Steric Research Articles

Structurally characterized aluminum alkoxide derivatives for aerosol spray materials production

The synthesis of a family of aluminum alkoxides was undertaken via the reaction of trimethyl aluminum (Al(CH3)3) using a series of sterically varied ortho-substituted phenols (H-OAr), including: 2-methyl phenol (H-oMP), 2-isopropyl phenol (H-oPP), 2-phenyl phenol (H-oPhP), 2,6-di-methyl phenol (H-DMP), 2,6-di-isopropyl phenol (H-DIP), and 2,6-di-phenyl phenol (H-DPhP). The products isolated using the least sterically encumbered phenoxides proved to generate the homoleptic compounds: [(oMP)Al((μ-oMP)2Al(oMP)2)2] (1), and [Al(μ-oPP)(oPP)2]2 (2), [Al(μ-oPP)(oPP)2(THF)]2 (2-THF), and [Al(μ-oPhP)(oPhP)2]2 (3). As the steric bulk was increased only partial substitution was achieved forming the alkyl, alkoxide compounds: [Al(μ-OAr)(CH3)(OAr)]2 (OAr = trans-DMP (4a), cis-DIP (5a), trans-DPhP (6a)). Sub-stoichiometric metathesis reactions for the smaller OAr ligands were undertaken to produce a series of [Al(CH3)3-x(OAr)x]2 where × = 2: OAr = trans-oMP (1a); x = 1, OAr = oMP (1b), and DMP (4b). Alternatively, the use of neo-pentanol (H-ONep) led to the homoleptic species [(ONep)Al((μ-ONep)2Al(ONep)2)2] (7) and heteroleptic [Al(μ-ONep)(CH3)2]2 (7b). Efforts to generate 7 from [Al(OPri)3]4 resulted in the production of the mixed ligated species [Al4(μ-OPri)6(ONep)6] (8). The compounds were fully characterized using a variety of analytical tools as well as multinuclear NMR (1H, 13C, 27Al) spectroscopy. Select species were used for aerosol spray pyrolysis for the anticipated production of alumina (Al2O3) materials. The final products from 1, 1b, 7, and 7b proved to generate amorphous mesoparticles of size 2.1(0.1), 2.6(0.2), 2.7(0.2), and 2.5(0.2) μm, respectively as determined by SEM and pXRD analyses. Data collected using Single Particle Aerosol Mass Spectrometry (SPAMS) revealed that Al0 particles had been produced instead of the expected Al2O3 ceramic materials.

Pd‐Catalyzed Cross‐Coupling of Alkylzirconocenes and Aryl Chlorides

Comprehensive SummaryAlkylzirconocenes, readily prepared by hydrozirconation of alkenes with Schwartz's reagent, are perspective yet rarely exploited partners in transition‐metal catalyzed cross‐coupling reaction. The notoriously low nucleophilicity of alkylzirconocenes and the potential β‐H elimination restrict their application in cross‐coupling. Herein, we report the first Pd‐catalyzed aryl‐alkyl cross‐coupling of alkylzirconocenes and aryl halides. A commercially available N‐heterocyclic carbene (IPr) as the ligand for palladium catalyst is critical to enable the challenging process. This mild protocol does not require base additives and tolerates a broad scope of both coupling partners bearing various functional groups and heterocycles. Moreover, both terminal and internal alkenes are applicable, and the latter undergo “chain walking”, giving the terminal coupling product exclusively. Preliminary mechanistic studies reveal a precatalyst activation pathway and inhibited β‐H elimination due to steric bulk of NHC ligand.

Electron-Deficient Ru(II) Complexes as Catalyst Precursors for Ethylene Hydrophenylation

Ruthenium(II) complexes with the general formula TpRu(L)(NCMe)Ph (Tp = hydrido(trispyrazolyl)borate, L = CO, PMe3, P(OCH2)3CEt, P(pyr)3, P(OCH2)2(O)CCH3) have previously been shown to catalyze arene alkylation via Ru-mediated arene C–H activation including the conversion of benzene and ethylene to ethylbenzene. Previous studies have suggested that the catalytic performance of these TpRu(II) catalysts increases with reduced electron-density at the Ru center. Herein, three new structurally related Ru(II) complexes are synthesized, characterized, and studied for possible catalytic benzene ethylation. TpRu(NO)Ph2 exhibited low stability due to the facile elimination of biphenyl. The Ru(II) complex (TpBr3)Ru(NCMe)(P(OCH2)3CEt)Ph (TpBr3 = hydridotris(3,4,5-tribromopyrazol-1-yl)borate) showed no catalytic activity for the conversion of benzene and ethylene to ethylbenzene, likely due to the steric bulk introduced by the bromine substituents. (Ttz)Ru(NCMe)(P(OCH2)3CEt)Ph (Ttz = hydridotris(1,2,4-triazol-1-yl)borate) catalyzed approximately 150 turnover numbers (TONs) of ethylbenzene at 120 °C in the presence of Lewis acid additives. Here, we compare the activity and features of catalysis using (Ttz)Ru(NCMe)(P(OCH2)3CEt)Ph to previously reported catalysis based on TpRu(L)(NCMe)Ph catalyst precursors.

Planarized Phenyldithienylboranes: Effects of the Bridging Moieties and π-Extension on the Photophysical Properties and Lewis Acidity.

Two kinds of planarized phenyldithienylboranes, which contain (CH3 )2 C- or CH2 -bridging moieties, were synthesized. The difference of the bridging moieties affects their packing structures and photophysical properties. In particular, the (CH3 )2 C-bridged derivative exhibits a large Stokes shift, unusual for such planarized compounds, that results from a large structural relaxation in the excited state. A series of π-extended derivatives was synthesized, among which a p-(diphenylamino)phenyl-substituted derivative shows large solvatochromism in the fluorescence spectra, while maintaining high quantum yields even in polar solvents. The Lewis acidity of the phenyldithienylborane derivatives was also assessed by titration with pyridine. The Lewis acidity of the boron center is affected not only by the difference in the steric bulk of the bridging moieties, but also by the electronic effect of the substituents introduced at remote positions relative to the boron atom. These results demonstrate the characteristic features of planarized phenyldithienylboranes as building blocks for boron-based π-electron materials.

Dynamics of rotation in two‐coordinate thiazolyl copper(I) carbazolyl complexes

Two‐coordinate carbene Cu(Ι) amide complexes with sterically bulky groups such as the diisopropyl phenyl (dipp) on the carbenes have been shown to have comparable performance to the phosphorescent emitters bearing heavy atoms such as iridium and platinum. These bulky groups enforce a coplanar molecular structure and suppress the nonradiative decay rates. Here, three different two‐coordinate Cu(Ι) complexes were investigated that bear a common thiazole carbene, 3‐(2,6‐diisopropylphenyl)‐4,5‐dimethylthiazol‐2‐ylidene, with only a single dipp group, and carbazolyl ligands with substituents of varying steric bulk ortho to N. These substituents have a negligible impact on luminescence energies of the complexes but serve to modulate the rotation barriers along the metal–ligand coordinate bond. The geometric arrangement of ligands (syn‐ or anti‐conformer) in complexes with alkyl substituents were found to differ, being syn in the solid state versus anti in solution as revealed by crystallographic analysis and nuclear magnetic resonance spectroscopy. In addition, calculations were performed to determine potential energy surfaces for different conformations of the three complexes to provide a theoretical evaluation of rotation barriers around the metal–ligand bond axis. The relationship between rotation barriers and photophysical properties demonstrate that rates for nonradiative decay decrease with increasing bulk of the substituents on the carbazolyl ligand.

Improved Electrophile Design for Exquisite Covalent Molecule Selectivity.

Covalent inhibitors are viable therapeutics. However, off-target reactivity challenges the field. Chemists have attempted to solve this issue by varying the reactivity attributes of electrophilic warheads. Here, we report the development of an approach to increase the selectivity of covalent molecules that is independent of warhead reactivity features and can be used in concert with existing methods. Using the scaffold of the Bruton's tyrosine kinase (BTK) inhibitor Ibrutinib for our proof-of-concept, we reasoned that increasing the steric bulk of fumarate-based electrophiles on Ibrutinib should improve selectivity via the steric exclusion of off-targets but retain rates of cysteine reactivity comparable to that of an acrylamide. Using chemical proteomic techniques, we demonstrate that elaboration of the electrophile to a tert-butyl (t-Bu) fumarate ester decreases time-dependent off-target reactivity and abolishes time-independent off-target reactivity. While an alkyne-bearing probe analogue of Ibrutinib has 247 protein targets, our t-Bu fumarate probe analogue has only 7. Of these 7 targets, BTK is the only time-independent target. The t-Bu inhibitor itself is also more selective for BTK, reducing off-targets by 70%. We investigated the consequences of treatment with Ibrutinib and our t-Bu analogue and discovered that only 8 proteins are downregulated in response to treatment with the t-Bu analogue compared to 107 with Ibrutinib. Of these 8 proteins, 7 are also downregulated by Ibrutinib and a majority of these targets are associated with BTK biology. Taken together, these findings reveal an opportunity to increase cysteine-reactive covalent inhibitor selectivity through electrophilic structure optimization.

Norbornene and methyl methacrylate polymerizations catalyzed by palladium(II) complexes bearing aminomethylpyridine and aminomethylquinoline derivatives

A series of Pd(II) complexes, 1–4 bearing N,N-bidentate aminomethylpyridine and aminomethylquinoline derivatives were synthesized and characterized. Single crystal X-ray diffraction analysis demonstrated that tetra-coordinated Pd(II) complexes adopted distorted square planar geometries around the metal center. In the presence of modified methylaluminoxane (MMAO) as a co-catalyst, Pd(II) complexes 1–4 exhibited significant activities (up to 43.2×105 gPNB mol Pd−1 h−1) towards the addition polymerization of norbornene (NB) at 25 ℃. Insoluble poly(norbornene) (PNB) was obtained by all the tested catalytic systems, i.e., 1–4/MMAO. The catalytic capabilities of synthesized Pd(II) complexes were also tested towards methyl methacrylate (MMA) in the presence of modified methyl aluminoxane MMAO. Complex 3 with quinoline/piperidine functionalities showed the highest catalytic activity of 8.83×104 gPMMA mol Pd−1 h−1 at 60°C and resulted in high molecular weight PMMA (Mw = 2.16×106 g mol−1). All the complexes yielded syndiotactic poly(methyl methacrylate) (PMMA) (rr = 0.70). Notably, the steric bulk and electronic properties of the ligand framework affect their activities towards NB and MMA polymerizations, whereas, for PMMA, the stereoselectivities remained unaffected.

Secondary Coordination Sphere Influences the Formation of Fe(III)-O or Fe(III)-OH in Nitrite Reduction: A Synthetic and Computational Study.

The reduction of nitrite (NO2-) to generate nitric oxide (NO) is a significant area of research due to their roles in the global nitrogen cycle. Here, we describe various modifications of the tris(5-cyclohexyliminopyrrol-2-ylmethyl)amine H3[N(piR)3] ligand where the steric bulk and acidity of the secondary coordination sphere were explored in the non-heme iron system for nitrite reduction. The cyclohexyl and 2,4,6-trimethylphenyl variants of the ligand were used to probe the mechanism of nitrite reduction. While previously stoichiometric addition of nitrite to the iron(II)-species generated an iron(III)-oxo complex, changing the secondary coordination sphere to mesityl resulted in an iron(III)-hydroxo complex. Subsequent addition of an electron and two protons led to the release of water and regeneration of the starting iron(II) catalyst. This sequence mirrored the proposed mechanism of nitrite reduction in biological systems, where the distal histidine residue shuttles protons to the active site. Computational studies aimed at interrogating the dissimilar behavior of the cyclohexyl and mesityl ligand systems resulting in Fe(III)-oxo and Fe(III)-hydroxo complexes, respectively, shed light on the key role of H-bonds involving the secondary coordination sphere in the relative stability of these species.

Scaffold stability and P14' residue steric hindrance in the differential inhibition of FXIIa by Aedes aegypti trypsin inhibitor versus Infestin-4.

Kazal-type protease inhibitors strictly regulate Factor XIIa (FXIIa), a blood-clotting serine protease. However, when negatively charged surface of prosthetic device come into contact with FXII, it undergoes conformational change and auto-activation, leading to thrombus formation. Some research suggests that Kazal-type protease inhibitor specificity against FXIIa is governed solely by the reactive-site loop sequence, as this sequence makes most-if not all-of the direct contacts with FXIIa. Here, we sought to compare the inhibitory properties of two Kazal-type inhibitors, Infestin-4 (Inf4), a potent inhibitor of FXIIa, and Aedes aegypti trypsin inhibitor (AaTI), which does not inhibit FXIIa, to better understand Kazal-type protease specificity and determine the structural components responsible for inhibition. There are only three residue differences in the reactive-site loop between AaTI and Inf4. Through site-directed mutagenesis, we show that the reactive-site loop is only partially responsible for the inhibitory specificity of these proteases. The protein scaffold of AaTI is unstable due to an elongated C5C6 region. Through chimeric study, we show that swapping the protease-binding loop and the C5C6 region from Inf4 with that of AaTI can partially enhance the inhibitory activity of the AaTI_Inf4 chimera. Furthermore, the additional substitution of Asn at the P14′ position of AaTI with Gly (Gly27 in Inf4) absolves the steric clashing between AaTI and the surface 140-loop of FXIIa, and increases the inhibition of the chimeric AaTI to match that of wild-type Inf4. Our findings suggest that ancillary regions in addition to the reactive-site loop sequence are important factors driving Kazal-type inhibitor specificity.

Low‐valent Mg(I) complexes by ball‐milling

AbstractMechanochemistry has great potential in the syntheses of low‐valent Mg(I) complexes. Magnesium iodide precursors with three different β‐diketiminate (BDI) ligands of varying bulk have been reduced with K/KI (or Na/NaCl) using the ball‐mill. Depending on the steric bulk of the ligand, the raw products are intensely colored powders, indicating the presence of (BDI)Mg⋅ radicals. Extraction with pentane gave (BDI)Mg−Mg(BDI) in excellent yields. Reaction of the powder with H2 prior to extraction gave [(BDI)MgH]2. Extraction with benzene gave (BDI)Mg(C6H6)Mg(BDI) with a dearomatized puckered benzene dianion. Ball‐milling in the presence of triphenylbenzene gave a dinuclear Mg complex with a Ph3C6H3‐dianion which slowly decomposed to (BDI)Mg−Mg(BDI) and Ph3C6H3.

Reactions of a Dimethylxanthene‐Derived Frustrated Lewis Pair with Silanes and Stannanes

AbstractThe reactivity towards Si−H and Sn−H bonds of a dimethylxanthene‐based frustrated Lewis pair featuring −PiPr2 and −B(C6F5)2 functions in the 4‐, and 5‐positions is reported. In the case of silanes, greater steric bulk appears to impede reactivity, with only PhSiH3 and SiH4 showing unambiguous evidence for Si−H bond activation. In the case of PhSiH3, the silylphosphonium borohydride 1iPr(SiH2Ph)(H) is formed by Si−H bond activation across the P/B manifold. 1iPr(SiH2Ph)(H) loses PhSiH3 in hydrocarbon solution and therefore can only be crystallized from the neat silane. On heating, it undergoes a metathesis process leading to installation of the −SiH2Ph function at the 5‐position of the xanthene scaffold, with accompanying migration of the boryl group (as Piers’ borane, HB(C6F5)2) to the phosphine. Similar chemistry is observed with SiH4 (although occurring much more readily), and such processes are thought to be mechanistically similar to related rearrangements occurring with the boranes HBpin and HBcat. By contrast, the activation of the weaker Sn−H bonds found in stannanes occurs more readily, even for bulkier substrates, and the stannyl‐phosphonium borohydrides 1iPr(SnnBu3)(H) and 1iPr(SnPh3)(H) are obtained from the room temperature reactions with nBu3SnH and Ph3SnH, respectively.

The Influence of Silane Steric Bulk on the Formation and Dynamic Behavior of Silyl Palladium Hydrides

Silanes play a versatile role in catalytic transformations, acting as hydride sources, transmetalation reagents, and starting materials in the synthesis of highly valued organosilicon compounds and polymers. Their use in catalysis with palladium is widespread, commonly proposed to proceed via oxidative addition of Si–H to Pd(0); however, little is known about this fundamental reaction. Here, we show that the formation of silyl palladium hydride complexes (dcpe)PdH(SiR3), which exist in equilibrium with starting materials [(μ-dcpe)Pd]2 (dcpe = dicyclohexyl(phosphino)ethane) and tertiary silanes HSiR3 in solution, is dependent on the steric profile of the silanes employed. A lower Keq is observed with increasing steric encumbrance at silicon, correlating well with each substituent’s Charton value, and van’t Hoff analyses show the reaction with sterically congested silanes to be less thermodynamically favorable. Variable temperature kinetics studies likewise reveal a preference for unhindered silanes as determined by Charton and Eyring analyses. On the other hand, the intramolecular ligand exchange of H/SiR3 on the formed complexes is unaffected by silane steric bulk. Together, the energetic parameters derived for each of these steps reveal that thermodynamic factors are primarily responsible for favoring (silyl)Pd(H) formation with less sterically bulky silanes. These results present the first systematic study on the role of silane steric effects in oxidative addition of Si–H to Pd(0) and help to inform organosilicon chemistry with late transition metals.

A High-Throughput Approach to Repurposing Olefin Polymerization Catalysts for Polymer Upcycling.

Efficient and economical plastic waste upcycling relies on the development of catalysts capable of polymer degradation. A systematic high-throughput screening of twenty-eight polymerization catalyst precursors, belonging to the catalyst families of metallocenes, ansa-metallocenes, and hemi- and post-metallocenes, in cis-1,4-polybutadiene (PB) degradation reveals, for the first time, important structure-activity correlations. The upcycling conditions involve activation of the catalysts (at 0.18 % catalyst loading) with tri-iso-butyl aluminum at 50 °C in toluene. The data indicate the ability to degrade PB is a general reactivity profile of neutral group 4 metal hydrides. A simple quantitative-structure activity relationship (QSAR) model utilizing two descriptors for the distribution of steric bulk in the active pocket and one measuring the metal ion electrophilicity reveals the degradation ability improves with increased but not overbearing steric congestion and lower electrophilicity.

A High‐Throughput Approach to Repurposing Olefin Polymerization Catalysts for Polymer Upcycling

AbstractEfficient and economical plastic waste upcycling relies on the development of catalysts capable of polymer degradation. A systematic high‐throughput screening of twenty‐eight polymerization catalyst precursors, belonging to the catalyst families of metallocenes, ansa‐metallocenes, and hemi‐ and post‐metallocenes, in cis‐1,4‐polybutadiene (PB) degradation reveals, for the first time, important structure–activity correlations. The upcycling conditions involve activation of the catalysts (at 0.18 % catalyst loading) with tri‐iso‐butyl aluminum at 50 °C in toluene. The data indicate the ability to degrade PB is a general reactivity profile of neutral group 4 metal hydrides. A simple quantitative‐structure activity relationship (QSAR) model utilizing two descriptors for the distribution of steric bulk in the active pocket and one measuring the metal ion electrophilicity reveals the degradation ability improves with increased but not overbearing steric congestion and lower electrophilicity.

Palladium-Catalyzed Miyaura Borylation of Overly Crowded Aryl Chlorides Enabled by a Complementary Localized/Remote Steric Bulk of Ligand Chassis

Palladium-Catalyzed Miyaura Borylation of Overly Crowded Aryl Chlorides Enabled by a Complementary Localized/Remote Steric Bulk of Ligand Chassis

Reactivity of Iridium Complexes of a Triphosphorus-Pincer Ligand Based on a Secondary Phosphine. Catalytic Alkane Dehydrogenation and the Origin of Extremely High Activity.

The selective functionalization of alkanes and alkyl groups is a major goal of chemical catalysis. Toward this end, a bulky triphosphine with a central secondary phosphino group, bis(2-di-t-butyl-phosphinophenyl)phosphine (tBuPHPP), has been synthesized. When complexed to iridium, it adopts a meridional ("pincer") configuration. The secondary phosphino H atom can undergo migration to iridium to give an anionic phosphido-based-pincer (tBuPPP) complex. Stoichiometric reactions of the (tBuPPP)Ir complexes reflect a distribution of steric bulk around the iridium center in which the coordination site trans to the phosphido group is quite crowded; one coordination site cis to the phosphido is even more crowded; and the remaining site is particularly open. The (tBuPPP)Ir precursors are the most active catalysts reported to date for dehydrogenation of n-alkanes, by about 2 orders of magnitude. The electronic properties of the iridium center are similar to that of well-known analogous (RPCP)Ir catalysts. Accordingly, DFT calculations predict that (tBuPPP)Ir and (tBuPCP)Ir are, intrinsically, comparably active for alkane dehydrogenation. While dehydrogenation by (RPCP)Ir proceeds through an intermediate trans-(PCP)IrH2(alkene), (tBuPPP)Ir follows a pathway proceeding via cis-(PPP)IrH2(alkene), thereby circumventing unfavorable placement of the alkene at the bulky site trans to phosphorus. (tBuPPP)Ir and (tBuPCP)Ir, however, have analogous resting states: square planar (pincer)Ir(alkene). Alkene coordination at the crowded trans site is therefore unavoidable in the resting states. Thus, the resting state of the (tBuPPP)Ir catalyst is destabilized by the architecture of the ligand, and this is largely responsible for its unusually high catalytic activity.

2H1C Mimicry: Bioinspired Iron and Zinc Complexes Supported by N,N,O Phenolate Ligands

AbstractIn pursuit of mimicking the ubiquitous 2H1C motif in mononuclear non‐heme iron enzymes, two new bioinspired N,N,O phenolate ligands, BenzImNNO and ImPh2NNO, are synthesised and their coordination chemistry with zinc(II) and iron(II) is explored. BenzImNNO coordinates by means of an anionic κ3‐N,N,O donor set and readily forms homoleptic bisligated complexes, also in the presence of equimolar amounts of metal salt. In contrast, the increased steric bulk of ImPh2NNO promotes the formation of dinuclear complexes, [M2(ImPh2NNO)2(OTf)2] (M=Fe, Zn), with facially opposing metal sites, as a result of its unique bridging μ2:κ2‐N,N:κ1‐O coordination mode. We investigate the robustness of the ligand's dinucleating coordination mode during oxidative transformations and demonstrate that its coordination mode is retained upon triflate substitution for a biorelevant thiophenolate co‐ligand.

Conversion of Uranium(III) Anilido Complexes to Uranium(IV) Imido Complexes via Hydrogen Atom Transfer

A family of low-valent uranium(III) anilido complexes supported by the bulky hydrotris(3,5-dimethylpyrazolyl)borate (Tp*) ligand was synthesized by combining Tp*2UBn (Bn = benzyl) (1-Bn) with anilines of varying steric bulk and electronic profiles, including 4-fluoroaniline, 3,5-difluoroaniline, 3,5-bis(trifluoromethyl)aniline, 3,5-dimethylaniline, 2,4,6-trimethylaniline, and 2,4,6-tri-tBu-aniline. The corresponding uranium(III) anilido species, Tp*2UNH(4-fluorophenyl) (2-pF), Tp*2UNH(3,5-difluorophenyl) (2-bisF), Tp*2UNH(3,5-bis(trifluoromethyl)phenyl) (2-bisCF3), Tp*2UNH(3,5-dimethylphenyl) (2-bisCH3), Tp*2UNH(2,4,6-trimethylphenyl) (2-Mes), and Tp*2UNH(2,4,6-tri-tBu-phenyl) (2-Mes*), were isolated, and reactivity was explored. Conversion to their respective uranium(IV) imido species (3-pF, 3-bisF, 3-bisCF3, 3-bisCH3, 3-Mes, and 3-Mes*) was achieved by hydrogen atom transfer using either Gomberg’s dimer or the 2,4,6-tri-tBu-phenoxy radical (·OMes*) which eliminates the need to use potentially explosive organic azides, a reagent that has been commonly used for the synthesis of uranium(IV) imido complexes. For comparison of yields and purity of all methods, the uranium imido complexes were also prepared using the corresponding organic azides. Where applicable, compounds were characterized by multinuclear NMR spectroscopy (1H, 11B, 19F), infrared spectroscopy, electronic absorption spectroscopy, and single crystal X-ray crystallography.

3d Metal Complexes in T-shaped Geometry as a Gateway to Metalloradical Reactivity.

ConspectusLow-valent, low-coordinate 3d metal complexes represent a class of extraordinarily reactive compounds that can act as reagents and catalysts for challenging bond-activation reactions. The pursuit of these electron-deficient metal complexes in low oxidation states demands ancillary ligands capable of providing not only energetic stabilization but also sufficiently high steric bulk at the metal center. From this perspective, pincer ligands are particularly advantageous, as their prearranged, meridional coordination mode scaffolds the active center while the substituents of the peripheral donor atoms provide effective steric shielding for the coordination sphere. In a T-shaped geometry, the transition metal complexes possess a precisely defined vacant coordination site, which, combined with the often observed high-spin electron configuration, exhibits unusually high selectivity of these compounds with respect to one-electron redox chemistry. In light of the intractable reaction pathways typically observed with related electronically unsaturated 3d transition metal complexes, the pincer coordination mode enables the isolation of low-valent compounds with more controlled and unique reactivity. We have thus investigated a series of T-shaped metal(I) complexes using three different types of pincer ligands, which may be regarded as "metalloradicals" due to their selectively exposed unpaired electrons.These compounds display remarkably high thermal stability and represent rarely observed "naked" monovalent metal species featuring both monomeric and dimeric structures. Extensive reactivity studies using various organic substrates highlight a strong tendency of these paramagnetic compounds to undergo one-electron oxidation, leading to the isolation of a plethora of metal(II) species with reduced organic ligands as unusual structural elements. The exploration of C2 symmetric T-shaped Ni(I) complexes as asymmetric catalysts also shows success in enantioselective hydrodehalogenation of geminal dihalogenides. In addition, this specific class of low-valent, low-coordinate complexes can be further diversified by introducing redox-active pincer ligands or building homobimetallic systems with two T-shaped units.This Account focuses on the discussion of selected examples of iron, cobalt, and nickel pincer complexes bearing a [P,N,P] or [N,N,N] donor set; however, their electronic structure and radical-type reactivity can be broadly extended to other pincer systems. The availability of various types of pincer ligands should allow fine-tuning of the reactivity of the T-shaped complexes. Given the unprecedented reactivity observed with these compounds, we expect the studies of T-shaped 3d metal complexes to be a fertile field for advancing base metal catalysis.

Cryo-EM structure of transcription termination factor Rho from Mycobacterium tuberculosis reveals bicyclomycin resistance mechanism

The bacterial Rho factor is a ring-shaped motor triggering genome-wide transcription termination and R-loop dissociation. Rho is essential in many species, including in Mycobacterium tuberculosis where rho gene inactivation leads to rapid death. Yet, the M. tuberculosis Rho [MtbRho] factor displays poor NTPase and helicase activities, and resistance to the natural Rho inhibitor bicyclomycin [BCM] that remain unexplained. To address these issues, we solved the cryo-EM structure of MtbRho at 3.3 Å resolution. The MtbRho hexamer is poised into a pre-catalytic, open-ring state wherein specific contacts stabilize ATP in intersubunit ATPase pockets, thereby explaining the cofactor preference of MtbRho. We reveal a leucine-to-methionine substitution that creates a steric bulk in BCM binding cavities near the positions of ATP γ-phosphates, and confers resistance to BCM at the expense of motor efficiency. Our work contributes to explain the unusual features of MtbRho and provides a framework for future antibiotic development.