Chromium Complexes with Benzanellated N-Heterocyclic Phosphenium Ligands-Synthesis, Reactivity and Application in Catalytic CO2 Reduction.

A chromium complex carrying two benzanellated N-heterocyclic phosphenium (bzNHP) ligands was prepared by a salt metathesis approach. Spectroscopic studies suggest that the anellation enhances the π-acceptor ability of the NHP-units, which is confirmed by the facile electrochemical reduction of the complex to a spectroscopically characterized radical anion. Co-photolysis with H2 allowed extensive conversion into a σ-H2-complex, which shows a diverse reactivity towards donors and isomerizes under H-H bond fission and shift of a hydride to a P-ligand. The product carrying phosphenium, phosphine and hydride ligands was also synthesized independently and reacts reversibly with CO and MeCN to yield bis-phosphine complexes under concomitant Cr-to-P-shift of a hydride. In contrast, CO2 was not only bound but reduced to give an isolable formato complex, which reacted with ammonia borane under partial recovery of the metal hydride and production of formate. Further elaboration of the reactions of the chromium complexes with CO2 and NH3BH3 allowed to demonstrate the feasibility of a Cr-catalyzed transfer hydrogenation of CO2 to methanol. The various complexes described were characterized spectroscopically and in several cases by XRD studies. Further insights in reactivity patterns were provided through (spectro)electrochemical studies and DFT calculations.

Azophosphines: Synthesis, Structure and Coordination Chemistry.

The conceptual replacement of nitrogen with phosphorus in common organic functional groups unlocks new properties and reactivity. The phosphorus-containing analogues of triazenes are underexplored but offer great potential as flexible and small bite-angle ligands. This manuscript explores the synthesis and characterisation of a family of air-stable azophosphine-borane complexes, and their subsequent deprotection to the free azophosphines. These compounds are structurally characterised, both experimentally and computationally, and highlight the availability of the phosphorus lone pair for coordination. This is confirmed by demonstrating that neutral azophosphines can act as ligands in Ru complexes, and can coordinate as monodentate or bidentate ligands in a controlled manner, in contrast to their nitrogen analogues.

Synthesis of substituted triazole-pyrazole hybrids using triazenylpyrazole precursors.

A synthesis route to access triazole-pyrazole hybrids via triazenylpyrazoles was developed. Contrary to existing methods, this route allows the facile N-functionalization of the pyrazole before the attachment of the triazole unit via a copper-catalyzed azide-alkyne cycloaddition. The developed methodology was used to synthesize a library of over fifty new multi-substituted pyrazole-triazole hybrids. We also demonstrate a one-pot strategy that renders the isolation of potentially hazardous azides obsolete. In addition, the compatibility of the method with solid-phase synthesis is shown exemplarily.

Stereospecific Synthesis of Cyclohexenone Acids by [3,3]-Sigmatropic Rearrangement Route.

Herein we report a modular synthetic method for the preparation of diaryl-substituted cyclohexenone acids starting from phenyl pyruvate and suitable enones. When the reaction is carried out in alkaline tert-butanol or toluene solutions in microwave-assisted conditions mainly anti configuration products are obtained with up to 86% isolated yield. However, when the reaction is carried out in alkaline water, a mixture of products with anti and syn conformations is obtained with up to 98% overall isolated yield. Mechanistically the product with anti conformation forms by a hemiketal-oxy-Cope type [3,3]-sigmatropic rearrangement-intramolecular aldol condensation route and syn product by an intermolecular aldol condensation-electrocyclization (disrotatory type) route.

Synthesis of bis-thiohydantoin derivatives as an antiproliferative agents targeting EGFR inhibitory pathway.

(R)/(S)-the two enantiomers of 3-substituted-1-[2-(5)-3-substituted-4-benzyl-5-oxo-4-phenyl-2-thioxoimid-azolidin-1-yl]ethyl/propyl-5-benzyl-5-phenyl-2-thioxoimidazolidin-4-ones were formed during the diastereoselective reaction between N,N″-1,ω-alkanediylbis[N'-organylthiourea] derivatives and 2,3-diphenylcyclopropenone in refluxing ethanol. The structures of the isolated compounds were confirmed by NMR, IR, mass spectra and elemental analyses. Moreover, single-crystal X-ray structure analysis was also used to elucidate the structure of the isolated compounds. The mechanism describes the reaction was also discussed. The tested compounds showed EGFR inhibitory activity with IC50 values ranging from 90 to 178 nM in comparison to the erlotinib as a reference with IC50 value of 70 nM. Compound 4c (R = allyl, n = 3) was found as the most potent antiproliferative, had the highest inhibitory effect on EGFR with an IC50 value of 90 nM, compared to erlotinib's IC50 value of 70 nM. The second and third-most active compounds were 4e (R = phenyl, n = 3) and 4d (R = ethyl, n = 3) and with IC50 values of 107 nM and 128 nM. These findings imply that the compounds tested had a significant antiproliferative effect as well as the ability to act as an EGFR inhibitor. Docking studies showed that compound 4c showed high affinity to EGFR based on its docking score (S; kcal/mol) within five test compounds.

Homolytic C-H Bond Activation by Phosphine-Quinone-Based Radical Ion Pairs.

Herein, we present the formation of transient radical ion pairs (RIPs) by single-electron transfer (SET) in phosphine-quinone systems and explore their potential for the activation of C-H bonds. PMes3 (Mes=2,4,6-Me3 C6 H2 ) reacts with DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) with formation of the P-O bonded zwitterionic adduct Mes3 P-DDQ (1), while the reaction with the sterically more crowded PTip3 (Tip=2,4,6-iPr3 C6 H2 ) afforded C-H bond activation product Tip2 P(H)(2-[CMe2 (DDQ)]-4,6-iPr2 -C6 H2 ) (2). UV/Vis and EPR spectroscopic studies showed that the latter reaction proceeds via initial SET, forming RIP [PTip3 ]⋅+ [DDQ]⋅- , and subsequent homolytic C-H bond activation, which was supported by DFT calculations. The isolation of analogous products, Tip2 P(H)(2-[CMe2 {TCQ-B(C6 F5 )3 }]-4,6-iPr2 -C6 H2 ) (4, TCQ=tetrachloro-1,4-benzoquinone) and Tip2 P(H)(2-[CMe2 {oQtBu -B(C6 F5 )3 }]-4,6-iPr2 -C6 H2 ) (8, oQtBu =3,5-di-tert-butyl-1,2-benzoquinone), from reactions of PTip3 with Lewis-acid activated quinones, TCQ-B(C6 F5 )3 and oQtBu -B(C6 F5 )3 , respectively, further supports the proposed radical mechanism. As such, this study presents key mechanistic insights into the homolytic C-H bond activation by the synergistic action of radical ion pairs.

Water Reduction and Dihydrogen Addition in Aqueous Conditions With ansa-Phosphinoborane.

Ortho-phenylene-bridged phosphinoborane (2,6-Cl2 Ph)2 B-C6 H4 -PCy2 1 was synthesized in three steps from commercially available starting materials. 1 reacts with H2 or H2 O under mild conditions to form corresponding zwitterionic phosphonium borates 1-H2 or 1-H2 O. NMR studies revealed both reactions to be remarkably reversible. Thus, when exposed to H2 , 1-H2 O partially converts to 1-H2 even in the presence of multiple equivalents of water in the solution. The addition of parahydrogen to 1 leads to nuclear spin hyperpolarization both in dry and hydrous solvents, confirming the dissociation of 1-H2 O to free 1. These observations were supported by computational studies indicating that the formation of 1-H2 and 1-H2 O from 1 are thermodynamically favored. Unexpectedly, 1-H2 O can release molecular hydrogen to form phosphine oxide 1-O. Kinetic, mechanistic, and computational (DFT) studies were used to elucidate the unique "umpolung" water reduction mechanism.

Diversity-Oriented Synthesis of [2.2]Paracyclophane-derived Fused Imidazo[1,2-a]heterocycles by Groebke-Blackburn-Bienaymé Reaction: Accessing Cyclophanyl Imidazole Ligands Library.

This report describes the synthesis of a [2.2]paracyclophane-derived annulated 3-amino-imidazole ligand library through a Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR) approach employing formyl-cyclophanes in combination with diverse aliphatic and aromatic isocyanides and heteroaromatic amidines. The GBB-3CR process gives access to skeletally-diverse cyclophanyl imidazole ligands, namely 3-amino-imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrazines. Additionally, a one-pot protocol for the GBB-3CR by an in situ generation of cyclophanyl isocyanide is demonstrated. The products were analyzed by detailed spectroscopic techniques, and the cyclophanyl imidazo[1,2-a]pyridine was confirmed unambiguously by single-crystal X-Ray crystallography. The cyclophanyl imidazole ligands can be readily transformed to showcase their useful utility in preparing N,C-palladacycles through regioselective ortho-palladation.

Thermo-Reversible Cellulose Micro Phase-Separation in Mixtures of Methyltributylphosphonium Acetate and γ-Valerolactone or DMSO.

We have identified cellulose solvents, comprised of binary mixtures of molecular solvents and ionic liquids that rapidly dissolve cellulose to high concentration and show upper-critical solution temperature (UCST)-like thermodynamic behaviour - upon cooling and micro phase-separation to roughly spherical microparticle particle-gel mixtures. This is a result of an entropy-dominant process, controllable by changing temperature, with an overall exothermic regeneration step. However, the initial dissolution of cellulose in this system, from the majority cellulose I allomorph upon increasing temperature, is also exothermic. The mixtures essentially act as 'thermo-switchable' gels. Upon initial dissolution and cooling, micro-scaled spherical particles are formed, the formation onset and size of which are dependent on the presence of traces of water. Wide-angle X-ray scattering (WAXS) and 13 C cross-polarisation magic-angle spinning (CP-MAS) NMR spectroscopy have identified that the cellulose micro phase-separates with no remaining cellulose I allomorph and eventually forms a proportion of the cellulose II allomorph after water washing and drying. The rheological properties of these solutions demonstrate the possibility of a new type of cellulose processing, whereby morphology can be influenced by changing temperature.

Functionalized C3-Symmetric Building Blocks-The Chemistry of Triaminotrimesic Acid.

A series of C3-symmetric fully substituted benzenes were prepared based on alkyl triamino-benzene-tricarboxylates. Starting with a one step-synthesis, the alkyl triamino-benzene-tricarboxylates were synthesized using the corresponding cyanoacetates. The reactivity of these electronically sophisticated compounds was investigated by the formation of azides, the click reaction of the azides and a Sandmeyer-like reaction. Caused by the low stability of triaminobenzenes, direct N-alkylation was rarely reported. The use of the stable alkyl triamino-benzene-tricarboxylates allowed us total N-alkylation under standard alkylation conditions. The molecular structures of the C3-symmetric structures have been corroborated by an X-ray analysis.

Annellated 1,3,4,2-Triazaphospholenes-Simple Modular Synthesis and a First Exploration of Ligand Properties.

The successful use of 1,3,4,2-triazaphospholenes (TAPs) as organo-catalysts stresses the need for efficient synthetic routes to these molecules. In this study, we establish the [1 + 4]-cycloaddition of PBr3 to azo-pyridines as a new approach to preparing pyrido-annellated TAPs in a single step from easily available precursors. The modular assembly of the azo-component via condensation of primary amines and nitroso compounds along with the feasibility of post-functionalization at the P-Br bond under conservation of the heterocyclic structure allows, in principle, to address a wide range of target molecules, which is illustrated by prototypical examples. The successful synthesis of a transition metal complex confirms for the first time the ability of a TAP to act as a P-donor ligand. Crystallographic studies suggest that hyperconjugation effects and intermolecular interactions induce a qualitatively similar ionic polarization of the P-Br bonds in TAPs as in better known isoelectronic diazaphospholenes.

Autoxidation of 4-Hydrazinylquinolin-2(1H)-one; Synthesis of Pyridazino[4,3-c:5,6-c']diquinoline-6,7(5H,8H)-diones.

An efficient synthesis of a series of pyridazino[4,3-c:5,6-c']diquinolines was achieved via the autoxidation of 4-hydrazinylquinolin-2(1H)-ones. IR, NMR (1H and 13C), mass spectral data, and elemental analysis were used to fit and elucidate the structures of the newly synthesized compounds. X-ray structure analysis and theoretical calculations unequivocally proved the formation of the structure. The possible mechanism for the reaction is also discussed.

Synthesis, Characterization, and In Vivo Study of Some Novel 3,4,5-Trimethoxybenzylidene-hydrazinecarbothioamides and Thiadiazoles as Anti-Apoptotic Caspase-3 Inhibitors.

The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a-g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a-g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes.

Synthesis and Ambiphilic Reactivity of Metalated Diorgano-Phosphonite Boranes.

Unprecedented metalated phosphonite boranes were prepared from PH-substituted precursors and silyl amides. Although potassium derivatives were thermally stable and could even be isolated and structurally characterised, lithiated analogues proved to be unstable towards self-condensation under cleavage of LiOR at ambient temperature. Reaction studies revealed that the metalated phosphonite boranes exhibit ambiphilic character. Their synthetic potential as nucleophilic building blocks was demonstrated in the synthesis of the first stannylated phosphonite representing a new structural motif in phosphine chemistry.

A Synthetic Strategy for Cofacial Porphyrin-Based Homo- and Heterobimetallic Complexes.

We present a straightforward and generally applicable synthesis route for cofacially linked homo- and heterobimetallic porphyrin complexes. The protocol allows the synthesis of unsymmetrical aryl-based meso-meso as well as ß-meso-linked porphyrins. Our method significantly increases the overall yield for the published compound known as o-phenylene-bisporphyrin (OBBP) by a factor of 6.8. Besides the synthesis of 16 novel homobimetallic complexes containing MnIII , FeIII , NiII , CuII , ZnII , and PdII , we achieved the first single-crystal X-ray structure of an unsymmetrical cofacial benzene-linked porphyrin dimer containing both planar-chiral enantiomers of a NiII 2 complex. Additionally, this new methodology allows access to heterobimetallic complexes such as the FeIII -NiII containing carbon monoxide dehydrogenase active site analogue. The isolated species were investigated by various techniques, including ion mobility spectrometry, DFT calculations, and UV/Vis spectroscopy. This allowed us to probe the influence of interplane distance on Soret band splitting.

Divergent Carbocatalytic Routes in Oxidative Coupling of Benzofused Heteroaryl Dimers: A Mechanistic Update.

Mildly thermal air or HNO3 oxidized activated carbons catalyse oxidative dehydrogenative couplings of benzo[b]fused heteroaryl 2,2'-dimers, e.g., 2-(benzofuran-2-yl)-1H-indole, to chiral 3,3'-coupled cyclooctatetraenes or carbazole-type migrative products under O2 atmosphere. DFT calculations show that the radical cation and the Scholl-type arenium cation mechanisms lead to different products with 2-(benzofuran-2-yl)-1H-indole, being in accord with experimental product distributions.

Atypical and Asymmetric 1,3-P,N Ligands: Synthesis, Coordination and Catalytic Performance of Cycloiminophosphanes.

Novel seven-membered cyclic imine-based 1,3-P,N ligands were obtained by capturing a Beckmann nitrilium ion intermediate generated in situ from cyclohexanone with benzotriazole, and then displacing it by a secondary phosphane under triflic acid promotion. These "cycloiminophosphanes" possess flexible non-isomerizable tetrahydroazepine rings with a high basicity; this sets them apart from previously reported iminophophanes. The donor strength of the ligands was investigated by using their P-κ1 - and P,N-κ2 -tungsten(0) carbonyl complexes, by determining the IR frequency of the trans-CO ligands. Complexes with [RhCp*Cl2 ]2 demonstrated the hemilability of the ligands, giving a dynamic equilibrium of κ1 and κ2 species; treatment with AgOTf gives full conversion to the κ2 complex. The potential for catalysis was shown in the RuII -catalyzed, solvent-free hydration of benzonitrile and the RuII - and IrI -catalyzed transfer hydrogenation of cyclohexanone in isopropanol. Finally, to enable access to asymmetric catalysts, chiral cycloiminophosphanes were prepared from l-menthone, as well as their P,N-κ2 -RhIII and a P-κ1 -RuII complexes.

Time-Resolved Spectroscopy and Electronic Structure of Mono-and Dinuclear Pyridyl-Triazole/DPEPhos-Based Cu(I) Complexes.

Chemical and spectroscopic characterization of the mononuclear photosensitizers [(DPEPhos)Cu(I)(MPyrT)]0/+ (CuL, CuLH) and their dinuclear analogues (Cu2 L', Cu2 L'H2 ), backed by (TD)DFT and high-level GW-Bethe-Salpeter equation calculations, exemplifies the complex influence of charge, nuclearity and structural flexibility on UV-induced photophysical pathways. Ultrafast transient absorption and step-scan FTIR spectroscopy reveal flattening distortion in the triplet state of CuLH as controlled by charge, which also appears to have a large impact on the symmetry of the long-lived triplet states in Cu2 L' and Cu2 L'H2 . Time-resolved luminescence spectroscopy (solid state), supported by transient photodissociation spectroscopy (gas phase), confirm a lifetime of some tens of µs for the respective triplet states, as well as the energetics of thermally activated delayed luminescence, both being essential parameters for application of these materials based on earth-abundant copper in photocatalysis and luminescent devices.

Metal-to-Metal Distance Modulated Au(I)/Ru(II) Cyclophanyl Complexes: Cooperative Effects in Photoredox Catalysis.

The modular synthesis of Au(I)/Ru(II) decorated mono- and heterobimetallic complexes with π-conjugated [2.2]paracyclophane is described. [2.2]Paracyclophane serves as a rigid spacer which holds the metal centers in precise spatial orientations and allows metal-to-metal distance modulation. A broad set of architectural arrangements of pseudo -geminal, -ortho, -meta, and -para substitution patterns were employed. Metal-to-metal distance modulation of Au(I)/Ru(II) heterobimetallic complexes and the innate transannular π-communication of the cyclophanyl scaffold provides a promising platform for the investigations of structure-activity relationship and cooperative effects. The Au(I)/Ru(II) heterobimetallic cyclophanyl complexes are stable, easily accessible, and exhibit promising catalytic activity in the visible-light promoted arylative Meyer-Schuster rearrangement.

Investigation of Luminescent Triplet States in Tetranuclear CuI Complexes: Thermochromism and Structural Characterization.

To develop new and flexible CuI containing luminescent substances, we extend our previous investigations on two metal-centered species to four metal-centered complexes. These complexes could be a basis for designing new organic light-emitting diode (OLED) relevant species. Both the synthesis and in-depth spectroscopic analysis, combined with high-level theoretical calculations are presented on a series of tetranuclear CuI complexes with a halide containing Cu4 X4 core (X=iodide, bromide or chloride) and two 2-(diphenylphosphino)pyridine bridging ligands with a methyl group in para (4-Me) or ortho (6-Me) position of the pyridine ring. The structure of the electronic ground state is characterized by X-ray diffraction, NMR, and IR spectroscopy with the support of theoretical calculations. In contrast to the para system, the complexes with ortho-substituted bridging ligands show a remarkable and reversible temperature-dependent dual phosphorescence. Here, we combine for the first time the luminescence thermochromism with time-resolved FTIR spectroscopy. Thus, we receive experimental data on the structures of the two triplet states involved in the luminescence thermochromism. The transient IR spectra of the underlying triplet metal/halide-to-ligand charge transfer (3 M/XLCT) and cluster-centered (3 CC) states were obtained and interpreted by comparison with calculated vibrational spectra. The systematic and significant dependence of the bridging halides was analyzed.