Dimeric Species Research Articles

Gd3+ Complexes for MRI Detection of Zn2+ in the Presence of Human Serum Albumin: Structure-Activity Relationships.

Zn2+-responsive magnetic resonance imaging (MRI) contrast agents are typically composed of a Gd chelate conjugated to a Zn2+-binding moiety via a linker. They allow for Zn2+ detection in the presence of human serum albumin (HSA). In order to decipher the key parameters that drive their Zn2+-dependent MRI response, we designed a pyridine-based ligand, PyAmC2mDPA, and compared the properties of GdPyAmC2mDPA to those of analogue complexes with varying Gd core, Zn-binding moiety, or linker sizes. The stability constants determined by pH potentiometry showed the good selectivity of PyAmC2mDPA for Gd3+ (log KGd = 16.27) versus Zn2+ (log KZn = 13.58), proving that our modified Zn2+-binding DPA moiety prevents the formation of previously observed dimeric species. Paramagnetic relaxation enhancement measurements indicated at least three sites that are available for GdPyAmC2mDPA binding on HSA, as well as a 2-fold affinity increase when Zn2+ is present (KD = 170 μM versus KDZn = 60 μM). Fluorescence competition experiments provided evidence of the higher affinity for site II vs site I, as well as the importance of both the Zn-binding part and the Gd core in generating enhanced HSA affinity in the presence of Zn2+. Finally, an analysis of nuclear magnetic relaxation dispersion (NMRD) data suggested a significantly increased rigidity for the Zn2+-bound system, which is responsible for the Zn2+-dependent relaxivity response.

Structural Investigation of Technetium Dibutylphosphate Species Using X-ray Absorption Fine Structure Spectroscopy.

The speciation of Tc after the extraction of Tc(IV) from H2O and 1 M HNO3 by dibutylphosphoric acid (HDBP) in dodecane has been studied by X-ray absorption fine structure (XAFS) spectroscopy. Results show the formation of dimeric species with Tc2O2 and Tc2O units, and the formulas [Tc2O2(DBP·HDBP)4] (1) and [Tc2O(NO3)2(DBP)2(DBP·HDBP)2] (2) were, respectively, proposed for the species extracted from H2O and 1 M HNO3. The interatomic Tc-Tc distances found in the Tc2O2 and Tc2O units [2.55(3) and 3.57(4) Å, respectively] are similar to the ones found in Tc(IV) dinuclear species. It is likely that the speciation of Tc(IV) in dodecane is due to the extraction of a species with a Tc2O unit for (2) and to the redissolution of a Tc(IV)-DBP solid for (1). The XAFS results for (1) and (2) were compared to that obtained for the extraction of Tc(IV) with TBP/HDBP/dodecane from 0.5 M HNO3, (3) which highlight the formation of Tc mononuclear nitrate species {i.e., [Tc(NO3)3(DBP)] or [Tc(NO3)2(DBP·HDBP)]}. These results confirm the importance of the preparation and speciation of the Tc(IV) aqueous solutions prior to extraction and how much this influences and drives the final Tc speciation in organic extraction. These studies outline the complexity of Tc separation chemistry and provide insights into the behavior of Tc during the reprocessing of used nuclear fuel.

DNA-bridging by an archaeal histone variant via a unique tetramerisation interface

In eukaryotes, histone paralogues form obligate heterodimers such as H3/H4 and H2A/H2B that assemble into octameric nucleosome particles. Archaeal histones are dimeric and assemble on DNA into ‘hypernucleosome’ particles of varying sizes with each dimer wrapping 30 bp of DNA. These are composed of canonical and variant histone paralogues, but the function of these variants is poorly understood. Here, we characterise the structure and function of the histone paralogue MJ1647 from Methanocaldococcus jannaschii that has a unique C-terminal extension enabling homotetramerisation. The 1.9 Å X-ray structure of a dimeric MJ1647 species, structural modelling of the tetramer, and site-directed mutagenesis reveal that the C-terminal tetramerization module consists of two alpha helices in a handshake arrangement. Unlike canonical histones, MJ1647 tetramers can bridge two DNA molecules in vitro. Using single-molecule tethered particle motion and DNA binding assays, we show that MJ1647 tetramers bind ~60 bp DNA and compact DNA in a highly cooperative manner. We furthermore show that MJ1647 effectively competes with the transcription machinery to block access to the promoter in vitro. To the best of our knowledge, MJ1647 is the first histone shown to have DNA bridging properties, which has important implications for genome structure and gene expression in archaea.

The Smallest Infectious Substructure Encoding the Prion Strain Structural Determinant Revealed by Spontaneous Dissociation of Misfolded Prion Protein Assemblies

It is commonly accepted that the prion replicative propensity and strain structural determinant (SSD) are encoded in the fold of PrPSc amyloid fibril assemblies. By exploring the quaternary structure dynamicity of several prion strains, we revealed that all mammalian prion assemblies exhibit the generic property of spontaneously generating two sets of discreet infectious tetrameric and dimeric species differing significantly by their specific infectivity. By using perturbation approaches such as dilution and ionic strength variation, we demonstrated that these two oligomeric species were highly dynamic and evolved differently in the presence of chaotropic agents. In general, our observations of seven different prion strains from three distinct species highlight the high dynamicity of PrPSc assemblies as a common and intrinsic property of mammalian prions. The existence of such small infectious PrPSc species harboring the SSD indicates that the prion infectivity and the SSD are not restricted only to the amyloid fold but can also be encoded in other alternative quaternary structures. Such diversity in the quaternary structure of prion assemblies tends to indicate that the structure of PrPSc can be divided into two independent folding domains: a domain encoding the strain structural determinant and a second domain whose fold determines the type of quaternary structure that could adopt PrPSc assemblies.

Thiazoline Carbene−Au(I)−Amide complexes exhibiting dimer electroluminescence

Two-coordinate coinage metal (Cu, Ag and Au) complexes with linear carbene–metal–amide (CMA) structure have recently emerged as promising thermally activated delayed fluorescence (TADF) emitters for OLED application. Herein we investigate a series of eight new Au(I) CMA complexes, which incorporate derivatives of 1,3-thiazoline as N-heterocyclic carbene (NHC) ligands. The complexes exhibit blue to green luminescence in thin films. A limitation of the torsional motions around the metal-ligand axis in a combination with the heavy gold atom effect enables highly efficient TADF with photoluminescence quantum yield (PLQY) of up to 0.99 and radiative rates nearing 1·106 s−1. A formation of emissive dimers of complex molecules was observed in vacuum processed OLEDs. Achieved dual electroluminescence from the redshifted (by 120 nm) dimeric species in a combination with co-occurring monomer emission opens potential application prospects in construction of single-emitter white OLEDs.

Seven-Membered Cyclic Diamidoalumanyls of Heavier Alkali Metals: Structures and C-H Activation of Arenes.

Like the previously reported potassium-based system, rubidium and cesium reduction of [{SiNDipp}AlI] ({SiNDipp} = {CH2SiMe2NDipp}2) with the heavier alkali metals [M = Rb and Cs] provides dimeric group 1 alumanyl derivatives, [{SiNDipp}AlM]2. In contrast, similar treatment with sodium results in over-reduction and incorporation of a formal equivalent of [{SiNDipp}Na2] into the resultant sodium alumanyl species. The dimeric K, Rb, and Cs compounds display a variable efficacy toward the C-H oxidative addition of arene C-H bonds at elevated temperatures (Cs > Rb > K, 110 °C) to yield (hydrido)(organo)aluminate species. Consistent with the synthetic experimental observations, computational (DFT) assessment of the benzene C-H activation indicates that rate-determining attack of the Al(I) nucleophile within the dimeric species is facilitated by π-engagement of the arene with the electrophilic M+ cation, which becomes increasingly favorable as group 1 is descended.

Unusual formation of Ir(III) complexes with non‐symmetrical NacNac ligands: Synthesis, characterization, and evaluation of catalytic activity in transfer hydrogenation reduction reactions

A new type of trans‐dichloro‐Ir(III) complexes derived from non‐symmetrical NacNac‐type ligands was unexpectedly obtained as the main reaction product from the former ligands and the dimeric species [Ir(COD)Cl2]. One equivalent of LH was reacted with an excess of [Ir(COD)Cl]2 in dichloromethane or toluene as solvent and at room temperature. The general formula of the product is [IrCl2(COD)L] and was isolated as a sole product instead of the expected Ir(I) compound [Ir(COD)L]; all the new Ir(III) were prepared in high yields as microcrystalline solids. They were all stable under laboratory atmosphere, lasting for weeks in solution and for months in solid state. The structure of each compound was examined by 1D and 2D nuclear magnetic resonance (NMR) and high‐resolution mass spectrometry (HRMS). Complex 1k was selected for an X‐ray diffraction study. Finally, an evaluation was made of the catalytic activity of all complexes in the transfer hydrogenation reaction of ketones and imines.

Aluminum-Boron Bond Formation by Boron Ester Oxidative Addition at an Alumanyl Anion.

The potassium diamidoalumanyl, [K{Al(SiNDipp)}]2 (SiNDipp = {CH2SiMe2NDipp}2), reacts with the terminal B-O bonds of pinacolato boron esters, ROBpin (R = Me, i-Pr), and B(OMe)3 to provide potsassium (alkoxy)borylaluminate derivatives, [K{Al(SiNDipp)(OR)(Bpin)}]n (R = Me, n = 2; R = i-Pr, n = ∞) and [K{Al(SiNDipp)(OMe)(B(OMe)2)}]∞, comprising Al-B σ bonds. An initial assay of the reactivity of these species with the heteroallene molecules, N,N'-diisopropylcarbodiimide and CO2, highlights the kinetic inaccessibility of their Al-B bonds; only decomposition at high temperature is observed with the carbodiimide, whereas CO2 preferentially inserts into the Al-O bond of [K{Al(SiNDipp)(OMe)(Bpin)}]2 to provide a dimeric methyl carbonate species. Treatment of the acyclic dimethoxyboryl species, however, successfully liberates a terminal alumaboronic ester featuring trigonal N2Al-BO2 coordination environments at both boron and aluminum.

Self-assembling of glutathione in aqueous environment: A combined experimental and theoretical study

Detailed concentration-dependent measurements of transient and stationary ultrasonically induced birefringence were combined with molecular docking and DFT techniques to study the formation of glutathione (GSH) self-aggregates in aqueous solutions. Molecular docking revealed the formation of dimers through hydrogen bonding with a binding free energy equal to −3.44 kcal/mol. The behavior of stationary birefringence measurements with concentration allowed us to assign the observed relaxation process to self-association mechanism between glutathione molecules. Systematic analysis of the birefringence traces in the transient region permitted the evaluation of the orientational relaxation times and the corresponding hydrodynamic volumes. Combining the concentration dependent spectroscopic data with supplementary measurements of several physical properties, such as mass density, shear viscosity, sound speed, isentropic compressibility, specific conductivity, and pH, the self-association scheme has been established. The chemical reactivity and the biological activity of the GSH monomer and dimer species were also evaluated and discussed in the context of the fair competence of GSH molecules to interact forming aggregates in aqueous environment.

Molten Sodium Batteries – Lewis Acidity of AlCl3/NaI Catholyte Impedes NaSICON Interface

Low temperature molten sodium batteries with sodium metal anodes, NaSICON solid-state separators, and sodium halide salt catholytes are low cost, earth-abundant technologies for grid-scale energy storage.1-3 We compared batteries with NaI/AlCl3-based molten salt catholytes of differing Lewis acidities at 110 °C. Batteries with >50 mol% AlCl3 (acidic catholytes) experienced a linear decline in energy efficiency during cycling, whereas batteries with >50 mol% NaI (basic catholytes) maintained 95% energy efficiency for 100 cycles (5 months) at 2.5 mA cm-2. A 3-electrode cell was developed, enabling electrochemical identification of the NaSICON-catholyte interface as the source of increased impedance. Complementary physical and chemical characterization of the NaSICON exposed to acidic and basic catholytes showed no changes in crystallinity, bulk morphology, or bulk chemical composition, but surface sensitive X-ray photoelectron spectroscopy (XPS) revealed subtle changes in the local NaSICON surface chemistry. In addition, Raman spectroscopy indicated that basic catholytes lack the dimer species Al2Cl6I- present in acidic catholytes. These results suggest that one means to enable efficient and stable battery cycling is maintaining Lewis-basic NaI/AlCl3, which avoids deleterious interactions at the NaSICON-catholyte interface. Recent progress towards achieving high cycling rates in these molten salt systems will also be shared.References L. J. Small, A. Eccleston, J. Lamb, A. C. Read, M. Robins, T. Meaders, D. Ingersoll, P. G. Clem, S. Bhavaraju and E. D. Spoerke, J. Power Sources, 360, 569 (2017).S. J. Percival, L. J. Small and E. D. Spoerke, J. Electrochem. Soc., 165, A3531 (2018).M. M. Gross, S. J. Percival, L. J. Small, J. Lamb, A. S. Peretti and E. D. Spoerke, ACS Appl. Energy Mater., 3, 11456 (2020). Sandia National Laboratories is a multi-mission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Borylated Subphthalocyanines: Versatile Precursors for the Preparation of Functional Bowl-Shaped Aromatics.

The peripheral borylation of porphyrinoids has become a key step to prepare advanced functional materials. This study reports the synthesis, electronic properties, and reactivity of borylated subphthalocyanines. These compounds, which are prepared by Suzuki-Miyaura borylation in excellent yields, are easily purified, display a great stability, and serve as powerful starting materials for the post-functionalization of SubPcs via cross-coupling reactions. Remarkably, this novel approach is more efficient than the methodologies already described and enables the preparation of exotic systems, such as SubPc dimeric species linked by C-C bonds, which are not accessible so far and present promising properties for optoelectronic devices.

Hydrolysis Reactions of the High Oxidation State Dimers Th2O4, Pa2O5, U2O6, and Np2O6. A Computational Study.

The energetics of the hydrolysis reactions for high oxidation states of the dimeric actinide species Th2IVO4, Pa2VO5, and U2VIO6 were calculated at the CCSD(T) level and those for triplet Np2VIO6 at the B3LYP level. Hydrolysis is initiated by the formation of a Lewis acid/base adduct with H2O (physisorbed product), followed by a proton transfer to form a dihydroxide molecule (chemisorbed product); this process was repeated until the initial actinide oxide is fully hydrolyzed. For Th2O4, hydrolysis (chemisorption) by the initial and subsequent H2O molecules prefers proton transfer to terminal oxo groups before the bridge oxo groups. The overall Th2O4 hydration pathway is exothermic with chemisorbed products preferred over the physisorption products, and the fully hydrolyzed Th2(OH)8 can form exothermically. Hydrolysis of Pa2O5 forms isomers of similar energies with no initial preference for bridge or terminal hydroxy groups. The most exothermic hydrolysis product for Pa is Pa2O(OH)8 and the most stable species is Pa2O(OH)8(H2O). Hydrolysis of U2O6 and Np2O6 with strong [O═An═O]2+ actinyl groups occurs first at the bridging oxygens rather than at the terminal oxo groups. The U2O6 and Np2O6 pathways predict hydrated products to be more favored than hydrolyzed products, as more H2O molecules are added. The stability of the U and Np clusters is predicted to decrease with increasing number of hydroxyl groups. The most stable species on the hydration reaction coordinate for U and Np is An2O3(OH)6(H2O).

Diverse Coordination Chemistry of the Whole Series Rare-Earth L-Lactates: Synthetic Features, Crystal Structure, and Application in Chemical Solution Deposition of Ln2O3 Thin Films.

Rare-earth (RE, Ln) carboxylates are widely studied as precursors of RE oxide-based nanomaterials; however, no systematic studies of RE L-lactates (HLact = 2-hydroxypropanoic acid) have been reported to date. In the present work, a profound structural investigation of RE L-lactates is carried out. A family of RE lactate complexes of the general formula LnLact3∙nH2O (Ln = La, Ce-Nd, Sm-Lu, Y; n = 2-3) are synthesized and characterized by CHN, TGA, and FTIR as well as by powder and single-crystal XRD methods.The existence of four novel structural types (1-Ln-4-Ln) is revealed. Compounds of the 1-Ln type (Ln = La, Ce, Pr) exhibit a chain polymeric structure, whereas 2-Ln-4-Ln compounds are molecular crystals consisting of dimeric (2-Ln; Ln = La, Ce-Nd) or monomeric (3-Ln-Ln = Sm-Lu, Y; 4-Ln-Ln = Sm-Gd, Y) species. The crystal structures of 1-Ln-4-Ln compounds are discussed in terms of their coordination geometry and supramolecular arrangement. Solutions of yttrium and lanthanum lactates with diethylenetriamine are applied for the chemical deposition of Y2O3 and La2O3 thin films.

Resolving the Mechanism for H2O2 Decomposition over Zr(IV)-Substituted Lindqvist Tungstate: Evidence of Singlet Oxygen Intermediacy.

The decomposition of hydrogen peroxide (H2O2) is the main undesired side reaction in catalytic oxidation processes of industrial interest that make use of H2O2 as a terminal oxidant, such as the epoxidation of alkenes. However, the mechanism responsible for this reaction is still poorly understood, thus hindering the development of design rules to maximize the efficiency of catalytic oxidations in terms of product selectivity and oxidant utilization efficiency. Here, we thoroughly investigated the H2O2 decomposition mechanism using a Zr-monosubstituted dimeric Lindqvist tungstate, (Bu4N)6[{W5O18Zr(μ-OH)}2] ({ZrW5}2), which revealed high activity for this reaction in acetonitrile. The mechanism of the {ZrW5}2-catalyzed H2O2 degradation in the absence of an organic substrate was investigated using kinetic, spectroscopic, and computational tools. The reaction is first order in the Zr catalyst and shows saturation behavior with increasing H2O2 concentration. The apparent activation energy is 11.5 kcal·mol-1, which is significantly lower than the values previously found for Ti- and Nb-substituted Lindqvist tungstates (14.6 and 16.7 kcal·mol-1, respectively). EPR spectroscopic studies indicated the formation of superoxide radicals, while EPR with a specific singlet oxygen trap, 2,2,6,6-tetramethylpiperidone (4-oxo-TEMP), revealed the generation of 1O2. The interaction of test substrates, α-terpinene and tetramethylethylene, with H2O2 in the presence of {ZrW5}2 corroborated the formation of products typical of the oxidation processes that engage 1O2 (endoperoxide ascaridole and 2,3-dimethyl-3-butene-2-hydroperoxide, respectively). While radical scavengers tBuOH and p-benzoquinone produced no effect on the peroxide product yield, the addition of 4-oxo-TEMP significantly reduced it. After optimization of the reaction conditions, a 90% yield of ascaridole was attained. DFT calculations provided an atomistic description of the H2O2 decomposition mechanism by Zr-substituted Lindqvist tungstate catalysts. Calculations showed that the reaction proceeds through a Zr-trioxidane [Zr-η2-OO(OH)] key intermediate, whose formation is the rate-determining step. The Zr-substituted POM activates heterolytically a first H2O2 molecule to generate a Zr-peroxo species, which attacks nucleophilically to a second H2O2, causing its heterolytic O-O cleavage to yield the Zr-trioxidane complex. In agreement with spectroscopic and kinetic studies, the lowest-energy pathway involves dimeric Zr species and an inner-sphere mechanism. Still, we also found monomeric inner- and outer-sphere pathways that are close in energy and could coexist with the dimeric one. The highly reactive Zr-trioxidane intermediate can evolve heterolytically to release singlet oxygen and also decompose homolytically, producing superoxide as the predominant radical species. For H2O2 decomposition by Ti- and Nb-substituted POMs, we also propose the formation of the TM-trioxidane key intermediate, finding good agreement with the observed trends in apparent activation energies.

The Mechanism of the Photodimerization of [60]Fullerene Derivatives: It is Still a Charge Separation Followed by a Back Transfer!

AbstractHerein, we present a systematic study of the photochemical behavior of a set of fullerene compounds bearing various organic addends attached to the fullerene cage. It has been shown that the yield of photodimerization products strongly depends on the structure and electronic properties of the material, primarily the electron affinity (acceptor strength) of the modified fullerene core. This finding being inconsistent with the conventional [2+2]cycloaddition mechanism and pointed to an alternative pathway. This proposed pathway involves photoinduced charge separation followed by back charge transfer events leading to the efficient generation of triplet excitons, which are responsible for the formation of dimerized species. The light‐induced charge separation pathway was confirmed by electron spin resonance spectroscopy and was supported by theoretical calculations. The revealed mechanism allows one to control the photochemical behavior of the fullerene derivatives via rational structural engineering: some of the compounds were shown to be fully resistant to photodimerization, which makes them promising candidates in the development of stable organic photovoltaics. Furthermore, this approach could be used to suppress back charge transfer in donor‐acceptor blends and hinder the formation of triplet excitons which represents one a major energy loss channel in the current generation of organic solar cells.

Theoretical Investigation of the Mechanism of the Hock Rearrangement with InCl3 as Catalyst**

AbstractThe Hock rearrangement is an acid catalyzed reaction involving organic hydroperoxides and resulting in an oxidative cleavage of adjacent C−C bonds. It has significant industrial applications, like the production of phenol (cumene process), but it remains scarcely used in organic synthesis. In addition, its detailed mechanism has never been studied. Thus, we report herein a theoretical study of the Hock rearrangement, using InCl3 as a Lewis acid catalyst. The aim of this work was to fully understand the mechanism of this fundamental reaction, and to rationalize the influence of the substrate electronic properties on the reaction outcome. Furthermore, the structure of the active indium(III) catalyst interacting with the peroxide substrate was investigated, revealing the co‐existence of several energetically close reaction pathways. The coordinated monomeric form of the Lewis acid emerges as the most active catalyst compared to dimeric species. However, we show that In2Cl6 species coordinated to the substrate are central in this catalytic cycle, primarily serving as a reservoir of active monomeric species.

Methane Oxidation over Cu2+/[CuOH]+ Pairs and Site‐Specific Kinetics in Copper Mordenite Revealed by Operando Electron Paramagnetic Resonance and UV/Visible Spectroscopy

AbstractCu‐exchanged mordenite (MOR) is a promising material for partial CH4 oxidation. The structural diversity of Cu species within MOR makes it difficult to identify the active Cu sites and to determine their redox and kinetic properties. In this study, the Cu speciation in Cu‐MOR materials with different Cu loadings has been determined using operando electron paramagnetic resonance (EPR) and operando ultraviolet‐visible (UV/Vis) spectroscopy as well as in situ photoluminescence (PL) and Fourier‐transform infrared (FTIR) spectroscopy. A novel pathway for CH4 oxidation involving paired [CuOH]+ and bare Cu2+ species has been identified. The reduction of bare Cu2+ ions facilitated by adjacent [CuOH]+ demonstrates that the frequently reported assumption of redox‐inert Cu2+ centers does not generally apply. The measured site‐specific reaction kinetics show that dimeric Cu species exhibit a faster reaction rate and a higher apparent activation energy than monomeric Cu2+ active sites highlighting their difference in the CH4 oxidation potential.

Methane Oxidation over Cu2+ /[CuOH]+ Pairs and Site-Specific Kinetics in Copper Mordenite Revealed by Operando Electron Paramagnetic Resonance and UV/Visible Spectroscopy.

Cu-exchanged mordenite (MOR) is a promising material for partial CH4 oxidation. The structural diversity of Cu species within MOR makes it difficult to identify the active Cu sites and to determine their redox and kinetic properties. In this study, the Cu speciation in Cu-MOR materials with different Cu loadings has been determined using operando electron paramagnetic resonance (EPR) and operando ultraviolet-visible (UV/Vis) spectroscopy as well as in situ photoluminescence (PL) and Fourier-transform infrared (FTIR) spectroscopy. A novel pathway for CH4 oxidation involving paired [CuOH]+ and bare Cu2+ species has been identified. The reduction of bare Cu2+ ions facilitated by adjacent [CuOH]+ demonstrates that the frequently reported assumption of redox-inert Cu2+ centers does not generally apply. The measured site-specific reaction kinetics show that dimeric Cu species exhibit a faster reaction rate and a higher apparent activation energy than monomeric Cu2+ active sites highlighting their difference in the CH4 oxidation potential.

Synthesis and Characterization of a New Cu(II) Paddle-Wheel-like Complex with 4-Vinylbenzoate as an Inorganic Node for Metal–Organic Framework Material Design

A new Cu(II) paddle-wheel-like complex with 4-vinylbenzoate was synthesized using acetonitrile as the solvent. The complex was characterized by X-ray crystal diffraction, FT-IR, diffuse reflectance spectroscopy, thermogravimetric, differential scanning calorimetric, magnetic susceptibility, and electronic paramagnetic resonance analyses. The X-ray crystal diffraction analysis indicated that each copper ion was bound at an equatorial position to four oxygen atoms from the carboxylate groups of the 4-vinylbenzoate ligand in a square-based pyramidal geometry. The distance between the copper ions was 2.640(9) Å. The acetonitrile molecules were coordinated at the axial position to the copper ions. Exposure of the Cu(II) complex to humid air promoted the gradual replacement of the coordinated acetonitrile by water molecules, but the complex structure integrity remained. The EPR spectra exhibited signals attributed to the presence of a mixture of the monomeric (S = ½) and dimeric (S = 1) copper species in a possible 3:1 ratio. The magnetic studies revealed a peak at 50–100 K, which could be associated with the oxygen absorption capacity of the Cu(II)–vba complex.

Folding-Assisted Peptide Disulfide Formation and Dimerization.

Disulfide bonds form covalent bonds between distal regions of peptides and proteins to dramatically impact their folding, stability, and oligomerization. Given the prevalence of disulfide bonds in many natural products, considerable effort has been invested in site-selective disulfide bond formation approaches to control the folding of chemically synthesized peptides and proteins. Here, we show that the careful choice of thiol oxidation conditions can lead to monomeric or dimeric species from fully deprotected linear bisthiol peptides. Starting from a p53-derived peptide, we found that oxidation under aqueous (nondenaturing) conditions produces antiparallel dimers with enhanced α-helical character, while oxidation under denaturing conditions promotes formation of a nonhelical intramolecular disulfide species. Examination across peptide variants suggests that intramolecular disulfide formation is robust across diverse peptide sequences, while dimerization is sensitive to both the α-helical folding of the linear peptide and aromatic residues at the dimerization interface. All disulfide species are more resistant to protease degradation than the linear peptide but are easily reduced to restore the initial bisthiol peptide. Both disulfide formation approaches are compatible with α-helix-stabilizing cross-linkers. These results provide an approach for using disulfide bonds to control peptide folding and oligomerization to better understand how folding influences interactions with diverse molecular targets.