Intrinsic Reactivity Differences Research Articles

New Frontiers in Nonheme Enzymatic Oxyferryl Species.

Non-heme mononuclear iron dependent (NHM-Fe) enzymes exhibit exceedingly diverse catalytic reactivities. Despite their catalytic versatilities, the mononuclear iron centers in these enzymes show a relatively simple architecture, in which an iron atom is ligated with 2-4 amino acid residues, including histidine, aspartic or glutamic acid. In the past two decades, a common high-valent reactive iron intermediate, the S=2 oxyferryl (Fe(IV)-oxo or Fe(IV)=O) species, has been repeatedly discovered in NHM-Fe enzymes containing a 2-His-Fe or 2-His-1-carboxylate-Fe center. However, for 3-His/4-His-Fe enzymes, no common reactive intermediate has been identified. Recently, we have spectroscopically characterized the first S=1 Fe(IV) intermediate in a 3-His-Fe containing enzyme, OvoA, which catalyzes a novel oxidative carbon-sulfur bond formation. In this review, we summarize the broad reactivities demonstrated by S=2 Fe(IV)-oxo intermediates, the discovery of the first S=1 Fe(IV) intermediate in OvoA and the mechanistic implication of such a discovery, and the intrinsic reactivity differences of the S=2 and the S=1 Fe(IV)-oxo species. Finally, we postulate the possible reasons to utilize an S=1 Fe(IV) species in OvoA and their implications to other 3-His/4-His-Fe enzymes.

The intrinsic reactivity of coal char conversion compared under different conditions of O2/CO2, O2/H2O and air atmospheres

The reasons for the intrinsic reactivity differences in coal char conversion under an O2/H2O atmosphere compared with that under an O2/CO2 or O2/N2 atmosphere have been investigated in a thermogravimetric analyzer by a simple variable activation energy (SVAE) method combined with an adsorption/desorption reaction mechanism. The results show that only CO2 or H2O chemisorption occurred in the non-isothermal experiments, not gasification; however, the intrinsic reaction rate (IRR) of coal char conversion at the same O2 concentration still increases in an orderly manner under O2/CO2, O2/N2 and O2/H2O atmospheres. This result is due to the different chemisorption mechanisms of CO2 and H2O, namely, the production of C(CO), C(OH) and C(H) from CO2 and H2O chemisorption. At the same O2 concentration, the trends and magnitudes of variable activation energies for coal char combustion under O2/CO2 and O2/N2 atmospheres are similar, while they are very different from those under O2/H2O conditions. Therefore, CO2 has little influence on the reactivity, while H2O changes the reactivity. In addition, according to the developed reaction mechanism, it is concluded that the SVAE method contributes to the characteristic intrinsic reactivity of coal char conversion under different atmospheres.

Bottom up Stabilization of CsPbBr3 Quantum Dots-Silica Sphere with Selective Surface Passivation via Atomic Layer Deposition

All-inorganic perovskite quantum dots suffer from poor stability in a humid and heat environment. In this article, CsPbBr3 quantum dots (CsPbBr3 QDs) are stabilized by coating nanoscale alumina on a CsPbBr3 QDs-silica luminescent sphere (CsPbBr3 QDs-SLS) via atomic layer deposition (ALD). Utilizing the intrinsic reactivity differences toward precursors, the surface defect sites of CsPbBr3 QDs are selectively passivated. The inorganic alumina coating layers can effectively reduce the ion migration and crystal deformation of CsPbBr3 QDs. In situ quartz crystal microbalance measurements show that organic ligands remain attached to the CsPbBr3 QDs surface during the ALD coating process. NMR, XPS, and first-principles calculations are performed to reveal the interaction strength between CsPbBr3 QDs-SLS and precursors. The surface passivation of alumina on CsPbBr3 QDs-SLS effectively stabilizes the QDs without reducing the photoluminescent quantum yield.

Conformation-induced remote meta-C–H activation of amines

Achieving site selectivity in C–H functionalization is a long-standing challenge in organic synthesis. The small differences in intrinsic reactivity of C–H bonds in a given organic molecule often lead to poor discrimination by a catalyst. One solution to this problem is to distinguish C–H bonds based on their location with respect to a particular functional group. In this context, the activation of C–H bonds 5 or 6 bonds away from a functional group via cyclometalation has been extensively studied.1-13 However, directed activation of C–H bonds that are distal (>6 bonds away) from functional groups has remained difficult, especially when the target C–H bonds are geometrically inaccessible through directed metalation due to the ring strain encountered in cyclometalation.14,15 Herein we report a recyclable template that directs the olefination and acetoxyation of distal meta-C–H bonds (as far as 11 bonds away) of anilines and benzylic amines. Remarkably, this template is able to direct the meta-selective C–H functionalization of bicyclic heterocycles via highly strained tricyclic cyclophane-like palladated intermediates. X-ray and NMR studies reveal that the conformational biases induced by a single fluorine substitution in the template can be enhanced by a ligand to switch from ortho- to meta-selectivity.

Oxidative dissolution of 4C- and NC-pyrrhotite: Intrinsic reactivity differences, pH dependence, and the effect of anisotropy

The crystallographic diversity of pyrrhotite (Fe1−xS), one of the most common iron sulfide minerals, offers insights into how mineral–fluid interactions are controlled by crystal structures. We have conducted oxidative dissolution experiments on monoclinic 4C-pyrrhotite and ‘hexagonal’ NC-pyrrhotite in aqueous H2O2/H2SO4 and FeCl3/HCl media at pH between 1.8 and 2.9 using polished surfaces of single crystals. Quantification and detailed characterization of the reaction interfaces has been accomplished by confocal 3D topometry and transmission electron microscopy (TEM) in conjunction with focused ion beam (FIB) preparation. Crystallographically coherent intergrowths of 4C- and NC-pyrrhotite in a single sample allowed unambiguous identification of strong intrinsic reactivity differences between the two closely related phases. On {110} faces in the H2O2 medium at 35°C and pH below 2.70, NC-pyrrhotite (N∼4.85) reacts about 50–80% faster than 4C-pyrrhotite. Above pH 2.70, the behavior inverts and 4C-pyrrhotite dissolves faster, while overall reaction rates drop drastically by up to two orders of magnitude. Because the two pyrrhotite phases show only marginally different Fe/S ratios but substantial differences in structural complexity with regards to vacancy ordering, we attribute the reactivity differences to structurally controlled processes at the mineral–water interface. The transition at pH 2.70 is close to the reported isoelectric point of pyrrhotite. We attribute the pH dependent changes in reaction rates and behaviors to protonation/deprotonation of surface sulfhydryl groups and related changes in speciation and bonding mode of reactive oxygen species at the mineral interface. At pH <2.70, we find elemental sulfur as a frequent reaction product in H2O2 and FeCl3 media, indicating incomplete sulfur oxidation. Above pH 2.70, elemental sulfur was not found in H2O2 experiments (no data for FeCl3). Our results show that the effects of crystal anisotropy are strong and directional preference of dissolution changes at the pH 2.70 transition point as well, leading to complex sub-μm-scale textural development at the reaction interfaces throughout the pH range studied. High resolution TEM imaging of cross sections through reacted mineral surfaces show crystalline pyrrhotite up to the reaction interface and the absence of significant non-equilibrium layers or S-enriched (poly)sulfides.

The α-effect in elimination reactions and competing mechanisms in the gas phase

Our recent studies of the α-effect (enhanced reactivity of nucleophiles with lone pair electrons adjacent to the attacking group) have shown increased nucleophilicity for HOO− in a series of bimolecular substitution (SN2) reactions in the gas phase supporting an intrinsic origin of the effect. Our current work continues to explore the intrinsic behavior of α-nucleophiles by examining other reaction systems and mechanisms. We evaluate intrinsic reactivity differences in the elimination (E2) reactions of a series of anions with tert-butyl chloride by a Brønsted-type correlation. Additional analysis in the E2 reaction with tert-butyl chloride and the SN2 reaction with methyl chloride is accomplished by reagent pairing of normal and α-nucleophiles of nearly identical proton affinities [FCH2CH2O−, C6H5CH2O−, (CH3)3COO−]. Finally, the relationship between product distributions and the magnitude of the α-effect in the competing reactions of dimethyl methylphosphonate (DMMP) and methyl formate is assessed by reagent pairing (HOO− versus HO−, CH3O−, C2H5O−, and (CH3)2CHO−). While our results do not indicate significant differences between the α-anions and the normal anions for the E2 mechanism, enhanced nucleophilicity is observed for both (CH3)3COO− and HOO−. Unlike condensed phase studies, the magnitude of the α-effect in the methyl formate reactions at the sp3 carbon (nucleophilic substitution, SN2) and the sp2 carbon (addition-elimination at the carbonyl center, BAC2) are nearly identical. In the context of hard and soft acids and bases, the behavior of the α-nucleophiles can be rationalized by “soft” base behavior.

Structural, Mechanistic, and Computational Analysis of the Effects of Anomeric Fluorines on Anomeric Fluoride Departure in 5-Fluoroxylosyl Fluorides

The effects of fluorine substitution at the C-5 center of pyranosyl fluorides on the reactivity at the C-1 anomeric center was probed by studying a series of 5-fluoroxylosyl fluoride derivatives. X-ray structures of their per-O-acetates detailed the effects on the ground-state structures. First-order rate constants for spontaneous hydrolysis, in conjunction with computational studies, revealed that changes in the stereochemistry of the 5-fluorine had minimal effects on the solvolysis rate constants and that the observed rate reductions were broadly similar to those caused by additional fluorine substitution at C-1 but significantly less than those due to substitution at C-2. Differences in the trapping behavior of 5- versus 2-fluoro-substituted glycosyl fluorides with α- and β-glycosidases arise more from differences in steric effects and hydrogen-bonding interactions than from intrinsic reactivity differences.

Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity

Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the “intrinsic reactivity” of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant (“Tier 2-like”) viruses, globally sensitive (“Tier 1”) viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and by envelope glycoprotein reactivity to the inhibitor/antibody binding event. Quantitative differences in intrinsic reactivity contribute to HIV-1 strain variability in global susceptibility to neutralization and explain the long-observed relationship between increased inhibitor sensitivity and decreased entry requirements for target cell CD4.

NMR and FTIR investigation of the solution imidization kinetics of model compounds of PMDA/ODA polyamic ethyl ester

Meta- and para-diethyl-p,p-oxydiphenylene pyromellitamide (DOP), the model compounds of the meta and para PMDA/ODA polyamic ethyl ester, were synthesized and characterized by NMR and FTIR spectroscopy. Investigation of the imidization in d6-DMSO solution using NMR and FTIR techniques has shown that both the half imide and imide were formed. Quantitative analysis of the curing rates and degrees of conversion of the isomers in dilute d6-DMSO solution as a function of time under isothermal conditions or as function of temperature at fixed time (1 h) indicated that the kinetics of the ring closure reaction of the meta and para isomers were the same within 10%. This suggests that intrinsic reactivity differences between the isomers do not have much effect on the imidization process and do not account for the differences in rate that have been observed for the meta and para polymers in the solid state. No interconversion between the two isomeric forms occurred below 180°C, as has been observed for polyamic acids and their model compounds. The degree of conversion strongly depended on the reaction temperature and increased quickly after 170°C. The rate constant of the second ring closure reaction was found to be approximately three to four times the rate constant of the first ring closure reaction. © 1996 John Wiley & Sons, Inc.

Active-site mobility inhibits reductive dehalogenation of 1,1,1-trichloroethane by cytochrome P450cam.

Recent studies by Wackett and co-workers have shown that cytochrome P450cam is capable of reductively dehalogenating hexachloroethane at a significant rate, but that no appreciable dehalogenation of 1,1,1-trichloroethane is observed. A growing body of evidence indicates that differences in intrinsic reactivity can not completely explain this observation. We therefore explored the possible role of differences in preferred binding orientation and in active-site mobility. A detailed analysis of molecular dynamics trajectories with each of these substrates bound at the active site of P450cam is presented. While the dynamics and overall time-average structure calculated for the protein are similar in the two trajectories, the two substrates behave quite differently. The smaller substrate, 1,1,1-trichloroethane, is significantly more mobile than hexachloroethane and has a preferred orientation in which the substituted carbon is generally far from the heme iron. In contrast, for hexachloroethane, one of the chlorine atoms is nearly always in van der Waals contact with the heme iron, which should favor the initial electron transfer step.