How to Deal with Charge in the Ranking of Lewis Acidity: Critical Evaluation of an Extensive Set of Cationic Lewis Acids.

The quantification of Lewis acidity is of fundamental and applied importance in chemistry. However, if neutral and charged Lewis acids are compared, a coherent ranking has been elusive, and severe uncertainties were accepted. With this study, we present a systematic computational analysis of Lewis base affinities of 784 mono-, di- and tricationic Lewis acids and their comparison with 149 representative neutral Lewis acids. Evaluating vacuum fluoride ion affinities (FIA) reveals a charge-caused clustering that prohibits any meaningful ranking. Instead, solvation-corrected FIAsolv is identified as a metric that overcomes charge sensitivity in a balanced manner, allowing for a coherent evaluation of Lewis acidity across varying charge states. Analyzing the impact of molecular volume on solvation-induced FIA damping provides rationales for fundamental trends and guidelines for the choice or design of neutral and cationic Lewis acids in the condensed phase. Exploring alternative scales, explicit counteranion effects, and selected experimental case studies reaffirms the advantages of solvation-corrected FIAsolv as the most versatile and practical approach for the quantitative ranking of general (thermodynamic) Lewis acidity.

Intramolecular dearomative 1,4-addition of silyl and germyl radicals to a phenyl moiety.

Herein, we present that the radicals [Ph3PC(Me)EMes2]˙ (2Si and 2Ge) can be generated from the α-silylated and α-germylated phosphorus ylides Ph3PC(Me)E(Cl)Mes2 (1Si and 1Ge) through one-electron reduction with Jones' dimer (MesNacNacMg)2 in benzene. Although isolation of the free radicals was not possible, the products of the intramolecular addition of the radicals to a phenyl substituent of the phosphorus moiety, followed by subsequent reaction with 2Si or 2Ge to the isolated species 3Si and 3Ge, respectively, were observed. This transformation witnesses a dearomative 1,4-addition of tetryl radical species to the phenyl scaffold in a stereoselective anti-fashion.

Quo Vadis CO2 Activation: Catalytic Reduction of CO2 to Methanol Using Aluminum and Gallium/Carbon-based Ambiphiles.

We report on so-called "hidden FLPs" (FLP: frustrated Lewis pair) consisting of a phosphorus ylide featuring a group 13 fragment in the ortho position of a phenyl ring scaffold to form five-membered ring structures. Although the formation of the Lewis acid/base adducts was observed in the solid state, most of the title compounds readily react with carbon dioxide to provide stable insertion products. Strikingly, 0.3-3.0 mol% of the reported aluminum and gallium/carbon-based ambiphiles catalyze the reduction of CO2 to methanol with satisfactory high selectivity and yields using pinacol borane as stoichiometric reduction equivalent. Comprehensive computational studies provided valuable mechanistic insights and shed more light on activity differences.

A crystalline aluminium-carbon-based ambiphile capable of activation and catalytic transfer of ammonia in non-aqueous media.

Despite recent achievements in the field of frustrated Lewis pairs (FLPs) for small molecule activations, the reversible activation and catalytic transformations of N-H-activated ammonia remain a challenge. Here we report on a rare combination of an aluminium Lewis acid and a carbon Lewis base. A so-called hidden FLP consisting of a phosphorus ylide featuring an aluminium fragment in the ortho position of a phenyl ring scaffold is introduced. Although the formation of the Lewis acid/base adduct is observed in the solid state, which at first glance leads to formally quenched FLP reactivity, we show that the title compound readily reacts with non-aqueous ammonia thermoneutrally and splits the N-H bond reversibly at ambient temperature. In addition, NH3 transfer reactions mediated by a main-group catalyst are presented. This proof-of-principle study is expected to initiate further activities in utilizing N-H-activated ammonia as a readily available, atom-economical nitrogen source.

Synthesis, Crystal Structures, and Ion Pairing of κ6 N Complexes with Rare-Earth Elements in the Solid State and in Solution.

The rare earth element complexes (Ln=Y, La, Sm, Lu, Ce) of several podant κ6 N-coordinating ligands have been synthetized and thoroughly characterized. The structural properties of the complexes have been investigated by X-ray diffraction in the solid state and by advanced NMR methods in solution. To estimate the donor capabilities of the presented ligands, an experimental comparison study has been conducted by cyclic voltammetry as well as absorption experiments using the cerium complexes and by analyzing 89 Y NMR chemical shifts of the different yttrium complexes. In order to obtain a complete and detailed picture, all experiments were corroborated by state-of-the-art quantum chemical calculations. Finally, coordination competition studies have been carried out by means of 1 H and 31 P NMR spectroscopy to investigate the correlation with donor properties and selectivity.

Boron-Centered Lewis Superacid through Redox-Active Ligands: Application in C-F and S-F Bond Activation.

A series of redox-responsive ferrocenyl-substituted boranes and boronic esters were synthesized. Oxidation of the ferrocenyl ligand to the ferrocenium resulted in a drastic increase in the Lewis acidity beyond the strength of SbF5 , which was investigated experimentally and computationally. The resulting highly Lewis acidic boron compounds were used for catalytic C-F and S-F bond activation.

Heterobimetallic Gold/Ruthenium Complexes Synthesized via Post-functionalization and Applied in Dual Photoredox Gold Catalysis.

The synthesis of heterobimetallic AuI /RuII complexes of the general formula syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 is reported. The ditopic bridging ligand L1∩L2 refers to a P,N hybrid ligand composed of phosphine and bipyridine substructures, which was obtained via a post-functionalization strategy based on Diels-Alder reaction between a phosphole and a maleimide moiety. It was found that the stereochemistry at the phosphorus atom of the resulting 7-phosphanorbornene backbone can be controlled by executing the metal coordination and the cycloaddition reaction in a different order. All precursors, as well as the mono- and multimetallic complexes, were isolated and fully characterized by various spectroscopic methods such as NMR, IR, and UV-vis spectroscopy as well as cyclic voltammetry. Photophysical measurements show efficient phosphorescence for the investigated monometallic complex anti-[(L1∩L2){Ru(bpy)2 }][PF6 ]2 and the bimetallic analogue syn-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 , thus indicating a small influence of the {AuCl} fragment on the photoluminescence properties. The heterobimetallic AuI /RuII complexes syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 are both active catalysts in the P-arylation of aryldiazonium salts promoted by visible light with H-phosphonate affording arylphosphonates in yields of up to 91 %. Both dinuclear complexes outperform their monometallic counterparts.

A neutral, acyclic, borataalkene-like ligand for group 11 metals: L- and Z-type ligands side by side.

The overall neutral α-borylated phosphorus ylide Ph3PC(Me)BEt2 behaves like a polar borataalkene and can act as acyclic, ambiphilic π-type ligand with L- and Z-type functionalities side by side. In the complexes [MX{η2-Ph3PC(Me)BEt2}] (M = Cu, (Ag), Au; X = Cl, NTf2), the bonding is dominated by the highly nucleophilic ylidic carbon atom (L-type ligand). The Lewis acidic boron atom furnishes nonetheless a small but significant bonding contribution (Z-type ligand).

Accessing Cationic α-Silylated and α-Germylated Phosphorus Ylides.

The synthesis and full characterization of α-silylated (α-SiCPs; 1-7) and α-germylated (α-GeCPs; 11-13) phosphorus ylides bearing one chloride substituent R3 PC(R1 )E(Cl)R2 2 (R=Ph; R1 =Me, Et, Ph; R2 =Me, Et, iPr, Mes; E=Si, Ge) is presented. The molecular structures were determined by X-ray diffraction studies. The title compounds were applied in halide abstraction studies in order to access cationic species. The reaction of Ph3 PC(Me)Si(Cl)Me2 (1) with Na[B(C6 F5 )4 ] furnished the dimeric phosphonium-like dication [Ph3 PC(Me)SiMe2 ]2 [B(C6 F5 )4 ]2 (8). The highly reactive, mesityl- or iPr-substituted cationic species [Ph3 PC(Me)SiMes2 ][B(C6 F5 )4 ] (9) and [Ph3 PC(Et)SiiPr2 ][B(C6 F5 )4 ] (10) could be characterized by NMR spectroscopy. Carrying out the halide abstraction reaction in the sterically demanding ether iPr2 O afforded the protonated α-SiCP [Ph3 PCH(Et)Si(Cl)iPr2 ][B(C6 F5 )4 ] (6 dec) by sodium-mediated basic ether decomposition, whereas successfully synthesized [Ph3 PC(Et)SiiPr2 ][B(C6 F5 )4 ] (10) readily cleaves the F-C bond in fluorobenzene. Thus, the ambiphilic character of α-SiCPs is clearly demonstrated. The less reactive germanium analogue [Ph3 PC(Me)GeMes2 ][B{3,5-(CF3 )2 C6 H3 }4 ] (14) was obtained by treating 11 with Na[B{3,5-(CF3 )2 C6 H3 }4 ] and fully characterized including by X-ray diffraction analysis. Structural parameters indicate a strong CYlide -Ge interaction with high double bond character, and consequently the C-E (E=Si, Ge) bonds in 9, 10 and 14 were analyzed with NBO and AIM methods.

Multistimuli-Responsive [3]Dioxaphosphaferrocenophanes with Orthogonal Switches.

Novel multistimuli-responsive phosphine ligands comprising a redox-active [3]dioxaphosphaferrocenophane backbone and a P-bound imidazolin-2-ylidenamino entity that allows switching by protonation are reported. Investigation of the corresponding metal complexes and their redox behaviour are reported and show the sensitivity of the system towards protonation and metal coordination. The experimental findings are supported by DFT calculations. Protonation and oxidation events are applied in Rh-catalysed hydrosilylations and demonstrate a remarkable influence on reactivity and/or selectivity.

Phosphine-substituted 1,2,3-triazoles as P,C- and P,N-ligands for photoluminescent coinage metal complexes.

A series of homo- and hetero-polynuclear coinage metal complexes based on a phosphine-substituted 1,2,3-triazole system is presented. Besides the P,N-ligand 1-benzyl-4-(diphenylphosphanyl)-1H-1,2,3-triazole (LPN), the P,C-donor ligand 1-benzyl-4-(diphenylphosphanyl)-3-methyl-1H-1,2,3-triazolium (LPCH+), featuring a potential mesoionic carbene moiety, was obtained by methylation of LPN. Starting from the monogold chloride complexes AuCl(LPN/LPC), the syntheses of a heterotrinuclear Au2Cu complex as well as a digold carbene complex are described. The multinuclear complexes show metallophilic interactions. Their photophysical properties were investigated by temperature-dependent photoluminescence (PL) measurements. In particular, the digold complex shows interesting PL properties including narrow exciton peaks arising in the excitation and emission spectra below 50 K. These might be related to the molecular 'chains' in the crystal structure of the digold complex, formed by phenyl ligand stacking.

Protein kinase A regulates inflammatory pain sensitization by modulating HCN2 channel activity in nociceptive sensory neurons.

Several studies implicated cyclic adenosine monophosphate (cAMP) as an important second messenger for regulating nociceptor sensitization, but downstream targets of this signaling pathway which contribute to neuronal plasticity are not well understood. We used a Cre/loxP-based strategy to disable the function of either HCN2 or PKA selectively in a subset of peripheral nociceptive neurons and analyzed the nociceptive responses in both transgenic lines. A near-complete lack of sensitization was observed in both mutant strains when peripheral inflammation was induced by an intradermal injection of 8br-cAMP. The lack of HCN2 as well as the inhibition of PKA eliminated the cAMP-mediated increase of calcium transients in dorsal root ganglion neurons. Facilitation of Ih via cAMP, a hallmark of the Ih current, was abolished in neurons without PKA activity. Collectively, these results show a significant contribution of both genes to inflammatory pain and suggest that PKA-dependent activation of HCN2 underlies cAMP-triggered neuronal sensitization.

Sex and age interaction with genetic association of atherogenic uric acid concentrations.

BACKGROUND: High serum uric acid levels are associated with gout, atherosclerosis and cardiovascular disease. Three genes (SLC2A9, ABCG2, and SLC17A3) were reported to be involved in the regulation of uric acid levels. DESIGN AND METHODS: SNPs rs2231142 (ABCG2) and rs1165205 (SLC17A3) were genotyped in three cohorts (n=4492) and combined with previously genotyped SNPs within SLC2A9 (rs6855911, rs7442295, rs6449213, rs12510549). RESULTS: Each copy of the minor allele decreased uric acid levels by 0.30-0.38 mg/dL for SLC2A9 (p values: 10(-20)-10(-36)) and increased levels by 0.34 mg/dL for ABCG2 (p=1.1x10(-16)). SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed graded associations with uric acid levels of 0.111 mg/dL per risk allele (p=3.8x10(-42)). In addition, we observed a sex-specific interaction of age with the association of SLC2A9 SNPs with uric acid levels, where increasing age strengthened the association of SNPs in women and decreased the association in men. CONCLUSIONS: Genetic variants within SLC2A9,ABCG2 and SLC17A3 show highly significant associations with uric acid levels, and for SNPs within SLC2A9 this association is strongly modified by age and sex.