A versatile fluorinated azamacrocyclic chelator enabling 18F PET or 19F MRI: a first step towards new multimodal and smart contrast agents.

Macrocyclic chelators play a central role in medical imaging and nuclear medicine owing to their unparalleled metal cation coordination abilities. Their functionalization by fluorinated groups is an attractive design, to combine their properties with those of 18F for Positron Emission Tomography (PET) or natural 19F for Magnetic Resonance Imaging (MRI), and access potential theranostic or smart medical imaging probes. For the first time, a compact fluorinated macrocyclic architecture has been synthesized, based on a cyclen chelator bearing additional pyridine coordinating units and simple methyltrifluoroborate prosthetic groups. This ligand and its corresponding model Zn(ii) complex were investigated to evaluate the 18F-PET or 19F MRI abilities provided by this novel molecular structure. The chelator and the complex were obtained via a simple and high-yielding synthetic route, present excellent solvolytic stability of the trifluoroborate groups at various pH, and provide facile late-stage 18F-radiolabeling (up to 68% radiochemical yield with high activity) as well as a satisfying detection limit for 19F MRI imaging (low mM range).

Unraveling C-Selective Ring-Opening of Phosphiranes with Carboxylic Acids and Other Nucleophiles: A Mechanistically-Driven Approach.

Phosphiranes are weak Lewis bases reacting with only a limited number of electrophiles to produce the corresponding phosphiranium ions. These salts are recognized for their propensity to undergo reactions with oxygen pronucleophiles at the phosphorus site, leading to the formation of phosphine oxide adducts. Building on a thorough mechanistic understanding, we have developed an unprecedented approach that enables the selective reaction of carboxylic acids, and other nucleophiles, at the carbon site of phosphiranes. This method involves the photochemical generation of highly reactive carbenes, which react with 1-mesitylphosphirane to yield ylides. The latter undergoes a stepwise reaction with carboxylic acids, resulting in the production of the desired phosphines. In addition to DFT calculations, we have successfully isolated and fully characterized the key intermediates involved in the reaction.

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.

Copper-catalysed perarylation of cyclopentadiene: synthesis of hexaarylcyclopentadienes.

While hexaphenylsilacyclopentadiene (hexaphenylsilole) is viewed as an archetypal Aggregation-Induced Emission (AIE) luminogen, its isostructural hydrocarbon surrogate hexaphenylcyclopentadiene has strikingly never been investigated in this context, most probably due to a lack of synthetic availability. Herein, we report a straightforward synthesis of hexaphenylcyclopentadiene, via the direct perarylation of cyclopentadiene upon copper(i) catalysis under microwave activation, with the formation of six new C-C bonds in a single synthetic operation. Using zirconocene dichloride as a convenient source of cyclopentadiene and a variety of aryl iodides as coupling partners, this copper-catalysed cross-coupling reaction gave rise to a series of unprecedented hexaarylcyclopentadienes. The latter are direct precursors of extended π-conjugated polycyclic compounds, and their cyclodehydrogenation under Scholl reaction conditions yielded helicenic 17,17-diarylcyclopenta[l,l']diphenanthrenes. These structurally complex polyannelated fluorene derivatives can now be prepared in only two synthetic steps from cyclopentadiene.

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.

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.

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.

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.

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.

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.

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.

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.

Novel N(SCF3)(CF3)-amines: synthesis, scalability and stability.

We disclosed herein a straightforward strategy for the synthesis of unprecedented N-((trifluoromethyl)thio), N-(trifluoromethyl) amines using a combination of isothiocyanates with a fluoride source and an electrophilic trifluoromethylthiolation reagent. More interestingly, the scalability of the methodology has been demonstrated and the stability of the new motif has been studied.

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.

Electrophilicity of neutral square-planar organosilver(III) compounds.

Neutral Ag(III) complexes stabilised with just monodentate ligands are here unambiguously established. In a series of square-planar (CF3)3Ag(L) compounds with hard and soft Group 15 donor ligands, L, the metal center has been found to exhibit substantial acidity favouring apical coordination of an additional ligand under no coordination constraints.

Using a diphenyl-bi-(1,2,4-triazole) tricarbonylrhenium(I) complex with intramolecular π-π stacking interaction for efficient solid-state luminescence enhancement.

Since intramolecular π-π stacking interactions can modify the geometry, crystal packing mode, or even the electronic properties of transition metal complexes, they are also likely to influence the solid-state luminescence properties. Following this concept, a new tricarbonylrhenium(I) complex (Re-BPTA) was designed, based on a simple symmetrical 5,5'-dimethyl-4,4'-diphenyl-3,3'-bi-(1,2,4-triazole) organic ligand. The complex was prepared in good yield using a three-step procedure. The crystallographic study revealed that both phenyl rings are located on the same side of the molecule, and twisted by 71° and 62°, respectively, with respect to the bi-(1,2,4-triazole) unit. They overlap significantly, although they are slipped parallel to each other to minimize the intramolecular interaction energy. The π-π stacking interaction was also revealed by 1H NMR spectroscopy, in good agreement with the results of theoretical calculations. In organic solutions, a peculiar electrochemical signature was observed compared to closely-related pyridyl-triazole (pyta)-based complexes. With regard to the optical properties, the stiffness of the Re-BPTA complex led to the stabilization of the 3MLCT state, and thus to an enhancement of the red phosphorescence emission compared to the more flexible pyta complexes. However, an increased sensitivity to quenching by oxygen appeared. In the microcrystalline phase, the Re-BPTA complex showed strong photoluminescence (PL) emission in the green-yellow wavelength range (λPL = 548 nm, ΦPL = 0.52, 〈τPL〉 = 713 ns), and thus a dramatic solid-state luminescence enhancement (SLE) effect. These attractive emission properties can be attributed to the fact that the molecule undergoes little distortion between the ground state and the triplet excited state, as well as to a favorable intermolecular arrangement that minimizes detrimental interactions in the crystal lattice. The aggregation-induced phosphorescence emission (AIPE) effect was clear, with a 7-fold increase in emission intensity at 546 nm, although the aggregates formed in aqueous medium were much less emissive than the native microcrystalline powder. In this work, the rigidity of the Re-BPTA complex is reinforced by the intramolecular π-π stacking interaction of the phenyl rings. This original concept provides a rhenium tricarbonyl compound with very good SLE properties, and could be used more widely to successfully develop this area of research.

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.

Imine-stabilized silylium ions: synthesis, structure and application in catalysis.

Novel norbornene-based imine-stabilized silylium ions 2 have been synthesized via the simple reaction of sulfide-stabilized silylium ion 1 with carbonyl derivatives. Those silylium ions were fully characterized in solution and in the solid state by NMR spectroscopy and X-ray diffraction analysis as well as DFT calculations. Unlike the previously reported phosphine-stabilized silylium ion VI, behaving as a Lewis pair, calculations show that 2 have a strong Lewis acid character. Indeed, imine-stabilized silylium ions 2 are able to activate Si-H bonds and catalyzed the hydrosilylation of carbonyl derivatives under mild conditions.

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.

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.