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Deuteration of amine compounds has been widely of concern because of its practical role in organic reaction mechanisms and drug research; however, only limited deuteration label methods are accessible with D 2 O as a deuterium source. Herein, we propose a convenient deuteration protocol, including preparing D 2 by the AlGa activation method, using PtRu nanowires as catalysts, and utilizing the elementary step in the couple reaction involving an imine unit, to realize the rapid preparation of a secondary amine with a diversified deuteration label. The self-coupling between nitriles not only provides a symmetric secondary amine with four α-D atoms but also produces high-valued ND 3 in an atomic-economic way.

We explore Riemannian optimization methods for Restricted-Open-shell Hartree-Fock (ROHF) and Complete Active Space Self-Consistent Field (CASSCF) methods. After showing that ROHF and CASSCF can be reformulated as optimization problems on so-called "flag manifolds", we review Riemannian optimization basics and their application to these specific problems. We compare these methods to traditional ones and find robust convergence properties without fine-tuning of numerical parameters. Our study suggests that Riemannian optimization is a valuable addition to orbital optimization for ROHF and CASSCF, warranting further investigation.

A method for the construction of trifluorinated-5-methylenepyrrolidinone is reported. This strategy combines an acid-catalyzed two-carbon homologation process between ynamides and aldehydes, providing CF 3 -substituted dienes followed by a metal-free domino hydroamination/isomerization/transamidation sequence, delivering trifluorinated-5-methylenepyrrolidinone stereoselectively.

Alzheimer's disease is a progressive neurodegenerative disorder that significantly contributes to dementia. The lack of effective therapeutic interventions presents a significant challenge to global health. We have developed a set of short peptides (PN Gln ) conjugated with a dual-functional fluorophoric amino acid (N Gln ). The lead peptide, P2N Gln , displays a high affinity for Cu 2+ , maintaining the metal ion in a redox-inactive state. This mitigates the cytotoxicity generated by reactive oxygen species (ROS), which are produced by Cu 2+ under the reductive conditions of Asc and Aβ 16 or Aβ 42 . Furthermore, P2N Gln inhibits both Cu-dependent and -independent fibrillation of Aβ 42 , along with the subsequent toxicity induced by Aβ 42 . In addition, P2N Gln exhibits inhibitory effects on the production of lipopolysaccharide (LPS)-induced ROS and reactive nitrogen species (RNS) in microglial cells. In vitro and cellular studies indicate that P2N Gln could significantly reduce Aβ-Cu 2+ -induced ROS production, amyloid toxicity, and neuroinflammation, offering an innovative strategy against Alzheimer's disease., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Zwitterionic thiolate ligands have the potential to introduce novel assembly modes and functions for noble metal clusters. However, their utilization in the synthesis of silver clusters remains understudied, particularly for the clusters containing reductive Ag(0) species. In this article, we report the first synthesis of a mixed-valence silver(0/I) cluster protected by zwitterionic Tab as thiolate ligands (Tab = 4-(trimethylammonio)benzenethiolate), denoted as [Ag 22 (Tab) 24 ](PF 6 ) 20 ·16CH 3 OH·6Et 2 O ( Ag 22 ·16CH 3 OH·6Et 2 O), alongside an Ag(I) cluster [Ag 20 (Tab) 12 (PhCOO) 10 (MeCN) 2 (H 2 O)](PF 6 ) 10 ·11MeCN ( Ag 20 ·11MeCN). Ag 22 has a distinct hierarchical supratetrahedral structure with a central {Ag 6 } kernel surrounded by four [Ag 4 (Tab) 6 ] 4+ units. High-resolution electrospray ionization mass spectra demonstrate that Ag 22 has two free electrons, indicating a superatomic core. Ag 20 has a drum-like [Ag 12 (Tab) 6 (PhCOO) 6 (H 2 O)] 6+ inner core capped by two tetrahedral-like [Ag 4 (Tab) 3 (PhCOO) 2 (MeCN)] 2+ units. Ag 20 can be transformed into Ag 22 after its reaction with NaBH 4 in solution. Antibacterial measurements reveal that Ag 22 has a significantly lower minimum inhibitory concentration than that of the Ag 20 cluster. This work not only extends the stabilization of silver(0/I) clusters to neutral thiol ligands but also offers new materials for the development of novel antibacterial materials.

Coarse-grained (CG) molecular dynamics (MD) simulations have grown in applicability over the years. The recently released version of the Martini CG force field (Martini 3) has been successfully applied to simulate many processes, including protein-ligand binding. However, the current ligand parametrization scheme is manual and requires an a priori reference all-atom (AA) simulation for benchmarking. For systems with suboptimal AA parameters, which are often unknown, this translates into a CG model that does not reproduce the true dynamical behavior of the underlying molecule. Here, we present Bartender, a quantum mechanics (QM)/MD-based parametrization tool written in Go. Bartender harnesses the power of QM simulations and produces reasonable bonded terms for Martini 3 CG models of small molecules in an efficient and user-friendly manner. For small, ring-like molecules, Bartender generates models whose properties are indistinguishable from the human-made models. For more complex, drug-like ligands, it is able to fit functional forms beyond simple harmonic dihedrals and thus better captures their dynamical behavior. Bartender has the power to both increase the efficiency and the accuracy of Martini 3-based high-throughput applications by producing numerically stable and physically realistic CG models.

The ultrafast nonadiabatic excited state dynamics of (PTZ-N-benzyl-acetylide) ( trans -bis-trimethylphosphine) Pt(II) (acetylide-NDI-bis-methyl) 1 , representative of a series of Pt(II) donor-bridge-acceptor assemblies experimentally studied by the Weinstein group, University of Sheffield, is investigated by means of wavepacket propagations based on the multiconfiguration time-dependent Hartree (MCTDH) method. On the basis of electronic structure data obtained at the time-dependent density functional theory (TD-DFT) level, the subpicosecond decay is simulated by solving an 11 electronic states multimode problem, up to 18 vibrational normal modes, including both spin-orbit coupling (SOC) and vibronic coupling. A careful analysis of the results, within the diabatic representation, provides the key features of the spin-vibronic mechanism at work in this complex, distinguishing between the spin-orbit and vibronically activated ultrafast processes within the excited states manifold. The knowledge of the key active normal modes that promote selectively the population of specific electronic excited states opens a route toward optical control by selectively exciting these modes in order to drive the associated nonadiabatic processes. Relevant simulations, over 2 ps, are proposed to assess the impact of these selective vibrational excitations on the branching ratio between the primary photoproducts, namely, bridge-acceptor charge-transfer (CT) and donor-acceptor charge-separated (CS) electronic states. Whereas the excitation of the localized acetylide bridge C≡C bond stretching does not modify drastically the population of the low-lying electronic states within the first two ps, vibrational excitation of the out-of-plane twisting motion of the N-benzyl group linked to the donor entity favors the population of the 1,3 CS states at the expense of the lowest 1,3 CT states. This quantum study opens the route to IR optical control experiments based on the specific alteration of vibrational normal modes that activate vibronic couplings between key electronic excited states. However, the presence of critical crossings along the PES channels associated with these normal modes and the role of concurrent SOC driven ultrafast transfers of population should not be underestimated.

We report the synthesis and structural characterization of a 2D metal-organic framework with AB-packing layers, [Co 2 (pybz) 2 (CH 3 COO) 2 ]·DMF ( Co2 , pybz= 4-(4-pyridyl)benzoate), containing a stable (4,4)-grid network fabricated by paddle-wheel nodes, ditopic pybz, and acetate ligands. After removal of the guest, the layer structure is retained but reorganized into an ABCD packing mode in the activated phase ( Co2a ). Consequently, the intralayer square windows (7.2 × 5.0 Å 2 ) close, while the interlayer separation is decreased slightly from 3.69 to 3.45 Å, leaving a narrow gap. Importantly, the dangling methyl group of the acetate with H-bonds to the adjacent layers and also the well-distributed π-π interactions between the aromatic rings of neighboring layers facilitate the structural stability. These weak supramolecular interactions further allow for favorable dynamic exfoliation of the layers, which promotes efficient adsorption of C 2 H 2 (41.6 cm 3 g -1 ) over CO 2 with an adsorption ratio of 6.3 (0.5 bar, 298 K). The effective separation performance of equimolar C 2 H 2 /CO 2 was verified by cycling breakthrough experiments and was even tolerable to moisture (R.H = 52%). DFT calculations, in situ PXRD, and PDF characterization reveal that the favorable retention of C 2 H 2 rather than that of CO 2 is due to its H-bond formation with the paddle-wheel oxygen atoms that triggers the increase in interlayer separation during C 2 H 2 adsorption.

Finding collective variables to describe some important coarse-grained information on physical systems, in particular metastable states, remains a key issue in molecular dynamics. Recently, machine learning techniques have been intensively used to complement and possibly bypass expert knowledge in order to construct collective variables. Our focus here is on neural network approaches based on autoencoders. We study some relevant mathematical properties of the loss function considered for training autoencoders and provide physical interpretations based on conditional variances and minimum energy paths. We also consider various extensions in order to better describe physical systems, by incorporating more information on transition states at saddle points, and/or allowing for multiple decoders in order to describe several transition paths. Our results are illustrated on toy two-dimensional systems and on alanine dipeptide.

Three new ligands based on the alloxazine core appended with pyridyl coordinating groups have been designed, synthesized, and characterized. The ligands are revealed to be redox-active in DMF solution, as attested to by CV and combined CV/EPR studies. The spin of the reduced species appears to be delocalized on the alloxazine core, as attested to by DFT calculations. The coordination abilities of one of the ligands toward Cu 2+ or Ni 2+ 3d cations revealed the formation of the first alloxazine-based 3D coordination polymers, presenting strong π-π stacking and substantial cavities. Preliminarily charge/discharge experiments in Li batteries evidence Li + insertion in such systems.

The mechanism of isomerization of the known 2-phenyl,pyridine ( phpy ) derivatives [Ru( phpy -κC,N) (MeCN -trans- N)( terpy )]PF 6 , 2 , to [Ru( phpy -κC,N)(MeCN -trans- C)( terpy )]PF 6 ( terpy = 2,2';6',2″-terpyridine), 3 , at temperatures >50 °C has been investigated both by 1 H NMR spectroscopy and by DFT calculations. The photoisomerization of 2 to 3 by UV light occurred also quantitatively in MeCN after 20 h at room temperature. A similar behavior to that of 2 could be established for the related compound [Ru(3-acridine-2'-C 5 H 4 N-κC,N)(MeCN -trans- N)(2,2';6',2″-terpyridine)]PF 6 , 6 (acridine = dibenzo[ b , e ]pyridine or 2,3-benzoquinoline), that was obtained from the reaction between [Ru(3-acridine-2'-C 5 H 4 N-κC,N) (MeCN) 4 ]PF 6 , 4 , and terpy in MeOH/MeCN at 60 °C for 24 h. Similar to 2 , the isomerization of 6 to [Ru(3-acridine-2'-C 5 H 4 N-κC,N)(MeCN -trans- C) ( terpy )]PF 6 , 7 , could be induced thermally (48 h at 60 °C in pure MeOH) or photochemically under UV radiation in MeCN at room temperature. A compound closely related to 7 but in which MeCN was replaced by H 2 O was described earlier (Tanaka et al. Inorg. Chem. 2012 , 51, 5386-539). The presence of water on this compound had a dramatic effect as far as the coordination of terpy was concerned as its isomerization to a compound related to 6 (in which H 2 O instead of MeCN is coordinated to Ru) occurred indeed photochemically via irradiation with visible light.

The structure, bonding, and properties of a series of atypical pentanuclear nickel hydride clusters supported by electron-rich i Pr 3 P of the type [( i Pr 3 P)Ni] 5 H n ( n = 4, 6, 8; H 4 , H 6 , H 8 ) and their anionic models where i Pr 3 P are substituted by H - ( H 4 ' , H 6 ' , H 8 ' ) were investigated by density functional theory (DFT) calculations. All clusters were calculated to adopt a similar square pyramidal core geometry. Calculations indicate singlet ground states with small singlet-triplet gaps for H 4 and H 6 , similar to previously reported experimental values. Molecular orbital theory description clusters were investigated using the simplified model complexes [HNi] 5 H n 5- ( n = 4, 6, 8; H 4 ' , H 6 ' , H 8 ' ). The results show that there are three skeletal electron pairs (SEPs) in H 4 ' . The addition of two molecules of H 2 to form H 6 ' and H 8 ' results in the partial or full occupation of two degenerate MOs ( e* set) that give two SEPs and one SEP, respectively. Indeed, the occupation of these low-lying weakly antibonding orbitals governs the multielectron chemistry available for these clusters and plays a role in their unique reactivity.

Eugenol and isoeugenol are well acknowledged to possess antioxidant and thus cytoprotective activities. Yet both compounds are also important skin sensitizers, compelling the cosmetics and fragrance industries to notify their presence in manufactured products. While they are structurally very similar, they show significant differences in their sensitization properties. Consequently, eugenol and isoeugenol have been the subject of many mechanistic studies where the final oxidation forms, electrophilic ortho -quinone and quinone methide, are blamed as the reactive species forming an antigenic complex with nucleophilic residues of skin proteins, inducing skin sensitization. However, radical mechanisms could compete with such an electrophilic-nucleophilic pathway. The antioxidant activity results from neutralizing reactive oxygen radicals by the release of the phenolic hydrogen atom. The so-formed phenoxyl radicals can then fully delocalize upon the structure, becoming potentially reactive toward skin proteins at several positions. To obtain in-depth insights into such reactivity, we investigated in situ the formation of radicals from eugenol and isoeugenol using electron paramagnetic resonance combined with spin trapping in reconstructed human epidermis (RHE), mimicking human skin and closer to what may happen in vivo . Two modes of radical initiation were used, exposing RHE to (i) horseradish peroxidase (HRP), complementing RHE metabolic capacities, and mimicking peroxidases present in vivo or (ii) solar light using a AM 1.5 solar simulator. In both experimental approaches, where the antioxidant character of both compounds is revealed, oxygen- and carbon-centered radicals were formed in RHE. Our hypothesis is that such carbon radicals are relevant candidates to form antigenic entities prior to conversion into electrophilic quinones. On this basis, these studies suggest that pro- or prehapten fingerprints could be advanced depending on the radical initiation method. The introduction of HRP suggested that eugenol and isoeugenol behave as prohaptens, while when exposed to light, a prehapten nature could be highlighted.

Trifluoromethyl analogues of methylerythritol phosphate (MEP) and 2- C -methyl-erythritol 2,4-cyclodiphosphate (MEcPP), natural substrates of key enzymes from the MEP pathway, were prepared starting from d-glucose as the chiral template to secure absolute configurations. The obligate trifluoromethyl group was inserted with complete diastereoselectivity using the Ruppert-Prakash nucleophile. Target compounds were assayed against the corresponding enzymes showing that trifluoro-MEP did not disrupt IspD activity, whereas trifluoro-MEcPP induced 40% inhibition of IspG at 1 mM.

This Letter introduces the so-called Quasi Time-Reversible scheme based on Grassmann extrapolation (QTR G-Ext) of density matrices for an accurate calculation of initial guesses in Born-Oppenheimer Molecular Dynamics (BOMD) simulations. The method shows excellent results on four large molecular systems that are representative of real-life production applications, ranging from 21 to 94 atoms simulated with Kohn-Sham (KS) density functional theory surrounded with a classical environment with 6k to 16k atoms. Namely, it clearly reduces the number of self-consistent field iterations while at the same time achieving energy-conserving simulations, resulting in a considerable speed-up of BOMD simulations even when tight convergence of the KS equations is required.

The assembly of a [2]semirotaxane from a half-dumbbell endowed with a pyrazine coordination site and a bis-Zn(II) porphyrin cage as a multisite ring is reported. The threading is allosterically driven by the coordination of silver(I) ions to the multiple binding sites of the cage linkers, as shown by NMR studies. Addition of chloride ions destabilizes [2]semirotaxane, leading to its disassembly into its cage and half-dumbbell components.

A rare example of pyrimidine-based ESIPT-capable compounds, 2-(2-hydroxyphenyl)-4-(1 H -pyrazol-1-yl)-6-methylpyrimidine ( HL H ), was synthesized (ESIPT─excited state intramolecular proton transfer). Its reactions with zinc(II) salts under basic or acidic conditions afforded a dinuclear [Zn 2 L H 2 Cl 2 ] complex and an ionic (H 2 L H ) 4 [ZnCl 4 ] 2 ·3H 2 O solid. Another ionic solid, (H 2 L H )Br , was obtained from the solution of HL H acidified with HBr. In both ionic solids, the H + ion protonates the same pyrimidinic N atom that accepts the O-H···N intramolecular hydrogen bond in the structure of free HL H , which breaks this hydrogen bond and switches off ESIPT in these compounds. This series of compounds which includes neutral HL H molecules and ionic ( L H ) - and ( H 2 L H ) + species allowed us to elucidate the impact of protonation and coordination coupled deprotonation of HL H on the photoluminescence response and on altering the emission mechanism. The neutral HL H compound exhibits yellow emission as a result of the coexistence of two radiative decay channels: (i) T 1 → S 0 phosphorescence of the enol form and (ii) anti-Kasha S 2 → S 0 fluorescence of the keto form, which if feasible due to the large S 2 -S 1 energy gap. However, owing to the efficient nonradiative decay through an energetically favorable conical intersection, the photoluminescence quantum yield of HL H is low. Protonation or deprotonation of the HL H ligand results in the significant blue-shift of the emission bands by more than 100 nm and boosts the quantum efficiency up to ca. 20% in the case of [Zn 2 L H 2 Cl 2 ] and (H 2 L H ) 4 [ZnCl 4 ] 2 ·3H 2 O . Despite both (H 2 L H ) 4 [ZnCl 4 ] 2 ·3H 2 O and (H 2 L H )Br have the same ( H 2 L H ) + cation in the structures, their emission properties differ significantly, whereas (H 2 L H )Br shows dual emission associated with two radiative decay channels: (i) S 1 → S 0 fluorescence and (ii) T 1 → S 0 phosphorescence, (H 2 L H ) 4 [ZnCl 4 ] 2 ·3H 2 O exhibits only fluorescence. This difference in the emission properties can be associated with the external heavy atom effect in (H 2 L H )Br , which leads to faster intersystem crossing in this compound. Finally, a huge increase in the intensity of the phosphorescence of (H 2 L H )Br on cooling leads to pronounced luminescence thermochromism (violet emission at 300 K, sky-blue emission at 77 K).

This study introduces a new de novo design algorithm called GENERA that combines the capabilities of a deep-learning algorithm for automated drug-like analogue design, called DeLA-Drug , with a genetic algorithm for generating molecules with desired target-oriented properties. Specifically, GENERA was applied to the angiotensin-converting enzyme 2 (ACE2) target, which is implicated in many pathological conditions, including COVID-19. The ability of GENERA to de novo design promising candidates for a specific target was assessed using two docking programs, PLANTS and GLIDE. A fitness function based on the Pareto dominance resulting from computed PLANTS and GLIDE scores was applied to demonstrate the algorithm's ability to perform multiobjective optimizations effectively. GENERA can quickly generate focused libraries that produce better scores compared to a starting set of known ACE-2 binders. This study is the first to utilize a DL-based algorithm designed for analogue generation as a mutational operator within a GA framework, representing an innovative approach to target-oriented de novo design.

Composite hydrogels composed of low-molecular-weight peptide self-assemblies and polysaccharides are gaining great interest as new types of biomaterials. Interactions between polysaccharides and peptide self-assemblies are well reported, but a molecular picture of their impact on the resulting material is still missing. Using the phosphorylated tripeptide precursor Fmoc-FF p Y (Fmoc, fluorenylmethyloxycarbonyl; F, phenylalanine; Y, tyrosine; p , phosphate group), we investigated how hyaluronic acid (HA) influences the enzyme-assisted self-assembly of Fmoc-FFY generated in situ in the presence of alkaline phosphatase (AP). In the absence of HA, Fmoc-FFY peptides are known to self-assemble in nanometer thick and micrometer long fibers. The presence of HA leads to the spontaneous formation of bundles of several micrometers thickness. Using fluorescence recovery after photobleaching (FRAP), we find that in the bundles both ( i ) HA colocalizes with the peptide self-assemblies and ( ii ) its presence in the bundles is highly dynamic. The attractive interaction between negatively charged peptide fibers and negatively charged HA chains is explained through molecular dynamic simulations that show the existence of hydrogen bonds. Whereas the Fmoc-FFY peptide self-assembly itself is not affected by the presence of HA, this polysaccharide organizes the peptide nanofibers in a nematic phase visible by small-angle X-ray scattering (SAXS). The mean distance d between the nanofibers decreases by increasing the HA concentration c , but remains always larger than the diameter of the peptide nanofibers, indicating that they do not interact directly with each other. At a high enough HA concentration, the nematic organization transforms into an ordered 2D hexagonal columnar phase with a nanofiber distance d of 117 Å. Depletion interaction generated by the polysaccharides can explain the experimental power law variation d ∼ c - 1 / 4 and is responsible for the bundle formation and organization. Such behavior is thus suggested for the first time on nano-objects using polymers partially adsorbing on self-assembled peptide nanofibers.

Computing accurate rate constants for catalytic events occurring at the surface of a given material represents a challenging task with multiple potential applications in chemistry. To address this question, we propose an approach based on a combination of the rare event sampling method called adaptive multilevel splitting (AMS) and ab initio molecular dynamics. The AMS method requires a one-dimensional reaction coordinate to index the progress of the transition. Identifying a good reaction coordinate is difficult, especially for high dimensional problems such as those encountered in catalysis. We probe various approaches to build reaction coordinates such as support vector machine and path collective variables. The AMS is implemented so as to communicate with a density functional theory-plane wave code. A relevant case study in catalysis, the change of conformation and the dissociation of a water molecule chemisorbed on the (100) γ-alumina surface, is used to evaluate our approach. The calculated rate constants and transition mechanisms are discussed and compared to those obtained by a conventional static approach based on the Eyring-Polanyi equation with harmonic approximation. It is revealed that the AMS method may provide rate constants that are smaller than those provided by the static approach by up to 2 orders of magnitude due to entropic effects involved in the chemisorbed water molecule.

Cu chelation in biological systems is of interest as a tool to study the metabolism of this essential metal or for applications in the case of diseases with a systemic or local Cu overload, such as Wilson's or Alzheimer's disease. The choice of the chelating agent must meet several criteria. Among others, affinities and kinetics of metal binding and related metal selectivity are important parameters of the chelators to consider. Here, we report on the synthesis and characterization of Cu-binding properties of two ligands, L1 and L2, derivatives of the well-known peptidic Cu II -binding motif Xxx-Zzz-His (also called ATCUN), where Cu II is bound to the N-terminal amine, two amidates, and the imidazole. In either L, the N-terminal amine was replaced with a pyridine, and for L2, one amide was replaced with an amine compared to Xxx-Zzz-His. In particular, L2 showed several interesting features, including a Cu II -binding affinity with a log  K D app = -16.0 similar to that of EDTA and stronger than all reported ATCUN peptides. L2 showed high selectivity for Cu II over Zn II and other essential metal ions, even under the challenging conditions of the presence of human serum albumin. Further, L2 showed fast and efficient Cu II redox silencing qualities and Cu II -L2 was stable in the presence of mM GSH concentrations. Benefitting the fact that L2 can be easily elongated on its peptide part by standard SPPS to add other functions, L2 has attractive properties as a Cu II chelator for application in biological systems.

A multi-responsive receptor consisting of two (acridinium-Zn(II) porphyrin) conjugates has been designed. The binding constant between this receptor and a ditopic guest has been modulated (i) upon addition of nucleophiles converting acridinium moieties into the non-aromatic acridane derivatives and (ii) upon oxidation of the porphyrin units. A total of eight states has been probed for this receptor resulting from the cascade of the recognition and responsive events. Moreover, the acridinium/acridane conversion leads to a significant change of the photophysical properties, switching from electron to energy transfer processes. Interestingly, for the bis(acridinium-Zn(II) porphyrin) receptor, charge-transfer luminescence in the near-infrared has been observed.

Quantum entanglement between the spin states of a metal center and radical ligands is suggested in an iron(II) [Fe(dipyvd) 2 ] 2+ compound (dipyvd = 1-isopropyl-3,5-dipyridil-6-oxoverdazyl). Wave function ab initio (Difference Dedicated Configuration Interaction, DDCI) inspections were carried out to stress the versatility of local spin states. We named this phenomenon excited state spinmerism , in reference to our previous work (see Roseiro et al., ChemPhysChem 2022 , e202200478) where we introduced the concept of spinmerism as an extension of mesomerism to spin degrees of freedom. The construction of localized molecular orbitals allows for a reading of the wave functions and projections onto the local spin states. The low-energy spectrum is well-depicted by a Heisenberg picture. A 60 cm -1 ferromagnetic interaction is calculated between the radical ligands with the S total = 0 and 1 states largely dominated by a local low-spin S Fe = 0. In contrast, the higher-lying S total = 2 states are superpositions of the local S Fe = 1 (17%, 62%) and S Fe = 2 (72%, 21%) spin states. Such mixing extends the traditional picture of a high-field d 6 Tanabe-Sugano diagram. Even in the absence of spin-orbit coupling, the avoided crossing between different local spin states is triggered by the field generated by radical ligands. This puzzling scenario emerges from versatile local spin states in compounds which extend the traditional views in molecular magnetism.

A series of ten cationic complexes of the general formula [(C^C)Au(P^P)]X, where C^C = 4,4'-di- tert -butyl-1,1'-biphenyl, P^P is a diphosphine ligand, and X is a noncoordinating counteranion, have been synthesized and fully characterized by means of chemical and X-ray structural methods. All the complexes display a remarkable switch-on of the emission properties when going from a fluid solution to a solid state. In the latter, long-lived emission with lifetime τ = 1.8-83.0 μs and maximum in the green-yellow region is achieved with moderate to high photoluminescence quantum yield (PLQY). This emission is ascribed to an excited state with a mainly triplet ligand-centered ( 3 LC) nature. This effect strongly indicates that rigidification of the environment helps to suppress nonradiative decay, which is mainly attributed to the large molecular distortion in the excited state, as supported by density functional theory (DFT) and time-dependent DFT (TD-DFT) computation. In addition, quenching intermolecular interactions of the emitter are avoided thanks to the steric hindrance of the substituents. Emissive properties are therefore restored efficiently. The influence of both diphosphine and anion has been investigated and rationalized as well. Using two complexes as examples and owing to their enhanced optical properties in the solid state, the first proof-of-concept of the use of gold(III) complexes as electroactive materials for the fabrication of light-emitting electrochemical cell (LEC) devices is herein demonstrated. The LECs achieve peak external quantum efficiency, current efficiency, and power efficiency up to ca. 1%, 2.6 cd A -1 , and 1.1 lm W -1 for complex 1PF 6 and 0.9%, 2.5 cd A -1 , and 0.7 lm W -1 for complex 3 , showing the potential use of these novel emitters as electroactive compounds in LEC devices.

We report herein a domino reaction to construct 2-amido-5-fluoropyrroles from CF 3 -substituted N -allenamides. The in situ generated gem -difluorinated ene-ynamides derived from CF 3 -substituted N -allenamides, when subjected to silver catalysis with a primary amine, undergo simultaneous hydroamination of the ynamide moiety followed by a 5- endo-trig addition/β-fluoride elimination sequence, enabling the construction of 2-amido-5-fluoropyrroles. This transformation features excellent functional group compatibility. By employing 2-aminophenols, functionalized benzo-oxazoles were produced.

The choice of molecular orbitals is decisive in configuration interaction calculations. In this letter, a democratic description of the ground and excited states follows an orthogonally constrained orbital optimization to produce state-specific orbitals. The approach faithfully recovers the excitation energy of a four-electron Hubbard trimer, whereas state-average calculations can miss the value by a factor 2.5. The method emphasizes the need for orbital optimization to reduce configuration interaction expansions and to reach spectroscopic accuracy.

α-Pyridyl thiosemicarbazones (TSC) such as Triapine (3AP) and Dp44mT are a promising class of anticancer agents. Contrary to Triapine, Dp44mT showed a pronounced synergism with Cu II , which may be due to the generation of reactive oxygen species (ROS) by Dp44mT-bound Cu II ions. However, in the intracellular environment, Cu II complexes have to cope with glutathione (GSH), a relevant Cu II reductant and Cu I -chelator. Here, aiming at rationalizing the different biological activity of Triapine and Dp44mT, we first evaluated the ROS production by their Cu II -complexes in the presence of GSH, showing that Cu II -Dp44mT is a better catalyst than Cu II -3AP. Furthermore, we performed density functional theory (DFT) calculations, which suggest that a different hard/soft character of the complexes could account for their different reactivity with GSH.

A mixed-ligand phthalocyanine/porphyrin yttrium(III) radical double-decker complex ( DD ) was synthesized using the custom-made 5,10,15-tris(4-methoxyphenyl)-20-(4-((trimethylsilyl)ethynyl)phenyl)porphyrin. The trimethylsilyl functionality was then used to couple two such complexes into biradicals through rigid tethers. Glaser coupling was used to synthesize a short-tethered biradical ( C1 ) and Sonogashira coupling to synthesize longer-tethered ones ( C2 and C3 ). Field-swept echo-detected (FSED), saturation recovery, and spin nutation-pulsed electron paramagnetic resonance experiments revealed marked similarities of the magnetic properties of DD with those of the parent [Y(pc) 2 ] • complex, both in the solid state and in CD 2 Cl 2 /CDCl 3 4:1 frozen glasses. FSED experiments on the biradicals C2 and C3 revealed a spectral broadening with respect to the spectra of DD and [Y(pc) 2 ] • assigned to the effect of dipolar interactions in solution. Apart from the main resonance, satellite features were also observed, which were simulated with dipole-dipole pairs of shortest distances, suggesting spin delocalization on the organic tether. FSED experiments on C1 yielded spectral line shapes that could not be simulated as the integration of the off-resonance echoes was complicated by field-dependent modulations. While, for all dimers, the on-resonance spin nutation experiments yielded Rabi oscillations of the same frequencies, off-resonance nutations on C1 yielded Rabi oscillations that could be assigned to a M S = -1 to M S = 0 transition within a S = 1 multiplet. The DFT calculations showed that the trans conformation of the complexes was significantly more stable than the cis one and that it induced a marked spin delocalization over the rigid organic tether. This "spin leakage" was most pronounced for the shortest biradical C1 .

Two-dimensional (2D) chirality has been actively studied in view of numerous applications of chiral surfaces such as in chiral resolutions and enantioselective catalysis. Here, we report on the expression and amplification of chirality in hybrid 2D metallosupramolecular networks formed by a nucleobase derivative. Self-assembly of a guanine derivative appended with a pyridyl node was studied at the solution-graphite interface in the presence and absence of coordinating metal ions. In the absence of coordinating metal ions, a monolayer that is representative of a racemic compound was obtained. This system underwent spontaneous resolution upon addition of a coordinating ion and led to the formation of a racemic conglomerate. The spontaneous resolution could also be achieved upon addition of a suitable guest molecule. The mirror symmetry observed in the formation of the metallosupramolecular networks could be broken via the use of an enantiopure solvent, which led to the formation of a globally homochiral surface.

Although it has been studied extensively throughout the past 20 years, the environmental impact of e-commerce can still be considered a controversial subject. Particularly for those wondering whether online shopping constitutes a more environmentally friendly alternative to traditional store-based shopping, evidence can be found that quantitatively supports affirmative as well as opposing claims. Findings differ widely because the contexts and assumptions of the studies from which they are drawn differ widely as well. To advance our understanding of this question and inform actions that can actually reduce the environmental impact of shopping, we carried out a systematic quantitative review of environmental impact assessments that compares the carbon footprint of online and store purchases. Based on over twenty scientific studies, we compiled a dataset of 244 purchases, their estimated carbon footprint and information on the contextual, distribution, behavioral, and geographical conditions on which the calculations are based. We conclude from the reviewed studies that online purchases generally generate a lower carbon footprint than store purchases, but only in the case of car-dependent lifestyles, and possibly only because the studies largely overlook transformations in consumer behavior and in the consumption landscape.

Conductive organic nanocomposites have been widely employed to achieve a variety of purposes, particularly for energy storage applications, making it necessary to investigate transport properties such as electron and heat transport qualities based on geometric shapes and component materials. Due to the solid B-B bonds, unique atomic structure, and energy storage potential, borophene has received significant attention due to its reported ultrahigh mechanical modulus and metallic conduction. Herein, we investigated the effect and interaction of content materials (volume fraction) and geometric parameters such as the aspect ratio and orientation of borophene nanoplatelet (BNP) inclusions on the mechanical integrity and transport features (electrical and thermal conductivities) of a poly(3,4-ethylene dioxythiophene):poly(4-styrene sulfonate) (PEDOT:PSS) electrode. The boundary condition is crucial in developing the predictive models for the optimized mechanical and transport properties of the composites. The effective modulus, electrical conductivity, and thermal conductivity of the BNP-reinforced PEDOT:PSS-based nanocomposite are evaluated using the periodic boundary condition, the representative volume element-based finite element homogenization, and statistical analysis response surface techniques. The optimal parameters for the PEDOT:PSS/BNP nanocomposite for energy storage application are predicted based on the desirability function to have a 13.96% volume fraction of BNPs, having an aspect ratio of 0.04 at 45° inclination. The desirability value achieved for the material hinges was 0.78 with a predicted Young's modulus of 6.73 GPa, the electrical conductivity was 633.85 S/cm, and the thermal conductivity was 1.96 W/m K at a generally high predictive performance of <0.03 error. The effective thermal conductivity of the nanocomposite was determined by considering Kapitsa nanoeffects, which exhibit an interfacial thermal resistance of 2.42 × 10 -9 m 2 K/W. Based on these improved findings, the enhanced PEDOT:PSS/BNP nanocomposite electrode would be a promising material for metal-ion batteries., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Flexibility is essential for many proteins to function, but can be difficult to characterize. Experiments lack resolution in space and time, while the time scales involved are prohibitively long for straightforward molecular dynamics simulations. In this work, we present a multiple state transition path sampling simulation study of a protein that has been notoriously difficult to characterize in its active state. The GTPase enzyme KRas is a signal transduction protein in pathways for cell differentiation, growth, and division. When active, KRas tightly binds guanosine triphosphate (GTP) in a rigid state. The protein-GTP complex can also visit more flexible states, in which it is not active. KRas mutations can affect the conversion between these rigid and flexible states, thus prolonging the activation of signal transduction pathways, which may result in tumor formation. In this work, we apply path sampling simulations to investigate the dynamic behavior of KRas-4B (wild type, WT) and the oncogenic mutant Q61L (Q61L). Our results show that KRas visits several conformational states, which are the same for WT and Q61L. The multiple state transition path sampling (MSTPS) method samples transitions between the different states in a single calculation. Tracking which transitions occur shows large differences between WT and Q61L. The MSTPS results further reveal that for Q61L, a route to a more flexible state is inaccessible, thus shifting the equilibrium to more rigid states. The methodology presented here enables a detailed characterization of protein flexibility on time scales not accessible with brute-force molecular dynamics simulations.

In order to better foramize it, the notorious inverse-QSAR problem (finding structures of given QSAR-predicted properties) is considered in this paper as a two-step process including (i) finding "seed" descriptor vectors corresponding to user-constrained QSAR model output values and (ii) identifying the chemical structures best matching the "seed" vectors. The main development effort here was focused on the latter stage, proposing a new attention-based conditional variational autoencoder neural-network architecture based on recent developments in attention-based methods. The obtained results show that this workflow was capable of generating compounds predicted to display desired activity while being completely novel compared to the training database (ChEMBL). Moreover, the generated compounds show acceptable druglikeness and synthetic accessibility. Both pharmacophore and docking studies were carried out as "orthogonal" in silico validation methods, proving that some of de novo structures are, beyond being predicted active by 2D-QSAR models, clearly able to match binding 3D pharmacophores and bind the protein pocket.

We present a novel cluster analysis implemented in our open-source software TRAVIS and its application to realistic and complex chemical systems. The underlying algorithm is exclusively based on atom distances. Using a two-dimensional model system, we first introduce different cluster analysis functions and their application to single snapshots and trajectories including periodicity and temporal propagation. Using molecular dynamics simulations of pure water with varying system size, we show that our cluster analysis is size-independent. Furthermore, we observe a similar clustering behavior of pure water in classical and ab initio molecular dynamics simulations, showing that our cluster analysis is universal. In order to emphasize the application to more complex systems and mixtures, we additionally apply the cluster analysis to ab initio molecular dynamics simulations of the [C 2 C 1 Im][OAc] ionic liquid and its mixture with water. Using that, we show that our cluster analysis is able to analyze the clustering of the individual components in a mixture as well as the clustering of the ionic liquid with water.

The atomically thick two-dimensional (2D) materials are at the forefront of revolutionary technologies for energy storage devices. Due to their fascinating physical and chemical features, these materials have gotten a lot of attention. They are particularly appealing for a wide range of applications, including electrochemical storage systems, due to their simplicity of property tuning. The MXene is a type of 2D material that is widely recognized for its exceptional electrochemical characteristics. The use of these materials in conjunction with conducting polymers, notably polypyrrole (PPy), has opened new possibilities for lightweight, flexible, and portable electrodes. Therefore, herein we report a comprehensive review of recent achievements in the production of MXene/PPy nanocomposites. The structural-property relationship of this class of nanocomposites was taken into consideration with an elaborate discussion of the various characterizations employed. As a result, this research gives a narrative explanation of how PPy interacts with distinct MXenes to produce desirable high-performance nanocomposites. The effects of MXene incorporation on the thermal, electrical, and electrochemical characteristics of the resultant nanocomposites were discussed. Finally, it is critically reviewed and presented as an advanced composite material in electrochemical storage devices, energy conversion, electrochemical sensors, and electromagnetic interference shielding., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Biphenol-based ligands have proven their ability to bind titanium(IV) centers and generate sophisticated self-assembled structures in which auxiliary nitrogen ligands often complete the coordination sphere of the metal and improve stability. Here, a central 4,4'-bipyridine, which acts as both a spacer and a source of monodentate nitrogen to complete the coordination sphere of the Ti(IV) complex, was incorporated within two bis-2,2'-biphenol strands, 3 H 4 and 4 H 4 . Both proligands possess structural features that are well adapted to form self-assembled structures built from titanium-oxygen-nitrogen units; however, their different degrees of torsional freedom strongly influenced the nuclearity of the complexes formed. The presence of a phenyl spacer between the bipyridine and the biphenol moieties of 3 H 4 provided enough flexibility for the ligand to wrap around one titanium(IV) center to form a mononuclear complex Ti( 3 )(DMF) 2 in the presence of dimethylformamide (DMF). Assembly of the more rigid ligand 4 H 4 with Ti(O i Pr) 4 afforded a tetranuclear complex Ti 4 ( 4 ) 2 ( 4 H) 2 (OEt) 2 containing four stacked 4,4'-bipyridine units as shown by the X-ray structure of the complex. Density functional theory studies suggested that the assembly of this tetrametallic complex involves a dimetallic intermediate with TiO 6 nodes that is converted to the thermodynamically stable tetranuclear complex with two TiO 6 nodes and two TiO 5 N units with enhanced covalent character.

In this paper, density functional theory (DFT) simulations are used to evaluate the possible use of a graphene oxide-based poly(ethylene glycol) (GO/PEG) nanocomposite as a drug delivery substrate for cephalexin (CEX), an antibiotic drug employed to treat wound infection. First, the stable configuration of the PEGylated system was generated with a binding energy of -25.67 kcal/mol at 1.62 Å through Monte Carlo simulation and DFT calculation for a favorable adsorption site. The most stable configuration shows that PEG interacts with GO through hydrogen bonding of the oxygen atom on the hydroxyl group of PEG with the hydrogen atom of the carboxylic group on GO. Similarly, for the interaction of the CEX drug with the GO/PEG nanocomposite excipient system, the adsorption energies are computed after determining the optimal and thermodynamically favorable configuration. The nitrogen atom from the amine group of the drug binds with a hydrogen atom from the carboxylic group of the GO/PEG nanocomposite at 1.75 Å, with an adsorption energy of -36.17 kcal/mol, in the most stable drug-excipient system. Drug release for tissue regeneration at the predicted target cell is more rapid in moist conditions than in the gas phase. The solubility of the suggested drug in the aqueous media around the open wound is shown by the magnitude of the predicted solvation energy. The findings from this study theoretically validate the potential use of a GO/PEG nanocomposite for wound treatment application as a drug carrier for sustained release of the CEX drug., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Azacalix[ n ]arenes (ACAs) are lesser-known cousins of calix[ n ]arenes that contain amine bridges instead of methylene bridges, so they generally have higher flexibility due to enlarged cavities. Herein, we report a highly substituted cationic azacalix[4]arene-based covalent organic framework ( ACA-COF ) synthesized by the Zincke reaction under microwave irradiation. The current work is a rare example of a synthetic strategy that utilizes the chemical functionalization of an organic macrocycle to constrain its conformational flexibility and, thereby, produce an ordered material. Considering the ACA cavity dimensions, and the density and diversity of the polar groups in ACA-COF , we used it for adsorption of uric acid and creatinine, two major waste products generated during hemodialysis treatment in patients with renal failure. This type of application, which has the potential to save ∼400 L of water per patient per week, has only been recognized in the last decade, but could effectively address the problem of water scarcity in arid areas of the world. Rapid adsorption rates (up to k = 2191 g mg -1 min -1 ) were observed in our COF, exceeding reported values by several orders of magnitude.

Glutathione (GSH) is the most abundant thiol in mammalian cells and plays a crucial role in maintaining redox cellular homeostasis. The thiols of two GSH molecules can be oxidized to the disulfide GSSG. The cytosolic GSH/GSSG ratio is very high (>100), and its reduction can lead to apoptosis or necrosis, which are of interest in cancer research. Cu II ions are very efficient oxidants of thiols, but with an excess of GSH, Cu I n (GS) m clusters are formed, in which Cu I is very slowly reoxidized by O 2 at pH 7.4 and even more slowly at lower pH. Here, the aerobic oxidation of GSH by Cu II was investigated at different pH values in the presence of the anticancer thiosemicarbazone Dp44mT, which accumulates in lysosomes and induces lysosomal membrane permeabilization in a Cu-dependent manner. The results showed that Cu II -Dp44mT catalyzes GSH oxidation faster than Cu II alone at pH 7.4 and hence accelerates the production of very reactive hydroxyl radicals. Moreover, GSH oxidation and hydroxyl radical production by Cu II -Dp44mT were accelerated at the acidic pH found in lysosomes. To decipher this unusually faster thiol oxidation at lower pH, density functional theory (DFT) calculations, electrochemical and spectroscopic studies were performed. The results suggest that the acceleration is due to the protonation of Cu II -Dp44mT on the hydrazinic nitrogen, which favors the rate-limiting reduction step without subsequent dissociation of the Cu I intermediate. Furthermore, preliminary biological studies in cell culture using the proton pump inhibitor bafilomycin A1 indicated that the lysosomal pH plays a role in the activity of Cu II -Dp44mT.

Graph-based architectures are becoming increasingly popular as a tool for structure generation. Here, we introduce novel open-source architecture HyFactor in which, similar to the InChI linear notation, the number of hydrogens attached to the heavy atoms was considered instead of the bond types. HyFactor was benchmarked on the ZINC 250K, MOSES, and ChEMBL data sets against conventional graph-based architecture ReFactor, representing our implementation of the reported DEFactor architecture in the literature. On average, HyFactor models contain some 20% less fitting parameters than those of ReFactor. The two architectures display similar validity, uniqueness, and reconstruction rates. Compared to the training set compounds, HyFactor generates more similar structures than ReFactor. This could be explained by the fact that the latter generates many open-chain analogues of cyclic structures in the training set. It has been demonstrated that the reconstruction error of heavy molecules can be significantly reduced using the data augmentation technique. The codes of HyFactor and ReFactor as well as all models obtained in this study are publicly available from our GitHub repository: https://github.com/Laboratoire-de-Chemoinformatique/HyFactor.

Treating large bone defects or fragile patients may require enhancing the bone regeneration rate to overcome a weak contribution from the body. This work investigates the osteogenic potential of nutrient fisetin, a flavonoid found in fruits and vegetables, as a doping agent inside the structure of a SiO 2 -CaO bioactive glass-poly(caprolactone) (BG-PCL) hybrid scaffold. Embedded in the full mass of the BG-PCL hybrid during one-pot synthesis, we demonstrate fisetin to be delivered sustainably; the release follows a first-order kinetics with active fisetin concentration being delivered for more than 1 month (36 days). The biological effect of BG-PCL-fisetin-doped scaffolds (BG-PCL-Fis) has been highlighted by in vitro and in vivo studies. A positive impact is demonstrated on the adhesion and the differentiation of rat primary osteoblasts, without an adverse cytotoxic effect. Implantation in critical-size mouse calvaria defects shows bone remodeling characteristics and remarkable enhancement of bone regeneration for fisetin-doped scaffolds, with the regenerated bone volume being twofold that of nondoped scaffolds and fourfold that of a commercial trabecular bovine bone substitute. Such highly bioactive materials could stand as competitive alternative strategies involving biomaterials loaded with growth factors, the use of the latter being the subject of growing concerns., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The first synthesis of gem -difluorinated ene-ynamides is presented via deprotonation of trifluoromethylated N -allenamides and δ extrusion of fluorine. These highly reactive building blocks, owing to their dual functional groups, offer a unique entry to difluorinated dienes and to stereodefined, monofluoro-substituted dienes. Stereoselective addition to the ynamide moiety led to difluorinated dienes. A stereocontrolled domino δ elimination reaction followed by an addition/elimination sequence from trifluoromethylated N -allenamides provided exclusively stereodefined monofluorinated ene-ynamides.

A synthesis of new-to-nature aza-iridoids via ynamides is presented. ZrCl 4 proved to be the best acid to perform this transformation. Various ynamides were accommodated, and seco -iridoids could be obtained as well. Aza-iridoids were infiltrated into leaves of Scrophularia Nodosa , an iridoid-producing plant species. High-resolution mass spectrometry coupled to computational metabolomic approaches was employed for the detection of aza-iridoid bioconversion products.

The steric strain around copper(I) in typical [Cu(NN R ) 2 ] + complexes, where NN R is a diimine ligand substituted in α-positions of the nitrogen atoms by R, is known to strongly impact the excited-state properties. Generally speaking, the larger the R, the longer the emission lifetime and the higher the quantum yield. However, the stability of the coordination scaffold can be at stake if the steric strain imposed by R is too large. In this work, we explore a way of fine-tuning the steric strain around Cu(I) to reach a balance between high emission quantum yield and stability in a highly bulky copper(I) complex. Taking stable [Cu(dipp) 2 ] + and unstable [Cu(dtbp) 2 ] + (where dipp and dtbp are, respectively, 2,9-diisopropyl-1,10-phenanthroline and 2,9-di- tert -butyl-1,10-phenanthroline) as the boundary of two least and most sterically strained structures, we designed and characterized the nonsymmetrical ligand 2-isopropyl-9- tert -butyl-1,10-phenanthroline (L1) and corresponding complex [Cu(L1) 2 ] + (Cu1). The key experimental findings are that Cu1 exhibits a rigid tetrahedral geometry in the ground state, close to that of [Cu(dtbp) 2 ] + and with an intermediate stability between that of [Cu(dipp) 2 ] + and [Cu(dtbp) 2 ] + . Conversely, the nonsymmetrical nature of ligand L1 leads to a shorter emission lifetime and smaller quantum yield than those of either [Cu(dipp) 2 ] + or [Cu(dtbp) 2 ] + . This peculiar behavior is rationalized through the in depth analysis of the ultrafast dynamics of the excited state measured with optical transient absorption spectroscopy and theoretical calculations performed on the ground and excited state of Cu1. Our main findings are that the obtained complex is significantly more stable than [Cu(dtbp) 2 ] + despite the sterically strained coordination sphere. The nonsymmetrical nature of the ligand translates into a strongly distorted structure in the excited state. The distortion can be described as a rocking motion of one ligand, entailing the premature extinction of the excited state via several deactivation channels.

This work introduces CGRdb2.0─an open-source database management system for molecules, reactions, and chemical data. CGRdb2.0 is a Python package connecting to a PostgreSQL database that enables native searches for molecules and reactions without complicated SQL syntax. The library provides out-of-the-box implementations for similarity and substructure searches for molecules, as well as similarity and substructure searches for reactions in two ways─based on reaction components and based on the Condensed Graph of Reaction approach, the latter significantly accelerating the performance. In benchmarking studies with the RDKit database cartridge, we demonstrate that CGRdb2.0 performs searches faster for smaller data sets, while allowing for interactive access to the retrieved data.

What happens at the ionic-liquid (IL)/water interface when the Eu 3+ cation is complexed and extracted by bis(dimethyltriazinyl) pyridine "BTP" ligands has been investigated by molecular dynamics and potential of mean force simulations on the interface crossing by key species: neutral BTP, its protonated BTPH + form, Eu 3+ , and the Eu(BTP) 3 3+ complex. At both the [BMI][Tf 2 N]/water and [OMI][Tf 2 N]/water interfaces, neither BTP nor Eu(BTP) 3 3+ are found to adsorb. The distribution of Eu(BTP) 2 3+ and Eu(BTP) 3+ precursors of Eu(BTP) 3 3+ , and of their nitrate adducts, implies the occurrence of a stepwise complexation process in the interfacial domain, however. The analysis of the ionic content of the bulk phases and of their interface before and after extraction highlights the role of charge buffering by interfacial IL cations and anions, by different amounts depending on the IL. Comparison of ILs with octanol as the oil phase reveals striking differences regarding the extraction efficiency, the affinity of Eu(BTP) 3 3+ for the interface, the effects of added nitric acid and of counterions (NO 3 - vs Tf 2 N - ), charge neutralization mechanisms, and the extent of "oil" heterogeneity. Extraction into octanol is suggested to proceed via adsorption at the surface of water pools, nanoemulsions, or droplets, with marked counterion effects.