λ6‐sulfanes, by capitalizing on the labile S−Cl bond  with lithium hydroxide formed the alkynyl 113 and (E)‐alkenyl‐aryltetrafluoro‐λ6‐sulfanes 114 in excellent yields, with no decomposition of the SF4 group. In 2018, Shibata and co‐workers synthesized pyridyltetrafluoro‐λ6‐sulfanes with alkenyl 115 or alkyl 116 substituents through a radical addition of pyridine‐SF4Cl to terminal alkynes and alkenes .In 2014, Welch and co‐workers developed a BEte Scheme A. 4Cl to terminal alkynes and alkenes under irradiation with light  became an interesting fluorine‐containing building block because of its thermal and chemical stability5 moiety is comparable to that of CF3 and its electron‐withdrawing effect suggests that the effects of SF5 and CF3 groups are similar in magnitude.5 group has been measured to be as high as 3.65, compared to a value of 3.36 for the CF3 group.5 group is the newest member of a short list of functional groups that possess both high electronegativity and high lipophilicity, two properties that are generally juxtaposed. As a result of such unique properties, aryl‐SF5 compounds have attracted attention, and synthetic efforts towards their preparation have been the focus of intensive research.5 span from applications as tBu and CF3 isosteres in medicinal chemistry, w2 for the conversion of diaryldisulfides 126 and 127 into the corresponding Ar−SF5 compounds 129 and 130  into Ar−SF5 compounds  provided good yields.3 into Ar−SF5. It was finally proposed that the reaction proceeds through a radical mechanism after homolytic cleavage of the F−F bond. Propagation and termination steps are almost barrierless and the reaction depends on the stability of the Ar−SF4 radical species. However, further mechanistic insights are required to elucidate the mechanism for the direct fluorination of diaryldisulfides using F2.In 2016 and 2019, Beier and co‐workers reported the direct fluorination of 2 Scheme .[73] B5.24Cl species have been used as synthetic precursors of Ar−SF5 through Cl−F exchange. Compared to the direct fluorination of thiols or diaryldisulfides, the use of Ar−SF4Cl as precursors leads to higher yields of the desired Ar−SF5 under milder and safer conditions. In 2012, Umemoto et al. converted a wide range of Ar−SF4Cl into their corresponding Ar−SF5 compounds in good to excellent yields under mild reaction conditions, through a Cl–F exchange using either ZnF2‐HF (KHF2) or SbIII/V fluorides  with different dienes, as demonstrated by Hoover and Coffmann  with an overall yield of 70 %. The key step in this synthesis is the radical addition of SF5Cl to an alkene, thereby forging a C−SF5 bond in almost quantitative yield (Scheme Sergeeva and Dolbier developed a convenient three‐step synthesis of Ph‐SFd Scheme A.[80](191) by the initial addition of SF5Cl to benzobarralene 189. Elimination of the ethylene bridge by a cycloaddition/retro‐cycloaddition sequence with 3,6‐bis‐(2‐pyridyl)‐1,2,4,5‐tetrazine afforded the Ar−SF5191 in good yield  is consistent with ab initio computational studies, which revealed a SF5⋅⋅⋅HO hydrogen bond that renders additional stabilization to the product. Duda and Lentz prepared pentafluoro‐λ6‐sulfane (201) in high yields in two steps from 3,3,3‐trifluoropropyne (199) by the addition of SF5Br followed by a dehydrobromination reaction (Scheme 5 group at the ortho position of arenes (202). Carreira and co‐workers reported a synthetic strategy for preparing SF5‐containing N‐heterocyclic building blocks, such as quinolinones, quinolines, and pyridines (Scheme 5‐acetate (204) proved to be an excellent candidate to participate in aldol reactions, providing a wide range of 3‐SF5‐quinolinones in good to excellent yields. These compounds can be rapidly converted into the corresponding quinolines 205 using either POCl3 or POBr3.Ponomarenko et al. reported the Et5 Scheme A.[82] n Scheme B.[83] s Scheme C.[84] 5 group is considered a bioisostere of the CF3 and tBu groups, the authors compared the physicochemical properties of 3‐SF5‐quinolinone with its CF3 and tBu analogues. Preliminary collected data showed that SF5 exhibits higher lipophilicity than CF3, but lower than the tBu group. The membrane permeability increases in the order SF5<tBu<CF3. In terms of pKa values, the SF5‐quinolinone was the most acidic. Concerning the solubility, both the CF3 and SF5 compounds are considerably more soluble than the tBu counterpart.Since the SFortho‐SF5‐benzyne (208) by a lithiation/elimination sequence starting from 2‐fluoro‐SF5‐benzene 207 , where the ortho‐substituted diaryldisulfides are still the main limitation to expand the substrate scope.All these synthetic alternatives allow access to 6VI fluorides, where the central S atom is substituted with 2, 3, 4, or 5 F atoms, thus defining the fluorination level. Level 2 fluorinated compounds have been successfully prepared by using XeF2/Et3NCl as an oxidative fluorinating system, a method that still remains in use nowadays. Remarkably, these compounds have gained much attention recently, as the corresponding sulfoxonium cations have been shown to be super‐Lewis acids for organic transformations.This Minireview highlights different approaches toward the synthesis aryl‐S3 compounds are good linchpin reagents for the synthesis of sulfonimidoyl fluorides.Level 3 fluorination is still an underdeveloped platform, with untapped potential for synthesis. It is clear that ArSOF4Cl compounds have shown that strong oxidants such as F2 and Cl2 can be replaced by the safer and easy‐to‐handle TCCA/KF system.Whereas levels 2 and 3 are still underdeveloped, their higher fluorinated analogues (levels 4 and 5) have been widely studied and their synthesis widely explored. In this regard, recent advances in the use of Ar−SF5 compounds in medicinal chemistry. The current synthetic approaches rely on the Cl–F exchange from the corresponding Ar−SF4Cl compounds. Alternatively, other synthetic procedures that employ SF5Cl gas as a precursor to the SF5 group have also been successful, although the synthesis of the aryl ring is required.Finally, the synthesis of arylsulfanyl pentafluorides have been the most studied and improved, as a result of the recent interest of Ar−SF5 group in medicinal chemistry and biology, this area will also evolve to avoid the use of toxic SF5Cl as a SF5 radical precursor, and the use of the greener, but less reactive, SF6 gas. The very few examples of this latter approach already show the promising synthetic utility of SF6 gas as a building block for sulfur(VI) fluoride synthesis.Despite the excellent advances in the synthesis of (hetero)arylsulfur(VI) fluorides and their successful applications, the reported approaches still suffer from several disadvantages, such as narrow substrate scope and harsh reaction conditions. Thus, we envision that innovative work in this area is likely to arise from new greener and milder synthetic methods. Moreover, as a result of the high interest in the SFThe authors declare no conflict of interest.Marc Magre earned his PhD under the supervision of Prof. Montserrat Diéguez and Prof. Oscar Pàmies at Universitat Rovira i Virgili (Spain) in 2016, working on tailor‐made chiral Pd‐ and Ir‐based catalysts for enantioselective transformations. In 2017, he joined the group of Prof. Magnus Rueping  as a postdoctoral researcher, where he developed novel magnesium‐catalyzed hydrofunctionalizations of unsaturated systems. In 2020, he joined the Max Planck Institut für Kohlenforschung  as a postdoctoral researcher in the group of Dr. Josep Cornella, where he focuses on bismuth catalysis.2O activationShengyang Ni was born in Yancheng (China), in 1992. He earned his PhD under the supervision of Prof. Yi Pan at Nanjing University (China) in 2019, working on Ni‐catalyzed reductive cross‐coupling reactions. During this time, he was a visiting PhD student (2017–2019) in the group of Prof. Phil Baran at Scripps Research Institute (US). After his PhD, he stayed in the same group to continue his postdoctoral research. In 2021, he joined the Max Planck Institut für Kohlenforschung  as a postdoctoral researcher in the group of Dr. Josep Cornella, where he focuses on Ni‐catalyzed N.Josep Cornella (Pep) studied chemistry at the University of Barcelona (2008) and completed his PhD in 2012 at Queen Mary University (UK) under the supervision of Prof. Igor Larrosa. He then pursued postdoctoral studies in the groups of Prof. Ruben Martin  as a Marie Curie Postdoctoral Fellow and Prof. Phil S. Baran  as a Beatriu de Pinos Fellow. In 2017, he was appointed as a Max Planck Research Group Leader in the Department of Organometallic Chemistry at the Max‐Planck‐Institut für Kohlenforschung in Mülheim an der Ruhr, Germany, where he leads the Sustainable Catalysis Laboratory.


Special attention is paid to discriminating the roleof the lone pair Sn2+ cation from the structural distortiveeffect along the Mo/W substitution process, which is crucial to disentanglethe driven force of the transition phase. Furthermore, the reverseα → β transition observed at high temperature inSnWO4 is rationalized on the same basis as a negative pressureeffect associated with a decreasing of W6+ percentage inthe solid solution. This work opens a versatile chemical approachin which the types of interactions along the formation of solid solutionsare clearly differentiated and can also be used to tune their properties,providing opportunities for the development of new materials.The chemical pressure approach offers a new paradigmfor propertycontrol in functional materials. In this work, we disclose a correlationbetween the β → α pressure-induced phase transitionin SnMoO Thesestrains can recreate the response of the material under stress conditionsfacilitating the equivalence between physical or mechanical pressureand chemical pressure. The concomitant changes in the bonding networkintroduced by the guest elements have been less studied. They alsoproduce an impact on the behavior of the materials11 that are difficult to separate from thepure structural perturbations. The knowledge of these new interactionsis crucial for precise control of the properties emerging throughthese chemical doping processes.Chemical pressure is an efficienttool to tune properties and create functional materials.15 In spite of being in the next period, tungsten showsa similar atomic radius as molybdenum due to the well-known lanthanidecontraction. This good size matching guarantees the alloying of thetwo semiconductors in a wide composition range and avoids the phaseseparation that otherwise would occur originated by large lattice-mismatchingstrains.Solid solutions of semiconductorsare pertinent examples to illustratehow the interactions associated with the doping process mimic theeffect of thermodynamic variables (pressure and temperature) and alsomodulate the properties of advanced materials with extended functionalities. Amx1–WxO4 (x = 0–1),the two end compounds show however different space groups at roomconditions: SnMoO4 crystallizes in the P213 cubic β phase, whereas the Pnna α phase of SnWO4 is orthorhombic. The band structure isdifferent too. At room conditions, α-SnWO4 presentsa small and indirect band gap,16 whileβ-SnMoO4 presents a band gap around 1.5 eV higher.17 As announced by Walsh et al.,18 compounds combining lone pair ns2 cations  and d0 transition metals  constitute promising candidates toimprove photocatalyst properties in hydrogen economy thanks to thepossibilities they offer to tune their electronic band structure.17 Moreover, the polyhedral distortions of bothcation environments lead to metallic off-center positions well-studiedfor the potential use of these compounds as multiferroic materials.19In the case of SnMox composition. Moreover, around 0.8GPa, β-SnMoO4 transforms to the α phase, whereasα-SnWO4 is observed to transform to the β phaseat high temperature.20 Therefore, by increasing(decreasing) the W content, the actual symmetry of the system shouldchange as happens with increasing pressure (temperature) in the pureβ-SnMoO4 (α-SnWO4) compound. Allthese possibilites are illustrated in A transition between the two structuresshould be expected at someintermediate d-type elements,the factors associated with differences in the electronic structureof the two transition metals should be key to understand the sought-afteranalogy between physical and chemical pressure. Fortunately, a deepunderstanding of the structural distortions of d0 cations, as Mo6+ and W6+, in crystallineenvironments involving lone pair cations (Sn2+) was providedby Halasyamani et al.21 These authors remark the differentiatingrole of the atomic electronegativity to classify Mo6+ asa strong distorter and W6+ as a moderate distorter.21Given the size matching between both x1–WxO4 solid solution (x = 0–1). The structuraland electronic interplay associated with the W6+/Mo6+ exchange is investigated to show how the properties of thesolid solution can be modulated by the precise control of its composition.It is an attractive example to highlight that the new interactionsemerging from the doping process are responsible for the chemicalpressure impact on the material. Our challenge is twofold. First,we seek to illustrate the equivalence between the thermodynamic variablesand the chemical pressure effects so we can substitute the impactof pressure and/or temperature with chemical doping. Second, we pursueto make explicit that this equivalence has not a genuine structuralorigin but is caused by the different chemistry of both d0 cations when coupled to the lone pair Sn2+ cation. Relying on the work of Halasyamani and collaborators21 and the revised classical lone pair model of Walsh et al.,18 a coherent explanation of the different behaviorof both transition metal (T) compounds can support our findings.In the present paper, we address the dopingprocess along the SnMox1–WxO4 solid solutions with x = 0, 0.25, 0.50,0.75, and 1. To clearly understand how chemical doping affects globallyand locally the structures, we first briefly describe the unit cellsof the β and α phases. The β phase structure belongsto the cubic P213 space group. This structureis constituted by slightly deformed [TO4] tetrahedra , which are interconnected with strongly distorted [SnO6] octahedra. The α phase structure belongs to the orthorhombic Pnna space group. It is composed by layers of [TO4] tetrahedra  stacked along the c directionand separated by layers of Sn2+ cations, which are eightfoldcoordinated by oxygen atoms, forming [SnO8] cubic antiprismpolyhedra  file . The cubic cell parameters are 7.131 and 7.073 Å, forβ-SnMoO4 and β-SnWO4, respectively.Lattice parameters of the α-SnMoO4 are a = 5.597 Å, b = 10.717 Å, and c = 5.423 Å, while for α-SnWO4, theyare a = 5.605 Å, b = 10.574Å, and c = 5.498 Å. The similarity betweenthese values in both compounds evidences that differences in the T6+ atomic size do not introduce meaningful changes in the latticeparameters. However, looking at the local coordination polyhedra,we find that MoO4 distortions calculated using the quadraticelongation and bond angle variance parameters22 are slightly larger than in WO4 tetrahedra, as anticipatedby Halasyamani in the analysis of second order Jahn-Teller effectsin d0 T cations. We also notice that transitionmetal polyhedral distortions are greater in the α than in theβ phase, which have implications in the phase stability as wewill discuss later. Distortion parameters are collected in Table S4 of the SI file.The calculated static lattice parameters and optimizedatomic positionsfor the Mo and W compounds in both α and β polymorphsare collected in the 4 and at high temperature for the SnWO4 compound.As pointed out above, pressure induces a β → αphase transition in the SnMoO4, whereas α-SnWO4 transforms to the β phase at high temperature.20 Our simulations successfully reproduce the experimentalfacts and quantify the pressure of the β-SnMoO4 →α-SnMoO4 transition at 0.77 GPa and the α-SnWO4 → β-SnWO4 transition temperatureat 1200 K . The availableexperimental observations found that the βphase is thermodynamically favored at room conditions for SnMoO00 K see S1. FigurWe can alternatively move from the β phaseto the αone, just replacing Mo by W atoms or from the α phase to theβ one replacing W by Mo atoms. In what follows, we demonstratethat these solid–solid transitions can be controlled throughthe new interactions emerging in chemical doping processes. Beingpressure and temperature opposite effects, it is interesting to resortto the concept of chemical pressure to provide a unified insight ofthe whole phenomena.x1–WxO4 solidsolutions,the substitution of Mo by W atoms was performed with molar fractionsof x = 0, 0.25, 0.50, 0.75, and 1, both for the αand β phases. Further details of the simulation procedure aregiven in the SI file along with the optimized structure parametersand atomic positions of these solid solutions (see Tables S2 and S3). The comparison of the calculated cell parametersof these solid solutions with other available experimental and theoreticalvalues shows a good agreement.23For the calculations of the SnMox1–WxO4 solid solutionis as follows. Up to x = 0.43, the stable structurecorresponds to the cubic β phase with an energy lower than theα one with the same composition. From x = 0.43to 1, the orthorhombic structure of the α phase becomes thestable one, since it has a lower energy than the corresponding compositionof the β phase. Therefore, our simulations are able to identifya structural phase transition from the β to the α phasewhen the doping of SnMoO4 with W atoms amounts to xW = 0.43. Likewise, starting with SnWO4 and substituting W by Mo, the α → β transitionis predicted at xMo = 0.57. It is clearfrom these results that by selecting the precise amount of the dopingagent we can control the actual structure of the solid solution mimickingthe effect of pressure and temperature. We quantify the pressure exertedby W atoms in the xW = 0.43 solid solutionas 0.77 GPa, since this value is the physical pressure found for theβ → α transition in SnMoO4. Likewise,the temperature of 1200 K determined for the α → βtransition in SnWO4 is associated with xMo = 0.57 .Under the unified perspective provided by chemical pressure, we seethat both pressure and temperature effects on these pure SnMoO4 and SnWO4 compounds can be reproduced.The energy evolution of the SnMop in GPa) and chemical (x in molar fraction) pressure is presented in x values with the physical pressuresthat show the same ΔGβ–α values. For instance, the value of ΔGβ–α = 0.218 eV for xW = 0.50 corresponds to a physical pressure of −2.2GPa when applied to the SnWO4 and to 1.7 GPa when exertedon SnMoO4. Using this correspondence, in the SnMox1–WxO4 solidsolution with a molar fraction of xW =0.43, a value of −3 GPa is obtained for the pressure at whichthe transition from the α to the β phase takes place.Overall,we can conclude that chemical pressure provides an efficientway to compress and expand crystalline structures. As compressionsare commonly related to positive pressures, the equivalence betweenphysical and chemical pressure is easily understood. Concerning latticeexpansions, the same formal ideas can be used to link the effect ofchemical pressure with negative physical pressures. A general correlationbetween physical . Our results thus provide anexample of how negative pressures through chemical doping can modulatethe band gap in these materials. Indeed, new synthetic methods likeheterostructural alloying might be used to stabilize these negativepressure polymorphs.24The possibility of achieving negative pressureregions by chemicaldoping has not to be neglected as recently remarked by Wang et al.:6+ and W6+ cations havea similar size. To answer this question, we analyze the role playedby the lone electron pair (E) of the Sn2+ cations. The activity of the lone pair is known to be dependenton the electronegativity of the ligand.25 As emphasized by Lin et al.,5 chemicalpressure induces modifications in the material behavior caused notonly by size effects but also due to new chemical interactions emergingfrom changes in the electronic structure. In agreement with previousstudies of Sn oxides containing d0 cations,21 the greater degree of distortion in Mo than W polyhedra is clearlyillustrated by the specific features of the charge density and theelectron localization function. Our ELF analysis reveals the existenceof SnO3E and SnO4E units within the octahedra and cubic antiprism polyhedra, respectively. The oxygens of the SnO3E units correspond to the three shortestSn–O distances of the SnO6 octahedra leading tothe (approximated) AX3E trigonal pyramidal geometry of the VSEPR model. Similarly, the SnO4E units are constituted by the oxygen atomswith the shortest (2 + 2) Sn–O distances in the SnO8 cubic antiprism, resembling the AX4E seesaw VSEPR geometry. It is very relevant to notice thatSnO3E units only appear in the βphase, whereas SnO4E units are associatedwith the α phase. Both Sn2+ and T6+ centeredcoordination polyhedra are linked by bridging oxygens (Ob). This feature is key to understand the preference for the mostdense packing found in the α phase either at normal conditionsin SnWO4 or at high pressure in SnMoO4.The questionthat remains is which is the driving force of thesephase transitions if Mo18 that can advance in thefinal solution. In the extended molecular orbital-type diagram depictedin s orbital and the 2p orbital of the oxygenbridging both polyhedra generates an antibonding state (populatedfirst with a loosely pair of electrons) that is able to mix with theempty 5p orbital of tin and finally stabilize thetwo antibonding electrons. The amount of stabilization depends onthe degree of interaction of the lone electron pair 5s orbital with the 2p orbital of the bridging oxygen.As this interaction depends on the relative energy of these orbitals,the electronegativity of the transition metal to which the bridgingoxygen is bonded plays a role since it modifies the energy of the2p oxygen orbital.We propose an extension of the revised classical lone pair modelof Walsh et al.19 the strongdistorted character of Mo6+ is associated with a higherelectronegativity when compared with the moderate distorter W6+. Such a higher electronegativity of Mo results into a strongercovalent Mo–Ob bond leading to an energy loweringof the 2p Ob orbital. The hybridizationbetween the 5s and 5p states ofthe Sn2+ cation is then facilitated in a greater degreein the Mo compound, increasing the stereoactivity of the lone electronpair. These conclusions are further supported by the values obtainedin the Crystal Orbital Hamilton Population (COHP) analysis28 of the Sn–O bonds. Systematically, COHP interaction energiesare revealed to be stronger for Mo pure phases (−2.865 eV αand −3.249 eV β) than for the W ones (−2.620 eVα and −3.178 eV β). The COHP analysis also evidencesthe greater lone pair activity of the Sn2+ cation in theMo than in the W compound, since the calculated overlapping Sn–Ovalues are 0.059 (α) and 0.073 (β) in SnMoO4 and 0.049 (α) and 0.070 (β) in SnWO4.According to Halasyamani,6+ cationwith a higher stereoactivity of the lone pair cation, we argue whethera higher activity shows a preference for the SnO3E or SnO4E units. Accordingto the VSEPR model, it seems reasonable to associate with the morerigid unit (SnO3E) the existence of greaterlone pair effects, since this unit has a lower number of structuraldegrees of freedom. Notice that the SnO3E unit is only present in the β phase. The COHP interactionenergies collected above also reveal greater values for the βthan for the α phase. Therefore, we have found that higher (lower)COHP values in the stable β (α) phase are concomitantwith the greater (lower) activity of the lone pair in the Mo (W) compound.Moreover, as pressure increases, the energy costs due to the strainedenergy in the SnO3E unit are finally releasedthanks to the transition to the α phase. In the case of theMo compound, the energetic balance is favorable due to the increasingin the coordination number. Similarly, the preference for the mostrigid and more active lone pair of the β phase in the case ofthe W compound at negative pressure compensates for the decrease inthe coordination number when transforming from the α phase.We assume that these arguments can be transferred to the high-temperatureregime, since volumes are the same at the transition temperature andat the transition negative pressure.Once we have linked the presence of the Mox1–WxO4 solid solutionfacilitates the linking between physical and chemical pressure. Wehave shown that by replacing Mo6+ by W6+, thesame phase transition as the one induced by physical pressure is observed.We have been able to map one magnitude into the other, thus providingquantitative proof of their equivalence in positive and negative regions.One of our findings has been to associate the preference of the d0 transition metal with the lone pair activity,i.e., either with the SnO3E or the SnO4E units. Such a linking is supported by thestructural analysis of Halasyamani et al.21 and the extended MO diagram of Walsh18 in d0 compounds containing lone electronpairs. Our results are able to explain the preference for the densestpacking found in the α phase either at normal conditions whenthe moderate distorter cation W6+ is involved or at highpressure in SnMoO4. This study highlights the usually overlookedrole played by the electronic structure of the guest atom when discussingchemical pressure effects. Since size effects are not meaningful inour system due to similar ionic radii of the two 3d cations, electronic structure modifications are here the main responsibleto control the thermodynamic stability of particular compositionsof the SnMox)and covering interesting phenomena such as multiferroic behavior,low thermal conductivity, or nonlinear optics are worth to be exploredfollowing our approach, since lone pair activity might be used toeffectively design new functional materials.In summary, the behaviorof the SnMoTable S1). The HSE06 hybridfunctional provides an overall better agreement with the experimentalresults regarding lattice parameters and band gap values and was usedin our work unless otherwise specified. The electron localizationfunction (ELF) scalar field29 was evaluatedto identify core, valence, and electron pairs regions of the optimizedstructures, whereas the crystal orbital Hamilton population28 (COHP) analysis was used to calculate bonding interaction energies.Pressure, temperature, and composition stability regions are determinedfor the two structures of the solid solution evaluating Gibbs energydifferences. See further details in the computational section of the Supporting Information file.First-principles calculationsunder the density functional theory(DFT) framework employing the functionals B3LYP and HSE06 have beenperformed (see


Despite their importance, shifts in terrestrial N loss pathways driven by global change are highly uncertain. Here we present a coupled soil-atmosphere isotope model (IsoTONE) to quantify terrestrial N losses and N2O emission factors from 1850-2020. We find that N inputs from atmospheric deposition caused 51% of anthropogenic N2O emissions from soils in 2020. The mean effective global emission factor for N2O was 4.3 ± 0.3% in 2020 (weighted by N inputs), much higher than the surface area-weighted mean (1.1 ± 0.1%). Climate change and spatial redistribution of fertilisation N inputs have driven an increase in global emission factor over the past century, which accounts for 18% of the anthropogenic soil flux in 2020. Predicted increases in fertilisation in emerging economies will accelerate N2O-driven climate warming in coming decades, unless targeted mitigation measures are introduced.Anthropogenic nitrogen inputs cause major negative environmental impacts, including emissions of the important greenhouse gas N Soil nitrogen isotopic composition is used to drive the IsoTONE model, which is constrained with measurements of tropospheric nitrous oxide isotopic composition. The model results reveal causes of rising mean global nitrous oxide emission factor. The atmospheric N2O mole fraction has increased from ~270 nmol mol−1 in the preindustrial era to >332 nmol mol−1 today3. The primary global source of N2O is production during N cycling by microbiota in soils . Soil N cycling also releases NO and N2, which directly impact tropospheric ozone production, climate, and soil N content and loss pathways5. N cycling and thus N gas production are strongly enhanced by direct and indirect anthropogenic N inputs8. Agricultural fertilisation accounts for around two thirds of anthropogenic N inputs9, with the remainder contributed by biological N2 fixation and deposition of NOx and NH3. Most anthropogenic N is not incorporated into crops or soils but lost to the environment10, representing huge monetary losses for the agricultural sector and causing a cascade of environmental problems13. In the coming decades, N inputs are expected to grow in line with increasing agricultural production, and to shift towards tropical regions and emerging economies as strict N pollution controls are introduced in many developed regions18. Effective management of N fertiliser to achieve high N use efficiency is key to balancing food production with environmental protection and thus reducing N2O emissions20. However, mitigation is challenging, and N2O emissions are currently exceeding the highest predicted scenarios2.Nitrous oxide  and denitrification (anaerobic) are the main processes emitting N gases  from soils. The proportion of N inputs released as particular N gases can be described with the emission factor (EF); for example, an EF for N2O of 2% means that 2% of annual N inputs are released as N2O. On the global scale, the impacts of climate change on N-gas production processes are poorly known: Warming is generally expected to enhance microbial activity and increase N-gas EFs, however interactions between factors such as N availability, plant growth, and precipitation changes are poorly constrained. Moreover, it is unknown if increased nitrification or denitrification rates would in fact lead to increased N gas production24. The proportion of N lost by leaching globally is not expected to change significantly over time in response to warming due to the contrasting effects of increased N mineralization and reduced moisture availability27. However, leaching losses and predicted responses to warming vary widely between different regions depending on soil, hydrological and ecosystem parameters, and may also be strongly affected by precipitation regime changes29. Moreoever, increasing atmospheric CO2 generally enhances plant growth and N uptake, thus impacting the availability of N in soils for different loss pathways31. Process models have been used to simulate N loss pathways in a changing climate (e.g.34). These models used generally require large amounts of input data and parameterisations as well as high computing power, which makes it difficult to iteratively constrain and optimize model parameters with observations using typical inversion frameworks and likelihood approaches, and complicates investigations of global or long-term emissions. Top-down modelling efforts can give robust estimates of global emissions for recent decades37, however without the incorporation of isotopes, these approaches cannot provide mechanistic information.N is lost from terrestrial ecosystems through several major pathways: Microbial and abiotic δ15Nsoil) has been proposed as an integrated indicator of N loss partitioning in natural systems41. Leaching of soluble N species , hereafter abbreviated as δ15N, and tje N2O 15-N isotopic site preference, hereafter referred to as δ15NSP  approach with 120 000 iterations, described in detail in Supplementary Note 2O emissions are dominated by N inputs from fixation . In contrast, anthropogenic soil emissions are dominated by N inputs from deposition (70% of 1940 and 51% of 2020 emissions), although fertilisation is becoming increasingly important (14% of 1940 and 22% of 2020 emissions)  using data from 123 ground-based sites  was produced from denitrification and 39% (4.7 ± 0.8 Tg N2O-N a−1) from nitrification. The contribution of nitrification to soil N2O emissions has decreased very slightly from 40% in 1850 to 39% in 2020  estimate for 202056 . This agrees very well with a recent ensemble analysis, which estimated a total anthropogenic flux of 7.3 (4.2–11.4) Tg N2O-N a−1 2. We find that deposition N accounts for 41 ± 14% of all anthropogenic emissions in 2020 compared to 19 ± 12% direct emissions from fertilisation, 21 ± 15% from enhanced fixation, and 19% from non-soil sources: Deposition N inputs clearly contribute the majority of anthropogenic emissions. This finding is in contrast to the results of Tian et al.2, who report that direct N2O emissions from fertilisation are dominant. These contrasting results are due in part to the classification of all emissions above the 1850 baseline  being classified as anthropogenic in this study, whereas in previous studies some or all of these processes are not considered in the calculation of the anthropogenic burden. Moreover, our results suggest that emission factors could be significantly underestimated from field measurements (see Sections 1 and 1), likely due to the highly dynamic nature of N2O emissions, which are not adequately captured with sparse sampling58. Moreover, measured EFs are often based only on growing season emissions, which can lead to a strong underestimation of annual emissions that could be particularly important in cold regions61. EFs will be particularly underestimated from field measurements made at agricultural sites, where a significant proportion of N is removed through harvest or immobilization as described by fert_EF_red, thus leading to low EFs. These combined effects will lead to underestimation of deposition emissions when measured EFs are applied at non-agricultural sites in bottom up-N2O emission frameworks.The anthropogenic N2O emissions was between 0 and 0.04 Tg N2O-N a−1 a−1 until ~1945  compared to the average of the last 50 years (0.09 ± 0.06 Tg N2O-N a−1 a−1), in agreement with two recent studies37. This caused the rate of change for the tropospheric N2O burden to peak at 0.026 nmol mol−1 a−1 a−1 . Total gas production accounts for the largest proportion of N losses in warm, dry regions, whereas N2O EFs are highest in non-desert tropical regions, in particular sub-Saharan Africa, southern India, China, and south east Asia, and low in drier and colder areas. This agrees well with results from refs. 70. Geoclimate-driven variability in emission factors can be clearly seen in regions underrepresented in EF compilations, such as Australia, which shows a clear gradient from low to high N2O EFs between the dry centre and wetter coastal and northern regions, but very little gradient in total N gas production. This pattern, whereby arid regions show relatively high N gas production dominated by NO, but low N2O EFs, can be seen across central North America, the Sahara, Australia, and central Asia. This suggests global applicability of the experimental results from ref. Soil moisture, N content, mean annual precipitation and soil bulk density  were the main parameters causing broad geoclimatic gradients in Nons Fig.  and 13, 2O  indicating moderate agreement. However, the slope of 0.15 suggested that measurements may consistently underestimate EFs due to insufficient measurement frequency and duration and the importance of ‘hot spots’ and ‘hot moments’ for annual N2O emission totals75. The impact of climate change—in particular changing precipitation patterns—on N2O emissions in rapidly developing regions like sub-Saharan Africa and India is not yet captured by observations, and should be a focus of future studies. Understanding the large-scale impact of moisture availability and other climate parameters on N loss processes through targeted measurements campaigns and model development will be key to predicting interactions between climate change-driven precipitation changes and N2O emissions.The spatial distribution of N inputs plays a key role in determining the overall global EF for N2O Fig. . The mea2O lost to different pathways shows clear temporal changes, particularly for fertilisation N inputs, which show an increase in mean EF of N2O from <4% prior to 1940 to >5% in 2020  towards emerging economies in warmer regions with higher EFs 2, which suggests an increase in the global emission factor for N2O. We developed and applied a coupled soil-atmosphere nitrogen isotope model framework—‘IsoTONE’—using soil δ15N as an emission proxy to understand the processes underlying spatiotemporal dynamics of global N2O emissions. This model set up developed in this study used isotopic composition to trace different N loss and N2O production processes, with a Markov Chain Monte Carlo approach implemented to constrain the model using tropospheric time series of N2O isotopic composition. Results from IsoTONE agree well with the CAMS inversion model49, providing confidence in both methodologies. Compared to CAMS, IsoTONE is able to harness isotopic information to understand spatial variability in emission factors and production and loss processes; moreover, the simplified approach means IsoTONE has low computational requirements and can be used to explore questions requiring many simulations.N2O emissions, but deposition N inputs account for the majority of anthropogenic emissions. Fertilisation N inputs are responsible for multidecadal variability in emissions, whereas subdecadal variability in N2O emissions is driven by biological N fixation. We show that the effective (N-input weighted) EF in 2020 is 4.3 ± 0.3%, much higher than the IPCC default value of 1.4%. N2O EFs are highly spatially heterogeneous—highest in warm, wet ecosystems—and thus strongly underestimated by default values based on area-weighted means. N2O EFs have increased over the past century, driven by climate warming as well as spatial redistribution of fertiliser N inputs. These two phenomena have led to additional emissions of 0.8 ± 0.4 and 0.5 ± 0.3 Tg N2O-N a−1 respectively between 1940 and 2020. Feedbacks between climate warming, spatial changes in agriculture, and N2O emissions should be considered in the development of emission projections and mitigation policies. Monitoring of annual N2O emissions as well as the soil δ15N emission proxy in both understudied regions and regions with particularly high emission factors will be key to reduce uncertainty, focus mitigation efforts, and combat rising N2O emissions.The model results show that fixation N inputs drive the majority of natural N77. Global soil organic carbon estimates and topsoil (0–30 cm) bulk density were taken from the Harmonized World Soil Database with a spatial resolution of 30 arc seconds79. Aridity index at a spatial resolution of 30 arc seconds was taken from the Global Aridity Index and Potential Evapotranspiration Climate Database (v2)80. Global soil pH at >60,000 sites worldwide was taken from the database compiled by Slessarev et al.81. The Worldwide Organic Soil Carbon and Nitrogen Dataset82 was used to estimate soil organic nitrogen content with data from >4000 sites rasterised using linear interpolation. Total fertiliser N inputs were taken from the Land Use Harmonization Database (LUH) with the historical dataset used for 1800–2015 (LUH2 v2h) and the future forcing dataset for 2015–2020 (LUH2 v2f)9. The Community Atmosphere Biosphere Land Exchange (CABLE) Australian community land surface model  was used to estimate global mean water-filled pore space (WFPS), fractional NH3 losses  and deposition and fixation N inputs 84. All datasets were converted to the model grid with 0.5∘ × 0. 5∘ resolution for −180∘ to +180∘ longitude and −60∘ to +85∘ latitude (720 × 290 gridcells) using the Python function scipy.interpolate.griddata with linear interpolation.Mean annual surface temperature (MAT) and precipitation (MAP) at 10 minute spatial resolution were taken from the Climate Research Unit high resolution global climatology datasetδ15Nsoil for >6000 soil samples from natural  sites was compiled by Craine et al.41. This database also includes ancillary data such as MAT, MAP, carbon and nitrogen concentration, C:N ratio, soil texture, density and pH, and site coordinates and elevation, although not all parameters are available for all samples. Geographical coverage was improved by adding a further 748 samples88, including unpublished data for 112 samples from Australia  and 392 from Africa  at the same geographical locations to gapfill the ancillary data  with the Python package Keras . A bootstrapping approach was used to estimate uncertainty in gridded δ15Nsoil.Data for 2O mixing ratio and isotopic composition since the preindustrial era formed the core set of observational data used to constrain simulation results in this study , as well as firn air sampled during the 2018 East GReenland Ice coring Project (EGRIP) campaign99 covering the period from 1982 to the present day, all measured at Empa, Switzerland. Additionally, mixing ratio, δ15N and δ15NSP data from CGAA (1979-2005) and firn air (1939-1995) from ref. δ15N, and +1.5‰ and +1.3‰ for firn and CGAA data for δ15NSP. To extend the isotopic timeseries further back, ice core and interstitial snowpack air measurements from the Greenland Ice Sheet Project II (GISP II)46 were also used, covering the period from 1785–1990. This dataset showed no offset for δ15N compared to the Empa dataset, and did not include δ15NSP measurements. Other available datasets  were not integrated, as they would not have improved the temporal range of the combined dataset, and would have introduced additional calibration scale uncertainty.A tropospheric background time series of Nudy Fig. . The bac2O mixing ratio in the preindustrial era was constrained using two Antarctic ice core datasets—from ref. 2O mixing ratio available at the World Data Centre for Greenhouse Gases  supported by the Global Atmosphere Watch (GAW) Program at Jungfraujoch (2005-present) and the Cape Grim Baseline Atmospheric Pollution Station  were used. Cape Grim data comprise measurements from three instruments covering different time periods, so overlapping periods were used to correct scale offsets, with the most recent dataset (1993–2018) used as an anchor. The dataset from 1981–1994 was +0.03 nmol mol−1 offset from the most recent dataset, and the dataset from 1978–1985 was −0.07 nmol mol−1 offset from the 1981–1994 dataset.N−1, 0.5‰ and 1.2‰ for mixing ratio, δ15N and δ15NSP, compared to 0.8 nmol mol−1, 0.2‰ and 0.6‰ for mixing ratio, δ15N and δ15NSP for 2000–2020, reflecting both the strong improvement in measurement techniques for recent in situ data and the particular challenges of firn and ice core measurements. The trend in mixing ratio for averaged data over the last 40 years was +0.8 nmol mol−1 a−1, with trends of −0.03‰ a−1 and −0.006‰ a−1 observed for δ15N and δ15NSP respectively.To allow comparison to simulated results and minimize the impact of any strong episodic local sources, average values for mixing ratio and isotopic composition were binned into 25-year intervals (1740–1940) and 2-year intervals (1940–2018)  for >300 sites has been compiled in the ‘Global N2O Database’102. This database also includes ancillary data such as MAT, MAP, carbon and nitrogen concentration, C:N ratio, soil texture, density and pH, and site coordinates and elevation, although not all parameters are included for all samples. The sample-specific reported ancillary data was compared to the global gridded datasets at the same geographical locations (see Supplementary Note 2O emission factors).Data for N39, coupled to an extended version of the atmospheric box model described in ref. 2O fluxes as well as tropospheric mixing ratio and isotopic composition from 1800 to 2020. The full coupled model was written in Python and will be hereafter referred to as the IsoTONE model (ISOtopic Tracing Of Nitrogen in the Environment). A schematic of the model is shown in Fig. The model used in this study is an extension of the simple soil isotope model presented by Bai et al.δ15Nsoil . The module is based on the equations used by Houlton, Bai38 and Bai et al.39, which state that the δ15Nsoil reflects the balance between N inputs (i), with a relatively constant rate and isotopic composition, and variable N losses. Loss pathways are divided into leaching (L), with low isotopic fractionation; NH3 volatilization, with high isotopic fractionation but a low contribution to total losses (NH3); and abiotic and microbial gas production (G), with high and variable isotopic fractionation. At steady state, inputs must equal outputs for both total amounts and isotopic composition:ε is the fractionation factor (k is the reaction rate) for the respective loss pathway and δ15Ni was set as −1.5‰39. Assuming steady state, the fraction of N loss accounted for by leaching (fL), NH3 volatilization (fNH3) and gas production (fG) can be calculated from δ15Nsoil. The steady state assumption is only valid for natural ecosystems, thus only δ15Nsoil measurements from natural sites were used to initialise the model. Unlike39, 14N and 15N were traced separately in Eq. , and necessitated an iterative solution to Eq.  was estimated to be 1‰39. Fractionation during NH3 volatilization (εNH3) was estimated to be −17.9‰ based on the equation in ref. εG) was estimated based on the relative contributions of the two dominant microbial processes: (i) Fractionation for N2O production during nitrification of εnit) was estimated as −56.6 ± 7.3‰ with δ15NSP of 29.9 ± 2.9‰106. (ii) Fractionation for N2O production during denitrification of εdenit) was estimated by adding the fractionation factor for reduction of 2O (−14.9 ± 6.7‰)106, thus εdenit = −46.2‰. δ15NSP for N2O produced from denitrification was estimated as −1.6 ± 3.0‰ (iii) Fractionation for N2O reduction during denitrification (εred) was estimated as −6.6 ± 2.7‰ with δ15NSP of −5 ± 3‰106.We assumed that N loss processes are primarily linked with the inorganic N pools  to the model such that net or effective fractionation = ε × frac_ex for all modelled processes. Thereby, frac_ex = 1 would reflect a well-mixed soil gas reservoir where effective fractionation is equal to expectations from laboratory measurements, and frac_ex = 0 would reflect a completely closed soil gas environment where all reactions go to completion within separate pores and thus no effective fractionation is observed. The initial value of frac_ex was set to 0.7 and it was optimized in the MCMC framework (see Methods: Optimization of model N cycle parameters) assuming a uniform error distribution between 0.3 and 1.0. In reality, different values for frac_ex may be expected for different processes and environments, in particular depending on soil texture and pore structure, however this cannot be determined within the available model-data framework.These fractionation factors refer to the immediate production or consumption of N substrates and N∘ × 0. 5∘ grid from −60∘ to 80∘ latitude and −180∘ to 180∘ longitude. The δ15N grid . For each grid cell, the soil model was initialised with an available soil nitrogen pool of size 1 (unitless) with δ15N of 0‰, and a soil N2O pool of of size 1 (unitless) with δ15N and δ15NSP of 0‰. The 14N input rate (ki) was set at 1 (unitless) and the 15N input rate  calculated using δ15Ni of 0.5‰ (based on114). Changing the unitless pool sizes affects only the number of iterations until steady state is reached in the model, and not the final result of the model. Reducing δ15Ni by 1‰ increased the calculated mean global fG by ~1%, while increasing δ15Ni by 1‰ increased the calculated mean global fG by ~5%, with very little impact of spatial distribution of fG.The soil model was run on an 0. 5n = 4). For the first iteration, fG was set at 0.1 for all gridcells. fNH3 was estimated using the CABLE model83. fNH3 is nearly always <0.05, therefore the model results are not highly sensitive to the parameterisation of fNH3. fL was then determined as 1 − fG − fNH3. Partitioning of total gas losses (fG) into N2O, N2 and NO  and nitrification (fnit) contributions to N2O production were estimated with a sigmoid fit to available experimental data  was compared to the δ15N value for the gridcell (δ15Nsoil) to find an improved fG for the next iteration according to:To solve Eq.  for eachδ15Nsoil and modelled δ15Nss agreed within 0.01‰ and final values of fG and fL were accepted.Following four iterations, fG and fL, the soil module estimated N2O production rate and isotopic composition for each grid cell. The production rates for 14N-N2O and 15N-N2O were calculated from the fractionation factors for each pathway multiplied by frac_ex; both 15Nα and 15Nβ were traced separately to consider N2O δ15NSP. For example, the 14N reaction rate for nitrification N2O production was estimated as 15N as:In addition to the calculation of 2 was assumed to represent the consumption of N2O via complete denitrification, as no other significant N2 sources are known, thus the extent of N2O reduction could be estimated and its isotopic effect calculated. N2O production and consumption were estimated in each step of the steady state calculation to give a final N2O flux and isotopic composition (δ15N and δ15NSP) for each gridcell to pass on to the atmospheric module described in the following subsection.Analogously, rates for each isotopic variant were also calculated for denitrification production and reduction. The production of N2O background mixing ratio and isotopic composition. Absolute N emissions into the tropospheric box were calculated using the fractional estimates of losses for each grid cell from the soil module, combined with annual N inputs to each grid cell for fixation, deposition and fertilisation for the period 1800–2020. Fertiliser N inputs were taken from the LUH database and covered the whole time period . Deposition N inputs for 1860–2050 were from ref. 17, where fixation is calculated using resource optimization with temperature dependence84. The 1901 fixation values were used to estimate fixation in earlier years and the 1860 values for deposition in earlier years, thus assuming negligible anthropogenic influence before 1850. As none of the N input datasets included significant anthropogenic inputs before 1850, 1850 is taken as the preindustrial ‘baseline’ throughout this study.The atmospheric module takes the fractional losses, estimated by the soil module described in the previous subsection, and uses a two-box model representing a well-mixed troposphere and stratosphere to reconstruct N117. Previous studies have shown that a large proportion of fertiliser N is incorporated into crops and therefore removed during harvest, as well as potentially stored in soils (117 and references therein)—thus not available for ‘normal’ N loss partitioning. Therefore, we added a factor fert_EF_red to the model to account for N that is harvested or stored. Fertiliser N inputs are multiplied by fert_EF_red to account for the removal of harvested N or stored in soils before losses by other pathways are calculated; fert_EF_red of 0 would mean that all N is removed in harvest, and fert_EF_red of 1 would mean no N is removed. The isotopic impact of harvest N exports cannot be accounted for within the scope of this study, as the required input data  is not currently available. Harvest N will be explicitly incorporated into a future version of the IsoTONE framework. EF changes with fertilisation rate were not considered: A recent meta-analysis showed that the dependence of EF on fertilisation rate is highly variable, and at the global scale EF is not strongly dependent on fertilisation rate118, although some studies have shown a strong non-linear relationship between EF and N inputs at the site and regional scale119. Tian et al.2 report that recent increases in EF for direct soil emissions are likely due to climate change feedbacks and interactions, rather than a direct increase in EF due to increasing fertiliser application. As more evidence regarding the non-linearity of fertiliser EFs becomes available, this will be incorporated into the IsoTONE model.Deposition and fixation inputs were assumed to generally fulfil the steady state criteria required by the soil module, however harvest N exports mean that this assumption is not valid for fertiliser N inputs. Harvested N is often returned to the soil or atmosphere via manure or deposition at a different location120 and likely increasing in a warming climate by between 0.5 and 1.0 Tg N2O-N −1, with a best estimate of 0.6 ± 0.2 Tg N2O-N −1121. We assume that this increase in emissions relates to a general sensitivity of microbial activity to temperature, and is therefore likely to affect production of N2 and NO as well as N2O. We therefore incorporated a temperature sensitivity increase of 10% of microbial N emissions from the year 1800 per degree of warming (temp_sens = 1.1 ± 0.04) for N2O, N2 and NO, which corresponds to 0.6 Tg N2O-N −1 according to the best estimate of 6.3 ± 1.1 Tg-N a−1 for N2O emissions in the preindustrial era8. Temperature anomalies from the CRUTEM-4.6.0 dataset were used to drive the temperature sensitivity calculation122. N losses through leaching were consequently reduced to maintain N mass balance.Previous studies have shown that microbial N gas production is temperature sensitive2O, NO and N2 were calculated for each input type for each grid cell incorporating both fert_EF_red and temperature sensitivity of emissions. In addition, EDGAR  gridded emissions for the major non-soil anthropogenic N2O emission categories  were added to estimate total terrestrial N2O emissions. Isotopic composition was estimated as δ15N = 3.9 ± 2.9 and δ15NSP = 17.6 ± 0.5 for power industry, δ15N = −7.2 ± 1.2 and δ15NSP = 10.0 ± 4.3 for road transport, δ15N = −8.3 ± 10.6 and δ15NSP = 3.3 ± 5.5 for chemical processes, and δ15N = −11.6 ± 12.7 and δ15NSP = 10.0 ± 5.7 for wastewater treatment43. Isotopic composition of natural soil N2O emissions was given by the soil module for each grid cell, and weighted by the emissions per grid cell to calculate overall isotopic composition of soil N2O emissions. The δ15N isotopic composition of fertiliser N inputs is estimated to be 3‰126 compared to −1.5‰ for natural N inputs39, thus increasing the δ15N of emitted N2O. Total global emissions were found by adding the oceanic emissions (Focean) to the global terrestrial emissions using the flux and isotopic compositions listed in Supplementary Table Yearly soil emissions of N2O was emitted into a two-box atmospheric model comprising a well-mixed troposphere and a well-mixed stratosphere, based on the model described in ref. 127, which is the time resolution of the model. Previous versions of this model explicitly calculate the required preindustrial terrestrial N2O flux to achieve steady state in the preindustrial era accounting for best estimates of tropospheric N2O mixing ratio, N2O lifetime, and stratosphere-troposphere exchange. However, in the atmosphere module of IsoTONE, preindustrial terrestrial emissions (Fterr) are prescribed by the soil module. An iterative calculation (maximum of 20 iterations) is therefore used to optimize the preindustrial oceanic N2O flux (Focean) and the troposphere-stratosphere exchange term (T_to_S) by shifting these two terms stepwise according to their prior uncertainty  and molestrop and molesstrat are the moles of air in the troposphere and the stratosphere (1.5 and 0.27 × 1020 moles respectively). This iteration meant that optimized values for both Focean and T_to_S were found for each solution of the model, although they were not explicitly targeted in the inversion described in the following subsection. Focean was not varied with time, as recent results suggest that the oceanic flux is relatively stable compared to the terrestrial flux2. Smaller, dynamic aquatic and semiaquatic ecosystems, such as estuaries and coastal wetlands, show highly dynamic and variably N cycling and N2O emissions130, but are too small to be resolved at the global scale of this study.Total global N2O fluxes and mixing ratio, model calculations proceeded as described by Yu et al.45 and will therefore only be briefly presented here. First, net stratospheric fractionation and the isotopic composition of the preindustrial stratosphere were found for δ15N and δ15NSP assuming steady state. The model was then run forwards with annual time steps using annual terrestrial emissions and isotopic composition provided by the soil module of IsoTONE. At each time step, N2O inputs and destruction were considered to estimate the rate of change in N2O mixing ratio and isotopic composition, and thus calculate a time series of mixing ratio, δ15N and δ15NSP for a well-mixed troposphere45.Once steady state was achieved for preindustrial N2O emission factors from the Global N2O Database, binned for 16 climatic zones (see Methods: N2O fluxes and emission factors). Temporal variability was constrained using a combined background tropospheric timeseries of N2O mixing ratio and isotopic composition (δ15N and δ15NSP) from several different sites, averaged for 25-year blocks from 1740 to 1940 and for 2 year blocks from 1940 to 2020 to give a total of 49 data points  but highly covariable. Observation uncertainty was defined as the standard deviation of measurements within each spatial or temporal block. Model uncertainty was set at 0.5 nmol mol−1 for N2O mixing ratio, 0.1‰ for δ15N and δ15NSP, and 0.5 for climate zone EF. The incorporation of isotopic composition in the atmospheric model gave an implicit sensitivity to the spatial distribution of emissions, as the isotopic composition of emitted N2O depends on the dominant emission processes in a particular gridcell, thus allowing the model to distinguish between changes in different regions and input types.Twelve key model parameters were optimised using a Markov Chain Monte Carlo (MCMC) approach , which was sufficient to achieve stable results with no significant difference between posterior parameters by step size, and no change in posterior parameters following more iterations. All tested and accepted parameter sets were saved; tested parameter sets were used to check coverage of the parameter uncertainty space  were not explicitly varied in the MCMC but were calculated to achieve steady state in the atmospheric module in each accepted iteration, thus posterior estimates for these parameters were also obtained.Once parameters were varied within an iteration The uncertainty in posterior parameters shown in Supplementary Table Supplementary InformationPeer Review File


The −NO2.− group goes to occupy an axial position of the metal ion, thus establishing a significant electronic interaction with the metal center. In particular, the ESR spectrum supports the occurrence of an electron transfer from −NO2.− to the metal, which therefore presents a significant NiI character. On re‐oxidation, the nitrobenzyl side chain detaches and the NiII complex is restored, providing an example of a fully reversible redox driven intramolecular motion.A radical anion −NO An electrochemically driven intra‐molecular motion on cathodic reduction of the NiII macrocyclic complex a, the electron first goes on the nitro group (b), then, following the swinging motion of the nitrobenzyl side chain, it is transferred onto the metal centre, giving rise to an authentic NiI (d9) scorpionate complex (c). II, CuII) giving a kinetically stable species, especially resistant to demetalation; and (ii) the tendency of the flexible pendant arm to further coordinate the metal ion in one of the axial positions of the coordination polyhedron , according to a labile binding mode.scorpionands.Tetraaza macrocycles  carrying a pendant side‐chain equipped with an additional, potentially coordinating nitrogen atom represent a class of quinquedentate ligands for transition metal ions which couple two distinct properties: (i) the capability of the rigid tetraaza ring to incorporate the metal ]3+. Above pH 2.8, the NH3+ group deprotonates and the −NH2 fragment goes to bind the metal. An octahedral high‐spin [NiII(L)H2O]2+ species forms, according to the equilibrium illustrated in Figure KA is 2.8.This is the case of the nickel(II) complex of penta‐amine 2 group of the pendant arm with respect to chosen reference systems 2+ (log K5=0.8). This leaves room to a determining additional term, related to the facilitated binding of a donor group linked by a short aliphatic chain to an already metal bound donor atom (a chelate effect).The remarkable higher acidity of the −NH2 (pKA=3.37), whose pendant amine group has been equipped with a light‐emitting subunit (9‐anthracenyl), the position of the side‐chain is signalled by fluorescent emission, whether bound (fluorescence OFF) or not bound (fluorescence ON).3 (light emitting subunit: dansylamide), whose coordinating group, a sulfonamide, deprotonates and binds the metal with a pKA=4.65.In the nickel(II) complex of scorpionand 2 pKA=3.37, w2 pKA=3.37, w4, N‐nitrobenzylcyclam.II(4)]2+ complex ]2+ complex shows a pKA of 10.71, a value remarkably lower than that of the reference system 4‐nitrotoluene, pKA=20.6, which confirms the central role of the chelate effect on the stabilisation of scorpionate complexes.Scorpionands containing donor atoms different from nitrogen are more rare. A special case refers to the macrocycle 2.− radical group could bind the metal centre according to a scorpionate mode. We report here a study on the electrochemical behaviour of the [NiII(4)]2+ complex in MeCN. ESR studies on the solution stable [Ni(4)]+ species, obtained through one‐electron reduction in a controlled potential electrolysis experiment, supported the occurrence of an electron transfer from −NO2.− to the metal, which therefore presents a significant NiI character.At this stage, we wanted to verify whether: (i) a negative charge on the nitro group could be generated also by direct electrochemical reduction, and (ii) the electrogenerated −NOMaterials and instrumental methods: Unless otherwise stated, all reagents and solvents were supplied by Sigma‐Aldrich and used as received. Nitrobenzylcyclam ‐1,4,8,11‐tetra‐azacyclotetradecane) was synthesised through a modification of a previously reported procedure,1H NMR spectra were obtained on a Bruker Avance 400 spectrometer. IR spectra were recorded on a Thermo Fisher Nicolet iS20 equipped with an ATR accessory. Anhydrous MeCN (99.8 %) and [Bu4N]ClO4 (>98 %) for electrochemical studies were purchased from Sigma‐Aldrich and used as received.Electrochemical measurements: Cyclic voltammetry (CV), differential pulse voltammetry (DPV) and controlled potential coulometry (CPC) were performed with a BAS 100B potentiostat/galvanostat, under the control of a PC, with dedicated software. CV and DPV experiments were carried out in a three‐electrode cell on anhydrous MeCN  solutions of the investigated compounds . A platinum electrode was used as a working electrode, a platinum wire as an auxiliary electrode, and Ag/Ag+ as the pseudo‐reference electrode made by a clean silver wire dipped into a MeCN filling solution 10−2 M in AgNO3 and 0.1 M in [Bu4N]ClO4. In each experiment ferrocene was added as an internal standard. CPC experiments were carried out on an MeCN solution of complex [Ni(4)]2+ using a platinum gauze as a working electrode. The counter‐electrode compartment was separated from the working compartment by a reverse U‐shaped bridge, filled with MeCN 0.1 M [Bu4N]ClO4. The reference electrode, a platinum wire dipped in the working cell, was calibrated through CV experiments prior to CPC. Absorption spectra of the solution were measured in the working cell during the electrolysis experiment by using a quartz fibre optic probe , connected to a diode‐array spectrophotometer .ESR measurements were performed with a Bruker EMX‐10/12  operating in the X‐band and equipped with a ER4119HS cavity and temperature control.II(nitrobenzylcyclam)]2+ in an MeCN solution was electrochemically investigated. For comparative purposes, the redox behaviour of MeCN solutions of nitrobenzene and of [NiII(cyclam)]2+ was electrochemically investigated under the same conditions. Figure 5) in MeCN made 0.1 M in [Bu4N]ClO4.The redox behaviour of 2+, made 0.1 M in Bu4NClO4. It is observed that the complex undergoes a reversible one‐electron oxidation to NiIII with E1/2=0.57 V versus Fc+/Fc and one‐electron reduction to NiI with E1/2=−1.84 V versus Fc+/Fc. The authenticity of nickel oxidation states had been determined through ESR studies on an electrolysed frozen MeCN solutions .[Coordination of NiII(4)]2+ system. The complex presents an anodic wave at E1/2=0.81 V. Such a wave can be ascribed to a metal centred oxidation process involving the formation of a NiIII complex. Noticeably, the NiII‐to−NiIII oxidation process for the N‐nitrobenzyl cyclam complex takes place at a distinctly more positive potential than that observed for the cyclam complex. According to a traditional Crystal Field perspective, on oxidation of NiII to NiIII in a tetramine complex of square planar geometry one electron is abstracted from the highest energy orbital, that is, dxy. Replacement of a secondary amine nitrogen atom with a benzylic tertiary nitrogen atom is expected to reduce the strength of the metal ligand interaction. This is confirmed by the values of the NiII−N distances observed in the crystalline square‐planar low‐spin complex salt [NiII(4)](CF3SO4)2:II−Nsec=1.93 Å, 1.94 Å, 1.93 Å; Ni−Ntert=1.99 Å. This lowers the energy of the dxy level, thus making the electron removal more difficult. However, it is the reduction behaviour that shows the more significant differences. In particular, a first reduction wave is observed at a E1/2=−0.85 V, that is, 1 V less negative than observed for [NiII(cyclam)]2+.Figure −1.Figure E1/2 values corresponding to those observed in DPV studies. Small waves in the CV profile of [Ni(4)]2+ (around −400/−500 mV) should be ascribed to impurities and are not observed in the corresponding DPV profile ]2+ complex, followed by decomposition. The occurrence of such a phenomenon was confirmed by control potential electrolysis experiments (see below).In all cases quasi‐reversible waves were observed with le of [Ni]2+ ]2+ complex was spectroscopically investigated. A bulk solution of the reduced form of [NiII(4)]2+ was prepared by an exhaustive controlled potential electrolysis experiment on an MeCN solution of the [NiII(4)](ClO4)2 complex salt. The potential of the working electrode (a platinum gauze) was set at −1.1 V, that is, 250 mV more negative than the E1/2 value of the first reduction wave. According to Nernst's equation, a ΔE of −236 mV (=59×4) ensures a ratio of the concentrations of NiI and NiII species of 1000/1. Moreover, the value of the set potential is well before the potential of the second reduction wave, which excluded any contamination by the second reduction product. The electrolysis experiment was monitored by measuring the absorption spectra with an optical fibre dipped in the solution and connected to a diode array spectrophotometer. The family of recorded spectra is shown in Figure The stability of the first reduction product of the + was investigated by carrying out ESR investigations on the electrolysed solution. Figure −4 M in the metal complex, frozen at 113 K.The nature of the reduced species 2+ species).The process is fully reversible, as shown by the fact that the reverse controlled potential electrolysis experiment makes the bright yellow colour vanish, while the EPR signal disappears ]2+/+)−E1/2(NiII/I(cyclam)]2+/+)=1.0 V. On assuming that ΔE1/2=ΔE°, the corresponding ΔG° can be calculated: ΔG°=−nFΔE°=−23.06 kcal mol−1, which is the free energy change associated to the following equilibrium:The effect of −NOK of Eq. (1) is 1017, which highlights the dramatic effect of axial coordination of a pendant arm equipped with −NO2.− on the formation of the NiI state.It follows that the constant II(cyclam) subunit, the nitrobenzene fragment is reduced at a potential of −0.83 V, a value much less negative than that of the isolated nitrobenzene fragment (−1.56 V). Ease of reduction has to be ascribed to the fact that the electron released by the electrode is in most part transferred to nickel and that the achievement of the NiI state is facilitated by the pendant arm coordination.It has been mentioned that, in complexes with pH‐sensitive scorpionands, metal chelation modifies the distinctive property of the pendant arm, by increasing significantly its Brønsted acidity. In the case of electrochemically active scorpionands the distinctive property under investigation is the tendency of the nitrobenzene group to be reduced. Indeed, when linked to the Ni+) induced a progressive and moderate anodic shift of the reduction wave of the nitrobenzene fragment, in CV experiments carried out in MeCN solvent. The effect was merely electrostatic and, in contrast to what observed in this work, ESR studies showed that no electron transfer took place from the reduced nitrobenzene fragment to the metal.+.Crown ethers equipped with a nitrobenzyl functionality have been previously reported by Gokel .2.− radical group can coordinate a metal centre in a scorpionand complex, and (ii) a definite and reversible intramolecular motion (the swinging of the pendant arm) can be promoted by a variation of the redox potential. The first classical example of redox promoted molecular movements refer to catenanes and rotaxanes designed by Stoddart (in which the redox change modified the π‐donor/acceptor properties of given fragments inserted in the axle or in the wheel)I/CuII couple).1–4, the stationary unit (the tetramine macrocycle) and the mobile moiety (the pendant arm) are covalently linked. While pH‐controlled swinging of the side‐chain in scorpionate complexes of type 1–3 is known since 1977, present work has demonstrated that the pendant arm can be made oscillate at will by a change of the redox potential.This work has demonstrated (i) that the −NOII(4)]+ is unique, in that it is able to convert into a definite motion the energy of either chemical (acid‐base) or electrochemical nature.Among scorpionand complexes, [NiThe authors declare no conflict of interest.1As a service to our authors and readers, this journal provides supporting information supplied by the authors. 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