Stopping Hydrogen Migration in its Tracks: The First Successful Synthesis of Group Ten Scorpionate Complexes Based on Azaindole Scaffolds

The first successful synthesis and characterization of group 10 complexes featuring flexible scorpionate ligands based on 7-azaindole heterocycles are reported herein. Addition of 2 equiv of either K­[HB­(azaindolyl)3] or Li­[HB­(Me)­(azaindolyl)2] to [M­(μ-Cl)­(η,1η2-COEOMe)]2 leads to the formation of 2 equiv of the complexes [M­{κ3-N,N,H-HB­(azaindolyl)3}­(η,1η2-COEOMe)] and [M­{κ3-N,N,H-HB­(Me)­(azaindolyl)2}­(η,1η2-COEOMe)] (where M = Pt, Pd; COEOMe = 8-methoxycyclooct-4-en-1-ide), respectively. In these reactions, the borohydride group is directed toward the metal center forming square based pyramidal complexes. In contrast to analogous complexes featuring other flexible scorpionate ligands, no hydrogen migration from boron is observed in the complexes studied. The fortuitous line widths observed in some of the 11B NMR spectra allow for a closer inspection of the B–H···metal unit in scorpionate complexes than has previously been possible

Scorpionate ligands based on 2-Mercaptopyridine : a ligand with a greater propensity to sting?

The synthesis and characterization of the first platinum group metal complexes of the recently reported ligand [H2B(mp)2]− (where mp = 2-mercaptopyridyl) are presented herein. Addition of 2 equiv of Na[H2B(mp)2] to [MCl(COD)]2 (where M = Rh, Ir; COD = 1,5-cyclooctadiene) leads to the hydride migration products [Rh{κ3-SSB-BH(mp)2}(η3-C8H13)] and [Ir(H){κ3-SSB-BH(mp)2}(η4-C8H12)], respectively. Structural characterization of the rhodium complex reveals a notably short rhodium–boron distance of 2.054(2) Å. The reactivity observed for the rhodium complex is different from that of all known scorpionate ligands, suggesting a higher propensity for hydride migration within the 2-mercaptopyridine-based ligands. The complex [Ir(Cl){κ3-SSB-BH(mp)2}(η4-C8H12)], which is formed via hydride/halide exchange in chloroform, is also structurally characterized. The new complexes provide rare examples of metallaboratrane complexes where one hydrogen substituent remains at the boron center

Balancing ring and stopper group size to control the stability of doubly threaded [3]rotaxanes

Synthesizing doubly threaded [3]rotaxanes requires the use of larger rings than more traditional singly threaded [2]rotaxanes. A key challenge in accessing stable doubly threaded [3]rotaxanes with large rings is finding the right combination of ring to stopper size. In this study, a series of doubly threaded [3]rotaxanes derived from five different sized macrocycles in the size range of 40–48 atoms and two different stopper groups, which contain 1 or 2 tris(p-t-butylbiphenyl)methyl moieties, were prepared and their kinetic stability examined. These interlocked compounds were synthesized using a metal-templated approach and fully characterized utilizing a combination of mass spectrometry, NMR spectroscopy, and size-exclusion chromatography techniques. The effect of ring size on the stability of the doubly threaded [3]rotaxane was investigated via kinetic stability tests monitored using 1H-NMR spectroscopy. By tightening the macrocycle systematically every 2 atoms from 48 to 40 atoms, a wide range of doubly threaded interlocked molecules could be accessed in which the rate of room temperature slippage of the macrocycle from the dumbbells could be tuned. Using the larger stopper group with a 48-atom ring results in no observable rotaxane, 46–44 atom macrocycles result in metastable rotaxane species with a slippage half-life of ∼5 weeks and ∼9 weeks, respectively, while macrocycles of 42 atoms or smaller yield a stable rotaxane. The smaller sized stopper is not able to fully stabilize any of the [3]rotaxane structures but metastable [3]rotaxanes are obtained with slippage half-lives of 25 ± 2 hours and 13 ± 1 days using macrocycles with 42 or 40 atoms, respectively. These results highlight the dramatic effect that relatively small ring size changes can have on the structure of doubly threaded [3]rotaxanes and lay the synthetic groundwork for a range of higher order doubly threaded interlocked architectures

Stopping hydrogen migration in its tracks: the first successful synthesis of group ten scorpionate complexes based on Azaindole scaffolds

The first successful synthesis and characterization of group ten complexes featuring flexible scorpionate ligands based on 7-azaindole heterocycles are reported herein. Addition of two equivalents of either K[HB(azaindolyl)3] or Li[HB(Me)(azaindolyl)2] to [M(μ-Cl)(η1,η2-COEOMe)]2 leads to the formation of two equivalents of the complexes [M{κ3-N,N,H-HB(azaindolyl)3}(η1,η2-COEOMe)] and [M{κ3-N,N,H-HB(Me)(azaindolyl)2}(η1,η2-COEOMe)] (where M = Pt, Pd; COEOMe = 8-methoxycyclooct-4-en-1-ide), respectively. In these reactions, the borohydride group is directed towards the metal center forming square based pyramidal complexes. In contrast to analogous complexes featuring other flexible scorpionate ligands, no hydrogen migration from boron is observed in the complexes studied. The fortuitous linewidths observed in some of the 11B NMR spectra allow for a closer inspection of the B–H•••metal unit in scorpionate complexes than has previously been possible

Poly(<i>p</i>‑phenylenediethynylene phosphine)s and Related π‑Conjugated Phosphine–Diyne Polymers: Synthesis, Characterization and Photophysical Properties

Despite the considerable synthetic challenge, polymers that incorporate phosphorus atoms within or adjacent to a π-conjugated backbone framework are of interest due to the ability to modulate the photophysical properties of the polymer based on the chemical environment at phosphorus. We report the synthesis and characterization of poly­(<i>p</i>-phenylenediethlynylene phosphine)­s, <b>1a</b>–<b>1e</b>, a new class of σ–π conjugated polymer. Polymers <b>1a</b>–<b>1e</b> were prepared by a Ni-catalyzed coupling of dialkynes with phenyldichlorophosphine in the presence of excess triethylamine and have molecular weights (<i>M</i>_w) up to 12,000 g mol^–1 (vs. polystyrene). While the polymers <b>1b</b>–<b>1e</b> are nonfluorescent, blue fluorescence is observed upon oxidation of the phosphorus centers (Φ_soln = 0.12–0.28). Polymers <b>1b</b>·O–<b>1e</b>·O also exhibit yellow/green fluorescence in the solid state (Φ_solid = 0.04–0.08). These results introduce a fascinating new class of main group-containing macromolecule and lay the groundwork for their utilization in sensory applications and/or their incorporation into optoelectrical devices

An Addition–Isomerization Mechanism for the Anionic Polymerization of MesPCPh₂ and <i>m</i>‑XylPCPh₂

We report that the anionic polymerization of P-mesityl and <i>m</i>-xylyl-substituted phosphaalkenes follows an unusual addition–isomerization mechanism. Specifically, the polymerization of ArPCPh₂ [Ar = Mes (<b>1a</b>), <i>m</i>-Xyl (<b>1b</b>)] involves the hindered nucleophilic anion intermediate, Ⓟ–P­(Ar)–CPh₂^–, which undergoes a proton migration from the <i>o</i>-CH₃ of the Mes/<i>m</i>-Xyl moiety to the −CPh₂ moiety to afford a propagating benzylic anion. This mechanism is supported by the preparation of model compounds MeP­(CHPh₂)-4,6-Me₂C₆H₂–2-CH₂–CPh₃ (<b>2a</b>) or MeP­(CHPh₂)-6-MeC₆H₃–2-CH₂–CPh₃ (<b>2b</b>), which were both crystallographically characterized. Polymerization of <b>1a</b> or <b>1b</b> in THF solution using <i>n</i>-BuLi (2 mol %) revealed ¹H and ¹³C NMR signals assigned to −CH₂– and −CHPh₂ groups consistent with an addition–isomerization polymerization mechanism to afford poly­(methylene­phosphine) <b>3a</b> or <b>3b</b>. A large kinetic isotope effect (≤23) was determined for the <i>n</i>-BuLi-initiated polymerization of <b>1a</b>-<i>d</i>₉ compared to <b>1a</b> in THF at 50 °C, consistent with C–H (or C–D) activation as the rate-determining step. This C–H activation step was modeled using DFT computations which revealed that the intramolecular proton transfer from the <i>o</i>-CH₃ of the Mes moiety to the −CPh₂ moiety has an activation energy (<i>E</i>_a = +18.5 kcal mol^–1). For comparison, this computational value was quite close to the experimentally measured activation energy of propagation ArPCPh₂ in THF [<i>E</i>_a = 14.0 ± 0.9 kcal mol^–1 (<b>1a</b>), 15.6 ± 2.8 kcal mol^–1 (<b>1b</b>)]

Understanding How Cationic Polymers’ Properties Inform Toxic or Immunogenic Responses via Parametric Analysis

Cationic polymers are widely used materials in diverse biotechnologies. Subtle variations in these polymers’ properties can change them from exceptional delivery agents to toxic inflammatory hazards. Conventional screening strategies optimize for function in a specific application rather than observing how underlying polymer–cell interactions emerge from polymers’ properties. An alternative approach is to map basic underlying responses, such as immunogenicity or toxicity, as a function of basic physicochemical parameters to inform the design of materials for a breadth of applications. To demonstrate the potential of this approach, we synthesized 107 polymers varied in charge, hydrophobicity, and molecular weight. We then screened this library for cytotoxic behavior and immunogenic responses to map how these physicochemical properties inform polymer–cell interactions. We identify three compositional regions of interest and use confocal microscopy to uncover the mechanisms behind the observed responses. Finally, immunogenic activity is confirmed in vivo. Highly cationic polymers disrupted the cellular plasma membrane to induce a toxic phenotype, while high molecular weight, hydrophobic polymers were uptaken by active transport to induce NLRP3 inflammasome activation, an immunogenic phenotype. Tertiary amine- and triethylene glycol-containing polymers did not invoke immunogenic or toxic responses. The framework described herein allows for the systematic characterization of new cationic materials with different physicochemical properties for applications ranging from drug and gene delivery to antimicrobial coatings and tissue scaffolds

An Addition–Isomerization Mechanism for the Anionic Polymerization of MesPCPh₂ and <i>m</i>‑XylPCPh₂

We report that the anionic polymerization of P-mesityl and <i>m</i>-xylyl-substituted phosphaalkenes follows an unusual addition–isomerization mechanism. Specifically, the polymerization of ArPCPh₂ [Ar = Mes (<b>1a</b>), <i>m</i>-Xyl (<b>1b</b>)] involves the hindered nucleophilic anion intermediate, Ⓟ–P­(Ar)–CPh₂^–, which undergoes a proton migration from the <i>o</i>-CH₃ of the Mes/<i>m</i>-Xyl moiety to the −CPh₂ moiety to afford a propagating benzylic anion. This mechanism is supported by the preparation of model compounds MeP­(CHPh₂)-4,6-Me₂C₆H₂–2-CH₂–CPh₃ (<b>2a</b>) or MeP­(CHPh₂)-6-MeC₆H₃–2-CH₂–CPh₃ (<b>2b</b>), which were both crystallographically characterized. Polymerization of <b>1a</b> or <b>1b</b> in THF solution using <i>n</i>-BuLi (2 mol %) revealed ¹H and ¹³C NMR signals assigned to −CH₂– and −CHPh₂ groups consistent with an addition–isomerization polymerization mechanism to afford poly­(methylene­phosphine) <b>3a</b> or <b>3b</b>. A large kinetic isotope effect (≤23) was determined for the <i>n</i>-BuLi-initiated polymerization of <b>1a</b>-<i>d</i>₉ compared to <b>1a</b> in THF at 50 °C, consistent with C–H (or C–D) activation as the rate-determining step. This C–H activation step was modeled using DFT computations which revealed that the intramolecular proton transfer from the <i>o</i>-CH₃ of the Mes moiety to the −CPh₂ moiety has an activation energy (<i>E</i>_a = +18.5 kcal mol^–1). For comparison, this computational value was quite close to the experimentally measured activation energy of propagation ArPCPh₂ in THF [<i>E</i>_a = 14.0 ± 0.9 kcal mol^–1 (<b>1a</b>), 15.6 ± 2.8 kcal mol^–1 (<b>1b</b>)]

Preparation and reactivity of rhodium and iridium complexes containing a methylborohydride based unit supported by two 7-azaindolyl heterocycles

The synthesis and characterisation of a new anionic flexible scorpionate ligand, methyl(bis-7-azaindolyl)borohydride [MeBai]- is reported herein. The ligand was coordinated to a series of group nine transition metal centres forming the complexes, [Ir(MeBai)(COD)] (1), [Rh(MeBai)(COD)] (2), [Rh(MeBai)(CODMe)] (2-Me) and [Rh(MeBai)(NBD)] (3), where COD = 1,5-cyclooctadiene, CODMe = 3-methyl-1,5-cyclooctadiene and NBD = 2,5-norbornadiene. In all cases, the boron based ligand was found to bind to the metal centres via a κ3-N,N,H coordination mode. The ligand and complexes were fully characterised by spectroscopic and analytical methods. The structures of the ligand and three of the complexes were confirmed by X-ray crystallography. The potential for migration of the "hydride" or "methyl" units from boron to the metal centre was also explored. During these studies an unusual transformation, involving the oxidation of the rhodium centre, was observed in complex 2. In this case, the η4-COD unit transformed into a η1,η3-C8H12 unit where the ring was bound via one sigma bond and one allyl unit. This is the first time such a transformation has been observed at a rhodium centre