Kinetics and Products of the Acid-Catalyzed Ring-Opening of Atmospherically Relevant Butyl Epoxy Alcohols

Epoxydiols are produced in the gas phase from the photo-oxidation of isoprene in the absence of significant mixing ratios of nitrogen oxides (NO_x). The reactive uptake of these compounds onto acidic aerosols has been shown to produce secondary organic aerosol (SOA). To better characterize the fate of isoprene epoxydiols in the aerosol phase, the kinetics and products of the acid-catalyzed ring-opening reactions of four hydroxy-substituted epoxides were studied by nuclear magnetic resonance (NMR) techniques. Polyols and sulfate esters are observed from the ring-opening of the epoxides in solutions of H_2SO_4/Na_2SO_4. Likewise, polyols and nitrate esters are produced in solutions of HNO_3/NaNO_3. In sulfuric acid, the rate of acid-catalyzed ring-opening is dependent on hydronium ion activity, sulfate ion, and bisulfate. The rates are much slower than the nonhydroxylated equivalent epoxides; however, the hydroxyl groups make them much more water-soluble. A model was constructed with the major channels for epoxydiol loss (i.e., aerosol-phase ring-opening, gas-phase oxidation, and deposition). In the atmosphere, SOA formation from epoxydiols will depend on a number of variables (e.g., pH and aerosol water content) with the yield of ring-opening products varying from less than 1% to greater than 50%

Characterization and Dynamics of Substituted Ruthenacyclobutanes Relevant to the Olefin Cross-Metathesis Reaction

The reaction of the phosphonium alkylidene [(H_(2)IMes)RuCl2═CHP(Cy)_3)]^(+) BF_(4)^− with propene, 1-butene, and 1-hexene at −45 °C affords various substituted, metathesis-active ruthenacycles. These metallacycles were found to equilibrate over extended reaction times in response to decreases in ethylene concentrations, which favored increased populations of α-monosubstituted and α,α′-disubstituted (both cis and trans) ruthenacycles. On an NMR time scale, rapid chemical exchange was found to preferentially occur between the β-hydrogens of the cis and trans stereoisomers prior to olefin exchange. Exchange on an NMR time scale was also observed between the α- and β-methylene groups of the monosubstituted ruthenacycle (H_(2)IMes)Cl_(2)Ru(CHRCH_(2)CH_(2)) (R = CH_3, CH_(2)CH_3, (CH_2)_)_(3)CH_3). EXSY NMR experiments at −87 °C were used to determine the activation energies for both of these exchange processes. In addition, new methods have been developed for the direct preparation of metathesis-active ruthenacyclobutanes via the protonolysis of dichloro(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)(benzylidene) bis(pyridine)ruthenium(II) and its 3-bromopyridine analogue. Using either trifluoroacetic acid or silica-bound toluenesulfonic acid as the proton source, the ethylene-derived ruthenacyclobutane (H_(2)IMes)Cl_(2)Ru(CH_(2)CH_(2)CH_(2)) was observed in up to 98% yield via NMR at −40 °C. On the basis of these studies, mechanisms accounting for the positional and stereochemical exchange within ruthenacyclobutanes are proposed, as well as the implications of these dynamics toward olefin metathesis catalyst and reaction design are described

Get5 Carboxyl-terminal Domain Is a Novel Dimerization Motif That Tethers an Extended Get4/Get5 Complex

Tail-anchored trans-membrane proteins are targeted to membranes post-translationally. The proteins Get4 and Get5 form an obligate complex that catalyzes the transfer of tail-anchored proteins destined to the endoplasmic reticulum from Sgt2 to the cytosolic targeting factor Get3. Get5 forms a homodimer mediated by its carboxyl domain. We show here that a conserved motif exists within the carboxyl domain. A high resolution crystal structure and solution NMR structures of this motif reveal a novel and stable helical dimerization domain. We additionally determined a solution NMR structure of a divergent fungal homolog, and comparison of these structures allows annotation of specific stabilizing interactions. Using solution x-ray scattering and the structures of all folded domains, we present a model of the full-length Get4/Get5 complex

Lewis Acid Enhancement of Proton Induced CO_2 Cleavage: Bond Weakening and Ligand Residence Time Effects

Though Lewis acids (LAs) have been shown to have profound effects on carbon dioxide (CO_2) reduction catalysis, the underlying cause of the improved reactivity remains unclear. Herein, we report a well-defined molecular system for probing the role of LA additives in the reduction of CO_2 to carbon monoxide (CO) and water. Mo(0) CO_2 complex (2) forms adducts with a series of LAs, demonstrating CO_2 activation that correlates linearly with the strength of the LA. Protons induce C–O cleavage of these LA adducts, in contrast to the CO_2 displacement primarily observed in the absence of LA. CO_2 cleavage shows dependence on both bond activation and the residence time of the bound small molecule, demonstrating the influence of both kinetic and thermodynamic factors on promoting productive CO_2 reduction chemistry

Structures of the Sgt2/SGTA Dimerization Domain with the Get5/UBL4A UBL Domain Reveal an Interaction that Forms a Conserved Dynamic Interface

In the cytoplasm, the correct delivery of membrane proteins is an essential and highly regulated process. The posttranslational targeting of the important tail-anchor membrane (TA) proteins has recently been under intense investigation. A specialized pathway, called the guided entry of TA proteins (GET) pathway in yeast and the transmembrane domain recognition complex (TRC) pathway in vertebrates, recognizes endoplasmic-reticulum-targeted TA proteins and delivers them through a complex series of handoffs. An early step is the formation of a complex between Sgt2/SGTA, a cochaperone with a presumed ubiquitin-like-binding domain (UBD), and Get5/UBL4A, a ubiquitin-like domain (UBL)-containing protein. We structurally characterize this UBD/UBL interaction for both yeast and human proteins. This characterization is supported by biophysical studies that demonstrate that complex formation is mediated by electrostatics, generating an interface that has high-affinity with rapid kinetics. In total, this work provides a refined model of the interplay of Sgt2 homologs in TA targeting

Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders

Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death with average survival times of 2 ‐ 5 years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a protein whose stability and aggregation propensity are affected by point mutations spanning the protein. Here, we use an epitope‐specific, high‐throughput screen to identify peptides that both stabilize the native conformation of SOD1 as well as accelerate its folding by 2.5‐fold. Ligands targeted to the electrostatic loop on the periphery of the protein tightened the non‐metalated structure and accelerated its folding. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics

Redox and pH gradients drive amino acid synthesis in iron oxyhydroxide mineral systems

Iron oxyhydroxide minerals, known to be chemically reactive and significant for elemental cycling, are thought to have been abundant in early-Earth seawater, sediments, and hydrothermal systems. In the anoxic Fe^(2+)-rich early oceans, these minerals would have been only partially oxidized and thus redox-active, perhaps able to promote prebiotic chemical reactions. We show that pyruvate, a simple organic molecule that can form in hydrothermal systems, can undergo reductive amination in the presence of mixed-valence iron oxyhydroxides to form the amino acid alanine, as well as the reduced product lactate. Furthermore, geochemical gradients of pH, redox, and temperature in iron oxyhydroxide systems affect product selectivity. The maximum yield of alanine was observed when the iron oxyhydroxide mineral contained 1:1 Fe(II):Fe(III), under alkaline conditions, and at moderately warm temperatures. These represent conditions that may be found, for example, in iron-containing sediments near an alkaline hydrothermal vent system. The partially oxidized state of the precipitate was significant in promoting amino acid formation: Purely ferrous hydroxides did not drive reductive amination but instead promoted pyruvate reduction to lactate, and ferric hydroxides did not result in any reaction. Prebiotic chemistry driven by redox-active iron hydroxide minerals on the early Earth would therefore be strongly affected by geochemical gradients of E_h, pH, and temperature, and liquid-phase products would be able to diffuse to other conditions within the sediment column to participate in further reactions

Lewis Acid Enhancement of Proton Induced CO_2 Cleavage: Bond Weakening and Ligand Residence Time Effects

Though Lewis acids (LAs) have been shown to have profound effects on carbon dioxide (CO_2) reduction catalysis, the underlying cause of the improved reactivity remains unclear. Herein, we report a well-defined molecular system for probing the role of LA additives in the reduction of CO_2 to carbon monoxide (CO) and water. Mo(0) CO_2 complex (2) forms adducts with a series of LAs, demonstrating CO_2 activation that correlates linearly with the strength of the LA. Protons induce C–O cleavage of these LA adducts, in contrast to the CO_2 displacement primarily observed in the absence of LA. CO_2 cleavage shows dependence on both bond activation and the residence time of the bound small molecule, demonstrating the influence of both kinetic and thermodynamic factors on promoting productive CO_2 reduction chemistry

Tuning of Metal Complex Electronics and Reactivity by Remote Lewis Acid Binding to π-Coordinated Pyridine Diphosphine Ligands

Metal complexes supported by ligands with chemically modifiable pendant groups are of interest for controlling reactivity. We report on the coordination chemistry and reactivity of a multidentate phosphine ligand framework that contains a Lewis acid binding site. 3,5-Bis(2-phosphinophenyl)pyridine coordinates low-oxidation-state metal centers such as Ni^0 and Pd^0 via the phosphine donors and the π system of the heterocycle. Electrophilic reagents such as B(C_6F_5)_3, Me+, and BCy_2OTf bind the available pyridine nitrogen, generating the Ni complexes 2Ni-B(C_6F_5)_3, 2Ni-Me, and 2Ni-BCy_2OTf, respectively. Analogous compounds were prepared for Pd (2Pd, 2Pd-B(C_6F_5)_3, and 2Pd-H). The effect of Lewis acid binding was evaluated by single-crystal X-ray diffraction studies and spectroscopy. Lewis acid binding to 2Pd leads to a stronger η1 interaction between the metal and the heterocycle π system. Ni binds in an η^2 fashion, but the Lewis acid free species is not monomeric. Ni coordination results in disruption of pyridine aromaticity, as indicated by localization of double- and single-bond character in the solid state. CO adducts were prepared for Lewis acid free (4Ni) and Lewis acid bound species (H+-, Me+-, and B(C_6F_5)_3-bound; 4Ni-H, 4Ni-Me, and 4Ni-B(C_6F_5)_3) that show a significant shift of the CO stretching frequency from 1930 to 1966–1976 cm^(–1), respectively, indicating communication of ligand electronics to the metal center. An NO adduct (5Ni) with negligible metal–pyridine interactions was obtained upon sequential reaction of 2Ni with [OMe_3][BF_4] and then [NO][BF_4]. Treatment of 2Ni with silanes and boranes results in pyridine dearomatization involving heteroatom–H bond activation, with the heteroatom binding to the pyridine nitrogen and the hydrides delivered to the ortho position of pyridine. This reactivity demonstrates that the pendant pyridine is drastically affected by metal binding, enabling unusual ligand-based substrate activation. The described chemistry highlights a strategy for tuning the properties of metal centers by ligand postsynthetic modifications

Total Synthesis and Characterization of 7-Hypoquinuclidonium Tetrafluoroborate and 7-Hypoquinuclidone BF_3 Complex

Derivatives of the fully twisted bicyclic amide 7-hypoquinuclidone are synthesized using a Schmidt–Aubé reaction. Their structures were unambiguously confirmed by X-ray diffraction analysis and extensive spectroscopic characterization. Furthermore, the stability and chemical reactivity of these anti-Bredt amides are investigated. 7-Hypoquinuclidonium tetrafluoroborate is shown to decompose to a unique nitrogen bound amide–BF_3 complex of 7-hypoquinuclidone under anhydrous conditions and to react instantaneously with water making it one of the most reactive amides known to date