Dimeric Complex Research Articles

Tuning the sterics: Rh-catalyzed hydroformylation reactions with ferrocene based diphosphorus ligands

The mono- and bidentate ligands FcPPh2 (1), FcPtBu2 (2), FcPMes2 (3), Fc’(PPh2)2 (dppf), Fc’(PMes2)2 (4), Fc’(PMes2)(PPh2) (5), and Fc’(PMes2)(PtBu2) (6) (Fc and Fc’ stand for 1- and 1,1′-substituted ferrocene, respectively) were reacted with Rh(I)-precursors. Maintaining P:Rh stoichiometric ratios of 2:1, dimeric Vaska-type complexes featuring P-Rh-P bridges (7–15), and monomeric complexes with [Rh(CO)2(acac)] moieties (16–22) were obtained. Complexes 16–22 were further applied in the Rh-catalyzed hydroformylation of 1-octene, while the linear-to-branched ratio (l/b) of the formed aldehydes decreases with the increase of steric bulk at the P atoms, which was further verified by theoretical calculations. For ligands 3–5, activation of the C–H bonds of the o-CH3 units of the mesityl substituent occurred with Rh(I), forming complexes with rare five-membered [C3PRh(III)] rings (10, 18a, 20 and 21a). Complexes 8, 10, 11, 13, 15 and 17 were unambiguously characterized by means of single crystal X-ray diffraction.

Sequential replacement of PSD95 subunits in postsynaptic supercomplexes is slowest in the cortex.

The concept that dimeric protein complexes in synapses can sequentially replace their subunits has been a cornerstone of Francis Crick's 1984 hypothesis, explaining how long-term memories could be maintained in the face of short protein lifetimes. However, it is unknown whether the subunits of protein complexes that mediate memory are sequentially replaced in the brain and if this process is linked to protein lifetime. We address these issues by focusing on supercomplexes assembled by the abundant postsynaptic scaffolding protein PSD95, which plays a crucial role in memory. We used single-molecule detection, super-resolution microscopy and MINFLUX to probe the molecular composition of PSD95 supercomplexes in mice carrying genetically encoded HaloTags, eGFP, and mEoS2. We found a population of PSD95-containing supercomplexes comprised of two copies of PSD95, with a dominant 12.7 nm separation. Time-stamping of PSD95 subunits in vivo revealed that each PSD95 subunit was sequentially replaced over days and weeks. Comparison of brain regions showed subunit replacement was slowest in the cortex, where PSD95 protein lifetime is longest. Our findings reveal that protein supercomplexes within the postsynaptic density can be maintained by gradual replacement of individual subunits providing a mechanism for stable maintenance of their organization. Moreover, we extend Crick's model by suggesting that synapses with slow subunit replacement of protein supercomplexes and long-protein lifetimes are specialized for long-term memory storage and that these synapses are highly enriched in superficial layers of the cortex where long-term memories are stored.

Binding Interaction Between Two Mutant Myocilin Olfactomedin Domain Monomers in a Homodimer.

In myocilin-associated glaucoma, pathogenic missense mutations accumulate mainly in the olfactomedin domain (mOLF) of myocilin. This makes the protein susceptible to aggregation, where mOLF-mOLF dimerization is possibly an initial stage. Nevertheless, there are no molecular level studies that have probed the nature of interactions occurring between two mOLF domains and the key characteristics of the resulting dimer complex. In this work, we used AlphaFold2 to obtain an I477N mutant mOLF structure with high quality followed by a stable I477N mOLF-mOLF homodimer model using molecular docking combined with molecular dynamics simulations. Moreover, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods coupled with per-residue energy decomposition studies are carried out to identify the key residues involved in the binding interaction. Based on these results, we provide insights into the molecular level understanding of the intermolecular interaction between two mOLF domains in an I477N homodimer. Hydrogen bonds, salt bridges, and favorable van der Waals interactions are observed in the binding interface of the homodimer. Additionally, our results suggest that I477N mutant mOLF aggregation could be a multistep process, beginning with an initial mOLF-mOLF dimerization mainly mediated by residues such as Asp395 and Arg681. Also, the peptides P1 (residues 326-337) and P3 (residues 426-442) of the mOLF domain, previously identified as pertinent for myocilin aggregation, could potentially contribute to a subsequent stage of myocilin aggregation, the first step being mOLF-mOLF dimerization.

Homogeneous catalytic oxidation of thymol with dinuclear Cu(II)-2-phenyl propionate-bipyridine complex

A carboxylate-bridged dinuclear copper(II) complex, [Cu2(μ2-η2:η1(ppa)2(μ2-η1:η1 (ppa)bpy)2]·ClO4·H2O (ppa (C9H9OO) = 2-phenyl propionate, bpy = 2,2′-bipyridine), was prepared and its structure was determined by X-ray diffraction analysis. The octacoordinated Cu(II) dimer complex exhibits an asymmetric conformation, with the metal centers linked by two distinct modes of the carboxylate group. These include an asymmetric chelating bridging bidentate involving two ppa ligands and a syn-syn bidentate bridging mode involving one ppa ligand. The complex was employed as a catalyst for the oxidation of thymol, demonstrating a high degree of quantitative conversion and selectivity with TBHP across a range of solvents at moderate temperatures. The homogeneous catalytic system, comprising Cu(II)-2-phenyl propionate-bipyridine, tert-butylhydroperoxide (TBHP) as oxidant, and a polar aprotic solvent (acetonitrile or acetone), demonstrated high turnover numbers (TOF) in the absence of any additives. The impact of temperature, solvent, the ratio of thymol to TBHP, different oxidants and the quantity of catalyst on the catalytic activity and product selectivity was examined. Under optimized conditions, the maximum conversion of thymol (100 %) was obtained with 100 % selectivity to thymoquinone with TBHP after 35 min at the thymol to catalyst mole ratio of 267 (TOF = 449 h−1) in acetonitrile (MeCN) at 55 °C. Based on the available evidence, this activity and selectivity to thymoquinone represent the highest reported level of performance achieved by a homogeneously copper-catalysed process.

Structural Diversity of Cadmium Complexes with N‐Heterocyclic Carbene‐Isothiocyanate Zwitterionic Ligand

In this study, we discuss the synthesis and structural characterization of three N‐heterocyclic carbene isothiocyanate zwitterionic ligands, 1,3‐bis(2,6‐diisopropylphenyl)‐2‐N‐phenyl‐thiocarbamoyl imidazolium (ImDipp ‐CSNPh, L1), 1,3‐bis(tert‐butyl)‐2‐N‐phenylthiocarbamoyl imidazolium (ImtBu‐CSNPh, L2) and 1,3‐bis(2,4,6‐trimethylphenyl)‐2‐N‐phenylthiocarbamoyl imidazolium (ImMes‐CSNPh, L3) and their cadmium complexes, [(ImDipp‐CSNPh)2CdCl][CdCl3] (1) and [(ImtBu‐CSNPh)2Cd2Cl6] (2). Both bench‐stable cadmium complexes were synthesized by directly reacting the corresponding NHC‐CSNPh adducts with anhydrous cadmium chloride. The solid‐state structures of zwitterionic NHC‐isothiocyanate betaine adducts (L1‐L3) and cadmium complexes (1 and 2) were investigated with the assistance of single crystal X‐ray diffraction analysis. A steric modification of N‐substituent on NHC governs a unique structural change from betaine ImDipp‐CSNPh coordinated cationic cadmium complex to neutral dimeric cadmium complex with ImtBu‐CSNPh.

Mono-Palmitoyl-N-Alkylurea Ligands as Specific Activators of Human Toll-Like Receptor 2/6 Heterodimer.

Ligands for Toll-like-receptor 2 (TLR2) have demonstrated significant potential as immune-stimulating components in synthetic vaccines. Activation of TLR2 relies on the formation of dimeric complexes with either TLR1 or TLR6 and the nature of these dimers can impact therapeutic outcomes. The lipopeptide-based TLR2 ligands Pam3CysSK4 and Pam2CysSK4 have been extensively studied, and their recognition by different TLR-receptor heterodimers, TLR2/TLR1 and TLR2/TLR6, respectively, has been established. However, the high lipophilicity of these ligands, containing multiple palmitoyl residues, can result in solubility issues when used as vaccine adjuvants. To address this, we previously synthesized a less lipophilic ligand containing a single palmitoyl chain called mini-UPam, which effectively stimulates human moDC maturation. We here probe the receptor-dimer specificity of several mini-Upam derivatives and reveal that these mini-UPam are hTLR2/TLR6 selective ligands and that the introduction of longer urea alkyl chains does not shift the binding specificity to hTLR2/TLR1 heterodimers, in contrast to their Pam2CysSK4 and Pam3CysSK4 counterparts, pointing to a different binding mode of the UPam ligands.

Allostery in homodimeric SARS-CoV-2 main protease

Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease Mpro of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of Mpro with three peptide substrates. Crystal structures show how the plasticity of Mpro is exploited to face differences in the sequences of the natural substrates. Importantly, unlike in the free form, the Mpro dimer in complex with these peptides is asymmetric and the structures of the substrates nsp5/6 and nsp14/15 bound to a single subunit show allosteric communications between active sites. We identified arginines 4 and 298 as key elements in the transition from symmetric to asymmetric dimers. Kinetic data allowed the identification of positive cooperativity based on the increase in the processing efficiency (kinetic allostery) and not on the better binding of the substrates (thermodynamic allostery). At the physiological level, this allosteric behavior may be justified by the need to regulate the processing of viral polyproteins in time and space.

Synthesis and anion binding properties of (thio)urea functionalized Ni(II)-salen complexes.

Salen ligands (salen = N,N'-ethylenebis(salicylimine)) are well-known for their versatility and widespread utility in chelating metal complexes. However, installation of hydrogen-bonding units on the salen framework, particularly functional groups that require amine-based precursors such as (thio)ureas, is difficult to achieve without the use of protecting group strategies. In this report, we show that the phenylketone analog of salicyladehyde is a stable alternative that enables the facile installation of hydrogen bonding (thio)urea groups on the salen scaffold, thus imparting anion binding abilities to a metal salen complex. Synthesis of symmetric N-phenyl(thio)urea salen ligands functionalized at the 3,3'-position and an unsymmetric salen ligand with N-phenylurea at the 5-position was achieved. Subsequent metalation with nickel(II) acetate afforded the nickel(II) complexes that were investigated for their anion binding properties towards F-, Cl-, Br-, CH3COO-, and H2PO4-. Solid-state structures of the nickel(II) complexes as well as the Cl- bound dimer of the symmetric urea complex were obtained. The unusual acidity of the (thio)urea groups is reflected in the pKa-dependent anion binding behavior of the nickel(II) complexes, as elucidated by 1H and 19F Nuclear Magnetic Resonance (NMR) spectroscopy and Diffusion Ordered Spectroscopy (DOSY) experiments.

An in-silico study on boronyl-based novel liquid crystalline series

We explore a novel liquid crystalline (LC) series nXB having an alkyl chain length (CnH2n+1) and boronyl group (BO) at terminals using density functional theory. The properties of BO-substituted 2XB molecule are found to be similar to 2CB, a well-known LC compound. Further, this novel compound prefers stacking interaction forming a dimeric complex similar to other LC compounds. These results suggest the potential of BO-substituted compounds to form new LC series. Various electronic parameters of this new nXB series are calculated in the gas phase and solvent effects are also taken into account for n = 1–12. The variation in these parameters clearly reveals the alteration in the trend leading to the odd–even effect, as observed in typical nCB compounds. In particular, the odd–even phenomenon for dipole moment has been discussed in the gas phase as well as in solvents. Thus, our findings predict a novel liquid crystalline series having analogous properties with cyanobiphenyl liquid crystalline series.

Corrolato(oxo)antimony(V) Dimer with Hydrogen-Bond Donor Groups in Secondary Coordination Sphere as a Catalyst for Hydrogen Evolution Reaction.

The focus is on developing alternative molecular catalysts using main-group elements and implementing strategic improvements for sustainable hydrogen production. For this purpose, a FB corrole with a (2-(2-((4-methylphenyl)sulfonamido)ethoxy)phenyl) group inserted into the meso position (C-10) of the corrole, along with its high-valent (corrolato)(oxo)antimony(V) dimer, was synthesized. In the crystal structure analysis of the FB corrole and the (corrolato)(oxo)antimony(V) dimer complex, it was noted that the sulfonamido group in the ligand periphery sits atop the corrole ring. The electrochemical hydrogen evolution reaction (HER) of the (corrolato)(oxo)antimony(V) dimer was studied and compared with a previously reported (corrolato)(oxo)antimony(V) complex, which lacks hydrogen-bond donor groups in the secondary coordination sphere. The newly designed molecules, featuring hydrogen-bond donor groups in the secondary coordination sphere, demonstrated clear superiority in the electrochemical HER. Controlled potential electrolysis was employed to evaluate the charge accumulation associated with hydrogen generation in a homogeneous three-electrode system in the presence of 50 mM TFA. The produced hydrogen exhibits a Faradaic efficiency of approximately 80.96%, a turnover frequency (TOF) of 0.44 h-1, and a production rate of 52.83 μL h-1, highlighting the effective catalytic activity of the (corrolato)(oxo)antimony(V) dimer in hydrogen evolution.

Synthesis, crystal structure, hirshfeld surface analysis, and computational studies of dimeric and polymeric cadmium complexes

In the current investigation, a new dimeric [Cd(DNBA)2(py)2]2 and a polymeric [Cd(DNBA)2(pyz)2]n cadmium complexes have been prepared by the reaction of 3,5-dinitrobenzoic acid (main ligand), nitrogen donor auxiliary ligands (pyridine and pyrazine), and Cd(II) sulphate in aqueous media. The crystal structures of the synthesized compounds were determined by single-crystal X-ray diffraction analysis. The crystal structures were investigated in terms of the coordination geometry, dihedral angles between various rings, and intermolecular interactions. The solid-state assembly was stabilized by various interatomic contacts, explored by Hirshfeld surface analysis. Void analysis was performed to predict the response of crystals to the applied stress. The optimized molecular geometries of the compounds were achieved utilizing the DFT approach along with the B3LYP functional/6–311G(d,p)/LANL2DZ basic set. MEP maps, molecular orbital theory, and quantum chemical parameters for the synthesized compounds were generated using the same level of theory.

Investigating the Impact of the Parkinson's-Associated GBA1 E326K Mutation on β-Glucocerebrosidase Dimerization and Interactome Dynamics Through an In Silico Approach.

Heterozygous mutations or genetic variants in the GBA1 gene, which encodes for the β-glucocerebrosidase (GCase), a lysosomal hydrolase enzyme, may increase the risk of Parkinson's disease (PD) onset. The heterozygous E326K form is one of the most common genetic risk factors for PD worldwide, but, to date, the underlying molecular mechanisms remain unclear. Here, we investigate the effect of the E326K on the structure, stability, dimerization process, and interaction mode with some proteins of the interactome of GCase using multiple molecular dynamics (MD) simulations at pH 5.5 and pH 7.0 to mimic the lysosomal and endoplasmic reticulum environments, respectively. The analysis of the MD trajectories highlights that the E326K mutation did not significantly alter the structural conformation of the catalytic dyad but significantly makes the structure of the dimeric complexes unstable, especially at lysosomal pH, potentially impacting the organization of the quaternary structure. Furthermore, the E326K mutation significantly impacts protein interactions by altering the binding mode with the activator Saposin C (SapC), reducing the binding affinity with the inhibitor α-Synuclein (α-Syn), and increasing the affinity for the Lysosomal integral membrane protein-2 (LIMP-2) transporter.

Structural Variety in Transition Metal Complexes of Tripodal Ligands Containing Mixed Quinolyl and Pyridyl Donors.

The syntheses of the tripodal tetraamine ligands 2-(pyridin-2-yl)-N,N-bis(quinolin-2-ylmethyl)ethan-1-amine (DQPEA), N-(pyridin-2-ylmethyl)-2-(quinolin-2-yl)-N-(2-(quinolin-2-yl)ethyl)ethan-1-amine (DQEPMA), 2-(pyridin-2-yl)-N,N-bis(2-(quinolin-2-yl)ethyl)ethan-1-amine (DQEPEA), N,N-bis(pyridin-2-ylmethyl)-2-(quinolin-2-yl)ethan-1-amine (QEDPMA), and 2-(pyridin-2-yl)-N-(2-(pyridin-2-yl)ethyl)-N-(2-(quinolin-2-yl)ethyl)ethan-1-amine (QEDPEA) containing mixed quinolyl and pyridyl moieties are reported, with 2-vinylquinoline being used to attach quinolylethyl arms to the aliphatic N atom. X-ray crystal structures of [(Mn(DQPEA))2O2](ClO4)2 ⋅ (CH3CN)2, [Cu(DQPEA)NCCH3](ClO4)2, [Zn(DQPEA)NCCH3](ClO4)2, [Pd(DQEPEA)Cl]Cl ⋅ 11H2O are detailed, with four, five, and six-coordination observed. In addition, the dimeric complex [(DPEA)Co(μ-OH)3Co(DPEA)](ClO4)3 ⋅ 0.5H2O ⋅ MeCN containing the tridentate DPEA ligand formed by N-dealkylation of QEDPEA is reported. Calculations suggest that the very short Co…Co distance of 2.5946(6) Å in this complex is unlikely to be due to a Co-Co bond.

A Structural and Functional Mimic of P680.

One or multiple chlorophyll molecules are employed in the reaction center of photosystem II's main electron donor (defined as P680). We have a poor understanding of how the reaction center facilitates water oxidation and the roles that mono- and/or multimeric chlorophyll groups play when P680 oxidizes a neighboring tyrosine in order to drive water oxidation at the oxygen evolving complex. We have prepared a dimeric MgII-porphyrin complex [Mg2(BTPP)] (1, H4-BTPP = 1,2-bis-(10,15,20-triphenylporphyrin-5-yl)-benzene) as a structural and functional mimic of the dimeric core of P680. 1 was oxidized by one-electron to the corresponding π-cation radical complex 2. The radical cation was characterized by UV-Vis-NIR, FT-IR, and EPR spectroscopic techniques. 2 was shown to be reactive towards phenols to give the corresponding phenoxyl radicals, mimicking the reactivity of the P680 cation radical which oxidizes tyrosine to tyrosyl radical. Critically, the dimeric π-cation radical showed markedly higher rates of proton coupled electron transfer oxidation (PCET) of phenols when compared to its monomeric counterpart [Mg(TPP)] (TPP = 5,10,15,20-tetraphenylporphyrin). Our findings demonstrate that MgII-porphyrin complexes are reliable mimics of photosynthetic PCET processes and suggest that photosynthetic reaction centers with multiple π-conjugated complexes likely lower the barrier to PCET oxidation by π-cation radical species.

Bimetallic Uranium Complexes with 2,6-Dipicolinoylbis(N,N-Dialkylthioureas).

2,6-Dipicolinoylbis(N,N-dialkylthioureas), H2LR, readily react with uranyl salts under formation of monomeric or dimeric complexes of the compositions [UO2(LR)(solv)] (solv = donor solvents such as H2O, MeOH or DMF) or [{UO2(LR)(µ-OMe)}2]2- (1). In such complexes, the uranyl ions are exclusively coordinated by the "hard" O,N,O or N,N,N donor atom sets of the central ligand unit and the lateral sulfur donor atoms do not participate in the coordination. Different conformations have been found for the dimeric anions. The bridging methanolato ligands and the four uncoordinated sulfur atoms can adopt different orientations with respect to the equatorial coordination spheres of the uranyl units. The presence of non-coordinated sulfur atoms offers the opportunity for the coordination of additional, preferably "soft" metal ions. Thus, reactions with [AuCl(PPh3)], lead acetate or acetates of transition metal ions such as Ni2+, Co2+, Fe2+, Mn2+, Zn2+, or Cd2+, were considered for the syntheses of bimetallic complexes. Various oligometallic complexes with uranyl units were prepared: [{UO2(LR)(μ-OMe)(Au(PPh3)}2] (2), [(UO2)3Pb2(LR)4(MeOH)2(μ-OMe)2] (3), [M{UO2(LR)(OAc)}2] (M= Zn, Ni, Co, Fe, Mn or Cd) (R = Et: 5, RR = morph: 6), or [(UO2)(NiI)2(LR)2] (7). The products were extensively studied spectroscopically and by X-ray diffraction.

Structural and theoretical insights into the influence of thiocyanate ligands on divalent metal complexes with terpyridine derivatives

Four complexes with terpyridine derivative, thiocyanate anion, and selected d-electron metals were studied. The obtained complexes of the formulation [M(ftpy)(SCN)2(CH3OH)]•DMF (M = Mn (1), Co (2), Ni (3)) and [Cu(ftpy)(NCS)2]•H2O (4), where ftpy = 4′‐(furan-2-yl)-2,2′:6′,2′′‐terpyridine, were characterized using FTIR and UV–Vis spectroscopies, magnetic studies, elemental analysis, and single crystal X-ray crystallography. All compounds crystallize in a triclinic crystal system with space group P1¯ and 1–3 are isomorphous and isostructural. The effect of the modification of the terpyridine ligand and the presence of the thiocyanate ligand on the structure has been verified. Interesting dependence was found in the structure of compound 4, where the two thiocyanate ligands are differently coordinated, one via N and the other via S, and the formation of complex dimers connected through hydrogen bonds is observed. The π-stacking interactions and the resulting solid-state architectures of compounds 1–4 were inspected through a combination of DFT calculations, QTAIM, and NCIPlot analyses, and the stability of the complexes was studied by UV–Vis spectroscopy in various solvents.

Stable Cu (I) Complexes for Intracellular Cu-Catalyzed Azide Alkyne Cycloaddition.

The copper-catalyzed azide-alkyne cycloaddition (CuAAC) has heralded a new era of chemical biology and biomedicine. However, caveats of CuAAC include formation of reactive oxygen species (ROS) and other copper-related toxicity. This limits utility in sensitive biological samples and matrices. Towards addressing these caveats, we synthesized and fully characterized two air and water stable trinuclear Cu (I) dimer complexes. The complexes were stable to oxidation in the presence of hydrogen peroxide, acid, base, and other chelators, which was reasoned to be due to the linear benzimidazole-Cu-benzimidazole geometry. Computational investigations of the catalytic cycle implicated two of the three coppers in the trimer complex as the active metal centers. The complexes were shown to catalyze the reaction at far below sub-toxic concentrations for intracellular click reactions to label triple negative breast cancer cells and compared to the current CuSO-4-THPTA standard.

Molecular dynamics simulations of uranyl and plutonyl cations in a task-specific ionic liquid.

Ionic liquids (ILs) are a unique class of solvents with potential applications in advanced separation technologies relevant to the nuclear industry. ILs are salts with low melting points and a wide range of tunable physical properties, such as viscosity, hydrophobiciy, conductivity, and liquidus range. ILs have negligible vapor pressure, are often non-flammable, and can have high thermal stability and a wide electrochemical window, making them attractive for use in separations processes relevant to the nuclear industry. Metal salts generally have a low solubility in ILs; however, by incorporating new functional groups into the IL cation or anion that promote complexation with the metal, the solubility can be greatly increased. One such task-specific ionic liquid (TSIL) is 1-carboxy-N, N, N-trimethylglycine bis(trifluoromethylsulfonyl)imide ([Hbet][Tf2N]) [Nockemann et al., J. Phys. Chem. B 110, 20978-20992 (2006)]. Water, which is detrimental for electrochemical separations, is a common impurity in ILs and can coordinate with actinyl cations, particularly in ILs containing only weakly coordinating components. Understanding the behavior of actinides in TSIL/water mixtures on a molecular level is vital for designing improved separations processes. Classical molecular dynamics simulations of uranyl(VI) and plutonyl(VI) in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][Tf2N]) with deprotonated Hbet (betaine) and water have been performed to understand the coordination and dynamics of the actinyl cations. We find that betaine is a much stronger ligand than water and prefers to coordinate the metal in a bidentate manner. Potential of mean force simulations yield a relative free energy for betaine coordination of approximately -120 to -90 kJ/mol in mixtures with water. As the amount of betaine coordinated to the actinide increases, the diffusion coefficient of the actinyl cation decreases. Moreover, the betaine ligand is able to bridge between two metal centers, resulting in dimeric complexes with actinide-actinide distances of ∼5Å. Potential of mean force simulations show that these structures are stable, with relative free energies of up to -40 kJ/mol. The crystal structure for [(UO2)2(bet)6(H2O)2][Tf2N]4 shows that the betaine bridges between two uranium atoms to form dimeric complexes similar to those found in our simulations [Nockemann et al. Inorg. Chem. 49, 3351-33601 (2010)].

Influence of 1,2,4-Tri-tert-butylcyclopentadienyl Ligand on the Reactivity of the Thorium Bipyridyl Metallocene [η5-1,2,4-(Me3C)3C5H2]2Th(bipy)

The thorium bipyridyl metallocene (Cp3tBu)2Th(bipy) (1; Cp3tBu = η5-1,2,4-(Me3C)3C5H2) shows a rich reactivity toward a series of small molecules. For example, complex 1 may act as a synthon for the (Cp3tBu)2Th(II) fragment as illustrated by its reactivity toward to CuI, hydrazine derivative (PhNH)2, Ph2E2 (E = S, Se), elemental sulfur (S8) and selenium (Se), organic azides, CS2, and isothiocyanates. Moreover, in the presence of polar multiple bonds, such as those in ketones Ph2CO and (CH2)5CO, aldehydes p-MePhCHO and p-ClPhCHO, seleno-ketone (p-MeOPh)2CSe, nitriles PhCN, Ph2CHCN, C6H11CN, and p-(NC)2Ph, and benzoyl cyanide PhCOCN, C-C coupling occurs to furnish (Cp3tBu)2Th[(bipy)(Ph2CO)] (10), (Cp3tBu)2Th[(bipy)((CH2)5CO)] (11), (Cp3tBu)2Th[(bipy)(p-MePhCHO)] (12), (Cp3tBu)2Th[(bipy)(p-ClPhCHO)] (13), (Cp3tBu)2Th[(bipy){(p-MeOPh)2CSe}] (14), (Cp3tBu)2Th[(bipy)(PhCN)] (16), (Cp3tBu)2Th[(bipy)(Ph2CHCN)] (17), (Cp3tBu)2Th[(bipy)(C6H11CN)] (18), [(Cp3tBu)2Th]2{μ-(bipy)[p-Ph(CN)2](bipy)} (20), and (Cp3tBu)2Th{(bipy)[PhC(CN)O]} (21), respectively. Nevertheless, ketazine (PhCH═N)2 or benzyl nitrile PhCH2CN forms the dimeric complexes [(Cp3tBu)Th]2[μ-NC(Ph)(bipy)]2 (15) and (Cp3tBu)2Th[(bipy){C(═CHPh)NH}] (19), respectively. In contrast, C-N bond cleavage and C-C coupling processes occur upon addition of isonitriles Me3CNC and C6H11NC to 1 to yield the thorium isocyanido amido complexes (Cp3tBu)2Th[4-(Me3C)bipy](NC) (22) and (Cp3tBu)2Th[4-(C6H11)bipy](NC) (23), respectively. Furthermore, a single-electron transfer (SET) process ensues when 1 equiv of CuI is added to 1 to yield the Th(VI) bipyridyl iodide complex (Cp3tBu)2Th(I)(bipy) (3).

Insights into the Main Protease of SARS-CoV-2: Thermodynamic Analysis, Structural Characterization, and the Impact of Inhibitors.

The main protease (Mpro) of SARS-CoV-2 is an essential enzyme for coronaviral maturation and is the target of Paxlovid, which is currently the standard-of-care treatment for COVID-19. There remains a need to identify new inhibitors of Mpro as viral resistance to Paxlovid emerges. Here, we report the use of native mass spectrometry coupled with 193 nm ultraviolet photodissociation (UVPD) and integrated with other biophysical tools to structurally characterize Mpro and its interactions with potential covalent inhibitors. The overall energy landscape was obtained using variable temperature nanoelectrospray ionization (vT-nESI), thus providing quantitative evaluation of inhibitor binding on the stability of Mpro. Thermodynamic parameters extracted from van't Hoff plots revealed that the dimeric complexes containing each inhibitor showed enhanced stability through increased melting temperatures as well as overall lower average charge states, giving insight into the basis for inhibition mechanisms.