Synthesis and reactivity of N-heterocyclic carbene (NHC)-supported heavier nitrile ylides.

The synthesis and isolation of stable heavier analogues of nitrile ylide as N-heterocyclic carbene (NHC) adducts of phosphasilenyl-tetrylene [(NHC)(TerAr)Si(H)PE14(TerAr)] (E14 = Ge 1, Sn 2; TerAr = 2,6-Mes2C6H3, NHC = IMe4) are reported. The delocalized Si-P-E14 π-conjugation was examined experimentally and computationally. Interestingly, the germanium derivative 1 exhibits a 1,3-dipolar nature, leading to an unprecedented [3 + 2] cycloaddition with benzaldehyde, resulting in unique heterocycles containing four heteroatoms from group 14, 15, and 16. Further exploiting the nucleophilicity of germanium, activation of the P-P bond of P4 was achieved, leading to a [(NHC)(phosphasilenyl germapolyphide)] complex. Moreover, the [3 + 2] cycloaddition and the σ-bond activation by 1 resemble the characteristics of the classic nitrile ylide.

Potent Anticancer Activity of a Dinuclear Gold(I) bis-N-Heterocyclic Imine Complex Related to Thioredoxin Reductase Inhibition in Vitro.

A dinuclear gold(I) complex featuring a strongly donating bis-N-heterocyclic imine ligand was synthesised and characterised by different methods, including single crystal X-ray diffraction (SC-XRD) analysis. The compound has been tested for its antiproliferative effects in a panel of human cancer cell lines in vitro, showing highly selective anticancer effects, particularly against human A549 non-small cell lung cancer cells (NSCLC), with respect to non-tumorigenic cells (VERO). The accumulation of the compound in A549 and VERO cells was studied by high-resolution continuum source atomic absorption spectrometry (HRCS-AAS), revealing that the anticancer effects are not particularly related to the different amounts of gold taken up by the cells over 72 h. Enzyme inhibition studies to evaluate the activity of the seleno-enzyme thioredoxin reductase (TrxR) in cancer cell extracts show that the gold(I) compound is a potent inhibitor (IC50=0.567±0.208 µM), while the free ligand is ineffective. This result correlates with the observed compound's selectivity towards A549 cells overexpressing the enzyme.

Anions featuring an aluminium-silicon core with alumanyl silanide and aluminata-silene characteristics.

Molecular species containing multiple bonds to aluminium have long been challenging synthetic targets. Despite recent landmark discoveries in this area, heterodinuclear Al-E multiple bonds (where E is a group-14 element) have remained rare and limited to highly polarized π-interactions (Al=E ↔ +Al-E-). Here we report the isolation of three alumanyl silanide anions that feature an Al-Si core stabilized by bulky substituents and a Si-Na interaction. Single-crystal X-ray diffraction studies, spectroscopic analysis and density functional theory calculations show that the Al-Si interaction possesses partial double bond character. Preliminary reactivity studies support this description of the compounds through two resonance structures: one that displays a predominant nucleophilic character of the sodium-coordinated silicon centre in the Al-Si core, as shown by silanide-like reactivity towards halosilane electrophiles and the CH-insertion of phenylacetylene. Moreover, we report an alumanyl silanide with a sequestered sodium cation. Cleavage of the Si-Na bond by [2.2.2]cryptand increases the double bond character of the Al-Si core to produce an anion with high aluminata-silene (-Al=Si) character.

Room Temperature Intermolecular Dearomatization of Arenes by an Acyclic Iminosilylene.

A novel nontransient acyclic iminosilylene (1), bearing a bulky super silyl group (-SitBu3) and N-heterocyclic imine ligand with a methylated backbone, was prepared and isolated. The methylated backbone is the feature of 1 that distinguishes it from the previously reported nonisolable iminosilylenes, as it prevents the intramolecular silylene center insertion into an aromatic C-C bond of an aryl substituent. Instead, 1 exhibits an intermolecular Büchner-ring-expansion-type reactivity; the silylene is capable of dearomatization of benzene and its derivatives, giving the corresponding silicon analogs of cycloheptatrienes, i.e. silepins, featuring seven-membered SiC6 rings with nearly planar geometry. The ring expansion reactions of 1 with benzene and 1,4-bis(trifluoromethyl)benzene are reversible. Similar reactions of 1 with N-heteroarenes (pyridine and DMAP) proceed more rapidly and irreversibly forming the corresponding azasilepins, also with nearly planar seven-membered SiNC5 rings. DFT calculations reveal an ambiphilic nature of 1 that allows the intermolecular aromatic C-C bond insertion to occur. Additional computational studies, which elucidate the inherent reactivity of 1, the role of the substituent effect, and reaction mechanisms behind the ring expansion transformations, are presented.

Room-Temperature-Observable Interconversion Between Si(IV) and Si(II) via Reversible Intramolecular Insertion Into an Aromatic C-C Bond.

An easily isolable silacycloheptatriene (silepin) 1 b was synthesized from the reaction of a N-heterocyclic imino (IPrN) substituted tribromosilane IPrNSiBr3 with the sterically congested bis(trimethylsilyl)triisopropylsilyl silanide KSi(TMS)2 Si(i Pr)3 (BTTPS). In solution, the Si(IV) silepin 1 b is in a thermodynamic equilibrium with the acyclic Si(II) silylene 1 a. The relative concentration of the Si(II) or Si(IV) isomers can be controlled by temperature variation and observed by variable temperature NMR and UV/Vis spectroscopy. DFT calculations show a small reaction barrier for the Si(II)⇌Si(IV) interconversion and a small energy gap between the Si(II) and Si(IV) species. The reactivity of 1 a/b is demonstrated on a variety of small molecules.

Isolation and Reactivity of Tetrylene-Tetrylone-Iron Complexes Supported by Bis(N-Heterocyclic Imine) Ligands.

The germanium iron carbonyl complex 3 was prepared by the reaction of dimeric chloro(imino)germylene [IPrNGeCl]2 (IPrN=bis(2,6-diisopropylphenyl)imidazolin-2-iminato) with one equivalent of Collman's reagent (Na2 Fe(CO)4 ) at room temperature. Similarly, the reaction of chloro(imino)stannylene [IPrNSnCl]2 with Na2 Fe(CO)4 (1 equiv) resulted in the Fe(CO)4 -bridged bis(stannylene) complex 4. We observed reversible formation of bis(tetrylene) and tetrylene-tetrylone character in complexes 3 vs. 5 and 4 vs. 6, which was supported by DFT calculations. Moreover, the Li/Sn/Fe trimetallic complex 12 has been isolated from the reaction of [IPrNSnCl]2 with cyclopentadienyl iron dicarbonyl anion. The computational analysis further rationalizes the reduction pathway from these chlorotetrylenes to the corresponding complexes.

Isolation of Cyclic Aluminium Polysulfides by Stepwise Sulfurization.

Despite the notable progress in aluminium chalcogenides, their sulfur congeners have rarely been isolated under mild conditions owing to limited synthetic precursors and methods. Herein, facile isolation of diverse molecular aluminium sulfides is achievable, by the reaction of N-heterocyclic carbene-stabilized terphenyl dihydridoaluminium (1) with various thiation reagents. Different to the known dihydridoaluminium 1Tipp , 1 features balanced stability and reactivity at the Al center. It is this balance that enables the first monomeric aluminium hydride hydrogensulfide 2, the six-membered cyclic aluminium polysulfide 4 and the five-membered cyclic aluminium polysulfide 6 to be isolated, by reaction with various equivalents of elemental sulfur. Moreover, a rare aluminium heterocyclic sulfide with Al-S-P five-membered ring (7) was obtained in a controlled manner. All new compounds were fully characterized by multinuclear NMR spectroscopy and elemental analysis. Their structures were confirmed by single-crystal X-ray diffraction studies.

Application of ferrocene-bridged N-heterocyclic carbene stabilised bis-phosphinidenes in Sn(II) complexation.

Two new bidentate ferrocene-bridged bis(N-heterocyclic carbene-phospinidenes) (bisNHCPs) were successfully isolated by treating 1,1'-bis-(dichlorophosphine)ferrocene with N-heterocyclic carbenes, followed by dechlorination using sodium naphthalenide. The bisNHCPs were used in complexation of various Sn(II) halides and Sn(II) bistriflate (SnX2 with X = Cl, Br, I, OTf). Transmetalation to a CuCl complex and Sn(II) transfer to a bisimine was performed to investigate the stannyliumylidenes' reactivity.

Bis(perfluoropinacolato)silane: A Neutral Silane Lewis Superacid Activates Si-F Bonds.

Despite the earth abundance and easy availability of silicon, only few examples of isolable neutral silicon centered Lewis superacids are precedent in the literature. To approach the general drawbacks of limited solubility and unselective deactivation pathways, we introduce a Lewis superacid, based on perfluorinated pinacol substituents. The compound is easily synthesized on a gram-scale as the corresponding acetonitrile mono-adduct 1⋅(MeCN) and was fully characterized, including single crystal X-ray diffraction analysis (SC-XRD) and state-of-the-art computations. Lewis acidity investigations by the Gutmann-Beckett method and fluoride abstraction experiments indicate a Lewis superacidic nature. The challenging Si-F bond activation of Et3 SiF is realized and promising catalytic properties are demonstrated, consolidating the potential applicability of silicon centered Lewis acids in synthetic catalysis.

An Isolable Three-Coordinate Germanone and Its Reactivity.

A rare three-coordinate germanone [IPrN]2 Ge=O (IPrN=bis(2,6-diisopropylphenyl)imidazolin-2-imino) was successfully isolated. The germanone has a rather high thermal stability in arene solvent, and no detectable change was observed at 80 °C for at least one week. However, high thermal stability of [IPrN]2 Ge=O does not prevent its reactivity toward small molecules. Structural analysis and initial reactivity studies revealed the highly polarized nature of the terminal Ge=O bond. Besides, the addition of phenylacetylene, as well as O-atom transfer with 2,6-dimethylphenyl isocyanide make it a mimic of nucleophilic transition-metal oxides. Mechanism for O-atom transfer reaction was investigated via DFT calculations, which revealed that the reaction proceeds via a [2+2] cycloaddition intermediate.

A Zwitterionic Heterobimetallic Gold-Iron Complex Supported by Bis(N-Heterocyclic Imine)Silyliumylidene.

The facile synthesis of the first bis-N-heterocyclic imine-stabilized chlorosilyliumylidene 1 is reported. Remarkably, consecutive reaction of 1 with PPh3 AuCl and K2 Fe(CO)4 gives rise to the unique heterobimetallic complex 1,2-(Mes NHI)2 -C2 H4 -ClSiAuFe(CO)4 (4). The overall neutral complex 4 bears an unusual linear Si-Au-Fe structure and a rare anagostic interaction between the d10 -configured gold atom and a CH bond of the mesityl ligand. According to the computational analysis and 57 Fe Mössbauer spectroscopy, the formal Fe-oxidation state remains at -II. Thus, the electronic structure of 4 is best described as an overall neutral-yet zwitterionic-heterobimetallic "Si(II)+ -Au(I)+ -Fe(-II)2- "-silyliumylidene complex, derived from double anion exchange. The computational analysis indicates strong hyperconjugative back donation from the gold(I) atom to the silyliumylidene ligand.

An Air-Stable Heterobimetallic Si2 M2 Tetrahedral Cluster.

Air- and moisture-stable heterobimetallic tetrahedral clusters [Cp(CO)2 MSiR]2 (M=Mo or W; R=SitBu3 ) were isolated from the reaction of N-heterocyclic carbene (NHC) stabilized silyl(silylidene) metal complexes Cp(CO)2 M=Si(SitBu3 )NHC with a mild Lewis acid (BPh3 ). Alternatively, treatment of the NHC-stabilized silylidene complex Cp(CO)2 W=Si(SitBu3 )NHC with stronger Lewis acids such as AlCl3 or B(C6 F5 )3 resulted in the reversible coordination of the Lewis acid to one of the carbonyl ligands. Computational investigations revealed that the dimerization of the intermediate metal silylidyne (M≡Si) complex to a tetrahedral cluster instead of a planar four-membered ring is due to steric bulk.

Dialumenes - aryl vs. silyl stabilisation for small molecule activation and catalysis.

Main group multiple bonds have proven their ability to act as transition metal mimics in the last few decades. However, catalytic application of these species is still in its infancy. Herein we report the second neutral NHC-stabilised dialumene species by use of a supporting aryl ligand (3). Different to the trans-planar silyl-substituted dialumene (3Si), compound 3 features a trans-bent and twisted geometry. The differences between the two dialumenes are explored computationally (using B3LYP-D3/6-311G(d)) as well as experimentally. A high influence of the ligand's steric demand on the structural motif is revealed, giving rise to enhanced reactivity of 3 enabled by a higher flexibility in addition to different polarisation of the aluminium centres. As such, facile activation of dihydrogen is now achievable. The influence of ligand choice is further implicated in two different catalytic reactions; not only is the aryl-stabilised dialumene more catalytically active but the resulting product distributions also differ, thus indicating the likelihood of alternate mechanisms simply through a change of supporting ligand.

Recent advances of group 14 dimetallenes and dimetallynes in bond activation and catalysis.

Since the first heavy alkene analogues of germanium and tin were isolated in 1976, followed by West's disilene in 1981, the chemistry of stable group 14 dimetallenes and dimetallynes has advanced immensely. Recent developments in this field veered the focus from the isolation of novel bonding motifs to mimicking transition metals in their ability to activate small molecules and perform catalysis. The potential of these homonuclear multiply bonded compounds has been demonstrated numerous times in the activation of H2, NH3, CO2 and other small molecules. Hereby, the strong relationship between structure and reactivity warrants close attention towards rational ligand design. This minireview provides an overview on recent developments in regard to bond activation with group 14 dimetallenes and dimetallynes with the perspective of potential catalytic applications of these compounds.

NHC-Stabilized Silyl-Substituted Chlorosilylene.

The first N-heterocyclic carbene (NHC) stabilized silyl-substituted chlorosilylene (1) was isolated via selective dehydrochlorination by NHC from silyl-based Si(IV) precursor tBu3SiSiHCl2. Compound 1 can form an iron chlorosilylene complex (2) with an iron carbonyl dimer and undergoes chloride/hydride metathesis to yield a stable NHC-silylene hydride borane adduct (3). Upon treatment with additional NHC, chlorosilylene 1 was converted into silyl-substituted silyliumylidene ions (4).

N-Heterocyclic Carbene-Stabilized Germanium and Tin Analogues of Heavier Nitriles: Synthesis, Reactivity, and Catalytic Application.

The synthesis of stable heavier analogues of nitriles as monomeric tetrylene-phosphinidenes MesTerEP(IDipp) (E = Ge, Sn; MesTer = 2,6-Mes2C6H3, IDipp = C([N-(2,6-iPr2C6H4)CH]2) was achieved by taking advantage of NHC (N-heterocyclic carbene, here IDipp) coordination to the low-valent phosphorus center. Multiple bonding character of the E-P bonds was examined experimentally and computationally. Both germanium and tin compounds undergo [2+2] cycloaddition with diphenylketene, whereas reaction of the tin derivative with tris(pentafluorophenyl)borane provided unique "push-pull" phosphastannene (MesTer)(Ar)Sn = P(IDipp) (Ar = C6F4[B(F)(C6F5)2]). Going further, we demonstrated the potential of tetrylene-phosphinidene complexes in catalytic hydroboration of carbonyl compounds.

Sleep quality in patients with primary aldosteronism.

OBJECTIVE: In subjects at high risk for sleep apnea (SA), aldosterone concentrations correlate with severity of SA and primary aldosteronism (PA) is very often diagnosed. Patients with PA show a high prevalence of SA. Treatment of PA either by adrenalectomy (ADX) or mineralocorticoid receptor (MR) blockade is thought to abolish the increased comorbidities. However, no data are available regarding effectiveness of different PA treatments on quality of sleep. DESIGN: This prospective multi-center study included 15 patients with newly diagnosed PA evaluated before and 0.7 ± 0.2 years after treatment initiation, and a second cohort including 81 patients who were evaluated 5.3 and 6.8 years after treatment initiation. Biochemical parameters, 24h blood pressure and three validated self-assessment questionnaires (Giessen Complaint List (GBB-24), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality-Index (PSQI)) were analyzed. RESULTS: Z-scores of exhaustion tendency of GBB significantly improved in newly diagnosed PA patients after treatment initiation (1.8 ± 1.4 vs. 1.0 ± 1.2, p=0.034). In the second cohort no differences were found in GBB-24, ESS and PSQI. No differences were found in all three questionnaires independently of type of PA therapy. However, female patients scored significantly higher than males in the PSQI (8.7 ± 3.6 vs 5.7 ± 4.2, p<0.005), indicating lower sleep quality, independently of the type of therapy. CONCLUSIONS: For the first time, we analyzed quality of sleep in patients with PA, demonstrating that therapy initiation improves exhaustion tendency. Surprisingly, female PA patients showed significantly more sleep disturbances than male PA patients several years after treatment initiation.