Kinetic Phenomena in Mechanochemical Depolymerization of Poly(styrene).

Synthetic polyolefinic plastics comprise one of the largest shares of global plastic waste, which is being targeted for chemical recycling by depolymerization to monomers and small molecules. One promising method of chemical recycling is solid-state depolymerization under ambient conditions in a ball-mill reactor. In this paper, we elucidate kinetic phenomena in the mechanochemical depolymerization of poly(styrene). Styrene is produced in this process at a constant rate and selectivity alongside minor products, including oxygenates like benzaldehyde, via mechanisms analogous to those involved in thermal and oxidative pyrolysis. Continuous monomer removal during reactor operation is critical for avoiding repolymerization, and promoting effects are exhibited by iron surfaces and molecular oxygen. Kinetic independence between depolymerization and molecular weight reduction was observed, despite both processes originating from the same driving force of mechanochemical collisions. Phenomena across multiple length scales are shown to be responsible for differences in reactivity due to differences in grinding parameters and reactant composition.

Carbonyl Migration in Uronates Affords a Potential Prebiotic Pathway for Pentose Production.

Carbohydrate biosynthesis is fundamental to modern terrestrial biochemistry, but how this collection of metabolic pathways originated remains an open question. Prebiotic sugar synthesis has focused primarily on the formose reaction and Kiliani-Fischer homologation; however, how they can transition to extant biochemical pathways has not been studied. Herein, a nonenzymatic pathway for pentose production with similar chemical transformations as those of the pentose phosphate pathway is demonstrated. Starting from a C6 aldonate, namely, gluconate, nonselective chemical oxidation yields a mixture of 2-oxo-, 4-oxo-, 5-oxo-, and 6-oxo-uronate regioisomers. Regardless at which carbinol the oxidation takes place, carbonyl migration enables ß-decarboxylation to yield pentoses. In comparison, the pentose phosphate pathway selectively oxidizes 6-phosphogluconate to afford the 3-oxo-uronate derivative, which undergoes facile subsequent ß-decarboxylation and carbonyl migration to afford ribose 5-phosphate. The similarities between these two pathways and the potential implications for prebiotic chemistry and protometabolism are discussed.

Erythrose and Threose: Carbonyl Migrations, Epimerizations, Aldol, and Oxidative Fragmentation Reactions under Plausible Prebiotic Conditions.

The prebiotic generation of sugars in the context of origins of life studies is of considerable interest. Among the important intramolecular processes of sugars are carbonyl migrations and accompanying epimerizations. Herein we describe the carbonyl migration-epimerization process occurring down the entire carbon chain of chirally pure d-tetroses sugars under mild conditions. Employing chirally pure 1-13 C-erythrose, 4-13 C-erythrose and 1-13 C-threose, we (1) identify all the species formed as the carbonyl migrates down the four-carbon chain and (2) assess the rates associated with the production of each of these species. Competing aldol reactions and oxidative fragmentation processes were also observed. Further observations of self-condensation of glycolaldehyde mainly yielding 2-keto-hexoses (sorbose and tagatose) and tetrulose also provides a basis for understanding the effect of carbonyl migrations on the product distribution in plausible prebiotic scenarios.

Water-Based Dynamic Depsipeptide Chemistry: Building Block Recycling and Oligomer Distribution Control Using Hydration-Dehydration Cycles.

The high kinetic barrier to amide bond formation has historically placed narrow constraints on its utility in reversible chemistry applications. Slow kinetics has limited the use of amides for the generation of diverse combinatorial libraries and selection of target molecules. Current strategies for peptide-based dynamic chemistries require the use of nonpolar co-solvents or catalysts or the incorporation of functional groups that facilitate dynamic chemistry between peptides. In light of these limitations, we explored the use of depsipeptides: biorelevant copolymers of amino and hydroxy acids that would circumvent the challenges associated with dynamic peptide chemistry. Here, we describe a model system of N-(α-hydroxyacyl)-amino acid building blocks that reversibly polymerize to form depsipeptides when subjected to two-step evaporation-rehydration cycling under moderate conditions. The hydroxyl groups of these units allow for dynamic ester chemistry between short peptide segments through unmodified carboxyl termini. Selective recycling of building blocks is achieved by exploiting the differential hydrolytic lifetimes of depsipeptide amide and ester bonds, which we show are controllable by adjusting the solution pH, temperature, and time as well as the building blocks' side chains. We demonstrate that the polymerization and breakdown of the depsipeptides are facilitated by cyclic morpholinedione intermediates, and further show how structural properties dictate half-lives and product oligomer distributions using multifunctional building blocks. These results establish a cyclic mode of ester-based reversible depsipeptide formation that temporally separates the polymerization and depolymerization steps for the building blocks and may have implications for prebiotic polymer chemical evolution.

Separations of Carbohydrates with Noncovalent Shift Reagents by Frequency-Modulated Ion Mobility-Orbitrap Mass Spectrometry.

An increased focus on characterizing the structural heterogeneity of carbohydrates has been driven by their many significant roles in extant life and potential roles in chemical evolution and the origin of life. In this work, multiplexed drift tube ion mobility-Orbitrap mass spectrometry methods were developed to analyze mixtures of disaccharides modified with noncovalent shift reagents. Since traditional coupling of atmospheric pressure drift tube ion mobility cells with Orbitrap mass analyzers suffers from low duty cycles (<0.1%), a frequency modulation scheme was applied to improve the signal-to-noise ratios (SNR). Several parameters such as the resolution setting and maximum injection time of the Orbitrap analyzer and the magnitude and duration of the frequency sweep were investigated for their impact on the sensitivity gains and resolution of disaccharide-shift reagent adducts. The sweep time and disaccharide concentration had a positive correlation with SNR. The magnitude of the frequency sweep had a negative correlation with SNR. However, increasing the frequency sweep improved the resolution of mixtures of disaccharide analytes. Application of frequency-modulated ion mobility-Orbitrap mass spectrometry to four noncovalently modified glucose dimers allowed for the differentiation of three out of these four analytes.

Organic acid shift reagents for the discrimination of carbohydrate isobars by ion mobility-mass spectrometry.

Carbohydrates are the most abundant class of biomolecules on Earth with a diverse array of biological functions. It is hypothesized that they likely had an important role in the development of life on the primoridal Earth as well. Since sugars have a variety of possible isobaric structures, it is necessary to characterize oligosaccharides beyond their molecular weight. Ion mobility-mass spectrometry (IM-MS) is a promising characterization technique for this purpose, as it is based on differences in charge and collision cross section (CCS). This study reports on the use of new noncovalent ligands as shift reagents to aid in the IM separations of disaccharides. A variety of organic acids were tested as shift reagents with traveling wave IM with the most promising ones being further investigated by drift tube IM. Drift tube IM provided higher resolution separations for the large majority of disaccharide complexes studied. Combining CCS results of the two most promising shift reagents allowed for the complete differentiation of all eight disaccharide standards examined in this study.

The Oligomerization of Glucose Under Plausible Prebiotic Conditions.

The prebiotic origin of polysaccharides, the largest class of biopolymers by mass in extant biology, has seldom been investigated experimentally. Herein, we report on the acid-catalyzed condensation of aqueous solutions of glucose, a model monosaccharide, under plausible prebiotic conditions employing a wet-dry (night-day) protocol with 0.01 M HCl at 50 °C. This protocol leads to the formation of oligosaccharides containing up to eight monomeric units identified by high resolution mass spectrometry. The regio- and stereochemistry of the oligomeric acetal linkages, as well as the quantitative analysis of glucose conversion, are elucidated by combining 1H, 13C and 2D NMR spectroscopy. Ten out of eleven possible acetal linkages, including α- and ß- anomers, have been identified with the α- and ß- 1,6-acetals being the dominant linkages observed. In addition, the acid-catalyzed oligomerization of several glucose disaccharides such as cellobiose, maltose, and gentiobiose are presented along with an accompanying comparison with the corresponding oligomerization of glucose.

The pH dependent mechanisms of non-enzymatic peptide bond cleavage reactions.

The non-enzymatic cleavage rates of amide bonds located in peptides in aqueous solution is pH-dependent and involves two distinct mechanisms: direct hydrolysis (herein termed "scission") and intramolecular aminolysis by the N-terminal amine (herein termed "backbiting"). While amide bond cleavage has been previously characterized using a variety of peptides, no systematic study has yet been reported addressing the effect of the pH on the interplay between the two amide bond cleavage pathways. In this study, the cleavage rates of the glycine dimer (GG), the glycine trimer (GGG), and the cyclic dimer (cGG), as well as the alanine trimer (AAA), were measured at pH 3, 5, 7, and 10 at 95 °C employing quantification based on 1H NMR. The distinct rate constants for scission and backbiting processes were obtained by solving the differential rate equations associated with the proposed kinetic model. Generalizations concerning the relative importance of the various amide bond cleavage pathways at pH 3, 5, 7, and 10 are presented. In particular, scission dominates at pH 10, while backbiting dominates at neutral pH. At the acidic pH of 3, both backbiting and scission are significant. The model of the reaction network, used in this work, enables the quantification of these multiple competing mechanisms and can be applied to longer peptides and to similar types of reaction networks.

Carbohydrate isomer resolution via multi-site derivatization cyclic ion mobility-mass spectrometry.

Oligosaccharides serve many roles in extant life and may have had a significant role in prebiotic chemistry on the early Earth. In both these contexts, the structural and isomeric diversity among carbohydrates presents analytical challenges necessitating improved separations. Here, we showcase a chemical derivatization approach, where 3-carboxy-5-nitrophenylboronic acid (3C5NBA) is used to label vicinal hydroxyl groups, amplifying the structural difference between isomers. We explore the applicability of state-of-the-art ion mobility - mass spectrometry (IM-MS) instrumentation in the analysis of derivatized carbohydrates. In particular we focus on the resolving power required for IM separation of derivatized isomers. A recently developed cyclic ion mobility (cIM) mass spectrometer (MS) was chosen for this study as it allows for multi-pass IM separations, with variable resolving power (Rp). Three passes around the cIM (Rp ∼ 120) enabled separation of all possible pairs of four monosaccharide standards, and all but two pairs of eight disaccharide standards. Combining cIM methodology with tandem mass spectrometry (MS/MS) experiments allowed for the major products of each of the 3C5NBA carbohydrate derivatization reactions to be resolved and unequivocally identified.

Base-Mediated Cascade Aldol Addition and Fragmentation Reactions of Dihydroxyfumaric Acid and Aromatic Aldehydes: Controlling Chemodivergence via Choice of Base, Solvent, and Substituents.

The diester derivative of dihydroxyfumaric acid (DHF) has been used exclusively as an electrophile in organic synthesis. However, the synthetic utility of DHF's nucleophilic reactivity, contained in the ene-diol moiety, has been underexplored. Inspired by recently observed pH-dependent chemodivergent nucleophilic aldol reactions of dihydroxyfumarate (DHF2-) with glyoxylate and formaldehyde, we report herein the control and synthetic application of base-controlled chemodivergent reactions between dihydroxyfumarate and aromatic and heteroaromatic aldehydes. With hydroxide as the base in a predominantly aqueous medium, aldol addition followed by deoxalation occurs to provide various 3-aryl-2,3-dihydroxypropanoic acids. With triethylamine as the base in THF, 1-aryl-2,3-dihydroxypropanones are the products of the reaction. In order to understand the difference in reactivity between DHF, its dicarboxylate, and its dimethyl ester, we undertook computational and experimental studies that provide a rationale as to why the dihydroxyfumarate (DHF2-) is a nucleophile while the corresponding diester reacts as an electrophile.

Effect of temperature modulations on TEMPO-mediated regioselective oxidation of unprotected carbohydrates and nucleosides.

Regioselective oxidation of unprotected and partially protected oligosaccharides is a much sought-after goal. Herein, we report a notable improvement in the efficiency of TEMPO-catalyzed oxidation by modulating the temperature of the reaction. Mono-, di-, and tri-saccharides are oxidized regioselectively in yields of 75 to 92%. The present method is simple to implement and is also applicable for selective oxidations of other mono- and poly-hydroxy compounds including unprotected and partially protected nucleosides.

Rapid resolution of carbohydrate isomers via multi-site derivatization ion mobility-mass spectrometry.

Identifying small sugar isomers can be challenging by ion mobility-mass spectrometry (IM-MS) alone due to their small collision cross section differences. Herein, we report IM-MS results for multi-site, covalent carbohydrate derivatization with 3-carboxy-5-nitrophenylboronic acid (3C5NBA). Following reaction in aqueous solutions at room temperature, 3C5NBA reacts with each mono- or disaccharide molecule to yield products that each have a distinguishable mobility signature. The reaction was rapid and resulted in the detection of products within 5 min after 3C5NBA was mixed with the analyte. Eight disaccharides that varied in linkage, composition, and configuration (α or ß) as well as four monosaccharides, d-glucose, d-galactose, d-mannose and d-fructose, were included in this study. The derivatives' drift times showed significant shifts, with up to 3-fold gains in resolution when compared to previous literature reports. Moreover, the specific MS/MS fragmentation information gathered from these sugar derivatives provided further validation of the isomers' structures.

Continuous Flow Chemistry: Reaction of Diphenyldiazomethane with p-Nitrobenzoic Acid.

Continuous flow technology has been identified as instrumental for its environmental and economic advantages leveraging superior mixing, heat transfer and cost savings through the "scaling out" strategy as opposed to the traditional "scaling up". Herein, we report the reaction of diphenyldiazomethane with p-nitrobenzoic acid in both batch and flow modes. To effectively transfer the reaction from batch to flow mode, it is essential to first conduct the reaction in batch. As a consequence, the reaction of diphenyldiazomethane was first studied in batch as a function of temperature, reaction time, and concentration to obtain kinetic information and process parameters. The glass flow reactor set-up is described and combines two types of reaction modules with "mixing" and "linear" microstructures. Finally, the reaction of diphenyldiazomethane with p-nitrobenzoic acid was successfully conducted in the flow reactor, with up to 95% conversion of the diphenyldiazomethane in 11 min. This proof of concept reaction aims to provide insight for scientists to consider flow technology's competitiveness, sustainability, and versatility in their research.

Anchimeric-Assisted Spontaneous Hydrolysis of Cyanohydrins Under Ambient Conditions: Implications for Cyanide-Initiated Selective Transformations.

Nitrile/cyanide hydrolysis is of importance from the perspective of organic chemistry, especially, prebiotic chemistry. Herein we report that cyanohydrins, generated by the reaction of cyanide with ß-keto acids and γ-keto-alcohols, spontaneously hydrolyze under ambient conditions (aqueous medium, RT, and a range of pH). The spontaneous hydrolysis is affected by an intramolecular proton transfer and an intramolecular 5-exo-dig attack, but with a twist. In the case of ß-keto acids, the hydrolysis is mediated by the neighboring carboxylic acid group only at pH values less than 7, whereas in the case of γ-keto-alcohols the hydrolysis is mediated by the neighboring hydroxyl group only at pH values greater than 7. The results, in combination with previous works, have implications for selective transformations of cyanide-initiated prebiotic systems chemistry.

Aqueous Suzuki Coupling Reactions of Basic Nitrogen-Containing Substrates in the Absence of Added Base and Ligand: Observation of High Yields under Acidic Conditions.

A series of aqueous heterogeneous Suzuki coupling reactions of substrates containing basic nitrogen centers with phenylboronic acid in the absence of added base and ligand is presented. High yields of products were obtained by employing aryl bromides containing aliphatic 1°, 2°, and 3° amine substituents, and good to high yields were obtained by employing a variety of substituted bromopyridines. In the former series, the pH of the aqueous phase changed from basic to acidic during the course of the reaction, while in the latter series the aqueous phase was on the acidic side of the pH scale throughout the entire course of reaction. A mechanistic interpretation for these observations, which generally preserves the oxo palladium catalytic cycle widely accepted in the literature, is presented.

Nucleoside phosphorylation by the mineral schreibersite.

Phosphorylation of the nucleosides adenosine and uridine by the simple mixing and mild heating of aqueous solutions of the organic compounds with synthetic analogs of the meteoritic mineral schreibersite, (Fe,Ni)3P under slightly basic conditions (pH ~9) is reported. These results suggest a potential role for meteoritic phosphorus in the origin and development of early life.

The effects of CO2 pressure and pH on the Suzuki coupling of basic nitrogen containing substrates.

The Suzuki coupling reaction of basic nitrogen containing substrates (2-bromo- and 2-chloro-4-aminopyridine, and 2-bromo and 2-chloropyridine) with phenylboronic acid using Pd(TPP)2Cl2/K3PO4 in acetonitrile-water biphasic solvent systems under a CO2 or a N2 atmosphere is discussed. It was observed that 2-halo-4-aminopyridine produced quantitative yields of coupled products under a CO2 atmosphere while the yields for the 2-halopyridines were poor. In contrast, the yields of coupled products for the 2-halopyridines substrates were quantitative under a N2 atmosphere while only poor yields were realized for the 2-halo-4-aminopyridines under the same conditions. Evidence is presented which suggests that the presence of CO2 alters the pH of the aqueous phase of the reaction system and the accompanying efficiency of the coupling process. Using a series of buffers to adjust the pH of the aqueous phase, the pH dependence associated with the efficiency of the coupling process is illustrated.

High-pressure sapphire cell for phase equilibria measurements of CO2/organic/water systems.

The high pressure sapphire cell apparatus was constructed to visually determine the composition of multiphase systems without physical sampling. Specifically, the sapphire cell enables visual data collection from multiple loadings to solve a set of material balances to precisely determine phase composition. Ternary phase diagrams can then be established to determine the proportion of each component in each phase at a given condition. In principle, any ternary system can be studied although ternary systems (gas-liquid-liquid) are the specific examples discussed herein. For instance, the ternary THF-Water-CO2 system was studied at 25 and 40 °C and is described herein. Of key importance, this technique does not require sampling. Circumventing the possible disturbance of the system equilibrium upon sampling, inherent measurement errors, and technical difficulties of physically sampling under pressure is a significant benefit of this technique. Perhaps as important, the sapphire cell also enables the direct visual observation of the phase behavior. In fact, as the CO2 pressure is increased, the homogeneous THF-Water solution phase splits at about 2 MPa. With this technique, it was possible to easily and clearly observe the cloud point and determine the composition of the newly formed phases as a function of pressure. The data acquired with the sapphire cell technique can be used for many applications. In our case, we measured swelling and composition for tunable solvents, like gas-expanded liquids, gas-expanded ionic liquids and Organic Aqueous Tunable Systems (OATS)(1-4). For the latest system, OATS, the high-pressure sapphire cell enabled the study of (1) phase behavior as a function of pressure and temperature, (2) composition of each phase (gas-liquid-liquid) as a function of pressure and temperature and (3) catalyst partitioning in the two liquid phases as a function of pressure and composition. Finally, the sapphire cell is an especially effective tool to gather accurate and reproducible measurements in a timely fashion.

Design, synthesis, and evaluation of nonaqueous silylamines for efficient CO2 capture.

A series of silylated amines have been synthesized for use as reversible ionic liquids in the application of post-combustion carbon capture. We describe a molecular design process aimed at influencing industrially relevant carbon capture properties, such as viscosity, temperature of reversal, and enthalpy of regeneration, while maximizing the overall CO2 -capture capacity. A strong structure-property relationship among the silylamines is demonstrated in which minor structural modifications lead to significant changes in the bulk properties of the reversible ionic liquid formed from reaction with CO2 .

Production of tartrates by cyanide-mediated dimerization of glyoxylate: a potential abiotic pathway to the citric acid cycle.

An abiotic formation of meso- and DL-tartrates in 80% yield via the cyanide-catalyzed dimerization of glyoxylate under alkaline conditions is demonstrated. A detailed mechanism for this conversion is proposed, supported by NMR evidence and (13)C-labeled reactions. Simple dehydration of tartrates to oxaloacetate and an ensuing decarboxylation to form pyruvate are known processes that provide a ready feedstock for entry into the citric acid cycle. While glyoxylate and high hydroxide concentration are atypical in the prebiotic literature, there is evidence for natural, abiotic availability of each. It is proposed that this availability, coupled with the remarkable efficiency of tartrate production from glyoxylate, merits consideration of an alternative prebiotic pathway for providing constituents of the citric acid cycle.