General Acid Catalysis Research Articles

The Role of General Acid Catalysis in the Mechanism of an Alkyl Transferase Ribozyme.

MTR1 is an in vitro-selected alkyl transferase ribozyme that transfers an alkyl group from O 6-alkylguanine to N1 of the target adenine in the RNA substrate (A63). The structure of the ribozyme suggested a mechanism in which a cytosine (C10) acts as a general acid to protonate O 6-alkylguanine N1. Here, we have analyzed the role of the C10 general acid and the A63 nucleophile by atomic mutagenesis and computation. C10 was substituted by n1c and n1c, c5n variants. The n1c variant has an elevated pK a (11.4 as the free nucleotide) and leads to a 104-fold lower activity that is pH-independent. Addition of the second c5n substitution with a lower pK a restored both the rate and pH dependence of alkyl transfer. Quantum mechanical calculations indicate that protonation of O 6-alkylguanine lowers the barrier to alkyl transfer and that there is a significantly elevated barrier to proton transfer for the n1c single substitution. The calculated pK a values are in good agreement with the apparent values from measured rates. Increasing the pK a of the nucleophile by A63 n7c substitution led to a 6-fold higher rate. The increased reactivity of the nucleophile corresponds to a βnuc of ∼0.5, indicating significant C-N bond formation in the transition state. Taken together, these results are consistent with a two-step mechanism comprising protonation of the O 6-alkylguanine followed by alkyl transfer.

Solvent and Temperature Dependencies of the Rates of Thermal Cis-to-Trans Isomerization of Tetra-(ortho)substituted 4-Aminoazobenzenes Containing 2,6-Dimethoxy Groups.

The kinetics of thermal cis-to-trans isomerization of two tetra-(ortho)substituted 4-aminoazobenzene derivatives containing 2,6-dimethoxy groups in the 4-aminobenzene ring and either 2',6'-dimethyl (1) or 2',6'-dichloro groups in another ring was studied in 16 and 9 solvents, respectively, at room temperature. In addition, the kinetics of isomerization of 1 was studied at variable temperatures in 6 solvents. The solvent effects were analyzed in terms of multiparameter correlations using the Kamlet-Taft, Catalan, and Laurence scales. The temperature dependencies were analyzed in terms of the isokinetic relationship by using Exner's method. The correlation analysis was also extended to several previously reported systems, including isomerization of unsubstituted 4-aminoazobenzene and push-pull 4-NR2-4'-NO2 azobenzenes. It was established that for all 4-aminoazobenzenes in contrast to push-pull azobenzenes, the increase in solvent dipolarity does not affect or even inhibit isomerization rates; however, the increase in solvent acidity induces large rate accelerations. The isokinetic relationship holds only in aprotic solvents, while in alcohols and water, the temperature dependencies do not pass through the common point at T = Tiso, indicating different mechanisms operating in protic and aprotic solvents. The acceleration effect by protic solvents does not represent a type of general acid catalysis as follows from the small solvent isotope effect kH/kD = 1.26 in water. It is suggested that protic solvents induce a change in the reaction mechanism supposedly from inversion to rotation by hydrogen bonding stabilization of the negative charge developed on the azo group in a resonance structure involving a 4-amino group.

N-Terminal Proline Editing for the Synthesis of Peptides with Mercaptoproline and Selenoproline: Mechanistic Insights Lead to Greater Efficiency in Proline Native Chemical Ligation.

Native chemical ligation (NCL) at proline has been limited by cost and synthetic access. In addition, prior examples of NCL using mercaptoproline have exhibited stalling of the reaction after thioester exchange, due to inefficient S → N acyl transfer. Herein, we develop methods, using inexpensive Boc-4R-hydroxyproline, for the solid-phase synthesis of peptides containing N-terminal 4R-mercaptoproline and 4R-selenoproline. The synthesis proceeds via proline editing on the N-terminus of fully synthesized peptides on the solid phase, converting an N-terminal Boc-4R-hydroxyproline to the 4S-bromoproline, followed by an SN2 reaction with potassium thioacetate or selenobenzoic acid. After cleavage from the resin and deprotection, peptides with functionalized N-terminal proline amino acids were obtained. NCL reactions with mercaptoproline proceeded slowly under standard NCL conditions, with the S-acyl transthioesterification intermediate observed as a major species. Computational investigations indicated that the bicyclic intermediates and transition states for S → N acyl transfer are sufficiently low in energy (10-15 kcal mol-1 above starting material) that ring strain cannot explain the slow S → N acyl transfer. Instead, the bicyclic zwitterionic tetrahedral intermediate has a low barrier for reversion to the S-acyl intermediate, causing reversion to the thioester (reverse reaction) to occur preferentially over elimination to generate the amide (forward reaction). We hypothesized that a buffer capable of general acid and/or general base catalysis could promote S → N acyl transfer and thus achieve greater efficiency in proline NCL. In the presence of 2 M imidazole at pH 6.8, NCL with mercaptoproline proceeded efficiently to generate the peptide with a native amide bond. NCL with selenoproline also proceeded efficiently to generate the desired products when a thiophenol thioester was employed as a ligation partner. After desulfurization or deselenization, the products obtained were identical to those synthesized directly, confirming that the solid-phase proline editing reactions proceeded stereospecifically and without epimerization.

Multiphase Reactions between Organic Peroxides and Sulfur Dioxide in Internally Mixed Inorganic and Organic Particles: Key Roles of Particle Phase Separation and Acidity.

Organic peroxides (POs) are ubiquitous in the atmosphere and particularly reactive toward dissolved sulfur dioxide (SO2), yet the reaction kinetics between POs and SO2, especially in complex inorganic-organic mixed particles, remain poorly constrained. Here, we report the first investigation of the multiphase reactions between SO2 and POs in monoterpene-derived secondary organic aerosol internally mixed with different inorganic salts (ammonium sulfate, ammonium bisulfate, or sodium nitrate). We find that when the particles are phase-separated, the PO-S(IV) reactivity is consistent with that measured in pure SOA and depends markedly on the water content in the organic shell. However, when the organic and inorganic phases are miscible, the PO-S(IV) reactivity varies substantially among different aerosol systems, mainly driven by their distinct acidities (not by ionic strength). The second-order PO-S(IV) rate constant decreases monotonically from 5 × 105 to 75 M-1 s-1 in the pH range of 0.1-5.6. Both proton catalysis and general acid catalysis contribute to S(IV) oxidation, with their corresponding third-order rate constants determined to be (6.4 ± 0.7) × 106 and (6.9 ± 4.6) × 104 M-2 s-1 at pH 2-6, respectively. The measured kinetics imply that the PO-S(IV) reaction in aerosol is an important sulfate formation pathway, with the reaction kinetics dominated by general acid catalysis at pH > 3 under typical continental atmospheric conditions.

Mimicking Enzymatic Non-Covalent Interactions with Functionalized Covalent Organic Frameworks for Improved Adsorption and Hydrolysis of Cellobiose.

Tuning catalytic centers in heterogeneous catalyst, both in a chemical and a spatial manner, is a powerful approach to improve the stability and the efficiency of catalysts. While the chemical aspects are largely understood, the spatial interactions around active sites, comprised of non-covalent interactions, are difficult to maintain and challenging to study. Herein, the unique properties of covalent organic frameworks (COFs) are utilized to establish an ideal reaction environment for the hydrolysis of cellobiose and other common disaccharides in mild, metal-free, and neutral aqueous conditions. The chosen COF, HCl-PSA-IM-COF-OMe ("HCl" for hydrochloric acid, "PSA" for propyl sulfonic acid, "IM" for imidazole, and "OMe" for methoxy), is modified to be ultra-stable in aqueous conditions and possesses sulfonic acid groups for general acid catalysis and for enhanced hydrogen bonding with reactants as well as intraporous chloride anions for oxocarbenium intermediate stabilization. In addition, the system also relies on the differences in adsorptive binding behavior, Kads , of the reactants and the products to the functionalized framework and benefits from a separate physical, kinetic process to boost the catalytic cycle. Due to its stability in aqueous conditions, HCl-PSA-IM-COF-OMe can be recycled and maintains its hydrolytic properties for five cycles before regeneration is needed.

Pre-steady-state kinetics and solvent isotope effects support the "billiard-type" transport mechanism in Na+ -translocating pyrophosphatase.

Membrane‐bound pyrophosphatase (mPPase) found in microbes and plants is a membrane H+ pump that transports the H+ ion generated in coupled pyrophosphate hydrolysis out of the cytoplasm. Certain bacterial and archaeal mPPases can in parallel transport Na+ via a hypothetical “billiard‐type” mechanism, also involving the hydrolysis‐generated proton. Here, we present the functional evidence supporting this coupling mechanism. Rapid‐quench and pulse‐chase measurements with [32P]pyrophosphate indicated that the chemical step (pyrophosphate hydrolysis) is rate‐limiting in mPPase catalysis and is preceded by a fast isomerization of the enzyme‐substrate complex. Na+, whose binding is a prerequisite for the hydrolysis step, is not required for substrate binding. Replacement of H2O with D2O decreased the rates of pyrophosphate hydrolysis by both Na+‐ and H+‐transporting bacterial mPPases, the effect being more significant than with a non‐transporting soluble pyrophosphatase. We also show that the Na+‐pumping mPPase of Thermotoga maritima resembles other dimeric mPPases in demonstrating negative kinetic cooperativity and the requirement for general acid catalysis. The findings point to a crucial role for the hydrolysis‐generated proton both in H+‐pumping and Na+‐pumping by mPPases.

Structural Analysis of a Non‐canonical Terpene Synthase

Natural products generated by biosynthetic enzymes provide complex structural diversity. Several fungal species have evolved to obtain this diversity by combining several core enzymes in a biosynthetic pathway, including polyketide synthases (PKS), nonribosonal peptides synthases (NRPS), and terpene cyclases (TC) along with accessorizing enzymes such as transferases and oxidoreductases. Combinations of different core enzymes in hybrid gene clusters affords structurally complex scaffolds unachievable with a single core enzyme. Recently, the Tang laboratory characterized a nine‐gene cluster from the fungal species, Aspergillus flavus, which encodes for two TCs, FlvE and FlvF, along with a single‐module NRPS, FlvI. Additionally, the flvfcluster contains multiple redox enzymes, including the short‐chain reductase FlvB, two P450s (FlvC and FlvD), and a didomain enzyme (FlvA) comprising a PLP‐dependent lyase and a non‐heme Fe α‐ketoglutarate‐dependent oxygenase. Other enzymes in the cluster include FlvG, a homolog of ornithine decarboxylase, and FlvH, a lysine N‐methyltransferase. Together, the flvf pathway produces flavunoidine, an alkaloidal terpenoid containing a tetracyclic and oxygenated sesquiterpene core connected to dimethylcadaverine and acylated with 5,5‐dimethyl‐L‐pipecolate. Notably, a unique feature of the flvf pathway is the enzyme, FlvF. Although annotated as a terpene cyclase, FlvF catalyzes the stereospecific C‐N bond formation attaching dimethylcadaverine to the sesquiterpene core, an unusual reaction given that FlvF has been proposed to take a secondary carbocation as substrate. The mechanism underlying this reaction has not been reported in any other terpene cyclase and is not well understood. Herein, we report the first crystal structure of FlvF determined at 2.6 Å resolution. The initial electron density map was phased using a search model generated by AlphaFold2 (with access provided by ColabFold) and refined with an Rwork/Rfree of 0.22/0.27, respectively. The structure adopts an alpha‐fold of class I terpene cyclases, and a search for structural homologs using the DALI server identifies the closest matches as the terpene cyclases FgGS, PaFS, and aristolochene synthase. Notably, FlvF does not contain the canonical metal‐binding motifs observed in class I cyclases. A bound molecule of Tris forms cation‐pi interactions with surrounding aromatic residues at the base of the active site, which might similarly stabilize a carbocation intermediate. Further analysis of the active site indicates multiple possibilities for general acid catalysis. Future structural and mechanistic studies are necessary to elucidate the mechanism of this enzyme.

Structure and mechanism of a methyltransferase ribozyme

Known ribozymes in contemporary biology perform a limited range of chemical catalysis, but in vitro selection has generated species that catalyze a broader range of chemistry; yet, there have been few structural and mechanistic studies of selected ribozymes. A ribozyme has recently been selected that can catalyze a site-specific methyl transfer reaction. We have solved the crystal structure of this ribozyme at a resolution of 2.3 Å, showing how the RNA folds to generate a very specific binding site for the methyl donor substrate. The structure immediately suggests a catalytic mechanism involving a combination of proximity and orientation and nucleobase-mediated general acid catalysis. The mechanism is supported by the pH dependence of the rate of catalysis. A selected methyltransferase ribozyme can thus use a relatively sophisticated catalytic mechanism, broadening the range of known RNA-catalyzed chemistry.

Dynamic Tuning in Synthetic Glycosidase for Selective Hydrolysis of Alkyl and Aryl Glycosides.

Enzymes use sophisticated conformational control to optimize the dynamics of their protein framework for efficient catalysis. Although it is difficult to employ a similar strategy to improve catalysis in a synthetic enzyme, we here report that modulation of the dynamics of the substrate in the active site is readily achievable in a complex between a molecularly imprinted nanoparticle and its acid cofactor, through tuning of the size and shape of the imprinted site. As the alkyl glucoside substrate is bound with increasing strength and held in a more tightly fitted pocket, the acid-catalyzed glycan hydrolysis becomes more difficult. A larger, wider active site, although less able to bind the substrate, affords a higher catalytic activity, likely due to easier alignment of the substrate and the acid cofactor for a general acid catalysis. The substrate selectivity is controlled by both the tightness of the aglycon-binding site and the orientation of the glycan-binding boroxole group.

Cover Feature: An Improved Protocol for the Morita‐Baylis‐Hillman Reaction Allows Unprecedented Broad Synthetic Scope (Eur. J. Org. Chem. 9/2022)

The Cover Feature illustrates the effect of acetic acid on the rate of the Morita–Baylis–Hillman reaction. The use of acetic acid as a fuel (additive) increases the reaction rate in all tested cases, with special emphasis on electron-rich electrophilic partners. We believe that a general acid catalysis mechanism is responsible for this increase in reaction rate. More information can be found in the Research Article by G. W. Amarante, F. Coelho et al.

Optimization of Surface Loading of the Silatrane Anchoring Group on TiO2.

Anchoring groups are usually needed for the attachment of small molecules to metal oxide surfaces such as in water-splitting dye-sensitized photoelectrochemical cells (WS-DSPECs). Here, we optimize the surface loading onto titanium dioxide surfaces of the silatrane anchoring group, a triethanolamine-protected trialkoxysilane. This anchoring group is not yet widely used because prior protocols afforded low surface coverage, but it has the advantage of high stability over a wide pH range and at both oxidizing and reducing potentials when bound. A new and improved method for estimating surface coverage is described here and used to determine that loading using previously reported binding protocols is very low. However, we were able to uncover several factors contributing to this low loading, which has allowed us to develop methods to greatly improve surface coverage for a variety of silatranes. Most notably, we were able to increase the loading of a model arylsilatrane by 145% through use of a benzoic acid additive. This is not general acid catalysis because alkylsilatranes are not similarly affected and 4-t-butylbenzoic acid, having a similar pKa to benzoic acid, is not effective. Because the bulky t-butyl group of the latter additive is not expected to pi-stack with our arylsilatrane, we have tentatively assigned this enhancement to aromatic stacking between the aromatic additive and the arylsilatrane.

An Improved Protocol for the Morita‐Baylis‐Hillman Reaction Allows Unprecedented Broad Synthetic Scope

AbstractThe Morita‐Baylis‐Hillman (MBH) reaction has been stablished as an important C−C bond‐forming transformation between carbonyl‐containing compounds and activated olefins. However, the slow reaction rate usually observed with electron‐rich electrophilic partners hinders a more widespread use of this reaction. In order to overcome this drawback, the effects of several Brønsted acids on the rate of DABCO‐catalyzed MBH reactions were evaluated. The protocol is operationally simple, involving neat and open‐flask conditions, and is compatible with a wide range of reagents. We suggest a general acid catalysis mechanism to be responsible for the rate increase. The synthetic versatility of the MBH adducts is exemplified with a two‐steps diastereoselective synthesis of the natural product (±)‐sitophilure. We hope this acid‐mediated protocol to have potential use as a general methodology for the MBH reaction.

Protic Ionic Liquid as Reagent, Catalyst, and Solvent: 1-Methylimidazolium Thiocyanate.

We propose a new concept of the triple role of protic ionic liquids with nucleophilic anions: a) a regenerable solvent, b) a Brønsted acid inducing diverse transformations via general acid catalysis, and c) a source of a nucleophile. The efficiency of this strategy was demonstrated using thiocyanate‐based protic ionic liquids for the ring‐opening of donor‐acceptor cyclopropanes. A wide variety of activated cyclopropanes were found to react with 1‐methylimidazolium thiocyanate under mild metal‐free conditions via unusual nitrogen attack of the ambident thiocyanate ion on the electrophilic center of the three‐membered ring affording pyrrolidine‐2‐thiones bearing donor and acceptor substituents at the C(5) and C(3) atoms, respectively, in a single time‐efficient step. The ability of 1‐methylimidazolium thiocyanate to serve as a triplex reagent was exemplarily illustrated by (4+2)‐annulation with 1‐acyl‐2‐(2‐hydroxyphenyl)cyclopropane, epoxide ring‐opening and other organic transformations.

Protic Ionic Liquid as Reagent, Catalyst, and Solvent: 1‐Methylimidazolium Thiocyanate

AbstractWe propose a new concept of the triple role of protic ionic liquids with nucleophilic anions: a) a regenerable solvent, b) a Brønsted acid inducing diverse transformations via general acid catalysis, and c) a source of a nucleophile. The efficiency of this strategy was demonstrated using thiocyanate‐based protic ionic liquids for the ring‐opening of donor‐acceptor cyclopropanes. A wide variety of activated cyclopropanes were found to react with 1‐methylimidazolium thiocyanate under mild metal‐free conditions via unusual nitrogen attack of the ambident thiocyanate ion on the electrophilic center of the three‐membered ring affording pyrrolidine‐2‐thiones bearing donor and acceptor substituents at the C(5) and C(3) atoms, respectively, in a single time‐efficient step. The ability of 1‐methylimidazolium thiocyanate to serve as a triplex reagent was exemplarily illustrated by (4+2)‐annulation with 1‐acyl‐2‐(2‐hydroxyphenyl)cyclopropane, epoxide ring‐opening and other organic transformations.

A cationic copolymer as a cocatalyst for a peroxidase-mimicking heme-DNAzyme.

Heme binds to a parallel-stranded G-quadruplex DNA to form a peroxidase-mimicking heme-DNAzyme. An interpolyelectrolyte complex between the heme-DNAzyme and a cationic copolymer possessing protonated amino groups was characterized and the peroxidase activity of the complex was evaluated to elucidate the effect of the polymer on the catalytic activity of the heme-DNAzyme. We found that the catalytic activity of the heme-DNAzyme is enhanced through the formation of the interpolyelectrolyte complex due to the general acid catalysis of protonated amino groups of the polymer, enhancing the formation of the iron(IV)oxo porphyrin π-cation radical intermediate known as Compound I. This finding indicates that the polymer with protonated amino groups can act as a cocatalyst for the heme-DNAzyme in the oxidation catalysis. We also found that the enhancement of the activity of the heme-DNAzyme by the polymer depends on the local heme environment such as the negative charge density in the proximity of the heme and substrate accessibility to the heme. These findings provide novel insights as to molecular design of the heme-DNAzyme for enhancing its catalytic activity.

Role of Carbonate Species on General Acid Catalysis of Bromide Oxidation by Hypochlorous Acid (HOCl) and Oxidation by Molecular Chlorine (Cl2).

Kinetic models for disinfectant decay and disinfection byproduct (DBP) formation are necessary for predicting water quality from the treatment plant to the tap. A kinetic model for conditions relevant to chloramine disinfection of drinking water (pH 6-9 and carbonate-buffered) was developed to simulate incomplete bromide (Br-) oxidation during short prechlorination periods because it is the first step in a complex system of reactions that leads to disinfectant loss and DBP formation. Hypochlorous acid and molecular chlorine were the free chlorine species relevant to Br- oxidation, and Cl2 hydrolysis and formation reactions were necessary to accurately simulate Cl2 concentrations instead of assuming equilibrium. Previous work has shown that Br- oxidation by HOCl and Cl2 formation are acid-catalyzed and Cl2 hydrolysis is base-catalyzed, but the impact of carbonate species had not been studied. This work showed that the carbonate species have an enhanced catalytic impact with rate constants up to 1000 times larger than would be estimated by the Brønsted relationship for similar acids, which causes the oxidation by HOCl rate constant (kHOCl) to nearly double and oxidation by Cl2 to occur above pH 7 in high-alkalinity waters.

Better late than never! Transition state character involved in the neutral solvolysis of an oxalic ester determined by the ionizing power of ethanol/water and methanol/water mixtures

Solvation effects and solvolysis extent are major aspects of the decomposition of esters, particularly in polar protic media. Among the many different ester derivatives, oxalic esters are substances that have two ester groups in the same molecular framework, but with potentially different reactivities. Aryl oxalic esters are commonly used in efficient organic chemiluminescent reactions, leading to important analytical and biological applications. We studied the decomposition of bis(2,4,6-trichlorophenyl) oxalate (TCPO) in 100, 98, 95, 90, 80, 70, 60, and 50% ethanol/water (EtOH/W) and 100, 90, 80, and 70% methanol/water (MeOH/W) mixtures (% in v/v). In these media, one phenolic residue is generated in a fast addition–elimination (step 1), followed by a second slower addition–elimination (step 2), thus, two rate constants are observed. Using a Grunwald–Winstein (G–W) relationship between these rate constants and the solvent ionizing power (Υ), we determined the sensibility (m) to solvation effects and charge development associated with the transition state (TS) of the rate-determining step (rds). We also determined the Gibbs free energy of activation (∆‡G, at 25 °C) associated with each step, and used it to rationalize the TS character of the rds, considering that in both steps a zwitterionic intermediate is generated and that the addition step is rate limiting. In EtOH/W binary mixtures a non-linear G–W plot was observed, and for 100–95% EtOH/W mixtures the sensibility was m = 1.0 (step 1, ∆‡G = 21.6 to 20.6 kcal mol−1) and 1.1 (step 2, ∆‡G = 23.9 to 23.0 kcal mol−1), indicating full ionization in the TS of the addition step. Smaller Y values in 90–50% EtOH/W reflect a more symmetrical TS, with not as many charges being generated (step 1, m = 0.196, ∆‡G = 20.3 to 19.4 kcal mol−1; step 2, m = 0.30, ∆‡G = 22.6 to 21.7 kcal mol−1). In 100%–70% MeOH/W binary mixtures, with Y values similar to those for 90–50% EtOH/W, m = 0.52 (step 1, ∆‡G = 20.3 to 18.8 kcal mol−1) and 0.27 (step 2, ∆‡G = 21.5 to 20.9 kcal mol−1) were observed. Particularly for step 1 in MeOH/W, the observation of a solvent kinetic isotope effect that varies from inverse (0.63 ± 0.09 in pure MeOH) to normal (1.9 ± 0.3 in 70% MeOH/W) is consistent with the significant participation of the solvent in TS stabilization, resembling general acid catalysis.

Computational mechanistic study of human liver glycerol 3‐phosphate dehydrogenase using ONIOM method

AbstractHuman liver glycerol 3‐phosphate dehydrogenase catalyzes transfer of a hydride anion from NADH to dihydroxyacetone phosphate (DHAP) forming L‐glycerol 3‐phosphate and NAD+ in a single step reaction. It is proposed that a hydride ion is transferred from NADH to the carbonyl carbon of DHAP through a general acid catalysis in which the carbonyl oxygen of DHAP is protonated by a nearby acidic residue. Based on the crystal structure of enzyme, it was suggested that one of the active site lysine residues (Lys120/Lys204) might act as general acid for the protonation of the carbonyl oxygen at DHAP. In this study, we formulated a number of computational systems to study the hydride transfer mechanism including main active site amino acid side chains, NADH cofactor, and DHAP. The calculations involved ONIOM method consisting of DFT and molecular mechanics (MM). We evaluated the energetics of the hydride transfer process in different model systems while probing the roles of active site residues, Lys120/Lys204/Asp260. Based on calculations, protonated Asp260 has more favorable energetics to act as the general acid catalysis as compared to Lys120/204 residues.

Coordination among Bond Formation/Cleavage in a Bifunctional-Catalyzed Fast Amide Hydrolysis: Evidence for an Optimized Intramolecular N-Protonation Event.

A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.

Fast oxidation of sulfur dioxide by hydrogen peroxide in deliquesced aerosol particles.

Atmospheric sulfate aerosols have important impacts on air quality, climate, and human and ecosystem health. However, current air-quality models generally underestimate the rate of conversion of sulfur dioxide (SO2) to sulfate during severe haze pollution events, indicating that our understanding of sulfate formation chemistry is incomplete. This may arise because the air-quality models rely upon kinetics studies of SO2 oxidation conducted in dilute aqueous solutions, and not at the high solute strengths of atmospheric aerosol particles. Here, we utilize an aerosol flow reactor to perform direct investigation on the kinetics of aqueous oxidation of dissolved SO2 by hydrogen peroxide (H2O2) using pH-buffered, submicrometer, deliquesced aerosol particles at relative humidity of 73 to 90%. We find that the high solute strength of the aerosol particles significantly enhances the sulfate formation rate for the H2O2 oxidation pathway compared to the dilute solution. By taking these effects into account, our results indicate that the oxidation of SO2 by H2O2 in the liquid water present in atmospheric aerosol particles can contribute to the missing sulfate source during severe haze episodes.