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International audience; These last decades, it has been widely assumed that 18-crown-6-ether (CE) plays a spectator role during the chemical processes occurring in isolated host-guest complexes between peptides or proteins and CE, after activation in mass spectrometers. Our present experimental and theoretical results challenge this hypothesis by showing that CE can abstract a proton or a protonated molecule from protonated peptides after activation by collisions in argon or electron capture/transfer. Furthermore, thanks to comparison between experimental and calculated values of collision cross-sections, we demonstrate that CE can change binding site after electron transfer. We also propose detailed mechanisms for these processes.

International audience; Microbiological reductive sulfidation (RS) has rarely been documented, although it represents an efficient strategy for thiol formation. In this work, we reported on the sulfate-respiring bacterium Desulfovibrio sp.86 that has previously demonstrated RS activity toward the pesticide chlordecone. The purpose of the study was to assess its substrate-versatility using a set of 28 carbonyls, to compare with chemical RS and to rationalize the observed trends using a dual experimental and theoretical approach. The chemical RS generally proceeds in two steps (S-O exchange using a sulfur donor like P4S10, reduction of the thione intermediate). Intriguingly, chlordecone was found to be converted into chlordecthiol following the first step. Hence, we designed a protocol and applied it to the 28 substrates to assess their propensity to be directly converted into thiols with the P4S10 treatment alone. Finally, we performed density functional theory calculations on these carbonyls and their thiocarbonyl derivatives to build a set of structural, electronic and thermodynamic parameters. The results showed that chemical and microbiological RS probably involved two distinct mechanisms. Chemically, we observed that several carbonyls, possessing electron-withdrawing groups and/or aromatic rings, were directly transformed into thiols in the presence of P4S10. The correlation obtained with the electron affinity of the thiones led us conclude that a probable single-electron reductive transfer occurred during the first step. We also found that Desulfovibrio sp.86 transformed a variety of aldehydes and ketones, without ever detecting thiones. No significant correlation was observed with the calculated parameters but a relationship between aldehyde RS biotransformation and bacterial growth was observed. Differences in selectivity with chemical RS open the way for further applications in organic synthesis.

The Tethered Counterion-Directed Catalysis (TCDC) approach has been applied to the enantioselective Au(I) catalyzed dearomatizations of 1-naphthols with allenamides. Stereocontrol is ensured by the intramolecular ion-pairing between the chiral gold-tethered phosphate and an iminium unit, that provides a rigid, well-defined chiral environment to the key electrophilic intermediate.

The association of a mycotoxin-ochratoxin A (OTA)-with a high-affinity DNA aptamer (anti-OTA) immobilized on a functionalized surface has been investigated at the molecular level. Anti-OTA aptamers are coupled by aminolysis in several steps on an acid-terminated alkyl monolayer grafted on a silicon substrate, and Fourier transform infrared spectroscopy in attenuated total reflection geometry is used to assess the immobilization of anti-OTA (in its unfolded single-strand form) and determine its areal density (ca. 1.4/nm2). IR spectra further demonstrate that the OTA/anti-OTA association is efficient and selective and that several association/dissociation cycles may be conducted on the same surface. The areal density of OTA measured after association on the surface (IR spectroscopy) and after dissociation from the surface (UV-vis spectroscopy) falls in the range 0.16-0.3/nm2 which is close to the areal density of a closed-packed monolayer of anti-OTA aptamers folded to form their G-quadruplex structure. The interactions between OTA and its aptamer at the surface are discussed with the help of density functional theory calculations-to identify the complex IR vibrational modes of OTA in solution-and UV-vis spectroscopy-to determine the protonation state of the adsorbing species (i.e., OTA dissolved in the buffer solution).

International audience; Platinum(IV) complexes are extensively studied for their activity against cancer cells as potential substitutes for the widely used platinum(II) drugs. PtIV complexes are kinetically inert and need to be reduced to PtII species to play their pharmacological action, thus acting as prodrugs. The mechanism of the reduction step inside the cell is however still largely unknown. Gas-phase activation of deprotonated platinum(IV) prodrugs was found to generate products in which platinum has a formal +3 oxidation state. IR multiple photon dissociation spectroscopy is thus used to obtain structural information helping to define the nature of both the platinum atom and the ligands. In particular, comparison of calculations at DFT, MP2 and CCSD levels with experimental results demonstrates that the localization of the radical is about equally shared between the dxz orbital of platinum and the pz of nitrogen on the amino group, the latter acting as a non-innocent ligand.

International audience; Tethering a metal complex to its phosphate counterion via a phosphine ligand enables a new strategy in Asymmetric Counteranion-Directed Catalysis (ACDC). A straightforward, scalable synthetic route gives access to the gold(I) complex of a chiral phosphine displaying a phos-phoric acid function. The complex generates a catalytically active species with an unprecedented intramolecular relationship between the cati-onic Au(I) center and the phosphate counterion. The benefits of tethering the two functions of the catalyst is demonstrated here in a tandem cycloisomerization/nucleophilic addition reaction, by attaining high enantioselectivity levels (up to 97% ee) at a remarkable low 0.2 mol% catalyst loading. Remarkably the method is also compatible with a silver-free protocol.

International audience; Quantum chemical calculations and NBO, ETS-NOCV, QTAIM and ELF interpretative approaches have been carried out on C-donor ligand-stabilized dihydrido borenium cations. Numerous descriptors of the C-B π-bond strength obtained from orbital localization, energy partitioning or topological methods as well as from structural and chemical parameters have been calculated for 39 C-donor ligands including N-heterocyclic carbenes and carbones. Comparison of the results allows the identification of relative and absolute descriptors of the π interaction. For both families of descriptors excellent correlations are obtained. This enables the establishment of a π-donation capability scale and shows that the interpretative methods, despite their conceptual differences, describe the same chemical properties. These results also reveal noticeable shortcomings in these popular methods, and some precautions that need to be taken to interpret their results adequately.

International audience; The complexes (Cy2PC3H6PCy2)Ni(η2-arene) (arene = toluene (3), naphthalene (4)) have been synthesized and studied in detail. Displacement reactions of the toluene ligand afford the complexes (Cy2PC3H6PCy2)Ni(η2-styrene) (5), (Cy2PC3H6PCy2)Ni(PhCN) (6), (Cy2PC3H6PCy2)Ni(CO)2 (7), (Cy2PC3H6PCy2)Ni(PPh3) (8), (Cy2PC3H6PCy2)Ni(PCy3) (9), {(Cy2PC3H6PCy2)Ni}2(μ-H)2 (10), (Cy2PC3H6PCy2)Ni(η2-CO2) (11), and [(Cy2PC3H6PCy2)Ni]2(μ,η2-1,5-COD) (12). The relative rates of ArCl oxidative addition at Ni complexes 3, 4, 6, 8, and 12 have been evaluated experimentally, and the mechanism has been calculated by DFT. Complexes 3 and 4 are efficient catalysts for the Suzuki–Miyaura reaction between chloroarenes and Ar′B(OH)2.

International audience; Metallotropism of the M[N(SiMe3)2]2 metal fragment in the tautomeric system IAR⇌ACR involving imidazolium salts/N‐heterocyclic carbenes with remote aminide/amine substituents, respectively, is manifested by its CNHC carbophilicity (R=tBu, M=Co, Fe) or NRaminido nitrogenophilicity (R=Cy, M=Co, Fe; R=Mes, M=Fe) and has been rationalized on the basis of steric and electronic effects. The thermolysis products of the [M{N(SiMe3)2}2]/ IAR⇌ACR system are also substituent‐dependent, leading to a rearranged aminide‐functionalized aNHC Co2 complex of an unprecedented type or to ring‐opened metallaketenimines; they are postulated to originate from different metalloisomers. The results are interpreted on the basis of the X‐ray diffraction analysis of 11 new compounds.

The linear, two-coordinate and isostructural heteroleptic [M(IPr){N(SiMe3)2}] (IPr = 1,3-bis(diisopropylphenyl)-imidazol-2-ylidene), formally MI complexes (M = Co, 3; Fe, 4) were obtained by the reduction of [M(IPr)Cl{N(SiMe3)2}] with KC8, or [Co(IPr){N(SiMe3)2}2] with mes*PH2, mes* = 2,4,6-tBu3C6H2. The magnetism of 3 and 4 implies CoII and FeII centres coupled to one ligand-delocalized electron, in line with XPS and XANES data; the ac susceptibility of 4 detected a pronounced frequency dependence due to slow magnetization relaxation. Reduction of [Fe(IPr)Cl{N(SiMe3)2}] with excess KC8 in toluene gave the heteronuclear ‘inverse-sandwich’ Fe–K complex 7, featuring η6-toluene sandwiched between one Fe0 and one K+ centre.

International audience; The role of Hartree-Fock exchange in describing the structural changes occurring upon reduction of bipyridine-based ligands and their complexes is investigated within the framework of density functional theory calculations. A set of 4 free ligands in their neutral and radical anionic forms, and 2 of their zinc complexes in their dicationic and monocationic radical forms, is used to compare a large panel of pure, conventional, and long-range corrected hybrid DFT functionals; coupled cluster single and double calculations are used alongside experimental results as benchmarks. Particular attention has been devoted to the magnitude of the change, upon reduction, of the D-parameter, which measures the difference between the Cpy-Cpy and the C-N bond lengths in bipyridine ligand and is known to experimentally correlate with the charge of the ligands. Our results indicate that the structural changes significantly depend on the amount of exact exchange included in the functional. A progressive evolution is observed for the free ligands, whereas two distinct sets of results are obtained for the complexes. Functionals with a small degree of HF exchange, e.g., B3LYP, do not adequately describe geometric changes for the considered species and, quite surprisingly, the same holds for the CC2 method. The best agreement to experimental and CCSD values is obtained with functionals that include a significant but not excessive part of exact exchange, e.g., CAM-B3LYP, M06-2X, and wB97X-D. The calculated localisation of the added electron after reduction, which depends on the self-interaction error, is used to rationalize these outcomes. Static correlation is also shown to play a role in the accurate description of electronic structure.

International audience; A one-pot methodology to synthesize metastable bicyclic 2,5-dihydrooxepines from cyclic 1,3-diketones and 1,4-dibromo-2-butenes is reported, through the retro-Claisen rearrangement of syn-2-vinylcyclopropyl diketone intermediates. High-level quantum chemical calculations were performed to understand the reaction selectivity and mechanisms towards [1,3] or [3,3]-sigmatropic rearrangements, highlighting the crucial influence of temperature in close relation to experimental results. The reaction was successfully applied to a short protecting group-free total synthesis of radulanin A, a natural 2,5-dihydrobenzoxepine, featuring an unprecedented aromatization strategy of the transient bicyclic 2,5-dihydrooxepine. We demonstrate for the first time the strong herbicidal potential of this natural product.

International audience; Double deprotonation of 2,6-bis-(di-tert-butylphosphinomethyl)-pyridine (tBuPNtBuP), with KCH2C6H5 afforded K2(tBuP*NatBuP*), Na = anionic amido N, tBuP* = di-tert-butyl vinylic P donor. The analogous [Li2(tBuP*NatBuP*)]2 (1) was reacted with [CrCl2(THF)2] and [ZrCl4(THT)2] to give the helical [Cr{Cr(tBuP*NatBuP*)Cl}2] (2) and [Zr(tBuP*NatBuP*)Cl2] (3), respectively. DFT calculations support dearomatisation of P*NaP* and its high donor ability.

International audience; We report an intramolecular Diels-Alder reaction efficiently accelerated by Schreiner's thiourea, to build a functionalized cytochalasin scaffold (periconiasin series) amenable to biological purpose. DFT calculation highlighted a unique multidentate cooperative hydrogen bonding in this catalysis. The deprotection end-game afforded a collection of diverse structures and showed the peculiar reactivity of the Diels-Alder cycloadducts upon functionalization. Biological studies revealed strong cytotoxicity of a few compounds on breast cancer cell lines, while preserving actin polymerization.

International audience; The two first steps of the Strecker synthesis of glycine, namely (a) addition of ammonia to formaldehyde to give aminomethanol and (b) its dehydration leading to methaneimine, is studied using high level quantum chemistry computations (G3B3). Water solvation is modeled by considering the effect of adding a discrete number of active or passive molecules of water (up to four) and by immersing the identified water-solute complexes in a conductor-like polarizable continuum solvent model. Activation of the reactants by protonation is also examined. Exhaustive search of microhydrated neutral and protonated aminomethanol has been performed using a combination of hierarchical and genealogical approaches. Critical energies associated with all the elementary reaction steps were estimated using the accurate G3B3 composite method thus providing benchmarks to discuss the possible occurrence of Strecker synthesis in prebiotic chemistry.

International audience; The enantioselective H-transfer hydrogenation of quinoline by Hantzsch ester is a relevant example of Brønsted acid catalyzed cascade reactions, with phosphoric acid being a privileged catalyst. The generally accepted mechanism points out the hydride transfer step as the rate- and stereodetermining step, however computations based on these models do not totally fit with experimental observations. We hereby present a computational study that enlightens the stereochemical outcome and quantitatively reproduces the experimental enantiomeric excesses in a series of H-transfer hydrogenations. Our calculations suggest that the high stereocontrol usually attained with BINOL-derived phosphoric acids results mostly from the steric constraints generated by an aryl substituent of the catalyst, which hinders the access of the Hantzsch ester to the catalytic site and enforces approach through a specific way. It relies on a new model involving the preferential assembly of one of the stereomeric complexes formed by the chiral phosphoric acid and the two reaction partners. The stereodetermining step thus occurs prior to the H-transfer step.

International audience; Extensive exploration of the potential energy surfaces of protonated Nα-acetylhistidine hydrated by 0–3 molecules of water was performed. The methodology combined hierarchical and genealogical (Darwin family tree) approaches using polarizable AMOEBA force field and M06 functional. It is demonstrated that this mixed approach allows recovering a larger number of conformers than the number recovered by using any one of the two methods alone. Hydration enthalpies of protonated Nα-acetylhistidine and of model compounds have been computed using higher theoretical methods, up to the G4MP2 procedure. Excellent agreement with experiment is observed for successive hydration of methylamonium and imidazolium cations using MP2/6-311++G(2d,2p)//M06/6-311++G(d,p) and G4MP2 methods, thereby validating the theory levels used for hydrated protonated Nα-acetylhistidine. It is found that the first hydration enthalpy of protonated Nα-acetylhistidine is ca. 10 kJ mol–1 lower than that of imidazolium, a result explained by the local environment of the positively charged imidazolium moiety.

A novel, sequential, palladium-catalyzed, cross-coupling reaction using N-tosylhydrazone and bromonitrobenzene derivatives followed by reductive cyclization has been developed. This transformation providing an efficient route to unexpected N-arylindole derivatives involves, in a one-pot reaction, the formation of one Csp2–Csp2 bond and two Csp2–N bonds together with the cleavage of one Csp2–heteroatom bond. Evaluation of the biological activity led to the identification of compound 5a, which displays potent activity at nanomolar concentrations against human colon carcinoma cell line.

International audience; This work aims to improve the computation of infrared spectra of gas-phase cations using DFT methods. Experimental IRMPD spectra for ten Zn and Ru organometallic complexes have been used to provide reference data for 64 vibrational modes in the 900-2000 cm-1 range. The accuracy of the IR vibrational frequencies predicted for these bands has been assessed over five DFT functionals and three basis sets. The functionals include the popular B3LYP and M06-2X hydrids and the range-separated hybrids (RSH) CAM-B3LYP, LC-BLYP and B97X-D. B3LYP gives the best mean absolute error (MAE) and root-mean-square error (RMSE) values of 7.1 and 9.6 cm-1 , whilst the best RSH functional, B97X-D, gives 12.8 and 16.6 cm-1 respectively. Using linear correlations instead of scaling factors improves the prediction accuracy significantly for all functionals. Experimental and computed spectra for a single complex can show significant differences even when the molecular structure is calculated correctly, and a means of defining confidence limits for any given computed structure is also provided.

International audience; We assess the pros and cons of a large panel of DFT exchange-correlation functionals for the prediction of the electronic structure of hydrogen-rich peptide radicals formed after electron attachment on a protonated peptide. Indeed, despite its importance in the understanding of the chemical changes associated with the reduction step, the question of the attachment site of an electron, and more generally of the reduced species formed in the gas phase through electron induced dissociation (ExD) processes in mass spectrometry, is still a matter of debate. For hydrogen-rich peptide radicals in which several positive groups and low lying π* orbitals can capture the incoming electron in ExD, inclusion of full Hartree-Fock exchange at long-range interelectronic distance is a prerequisite for an accurate description of the electronic states, excluding therefore several popular exchange-correlation functionals, e.g., B3LYP, M06-2X or CAM-B3LYP. However, we show that this condition is not sufficient by comparing the results obtained with asymptotically correct range separated hybrids (M11, LC-BLYP, LC-BPW91, ωB97, ωB97X and ωB97X-D) and with reference CASSCF-MRCI and EOM-CCSD calculations. The attenuation parameter ω significantly tunes the spin density distribution and the excited states vertical energies. The investigated model structures, ranging from methylammonium to hexapeptide, allow us to obtain a description of the nature and energy of the electronic states depending on: (i) the presence of hydrogen bond(s) around the cationic site(s); (ii) the presence of π* MOs; and (iii) the selected DFT approach. It turns out that, in the present framework, LC-BLYP and ωB97 yields the most accurate results.

The cystamine-based hybrid perovskite, α-[NH3(CH2)2S-S(CH2)2NH3]PbI4 (1a), can be transformed into its polymorph, β-[NH3(CH2)2S-S(CH2)2NH3]PbI4 (1b), by heat activation (T = 150 °C). The crystal structures have been characterised by single-crystal X-ray diffraction, whereas the phase transition was followed by both solid-state 1H,13C cross-polarisation magic-angle spinning (CPMAS) NMR spectroscopy and thermodiffractometry techniques. At 150 °C, compound 1a is transformed into 1b, and, remarkably, the β phase (1b) can be nearly retained down to room temperature, which means that both polymorphs 1a and 1b can coexist over a large temperature range. The structure of 1b has been solved, and it was found that cystamine molecules are disordered over two positions: the two related components with opposite helical conformations. Solid-state 1H,13C CPMAS NMR spectroscopic measurements show a significant broadening of the NMR spectroscopic line associated with two disordered carbon atoms when cooling 1b from 160 to 50 °C, thereby revealing the presence of exchange between these related atoms, and this favours a molecular dynamical disorder. Disulfide bridges of cystamine molecules are engaged in weak interactions with neighbours, either another cystamine molecule in 1a (SS***SS interactions), or iodine atoms in 1b (SS***I interactions). To evaluate the donating and accepting abilities of the disulfide bridge, and their impact on such weak interactions, a detailed partition of the interaction energy of ten dimer models has been calculated and revealed that the main contribution to the intermolecular bonding comes from the dispersion forces.

International audience; Aromatic enynes can be transformed into arylnaphthalenes or benzofulvenes depending on the reaction conditions. Under gold(I) catalysis, exclusive or major 6-endo-dig cyclization took place leading to arylnaphthalenes. However, a catalytic system based on palladium iodide/1,3-Bis(diphenylphosphino)propane, in the presence of cesium carbonate as a base was necessary to furnish exclusively 5-exo-dig cyclization pattern, regardless to the electronic effects of the substituents. In the latter transformation, a mechanistic study (Kinetic Isotopic Effect, Density Functional Theory) involving a C-H activation is suggested for the exclusive benzofulvenes formation.

International audience; There is high prospect that derivatives of pentazole can lead to high energy density materials. However these molecules are potentially hazardous because of their high formation enthalpies and weak N-N bonds. In order to devise efficient protocols, possible schemes for the synthesis of nitro and azido derivatives of pentazole, and their mono- and di-oxides, have been explored using quantum chemical methods. Reaction pathways have been investigated in detail, with particular emphasis on locating transition states and on obtaining a reliable treatment of solvent effects. Oxidation by ozone is found to be a favorable process, leading to some regioselectivity in favor of b-mono-oxides. Nitration by NO2+BF4- is also predicted to be favorable. In contrast the electrochemical azidation of N5- and its oxidized derivatives is found to be energetically inaccessible. Combination of the individual addition and oxidation steps leads to recommendations for future synthetic work. Finally the kinetic stability of products with respect to N2 and N2O elimination is assessed.

International audience; Electron capture and electron transfer dissociations are bioanalytical methods for fragmenting cations after reduction by an electron. Previous computational studies based on conventional DFT schemes have concluded that the first step of these processes, the attachment of the electron, leads to extensive delocalization of the spin density in the intermediate radical cation. Here, we show that most DFT methods produce unphysical results when studying single electron reduction of a dicationic peptide. This is not the case for post-HF methods and long-range corrected functionals which show satisfying electron affinities, intermolecular interaction energies and spin density trends. Our results suggest that the charged group with the highest electron affinity on the precursor cation is also the site of spin density in the electronic ground state after electron attachment. These findings have important implications for the interpretation of experimental data from electron-based processes in biomolecules and may guide the development of new functionals.

International audience; A new synthetic approach to hexahydroisoindol-4-ones is reported, based on the formal [3+2] cyclization reaction between N-arylsulfonylimines and cyclic conjugated dienes, under phosphine catalysis. Key substrates are 3-vinylcyclohex-2-enones with electron-withdrawing substituents (ester, amido, cyano, phosphoryl and keto groups) on the exocyclic double bond, which afford the three atom synthons for the construction of the pyrroline ring. Total syn stereoselectivity is observed in these annulations. The scope of the reaction has been demonstrated and mechanistic issues are considered, based on deuteration experiments and DFT calculations.

International audience; Square-planar platinum(II) complexes that combine chiral diphosphines and NHC ligands have been obtained in high yields from (NHC)Pt(0)(dvtms) complexes, via an oxidative addition/ligand exchange sequence. The use of suitable carbene−diphosphine pairs allows axially chiral, configurationally stable platinum complexes to be isolated. The Pt(II) complexes have been evaluated as precatalysts for the cycloisomerization reaction of an allyl propargylamine derivative. Their catalytic properties have been examined as a function of structural variations on both the diphosphine and the NHC units. For axially chiral species possible epimerization pathways have been envisioned and the inversion barriers have been estimated through computational studies

International audience; Alkylation of zinc-bound thiolates occurs in both catalytic and structural zinc sites of enzymes. Recent biomimetic studies have led to a controversy as to which mechanism is operative in thiolate alkylation. Building on one of these biomimetic complexes, we have devised a series of models that allow for an appraisal of the roles of charge, ligand nature, and hydrogen bonding to sulfur on reactivity. The reactions of these complexes with methyl iodide, leading to thioethers and zinc iodide complexes, have been examined by density functional theory calculations, in the gas phase as well as in an aqueous solution. In all cases, a S(N)2 reaction is favored over sigma-bond metathesis. Both the net electronic charge and the hydrogen bond play a significant role in the nucleophilicity of the thiolate. We find that the mechanistic diversity observed experimentally can be explained by the difference in the net charge of the complexes. A dianionic complex follows a dissociative pathway, whereas an associative one is preferred for a neutral system.

Electron capture dissociation (ECD) was studied with doubly charged dipeptide ions that were tagged with fixed-charge tris-(2,4,6-trimethoxyphenyl)phosphonium-methylenecarboxamido (TMPP-ac) groups. Dipeptides GK, KG, AK, KA, and GR were each selectively tagged with one TMPP-ac group at the N-terminal amino group while the other charge was introduced by protonation at the lysine or arginine side-chain groups to give (TMPP-ac-peptide + H)(2+) ions by electrospray ionization. Doubly tagged peptide derivatives were also prepared from GK, KG, AK, and KA in which the fixed-charge TMPP-ac groups were attached to the N-terminal and lysine side-chain amino groups to give (TMPP-ac-peptide-ac-TMPP)(2+) dications by electrospray. ECD of (TMPP-ac-peptide + H)(2+) resulted in 72% to 84% conversion to singly charged dissociation products while no intact charge-reduced (TMPP-ac-dipeptide + H)(+) ions were detected. The dissociations involved loss of H, formation of (TMPP + H)(+), and N-C(alpha) bond cleavages giving TMPP-CH(2)CONH(2)(+) (c(0)) and c(1) fragments. In contrast, ECD of (TMPP-ac-peptide-ac-TMPP)(2+) resulted in 31% to 40% conversion to dissociation products due to loss of neutral TMPP molecules and 2,4,6-trimethoxyphenyl radicals. No peptide backbone cleavages were observed for the doubly tagged peptide ions. Ab initio and density functional theory calculations for (Ph(3)P-ac-GK + H)(2+) and (H(3)P-ac-GK + H)(2+) analogs indicated that the doubly charged ions contained the lysine side-chain NH(3)(+) group internally solvated by the COOH group. The distance between the charge-carrying phosphonium and ammonium atoms was calculated to be 13.1-13.2 A in the most stable dication conformers. The intrinsic recombination energies of the TMPP(+)-ac and (GK + H)(+) moieties, 2.7 and 3.15 eV, respectively, indicated that upon electron capture the ground electronic states of the (TMPP-ac-peptide + H)(+*) ions retained the charge in the TMPP group. Ground electronic state (TMPP-ac-GK + H)(+*) ions were calculated to spontaneously isomerize by lysine H-atom transfer to the COOH group to form dihydroxycarbinyl radical intermediates with the retention of the charged TMPP group. These can trigger cleavages of the adjacent N-C(alpha) bonds to give rise to the c(1) fragment ions. However, the calculated transition-state energies for GK and GGK models suggested that the ground-state potential energy surface was not favorable for the formation of the abundant c(0) fragment ions. This pointed to the involvement of excited electronic states according to the Utah-Washington mechanism of ECD.

International audience; Hydrogen-atom loss and intramolecular hydrogen-atom migration in peptide radical and cation radical were investigated by quantum chemical calculations for models that include zero to three hydrogen bonds with the ammonium groups. Five different DFT functionals have been checked to study the geometry relaxation and fragmentation processes after electron attachment to peptide cations. The structural changes associated with the geometry relaxation are shown to be dependent on the level of calculation. Furthermore, comparison with CCSD(T) calculations indicates that an adequate description of the electronic state of the reduced protonated peptide is not a sufficient prerequisite to provide accurate energy barrier. Calculating fragmentation reactions of hydrogen-rich peptide cation radicals is pointed out to be a challenging task as none of the DFT functionals are fully effective to describe the whole process. M06-2X is an adequate choice if it provides the correct ground state, otherwise LC-BLYP should be chosen.The electron attachment site and the electron affinity value are highly sensitive to the number of hydrogen bonds with the ammonium group. An ammonium cation with zero, one, and, to a smaller extent, two hydrogen bonds easily captures an incoming electron and subsequently undergoes an H-atom loss process rather than a proton coupled electron transfer. This suggests an explanation for the low amount of c and z fragments observed upon ECD for small protonated peptides, where the ammonium groups cannot be highly intramolecularly “solvated”.

International audience; Combining electron capture dissociation mass spectrometry and infrared multiple photon dissociation action spectroscopy allows the formation, selection and characterisation of reduced metal complexes containing non-innocent ligands. Zinc complexes containing diazafluorenone ligands have been studied and the localisation of the single electron on the metal atom in the mono-ligated complex has been demonstrated.

This work expands on the recent synthesis and reactivity of the two-coordinate P(III)-containing dication [((Ph3P)2C)P(NiPr2)]2+ (3a2+). Two additional dications of general formula [((RPh2P)2C)P(NR′2)]2+ (3b2+, R = 1/2 (CH2)3, R′ = iPr; 3c2+, R = Ph, R′ = Cy) have been prepared. Solution and solid-state 31P NMR isotropic shifts for this dication class were observed around 360 ppm. Except for [3a][SbF6]2, the 31P CP/MAS NMR spectra reveal a high degree of structural disorder around the dicationic site in the solid state. Surprisingly, the synthesis of dication 3a2+ was only possible in the presence of AlCl4–, SbF6–, and substituted tetraarylborates, while the use of ClO4–, OTf–, BF4–, PF6–, and BPh4– resulted in complex product mixtures. Single-crystal X-ray analysis of dications 3a2+ and 3c2+ suggested a 4π allyl-like structure for the central CPN fragment, and this has been supported through detailed theoretical investigations. Initial reactivity studies between dications 3a2+/3c2+ and PMe3 show an equilibrium between the free dication and the target adduct. Furthermore, 3a2+ has been shown to be capable of O–H bond activation using water and methanol and polymerizes THF when it is dissolved in this solvent ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version

International audience; Phosphoric acids with planar chiral paracyclophane scaffolds have been prepared in optically pure form starting from 1,8-dibromobiphenylene, by means of a chiral phosphorodiamidate as the phosphorylating agent. Structural characterization and configurational assignment have been performed by X-ray diffraction studies. The acids promote the organocatalytic enantioselective H-transfer reduction of α-arylquinolines with up to 90% enantiomeric excess.

International audience; Using the σ- and п-donating properties of carbodiphosphorane ligands, we recently synthesized a phosphorus (III)-containing dication. It is observed to undergo interesting reactivity with PMe3, H2O and MeOH.

International audience; The bonding between model phosphinidene PH and two types of cyclic Arduengo's carbenes, the aromatic C3H4N2 (1) and the related saturated C3H6N2 (2) species, respectively, have been analyzed in terms of the electron localization function (ELF). In a first step, the bare carbenes have been studied, and then, in a second step, the changes brought about by PH complexation have been treated. It has been shown that the bonding mode essentially results from a dative bond formed by the nucleophilic carbenic carbon of the ring and the PH acceptor site. Some back bonding from P creates a partial double-bond character around the C-P unit. The latter character is more pronounced when PH is linked to the saturated carbene 2. A comparison of the ring aromatic properties, in terms of nucleus-independent chemical shifts has been achieved, showing that complexation of 1 by PH diminishes the ring aromaticity through relocalization of the electrons on the N atoms.

International audience; AM1 and PM3 underestimate frontier interactions with respect to steric repulsions. Therefore, if two structures differ by ~1 kcal/mol, their calculated ordering is unreliable. Activation eneries tend to increase with substitution, regardless of electronic effects. Atomic charges are sometimes unrealistic (in enolates, the negative charge is larger on C than on O). At van der Waals distances, acid-base and coulombic interactions can prevail over steric repulsions. At all distances, basicities are overestimated and nucleophilicities underestimated. This may lead to anomalous ion-molecule and transition structures in gas phase reactions. Transition structures are tighter than in ab initio calculations. Optimisations may give chemically unreasonable structures. Minimum energy paths are then difficult to obtain. Usually, but not systematically, PM3 gives more reliable structures and AM1 more realistic energies/

International audience; The oxidative addition of palladium(0) to the C2-protected 5-bromo-2-methylbenzimidazolium tetrafluoroborate 3 affords the complex trans-[PdBr(bimy)(PPh3)2]BF4 (4), which is the first complex of an unprecedented benzimidazole-derived ligand (bimy) with a potentially "mesoionic and remote" character. DFT calculations revealed that the bimy ligand bridges the gap between the mesoionic pyrazolin-4-ylidene and the anionic phenyl ligand. A preliminary catalytic study revealed the promising activity of 4 in the Sonogashira coupling of aryl bromides with phenylacetylene.

International audience; Carbenes derived from fivemembered heterocycles with different numbers of nitrogen atoms ranging from two to four lead formally either to normal N-heterocyclic or mesoionic carbenes with, in some cases, the same skeletal structure. The electronic structures of fourteen of these compounds were examined by means of DFT calculations at the B3LYP/aug-cc-pVTZ level. The examined parameters include the energies of the s-lone pair at C(carbene) atom and the pi-highest occupied molecular orbital (HOMO) of the protonated form, which are correlated to the first and second proton affinities. The singlet-triplet energy gap was used as a measure of the stability of the N-heterocyclic carbene (NHC) towards dimerisation. Natural population analysis provided insight into the variation of the p(pi) population and the natural charge at the C(carbene) atom with NHC structure. Additionally, the transition metal- NHC bond in L-AuCl and LTiCl4 and the nature of the orbital interactions between the NHC and the transition-metal fragment were analysed in detail by the extended transition state-natural orbitals for chemical valence (ETS-NOCV) approach at the BP86/TZ2P level. Similarities and differences between the NHC- gold and the NHC- titanium bond are discussed, and trends in key bonding properties can be traced back to the variation of the electronic parameters of the NHC.

International audience; This work deals with the development of a new family of planar chiral phosphoric acids, based on a ferrocenophane/paracyclophane scaffold. The synthetic approach has been improved by taking advantage of a chiral phosphorylating agent to access enantiomerically enriched acids via diastereomers separation. These phosphoric acids have been used as catalysts for the enantioselective H-transfer reduction of alpha-substituted quinolines with Hantzsch esters. Optimization of both the catalyst and the Hantzsch reductant allowed ee in the range 82-92% to be attained starting from alpha-arylquinolines.

International audience; This work aims to analyze and compare the intrinsic electronic densities in a series of neutral and anionic divalent carbon-donor derivatives. The σ-lone pair at the divalent carbon is the HOMO of these species. Structural factors have been identified that influence its energy, which is a measure of the σ-basicity. The π-electronic structure has been described as a function of the π-population. Our results show that no straightforward structural criteria correlate with the π-electronic distribution. However, the π-population, as well as the π-acidity and π-basicity, are related to the π-MOs. In all cases these π-MOs can be qualitatively obtained based on those of the protonated analogues by simply increasing the energy of the pπ orbital at the divalent carbon atom compared to normal sp2 carbon. Such an analysis allows a rationalization of the trends observed for the π-electronic structure of these ligands. Notably, this explains the values of the π-population at the divalent carbon center, which shows an increasing and continuous range from classical NHCs to mesoionic "carbenes".

International audience; A double ring-expansion methodology allows the stepwise synthesis of tri- and tetra-phosphaporhyrinogens. Structural and calculational methods reveal extended delocalisation about their phospholide centres.

International audience; Acid-base thermochemistry of isolated amino acids containing oxygen or sulfur in their side chain (serine, threonine, cysteine and methionine) have been examined by quantum chemical computations. Density functional theory (DFT) was used, with B3LYP, B97-D and M06-2X functionals using the 6-31+G(d,p) basis set for geometry optimizations and the larger 6-311++G(3df,2p) basis set for energy computations. Composite methods CBS-QB3, G3B3, G4MP2 and G4 were applied to large sets of neutral, protonated and deprotonated conformers. Conformational analysis of these species, based on chemical approach and AMOEBA force field calculations, has been used to identify the lowest energy conformers and to estimate the population of conformers expected to be present at thermal equilibrium at 298 K. It is observed that G4, G4MP2, G3B3, CBS-QB3 composite methods and M06-2X DFT lead to similar conformer energies. Thermochemical parameters have been computed using either the most stable conformers or equilibrium populations of conformers. Comparison of experimental and theoretical proton affinities and Delta(acid)H shows that the G4 method provides the better agreement with deviations of less than 1.5 kJ mol-1. From this point of view, a set of evaluated thermochemical quantities for serine, threonine, cysteine and methionine may be proposed: PA = 912, 919, 903, 938; GB = 878, 886, 870, 899; Delta(acid)H = 1393, 1391, 1396, 1411; Delta(acid)G = 1363, 1362, 1367, 1382 kJ mol-1. This study also confirms that a non-negligible Delta(p)S° is associated with protonation of methionine and that the most acidic hydrogen of cysteine in the gas phase is that of the SH group. In several instances new conformers were identified thus suggesting a reexamination of several IRMPD spectra.

International audience; The proton affinities of a series of mono- and polynuclear zinc-thiolate compounds, mimicking zing finger protein and metallothioneins sites, have been investigated by Density Functional Theory calculations. This allows to evaluate the intrinsic nucleophilicity of synthetic and natural zinc-bound thiolates and to compare their relative reactivities. The site specificity of the experimental thiolate alkylation for the Zn4Cys11 clusters in metallothioneins is well reproduced, as well as the relative reactivities of ZnHis2Cys2, ZnHisCys3 and ZnCys4 zinc finger sites. Our results also show that terminal thiolates, bound to only one Lewis acid, are more reactive than bridging thiolates. Synthetic inorganic clusters and the Zn4Cys9His2 cluster found in a cyanobacterial metallothionein are less reactive than Zn4Cys11 and Zn3Cys9 clusters in metallothioneins. These results allow discussing the influence of the protein backbone and residues on the reactivity of these natural clusters.

International audience; The determination of the structures and relative energies of microsolvated complexes remains an important challenge for theoretical chemistry because the number of possible aggregates rapidly increases when more solvent molecules are considered. Several approaches (chemical intuition, hierarchy of scheme, evolutionary trees...) have been previously proposed to identify the most stable geometries. In the present paper, we compare both the structures and interaction energies computed with different computational protocols for the model case of microhydrated protonated glycine, a system for which experimental complexation enthalpies are available. We compare the results obtained, one the one hand, by a hierarchical approach starting with a AMOEBA search followed by DFT and MP2 refinements, and, on the other hand, by a Darwinian tree that use evolutionary logic and only counter-poise corrected MP2 calculations. It is shown that the two approaches yield relatively similar conclusions, though some structures can only be identified by one of the two approaches. This paper therefore underlines the interest of applying more than one minima search tactic for pinpointing all possible microsolvated complexes.

International audience; Electron capture dissociation (ECD) of a series of five residue peptides led to the observation that these small peptides did not lead to the formation of the usual c/z ECD fragments, but to a, b, y and w fragments. In order to determine how general this behavior is for small sized peptides, the effect of peptide size on ECD fragments using a complete set of ECD spectra from the SwedECD spectra database was examined. Analysis of the database shows that b and w fragments are favored for small peptide sizes and that average fragment size shows a linear relationship to parent peptide size for most fragment types. From these data, it appears that most of the w fragments are not secondary fragments of the major z ions, in sharp contrast with the proposed mechanism leading to these ions. These data also show that c fragment distributions depend strongly on the nature of C-terminal residue basic site: arginine leads to loss of short neutral fragments, whereas lysine leads to loss of longer neutral fragments. It also appears that b ions might be produced by two different mechanisms depending on the parent peptide size. A model for the fragmentation pathways in competition is proposed. These relationships between average fragment size and parent peptide size could be further exploited also for CID fragment spectra and could be included in fragmentation prediction algorithms.

Density Functional Theory and post-Hartree Fock calculations reveal an unusual energy profile for Zn-S and Zn-N bond dissociation reactions in several [Zn(SR)(4)](2-) and [Zn(Im)(SR)(3)](-) complexes. The Zn-S bond dissociation in tetrathiolate dianions, which is highly exothermic in the gas phase, proceeds through a late transition state which can be rationalized on the basis of an avoided crossing resulting from Coulomb repulsion between the anionic fragments and ligand-to-metal charge-transfer in the [Zn(SR)(4)](2-) complexes. When solvation models for water, DMSO, or acetonitrile are included, some complexes become stable while others are metastable, so this constitutes the first theoretical model which is in full agreement with the experimental data for various [Zn(SR)(4)](2-), [Zn(SR)(3)](-), and [Zn(Im)(SR)(3)](-) complexes. The analysis given here indicates that the Zn(Cys)(4) and Zn(His)(Cys)(3) cores of numerous proteins are metastable with respect to Zn-S and Zn-N bond dissociation, respectively. This is consistent with the kinetic lability at the zinc-centers and illustrates that in nature, thermodynamic stability is imparted upon the zinc cores by the protein environment.

International audience; The planar chiral 2-phospha[3]ferrocenophane I has been shown to be the first efficient nucleophilic organocatalyst for the enantioselective synthesis of cyclopentenylphosphonates, through [3+2] cyclizations between diethyl allenylphosphonate and alpha,beta-unsaturated ketones. The same catalyst has also been applied to the highly enantioselective [3+2] cyclizations of allenic esters with dibenzylideneacetone and analogous bis-enones, leading to functionalised cyclopentenes with either monocyclic or spirocyclic structures (ee 84-95 %). It has been shown that the residual enone functions in the resulting cyclopentenes can be involved in subsequent cyclization steps to afford unprecedented C(2)-symmetric bis-cyclopentenylketones. In order to provide insight into the behaviour of FerroPHANE I as a chiral catalyst in [3+2] cyclisations, the energetically most favoured isomers of the key phosphine-allene adduct have been calculated by DFT methods. Factors likely to control the chiral induction process are highlighted.

International audience; The nucleophilicity of biomimetic zinc-thiolate complexes against methyl iodide has been studied. The activation barrier has been computed with the B3LYP functional. The reactivity depends on the global charge, the nature of the ligand set and the presence of hydrogen bonds. This shows that the understanding of zinc site nucleophilicity cannot be achieved by the knowledge of the atom donor set for zinc only, as currently done in the literature. Moreover, we show that sulfur proton affinity and activation barrier are directly proportional, thus providing a good nucleophilicity index for zinc-bound thiolate.

International audience; Histidine is a very common metal ligand in metalloenzymes. Besides being an efficient Lewis base, its electronic properties are essential to shape the metal ability to catalyze the reaction. Here we show that histidine's properties can be tuned, in turn, by an easy proton transfer to a nearby glutamate. We study this situation in Human Carbonic Anhydrase II (HCA II) in which one of the three histidines bound to zinc (His119) interacts also with a glutamate residue (Glu117). Proton transfer from His119 to Glu117 has been hypothesized in the past, however realistic modeling is performed here for the first time. We show that the carboxylate group of Glu117 behaves only as a hydrogen bond acceptor in the hydroxy form of HCA II. On the other hand, our results suggest that Glu117 could exist either as a hydrogen bond acceptor or as a proton acceptor in the aqua form of HCA II, the two isomers having almost the same thermodynamic stability. We propose that this proton shift may be used by the enzyme to facilitate the final displacement of bicarbonate by water.

International audience; In this study, we propose the first spectroscopic structural characterization of c-type ions produced by ECD of a peptide. The structure of c-type ions formed by electron capture dissociation and the overall mechanism leading to their formation are still a question of debate. Depending on the mechanism, c-type ions have been proposed to have either an enol-imine structure (-C(OH)NH) or an amide one (-C(O)-NH2). Since these ions are isomeric, mass spectrometry only cannot discriminate between them, but infrared spectroscopy can bring experimental evidence and help determine which scheme is operative. Using the coupling between a tunable free electron laser and a FT-ICR mass spectrometer, we show that c-type ions have an amide structure, characterized by an IR signature of the C=O stretch at 1731 cm(-1). This result is particularly interesting from the perspective of the elucidation of the ECD mechanism.