Synthesis and Lewis Acid Properties of Neutral Silver(III) Adducts Containing the AgIII(CF3)3 Moiety.

The acetonitrile AgIII complex [AgIII(CF3)3(NCCH3)] (2) has been reported independently by Eujen and Naumann in the last century, albeit with intriguing NMR discrepancy. In their reports, 2 was claimed to be obtained starting from either [AgIII(CF3)3Cl]- (3⋅Cl) or [AgIII(CF3)4]- (1) via halide abstraction using AgNO3 or acidic treatment, resp. These two synthetic routes are herein reinvestigated. The feasibility of Naumann's method is demonstrated, thus providing 2 yet accompanied by its s-triazinyl derivative [AgIII(CF3)3(C6H9N3)] (2'). The formation of 2' is unprecedented and was thereby investigated. Both 2 and 2' were isolated in pure fashion and fully characterized. In turn, halide extraction from 3⋅Cl leads to the AgIII-ONO2 anion 5 instead of 2, as evidenced by NMR spectroscopy, EA and Sc-XRD.

Silyliumylidene Ion Stabilized by Two σ-Donating Ni(0)- and Pd(0)-Fragments.

A silyliumylidene ion 2 stabilized by two σ-donating Ni(0)- and Pd(0)-fragments was successfully synthesized. Due to the σ-donation of M→Si interactions, 2 presents a pyramidalized cationic silicon center with a localized lone pair. The additional coordination of basic Pd(0) fragment to the mono-Ni(0)-stabilized silyliumylidene 1 results in a higher HOMO level and an unchanged HOMO-LUMO gap and thus, 2 remains highly reactive. Interestingly, the coordination mode at the Si center is closely related to the nature of M-ligands. Indeed, the donor/donor-stabilized silyliumylidene ion 2 has been transformed into a donor/acceptor-stabilized ion 13, featuring a trigonal planar Si center with a vacant orbital, just via a ligand exchange reaction from PCy3/NHC toward PMe3.

Selective synthesis of an elusive C-functional bis-cyclam and study of its inhibition of the CXCR4 chemokine receptor.

This article presents the controlled synthesis of a rare example of C,C'-linked bis-cyclam architecture in mild conditions through the "bis-aminal" route previously used for the advantageous synthesis of cyclam, N- and C-functional cyclams and N,N'-bis-cyclams. Two synthetic pathways were explored with the smart design of α,ß-unsaturated ketones or alkyl halides bis-cyclizing agents. The first led to the isolation of a key intermediate for the future design of N-functionalized bis-cyclams, whereas the second allowed the preparation of the targeted C,C'-xylylene-bis-cyclam under mild conditions with decent yield. This compound was then studied as a CXCR4 receptor inhibitor, one of the main applications known for bis-macrocyclic compounds, in particular in the context of HIV (human immunodeficiency virus) infection. Although results demonstrated that its potency is lower (i.e. 137-fold higher IC50) than the gold standard AMD3100 against HIV infection, clear evidence of CXCR4 inhibition is presented, confirming the potential of this novel architecture and related compounds in this research field.

Imidazoquinoline Derivatives as Potential Inhibitors of InhA Enzyme and Mycobacterium tuberculosis.

Tuberculosis is a serious public health problem worldwide. The search for new antibiotics has become a priority, especially with the emergence of resistant strains. A new family of imidazoquinoline derivatives, structurally analogous to triazolophthalazines, which had previously shown good antituberculosis activity, were designed to inhibit InhA, an essential enzyme for Mycobacterium tuberculosis survival. Over twenty molecules were synthesized and the results showed modest inhibitory efficacy against the protein. Docking experiments were carried out to show how these molecules could interact with the protein's substrate binding site. Disappointingly, unlike triazolophthlazines, these imidazoquinoline derivatives showed an absence of inhibition on mycobacterial growth.

An Organocopper(III) Fluoride Triggering C-CF3 Bond Formation.

Copper(III) fluorides are catalytically competent, yet elusive, intermediates in cross-coupling. The synthesis of [PPh4 ][CuIII (CF3 )3 F] (2), the first stable (isolable) CuIII -F, was accomplished via chloride addition to [CuIII (CF3 )3 (py)] (1) yielding [PPh4 ][CuIII (CF3 )3 Cl(py)] (1⋅Cl), followed by treatment with AgF. The CuIII halides 1⋅Cl and 2 were fully characterized using nuclear magnetic resonance (NMR) spectroscopy, single crystal X-ray diffraction (Sc-XRD) and elemental analysis (EA). Complex 2 proved capable of forging C-CF3 bonds from silyl-capped alkynes. In-depth mechanistic studies combining probes, theoretical calculations, trapping of intermediate 4a ([PPh4 ][CuIII (CF3 )3 (C≡CPh)]) and radical tests unveil the key role of the CuIII acetylides that undergo facile 2e- reductive elimination furnishing the trifluoromethylated alkynes (RC≡CCF3 ), which are industrially relevant synthons in drug discovery, pharma and agrochemistry.

N2 Functionalization via Molybdenum-Nitride Complex: Stepwise BH Bond Additions.

Reactivity of (triphosphine)MoIV-nitrido complex generated by N2 splitting, toward boranes is reported. The simple adduct Mo≡N→BH3 is observed with BH3.SMe2 while 1,2 addition is evidenced with 9-BBN leading to H-Mo=NBR2. A second addition of BH3.SMe2 is facile and forms an unprecedented complex featuring two bridging H between two B and the Mo centers. Addition of PMe3 or BH3.SMe2 promotes reductive elimination and N-H bond formation. The full sequence of functionalization at Mo≡N obtained after N2 splitting is therefore evidenced in this work.

Taming the Lewis Superacid Al(ORF)3 (RF=C(CF3 )3 ): DFT Guided Identification of the "Stable yet Reactive" Adduct SiPr2 →Al(ORF)3 ; Its Use as ORF- Abstractor from a "Ni-ORF" complex.

A DFT study of several L→Al(ORF )3 (L=Lewis bases) adducts allowed the identification of (i Pr2 S)→Al(ORF )3 1-Si Pr2 as a "stable yet reactive" adduct. 1-Si Pr2 was shown to act as a masked Lewis superacid able to release Al(ORF )3 under mild conditions. It could be used to abstract a ORF- ligand from (bipyMe2 )Ni(ORF )2 (bipyMe2 : 6,6'-dimethyl-2,2'-dipyridyl) and generate the nickel alkoxide complex [(bipyMe2 )Ni(ORF )(i Pr2 S)]+ [(RF O)3 Al-F-Al(ORF )3 ]- 5. Ligand exchange of i Pr2 S by Ph3 P yielded [(bipyMe2 )Ni(ORF )(PPh3 )]+ [(RF O)3 Al-F-Al(ORF )3 ]- 6.

One Ligand to Bind them All: S~C~S2- Carbon- and Sulfur-Based Gem-Dianion as Structuring Ligand for Iron Polymetallic Assemblies.

Numerous synthetic models of the FeMo-co cluster of nitrogenases have been proposed to find the simplest structure with relevant reactivity. Indeed, such structures are able to perform multi-electrons reduction processes, such as the conversion of N2 to ammonia, and of CO2 into methane and alkenes. The most challenging parameter to imitate is indeed the central carbide ligand, which is believed to maintain the integrity of iron sulfide assembly during the course of catalytic cycles. The study proposes the use of bis(diphenylthiophosphinoyl)methanediide (SCS)2- as an ideal platform for the synthesis of bi- and tetra-metallic iron complexes, in which the iron-carbon interaction is maintained upon structural diversification and redox state changes.

Luminescent fac-[ReX(CO)3(phenyl-pyta)] (X = Cl, Br, I) complexes: influence of the halide ligand on the electronic properties in solution and in the solid state.

Tricarbonylrhenium(I) complexes that incorporate a chloride ligand are promising photoluminescent materials, but those incorporating a bromide or iodide ligand have received very little attention regarding their solid-state properties. In this work, three rhenium(I) complexes differing only by the nature of their halide ligand (X = Cl, Br, and I) were compared. They are based on a fac-[ReX(CO)3(N^N)] framework where the N^N bidentate ligand is a 3-(2-pyridyl)-1,2,4-triazole unit functionalized by an appended phenyl group. DFT calculations showed that the character of the lowest energy transitions progressively changes from Re → N^N ligand (MLCT) to X → N^N ligand (XLCT) when increasing the size of the halogen atom. Regarding the electrochemical behavior, the chloride and bromide complexes 1-Cl and 1-Br were similar, while the iodide complex 1-I exhibited a strikingly different electrochemical signature in oxidation. From a spectroscopic viewpoint, all three complexes emitted weak red-orange phosphorescence in dichloromethane solution. However, in the solid state, marked differences appeared. Not only was 1-Cl a good emitter of yellow light, but it had strong solid-state luminescence enhancement (SLE) properties. In comparison, 1-Br and 1-I were less emissive and they showed better mechanoresponsive luminescence (MRL) properties, probably related to a loose molecular arrangement in the crystal packing and to the opening of vibrational non-radiative deactivation pathways. This study highlights for the first time how the nature of the halide ligand in this type of complex allows fine tuning of the solid-state optical properties, for potential applications either in bio-imaging or in the field of MRL-active materials.

A Phosphine Oxide-Functionalized Cyclam as a Specific Copper(II) Chelator.

Although cyclam-based ligands are among the strongest copper(II) chelators available, they also usually present good affinity for other divalent cations [Zn(II), Ni(II), and Co(II)], with no copper(II)-specific cyclam ligands having been described so far. As such a property is highly desirable in a wide range of applications, we present herein two novel phosphine oxide-appended cyclam ligands that could be efficiently synthesized through Kabachnik-Fields type reactions on protected cyclam precursors. Their copper(II) coordination properties were closely studied by different physicochemical techniques [electron paramagnetic resonance (EPR) and ultraviolet-visible (UV-vis) spectroscopies, X-ray diffraction, and potentiometry]. The mono(diphenylphosphine oxide)-functionalized ligand demonstrated a copper(II)-specific behavior, unprecedented within the cyclam family of ligands. This was evidenced by UV-vis complexation and competition studies with the parent divalent cations. Density functional theory calculations also confirmed that the particular ligand geometry in the complexes strongly favors copper(II) coordination over that of competing divalent cations, rationalizing the specificity observed experimentally.

Base-Stabilized Cationic Silyne with a π-Accepting Phosphonio Substituent.

A base-stabilized C-phosphonio-Si-amino-silyne 3 was synthesized, using an original method, through a coupling reaction between two Lewis-base-stabilized low-valent species: a silyliumylidene ion 1 and a P,S-bis-ylide 2 [C(0)-complex]. This new isolable cationic silyne 3 displays remarkably high stability at room temperature [t1/2 = 7 days in tetrahydrofuran (THF)] and a unique silyne reactivity thanks to the effect of phosphonio substituent.

New Insight into the Reactivity of S,S-Bis-ylide.

The present work focuses on the reactivity of S,S-bis-ylide 2, which presents a strong nucleophilic character, as evidenced by reactions with methyl iodide and CO2, affording C-methylated salts 3 and betaine 4, respectively. The derivatization of betaine 4 affords the corresponding ester derivative 6, which is fully characterized by using NMR spectroscopy and X-ray diffraction analysis. Furthermore, an original reaction with phosphenium ions leads to the formation of a transient push-pull phosphino(sulfonio)carbene 8, which rearranges to give stabilized sulfonium ylide derivative 7.

Reversible Isomerization Between Silacyclopropyl Cation and Cyclic (Alkyl)(Amino)Silylene.

A phosphine-stabilized silacyclopropyl cation 2 has been synthesized and fully characterized. Of particular interest, 2 reversibly isomerizes into the corresponding seven-membered cyclic (alkyl)(amino)silylene 3 at room temperature via a formal migratory ethylene insertion into the Si-P bond. Although silylene 3 has not been spectroscopically detected, its transient formation has been evidenced by the isolation of the corresponding disilene dimer 5 as well as by trapping reactions.

Labile Base-Stabilized Silyliumylidene Ions. Non-Metallic Species Capable of Activating Multiple Small Molecules.

Several base-stabilized silyliumylidene ions (2 and 3) with different ligands were synthesized. Their behaviour appeared strongly dependent on the nature of ligand. Indeed, in contrast to the poorly reactive silyliumylidene ions 3 c,d stabilized by strongly donating ligands (DMAP, NHC), the silylene- and sulfide-supported one (2-H and 3 a) exhibits higher reactivity toward various small molecules. Furthermore, their capability to successively activate multiple small molecules was clearly demonstrated by processes involving successive reactions with silane/formamide, CO2 and H2 . Moreover, HBPin adduct of 3 a (8-C) catalyzes the hydroboration of pyridine. Of particular interest, silylene-supported silyliumylidene complex 2-H is one of the rare species able to activate two H2 molecules.

Reductive Elimination at Pb(II) Center of an (Amino)plumbylene-Substituted Phosphaketene: New Pathway for Phosphinidene Synthesis.

A stable (amino)plumbylene-substituted phosphaketene 3 was synthesized by the successive reactions of PbCl2 with two anionic reagents (lithium amidophosphine and NaPCO). Of particular interest, the thermal evolution of 3, at 80 °C, leads to the transient formation of corresponding amino- and phosphanylidene-phosphaketenes (6 and 7), via a reductive elimination at the PbII center forming new N-P and P-P bonds. Further evolution of 6 gives a new cyclic (amino)phosphanylidene phosphorane 4, which shows a unique reactivity as a phosphinidene. This result provides a new synthetic route to phosphinidenes, extending and facilitating further their access.

Lewis Base Adducts of Phosphine-Stabilized Pb(II) Cations: Synthesis and Catalytic Hydroamination of Alkynes.

Phosphine-stabilized Pb(II) cations, generated by chloride abstraction from chloroplumbylene 1, readily react with Lewis bases (L) such as phosphines and amines to give the corresponding donor-acceptor complexes 3. These complexes 3 react with phenylacetlylene via alkyne insertion into the Pb-L bond to afford the corresponding vinylplumbylenes 4. Of particular interest, the stable complex 4-HNiPr2 (with a secondary amine) can be used as a hydroamination catalyst of phenylacetylene.

A Silylene Stabilized by a σ-Donating Nickel(0) Fragment.

A donor-stabilized silylene 4 featuring a Ni0 -based donating ligand was synthesized. Complex 4 exhibits a pyramidalized and nucleophilic SiII center and shows a peculiar behavior due to the cooperative reactivity of Si and Ni centers. Calculations indicate that the orientation of Ni-ligands with respect to the silylene moiety is crucial in determining the role of the Ni-fragment (Lewis acid or Lewis base) towards silylene. Indeed, a simple 90° rotation of the Si-Ni bond, reverses the role of Ni, and transforms a classical silylene→Ni0 complex into an unprecedented Ni0 →silylene complex.

Synthesis, Characterization and Reactivity of a σ-Donating Ni0 -Stabilized Silyliumylidene Ion.

The synthesis of a silyliumylidene cation complex 2 stabilized by a Ni0 -based donating ligand is reported. Experimental and theoretical studies demonstrate that the highly electrophilic SiII center is stabilized by a dative Ni→Si σ-interaction and π-donations from the amino- and Ni-moieties. Due to the energetically close frontier orbitals localized on the Si and Ni atoms, complex 2 presents a competitive reactivity at Si and Ni sites.

Cross-Coupling through Ag(I)/Ag(III) Redox Manifold.

In ample variety of transformations, the presence of silver as an additive or co-catalyst is believed to be innocuous for the efficiency of the operating metal catalyst. Even though Ag additives are required often as coupling partners, oxidants or halide scavengers, its role as a catalytically competent species is widely neglected in cross-coupling reactions. Most likely, this is due to the erroneously assumed incapacity of Ag to undergo 2e- redox steps. Definite proof is herein provided for the required elementary steps to accomplish the oxidative trifluoromethylation of arenes through AgI /AgIII redox catalysis (i. e. CEL coupling), namely: i) easy AgI /AgIII 2e- oxidation mediated by air; ii) bpy/phen ligation to AgIII ; iii) boron-to-AgIII aryl transfer; and iv) ulterior reductive elimination of benzotrifluorides from an [aryl-AgIII -CF3 ] fragment. More precisely, an ultimate entry and full characterization of organosilver(III) compounds [K]+ [AgIII (CF3 )4 ]- (K-1), [(bpy)AgIII (CF3 )3 ] (2) and [(phen)AgIII (CF3 )3 ] (3), is described. The utility of 3 in cross-coupling has been showcased unambiguously, and a large variety of arylboron compounds was trifluoromethylated via [AgIII (aryl)(CF3 )3 ]- intermediates. This work breaks with old stereotypes and misconceptions regarding the inability of Ag to undergo cross-coupling by itself.

Cyclam-Based Chelators Bearing Phosphonated Pyridine Pendants for 64Cu-PET Imaging: Synthesis, Physicochemical Studies, Radiolabeling, and Bioimaging.

Herein we present the preparation of two novel cyclam-based macrocycles (te1pyp and cb-te1pyp), bearing phosphonate-appended pyridine side arms for the coordination of copper(II) ions in the context of 64Cu PET imaging. The two ligands have been prepared through conventional protection-alkylation sequences on cyclam, and their coordination properties have been thoroughly investigated. The corresponding copper complexes have been fully characterized in the solid state (X-ray diffraction analysis) and in solution (EPR and UV-vis spectroscopies). Potentiometric studies combined with spectrometry have also allowed us to determine their thermodynamic stability constants, confirming their high affinity for copper(II) cations. The kinetic inertness of the complexes has been verified by acid-assisted dissociation experiments, enabling their use in 64Cu-PET imaging in mice for the first time. Indeed, the two ligands could be quantitatively radiolabeled under mild conditions, and the resulting 64Cu complexes have demonstrated excellent stability in serum. PET imaging demonstrated a set of features emerging from the combination of picolinates and phosphonate units: high stability in vivo, fast clearance from the body via renal elimination, and most interestingly, very low fixation in the liver. This is in contrast with what was observed for monopicolinate cyclam (te1pa), which had a non-negligible accumulation in the liver, owing probably to its different charge and lipophilicity. These results thus pave the way for the use of such phosphonated pyridine chelators for in vivo 64Cu-PET imaging.