However, these batteries following Li2CO3-product route usually deliver low output voltage (<2.5 V) and energy efficiency. Besides, Li2CO3-related parasitic reactions can further degrade battery performance. Herein, we introduce a soluble binuclear copper(I) complex as the liquid catalyst to achieve Li2C2O4 products in Li–CO2 batteries. The Li–CO2 battery using the copper(I) complex exhibits a high electromotive voltage up to 3.38 V, an increased output voltage of 3.04 V, and an enlarged discharge capacity of 5846 mAh g−1. And it shows robust cyclability over 400 cycles with additional help of Ru catalyst. We reveal that the copper(I) complex can easily capture CO2 to form a bridged Cu(II)-oxalate adduct. Subsequently reduction of the adduct occurs during discharge. This work innovatively increases the output voltage of Li–CO2 batteries to higher than 3.0 V, paving a promising avenue for the design and regulation of CO2 conversion reactions.Li–CO 2 batteries following Li2CO3-product route suffer from low output voltage and severe parasitic reactions. Herein, a soluble binuclear copper(I) complex is introduced as the liquid catalyst to achieve Li2C2O4 products in Li–CO2 batteries, which increases their output voltage to higher than 3.0 V.Li–CO Varieties of CCU technologies that can convert CO2 into value-added chemicals, such as methane dry reforming8, hydrogenation10, electrochemical reduction12, and photocatalytic reduction14, have been developed. In the past decade, a kind of energy storage device of Li–CO2 battery was proposed, offering an attractive tactic to utilize CO2 and produce electrical energy17. A typical Li–CO2 battery is composed of a lithium metal anode separated by an aprotic electrolyte from a porous CO2 cathode. The typical reversible reaction at the cathode involves the reduction of CO2 to form Li2CO3 and carbon on discharge, and the process is reversed on charge  is gaining increasing attention in the field of CO2 batteries usually present discharge voltages of around 2.5 V, sometimes even lower than 2.0 V in previous reports23. Generally, the quality of electrical energy is determined by the voltage supplied. An output voltage lower than 3.0 V leads to a low-quality electrical energy24. Obviously, the actual output voltage of Li–CO2 batteries is far lower than the theoretical value which is not high enough. Apart from the thermodynamic information of the reaction, the voltage that the battery can provide depends on the catalytic activity of catalysts and the transport properties of charge and mass in bulk and between phase boundaries.However, practical Li–CO26, noble metals28, and transition metal oxides30. Although they can remarkably reduce the charging overpotential, they have minimal effect in increasing the discharge voltage. It should be explained here that the catalytic characteristics of solid catalysts bring the difficulty of raising battery discharge voltage. As illustrated in Fig. 2. Specifically, three solid phases contain solid catalysts, Li2CO3, and carbon on the cathode surface. The liquid phase includes Li ions and dissolved CO2 in electrolyte. CO2 reduction during discharge occurs at the catalyst/electrolyte interface. The effect of catalytic reaction partially depends on the catalytic surface area of the solid catalyst particles on which CO2 is reduced. The sluggish kinetics of charge-transfer and mass-transport across multiphase interfaces aggravate the large voltage hysteresis. What’s more, active sites of solid catalysts are occupied by insulating and insoluble Li2CO3 products, leading to their invalidation32.On this basis, much efforts on solid catalysts have been exerted in raising the discharge voltage and reducing the charge voltage. The reported catalysts include carbon allotropes2CO3 itself usually occurs irreversibly during the charging process of Li–CO2 batteries 34 cause severe parasitic reactions. The gradual accumulation of irreversible byproducts threatens the stability of batteries. Thus, a catalyst designed with the strategy of Li2CO3-free pathway might be a good choice.It is worth mentioning that discharge products also affect the charging performance of the next cycle. In accordance with previous reports, electrochemical decomposition of Li2 reduction process, which is effective to reduce the discharge overpotential. The reported liquid catalysts, including 2,5-ditert-butyl-1,4-benzoquinone35, 2-ethoxyethylamine36, and tris-dichloro-ruthenium(II)37, can promote the discharge potential to a certain extent. However, batteries involving these catalysts still follow the Li2CO3 pathway. It might be better for the battery to discharge without taking the Li2CO3 path by liquid catalysts. As depicted in Fig. 2, and catalytic RMs are mixing at the molecular level in the liquid phase of electrolyte. Typical discharge process contains two steps. RM molecules capture CO2 to form RM–CO2 species first. The newly formed molecules then gain electrons at the cathode and are reduced to original RM and corresponding products (such as Li2C2O4). The liquid catalyst has more full contact with CO2 at the molecular level in the liquid phase, which effectively improves the reaction kinetics. The electrochemical redox process of the RM–CO2 at the electrode replaces the directly electrochemical reduction of CO2. This process allows to adjust the battery’s output voltage up to above 3.0 V by selecting and designing RM molecules  rather than solid one can reduce the number of phases involved in the COles Fig. .2 to oxalate chemicals38. This condition inspires us to introduce the catalytic effect of metal complexes into the design of Li–CO2 batteries. Moreover, Li2C2O4 as an electrochemical product can take the battery out of the troublesome Li2CO3 pathway. Herein, we introduce a binuclear copper(I) complex (denoted as Cu(I) RM) as the liquid catalyst in Li–CO2 batteries and study the battery performance, including the discharge potential, capacity, and cycle performance, in detail. In addition, we use a variety of spectroscopic analysis techniques, such as Raman and differential electrochemical mass spectrometry (DEMS), to explore the Li2CO3-free path experienced by the discharge process of the cathode. Furthermore, we employ an additional catalyst containing Ru nanoparticles to reduce the charge overpotential synergistically. This study increases the output voltage of Li–CO2 batteries to more than 3.0 V, which strongly promotes the practical application of this electric energy storage system.Apart from the abovementioned conventional liquid catalysts, some soluble metal complexes can also catalyze the electrochemical reduction of CO3CN)4]BF4 in dry acetonitrile (MeCN)39 (details of the preparation procedure are provided in the Methods section). 1H nuclear magnetic resonance spectroscopy (1H NMR) and electrospray ionization mass spectrometry (ESI-MS) were performed first to verify the molecular structure of the prepared ligand. As shown in Supplementary Fig. m/z) ratio of 545.25 matches well with that calculated for [C30H37N6S2]+ of the ligand 4]BF4 in MeCN. A prominent signal at the m/z ratio of 335.05 in Supplementary Fig. 2C30H36N6S2]2+, confirming the successful synthesis of the target complex.The binuclear Cu(I) RM was synthesized by the reaction of disulfide ligand with two equivalents of BF4  was added to the MeCN solution containing ligand  in an Ar glove box to acquire the Cu(I) RM.The binuclear Cu(I) RM was synthesized as described in previous literature28: RuCl3•xH2O (50 mg) was dissolved in ethylene glycol of 100 mL. Then Super P carbon (80 mg) was added in the solution, where the suspension was stirred for 3 h at 170 °C via an oil bath. The mixtures were filtered by deionized water and ethanol for several times after cooling to room temperature. The final products were dried at 120 °C under vacuum for 12 h.Ru@Super P was prepared in accordance with our previous study1H NMR (Bruker DRX500) was applied to analyze the molecular structures of the ligand. ESI-MS (Agilent 6460) was performed to collect information of the ligand and Cu(I) RM.All samples were transferred to different characterization equipment by using an air-tight sample module. Φ 3 mm) that was polished elaborately prior to use. The counter electrode was obtained by rolling the mixture of LiFePO4, Super P carbon, and polytetrafluoroethylene (PTFE) binder (W: W: W = 80: 10: 10) into a film (1.0 × 1.2 cm) and pressing on a stainless steel (SS) current collector. The pre-charged  LixFePO4 (x = 0.9) electrode was applied as the reference electrode, which had a stable potential of 3.45 V versus Li/Li+. The galvanostatic discharge-charge measurements were conducted in Swagelok batteries, including a Super P carbon (or Ru@Super P) cathode , a pre-charged LixFePO4 anode (Φ 12 mm), a glassy fiber separator , and a gas chamber. The cathode was prepared by rolling the mixture of Super P carbon (or Ru@Super P) and PTFE binder (W: W = 85: 15) into a film and pressing on a SS mesh. The mass loading of the electrode was 0.5 ± 0.2 mg cm−2. The thickness of a glassy fiber separator was 675 μm. All the electrodes were dried at 120 °C under vacuum for at least 12 h before assemblage. LiClO4 (0.1 M) in MeCN with or without Cu(I) RM (0.5 mM) was employed as electrolytes and the amount of electrolyte in each battery was about 300 μL.A three-electrode glass cell was first used to conduct CV tests. The working electrode was commercial glassy carbon . Galvanostatic tests were performed on LAND 2001A Battery Testing Systems  at 25 °C under Ar or CO2 atmosphere. The batteries were discharged and charged at a specific current of 100 mA g−1 and potential cut-offs of 2 V and 4.8 V. Galvanostatic discharge/charge cycling tests were conducted at a constant current density of 100 mA g−1 or 200 mA g−1 and a fixed capacity of 1000 mAh g−1. All current densities and capacities were normalized by the mass of active materials on the cathode. The specific energy based on active substance on the cathode was the product of specific capacity and output voltage.CV measurements were carried out on an electrochemical workstation  at 25 °C inside an Ar or CO−1. FTIR measurement was conducted on a FTIR spectroscope  with a wavenumber range of 4000–450 cm−1 and a resolution of 1.0 cm−1. The states of surface elements on the cathodes were characterized through XPS (Thermo Fisher Scientific Model K-Alpha spectrometer) equipped with Al Ka radiation (1486.6 eV) at a working voltage of 12 kV and a current of 10 mA. The morphology of cathodes was observed by SEM (Hitachi SU8010). The microstructure was further characterized by TEM (FEI TF20), and the SAED pattern was collected from a Gatan charge-coupled device camera. To evaluate the interaction between Cu(I) RM and CO2 in the electrolyte, ESI-MS and UV–vis absorption spectra data were collected. The UV–vis spectra were evaluated on a UV–vis spectrophotometer . XRD analysis was performed to analyze the crystalline structure of the catalyst by employing a Bruker D8 advanced diffractometer with Cu–Kα radiation (λ = 1.5406 Å) at a scan rate of 0.064° s−1. TG was carried out on an SDT Q600 TA instrument with a temperature range of 25–800 °C in O2 gas and the heating rate was 5 °C min−1.The discharged and recharged electrodes were washed with MeCN and dried sufficiently before characterization. The components of electrodes and electrolytes during different reaction stages were recorded by Raman spectroscopy  with the excitation light of an air-cooled He–Ne laser at 633 nm through a 50× long working distance lens (Leica Microsystems Inc.). To obtain apparent signals on the spectra and avoid the degradation of carbon cathode, the acquisition time was set as 120 s with 10% laser power. The resolution of Raman spectroscopy was around 1.0 cm2/Ar (V: V = 9: 1) was purged continuously to eliminate residual air first, after which 0.5 mM Cu(I) RM in MeCN (1 mL) was injected to the sealed vessel, and the remaining gas was purged to the mass spectrometer chamber (PrismaPro QMG 250 M2). The sealed vessel was connected by using two PEEK valves to the purge gas system. The electrochemical reaction was conducted by a home-made Li–CO2 battery mold with two PEEK valves connected to a quadrupole mass spectrometer with a turbomolecular pump (Pfeiffer Vacuum). During the charge process, ultrapure Ar was employed as carrier with a flux of 0.5 mL min−1. The DEMS battery was also performed on LAND 2001A Battery Testing Systems.In situ DEMS measurements were performed by chemical/electrochemical reactions. With regard to the chemical reaction, a mixture of COSupplementary Information


Semiempirical and Density Functional Theory (DFT) methods were used both including dispersion effects: PM6‐DH2, M06‐2X and B3LYP‐D3 along with the recently developed near linear‐scaling coupled cluster method DLPNO‐CCSD(T) for benchmark calculations. Our results given by QTAIM and non‐covalent interaction analysis confirmed the existence of hydrogen bonds created by —OH and —NH2. The trends in the energy decomposition analysis for the interaction energy, ΔEint, showed that the ΔEelstat contributions are equal or even a little bit higher than the values for ΔEdisp. Such important ΔEelstat attractive contribution comes mainly from the conventional hydrogen bonds formed by —OH and —NH2 functional groups with DNA not only with bps but specially with the sugar and phosphate backbone. This behavior is very different from that of phen and other classical intercalators that cannot form conventional hydrogen bonds, where the ΔEdisp is the most important attractive contribution to the ΔEint. The inclusion of explicit water molecules in molecular dynamics simulations showed, as a general trend, that the hydrogen bonds with the bps disappear during the simulations but those with the sugar and phosphate backbone remain in time, which highlights the important role of the sugar and phosphate backbone in the stabilization of these systems.The influence of hydrogen bonds in model intercalated systems between guanine‐cytosine and adenine‐thymine DNA base pairs (bps) was analyzed with the popular intercalator 1,10‐phenanthroline (phen) and derivatives obtained by substitution with —OH and —NH Hydrogen bond formation between phenanthroline derivatives and DNA sugar and phosphate backbone modulates the nature of the interaction from dispersion to electrostatic. Despite QM methods works usually with reduced models, the consideration of the sugar and phosphate backbone results mandatory to analyze the behavior of these systems where the intercalator may form conventional hydrogen bonds. We shall use 4,7‐(OH)2phen and 4,7‐(NH2)2phen as intercalators for our study 2phen and phen intercalators by means of ring models.2phen/CG)mg would be the system corresponding to the intercalation of 4,7‐(OH)2phen between GC/CG bps through the mg). In the following subsections, we shall discuss geometries and topological analysis of the studied structures, energetics, charge distribution and the evolution of the hydrogen bonded systems with time.We carried out semi‐empirical and DFT calculations including dispersion effects  for different structures of adenine‐thymine/thymine‐adenine (AT/TA) and guanine‐cytosine/cytosine‐guanine (GC/CG) bps including the 4,7‐(OH)2.1Ed) describes the stability of the interaction, being values close to zero a characteristic for weak interactions like π‐π and H‐bonds. To show a clearer picture only bond paths between intercalator and DNA are represented . For the represented intercalator‐ring model interactions, the bond paths where the functional groups —NH2 and —OH are involved are depicted with the corresponding values for the ρ, Ed, and distances. Apart from the conventional hydrogen bonds involving the —NH2 and —OH functional groups, several π‐π, CH/π, CH/n and even H···H interactions have been found. Similar H···H interactions for nearby hydrogen atoms were already found in our previous worksThe reader can find the cartesian coordinates of the optimized studied systems in the 2 and —OH groups not only with atoms contained in the bps but also, and more important, with atoms of the sugar and phosphate backbone for at least one of the groups. For 2phen/TA)mg system one of the —NH2 groups presents interactions with two heteroatoms of the nearby base pair, N7 and N6 of adenine 2phen/CG)mg system where again a —NH2 group presents two interactions with atoms of the base pair, N7 and O6 of guanine up‐right . For the intercalation of the 4,7‐(OH)2phen the general trend is that the —OH shows interactions with the atoms of the sugar and phosphate backbone although for the 2phen/TA)mg system one of the —OH functional groups still shows an interaction with the N6 atom of the adenine (down‐left), whereas for the 2phen/CG)mg system one —OH group presents a H‐bond with the O2 atom of the cytosine (up‐right). On the other hand, for the intercalation via MG, the H‐bond is formed with the sugar of the backbone (left).It is observed that the distortion of geometries leads to a fewer number of π‐π interactions showing the most coplanar arrangements higher numbers of π‐π interactions. In both systems, GC/X/CG and AT/X/TA, the intercalation via mg yields more distorted geometries than the intercalation via MG, . It is observed that this distortion is due to the presence of interactions of —NHs = 0.5 a.u.) isosurfaces. The gradient isosurfaces are presented in a color map attending to the corresponding values of sign(λ2)ρ . Blue represents large negative value, indicative of attractive interactions, while red represents large and positive values indicative of non‐bonding interaction (steric crowding). Values close to zero correspond to van der Waals interactions, very weak interactions. The results showed from the NCI analysis indicate a good agreement with the QTAIM study where the most stabilized regions are located around the BCPs found from QTAIM.To gain insight on the bonding scheme between the intercalator and DNA, the NCI index2 and —OH with heteroatoms located in the plane of the bps, only for 2phen/TA)mg a formal hydrogen bond with an O atom of one of the phosphates (right) is presented for one of the —OH groups of the intercalator. For the intercalation via MG different results are shown, the main trend being the formation of hydrogen bonds between the substituents, —NH2 and —OH, with the O atoms present in the sugar and phosphate backbones. The most favorable intercalation appears for 4,7‐(NH2)2phen, in this case both —NH2 groups interact with conventional hydrogen bonds, with a strengthened attractive non‐covalent bonding interaction represented by large negative values of sign(λ2)ρ in blue, with the O atoms of both sugar and phosphate backbones. For the intercalation of 4,7‐(OH)2phen via MG, just one —OH group present a conventional hydrogen bond with the terminal O atom of the sugar and phosphate backbone, while the other O atom of the —OH group presents interactions with H atoms of the adjacent sugars (left).For the AT/X/TA systems differences between the intercalation via mg and MG are observed. For the intercalation via mg we observe interactions of —NH2)2phen/CG we observe that one of the —NH2 groups yield a conventional hydrogen bond interaction with an O atom of the phosphate (left), while the other —NH2 group interacts mainly with heteroatoms of guanine, N7 and O6, (right‐up) with a considerable stabilizing interaction. This scheme is reproduced for the intercalation of GC/4,7‐(OH)2phen/CG via mg, where one of the —OH groups interact with an heteroatom of the base pair, O6 of cytosine (up‐right), and the other with an O atom of the sugar an phosphate backbone (left), in both cases these interactions are represented with a high negative value of (λ2)ρ for the NCI index. This is in agreement with the stabilization represented in the energy decomposition analysis (EDA) that will be observed below for the 2phen/CG)mg system where the stabilization by means of the electrostatic contribution is considerable. On the other hand, considering the 2phen/CG)MG system, it is shown that one of the —NH2 groups presents two hydrogen bond interactions with O atoms of the sugar (left) while the other —NH2 group presents only one hydrogen bond with a sugar (right). For the 2phen/CG)MG system, it is observed that just one —OH group presents one hydrogen bond with a sugar (right), showing a high negative value for the NCI isosurface. Again, the intercalations via MG in the GC/CG systems yield interactions with the sugar and phosphate backbones avoiding the formation of interactions with the heteroatoms of the bps.Regarding the GC/X/CG systems, the intercalation via mg, yields interactions with the heteroatoms of the bps as we have observed before for AT/X/TA systems. For GC/4,7‐ with the O atoms present in the sugar and phosphate backbone. On the other hand, —NH2 mainly yields two interactions thorough hydrogen atoms with the heteroatoms of the bps. These interactions present a less negative value for (λ2)ρ indicating a weaker interaction in comparison to that presented by —OH groups. Only in the case of 2phen/TA)MG and 2phen/CG)MG systems the —NH2 groups interact only with O atoms of the sugar and phosphate backbone with very negative values of the NCI index.Summarizing, regarding the differences between the implementation of the —NH2.2Eint between fragments can be split by the EDA into several contributions: the repulsive ΔEPauli, which takes into account the destabilizing interactions between occupied orbitals, the electrostatic contribution, ΔEelstat, which is the classical electrostatic interaction between the unperturbed charge distributions of the rigid fragments and the orbital interaction contribution, ΔEorb, which accounts for the charge transfer and polarization contributions. Moreover, if an explicit correction term for dispersion interactions is employed, such extra term, ΔEdisp, appears in the scheme.The interaction energy ΔEPauli) we observe the general trend for the intercalation via mg, where this repulsive contribution present higher values in comparison to the intercalation via MG, which could be attributed to repulsive interactions between the intercalator and the sugar and phosphate backbone, since in the intercalation via mg the intercalator is closer to sugar and phosphate backbone, whereas in the intercalation through the MG the sugar and phosphate backbone is farer away.Such EDA was carried out with the ADF software by means of the B3LYP‐D3 functional  and the obtained results represented in a cumulative diagram for the intercalated systems are shown in Figure 2, the ΔEelstat and ΔEorb contributions are considerably increased for the intercalation via mg in GC/X/CG systems, being almost doubled regard the non‐substituted intercalator, while the ΔEdisp shows a discrete increase after the substitution for the intercalation through the mg. For the intercalation via MG the general trend is that the ΔEelstat and ΔEorb contributions present less pronounced increases. A remarkable behavior in these attractive contributions is that the ΔEelstat is equal or even more important than the ΔEdisp. This behavior not only differs from the behavior obtained for phenEdisp was the most important attractive interaction. Thus, the substitution of phen with —OH and —NH2 shows a very different behavior. Nevertheless, this is not surprising considering the dual nature of the forces ruling the hydrogen bond interactions: dispersion and electrostatic forces.32 functional groups in the phen intercalator, conventional hydrogen bonds (between hard acids and hard bases) appear in which the electrostatic forces play a major role in the interactionEelstat contribution. On the other hand, we observe another characteristic behavior for these systems with —OH and —NH2 in the ΔEorb contribution, which becomes more important than for the unsubstituted phen. Because ΔEorb is associated to polarization and charge transfer processes, these more negative values of ΔEorb for the systems with —OH and —NH2 can be attributed again to the conventional hydrogen bonds formed between the 4,7‐(OH)2phen and 4,7‐(NH2)2phen ligands and the DNA, in which a more important charge transfer is produced between the intercalator and the DNA by means of these conventional hydrogen bonds as we will see below.If we consider the attractive contributions, it must be highlighted that after substitution of phen with —OH and —NHEint) gets reinforced after the substitution with —NH2 and —OH groups, being the most stabilized systems the 2phen/CG)mg and 2phen/CG)mg. These results for 4,7‐(NH2)2phen and 4,7‐(OH)2phen intercalating via mg could be explained with the hydrogen bonds and BCPs found at the same time with the sugar and phosphate backbone and the heteroatoms of the bps  with extended basis sets to have an idea of the accuracy of the ΔEint obtained through DFT‐D. Actually, after the consolidation of conventional DFT approximations, different studies were reported where a G2 modified composite methodology in which MP2 geometries and HF frequencies were substituted by the DFT ones and the QCISD(T) calculations were replaced by CCSD(T) ones.Even though DFT‐D methods contains corrections to dispersion contributions, since there are several functionals and different kinds of corrections to dispersion, one could think about some validation of the ΔThus, in order to obtain accurate benchmark results regarding the interaction energy between the considered fragments, intercalator and ring model of DNA, DLPNO‐CCSD(T) calculations were performed to corroborate the accuracy of the interaction energies obtained from the EDA results shown above. Figure According to the results obtained from the interaction energy between the considered fragments, computed at DLPNO‐CCSD(T) level, we observe that the trends obtained from the EDA analysis matches nicely with the accurate energies provided by the accurate benchmark DLPNO‐CCSD(T) results. In consequence, we may assume that the relative interaction energies between the substituted phen derivatives obtained by DFT‐D methods, and the contributions depicted above, are reliable.ESolv, was considered and added to the total interaction energy, ΔEint, from EDA to obtain the final energy in solution, ΔEaq mg  for the mg and 2phen/TA)MG  for the MG. Such systems were also the most stable systems when solvent effects were not taken into account and actually, the general trends in stabilization are maintained when comparing the systems with and without solvent effects. Thus, for the AT/X/TA systems, even the ΔESolv penalty changes the final energy of the systems; the trends in stabilization are maintained. Moreover, we observe that the ΔESolv penalties are more important for the systems intercalating via mg. Regarding the GC/CG systems the most stabilized systems considering the solvent effects are 2phen/CG)mg with a final energy of −29.0 kcal mol−1 for the mg and 2phen/CG)MG for which the final energy after considering desolvation penalty is −15.5 kcal mol−1 for the MG. In this case the trends when taking into account solvent effects are not the same than without consideration of solvent effects 2phen/CG)mg system. It means that, even we have strong conventional hydrogen bonds in the studied systems, the charge transfer between DNA and the intercalator will have minor role in the interaction. This behavior is in agreement with the ΔEorb numbers of the EDA observed in the previous section for which the highest value was for the 2phen/CG)mg structure although the ΔEorb contribution is always the lowest attractive term when comparing to ΔEelstat or ΔEdisp. On the other hand, an interesting behavior is observed for the sign of the charge of the intercalator. That is, the sign depends on the orientation of the intercalation process more than on the nature of the species involved in the process and for the systems intercalating through the mg the sign of the charge located on the intercalator is positive, whereas for the systems intercalating via MG the sign is negative. We would like to highlight this result because it breaks the classical behavior found in the bibliography for the studies of intercalators at QM level. Indeed, in the pioneer studies of Rěha et al.Eorb of the respective EDAs. Thus, when incorporating —NH2 and —OH groups to phen, which may form conventional hydrogen bonds, in the most sophisticated ring model including sugar and phosphate backbone, the addition of these new fragments along with the addition of the —NH2 and —OH groups could perturbate the final system in such a way that depending on the orientation of the intercalation, we would be able to reverse the sense of polarization we have in these biological processes. In these ring models with the 4,7‐(OH)2phen and 4,7‐(NH2)2phen intercalators the classical behavior of the intercalator as π‐electron acceptor occurs when the intercalation takes place through the MG where the in intercalator and bps remains almost coplanar and we find a high number of BCPs corresponding to π‐π interactions . The bonds formed with —OH remain stable during all the time of simulation (2 ps). Nevertheless, it must be said that when the systems arrive at this threshold an important distortion of the ring model and the entry of some water molecules into the intercalation pocket was found as a general trend for the studied ring model systems 2phen/TA)MG system, for which we have a NH···O hydrogen bond, this interaction is maintained during all the time of the MD simulation (2 ps). However, in the same system we find a NH···O(sugar) hydrogen bond that disappear about 600 fs. In the case of the 2phen/CG)mg system, for which we find a NH···O(phosphate) hydrogen bond, this interaction disappear about 1.1 ps. Finally, for the 2phen/CG)MG system, in which we have also a NH···O(phosphate) hydrogen bond, it disappears also about 1.3 ps. In this last 2phen/CG)MG structure we have also two NH···O(Sugar) interactions as for the 2phen/TA)MG system. Nevertheless, now, and different from the 2phen/TA)MG structure, such interaction remain during the 2 ps of the MD simulation. Interesting is the case of the NH···O(sugar left), which have very width fluctuations from 1.81 to 4.04 Å but at the end of the 2 ps MD simulation, the NH···O(sugar left) hydrogen bond distance is still 2.04 Å and therefore it is maintained during all the simulation time. All these trends in the MD simulation would be in agreement with the values of the ρ in the BCPs of the QTAIM analysis and the values of the isosurfaces of the NCI analysis corresponding to the monitored conventional hydrogen bonds since the values of ρ and such isosurfaces are higher for the conventional hydrogen bonds coming from the —OH than for those produced by the —NH2 functional groups. On the other hand, since the —OH group only have one H atom to form the hydrogen bonds, whereas the —NH2 group has two H atoms, competence could be produced in the latter case and more possibilities to form hydrogen bonds with the explicit water molecules are expected. These could be the reasons, along with the distortion of the ring models during the MD simulation, for the irregular behavior of the systems containing 4,7‐(NH2)2phen. Moreover, these results show not only the important role of the sugar and phosphate backbone to describe properly the intercalation of 4,7‐(OH)2phen and 4,7‐(NH2)2phen between DNA bps but also the limitations of the ring model, in which the lack of the stabilization produced by the rest of the stacked bps leads to the distortion of the system during the MD simulation 2 tetramer model where a 4,7‐(OH)2phen ligand was intercalated via mg in order to observe the evolution of the conventional hydrogen bonds with a more realistic model. The intercalation between the bps is according to the methodology explained below and similar MD simulation conditions has been performed as for the ring model. In Figure 2 intercalating the 4,7‐(OH)2phen ligand between AT/TA bps via mg is shown along with the corresponding solvation environment.As observed before at the end of the simulations 2phen ligand via mg, the whole structure keeps the geometrical arrangement along all the time of simulation. The main conclusion that arises from this MD simulation is that the π‐π stacking of the successive bps avoid the deformation observed above with the smaller ring systems where the solvent molecules interacted with the hydrogen bonds of the confronted bps.Performing again MD simulations until 2 ps, we observed that for the chosen larger system including the d(AATT)2phen in the tetramer DNA structure via mg, we observe that the hydrogen bond formed with the phosphate group remains unchanged along all the simulation . On the other hand, the other OH group that is located between the two bps presents a different behavior. After 7 ps the distance with the hydrogen bond formed with one O atom of a nearby base is increased and after this point this H atom remains equidistant between the two bps with a slight fluctuation of the distances. The main conclusion that arises from the MD simulations is that the conventional hydrogen bonds produced by the studied phen derivatives with the sugar and phosphate backbone tend to be stable with time, whereas those with the bps tend to disappear at some point of the MD simulation. On the other hand, after comparison of the MD simulation for the intercalated system in the d(AATT)2 DNA tetramer and the intercalated systems with the ring models, it is mandatory to use at least the DNA tetramer for MD simulations, which produces the stabilization of the system because of the stacking forces of the additional bps compared to the ring model, which becomes distorted at the end of the MD simulations because of the lack of such stacking stabilization that would be produced by the addition of the two more bps in the DNA tetramer.Attending to the evolution of the hydrogen bonds for the intercalated4,7‐(OH)32 functional groups 2phen and 4,7‐(NH2)2phen). We used semi‐empirical and DFT methods both including dispersion effects to analyze this kind of systems in which dispersion forces are crucial. When these phen derivatives intercalate between DNA bps the —OH and —NH2 groups are able to form hydrogen bonds not only with several atoms of the bps but also with atoms of the sugar and phosphate backbone, which help to the stabilization of this kind of ligands during the intercalation process with the eventual improvement of their cytotoxicity. We considered two possibilities for the orientation of the intercalation: (1) through the mg and (2) via MG.In order to analyze the effect of hydrogen bonds of phen derivatives in the structure, energetics, interaction properties and their evolution in time, optimizations and MD simulations were carried out on GC/CG and AT/TA ring model systems incorporating phen derivatives as intercalators, which were made from substitution of ‐H atoms in positions 4 and 7 by the —OH and —NH2 and —OH functional groups. This is mainly because the systems studied in this work, 4,7‐(OH)2phen and 4,7‐(NH2)2phen, are able to form hydrogen bonds not only with the heteroatoms of the surrounding bps of DNA but also with the O atoms of the sugar and phosphate backbone, the latter more stable in time. Such interactions with the backbone results of high importance in the behavior of the intercalator and its eventual cytotoxicity.After the study of the geometries, QTAIM topologies, NCI analysis, energetics, charges and the evolution of the systems with time by means of 2 ps MD simulations in a box of explicit water molecules, we concluded that the sugar and phosphate backbone plays a crucial role in the stabilization of the phen derivatives containing —NH2phen and 4,7‐(NH2)2phen ligands through the mg leads to a more negative ΔEint than their counterparts intercalating via MG as a general trend. This is because the intercalation through the mg is able to produce more conventional hydrogen bonds not only with the bps but also with the sugar and phosphate backbone than when intercalation is produced via MG. The second important conclusion derived from the EDA is that, different from our previous studiesEdisp was the most important attractive contribution to the interaction energy, now the ΔEelstat attractive contribution is equal or even a little bit more important than ΔEdisp. This is not surprising considering that now 4,7‐(OH)2phen and 4,7‐(NH2)2phen ligands with —OH and —NH2 functional groups are able to form conventional hydrogen bonds not only with the bps but also with the sugar and phosphate backbone and the electrostatic contribution in conventional hydrogen bonds results much more important than weaker CH/n, CH/π or H···H hydrogen bonds for which the dispersion contribution was dominant. The last remark from the EDA is that the ΔEorb accounting for charge transfer and polarization effects is more important for 4,7‐(OH)2phen and 4,7‐(NH2)2phen ligands than for phen, which is related again to the —OH and —NH2 functional groups that may form conventional hydrogen bonds and such interactions allow higher charge transfer as can be confirmed by the values of ρ in the corresponding BCPs and also by the values of the NCI isosurfaces located in these conventional hydrogen bonds formed by 4,7‐(OH)2phen and 4,7‐(NH2)2phen intercalators. The accuracy of the values for the interaction energies for such intercalation processes with 4,7‐(OH)2phen and 4,7‐(NH2)2phen intercalators has been also corroborated with benchmark calculations at DLPNO‐CCSD(T)/cc‐pVTZ level. The results indicate that the DFT‐D method for the EDA at B3LYP‐D3/TZP level faithfully reproduce the interaction energies between the DNA ring models and the considered phen derivatives.On the other hand, the information given by the EDA provides also very interesting conclusions. First of all, the intercalation of 4,7‐(OH)ESolv. Nevertheless, when adding this penalty to the ΔEint we still obtain important negative energies although the inclusion of the solvent effects may alter the final trends of the systems when comparing the final values of the ΔEaq energies to those of the ΔEint of the original EDA, which emphasizes the importance of taking into account solvent effects for this kind of processes. Thus, cytotoxic effects of this kind of ligands will depend not only on the intrinsic forces derived from the EDA but also on the solvent effects.The inclusion of solvent effects produces an important penalty, Δ2)2phen and 4,7‐(OH)2phen as electron acceptors/electron donors may be altered with the orientation of the intercalation process, through the mg or via MG, which would break with the classical consideration of the intercalators as electron acceptors.Eorb of the EDA.We also observed that the nature of the studied ligands 4,7‐(NH2)2phen and 4,7‐(OH)2phen ligands but also the inclusion of more stacked bps in order to stabilize the model. That is, whereas the hydrogen bonds formed between the —NH2 and —OH functional groups and heteroatoms of the bps change and disappear during the time of the simulation, conventional hydrogen bonds formed with the sugar and phosphate backbone may remain along the time, particularly those formed by the —OH functional group present in the intercalator. Nevertheless, limitations have to be highlighted with respect to the ring model when performing MD simulations in a box of explicit water molecules since distortion of the ring model is produced with time due to the lack of the stabilization that the rest of bps would produce if they were added to the ring model.Finally, the main conclusion that arises from the MD simulations is not only the important role of the sugar and phosphate backbone in order to describe properly the intercalation of 4,7‐2phen between GC/CG bps through the MG was achieved by rotating the 4,7‐(OH)2phen ligand in such a way that the N atoms became in the side of the MG, whereas —OH groups were in the side of the mg 2phen intercalator.In order to build our models, first of all, we considered the 4e1u structure from the Protein Data Bank (PDB). Because we are interested only in the intercalation, for this 4e1u structure we cleaned and removed all the atoms with the exception of the dppz intercalator and the surrounding atoms forming the intercalation pocket. That is, the GC/CG bps, sugars and phosphates. Sodium atoms were also added in order to balance the negative charges of the two phosphate groups and the dppz ligand was transformed manually into 4,7‐(OH)2phen for which we have the torsions associated to the C—C—O—H dihedral angle of each —OH functional group. Moreover, since the surrounding DNA pocket has several heteroatoms with electronic lone pairs to form hydrogen bonds with the hydroxyl groups of the 4,7‐(OH)2phen ligand some conformations will be more stable than others. Therefore, to carry out some conformational search associated to such rotamers and to find which hydrogen bonds with DNA are more stable, the following strategy was applied. First of all, a systematic conformational search by rotating 45° each single bond associated to the C—C—O—H torsions of each —OH functional group was carried out. That is, we fixed one torsion for the —OH group in position 4 and we rotated the other —OH group in position 7 in steps of 45°. Thus, for one fixed C—C—O—H torsion angle for the —OH in position 4 we obtained eight conformations by rotating the C—C—O—H torsion angle of the —OH in position 7. Once we had these eight conformations, we rotated 45° the torsion angle of the —OH (4) and we obtained the eight conformations corresponding to the —OH (7). This process was repeated until complete the eight conformations for the —OH (4) and it gave us a total of 64 conformations associated to the C—C—O—H rotations of the two —OH functional groups 2phen ligand. Subsequently, all the structures obtained from the systematic conformational search were optimized at PM6‐DH2 level.Because classical intercalators are flat ligands made from fused rings, they are very restricted to motion and their number of conformers is small. However, when substitution is produced with some group having single bonds, the degrees of freedom of these molecules increase and different conformations can be achieved due to single‐bond rotamers. This is the case of the hydroxyl group in 4,7‐(OH)Edisp term for dispersion the results of the EDA are reported with the B3LYP‐D3 functional with the explicit Grimme's D3 correction to dispersion contributionThe so‐called EDA2phen ligand intercalating via mg with the d(AATT)2 DNA tetramer obtained from the 4e1u PDB structure in a similar way that we obtained the intercalating ring systems before. The system was also put in a rectangular water box with edges no closer than 5 Å to any atom of the d(AATT)2 DNA tetramer intercalating the 4,7‐(OH)2phen ligand via mg. As for the ring models, the TIP3PBOX solvent model was considered with Chimera 1.13. Prior to simulation of 2 ps a relaxation pre‐process was carried out in which the d(AATT)2 DNA tetramer intercalating the 4,7‐(OH)2phen ligand was fixed along with the Na+ atoms and only H2O molecules were allowed to move in a pre‐simulation of 0.5 ps with time‐steps of 1 fs. Subsequently, and in order to minimize non‐desirable perturbations of the Na+ cations to the solute  that could affect the MD simulations, the Na+ cations were allowed to move along with H2O molecules during 0.5 ps with time‐steps of 1 fs and only the d(AATT)2 DNA tetramer intercalating the 4,7‐(OH)2phen ligand was fixed. After this pre‐process of relaxation the d(AATT)2 DNA tetramer intercalating the 4,7‐(OH)2phen ligand via mg was also allowed to move with Na+ atoms and H2O molecules to perform the MD simulation of 2 ps with time‐steps of 1 fs.We also determined the stability of the conventional hydrogen bonds during the time by performing 2 ps semi‐empirical MD simulations with the PM6‐DH2 Hamiltonian. We chose this time of simulation because bond vibrations and even chemical reactions may be appreciated within this time of simulation and in the case of the conventional hydrogen bonds studied in this work this scale of simulation should be enough to monitories their stability during time.Data S1. Supporting information.Click here for additional data file.


The correlation and agreement between PtcCO2 and PaCO2, PetCO2, and PaCO2 were evaluated.Children aged 2–8 years with American Society of Anesthesiologists (ASA) class I or II who underwent laparoscopic surgery under general anesthesia were selected. After anesthesia induction and tracheal intubation, PtcCO2 = 7.89 + 0.82 × PaCO2 ; PetCO2 = 9.87 + 0.64 × PaCO2 . The 95% limits of agreement (LOA) of PtcCO2 – PaCO2 average was 0.66 ± 4.92 mmHg, and the 95% LOA of PetCO2 – PaCO2 average was –4.4 ± 4.86 mmHg. A difference of ≤ 5 mmHg was noted between PtcCO2 and PaCO2 in 122/128 samples and between PetCO2 and PaCO2 in 81/128 samples (P < 0.01).A total of 32 patients were eventually enrolled in this study, resulting in 128 datasets. The linear regression equations were: PtcCO2 and PaCO2. Compared to PetCO2, PtcCO2 can estimate PaCO2 accurately and could be used as an auxiliary monitoring indicator to optimize anesthesia management for laparoscopic surgery in children; however, it is not a substitute for PetCO2.In pediatric laparoscopic surgery, a close correlation was established between PtcCOChiCTR2100043636.The online version contains supplementary material available at 10.1186/s12887-023-03836-2. The gold standard for measuring PaCO2 in clinical practice is arterial blood gas analysis (ABGA) [2 level continuously [Arterial carbon dioxide pressure (PaCOs (ABGA) . The pat2) has become a routine monitoring item for patients undergoing general anesthesia with tracheal intubation. Anesthesiologists can estimate PaCO2 based on PetCO2. However, several factors, including patient’s age, different types of surgery, combined cardiopulmonary diseases, and changes in pulmonary blood flow, can affect the accuracy of PetCO2 monitoring results, increasing the difference between PetCO2 and PaCO2 in practice [2 and PaCO2 shows a decrease with the delay of pneumoperitoneum during laparoscopic surgery; thus, PaCO2 values should be monitored intermittently by ABGA [2 is not a reliable predictor of PaCO2.End-tidal carbon dioxide partial pressure (PetCOpractice . The cor by ABGA . Therefo2) can be used to estimate PaCO2. PtcCO2 monitoring is based on an electrochemical principle. The probe’s internal heating electrode raises the local skin temperature. This results in the arterialization of dermal capillaries and improvement in their permeability, making it easier for CO2 to enter the tissue space and diffuse away from the skin surface. CO2 permeates the electrolyte layer via a high-permeability membrane on the sensor’s surface, altering the pH value of the electrolyte layer, which is related to the variation in the CO2 partial pressure [2 value is obtained by the monitor’s internal programming algorithm. PtcCO2 monitoring is a continuous and noninvasive method; however, due to advancements in monitoring technology and the miniaturization of the device, it is gaining increasingly popularity in clinical practice. Also, previous studies have shown that PtcCO2 monitoring is effective in perioperative settings [2, PtcCO2 has a better correlation and a smaller difference with PaCO2. Nevertheless, Bolliger et al. indicated that PtcCO2 monitoring does not accurately reflect PaCO2 and does not provide more useful monitoring data than PetCO2 [Transcutaneous carbon dioxide partial pressure .Currently, there are no clinical reports regarding PtcCOThe present study was approved by the Shenzhen Children’s Hospital Ethics Committee , and written informed consent was obtained from the parents. A total of 35 children who underwent laparoscopic surgery, aged 2–8 years, and ASA class Ι or II were recruited for this study. Patients who required a vasoconstrictor to maintain blood pressure during the procedure and those with insufficient pneumoperitoneum time (< 90 min) were excluded from this study.2), and blood pressure (BP)were monitored; the heart rate (HR) and BP were recorded as baseline values. Tracheal intubation was conducted following intravenous administration of benzenesulfonate cisatracurium 0.1 mg/kg and fentanyl 3 μg/kg. Breathing settings were established on the anesthesia machine: intermittent positive pressure ventilation, tidal volume 6–10 mL/kg, inspiration/expiration 1/2, inhalation oxygen concentration 50%, gas flow rate 2 L/min, and respiratory rate 15–25 times/min. PetCO2 level was continuously measured using the side-stream capnography . The respiratory rate and tidal volume were adjusted to maintain PetCO2 35–45 mmHg and airway pressure 10–25 cmH2O. Anesthesia was maintained with inhalation sevoflurane concentration at 2–3%, intravenous pumping of remifentanil 0.2 μg/kg/min, and benzenesulfonate cisatracurium 0.1 mg/kg/h. The dosage of benzenesulfonate cisatracurium was adjusted according to the results of muscle relaxation monitoring.Children were escorted to the anesthesia room by their parents, and 2.5 mg/kg propofol was administered to induce sleep. The child was then transported to the operating room under the close supervision of the anesthesiologist. Electrocardiogram, pulse oxygen saturation  was attached. The monitoring site was located on the forehead, and the electrode-heating temperature was adjusted to 42 °C. The monitor was calibrated, and the electrode membrane was changed before each use. Radial artery catheterization was performed to facilitate invasive arterial blood pressure monitoring and the acquisition of blood gas analysis samples. The laparoscopic pneumoperitoneum pressure was chosen based on the children's ages  and it was fine-tuned according to the surgical field's size when the pneumoperitoneum has just been established. Throughout the course of the procedure, there was no change in the pneumoperitoneum pressure. HR and BP were maintained within the range of ± 20% of the baseline value. The nasopharyngeal temperature of the child was maintained at 36–37 °C using an inflatable thermal blanket; the operating room temperature was set at 23–25 °C.After tracheal intubation, a PtcCO2 monitor sensor was removed during the postoperative recovery period of anesthesia; the local skin was cleaned and examined for signs of injury. After the removal of the arterial cannula, pressure dressings were applied. The tracheal tube was withdrawn when the child’s spontaneous breathing was recovered, with SpO2 maintained at 95% under inhaled air settings. Finally, the vital signs were observed carefully, and the child was transferred to the anesthesia recovery room for further monitoring after stabilization.PtcCO2, PetCO2, and PaCO2 values were recorded at each time point. A blood gas analyzer  was used to measure PaCO2. HR, BP, SpO2, tidal volume, respiratory rate, and body temperature at each time point. HR, BP, and the anesthesia machine’s respiratory parameters were stabilized for at least 5 min before recording the measured values.ABGA was conducted before (T0) and 30 min (T1), 60 min (T2), and 90 min (T3) after pneumoperitoneum. Also, PtcCO2 and PaCO2 or between PtcCO2 and PaCO2. A difference of ≤ 5 mmHg between PaCO2 and the other two noninvasive variables was clinically acceptable [2) test. P < 0.05 indicated a statistically significant difference.Data were analyzed using SPSS version 26.0. Measurement data were presented as mean ± standard deviation (SD). Pearson’s correlation coefficient and linear regression analysis were conducted to establish the correlation, and the Bland–Altman method was utilized to assess the agreement between PetCOceptable , 9 and c2, PetCO2, and PaCO2 at four time points (Table Three children were excluded from the research due to the pneumoperitoneum’s short duration (< 90 min), and 32 children  were eventually recruited. The average height and weight were 103.63 ± 11.98 cm and 17.45 ± 3.75 kg. Among them, 26 patients underwent laparoscopic pyeloplasty, and 6 patients underwent laparoscopic choledochal cyst excision. A total of 128 datasets were collected, consisting of simultaneous measurements of PtcCO2 and PaCO2 was 0.84 , and the linear regression equation was PtcCO2 = 7.89 + 0.82 × PaCO2  , and the linear regression equation was PetCO2 = 9.87 + 0.64 × PaCO2  . The 95% limits of agreement (LOA) of PtcCO2 – PaCO2 average was 0.66 ± 4.92 mmHg (mean ± 1.96 SD) . The 95% LOA of PetCO2 – PaCO2 average was –4.4 ± 4.86 mmHg (mean ± 1.96 SD) .Difference between PtcCOSD) Fig. . Differe2 is the most common gas utilized to create a pneumoperitoneum and provide a good operating view for the surgeon. However, the diffusion capacity of CO2 is strong, and the absorption of CO2 is sufficient in children due to factors such as the small volume of the abdominal cavity, the proximity of the capillaries to the peritoneum, and the larger abdominal surface area related to weight compared to adults [2 alters the body’s acid–base balance and stimulates sympathetic nerves, thus increasing catecholamine and cortisol release and leading to hemodynamic fluctuations [2 level during laparoscopic surgery and timely adjustment of the ventilator parameters is essential to avoid the disruption of physiological functions. PaCO2 levels are stabilized after 60 min of pneumoperitoneum [Since the development of minimally invasive surgery, the laparoscopic operation has gained increasingly popular in pediatric surgeries due to its advantages of less trauma, a short hospital stay, less postoperative wound pain, and fewer complications. COo adults . A risk tuations , 11. Cloritoneum ; hence, 2 is a routine measurement during the perioperative period and one of the primary indicators used to adjust ventilator parameters. However, factors that affect lung ventilation/perfusion may interfere with the accuracy of PetCO2 measurements, and thus, the use of PetCO2 in non-tracheal intubated patients is restricted. The increased abdominal pressure during laparoscopic surgery results in a diaphragmatic rise and an increase in thoracic pressure; subsequently, airway resistance and airway pressure also rise, with pulmonary vasoconstriction and reduced pulmonary blood flow. Pediatric patients are vulnerable to pneumoperitoneal pressure effects. This study revealed that during the entire monitoring process, a good correlation was established between PetCO2 and PaCO2, r = 0.83 (P < 0.01). Nevertheless, as the pneumoperitoneum time was prolonged, the correlation between PetCO2 and PaCO2 decreased gradually, which was consistent with previous findings [PetCOfindings , 9.2 monitoring in different types of surgery and patients [2 monitoring. The current results showed a close correlation between PtcCO2 and PaCO2, r = 0.84 (P < 0.01), and although the correlation was decreased with prolonged pneumoperitoneum time, it was not very significant compared to PetCO2. According to Bland–Altman analysis, a lesser mean difference was detected between PetCO2 and PaCO2 than between PetCO2 and PaCO2. Therefore, PtcCO2 performed better than PetCO2 in estimating PaCO2, which is in agreement with the previous results [2, PaCO2, and PtcCO2 to regulate the patient's acid–base, so there is no accumulation of CO2 during the whole operation. However, due to the limitations of PetCO2 monitoring, especially in the case of prolonged pneumoperitoneum, relying solely on PetCO2 to regulate the patient's respiratory parameters cannot guarantee that the patient is in acid–base balance, particularly for young children. And PtcCO2 can more accurately estimate PaCO2, so its application can reduce the risk of CO2 accumulation. Conway et al. conducted a meta-analysis on the effectiveness of PtcCO2 monitoring [2 trend throughout the monitoring process.Several clinical studies have focused on the application of PtcCOpatients –17 underpatients , 19. The results , 7, 9. Initoring  and demo2 level measured by PtcCO2 monitoring consists of two parts: one derived from the blood , and the other from the metabolism of the tissue cells [2 by opening the precapillary sphincter [2. Therefore, the PtcCO2 monitoring value is theoretically higher than that of PaCO2. PtcCO2 monitors used in clinical practice correct the initial measured value based on the selected heating temperature to reduce the deviation from PaCO2 [2 monitoring values were less than PaCO2 in 51/128 data sets; hence, the correction method for PtcCO2 monitors needs to be investigated further.The COue cells , 22. Thephincter . A rise om PaCO2 . In the 2 monitoring, including the temperature of the electrodes, the monitoring location of the sensor, and the patient’s clinical state. Nishiyama et al. demonstrated that when the anterior chest (between the clavicle and nipple) was chosen as the monitoring site, PtcCO2 correlated best with PaCO2 at 43 °C (R2 = 0.7568) among the different electrode-heating temperatures  in its setting, and the monitoring required less time to stabilize at higher temperatures as blood CO2 levels change, but required > 150 s [2 in preterm infants, the mean difference between PtcCO2 and PaCO2 was the smallest at 42 °C [2 monitoring; no adverse events were observed.Several factors affect PtcCO > 150 s . Accordiat 42 °C . A highe2 was correlated with PaCO2 when the monitoring sensor was located on the chest (R2 = 0.76) but not when it was located on the upper arm and forearm (R2 < 0.5) [2 showed a close correlation with PaCO2 than PtcCO2 before pneumoperitoneum; however, the mean difference between PtcCO2 and PaCO2 was smaller than the mean difference between PetCO2 and PaCO2. However, whether PetCO2 correlates better with PaCO2 than PtcCO2 in pediatric patients under non-pneumoperitoneal conditions with the forehead as the monitoring site needs to be studied further with a large sample size.Nishiyama et al. reported that PtcCO2 < 0.5) . When th2 produced by tissue metabolism cannot be carried away quickly, and PtcCO2 monitoring values increase gradually [2 can be utilized as one of the indicators for assessing a patient’s microcirculatory status, which is useful in guiding the treatment [2 monitoring in surgical patients with circulatory failure has been rarely reported, and the correlation between the PtcCO2 gradient changes and skin tissue perfusion status requires further clinical investigation. Other factors, such as poor skin contact with the fixed connection loop and insufficient gel, may allow contact between the probe and air, thus interfering with the monitoring results. CO2 permeability films that have not been replaced for a long time or are damaged or air bubbles under the film can also affect the accuracy of PtcCO2 monitoring.In the event that patients’ peripheral tissues and organs are not supplied adequately with blood, such as in shock, the COradually . Thus, Preatment . However2 monitoring is a continuous and noninvasive method that can be used to assess PaCO2 to some extent, its perioperative application is promoted in the different types of surgery and populations. Endotracheal intubation is not required for gastrointestinal endoscopy or other operations that can be performed using nerve blocks. The use of intravenous anesthetic medications intraoperatively can improve operating conditions and increase patient comfort during these procedures. When the nerve block is unsatisfactory, or when specific operations call for an enhanced level of sedation, supplemental narcotic medicines are required. Understanding the CO2 level of patients allows us to more precisely regulate the intravenous anesthetic medicine dosage. However, it is often difficult to accurately monitor the CO2 levels of patients during these operations. In this situation, PtcCO2 monitoring is a good choice. It has been shown [2 monitoring is an effective way to detect hypoventilation in patients, which reduces the incidence, extent, and duration of hypercapnia, improving the safety of patients under sedation. High-frequency ventilation is often used to maintain oxygenation in some airway procedures performed with a rigid bronchoscope. However, evaluating the ventilatory status of patients with PetCO2 in the open ventilation mode of high-frequency ventilation is challenging. As a result, we can adjust the parameters of high-frequency ventilation to avoid the accumulation of CO2 according to PtcCO2 [Since PtcCOen shown , 19, 28 o PtcCO2 .2 and PaCO2, and patients are more likely to develop respiratory acidosis. Oshibuchi M's study [2 can more accurately predict PaCO2 compared with PetCO2 in both two-lung ventilation and one-lung ventilation. It has been shown [2 monitoring remains highly accurate even when one-lung ventilation is prolonged (more than 2 h) and permissive hypercapnia is present.Usually, patients undergoing thoracic surgery have chronic lung diseases and require one-lung breathing in the lateral decubitus position during operation. These factors can affect lung ventilation/perfusion, leading to the increase of the difference between PetCO's study  showed ten shown  that Ptc2 monitoring effectively reflects PaCO2 levels and is more suitable for observing changes in CO2 fluctuations over time so that we can take appropriate treatment measures [2 monitoring, anesthesiologists are able to determine in time whether CO2 accumulation in patients is occurring so that the appropriate treatment can be administered.Most patients need to recover in anesthesia recovery room after surgery. Due to the presence of residual opioids and muscle relaxants, patients are at potential risk of developing respiratory depression, especially in elderly and obese patients. PtcCOmeasures . For ped2 monitoring also has some limitations. The monitoring site should be cleaned in advance to remove the hair and grease; also, the PtcCO2 monitor requires a calibration time of approximately 15 min before use and needs to be recalibrated either after the patient is removed from the monitoring site or after prolonged monitoring. When CO2 in the blood changes, PtcCO2 monitoring takes about 2 min to reflect PaCO2 with a degree of delay [2 monitor needs further improvement to facilitate its use during the perioperative period. Some studies have reported that PtcCO2 monitoring techniques are not based on electrochemical principles [2 is susceptible to various factors, it plays an essential role in determining the position of the tracheal tube, tube folding, and accidental decannulation [2 provides information about the patient’s pulmonary blood flow status and circulatory function [2 waveform, thereby deeming that PtcCO2 is not a substitute for PetCO2.PtcCOof delay . These finciples –36. Becanulation . Additiofunction , and the2 shows a close correlation with PaCO2 when the forehead is chosen as a monitoring site in children undergoing laparoscopic surgery. Compared to PetCO2, PtcCO2 can accurately estimate PaCO2 and could be used as an auxiliary monitoring indicator to optimize anesthesia management for laparoscopic surgery in children; however, it is not a substitute for PetCO2.In conclusion, PtcCOAdditional file 1.


A combination of the magnetic nanoparticles and deep eutectic solvent offers a novel, green, reusable catalyst with easy separation. Also, the catalyst structure was well characterized using techniques such as FT‐IR spectroscopy, XRD, SEM, TGA, BET, VSM, TEM, and energy‐dispersive X‐ray spectroscopy (EDS).K 2CO3/Glycerine as a deep eutectic solventK was anchored covalently onto magnetic Fe3O4@SiO2 core‐shell nanoparticles. This heterogeneous catalyst was effectively used for the selective oxidation of alcohols to corresponding carbonyl products with up to 95 % yields. Oxidation reactions, especially selective oxidation of alcohols using heterogeneous catalysts, have received growing attention and offer a green and sustainable route to value‐added chemicals.2F2/K2CO3 in DMSO, CF3SO2Na/LED, P‐doped carbon, hexachloroacetone, etc.Several different protocols and efficient methods have been suggested for oxidation reactions, especially for the selective oxidation of primary and secondary alcohols to corresponding products using a few‐layered phosphorene–graphitic carbon nitride nano heterostructure SOPerfluorinated solvents, among the used solvents for oxidative reactions, are essential due to their high oxygen solubility,According to the literature, DESs are used as a dual catalyst/solvent in organic synthesis, so they could be considered homogeneous catalysts.8b, 122CO3/Gly DES and investigate their catalytic activity for the selective oxidation of alcohols to their corresponding carbonyl compounds under mild conditions.Herein, we describe a highly economical method for the fabrication of active hybrid magnetic nanocomposites modified with K3O4 nanoparticles were synthesized in a chemical co‐precipitation method and subsequently coated with tetraethyl orthosilicate (TEOS) to obtain the Fe3O4@SiO2. Then, the Fe3O4@SiO2 was functionalized by as‐synthesized 3‐iodopropyltrimethoxysilane (IPS).In the present work, Fe2CO3‐Glycerol DES has been engrafted on the Fe3O4@SiO2/IPS nanoparticles as illustrated in Scheme K3O4@SiO2, Fe3O4@SiO2/IPS, and Fe3O4@SiO2/DES, were shown in Figure The catalyst characterization was performed using several techniques: FT‐IR spectroscopy, XRD, SEM, EDX, TGA, BET VSM, and TEM. The FTIR spectra of the Fe3O4@SiO2, the major peaks appeared around 568 cm−1 and 1085 cm−1 are respectively corresponding to Fe−O and Si−O stretching vibrations. FTIR spectra of both Fe3O4@SiO2/IPS , and the crystal structure of pure Fe3O4 remains unchanged after the immobilization of SiO2 and DES. The broad peak appearing at 21.05° is attributed to Si, which is shifted by adding a viscous DES. Similar to a previously reported sugar‐aided catalyst, this shift can be ascribed to the reflection of X‐ray arrays inside such a mucous environment after transmitting across crystalized nanoparticles Fe3O4@SiO2.The XRD pattern of the crystalline structure of the prepared Fe2 adsorption‐desorption isotherms for fresh Fe3O4@SiO2 and Fe3O4@SiO2/DES were also employed  technique as well as the differential thermal analysis (DTA). The first stage of weight loss at about 100 °C, was associated with the removal of possible solvents (organic and water) used in catalyst preparation. The second and the third steps of weight loss occurred at about 300 and 400 °C, which is the onset of the structural degradation of the DES and separation of the propyl part of the catalyst, respectively  as shown in Figure 3O4@SiO2/DES was about 5 emu ⋅ g−1 which is lower than that of Fe3O4 NPs with (about 25 emu ⋅ g−1) due to immobilization and coating with a high‐loaded DES layer as a non‐magnetic section.The magnetic properties of the Fe3O4@SiO2/DES nanoparticles were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Figures 3O4@SiO2/DES nanoparticles. According to these images, the surface morphology of the Fe3O4@SiO2/DES nanoparticles is uniform with a spherical shape. The average size of the nanoparticles was estimated at around 10 to 75 nm with a moderated degree of agglomeration, as shown in the 5 μm‐scaled SEM image. The 200‐nanometer‐scale image shows the nanoparticles being surrounded by a honey‐like mucus. For more surveys and more detailed images of the catalyst, TEM images were taken as exhibited in Figures The particle size and shape of Fe3O4@SiO2/DES nanoparticles also indicates the presence of potassium (8.9 %) and carbon (4.4 %) as two distinct elements in this DES and confirms grafting of the DES with the modified magnetic nanoparticles. Importantly, it was found that there is no iodine element in the catalyst structure demonstrating that DES anchored covalently onto functionalized magnetic nanoparticles. The low amount of the N fraction can be described as the trapped nitrogen of air inside of first DES as micro‐bubbles  spectrum of Fe3O4@SiO2/DES, the oxidation reactions were investigated. To obtain an optimum condition for different types of reactants, the amount of the catalyst, temperature, the presence or absence of solvent, and also the type of oxidants have been studied.To investigate the catalytic performance of the prepared Fe3O4@SiO2/DES as the catalyst, and hydrogen peroxide as a green oxidant. In an initial experiment, no product was observed when the mixture was heated to 80 °C for a long time in the absence of the catalyst. The reaction was then carried out in the presence of pure Fe3O4@SiO2 nanoparticles and neat DES separately and the desired product was yielded at 28 % and 32 %, respectively. Therefore, it seems that a combination of both nanoparticles and DESs contribute to the reaction progress. According to the results shown in Table 2O2 as oxidant at 60 °C.Oxidation of benzyl alcohol was carried out as a model reaction in the presence of FeSubsequently, substrate scope for the oxidation of various alcohols was investigated Table .7 a) was the aldehyde. The highest yields of these benzylic hydroxyls  were attributed to (3 a) and (4 a). It can be referred to as kinetically‐active sites of benzyl alcohols with 3‐nitro and 4‐chloro substitutes which played a crucial role in having an electron‐enriched C−H bond for oxidation. However, just substrate (3 a) converted to the corresponding carboxylic acid (10 %) besides the main product. This observation could be explained as the tendency of this alcohol to pass through a thermodynamically favorable path to produce a further oxidation product. In the case of the presence of a chlorine atom in ortho (2 a) or para (4 a) positions, the hydroxyl group tended to be oxidized to just an aldehyde. In a conclusion, it can be comprehended that if there are one or more electron‐donating groups on the phenyl ring of benzyl alcohols, the dominant product will be carboxylic acids besides its aldehydes (5 a and 7 a). By raising the number of electron‐donating groups on the phenyl ring of benzylic alcohol, the fraction of carboxylic acid to aldehyde becomes larger until it takes over one in OMe (5 a) with two methoxy substitutes (7 a). In 3,4‐dimethoxy benzyl alcohol (7 a), the main product was the corresponding carboxylic acid, which may be due to the presence of two strong electron‐donating substitutes in the meta and para positions. From a different viewpoint, either with or without a nitro group as an electron‐withdrawing substituent, the partial (10 %) oxidized carboxylic acid cannot be omitted. The secondary alcohol containing two aryl groups (6 a) afforded a 10 % yield under the optimized conditions.The dominant product in all cases, except for 3,4‐dimethoxy benzyl alcohol (10 a). Isopropyl alcohol (11 a) as secondary alcohol converted to the corresponding ketone in a longer reaction time with an overall 10 % yield. Diethanolamine (12 a) was not efficiently converted into the desired product. When 2‐hydroxyacetic acid (13 a) was treated under optimized conditions, oxalic acid was formed with a 73 % yield, accompanied by the formation of the corresponding aldehyde (25 %). Primary aliphatic alcohol (14 a) was oxidized more efficiently and the desired aldehyde was obtained in good yield (64 %) along with a moderate yield (32 %) of over oxidation product.Next, the catalytic oxidation of aliphatic alcohols was surveyed, and the highest conversion (95 %) was observed for butanol (2CO3/Gly) forms a simple hydrogen bond with H2O2 providing complex‐I. Then, the activation occurs with the external proton of complex‐I to make complex‐II. Next, the OOH anion attacks the activated intermediate, and subsequently the benzyl hydroperoxide intermediate forms with the removal of H2O. Finally, the last intermediate undergoes deprotonation by basic media, and eventually, the product obtains with again removal of H2O.According to the literature, the exact mechanism of the reaction is unclear.The reusability of the prepared nanoparticles from the reaction medium was investigated. After the completion of the model reaction, the catalyst was separated by an external magnet and washed several times with water then dried at 80 °C for 24 h and used for the next run. The catalyst was reused three times without any significant loss of catalytic activity.2CO3‐Gly to the modified magnetic nanoparticles as a green and efficient catalyst. The free‐metal catalytic oxidation of secondary and primary alcohols provides the corresponding carbonyl products and carboxylic acids, respectively, in good to high yields. Therefore, the unique design of Fe3O4@SiO2/IPS‐ K2CO3/Gly nanoparticles using earth‐abundant and inexpensive materials may offer an innovative approach for the exploration of highly active and stable heterogeneous catalysts for diverse catalytic applications.In summary, we have developed a highly economical method for oxidation of alcohols to corresponding carbonyl products using the anchored K−1 using spectroscopic‐grade and pure KBr. Powder X‐ray diffraction (XRD) patterns were recorded at room temperature with a Philips X‐Pert 1710 diffractometer using Co Kα radiation (λ=1.78897 Å) at a voltage of 40 kV and current of 40 mA to study the crystalline structure of the nanocatalyst, data were recorded from 10° to 80° (2θ) with the scan speed of 0.05° s−1. The morphology of nanoparticles was studied using Scanning Electron Microscopy  equipped with Energy‐Dispersive X‐ray (EDX) spectroscopy. Transmission Electron Microscopy (TEM) images were obtained using a CM120 apparatus with an accelerating voltage of 100 kV.The solvents and starting materials were purchased from Merck (Germany) and Sigma‐Aldrich (USA). Fourier Transform Infrared (FT‐IR) spectra of the prepared samples were recorded on a Thermo AVATAR FT‐IR spectrometer in the wavenumber range of 400–4000 cmm). The mixture was refluxed under argon flow for 24 h. To purify this activated organic linker, NaCl was removed by centrifugation, and the filtrate has been allowed to be dried. The yellow residue was dissolved in dichloromethane, filtered, and gradually evaporated to obtain the pure yellowish IPS.The IPS was prepared according to the procedure reported by Tavakol.3O4 nanoparticles were prepared through the co‐precipitation approach. Next silica shell formed on the outer layer of Fe3O4 MNPs using tetraethyl orthosilicate (TEOS) reagent in a basic aqueous medium with a pH of around 11.3O4@SiO2 nanoparticles are coated with IPS to obtain IPS‐functionalized Fe3O4@SiO2 (Fe3O4@SiO2/IPS) similar to Tavakol's method.3O4@SiO2 (1 g) was completely dispersed in 10 mL ethanol. In the next step, 4 mL IPS was added to the above mixture under stirring at 60 °C for about 8 h. The resulting precipitate was isolated from the reaction mixture by a magnet and cooled down. The final brown solid was washed several times with cold distilled water (4 °C) and acetone and dried to achieve the Fe3O4@SiO2/IPS.For this step, Fe2CO3‐Glycerol DES was prepared based on previous literature.2CO3 and the Glycerol were mixed with a molar ratio of 1 : 10 in a round‐bottomed flask. The reaction temperature reached 80 °C under vigorous stirring for about 15 min.The K3O4@SiO2/IPS (0.1 g) and K2CO3‐Glycerol DES (2 g) were mixed in a 50 mL round‐bottomed flask, and the suspension was stirred for 18 h at 90 °C. The reaction mixture was then cooled down to room temperature. The resulting precipitate was separated using an external magnet, washed five times with distilled water, chloromethane, and acetone, and dried to afford the final catalyst (Fe3O4@SiO2/DES).Based on the reported Tavakol's group technique,2O2 (3 mmol) was added Fe3O4@SiO2/DES (50 mg) as the catalyst under free solvent and the resulting mixture was stirred at 60 °C until the reaction was complete, as monitored by TLC. After an appropriate time, the used nanocatalyst was separated from the reaction media and recovered. After an organic‐aqueous work‐up, the reaction mixture was injected into GC for an accurate analysis of the products.To the mixture of benzyl alcohol (1 mmol) and HThe authors declare no conflict of interest.1


Here, we first obtain phase‐pure, colloidally stable nanocubes. Second, we elucidate the pathway by which copper(II) nitrate and oleylamine form Cu3N. We find that oleylamine is both a reductant and a nitrogen source. Oleylamine is oxidized by nitrate to a primary aldimine, which reacts further with excess oleylamine to a secondary aldimine, eliminating ammonia. Ammonia reacts with CuI to form Cu3N. Third, we investigated the surface chemistry and find a mixed ligand shell of aliphatic amines and carboxylates (formed in situ). While the carboxylates appear tightly bound, the amines are easily desorbed from the surface. Finally, we show that doping with palladium decreases the band gap and the material becomes semi‐metallic. These results bring insight into the chemistry of metal nitrides and might help the development of other metal nitride nanocrystals.The precursor conversion chemistry and surface chemistry of Cu 3N and Cu3PdN were obtained. The precursor conversion mechanism is elucidated; oleylamine is oxidized to a primary aldimine and the latter reacts further with oleylamine to a secondary aldimine, eliminating ammonia. Ammonia reacts with CuI to form Cu3N.Phase‐pure, colloidally stable Cu Upon doping, the lattice constant increases,Metal nitrides are a versatile class of materials with increasing interest.tructure.2, 5 T3N forms at relatively low temperature but decomposes at higher temperature (475 °C) to metallic copper (under inert atmosphere) or copper oxide (in air).[3N powders were based on aminolysis or the solvothermal decomposition of copper azides.[3N have been synthesized from Cu(OMe)2 in benzylamine,I in pyridine.3N nanocubes have been obtained from copper nitrate and alkylamine (Scheme Bulk Cu(in air).3, 8 Te Scheme .[4a, II is first fully reduced to Cu0 and subsequently reacts with dinitrogen (a possible decomposition product of the nitrate complex).−1),2 is thus not likely to react with elemental copper at 250 °C. There is currently insufficient evidence to claim a mechanism for the precursor conversion. Regarding the crystallization mechanism, it was shown that first small, amorphous particles form, which subsequently ripen into Cu3N nanocubes.Unfortunately, the reaction mechanism and the by‐products are not well established. Some authors claim that nitrate is the nitrogen source, and thus nitrogen is supposed to be reduced from its highest oxidation state in nitrate to its lowest oxidation state in nitride, and this process is presumably catalyzed by the amine ligand.3N nanocrystals is also unknown. Although alkylamines are the only ligand present during the synthesis, there are several examples where the ligands can convert to other ligands during nanocrystal synthesis, leading to surprising surface chemistries.3N nanocrystals have generally poor colloidal stability after purification.The surface chemistry of Cu3N (and Cu3PdN) nanocrystals, synthesized from copper nitrate . We first screened the different synthetic methods in the literature, and found the report of Vaughn et al. as the most reproducible.[3N nanocubes, we then redesigned the purification procedure to yield colloidally stable Cu3N nanocrystals. We uncovered the precursor conversion mechanism of the reaction. We found that nitrate and CuII both oxidize alkylamine to a primary aldimine, forming also CuI. Condensation of the primary aldimine with a second equivalent alkylamine, yields a secondary aldimine and ammonia. The latter is the active nitrogen precursor and reacts with CuI to Cu3N. Finally, the surface of these Cu3N and Cu3PdN particles has been analyzed. X‐ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared spectroscopy (FTIR) established the presence of carboxylate ligands on the surface, together with amine ligands. Advanced nuclear magnetic resonance (NMR) spectroscopy revealed the dynamics of ligands binding. These fundamental chemistry insights will enable the elucidation of formation mechanisms of other copper‐based colloidal nanocrystals and other metal nitrides.In this work, we aimed at elucidating the precursor conversion mechanism and surface chemistry of Cuoducible.19 We th3N was formed between 220 °C and 260 °C (after 15 minutes), with the highest crystallinity for 260 °C . Interestingly, the crystallite size was found to be quite independent of the reaction temperature; 10–11 nm according to the Scherrer analysis of the powder XRD (X‐ray diffraction) reflections. At 200 °C, no particles could be isolated. Furthermore, we took reaction aliquots at 5, 10, 15, 30, and 60 min at 240 °C and 260 °C. Each aliquot was purified and analyzed by transmission electron microscopy (TEM) to observe the nanocrystal growth throughout the reaction. At 240 °C, we observed both small dots and fully formed nanocubes up to 15 min of reaction time . The small particles presumably ripen in the bigger nanocubes since the former disappear at 30 min. After 60 minutes at 240 °C, the XRD showed pure Cu3N. By comparison, at 260 °C, the nanocubes were already fully formed after 15 min. After 30 min at 260 °C, the particles started to decompose and crystalline Cu0 was formed. Some Cu2O could also be detected as a minority phase after full decomposition. .We decided to optimize the procedure reported by Vaughn et al. by exploring the influence of different parameters.3N nanocrystals when the vacuum steps were omitted, or, when after applying vacuum (presumably removing water), 13 μL of water was injected into the reaction mixture . However, the same reaction in an open flask did not yield Cu3N , indicating that an important gaseous intermediate can escape from the reaction mixture. To work under controlled and reproducible conditions, we still choose to perform a short (30 min) degassing step at 50 °C, but it appears that the synthesis is robust against air or water contamination. We also found that both 30 and 60 equivalents of amine ligands yielded Cu3N nanocrystals . Based on the above optimization, we arrived at the conditions in Scheme The reported procedure has two steps where vacuum is applied. This leads us to investigate the role of water and whether an inert atmosphere is strictly necessary. Note that the precursor contains water . We obtained identical Cu−1) of oleylamine‐capped Cu3N nanocrystals .After applying the reported precipitation‐and‐redispersion cycles (with ethanol and toluene),3PdN) nanocrystals were also synthesized. The procedure was identical to that of Cu3N, except for the reaction temperature (240 °C) and the addition of 0.33 equivalents of palladium(II) acetylacetonate, alongside the Cu(NO3)2. The doped nanocrystals were purified with the optimized purification method. The synthesis yielded black nanoparticles that were colloidally stable (13 mg mL−1). According to TGA, ligands make up 13.22 w% of the dried mass (assuming perfect Cu3PdN stoichiometry) and the Cu3PdN yield is 91 % .Copper palladium nitride   for the Cu3N nanocubes and 10.2 nm (σ=1.4 nm) for the Cu3PdN nanocrystals. The solvodynamic diameter obtained from DLS analysis were 17 nm for Cu3N and 13 nm for Cu3PdN. The sizes obtained via DLS are in line with the sizes obtained via TEM since DLS determines the solvodynamic size of the whole particle, including the surface ligands. Both TEM and DLS support that the dispersions are highly stable since no aggregates are observed. XRD shows quite sharp reflections for Cu3N , while they are broader for Cu3PdN . Compared with the sizes obtained from TEM, it is clear that the Cu3PdN nanocrystals are polycrystalline. A real space refinement of the Pair Distribution Function further confirms the structure of Cu3N and Cu3PdN .The final dispersions of Cu) Figure . AccordiI to Cu3N, releasing three protons. The CuI species was generated by reduction of CuII by oleylamine upon heating. Cyclic voltammetry confirms a lower reduction potential of CuII to CuI upon addition of oleylamine (at room temperature).II reduction is the same primary aldimine as mentioned before.Regarding the precursor conversion mechanism, we found the proposed pathways in literature implausible and therefore proposed an alternative hypothesis in which the active nitride source is ammonia, see Scheme 3)2⋅3 H2O, does not dissolve in the solvent (hexadecane) until oleylamine is added, indicating the formation of a coordination complex. This is supported by the deep blue color of the reaction mixture, typical for CuII coordinated by amines.II to CuI. Concomitant with the color change, new resonances appear in the 1H NMR spectrum of the reaction mixture , and we observe in the 1H NMR spectrum a significant increase in the aldimine concentration . Given that the reaction is executed at a scale of 0.24 mmol Cu, and assuming that every nitrate (0.48 mmol) oxidizes one oleylamine molecule, this is the expected amount of ammonia . We can also quantify the aldimine formation by using the alkene resonance of oleylamine as the internal standard. For every aldimine, we find 18 oleyl chains, indicating a conversion of 5.5 %. Given that 7.6 mmol oleylamine was used, this amounts to 0.42 mmol aldimine. This value is in reasonable agreement with the amount of ammonia detected (taking into account the error on the ammonia measurement and the fact that oleylamine is only 70 % pure). This quantitative picture thus confirms our hypothesis and indicates a one‐to‐one stoichiometry between nitrate, aldimine, and ammonia. We did not obtain Cu3N in this experiment since we removed ammonia from the reaction mixture. This indicates that ammonia is essential in nitride formation. Literature shows that ammonia indeed reacts with copper salts to Cu3N.[Ammonia is detected in the reaction mixture by bubbling Ar through the reaction mixture during synthesis, and dissolving the gasses in either 40 mL or 80 mL water. A commercial ammonia test kit indicates a concentration of 200 mg L to Cu3N.11, 25II to CuI. This value is about half of the copper amount (0.24 mmol) and can be easily rationalized based on electron counting in the redox reactions. Indeed, the reduction of CuII to CuI is a one‐electron process while the oxidation of primary amine to aldimine is a two‐electron process  generated during the reduction of Cumount 0.2 mmol andmount 0.2 mmol and3N with dioctylamine and trioctylamine. As expected, the reaction did not produce Cu3N but Cu2O instead . This control experiment suggests that our proposed pathway—CuI reacting with in situ produced ammonia—is plausible.Our proposed pathway requires a primary amine. To further test our hypothesis, we thus attempted the synthesis of Cud Figure . Also in3N but rather oxidizes the amine to aldimine. Cu3PdN nanocrystals follows the same mechanism based on the formation of aldimine and ammonia during the reaction . The mechanism is reminiscent of the one for InN, where In3+ oxidizes primary amines into aldimine and nucleophilic attack of lithium oleylamide generates amide, NH2−.2+ alone does not seem to generate sufficient ammonia to form copper nitride since other copper salts do not generate copper nitride.3N is not yet favored. More detailed insight into the crystallization mechanism of Cu3N could shed light on this issue.We thus firmly established that nitrate is not the nitrogen source for Cup3/2 core level (932.7±0.1 eV) is commensurate with the expected CuI oxidation state for both samples , the contribution of these additional chemical states relative to the main CuI line is 12.3±0.5 rel. at.% for Cu3N and 17.9±0.5 rel.at.% for Cu3PdN, respectively. The Pd 3d core level  is commensurate with Pd0 or PdI with a spin‐orbit‐splitting of the doublet of 14.6 eV. In both samples, the N 1s core level . Oleate is most likely formed by oxidation of oleylamine by nitrate, as we reported earlier in the synthesis of cerium oxide nanocrystals.X‐ray photoelectron spectroscopy (XPS) was used to explore the surface chemistry. Survey spectra for both compounds  show spectral signatures from all expected elements. In addition, a small amount of Si was detected most likely from the silicone grease used during the synthesis. The binding energy (BE) position of the main feature in the Cu 2s Figure A. In adds Figure A and in 1H NMR spectra of Cu3N and Cu3PdN show the typical signature of an oleyl chain  determined by pulsed field gradient experiments on the Cu3N dispersion . For Cu3PdN, we noticed a second, very broad alkene resonance of low intensity underneath the sharp signal. A careful pulsed field gradient experiment revealed that the alkene resonance is a superposition of two species, one diffusing with D=48 μm2 s−1 and the other one with D=667 μm2 s−1  calculations. The experimental and theoretical results for Cu3N agree very well. The projected density of states calculations  show that the valence band of Cu3N is dominated by Cu 3d states with only minor mixing of Cu 3p states and minimal nitrogen contributions. The valence band maximum (VBM) position of Cu3N is 0.55±0.05 eV from the Fermi energy EF. In comparison, the valence spectrum of Cu3PdN shows additional intensity towards the EF from Pd states closing the VBM‐EF gap. In parallel, UV/Vis has been used to determine the optical band gap of the particles. An indirect band gap has been reported for Cu3N thin films according to theoretical band structure calculations.3PdN. In this work, we assumed an indirect optical band gap for both samples. A Tauc plot analysis resulted in an optical band gap of 1.4±0.1 eV and 0.2±0.1 eV for our Cu3N and Cu3PdN NCs, respectively , oxidized by both CuII, and nitrate. Nucleophilic addition and elimination of a second oleylamine molecule onto the primary aldimine released ammonia, which subsequently reacted with CuI to form Cu3N and Cu3PdN. The surface of the nanocrystals was capped by a mixture of oleylamine and oleate. The latter was formed in situ from the further oxidation of aldimine. The addition of palladium to copper nitride reduces the optical band gap as well as the separation between the valence band maximum (VBM) and Fermi energy EF.In conclusion, we successfully optimized the synthesis of CuThe 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.