Oxidation-induced ambiphilicity triggers N-N bond formation and dinitrogen release in octahedral terminal molybdenum(v) nitrido complexes.

Coupling of octahedral, terminal d1 molybdenum(v) nitrido complexes supported by a dianionic pentadentate ligand via N-N bond formation to give µ-dinitrogen complexes was found to be thermodynamically feasible but faces significant kinetic barriers. However, upon oxidation, a kinetically favored nucleophilic/electrophilic N-N bond forming mechanism was enabled to give monocationic µ-dinitrogen dimers. Computational and experimental evidence for this "oxidation-induced ambiphilic nitrido coupling" mechanism is presented. The factors influencing release of dinitrogen from the resulting µ-dinitrogen dimers were also probed and it was found that further oxidation to a dicationic species is required to induce (very rapid) loss of dinitrogen. The mechanistic path discovered for N-N bond formation and dinitrogen release follows an ECECC sequence (E = "electrochemical step"; C = "chemical step"). Experimental evidence for the intermediacy of a highly electrophilic, cationic d0 molybdenum(vi) nitrido in the N-N bond forming mechanism via trapping with an isonitrile reagent is also discussed. Together these results are relevant to the development of molecular catalysts capable of mediating ammonia oxidation to dihydrogen and dinitrogen.

A molecular extraction process for vanadium based on tandem selective complexation and precipitation.

Recycling vanadium from alternative sources is essential due to its expanding demand, depletion in natural sources, and environmental issues with terrestrial mining. Here, we present a complexation-precipitation method to selectively recover pentavalent vanadium ions, V(V), from complex metal ion mixtures, using an acid-stable metal binding agent, the cyclic imidedioxime, naphthalimidedioxime (H2CIDIII). H2CIDIII showed high extraction capacity and fast binding towards V(V) with crystal structures showing a 1:1 M:L dimer, [V2(O)3(C12H6N3O2)2]2-, 1, and 1:2 M:L non-oxido, [V(C12H6N3O2)2] ̶ complex, 2. Complexation selectivity studies showed only 1 and 2 were anionic, allowing facile separation of the V(V) complexes by pH-controlled precipitation, removing the need for solid support. The tandem complexation-precipitation technique achieved high recovery selectivity for V(V) with a selectivity coefficient above 3 × 105 from synthetic mixed metal solutions and real oil sand tailings. Zebrafish toxicity assay confirmed the non-toxicity of 1 and 2, highlighting H2CIDIII's potential for practical and large-scale V(V) recovery.

Ruthenium polyhydrides supported by rigid PCP pincer ligands: dynamic behaviour and reactions with CO2.

Two rigid ß-elimination immune PCcarbeneP pincer ligands, differing in their electron donor properties by variation of the substitution pattern on the aromatic linker arms, were complexed to ruthenium to form the dichlorides LRRuCl2 (R = H or NMe2). These compounds were converted to hydrido chlorides by treatment with dihydrogen (H2) and a base. By converting to tert-butoxide derivatives in situ under an atmosphere of H2, the poly hydride PCalkylP complexes LHRRu(H)3 compounds were generated. In these complexes, H2 has added across the RuC bond in the PCcarbeneP starting materials. The polyhydrides are dynamic in solution and extensive NMR studies helped to elucidate the speciation and fluxional processes operative in this dynamic system. The polyhydride complexes react rapidly with CO2 to give the PCcarbeneP formato hydride complexes LRRu(H)-κ2-O2CH. For R = H, the 1,2-hydride shift from the anchoring alkyl of the PCalkylP carbon to the metal is reversible, but for R = NMe2 it is irreversible. The CO2 incorporated into the formato ligand of these compounds exchanges with free CO2via a bimolecular mechanism that is more rapid for R = NMe2 than for R = H; plausible explanations for this observation are proffered. Experiments designed to evaluate the efficacy of the R = NMe2 formato hydride complex as a catalyst precursor for CO2 hydrogenation to formate salts reveal poor performance in comparison to state-of-the-art ruthenium-based catalysts. This is due primarily to the precipitation of a dimeric µ-κ2-κ1-CO3 carbonate complex that is not an active catalyst for the reaction.

Rhenium(I)-tricarbonyl complexes with methimazole and its selenium analogue: Syntheses, characterization and cell toxicity.

This study explores the effect of a thione/selone ligand on the cell toxicity (in vitro) and light activity of diimine Re(CO)3+ complexes. Six rhenium(I) complexes with general formula fac-[Re(CO)3(N,N')X]+ were prepared, where X = 2-mercapto-1-methylimidazole (methimazole; MMI), and 1-methylimidazole-2-selone (MSeI); N,N' = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (dmphen). Their triflate salts were characterized using single-crystal X-ray diffraction, 1H, 13C and 2D NMR, UV-vis and vibrational spectroscopy. Their cytotoxic properties were tested, showing significant cytotoxicity (IC50 = 8.0-55 µM) towards the human breast cancer cell line MDA-MB-231. The half-inhibitory concentration (IC50) for fac-[Re(CO)3(dmphen)(MMI)]+, the most toxic complex in this series (8.0 ± 0.2 µM), was comparable to that of the corresponding aqua complex fac-[Re(CO)3(dmphen)(H2O)]+ with IC50 = 6.0 ± 0.1 µM. The fac-[Re(CO)3(bpy)(MMI/MSeI)]+ complexes were somewhat less toxic towards the human embryonic kidney cell line HEK-293 T after 48 h of exposure. The stability of the complexes upon irradiation was monitored using UV-vis spectroscopy, with no CO released when exposed to UV-A light (λ = 365 nm).

Microporous Metal-Phosphonates with a Novel Orthogonalized Linker and Complementary Guests: Insights for Trivalent Metal Complexes from Divalent Metal Complexes.

The reliable self-assembly of microporous metal-phosphonate materials remains a longstanding challenge. This stems from, generally, more coordination modes for the functional group allowing more dense structures, and stronger bonding driving less crystalline products. Here, a novel orthogonalized aryl-phosphonate linker, 1,3,5-tris(4'-phosphono-2',6'-dimethylphenyl) benzene (H6 L3) has been used to direct formation of open frameworks. The peripheral aryl rings of H6 L3 are orthogonalized relative to the central aromatic ring giving a tri-cleft conformation of the linker in which small aromatic molecules can readily associate. When coordinated to magnesium ions, a series of porous crystalline metal-organic, and hydrogen-bonded metal-organic frameworks (MOFs, HMOFs) are formed (CALF-41 (Mg), HCALF-42 (Mg), -43 (Mg)). While most metal-organic frameworks are tailored based on choice of metal and linker, here, the network structures are highly dependent on the inclusion and structure of the guest aromatic compounds. Larger guests, and a higher stoichiometry of metal, result in increased solvation of the metal ion, resulting in networks with connectivities increasingly involving hydrogen-bonds rather than direct phosphonate coordination. Upon thermal activation and aromatic template removal, the materials exhibit surface areas ranging from 400-600 m2 /g. Self-assembly in the absence of aromatic guests yields mixtures of phases, frequently co-producing a dense 3-fold interpenetrated structure (1). Interestingly, a series of both more porous (530-900 m2 /g), and more robust solids is formed by complexing with trivalent metal ions (Al, Ga, In) with aromatic guest; however, these are only attainable as microcrystalline powders. The polyprotic nature of phosphonate linkers enables structural analogy to the divalent analogues and these are identified as CALF-41 analogues. Finally, insights to the structural transformations during metal ion desolvation in this family are gained by considering a pair of structurally related Co materials, whose hydrogen-bonded (HCALF-44 (Co)) and desolvated (CALF-44 (Co)) coordination bonded networks were fully structurally characterized.

Electrocatalyst decomposition pathways: torsional strain in a second sphere proton relay shuts off CO2RR in a Re(2,2'-bipyridyl)(CO)3X type electrocatalyst.

Group 7 tris(carbonyl) bipyridine complexes have been well explored as important CO2 reduction reaction (CO2RR) electrocatalysts and now represent an excellent platform for catalyst design. Recent synthetic focus has been on the installation of proton sources/relays within the primary/secondary coordination sphere. These proton sources have been implicated in directly assisting catalysis by acting as shuttles for proton transfer or through the stabilization of transition states through hydrogen bonding. Herein, we report a new ligand system for CO2RR electrocatalysts, which features an aryl amine appended to a quinoline-bipyridine core. While the geometrical arrangement of the aryl amine seems amenable to assisting CO2RR electrocatalysis, we find, through spectroelectrochemical and chemical reduction studies, the torsional strain imposed on the ligand induces a structural reorganization through loss of a hydrogen atom radical. This new complex, which utilizes the anionic nitrogen as a donor atom, and other Re complexes with the same coordination motif, have been found to be entirely inactive for CO2RR. Subsequent reduction yields hydrogenation of the complex through dearomatization of the quinoline backbone concomitant with decomposition products. While the electrocatalytic capability of the reported complexes is moderate, the study represents an important investigation into the deactivation of CO2RR electrocatalysts as a consequence of typical proton shuttle moieties and guides future ligand design by highlighting an oft overlooked structural parameter.

Unexpected Formation and Potent Antioxidant Activity of Macrocyclic Dimers Containing Disulfide and Selenide Groups.

During attempts to prepare spirodithiaselenuranes as GPx mimetics, a series of unexpected dimeric macrocycles was obtained, each containing two selenide and two disulfide moieties in rings ranging from 18- to 26-membered. The products showed potent GPx-like activity in an NMR assay based on their ability to catalyze the reduction of hydrogen peroxide with benzyl thiol. The high catalytic activity was attributed to transannular effects during selenide to selenoxide oxidation. This redox process was also characterized by an induction period that indicated autocatalysis in the formation of an intermediate selenoxide from the oxidation of the corresponding selenide.

A Mesoionic Carbene-Pyridine Bidentate Ligand That Improves Stability in Electrocatalytic CO2 Reduction by a Molecular Manganese Catalyst.

Tricarbonyl Group 7 complexes have a longstanding history as efficacious CO2 electroreduction catalysts. Typically, these complexes feature an auxiliary 2,2'-bipyridine ligand that assists in redox steps by delocalizing the electron density into the ligand orbitals. While this feature lends to an accessible redox potential for CO2 electroreduction, it also presents challenges for electrocatalysis with Mn because the electron density is removed from metal-ligand bonding orbitals. The results presented here thus introduce a mesoionic carbene (MIC) as a potent ligand platform to promote Mn-based electrocatalysis. The strong σ donation of the N,C-bidentate MIC is shown to help centralize the electron density on the Mn center while also maintaining relevant redox potentials for CO2 electroreduction. Mechanistic investigation supports catalytic turnover at two operative potentials separated by 400 mV. In the low operating potential regime at -1.54 V, Mn(0) species catalyze CO2 to CO and CO32-, which has a maximum rate of 7 ± 5 s-1 and is stable for up to 30.7 h. At higher operating potential at -1.94 V, "Mn(-1)" catalyzes CO2 to CO and H2O with faster turnovers of 200 ± 100 s-1, with the trade-off being less stability at 6.7 h. The relative stabilities of Mn complexes bearing MIC and 4,4'-di-tert-butyl-2,2'-bipyridine were compared by evaluation under the same electrolysis conditions and therefore elucidated that the MIC promotes longevity for CO evolution throughout a 5 h period.

Identification of ligand linkage vectors for the development of p300/CBP degraders.

To develop new degrader molecules from an existing protein ligand a linkage vector must be identified and then joined with a suitable E3 ligase without disrupting binding to the respective targets. This is typically achieved through empirically evaluating the degradation efficacy of a series of synthetic degraders. Our strategy for determining optimal linkage sites utilises biotinylated protein ligands, linked via potential conjugation sites of an inhibitor to confirm whether target protein is maintained after forming a conjugate. This method provides low-cost, qualitative evidence that the addition of a linker moiety at a specific position can be tolerated, guiding further optimisation. We demonstrate the application of this method through the exploration of linkage vectors on A-485, a known ligand of p300/CBP, and found a conjugation site through a urea moiety. Pomalidomide was then conjugated through this site with several different linkers and cell viability and degradation were assessed for this library using a myeloma cell line, MM1.S. Compound 18i, with a PEG4 linker, was found to be the most effective p300 degrader and linker length greater than 10 atoms afforded enhanced degradation.

Spontaneous Ammonia Activation Through Coordination-Induced Bond Weakening in Molybdenum Complexes of a Dianionic Pentadentate Ligand Platform.

Ammonia oxidation catalyzed by molecular compounds is of current interest as a carbon-free source of dihydrogen. Activation of N-H bonds through coordination to transition metal centers is a key reaction in this process. We report the substantial activation of ammonia via reaction with low-valent molybdenum complexes of a diborate pentadentate ligand system. Spontaneous loss of dihydrogen from (B2 Pz4 Py)MoII -NH3 at room temperature to produce the dinuclear µ-nitrido compound (B2 Pz4 Py)Mo-N-Mo(B2 Pz4 Py) is observed due to substantial N-H bond weakening upon coordination to Mo. Mechanistic details are supported through the experimental observation/characterization of terminal amido, imido and nitrido complexes and density functional theory computations. The generally under-appreciated role of bridging nitrido intermediates is revealed and discussed, providing guidance for further catalyst development for this process.

Bis[cyclic (alkyl)(amino)carbene] isomers: Stable trans-bis(CAAC) versus facile olefin formation for cis-bis(CAAC).

Isomeric bis(aldiminium) salts with a 1,4-cyclohexylene framework were synthesized. The first isolable bis(CAAC) was prepared from the trans-stereoisomer and its ditopic ligand competency was proven by conversion to iridium(I) and rhodium(I) complexes. Upon deprotonation, the cis-isomer yielded an electron rich olefin via a classic, proton-catalyzed pathway. The CC bond formation from the desired cis-bis(CAAC) was shown to be thermodynamically very favorable and to involve a small activation barrier. Compounds that can be described as insertion products of the cis-bis(CAAC) into the E-H bonds of NH3, CH3CN and H2O were also identified.

Orthogonalization of Polyaryl Linkers as a Route to More Porous Phosphonate Metal-Organic Frameworks.

The coordinative pliancy of the phosphonate functional group means that metal-phosphonate materials often self-assemble as well-packed structures with minimal porosity, as efficient inter-ligand packing is enabled. Here, we report a multistep synthesis of a novel aryl-phosphonate linker with an orthogonalized ligand core, 1,3,5-tris(4'-phosphonophenyl)-2,4,6-trimethylbenzene (H6 L2) designed to form more open structures. A series of crystalline metal-phosphonate frameworks (CALF-35 to -39) have been assembled by coordinating to divalent metals (Ba, Sr, Ca, Mg, Zn). H6 L2 is unable to pack efficiently and, as a consequence, yields several distinct microporous structures. The resulting structures are discussed in detail, with a focus on the solid-state packing of the sterically rigidified linker. Combined with larger cations (Sr, and Ba), H6 L2 packs in a parallel-offset manner, yielding isomorphous and microporous metal-organic frameworks (CALF-35 (Sr), and (Ba)). When coordinated to smaller metals (Ca, Mg, Zn), H6 L2 forms four new structures. Two Ca MOFs of different stoichiometry, (CALF-36 and 37) and a Mg MOF CALF-38 show narrow pores and have high selectivities for CO2 over N2 and CH4 . Finally, in CALF-39 (Zn), H6 L2 linkers pack in a herringbone fashion, resulting in a material with 10.9×10.1 Å2 square channels. The stability of all structures was tested, and the most porous structure, CALF-39 (Zn), was found to retain its structure and gas adsorption after immersion in water over pH 3-11.

Green Solvent-Processible N-H-Functionalized Perylene Diimide Materials for Scalable Organic Photovoltaics.

The growing demand for organic electronic devices warrants further development of the scalability and green solvent processibility of π-conjugated materials. Perylene diimide (PDI)-based materials have shown impressive performance as interlayers for electronic devices due to a low ELUMO energy and high charge mobility in films. The next step in the development of these materials is the transition toward scalable production and the fabrication of devices under ambient conditions. Here, we develop a green synthetic methodology to prepare a series of PDI-based electronically active materials (X2-5), which can be slot-die-coated into uniform thin films from green solvents in air. Compounds X2-5 comprised a monomeric PDI core with a functional cyclic secondary amine appended to the bay region. Bromine or cyano moieties are incorporated into the molecular scaffold to systematically tune optoelectronic properties. The utility of these materials is demonstrated by slot-die coating them from ethanol to serve as cathode interlayers in prototype air-processed conventional organic photovoltaics. Using a PM6:Y6 active layer, device power conversion efficiencies reached 10%, among the best reported under these conditions.

Regioselective Synthesis of C3-Hydroxyarylated Pyrazoles.

Pyrazoles are ubiquitous structures in medicinal chemistry. We report the first regioselective route to C3-hydroxyarylated pyrazoles obtained through reaction of pyrazole N-oxides with arynes using mild conditions. Importantly, this method does not require the C4 and C5 positions of the pyrazole to be functionalized to observe regioselectivity. Using this method, we completed the synthesis of a recently reported JAK 1/2 inhibitor. Our synthesis produces the desired product in 4 steps from commercially available starting materials.

Lowering Electrocatalytic CO2 Reduction Overpotential Using N-Annulated Perylene Diimide Rhenium Bipyridine Dyads with Variable Tether Length.

We report the design, synthesis, and characterization of four N-annulated perylene diimide (NPDI) functionalized rhenium bipyridine [Re(bpy)] supramolecular dyads. The Re(bpy) scaffold was connected to the NPDI chromophore either directly [Re(py-C0-NPDI)] or via an ethyl [Re(bpy-C2-NPDI)], butyl [Re(bpy-C4-NPDI)], or hexyl [Re(bpy-C6-NPDI)] alkyl-chain spacer. Upon electrochemical reduction in the presence of CO2 and a proton source, Re(bpy-C2/4/6-NPDI) all exhibited significant current enhancement effects, while Re(py-C0-NPDI) did not. During controlled potential electrolysis (CPE) experiments at Eappl = -1.8 V vs Fc+/0, Re(bpy-C2/4/6-NPDI) all achieved comparable activity (TONco ∼ 25) and Faradaic efficiency (FEco ∼ 94%). Under identical CPE conditions, the standard catalyst Re(dmbpy) was inactive for electrocatalytic CO2 reduction; only at Eappl = -2.1 V vs Fc+/0 could Re(dmbpy) achieve the same catalytic performance, representing a 300 mV lowering in overpotential for Re(bpy-C2/4/6-NPDI). At higher overpotentials, Re(bpy-C4/6-NPDI) both outperformed Re(bpy-C2-NPDI), indicating the possibility of coinciding electrocatalytic CO2 reduction mechanisms that are dictated by tether-length and overpotential. Using UV-vis-nearIR spectroelectrochemistry (SEC), FTIR SEC, and chemical reduction experiments, it was shown that the NPDI-moiety served as an electron-reservoir for Re(bpy), thereby allowing catalytic activity at lower overpotentials. Density functional theory studies probing the optimized geometries and frontier molecular orbitals of various catalytic intermediates revealed that the geometric configuration of NPDI relative to the Re(bpy)-moiety plays a critical role in accessing electrons from the electron-reservoir. The improved performance of Re(bpy-C2/4/6-NPDI)dyads at lower overpotentials, relative to Re(dmbpy), highlights the utility of chromophore electron-reservoirs as a method for lowering the overpotential for CO2 conversion.

Binding of histidine and human serum albumin to dirhodium(II) tetraacetate.

Reactions of the anticancer active dirhodium tetraacetate (1), Rh2(AcO)4 (AcO- = CH3COO-), with the amino acid histidine (HHis) and human serum albumin (HSA) were monitored over time and different metal: ligand ratios using UV-vis spectroscopy and/or electro-spray ionization mass spectrometry. Initially, histidine formed 1:1 and 1:2 adducts in aqueous solutions. The crystal structure of Rh2(AcO)4(L-HHis)2·2H2O (2) confirmed the axial coordination of histidine imidazole groups (average Rh-Naxial 2.23 Å). These adducts, however, were found to be unstable in solution over time (24 h). Heating Rh2(AcO)4 -histidine solutions to 40 °C (near body temperature) or 95 °C accelerated the formation of RhII2(AcO)2(His)2 and RhIII(His)2(AcO) complexes. The corresponding pH change from neutral to mildly acid (pH 4-5) indicates deprotonation of histidine NH3+ groups due to coordination to Rh ions, which simultaneously bind to histidine COO- groups, as evidenced by 13C NMR spectroscopy. In the case of HSA with 16 histidine and one cysteine residues, UV-vis spectroscopy indicates that mono- and di-histidine HSA adducts with Rh2(AcO)4 are formed. X-ray absorption spectroscopy showed almost the same Rh-Rh distance (2.41 ± 0.01 Å) for the Rh2(AcO)4 units as in 2, and a contribution from an axial thiol coordination (Rh-Saxial 2.62 ± 0.05 Å). The Rh2(AcO)4 - HSA complex was found to decompose partially (~15%) over 24 h at ambient temperature. The partial decomposition of Rh2(AcO)4 both through coordination to histidine or to human serum albumin, the most abundant protein in blood plasma, is a factor to consider for its efficacy as a potential anticancer agent.

A monoanionic pentadentate ligand platform for scandium-pnictogen multiple bonds.

A new monoanionic pentadentate ligand is designed to accommodate Sc = E bonds (E = N, P). The imido complex is stable enough to isolate and characterize, and reacts rapidly with CO2. The phosphinidene, on the other hand, is highly reactive and induces C-C bond cleavage to yield a phosphido-pyridyl complex which also undergoes rapid reacton with CO2.

One-Pot Synthesis of Aryl Selenonic Acids and Some Unexpected Byproducts.

The synthesis of aryl selenonic acids was achieved from diverse aryl bromides via a one-pot method involving metalation, selenation, and oxidation with hydrogen peroxide followed by ion exchange to afford the pure products in 77-90% yield. An o-hydroxymethyl derivative was found to dehydrate readily, affording the first example of a cyclic selenonic ester, while two minor byproducts were isolated and shown by X-ray crystallography to be mixed salts of aryl selenonic acids with either the corresponding aryl seleninic or selenious acid.

Rapid synthesis of pomalidomide-conjugates for the development of protein degrader libraries.

Current methods for the preparation of heterobifunctional pomalidomide-conjugates rely on methods that are often low yielding and produce intractable byproducts. Herein we describe our strategy for the reliable and succinct preparation of pomalidomide-linkers which is essential to the formation of these conjugates. We present the preparation of 18 pomalidomide-linkers in high yield compared to current literature methods. Our findings show that secondary amines consistently afford greater yields than their primary counterparts, a trend that we were able to exploit in the synthesis of several new pomalidomide homo-dimers in enhanced yields compared to similar literature syntheses. This trend was further utilised to develop the first one-pot synthesis of JQ1-pomalidomide conjugates in yields up to 62%, providing a method that is suited to rapid preparation of conjugate libraries as is frequently required for the development of new protein degraders.

The effect of sodium thiosulfate on cytotoxicity of a diimine Re(I) tricarbonyl complex.

Recently, diimine Re(i) tricarbonyl complexes have attracted great interest due to their promising cytotoxic effects. Here, we compare the cytotoxicity and cellular uptake of two Re(i) compounds fac-[(Re(CO)3(bpy)(H2O)](CF3SO3) (1) and Na(fac-[(Re(CO)3(bpy)(S2O3)])·H2O (bpy = 2,2'-bipyridine) (2). The Re-thiosulfate complex in 2 was characterized in two solvated crystal structures {Na(fac-[Re(CO)3(bpy)(S2O3)])·1.75H2O·C2H5OH}4 (2 + 0.75H2O + C2H5OH)4 and (fac-[Re(CO)3(bpy)(H2O)]) (fac-[Re(CO)3(bpy)(S2O3)])·4H2O (3). The cytotoxicity of 1 and 2 was tested in the MDA-MB-231 breast cancer cell line and compared with that of cisplatin. The cellular localization of the Re(i) complexes was investigated using synchrotron-based X-ray fluorescence microscopy (XFM). The results show that replacement of the aqua ligand with thiosulfate renders the complex less toxic most likely by distrupting its cellular entry. Therefore, thiosulfate could potentially have a similar chemoprotective effect against diimine fac-Re(CO)3 complexes as it has against cisplatin.