Ultrafast and long-time excited state kinetics of an NIR-emissive vanadium(iii) complex II. Elucidating triplet-to-singlet excited-state dynamics

We report the non-adiabatic dynamics of V^IIICl₃(ddpd), a complex based on the Earth-abundant first-row transition metal vanadium with a d² electronic configuration which is able to emit phosphorescence in solution in the near-infrared spectral region. Trajectory surface-hopping dynamics based on linear vibronic coupling potentials obtained with CASSCF provide molecular-level insights into the intersystem crossing from triplet to singlet metal-centered states. While the majority of the singlet population undergoes back-intersystem crossing to the triplet manifold, 1–2% remains stable during the 10 ps simulation time, enabling the phosphorescence described in Dorn et al. Chem. Sci., 2021, DOI: 10.1039/D1SC02137K. Competing with intersystem crossing, two different relaxation channels via internal conversion through the triplet manifold occur. The nuclear motion that drives the dynamics through the different electronic states corresponds mainly to the increase of all metal–ligand bond distances as well as the decrease of the angles of trans-coordinated ligand atoms. Both motions lead to a decrease in the ligand-field splitting, which stabilizes the interconfigurational excited states populated during the dynamics. Analysis of the electronic character of the states reveals that increasing and stabilizing the singlet population, which in turn can result in enhanced phosphorescence, could be accomplished by further increasing the ligand-field strength.

The ultrafast triplet-to-singlet mechanism, responsible for the photoluminescence of the open-shell V^IIICl₃(ddpd) complex – based on Earth-abundant vanadium – is unraveled using non-adiabatic dynamics in full dimensionality.     

Ni(0)-promoted activation of Csp2–H and Csp2–O bonds

A dinickel(0)–N₂ complex, stabilized with a rigid acridane-based PNP pincer ligand, was studied for its ability to activate C(sp²)–H and C(sp²)–O bonds. Stabilized by a Ni–μ–N₂–Na⁺ interaction, it activates C–H bonds of unfunctionalized arenes, affording nickel–aryl and nickel–hydride products. Concomitantly, two sodium cations get reduced to Na(0), which was identified and quantified by several methods. Our experimental results, including product analysis and kinetic measurements, strongly suggest that this C(sp²)–H activation does not follow the typical oxidative addition mechanism occurring at a low-valent single metal centre. Instead, via a bimolecular pathway, two powerfully reducing nickel ions cooperatively activate an arene C–H bond and concomitantly reduce two Lewis acidic alkali metals under ambient conditions. As a novel synthetic protocol, nickel(ii)–aryl species were directly synthesized from nickel(ii) precursors in benzene or toluene with excess Na under ambient conditions. Furthermore, when the dinickel(0)–N₂ complex is accessed via reduction of the nickel(ii)–phenyl species, the resulting phenyl anion deprotonates a C–H bond of glyme or 15-crown-5 leading to C–O bond cleavage, which produces vinyl ether. The dinickel(0)–N₂ species then cleaves the C(sp²)–O bond of vinyl ether to produce a nickel(ii)–vinyl complex. These results may provide a new strategy for the activation of C–H and C–O bonds mediated by a low valent nickel ion supported by a structurally rigidified ligand scaffold.

A structurally rigidified nickel(0) complex was found to be capable of cleaving both C(sp²)–H and C(sp²)–O bonds.     

Characterization and chemical reactivity of room-temperature-stable MnIII–alkylperoxo complexes

While alkylperoxomanganese(iii) (Mn^III–OOR) intermediates are proposed in the catalytic cycles of several manganese-dependent enzymes, their characterization has proven to be a challenge due to their inherent thermal instability. Fundamental understanding of the structural and electronic properties of these important intermediates is limited to a series of complexes with thiolate-containing N₄S⁻ ligands. These well-characterized complexes are metastable yet unreactive in the direct oxidation of organic substrates. Because the stability and reactivity of Mn^III–OOR complexes are likely to be highly dependent on their local coordination environment, we have generated two new Mn^III–OOR complexes using a new amide-containing N₅⁻ ligand. Using the 2-(bis((6-methylpyridin-2-yl)methyl)amino)-N-(quinolin-8-yl)acetamide (H^6Medpaq) ligand, we generated the [Mn^III(OO^tBu)(^6Medpaq)]OTf and [Mn^III(OOCm)(^6Medpaq)]OTf complexes through reaction of their Mn^II or Mn^III precursors with ^tBuOOH and CmOOH, respectively. Both of the new Mn^III–OOR complexes are stable at room-temperature (t_1/2 = 5 and 8 days, respectively, at 298 K in CH₃CN) and capable of reacting directly with phosphine substrates. The stability of these Mn^III–OOR adducts render them amenable for detailed characterization, including by X-ray crystallography for [Mn^III(OOCm)(^6Medpaq)]OTf. Thermal decomposition studies support a decay pathway of the Mn^III–OOR complexes by O–O bond homolysis. In contrast, direct reaction of [Mn^III(OOCm)(^6Medpaq)]⁺ with PPh₃ provided evidence of heterolytic cleavage of the O–O bond. These studies reveal that both the stability and chemical reactivity of Mn^III–OOR complexes can be tuned by the local coordination sphere.

A pair of room-temperature-stable Mn^III–alkylperoxo complexes were characterized and shown to oxidize PPh₃. Thermal decomposition studies provide evidence of both homolysis and heterolysis of the Mn^III–alkylperoxo O–O bond.     

Accelerating the insertion reactions of (NHC)Cu–H via remote ligand functionalization

Most ligand designs for reactions catalyzed by (NHC)Cu–H (NHC = N-heterocyclic carbene ligand) have focused on introducing steric bulk near the Cu center. Here, we evaluate the effect of remote ligand modification in a series of [(NHC)CuH]₂ in which the para substituent (R) on the N-aryl groups of the NHC is Me, Et, ^tBu, OMe or Cl. Although the R group is distant (6 bonds away) from the reactive Cu center, the complexes have different spectroscopic signatures. Kinetics studies of the insertion of ketone, aldimine, alkyne, and unactivated α-olefin substrates reveal that Cu–H complexes with bulky or electron-rich R groups undergo faster substrate insertion. The predominant cause of this phenomenon is destabilization of the [(NHC)CuH]₂ dimer relative to the (NHC)Cu–H monomer, resulting in faster formation of Cu–H monomer. These findings indicate that remote functionalization of NHCs is a compelling strategy for accelerating the rate of substrate insertion with Cu–H species.

Remote modification of an N-heterocyclic carbene ligand with bulky or electron-rich groups in [(NHC)Cu(μ-H)]₂ increases the rate of substrate insertion, which kinetics studies suggest arises from changes in the Cu–H monomer–dimer equilibrium.     

A (μ-hydrido)diborane(4) anion and its coordination chemistry with coinage metals

A tetra(o-tolyl) (μ-hydrido)diborane(4) anion 1, an analogue of [B₂H₅]⁻ species, was facilely prepared through the reaction of tetra(o-tolyl)diborane(4) with sodium hydride. Unlike common sp²–sp³ diborane species, 1 exhibited a σ-B–B bond nucleophilicity towards NHC-coordinated transition-metal (Cu, Ag, and Au) halides, resulting in the formation of η²-B–B bonded complexes 2 as confirmed by single-crystal X-ray analyses. Compared with 1, the structural data of 2 imply significant elongations of B–B bonds, following the order Au > Cu > Ag. DFT studies show that the diboron ligand interacts with the coinage metal through a three-center-two-electron B–M–B bonding mode. The fact that the B–B bond of the gold complex is much prolonged than the related Cu and Ag compounds might be ascribed to the superior electrophilicity of the gold atom.

A tetra(o-tolyl)(μ-hydrido)diborane(4) anion is facilely prepared via the reaction of tetra(o-tolyl)diborane(4) with NaH. It exhibits a σ-B–B bond nucleophilicity towards NHC-metal halides to give the corresponding η²-B–B bonded metal complexes.     

Nitride protonation and NH3 binding versus N–H bond cleavage in uranium nitrides

The conversion of metal nitrides to NH₃ is an essential step in dinitrogen fixation, but there is limited knowledge of the reactivity of nitrides with protons (H⁺). Herein, we report comparative studies for the reactions of H⁺ and NH₃ with uranium nitrides, containing different types of ancillary ligands. We show that the differences in ancillary ligands, leads to dramatically different reactivity. The nitride group, in nitride-bridged cationic and anionic diuranium(iv) complexes supported by –N(SiMe₃)₂ ligands, is resistant toward protonation by weak acids, while stronger acids result in ligand loss by protonolysis. Moreover, the basic –N(SiMe₃)₂ ligands promote the N–H heterolytic bond cleavage of NH₃, yielding a “naked” diuranium complex containing three bridging ligands, a nitride (N³⁻) and two NH₂ ligands. Conversely, in the nitride-bridged diuranium(iv) complex supported by –OSi(O^tBu)₃ ligands, the nitride group is easily protonated to afford NH₃, which binds the U(iv) ion strongly, resulting in a mononuclear U–NH₃ complex, where NH₃ can be displaced by addition of strong acids. Furthermore, the U–OSi(O^tBu)₃ bonds were found to be stable, even in the presence of stronger acids, such as NH₄BPh₄, therefore indicating that –OSi(O^tBu)₃ supporting ligands are well suited to be used when acidic conditions are required, such as in the H⁺/e⁻ mediated catalytic conversion of N₂ to NH₃.

Ancillary ligands alter the reactivity of U-nitrides with H⁺, relevant to N₂ conversion to NH₃. The amides lead to complete ligand loss and NH₃ activation, while for siloxides, the nitride is protonated to NH₃ leaving the ancillary ligands intact.     

Force-modulated reductive elimination from platinum(ii) diaryl complexes

Coupled mechanical forces are known to drive a range of covalent chemical reactions, but the effect of mechanical force applied to a spectator ligand on transition metal reactivity is relatively unexplored. Here we quantify the rate of C(sp²)–C(sp²) reductive elimination from platinum(ii) diaryl complexes containing macrocyclic bis(phosphine) ligands as a function of mechanical force applied to these ligands. DFT computations reveal complex dependence of mechanochemical kinetics on the structure of the force-transducing ligand. We validated experimentally the computational finding for the most sensitive of the ligand designs, based on MeOBiphep, by coupling it to a macrocyclic force probe ligand. Consistent with the computations, compressive forces decreased the rate of reductive elimination whereas extension forces increased the rate relative to the strain-free MeOBiphep complex with a 3.4-fold change in rate over a ∼290 pN range of restoring forces. The calculated natural bite angle of the free macrocyclic ligand changes with force, but ³¹P NMR analysis and calculations strongly suggest no significant force-induced perturbation of ground state geometry within the first coordination sphere of the (P–P)PtAr₂ complexes. Rather, the force/rate behavior observed across this range of forces is attributed to the coupling of force to the elongation of the O⋯O distance in the transition state for reductive elimination. The results suggest opportunities to experimentally map geometry changes associated with reactions in transition metal complexes and potential strategies for force-modulated catalysis.

The influence of mechanical force on the rates of model reductive elimination reactions depends on the structure of the force-transducing ligand and provides a measure of geometry changes upon reaching the transition state.     

Cooperative C–H activation of pyridine by PBP complexes of Rh and Ir can lead to bridging 2-pyridyls with different connectivity to the B–M unit

Pyridine and quinoline undergo selective C–H activation in the 2-position with Rh and Ir complexes of a boryl/bis(phosphine) PBP pincer ligand, resulting in a 2-pyridyl bridging the transition metal and the boron center. Examination of this reactivity with Rh and Ir complexes carrying different non-pincer ligands on the transition metal led to the realization of the possible isomerism derived from the 2-pyridyl fragment connecting either via B–N/C–M bonds or via B–C/N–M bonds. This M–C/M–N isomerism was systematically examined for four structural types. Each of these types has a defined set of ligands on Rh/Ir besides 2-pyridyl and PBP. A pair of M–C/M–N isomers for each type was computationally examined for Rh and for Ir, totaling 16 compounds. Several of these compounds were isolated or observed in solution by experimental methods, in addition to a few 2-quinolyl variants. The DFT predictions concerning the thermodynamic preference within each M–C/M–N isomeric match the experimental findings very well. In two cases where DFT predicts <2 kcal mol⁻¹ difference in free energy, both isomers were experimentally observed in solution. Analysis of the structural data, of the relevant Wiberg bond indices, and of the ETS-NOCV partitioning of the interaction of the 2-pyridyl fragment with the rest of the molecule points to the strength of the M–C(pyridyl) bond as the dominant parameter determining the relative M–C/M–N isomer favorability. This M–C bond is always stronger for the analogous Ir vs. Rh compounds, but the nature of the ligand trans to it has a significant influence, as well. DFT calculations were used to evaluate the mechanism of isomerization for one of the molecule types.

The thermodynamic preference between two isomeric products of C–H activation of pyridine, with 2-pyridyl bridging boron and iridium or rhodium, primarily depends on the M–C bond strength.     

Oxygen atom transfer promoted nitrate to nitric oxide transformation: a step-wise reduction of nitrate → nitrite → nitric oxide

Nitrate reductases (NRs) are molybdoenzymes that reduce nitrate (NO₃⁻) to nitrite (NO₂⁻) in both mammals and plants. In mammals, the salival microbes take part in the generation of the NO₂⁻ from NO₃⁻, which further produces nitric oxide (NO) either in acid-induced NO₂⁻ reduction or in the presence of nitrite reductases (NiRs). Here, we report a new approach of VCl₃ (V³⁺ ion source) induced step-wise reduction of NO₃⁻ in a Co^II-nitrato complex, [(12-TMC)Co^II(NO₃⁻)]⁺ (2,{Co^II–NO₃⁻}), to a Co^III–nitrosyl complex, [(12-TMC)Co^III(NO)]²⁺ (4,{CoNO}⁸), bearing an N-tetramethylated cyclam (TMC) ligand. The VCl₃ inspired reduction of NO₃⁻ to NO is believed to occur in two consecutive oxygen atom transfer (OAT) reactions, i.e., OAT-1 = NO₃⁻ → NO₂⁻ (r₁) and OAT-2 = NO₂⁻ → NO (r₂). In these OAT reactions, VCl₃ functions as an O-atom abstracting species, and the reaction of 2 with VCl₃ produces a Co^III-nitrosyl ({CoNO}⁸) with V^V-Oxo ({V^V O}³⁺) species, via a proposed Co^II-nitrito (3, {Co^II–NO₂⁻}) intermediate species. Further, in a separate experiment, we explored the reaction of isolated complex 3 with VCl₃, which showed the generation of 4 with V^V-Oxo, validating our proposed reaction sequences of OAT reactions. We ensured and characterized 3 using VCl₃ as a limiting reagent, as the second-order rate constant of OAT-2 (k₂^/) is found to be ∼1420 times faster than that of the OAT-1 (k₂) reaction. Binding constant (K_b) calculations also support our proposition of NO₃⁻ to NO transformation in two successive OAT reactions, as K_{b(Co^II–NO2⁻)} is higher than K_{b(Co^II–NO3⁻)}, hence the reaction moves in the forward direction (OAT-1). However, K_{b(Co^II–NO2⁻)} is comparable to K_b{CoNO}⁸, and therefore sequenced the second OAT reaction (OAT-2). Mechanistic investigations of these reactions using ¹⁵N-labeled-¹⁵NO₃⁻ and ¹⁵NO₂⁻ revealed that the N-atom in the {CoNO}⁸ is derived from NO₃⁻ ligand. This work highlights the first-ever report of VCl₃ induced step-wise NO₃⁻ reduction (NRs activity) followed by the OAT induced NO₂⁻ reduction and then the generation of Co-nitrosyl species {CoNO}⁸.

Single metal-induced reduction of NO₃⁻ → {NO₂⁻} → NO via oxygen atom transfer reaction.     

Cooperativity as quantification and optimization paradigm for nuclear receptor modulators

Nuclear Receptors (NRs) are highly relevant drug targets, for which small molecule modulation goes beyond a simple ligand/receptor interaction. NR–ligands modulate Protein–Protein Interactions (PPIs) with coregulator proteins. Here we bring forward a cooperativity mechanism for small molecule modulation of NR PPIs, using the Peroxisome Proliferator Activated Receptor γ (PPARγ), which describes NR–ligands as allosteric molecular glues. The cooperativity framework uses a thermodynamic model based on three-body binding events, to dissect and quantify reciprocal effects of NR–coregulator binding (K^I_D) and NR–ligand binding (K^II_D), jointly recapitulated in the cooperativity factor (α) for each specific ternary ligand·NR·coregulator complex formation. These fundamental thermodynamic parameters allow for a conceptually new way of thinking about structure–activity-relationships for NR–ligands and can steer NR modulator discovery and optimization via a completely novel approach.

A cooperativity framework describes the formation of nuclear receptor ternary complexes and deconvolutes ligand and cofactor binding into intrinsic affinities and a cooperativity factor, providing a conceptually new understanding of NR modulation.     

Direct metal–carbon bonding in symmetric bis(C–H) agostic nickel(i) complexes

Agostic interactions are examples of σ-type interactions, typically resulting from interactions between C–H σ-bonds with empty transition metal d orbitals. Such interactions often reflect the first step in transition metal-catalysed C–H activation processes and thus are of critical importance in understanding and controlling σ bond activation chemistries. Herein, we report on the unusual electronic structure of linear electron-rich d⁹ Ni(i) complexes with symmetric bis(C–H) agostic interactions. A combination of Ni K edge and L edge XAS with supporting TD-DFT/DFT calculations reveals an unconventional covalent agostic interaction with limited contributions from the valence Ni 3d orbitals. The agostic interaction is driven via the empty Ni 4p orbitals. The surprisingly strong Ni 4p-derived agostic interaction is dominated by σ contributions with minor π contributions. The resulting ligand–metal donation occurs directly along the C–Ni bond axis, reflecting a novel mode of bis-agostic bonding.

Symmetric Ni(i) agostic complexes reveal an unusual mode of bonding that is dominated by direct carbon-to-metal charge transfer.     

Preparations and properties of vanadium(III) complexes of bidentate and terdentate nitrogen-donor ligands

Summary Vanadium(III) chloride reacts with 1,10-phenanthroline and 2,2-bipyridyl, and with substituted derivatives of each ligand (B), in ethanol or in acetonitrile as solvent (L), to yield two different series of complexes. These are (a) the neutral species VCl₃BL, where B = 1,10-phenanthroline, 5-chloro-1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 2,2-bipyridyl, 4,4-dimethyl-2,2-bipyridyl, L = ethanol. The complexes in which B = 1,10-phenanthroline or 2,2-bipyridyl were also obtained with L = acetonitrile, (b) [VCl₂B₂]⁺[VCl₄B]^– where B is the same series of ligands listed above. Vanadium(III) chloride yields VCl₃ (terpy) with 2,2,2 -terpyridyl. All the complexes have been characterised by elemental analyses, conductance measurements, electronic- and i.r. spectral measurements, and by their temperature-range (297–77 K) magnetic moments; ring substituents have little influence on any chemical or physical properties of these complexes.     

Combining metal–metal cooperativity,metal–ligand cooperativity and chemical non-innocence in diiron carbonyl complexes

Several metalloenzymes, including [FeFe]-hydrogenase, employ cofactors wherein multiple metal atoms work together with surrounding ligands that mediate heterolytic and concerted proton–electron transfer (CPET) bond activation steps. Herein, we report a new dinucleating PNNP expanded pincer ligand, which can bind two low-valent iron atoms in close proximity to enable metal–metal cooperativity (MMC). In addition, reversible partial dearomatization of the ligand''s naphthyridine core enables both heterolytic metal–ligand cooperativity (MLC) and chemical non-innocence through CPET steps. Thermochemical and computational studies show how a change in ligand binding mode can lower the bond dissociation free energy of ligand C(sp³)–H bonds by ∼25 kcal mol⁻¹. H-atom abstraction enabled trapping of an unstable intermediate, which undergoes facile loss of two carbonyl ligands to form an unusual paramagnetic (S = ) complex containing a mixed-valent iron(0)–iron(i) core bound within a partially dearomatized PNNP ligand. Finally, cyclic voltammetry experiments showed that these diiron complexes show catalytic activity for the electrochemical hydrogen evolution reaction. This work presents the first example of a ligand system that enables MMC, heterolytic MLC and chemical non-innocence, thereby providing important insights and opportunities for the development of bimetallic systems that exploit these features to enable new (catalytic) reactivity.

The PNNP expanded pincer ligand can bind two iron centers in close proximity and display heterolytic and homolytic metal–ligand cooperativity.     

Covalency in actinide(iv) hexachlorides in relation to the chlorine K-edge X-ray absorption structure

Chlorine K-edge X-ray absorption near edge structure (XANES) in actinide^IV hexachlorides, [AnCl₆]²⁻ (An = Th–Pu), is calculated with relativistic multiconfiguration wavefunction theory (WFT). Of particular focus is a 3-peak feature emerging from U toward Pu, and its assignment in terms of donation bonding to the An 5f vs. 6d shells. With or without spin–orbit coupling, the calculated and previously measured XANES spectra are in excellent agreement with respect to relative peak positions, relative peak intensities, and peak assignments. Metal–ligand bonding analyses from WFT and Kohn–Sham theory (KST) predict comparable An 5f and 6d covalency from U to Np and Pu. Although some frontier molecular orbitals in the KST calculations display increasing An 5f–Cl 3p mixing from Th to Pu, because of energetic stabilization of 5f relative to the Cl 3p combinations of the matching symmetry, increasing hybridization is neither seen in the WFT natural orbitals, nor is it reflected in the calculated bond orders. The appearance of the pre-edge peaks from U to Pu and their relative intensities are rationalized simply by the energetic separation of transitions to 6d t_2gversus transitions to weakly-bonded and strongly stabilized a_2u, t_2u and t_1u orbitals with 5f character. The study highlights potential pitfalls when interpreting XANES spectra based on ground state Kohn–Sham molecular orbitals.

Chlorine K-edge XANES of An(iv) hexachlorides, calculated with multiconfiguration wavefunction theory, is interpreted in terms of similar metal–ligand covalency along the An = Th–Pu series.     

Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex

A series of five ruthenium complexes containing triphenyl phosphine groups known to enhance both cellular penetration and photoinduced ligand exchange, cis-[Ru(bpy)₂(P(p-R-Ph)₃)(CH₃CN)]²⁺, where bpy = 2,2′-bipyridine and P(p-R-Ph)₃ represent para-substituted triphenylphosphine ligands with R = –OCH₃ (1), –CH₃ (2) –H (3), –F (4), and –CF₃ (5), were synthesized and characterized. The photolysis of 1–5 in water with visible light (λ_irr ≥ 395 nm) results in the substitution of the coordinated acetonitrile with a solvent molecule, generating the corresponding aqua complex as the single photoproduct. A 3-fold variation in quantum yield was measured with 400 nm irradiation, Φ₄₀₀, where 1 is the most efficient with a Φ₄₀₀ = 0.076(2), and 5 the least photoactive complex, with Φ₄₀₀ = 0.026(2). This trend is unexpected based on the red-shifted metal-to-ligand charge transfer (MLCT) absorption of 1 as compared to that of 5, but can be correlated to the substituent Hammett para parameters and pK_a values of the ancillary phosphine ligands. Complexes 1–5 are not toxic towards the triple negative breast cancer cell line MDA-MB-231 in the dark, but 3 and 5 are >4.2 and >19-fold more cytotoxic upon irradiation with blue light, respectively. A number of experiments point to apoptosis, and not to necrosis or necroptosis, as the mechanism of cell death by 5 upon irradiation. These findings provide a foundation for understanding the role of phosphine ligands on photoinduced ligand substitution and show the enhancement afforded by –CF₃ groups on photochemotherapy, which will aid the future design of photocages for photochemotherapeutic drug delivery.

Ru(ii) complexes exhibit photoinduced exchange of coordinated CH₃CN and photocytotoxicity against breast cancer cells highly dependent on the substituents of the ancillary triphenylphospine ligand.     

Phosphorus-substituted carbene complexes: Chelates,pincers and spirocycles

The syntheses, structural characterizations and reactivity patterns of main group and late transition metal carbene complexes of the bis(phosphoranimino)methandiide, [C(Ph₂PNSiMe₃)₂]²⁻, and the carbodiphosphorane, Ph₃PCPPh₃, are described and compared to previously reviewed early transition metal analogues. Bimetallic spirocyclic aluminum complexes of the former ligand are accessed by spontaneous double deprotonation of the central carbon atom of the parent, CH₂(Ph₂PNSiMe₃)₂, by two equivalents of AlMe₃, whereas the synthesis of platinum complexes requires the intermediacy of the tetralithium dimer, [Li₂C(Ph₂PNSiMe₃)₂]₂, and elimination of LiCl from a metal chloride precursor. In contrast to the early transition metal analogues, which are N,C,N-pincer, Schrock-type alkylidenes, the C,N-chelated platinum complexes are more akin to Fischer carbenes, and their chemistry is dominated by the nucleophilicity of free nitrogen atom and insertions into labile N–Si bonds. Chelated and pincer carbene complexes of rhodium result from single and double orthometallations, respectively, of the phenyl rings in Ph₃PCPPh₃; the latter compounds represent a wholly new class of C,C,C-pincer complexes. Electronic structure calculations show that the metal–carbon interaction in these compounds may be described as a dative, two-electron, C → M σ-bond. The free bis(phosphoranimino)methandiide and carbodiphosphorane ligands, while not having formal six valence electron resonance forms, may be thought of as having “pull–pull” Fischer carbene character, but the metal to which they become coordinated ultimately dictates their chemistry.     

Transition-metal-mediated reduction and reversible double-cyclization of cyanuric triazide to an asymmetric bitetrazolate involving cleavage of the six-membered aromatic ring

Cyanuric triazide reacts with several transition metal precursors, extruding one equivalent of N₂ and reducing the putative diazidotriazeneylnitrene species by two electrons, which rearranges to N-(1′H-[1,5′-bitetrazol]-5-yl)methanediiminate (biTzI²⁻) dianionic ligand, which ligates the metal and dimerizes, and is isolated from pyridine as [M(biTzI)]₂Py₆ (M = Mn, Fe, Zn, Cu, Ni). Reagent scope, product analysis, and quantum chemical calculations were combined to elucidate the mechanism of formation as a two-electron reduction preceding ligand rearrangement.

Cyanuric triazide reacts with transition metal precursors, extruding N₂ and reducing the ligand by two electrons, which breaks an aromatic ring and rearranges to a bitetrazolylmethanediiminate (biTzI²⁻) ligand, forming two new aromatic rings.     

Osmium(ii) tethered half-sandwich complexes: pH-dependent aqueous speciation and transfer hydrogenation in cells

Aquation is often acknowledged as a necessary step for metallodrug activity inside the cell. Hemilabile ligands can be used for reversible metallodrug activation. We report a new family of osmium(ii) arene complexes of formula [Os(η⁶-C₆H₅(CH₂)₃OH)(XY)Cl]^+/0 (1–13) bearing the hemilabile η⁶-bound arene 3-phenylpropanol, where XY is a neutral N,N or an anionic N,O⁻ bidentate chelating ligand. Os–Cl bond cleavage in water leads to the formation of the hydroxido/aqua adduct, Os–OH(H). In spite of being considered inert, the hydroxido adduct unexpectedly triggers rapid tether ring formation by attachment of the pendant alcohol–oxygen to the osmium centre, resulting in the alkoxy tethered complex [Os(η⁶-arene-O-κ¹)(XY)]ⁿ⁺. Complexes 1C–13C of formula [Os(η⁶:κ¹-C₆H₅(CH₂)₃OH/O)(XY)]⁺ are fully characterised, including the X-ray structure of cation 3C. Tether-ring formation is reversible and pH dependent. Osmium complexes bearing picolinate N,O-chelates (9–12) catalyse the hydrogenation of pyruvate to lactate. Intracellular lactate production upon co-incubation of complex 11 (XY = 4-Me-picolinate) with formate has been quantified inside MDA-MB-231 and MCF7 breast cancer cells. The tether Os–arene complexes presented here can be exploited for the intracellular conversion of metabolites that are essential in the intricate metabolism of the cancer cell.

New Os(ii) half-sandwich complexes bearing a pendant alcohol prompt reversible tether-ring formation upon aquation, protecting Os against deactivation. Excitingly, these complexes mediate hydrogenation of pyruvate to lactate inside cancer cells.     

Spotlighting main group elements in polynuclear complexes

François Gabbaï, Cameron Jones and Connie Lu introduce the Chemical Science themed collection on the topic of main group elements in polynuclear complexes.

Efforts towards the incorporation of main group elements in polynuclear motifs or in the coordination sphere of transition metals have been a prevalent theme of coordination chemistry, and one that has delivered notable advances in the area of structure and bonding. In the past decade, this field has witnessed an increased emphasis on the influence of the main group moiety over the reactivity or physical properties of the resulting constructs. Through a collection of both invited and selected articles, this themed issue puts the spotlight on this developing field, while at the same time illustrating far-reaching applications in the areas of small molecule activation, catalysis and molecular magnetism.A number of papers in this themed issue highlight the significant recent progress that has been made in the development of homo- and heterometallic systems incorporating s- and p-block elements, both in low oxidation states (often element–element bonded) and normal oxidation states. These have found particular use as low toxicity, earth abundant alternatives to late transition metal complexes in stoichiometric and catalytic transformations of small molecule substrates to value added products. This theme is introduced in primary articles dealing with the reactivity of magnesium-based systems. As shown by Jones, Maron and co-workers, magnesium(i) dimers (LMg–MgL, L = β-diketiminate) are activated by coordination of simple Lewis bases, and are subsequently able to reductively couple carbon monoxide to form the deltate and transient ethenediolate dianions (C_nO_n²⁻, n = 3 and 2, respectively; DOI: 10.1039/D0SC00836B). In another contribution, β-diketiminato-stabilised magnesium diboronates are shown by Hill, McMullin and co-workers to act as rare “masked” sources of nucleophilic boryl anions for the synthetic transformation of imines (DOI: 10.1039/C9SC02087J). These two papers integrate with the content of two reviews that highlight the unique structures and reactivity of polynuclear complexes containing low valent group 2, 13 and 14 elements. One of these reviews, by Inoue and co-workers, focuses on the structures of ditetrelenes (R₂E^II E^IIR₂, E = group 14 element) and ditetrelynes (RE^I E^IR), and their remarkable reactivity towards small molecules (DOI: 10.1039/D0SC03192E). Another review by Crimmin and co-workers explores the role that magnesium(i) and aluminium(i) reductants play in C–H bond activation reactions, and the synergy that may arise when the main group reagent is combined with a transition metal (DOI: 10.1039/D0SC03695A). Showcasing the value that s-block metals may display in their normal valence, Williams and coworkers describe macrocyclic Mg^II/Zn^II heterodinuclear complexes as highly effective catalysts for epoxide/CO₂ ring opening co-polymerization (DOI: 10.1039/C9SC00385A). The broader significance of this concept is developed in a review on heterobimetallic complexes containing s-block metals, in which Hevia and her co-worker highlight the unique ability of such complexes to support cooperative catalysis (DOI: 10.1039/D0SC05116K). The Lewis acidity of s-block cations can also be harnessed to manipulate the covalency of metal–ligand interactions, as elegantly demonstrated by Arnold, Love, Vitova, Schreckenbach and co-workers, who investigate a series of uranyl(v) complexes featuring U O–E motifs (E = group 1 or 2 element, DOI: 10.1039/C8SC05717F).Reduced polynuclear main group complexes can also provide new platforms for the discovery of atypical reactivity as illustrated by Kong and co-workers, who report mono-base-stabilized 1,2-diboranylidenehydrazines, a set of compounds that feature an unprecedented BNN-1,3-dipole that readily adds to arenes or small molecules such as CO₂ (DOI: 10.1039/D0SC02162H). In keeping with the theme of reactive diboron-containing units, Braunschweig and co-workers show in another captivating report that B–B triply-bonded diborynes can add to diboranes to afford B₄ chains, a transformation that could pave the way to new polymers with polyboron units in the main chain (DOI: 10.1039/C9SC02544H). The synthetic potential offered by low oxidation state main group elements comes to the fore in two additional reports, both dealing with Si₆ clusters. In the first one, Scheschkewitz and co-workers show that these silicon clusters can be functionalised with tetrylene substituents, and can act as ligands towards group 9 metal fragments, yielding complexes which act as catalysts for alkene isomerisations (DOI: 10.1039/D0SC02861D). A second report by Lips and co-workers describes highly unsaturated and structurally dynamic Si₆R₄ species (R = amide) with exposed silicon vertices (DOI: 10.1039/D0SC01427C). Exposed silicon moieties can also be appended to classical ligands as demonstrated by Roesky and co-workers who report on cyclopentadienyl ligands substituted by a silylene (R₂Si:). These ligands not only act as two-electron Si donors towards transition metal fragments but also undergo isomerization or deprotonation reactions leading to sila-fulvenes (DOI: 10.1039/D0SC04174B). Reduced group 14 elements can also be directly incorporated in the five-membered ring of cyclopentadienyl-like ligands as illustrated by Müller, Albers and co-workers in a contribution dealing with the germacyclopentadienediyl [K₂(:GeC₄R₄)] as an η⁵-ligand and its conversion into the first germaaluminocene, [Cp*Al(η⁵-:GeC₄R₄)] (DOI: 10.1039/D0SC00401D).As stated in the introductory paragraph, positioning main group elements in the coordination sphere of transition metals provides access to unusual reactivities, as in a contribution by Ozerov and co-workers (DOI: 10.1039/D0SC04748A) who demonstrate the reversible addition of ethylene to a boryl-based bis(phosphine) iridium pincer complex. A unique aspect of this contribution is the concomitant participation of the iridium and boron centres in the coordination of the hydrocarbon ligand. The ability of boron to cooperate with an adjacent transition metal centre is again a leading theme in two additional contributions selected for inclusion in this issue. The first one concerns the reversible addition of H₂ across an Ni–B bond, as elegantly documented by Rodríguez, Lledós and co-workers (DOI: 10.1039/D0SC06014C), who also used a boryl-based pincer as a supporting ligand. Exploiting the somewhat counter-intuitive reality that gold is more electronegative than boron, Yamashita, Lin and co-workers show that gold(i) diarylboryl complexes react as gold-based nucleophiles with organic reagents bearing C O and C N bonds (DOI: 10.1039/D0SC05478J). The unique reactivity of late transition metal–boryl linkages pervades in another contribution by Conejero, Lledós and co-workers who detail the highly choreographed addition of boranes such as HBpin and HBcat to a cationic, T-shaped, cyclometallated Pt(ii) bis-carbene complex (DOI: 10.1039/D0SC05522K). Isolated species include σ-BH Pt^II complexes, en route to the formation of T-shaped Pt^II bis-carbene complexes. Last, Tilley, Eisenstein and co-workers remind us of the importance of main group hydrides in catalysis in a contribution that pinpoints the intermediacy of dinuclear nickel–silyl species in an alkene hydrosilylation reaction mediated by a cationic nickel complex (DOI: 10.1039/D0SC00997K).Within the theme of heterometallic cooperativity, we highlight three articles where group 13 elements were introduced into transition metal complexes to promote small-molecule activation. In each report, a unique ligand design is used to juxtapose the transition metal centre with the group 13 element(s). Szymczak and co-workers appended two Lewis acidic borane groups to a pincer ligand via flexible linkers. The pendant boranes were critical for the stabilization of a rare high-spin Fe^II dihydride complex by forging Fe–H → B interactions (DOI: 10.1039/C9SC00561G). Upon exposure to an arylisocyanide, a good π-acid, the reductive elimination of H₂ ensued to form the iron(0) complex. Such a step is reminiscent of the E₄ intermediate in nitrogenase, which is proposed to release the obligatory H₂ equivalent upon binding of N₂ [see Chem. Rev., 2014, 114, 4041]. Envisioning a more active role for boranes, Harman and co-workers use the diboraanthracene platform, whose redox flexibility and dynamic Lewis acidity can be orchestrated to promote reactivity at the bound transition metal (DOI: 10.1039/C9SC02792K). The authors isolate a key Au borohydride intermediate that reduces CO₂ to formate, and close a synthetic cycle from CO₂ to formic acid using only proton and electron equivalents. Moving down the group 13 to the heavier congeners, Lu and co-workers show that the choice of the heavy group 13 ion (Al, Ga, or In) that is directly appended to a nickel(0) centre can significantly tune the Ni electronics (DOI: 10.1039/C9SC02018G). In comparing a triad of non-classical Ni(η²-H₂) adducts, the identity of the group 13 ion was found to perturb the free energy and activation energy of H₂ binding by ∼5 kcal mol⁻¹. Lastly, in a timely review, Takaya details the growing momentum of using main group/metalloid complexes as supporting ligands for transition metal-based catalysis (DOI: 10.1039/D0SC04238B). Takaya’s review presents illustrative examples to showcase the diverse main group elements (groups 13–15) and strategies that are being harnessed for transition metal catalysis.Moving down the periodic table to the f-elements, several articles explore heterometallic lanthanide and actinide complexes that fundamentally challenge our understanding of bonding and electronic structure. Using mixed arene π-ligands, Liddle and co-workers isolated an unusual bent Th “sandwich” complex that is stitched by K⁺ ions into a tetrathorium cluster (DOI: 10.1039/D0SC02479A). Diaconescu, Huang and co-workers report inverted sandwich complexes of Sm and Y featuring a bridging biphenyl ligand and bridging K⁺ ions (DOI: 10.1039/D0SC03555F). Depending on the lanthanide element, these inverted sandwiches feature Sm^III–arene–Sm^III or Yb^II–arene–K⁺ bonding interactions, where the biphenyl ligand is formally tetraanionic or dianionic, respectively. Freedman and co-workers conducted an in-depth study on the electronic structures of Sn-based heterometallics that contain a direct bond between Sn and a first-row transition metal that is varied from Mn to Ni (DOI: 10.1039/D0SC03777J). The authors make a striking comparison between the high-spin configurations of the 3d ions and those of typical Ln coordination complexes, wherein the coordinate bonds are more ionic. They rationalize that the Sn group behaves as an inverted, weak-field ligand due to the large energy mismatch between the Sn 5s/5p and 3d atomic orbitals [see Chem. Rev., 2016, 116, 8173]. Controlling spin states is only one of several requisites for the design of single molecule magnets (SMMs). Layfield, Mansikkamäki and co-workers report a triad of dinuclear dysprosium complexes, where the exogenous borohydride donor is varied in both number and coordination (terminal to bridging) (DOI: 10.1039/D0SC02033H). The authors observed a favourable increase in the effective energy barrier for a dinuclear dysprosium complex with a Dy : BH₄ ratio of 2 : 1. Lastly, Nippe, Chibotaru and co-workers explore magneto-structural relationships in a series of trigonal prismatic Ln^III complexes (Gd to Lu) that are scaffolded by three doubly deprotonated ferrocene (FeCp₂)²⁻ ligands and capped by Li⁺ ions (DOI: 10.1039/D0SC01197E). By virtue of its size and axis of anisotropy, the authors were able to engender SMM behaviour for the Ho^III complex. The authors demonstrate that the Ln size and the nature of the Li⁺ solvate both influence the twist angle, where the ideal trigonal prism geometry (twist angle of 0°) results in the large anisotropy that is conducive to SMM behaviour.To illustrate the diversity of the field, this themed issue also highlights several additional contributions dealing with atypical phosphorus-containing ligands. For example, Scheer and co-workers show that the four-membered cyclo-P₄ ligand of organometallic tantalum complexes can be used as a square building block for the construction of molecular capsules upon combination with silver cations and an appropriate template (DOI: 10.1039/D0SC03437A). Two additional contributions document recent trends at the confluence of traditional organophosphorus chemistry and coordination chemistry. Gessner and co-workers review the unique properties of phosphorus ylides and their ability to stabilize low-valent main group species, leading to the formation of new main group ligands for transition metal-based catalysis (DOI: 10.1039/D0SC03278F). The second contribution comes from Normand, Sosa Carrizo and co-workers who decipher the ambiphilic properties of bis(iminophosphoranyl)phosphide ligands and suggest that they be regarded as containing a triphosphenium coordinating unit (DOI: 10.1039/D0SC04736H).This themed issue was assembled with the intent of spotlighting the role played by main group elements in polynuclear complexes. We hope that those reading these articles will appreciate the topical diversity of this research field, its relevance to various areas of chemistry, and the numerous future research opportunities it presents.     

Dynamic supramolecular self-assembly of platinum(ii) complexes perturbs an autophagy–lysosomal system and triggers cancer cell death

Self-assembly of platinum(ii) complexes to form supramolecular structures/nanostructures due to intermolecular ligand π–π stacking and metal–ligand dispersive interactions is widely used to develop functional molecular materials, but the application of such non-covalent molecular interactions has scarcely been explored in medical science. Herein is described the unprecedented biological properties of platinum(ii) complexes relevant to induction of cancer cell death via manifesting such intermolecular interactions. With conjugation of a glucose moiety to the planar platinum(ii) terpyridyl scaffold, the water-soluble complex [Pt(tpy)(C CArOGlu)](CF₃SO₃) (1a, tpy = 2,2′:6′,2′′-terpyridine, Glu = glucose) is able to self-assemble into about 100 nm nanoparticles in physiological medium, be taken up by lung cancer cells via energy-dependent endocytosis, and eventually transform into other superstructures distributed in endosomal/lysosomal and mitochondrial compartments apparently following cleavage of the glycosidic linkage. Accompanying the formation of platinum-containing superstructures are increased autophagic vacuole formation, lysosomal membrane permeabilization, and mitochondrial membrane depolarization, as well as anti-tumor activity of 1a in a mouse xenograft model. These findings highlight the dynamic, multi-stage extracellular and intracellular supramolecular self-assembly of planar platinum(ii) complexes driven by modular intermolecular interactions with potential anti-cancer application.

Self-assembly of platinum(ii) glycosylated arylacetylide gave transformable superstructures upon enzymatic action in cellulo, leading to perturbation of an autophagy-lysosomal system and cancer cell death.