Efficient epoxidation over dinuclear sites in titanium silicalite-1.

Titanium silicalite-1 (TS-1) is a zeolitic material with MFI framework structure, in which 1 to 2 per cent of the silicon atoms are substituted for titanium atoms. It is widely used in industry owing to its ability to catalytically epoxidize olefins with hydrogen peroxide (H2O2), leaving only water as a byproduct1,2; around one million tonnes of propylene oxide are produced each year using this process3. The catalytic properties of TS-1 are generally attributed to the presence of isolated Ti(IV) sites within the zeolite framework1. However, despite almost 40 years of experimental and computational investigation4-10, the structure of these active Ti(IV) sites is unconfirmed, owing to the challenges of fully characterizing TS-1. Here, using a combination of spectroscopy and microscopy, we characterize in detail a series of highly active and selective TS-1 propylene epoxidation catalysts with well dispersed titanium atoms. We find that, on contact with H217O2, all samples exhibit a characteristic solid-state 17O nuclear magnetic resonance signature that is indicative of the formation of bridging peroxo species on dinuclear titanium sites. Further, density functional theory calculations indicate that cooperativity between two titanium atoms enables propylene epoxidation via a low-energy reaction pathway with a key oxygen-transfer transition state similar to that of olefin epoxidation by peracids. We therefore propose that dinuclear titanium sites, rather than isolated titanium atoms in the framework, explain the high efficiency of TS-1 in propylene epoxidation with H2O2. This revised view of the active-site structure may enable further optimization of TS-1 and the industrial epoxidation process.

Platinum(IV) Prodrugs Incorporating an Indole-Based Derivative, 5-Benzyloxyindole-3-Acetic Acid in the Axial Position Exhibit Prominent Anticancer Activity.

Kinetically inert platinum(IV) complexes are a chemical strategy to overcome the impediments of standard platinum(II) antineoplastic drugs like cisplatin, oxaliplatin and carboplatin. In this study, we reported the syntheses and structural characterisation of three platinum(IV) complexes that incorporate 5-benzyloxyindole-3-acetic acid, a bioactive ligand that integrates an indole pharmacophore. The purity and chemical structures of the resultant complexes, P-5B3A, 5-5B3A and 56-5B3A were confirmed via spectroscopic means. The complexes were evaluated for anticancer activity against multiple human cell lines. All complexes proved to be considerably more active than cisplatin, oxaliplatin and carboplatin in most cell lines tested. Remarkably, 56-5B3A demonstrated the greatest anticancer activity, displaying GI50 values between 1.2 and 150 nM. Enhanced production of reactive oxygen species paired with the decline in mitochondrial activity as well as inhibition of histone deacetylase were also demonstrated by the complexes in HT29 colon cells.

Chemotherapeutic Potential of Chlorambucil-Platinum(IV) Prodrugs against Cisplatin-Resistant Colorectal Cancer Cells.

Chlorambucil-platinum(IV) prodrugs exhibit multi-mechanistic chemotherapeutic activity with promising anticancer potential. The platinum(II) precursors of the prodrugs have been previously found to induce changes in the microtubule cytoskeleton, specifically actin and tubulin of HT29 colon cells, while chlorambucil alkylates the DNA. These prodrugs demonstrate significant anticancer activity in 2D cell and 3D spheroid viability assays. A notable production of reactive oxygen species has been observed in HT29 cells 72 h post treatment with prodrugs of this type, while the mitochondrial membrane potential was substantially reduced. The cellular uptake of the chlorambucil-platinum(IV) prodrugs, assessed by ICP-MS, confirmed that active transport was the primary uptake mechanism, with platinum localisation identified primarily in the cytoskeletal fraction. Apoptosis and necrosis were observed at 72 h of treatment as demonstrated by Annexin V-FITC/PI assay using flow cytometry. Immunofluorescence measured via confocal microscopy showed significant changes in actin and tubulin intensity and in architecture. Western blot analysis of intrinsic and extrinsic pathway apoptotic markers, microtubule cytoskeleton markers, cell proliferation markers, as well as autophagy markers were studied post 72 h of treatment. The proteomic profile was also studied with a total of 1859 HT29 proteins quantified by mass spectroscopy, with several dysregulated proteins. Network analysis revealed dysregulation in transcription, MAPK markers, microtubule-associated proteins and mitochondrial transport dysfunction. This study confirms that chlorambucil-platinum(IV) prodrugs are candidates with promising anticancer potential that act as multi-mechanistic chemotherapeutics.

Synthesis and Characterisation of Fluorescent Novel Pt(II) Cyclometallated Complexes with Anticancer Activity.

Cancer poses a significant threat to global health and new treatments are required to improve the prognosis for patients. Previously, unconventional platinum complexes designed to incorporate polypyridyl ligands paired with diaminocyclohexane have demonstrated anticancer activity in KRAS mutated cells, previously thought to be undruggable and have cytotoxicity values up to 100 times better than cisplatin. In this work, these complexes were used as inspiration to design six novel cyclometallated examples, whose fluorescence could be exploited to better understand the mechanism of action of these kinds of platinum drugs. The cytotoxicity results revealed that these cyclometallated complexes (CMCs) have significantly different activity compared to the complexes that inspired them; they are as cytotoxic as cisplatin and have much higher selectivity indices in breast cancer cell lines (MCF10A/MCF-7). Complexes 1b, 2a, and 3b all had very high selectivity indexes compared to previous Pt(II) complexes. This prompted further investigation into their DNA binding properties, which revealed that they had good affinity to ctDNA, especially CMCs 1a and 3b. Their inherent fluorescence was successfully utilised in the calculation of their DNA binding affinity and could be useful in future work.

Synthesis and Characterisation of Platinum(II) Diaminocyclohexane Complexes with Pyridine Derivatives as Anticancer Agents.

Cisplatin-type covalent chemotherapeutics are a cornerstone of modern medicinal oncology. However, these drugs remain encumbered with dose-limiting side effects and are susceptible to innate and acquired resistance. The bulk of platinum anticancer research has focused on Cisplatin and its derivatives. Here, we take inspiration from the design of platinum complexes and ligands used successfully with other metals to create six novel complexes. Herein, the synthesis, characterization, DNA binding affinities, and lipophilicity of a series of non-traditional organometallic Pt(II)-complexes are described. These complexes have a basic [Pt(PL)(AL)]Cl2 molecular formula which incorporates either 2-pyrrolidin-2-ylpyridine, 2-(1H-Imidazol-2-yl)pyridine, or 2-(2-pyridyl)benzimidazole as the PL; the AL is resolved diaminocyclohexane. Precursor [Pt(PL)(Cl)2] complexes were also characterized for comparison. While the cytotoxicity and DNA binding properties of the three precursors were unexceptional, the corresponding [Pt(PL)(AL)]2+ complexes were promising; they exhibited different DNA binding interactions compared with Cisplatin but with similar, if not slightly better, cytotoxicity results. Complexes with 2-pyrrolidin-2-ylpyridine or 2-(2-pyridyl)benzimidazole ligands had similar DNA binding properties to those with 2-(1H-Imidazol-2-yl)pyridine ligands but were not as cytotoxic to all cell lines. The variation in activity between cell lines was remarkable and resulted in significant selectivity indices in MCF10A and MCF-7 breast cancer cell lines, compared with previously described similar Pt(II) complexes such as 56MESS.

Novel Planar Pt(II) Cyclometallated Cytotoxic Complexes with G-Quadruplex Stabilisation and Luminescent Properties.

Herein is described the development of a series of novel quadruplex DNA (QDNA)-stabilising cyclometallated square-planar metal complexes (CMCs). Melting experiments using quadruplex DNA (QDNA) demonstrated that interactions with the complexes increased the melting temperature by up to 19 °C. This QDNA stabilisation was determined in two of the major G-quadruplex structures formed in the human c-MYC promoter gene (c-MYC) and a human telomeric repeat sequence (H-Telo). The CMCs were found to stabilise H-telo more strongly than c-MYC, and the CMCs with the highest cytotoxic effect had a low-moderate correlation between H-telo binding capacity and cytotoxicity (R2 values up to 10 times those of c-MYC). The melting experiments further revealed that the stabilisation effect was altered depending on whether the CMC was introduced before or after the formation of QDNA. All CMCs' GI50 values were comparable or better than cisplatin in human cancer cell lines HT29, U87, MCF-7, H460, A431, Du145, BE2-C, SJ-G2, MIA, and ADDP. Complexes 6, 7, and 9 were significantly more cytotoxic than cisplatin in all cell lines tested and had good to moderate selectivity indices, 1.7-4.5 in MCF10A/MCF-7. The emission quantum yields were determined to be relatively high (up to 0.064), and emission occurred outside cellular autofluorescence, meaning CMC fluorescence is ideal for in vitro analyses.

Potent Chlorambucil-Platinum(IV) Prodrugs.

The DNA-alkylating derivative chlorambucil was coordinated in the axial position to atypical cytotoxic, heterocyclic, and non-DNA coordinating platinum(IV) complexes of type, [PtIV(HL)(AL)(OH)2](NO3)2 (where HL is 1,10-phenanthroline, 5-methyl-1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, AL is 1S,2S-diaminocyclohexane). The resultant platinum(IV)-chlorambucil prodrugs, PCLB, 5CLB, and 56CLB, were characterized using high-performance liquid chromatography, nuclear magnetic resonance, ultraviolet-visible, circular dichroism spectroscopy, and electrospray ionization mass spectrometry. The prodrugs displayed remarkable antitumor potential across multiple human cancer cell lines compared to chlorambucil, cisplatin, oxaliplatin, and carboplatin, as well as their platinum(II) precursors, PHENSS, 5MESS, and 56MESS. Notably, 56CLB was exceptionally potent in HT29 colon, Du145 prostate, MCF10A breast, MIA pancreas, H460 lung, A2780, and ADDP ovarian cell lines, with GI50 values ranging between 2.7 and 21 nM. Moreover, significant production of reactive oxygen species was detected in HT29 cells after treatment with PCLB, 5CLB, and 56CLB up to 72 h compared to chlorambucil and the platinum(II) and (IV) precursors.

Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates.

A new series of cytotoxic platinum(IV) complexes (1-8) incorporating halogenated phenylacetic acid derivatives (4-chlorophenylacetic acid, 4-fluorophenylacetic acid, 4-bromophenylacetic acid and 4-iodophenylacetic acid) were synthesised and characterised using spectroscopic and spectrometric techniques. Complexes 1-8 were assessed on a panel of cell lines including HT29 colon, U87 glioblastoma, MCF-7 breast, A2780 ovarian, H460 lung, A431 skin, Du145 prostate, BE2-C neuroblastoma, SJ-G2 glioblastoma, MIA pancreas, the ADDP-resistant ovarian variant, and the non-tumour-derived MCF10A breast line. The in vitro cytotoxicity results confirmed the superior biological activity of the studied complexes, especially those containing 4-fluorophenylacetic acid and 4-bromophenylacetic acid ligands, namely 4 and 6, eliciting an average GI50 value of 20 nM over the range of cell lines tested. In the Du145 prostate cell line, 4 exhibited the highest degree of potency amongst the derivatives, displaying a GI50 value of 0.7 nM, which makes it 1700-fold more potent than cisplatin (1200 nM) and nearly 7-fold more potent than our lead complex, 56MESS (4.6 nM) in this cell line. Notably, in the ADDP-resistant ovarian variant cell line, 4 (6 nM) was found to be almost 4700-fold more potent than cisplatin. Reduction reaction experiments were also undertaken, along with studies aimed at determining the complexes' solubility, stability, lipophilicity, and reactive oxygen species production.

An Anionic Dinuclear Ruthenium Dihydrogen Complex of Relevance for Alkyne gem-Hydrogenation.

During an investigation into the fate of ruthenium precatalysts used for light-driven alkyne gem-hydrogenation reactions with formation of Grubbs-type ruthenium catalysts, it was found that the reaction of [(IPr)(η6 -cymene)RuCl2 ] with H2 under UV-irradiation affords an anionic dinuclear σ-dihydrogen complex, which is thermally surprisingly robust. Not only are anionic σ-complexes in general exceedingly rare, but the newly formed species seems to be the first example lacking any structural attributes able to counterbalance the negative charge and, in so doing, prevent oxidative insertion of the metal centers into the ligated H2 from occurring.

A flow-based transition-metal-catalysed hydrogenolysis strategy to facilitate peptide side-chain deprotection.

Orthogonal deprotection methodologies are an invaluable tool for the construction of site-specially modified peptides. Here, we report a facile 10% Pd/CaCO3-based procedure to selectively mediate Nß-side-chain Cbz-lysis from extended peptide sequences in the presence of trityl and t-Butyl protecting groups.

NMR chemical shift analysis decodes olefin oligo- and polymerization activity of d0 group 4 metal complexes.

d0 metal-alkyl complexes (M = Ti, Zr, and Hf) show specific activity and selectivity in olefin polymerization and oligomerization depending on their ligand set and charge. Here, we show by a combined experimental and computational study that the 13C NMR chemical shift tensors of the α-carbon of metal alkyls that undergo olefin insertion signal the presence of partial alkylidene character in the metal-carbon bond, which facilitates this reaction. The alkylidene character is traced back to the π-donating interaction of a filled orbital on the alkyl group with an empty low-lying metal d-orbital of appropriate symmetry. This molecular orbital picture establishes a connection between olefin insertion into a metal-alkyl bond and olefin metathesis and a close link between the Cossee-Arlmann and Green-Rooney polymerization mechanisms. The 13C NMR chemical shifts, the α-H agostic interaction, and the low activation barrier of ethylene insertion are, therefore, the results of the same orbital interactions, thus establishing chemical shift tensors as a descriptor for olefin insertion.

Colloidal-ALD-Grown Core/Shell CdSe/CdS Nanoplatelets as Seen by DNP Enhanced PASS-PIETA NMR Spectroscopy.

Ligand exchange and CdS shell growth onto colloidal CdSe nanoplatelets (NPLs) using colloidal atomic layer deposition (c-ALD) were investigated by solid-state nuclear magnetic resonance (NMR) experiments, in particular, dynamic nuclear polarization (DNP) enhanced phase adjusted spinning sidebands-phase incremented echo-train acquisition (PASS-PIETA). The improved sensitivity and resolution of DNP enhanced PASS-PIETA permits the identification and study of the core, shell, and surface species of CdSe and CdSe/CdS core/shell NPLs heterostructures at all stages of c-ALD. The cadmium chemical shielding was found to be proportionally dependent on the number and nature of coordinating chalcogen-based ligands. DFT calculations permitted the separation of the the 111/113Cd chemical shielding into its different components, revealing that the varying strength of paramagnetic and spin-orbit shielding contributions are responsible for the chemical shielding trend of cadmium chalcogenides. Overall, this study points to the roughening and increased chemical disorder at the surface during the shell growth process, which is not readily captured by the conventional characterization tools such as electron microscopy.

Cp2Ti(κ2-tBuNCNtBu): A Complex with an Unusual κ2 Coordination Mode of a Heterocumulene Featuring a Free Carbene.

Although there are myriad binding modes of heterocumulenes to metal centers, the monometallic κ2-ECE (E = O, S, NR) coordination mode has not been reported. Herein, the synthesis, isolation, and physical characterization of Cp2Ti(κ2-tBuNCNtBu) (3) (Cp = cyclopentadienyl, tBu = tert-butyl), a strained 4-membered metallacycle bearing a free carbene, is described. Computational (DFT, CASSCF, QT-AIM, ELF) and solid-state CP-MAS 13C NMR spectroscopic analysis indicate that 3 is best described as a free carbene with partial Ti-Cß bonding that results from Ti-N π-bonding mixing with N-C-N σ-bonding of the bent N-C-N framework. Reactivity studies of 3 corroborate its carbene-like nature: protonation with [LutH]I results in the formation of a Ti-formamidinate (4), while oxidation with S8 yields a Ti-thioureate (5). Additionally, a related bridged dititanamidocarbene, (Cp2Ti)2(µ-η1,η1-CyNCNCy) (10) (Cy = cyclohexyl) is reported. Taken together, this work suggests that the 2-electron reduction of heterocumulene moieties can allow access to unusual free carbene coordination geometries given the proper stabilizing coordination environment from the reducing transition metal fragment.

"Canopy Catalysts" for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework.

A new family of structurally well-defined molybdenum alkylidyne catalysts for alkyne metathesis, which is distinguished by a tripodal trisilanolate ligand architecture, is presented. Complexes of type 1 combine the virtues of previous generations of silanolate-based catalysts with a significantly improved functional group tolerance. They are easy to prepare on scale; the modularity of the ligand synthesis allows the steric and electronic properties to be fine-tuned and hence the application profile of the catalysts to be optimized. This opportunity is manifested in the development of catalyst 1f, which is as reactive as the best ancestors but exhibits an unrivaled scope. The new catalysts work well in the presence of unprotected alcohols and various other protic groups. The chelate effect entails even a certain stability toward water, which marks a big leap forward in metal alkylidyne chemistry in general. At the same time, they tolerate many donor sites, including basic nitrogen and numerous heterocycles. This aspect is substantiated by applications to polyfunctional (natural) products. A combined spectroscopic, crystallographic, and computational study provides insights into structure and electronic character of complexes of type 1. Particularly informative are a density functional theory (DFT)-based chemical shift tensor analysis of the alkylidyne carbon atom and 95Mo NMR spectroscopy; this analytical tool had been rarely used in organometallic chemistry before but turns out to be a sensitive probe that deserves more attention. The data show that the podand ligands render a Mo-alkylidyne a priori more electrophilic than analogous monodentate triarylsilanols; proper ligand tuning, however, allows the Lewis acidity as well as the steric demand about the central atom to be adjusted to the point that excellent performance of the catalyst is ensured.

The Structure of Molecular and Surface Platinum Sites Determined by DNP-SENS and Fast MAS 195Pt Solid-State NMR Spectroscopy.

The molecular level characterization of heterogeneous catalysts is challenging due to the low concentration of surface sites and the lack of techniques that can selectively probe the surface of a heterogeneous material. Here, we report the joint application of room temperature proton-detected NMR spectroscopy under fast magic angle spinning (MAS) and dynamic nuclear polarization surface enhanced NMR spectroscopy (DNP-SENS), to obtain the 195Pt solid-state NMR spectra of a prototypical example of highly dispersed Pt sites (single site or single atom), here prepared via surface organometallic chemistry, by grafting [(COD)Pt(OSi(OtBu)3)2] (1, COD = 1,5-cyclooctadiene) on partially dehydroxylated silica (1@SiO2). Compound 1@SiO2 has a Pt loading of 3.7 wt %, a surface area of 200 m2/g, and a surface Pt density of around 0.6 Pt site/nm2. Fast MAS 1H{195Pt} dipolar-HMQC and S-REDOR experiments were implemented on both the molecular precursor 1 and on the surface complex 1@SiO2, providing access to 195Pt isotropic shifts and Pt-H distances, respectively. For 1@SiO2, the measured isotropic shift and width of the shift distribution constrain fits of the static wide-line DNP-enhanced 195Pt spectrum, allowing the 195Pt chemical shift tensor parameters to be determined. Overall the NMR data provide evidence for a well-defined, single-site structure of the isolated Pt sites.

Carbon-13 NMR Chemical Shift: A Descriptor for Electronic Structure and Reactivity of Organometallic Compounds.

Metal-bonded carbon atoms in metal-alkyl, metal-carbene/alkylidene, and metal-carbyne/alkylidyne species often show significantly more deshielded isotropic chemical shifts than their organic counterparts (alkanes, alkenes, and alkynes). While isotropic chemical shift is universally used to characterize a chemical compound in solution, it is an average value of the three principal components of the chemical shift tensor (δ11 > δ22 > δ33). The tensor components, which are accessible by solid-state NMR spectroscopy, can provide detailed information about the electronic structure (frontier molecular orbitals) at the observed nuclei. This information can be accessed in detail by quantum chemical calculations, most notably by an analysis of the paramagnetic contribution to the NMR shielding tensor. The paramagnetic term mainly results from the coupling of occupied and empty molecular orbitals close in energy-the frontier molecular orbitals-under the effect of the external magnetic field (B0). In organometallic compounds, a large deshielding of the isotropic carbon-13 chemical shift of the metal-bonded carbon atom is commonly related to the coupling between the occupied σM-C orbital and low-lying vacant orbitals of πM═C* character. The deshielding at the α-carbon hence probes the extent of σM-C and πM═C* interactions. This molecular orbital view readily explains the strong deshielding and large anisotropy (evidenced by the span Ω = δ11 - δ33) observed in metal alkylidenes and alkylidynes (200 < δiso < 400 ppm). Fischer carbenes are generally more deshielded than Schrock or Grubbs alkylidenes due to their low-lying πM═C* orbital. Chemical shift hence shows their higher electrophilic character, connecting NMR spectroscopy to reactivity patterns. Similarly, the α-carbon of metal-alkyls display deshielded chemical shifts in specific coordination environments. This deshielding, which is often prominently pronounced for cationic species, indicates the presence of partial π-bond character in the metal-carbon bond, making these bonds topologically equivalent to alkylidene π-bonds. The π-character in metal-alkyl bonds favors (i) α-H abstraction processes in metal bis-alkyl compounds yielding metal alkylidenes, (ii) [2 + 2]-retrocyclization of metallacyclobutanes that participate in olefin metathesis, (iii) olefin insertion in cationic metal alkyls thus explaining polymerization activity trends and the importance of α-H agostic interactions, and (iv) C-H bond activation on metal-alkyls via σ-bond metathesis. The presence of π-character in the metal-carbon bonds involved in these processes rationalizes the parallel reactivity patterns of metal-alkyls toward olefin insertion and σ-bond metathesis and the fact that σ-bond metathesis, olefin insertion, and olefin metathesis are commonly observed with metal atoms in the same ligand field. Because of the similarities in the frontier molecular orbitals involved in these processes, these reactions can be viewed as isolobal. This explains why certain fragments, such as bent metallocenes (d0 Cp2M) or T-shaped L3M, are ubiquitous in these reactions.

Synthetic strategies to access staphylococcus auto-inducing peptides as quorum sensing modulators.

The accessory gene regulator (agr) quorum-sensing system is arguably the most important regulator of staphylococcus virulence and has been the focus of tremendous interest in the development of effective therapies for pathogenic bacterial infections. With regards to chemotherapeutic based strategies, the significant proportion of currently reported agr-system modulating molecules are mimics of the native ArgC substrate, which is a thioester-based macrocyclic peptide know as the auto-inducing peptide. Over the past two decades, more than two-hundred synthetic analogues have been reported. This review traces the development of the synthetic strategies employed to synthesise these analogues with a particular focus on macrocyclisation. At present these synthetic approaches can be clustered into five broad categories (1) solution-phase cyclisation, (2) immobilised carbodiimide assisted cyclisation, (3) concomitant on-resin cleavage and macrocyclisation, (4) Boc-compatible chemoselective thioesterification, and (5) Fmoc-compatible chemoselective thioesterification. The advantages and limitation provided by each of the approaches are compared and contrasted with a view towards potential reaction scale-up.

Understanding 125Te NMR chemical shifts in disymmetric organo-telluride compounds from natural chemical shift analysis.

Organotellurium compounds of general formula X-Te-R display a broad range of chemical shifts that are very sensitive to the X and R substituents. In order to link the 125Te chemical shift of a series of perfluoroalkyl aryl tellurides to their electronic structure, the chemical shielding tensors of the 125Te nuclei were calculated by density functional theory (DFT) and further analyzed by a decomposition into contributions of natural localized molecular orbitals (NLMOs). The analysis indicated that the variation in 125Te chemical shifts in molecules 1-13 is mainly due to the magnetic coupling of the tellurium p-character lone pair with antibonding orbitals perpendicular to it {σ*(Te-X) and σ*(Te-C(Ar))} upon action of an external magnetic field. The strength of the coupling is affected by electronic properties of the X-substituents, polarization of the antibonding orbitals and presence of secondary interactions perturbing the energy of these orbitals. The lower in energy and the more polarized towards tellurium the antibonding orbitals are, the stronger is the coupling and the more deshielded the tellurium nucleus.

Probing the Electronic Structure of Spectator Oxo Ligands by 17O NMR Spectroscopy.

Spectator oxo ligands are ubiquitous in catalysis, in particular in olefin epoxidation and olefin metathesis. Here we use computationally derived 17O NMR parameters to probe the electronic structure of spectator oxo ligands in these two reactions. We show that 17O NMR parameters allow to distinguish between doubly-bonded and triply-bonded oxo ligands, giving detailed insights into the frontier molecular orbitals involved in the metaloxo bonds along the reaction pathway. On the one hand, our study shows that in olefin epoxidation catalysed by methyltrioxorhenium (MTO), the oxo ligand significantly changes its bonding mode upon formation of the oxygen-transferring Re-oxo-bisperoxo-species, changing its nature from a doubly bonded to a triply bonded oxo ligand. On the other hand, only minor changes in the binding mode are found along the olefin metathesis reaction pathway with Mo- and W-based oxo-alkylidene species, in which the oxo ligand behaves as a triply bonded ligand throughout the reaction. This finding contrasts earlier studies that proposed that the change of binding mode of the oxo ligand was key to metallacyclobutane formation.

Metal Alkyls with Alkylidynic Metal-Carbon Bond Character: Key Electronic Structures in Alkane Metathesis Precatalysts.

The homologation of alkanes via alkane metathesis is catalyzed at low temperatures (150 °C) by the silica-supported species (≡SiO)WMe5 and (≡SiO)TaMe4 , while (≡SiO)TaMe3 Cp* is inactive. The contrasting reactivity is paralleled by differences in the 13 C NMR signature; the former display significantly more deshielded isotropic chemical shifts (δiso ) and almost axially symmetric chemical shift tensors, similar to what is observed in their molecular precursors TaMe5 and WMe6 . Analysis of the chemical shift tensors reveals the presence of a triple-bond character in their metal-carbon (formally single) bond. This electronic structure is reflected in their propensity to generate alkylidynes and to participate in alkane metathesis, further supporting the role of alkylidynes as key reaction intermediates. This study establishes chemical shift as a descriptor to identify potential alkane metathesis catalysts.