Base Chemistry Research Articles

Imino‐ and Azasugar Protonation Inside Human Acid β‐Glucosidase, the Enzyme that is Defective in Gaucher Disease

AbstractGaucher disease is caused by mutations in human acid β‐glucosidase or glucocerebrosidase (GCase), the enzyme responsible for hydrolysis of glucosyl ceramide in the lysosomes. Imino‐ and azasugars such as 1‐deoxynojirimycin and isofagomine are strong inhibitors of the enzyme and are of interest in pharmacological chaperone therapy of the disease. Despite several crystal structures of the enzyme with the imino‐ and azasugars bound in the active site having been resolved, the actual acid–base chemistry of the binding is not known. In this study we show, using photoinduced electron transfer (PET), that 1‐deoxynojirimycin and isofagomine derivatives are protonated by human acid β‐glucosidase when bound, even if they are completely unprotonated outside the enzyme. While isofagomine derivative protonation to some degree was foreshadowed by earlier crystal structures, 1‐deoxynojirimycin derivatives were not believed to act as basic amines in the enzyme.

Solubilization of silica nanoparticles in alkanes and poly(α‐olefin)s by functionalized polyisobutylene oligomers

AbstractCovalent and noncovalent chemical methods that use oligomeric lipophilic agents to solubilize silica nanoparticles in heptane and poly(α‐olefin) (EPAO) solvents are described. While only modest solubilization efficiencies are seen with an octadecyl group, a variety of terminally functionalized polyisobutylene (PIB) derivatives are more efficient. Both covalent and noncovalent chemistry was found to be effective. Covalent modification solubilized up to 34 wt% of silica nanoparticles (SiNPs) as stable solutions in heptane or PAOs. Noncovalent modification was however more effective, solubilizing up to 70% of SiNPs in heptane or PAOs. The most successful covalent approach used PIB oligomers containing terminal triethoxysilane groups to covalently modify SiNPs. Alternatively, SiNPs that were first functionalized with amine groups could be solubilized in heptane or PAOs with polyisobutylene containing sulfonic acid groups using acid–base chemistry. Studies of these and other solubilization chemistry was also carried out using fluorescent labels, studies that confirmed the gravimetric analyses of the heptane‐solubilized SiNPs. Transmission electron microscopy of a PAO solution of these solutions showed that these SiNPs were present as small aggregates dispersed in the PAOs.

Fluorescent paper-based sensor based on carbon dots for detection of folic acid.

Paper-based devices have been very much in the foreground of analytical science recently. This work innovatively proposed a fluorescent paper-based sensor (FPS) constructed on a hybrid polydimethylsiloxane (PDMS)/paper platform where cellulose papers functionalized with carbon dots (CDs) as fluorophores by Schiff base chemistry were loaded on the grooves array of a designed PDMS plate. As a proof of concept, the performance of FPS was investigated with folic acid (FA) as the target analyte. Under optimal conditions, FPS enabled a rapid fluorescence quenching response to FA via inner filter effect in a wide range of 1-300μmolL-1 with the limit of detection of 0.28μmolL-1. The feasibility of FPS was further verified by the detection of FA in orange juice and urine samples with satisfactory results. The covalent modification of CDs on paper endowed the FPS with good assay reproducibility and stability. Interestingly, FPS achieved a more sensitive assay of FA than the conventional strategy, by which the same CDs were directly used to detect FA in a solution-based system. The FPS illuminated a novel strategy for construction of reliable and sensitive assays based on paper-based devices. It is of paramount importance for its practical application in biosensing and clinical diagnosis. Graphical abstract.

Preparation of nitrogen-containing carbon using a one-step thermal polymerization method for activation of peroxymonosulfate to degrade bisphenol A

Nitrogen-containing carbon materials (NCC-x) are promising metal-free catalysts for activation of peroxymonosulfate (PMS) to treat with aqueous organic pollutants. In this study, NCC-x were synthesized via a facile thermal polymerization method using urea and terephthalaldehyde as precursors. This method was derived from the polymerization method of graphitic carbon nitride (g-C3N4) and the reaction between the precursors was based on Schiff base chemistry. Compared with the synthesis of g-C3N4 using urea as the precursor, formation of a melamine ring was inhibited and the cyano groups were produced in NCC-x during the polymerization process. The obtained NCC-x catalysts had high specific surface areas, many graphite-nitrogen active sites, and high degrees of graphitization, thus exhibiting excellent activities for the degradation of bisphenol A via PMS activation. This study introduces a convenient method to obtain a highly efficient nitrogen-containing carbon PMS activator and the results are useful for the development of bisphenol A treatment by PMS activation using carbon-containing materials.

Making Acids and Bases MORE Basic: Supporting Students’ Conceptualization of Acid–Base Chemistry through a Laboratory Exercise That Connects Molecular-Level Representations to Symbolic Representations and Experimentally Derived Evidence

Acid–base chemistry is an important and challenging topic for virtually all chemistry students. Recent works have focused on conceptually linking molecular and symbolic representations to experimental evidence for many chemical concepts. In this work we describe a laboratory exercise designed to address students’ conceptual challenges regarding acid–base chemistry, particularly with respect to organic acids, titrations, and pKa’s. This work is part of a series of laboratory exercises developed for prehealth students using the MORE (model, observe, reflect, explain) pedagogy. In this lab, students titrated an amino acid with sodium hydroxide according to lab procedures typically used in a prehealth lab. Our work differs from traditional laboratories in the emphasis on connecting molecular-level representations to symbolic representations and experimentally derived evidence. Using this course environment, we sought to understand the ways in which students’ understandings (molecular-level, symbolic, or evidential) are coconstructed or discrete. We further sought to guide students toward connecting these understandings and report on our successes and areas for improvement.

Mono and dinuclear iridium(iii) complexes featuring bis-tridentate coordination and Schiff-base bridging ligands: the beneficial effect of a second metal ion on luminescence.

The synthesis and photophysical properties of a set of iridium(iii) complexes featuring tridentate N^N^O-coordinating ligands are described, of generic structure [Ir(N^C^N-dpyx)(N^N^O-Ln)]+ (n = 1 to 4) (dpyx = 1,3-dipyridyl-4,6-dimethylbenzene). The proligands HLn are Schiff bases synthesised by condensation of salicylaldehydes with N-methyl-hydrazinopyridines: they are able to coordinate to the Ir(iii) via lateral pyridine-N and phenolate-O- atoms and a central hydrazone-N atom; the four examples differ in the substitution pattern within the phenolate ring. The bis-tridentate coordination is confirmed by X-ray diffraction. The complexes are phosphorescent in solution at ambient temperature, with higher quantum yields and longer lifetimes than those of structurally related bis-cyclometallated complexes with an N^N^C-coordinating ligand. Related proligands H2L5 and H2L6 have been prepared from 4,6-bis(1-methyl-hydrazino)pyrimidine. They feature a central pyrimidine and two N^N^O units. They are shown to bind as ditopic, bis-tridentate ligands with two iridium(iii) ions, leading to unprecedented dinuclear complexes of the form [{Ir(N^C^N)}2(O^N^N-N^N^O-Ln)]2+ (n = 5, 6; N^C^N = dpyx or 1,3-dipyridyl-4,6-difluoro-benzene), with an intramolecular IrIr distance of around 6 Å determined crystallographically. Mononuclear analogues [Ir(N^C^N-dpyx)(N^N^O-HLn)]+ have also been isolated. The dinuclear complexes display a well-defined and unusually intense lowest-energy absorption band in the visible region, around 480 nm. They emit much more efficiently than their mononuclear counterparts, even though the emission wavelengths are comparable. Their superior performance appears to be due to an enhancement in the radiative rate constant, affirming conclusions drawn from recent related studies of dinuclear Ir(iii) and Pt(ii) complexes with ditopic, pyrimidine-based cyclometallating ligands.

General method for emulsion polymerization to yield functional terpolymers

Copolymerization methods are used to impart specific, desired functional properties (e.g. mechanical or bioactive) to a material for targeted applications in biomedicine, food and agriculture, consumer products, advanced manufacturing, and more. Many polymerization methods exist to achieve tailored copolymer architectures. Of them, emulsion polymerization offers unique and industrially convenient features that make for easily scalable processes because the synthesis occurs in water and the latexes usually do not need further purification. Because of the breadth of copolymer architectures and thus wide range of potential applications for latexes produced by emulsion polymerization, there is great value in defining general methods for emulsion polymerizations to yield copolymers, including routes for synthesis of functional monomer building blocks, to permit consistency and optimization of these processes. Herein we present a general emulsion polymerization method for synthesis of a copolymer consisting of three functional monomers, suitable for adaptation to alternate base chemistries, curing chemistries, and functional ligands. This protocol includes the synthesis of the functional monomers glycidyl methacrylate-iminodiacetic acid (GMA-IDA) and 4-benzolylphneyl methacrylate (BPM).•Our synthesized copolymer includes a glycidyl methacrylate (GMA) monomer functionalized with a metal-chelating iminodiacetic acid (IDA) ligand, a UV-curable monomer, 4-benzoylphenyl methacrylate (BPM), and an inert hydrophobic monomer, n‑butyl acrylate (BA).•The presented synthesis route demonstrates a general polymerization method that can be modified to copolymerize alternative functional monomers to create multi-functional polymers.

The impact of coupling assessments on conceptual understanding and connection-making in chemical equilibrium and acid–base chemistry

Science educators have developed a variety of assessment techniques to help students connect their scientific knowledge and bridge conceptual gaps. In chemistry, concept maps and creative exercises are the two notable assessments that have been implemented into multiple chemistry courses and indicated promising effects on students’ conceptual learning and connection-making between chemistry concepts. These two assessment techniques were usually implemented individually in research studies. Herein, we employed a quasi-experimental, mixed-methods approach to explore whether combining concept maps and creative exercises would reveal any synergistic effects for student learning of chemical equilibrium and acid–base chemistry in a college general chemistry course. In this study, student perceptions of the use of the two assessments were examined by open-ended surveys. Interestingly, students perceived creative exercises as an assessment technique while concept maps were viewed as a learning tool for studying or reviewing exams. Additionally, Students believed that concept maps assisted them in answering creative exercises, but not vice versa. The four study groups (control group, concept maps only, creative exercises only, and both concept maps and creative exercises) were compared through concept inventory pre and post-test questions. The results of an ANCOVA indicated that participation in the experimental groups did not significantly impact conceptual learning gains, as measured by the concept inventory post-test scores. However, focus group interviews indicated students from the experimental group that used both concept maps and creative exercises were able to provide more sophisticated scientific explanations for conceptual questions related to the topics of chemical equilibrium and acid–base chemistry. Implications of these research results, best practices for implementation of the two assessments, and future research are discussed.

Acid-base chemistry at the single ion limit.

We present the results of acid–base experiments performed at the single ion (H+ or OH−) limit in ∼6 aL volume nanopores incorporating electrochemical zero-mode waveguides (E-ZMWs). At pH 3 each E-ZMW nanopore contains ca. 3600H+ ions, and application of a negative electrochemical potential to the gold working electrode/optical cladding layer reduces H+ to H2, thereby depleting H+ and increasing the local pH within the nanopore. The change in pH was quantified by tracking the intensity of fluorescein, a pH-responsive fluorophore whose intensity increases with pH. This behavior was translated to the single ion limit by changing the initial pH of the electrolyte solution to pH 6, at which the average pore occupancy 〈n〉pore ∼3.6H+/nanopore. Application of an electrochemical potential sufficiently negative to change the local pH to pH 7 reduces the proton nanopore occupancy to 〈n〉pore ∼0.36H+/nanopore, demonstrating that the approach is sensitive to single H+ manipulations, as evidenced by clear potential-dependent changes in fluorescein emission intensity. In addition, at high overpotential, the observed fluorescence intensity exceeded the value predicted from the fluorescence intensity-pH calibration, an observation attributed to the nucleation of H2 nanobubbles as confirmed both by calculations and the behavior of non-pH responsive Alexa 488 fluorophore. Apart from enhancing fundamental understanding, the approach described here opens the door to applications requiring ultrasensitive ion sensing, based on the optical detection of H+ population at the single ion limit.

Identifying the Lewis Base Chemistry in Preventing the Deposition of Metal Oxides on Ketone-Enriched Carbon Cathodes for Highly Durable Metal-Air Batteries.

Metal-air batteries have exhibited unlimited potential and economic value because of their considerably high energy density. However, under repeated cycling, air cathodes undergo a well-known problem, the deposition of metal oxide, clogging the active surface and ultimately leading to the severe degradation of the cyclic performance. Herein, we address this challenge in a zinc-air battery by introducing ketone as the Lewis base into the air catalyst. As illustrated by in situ X-ray diffraction observations, the ketone-enriched material could generate an ultrahigh negative potential to prevent the access of negatively charged zincate ions and thus enable the nondeposition of zinc oxide on the air cathode because of the strong electrostatic repulsion. Using this strategy, we demonstrate 650 highly stable cycles of a zinc-air battery under a high rate (25 mA cm-2). Such a Lewis-base-assisted method opens up new avenues to prevent air cathodes from being poisoned for highly durable metal-air batteries.

Synthesis and electronic structure study on CsPbBr3 nanoplatelets: Thickness manipulation using surface ligands

Cesium Lead Halide based Perovskites have received significant attention due to their potential application in all inorganic solar cells. To date, there is only limited literature on their anisotropic nanostructures. Here, we report synthesis of 2D nanostructures of CsPbBr3 with thickness of few monolayers (MLs). Due to size quantization, the 2D nanostructure showed a blue shifted absorption from bulk absorption. We manipulate acid: amine (capping agents) ratios to achieve a monolayer level thickness control as evidenced by absorption spectroscopy and TEM analysis. The thickness of 1 ML-4 ML could be seamlessly controlled by varying the ratio. The study shows rich solution phase reaction dynamics during growth with size evolution over time. Additionally, we also compute band structure to validate the effect of size quantization on electronic structure for NPLs investigated. This study opens up possibility of synthesis of these nanostructures with good reaction control over growth of NPLs and also sheds light on complex acid base chemistry that exists in reaction.

Advances and challenges in modeling solvated reaction mechanisms for renewable fuels and chemicals

AbstractWe provide a critical overview of progress and challenges in computationally modeling multistep reaction mechanisms relevant for catalysis and electrocatalysis. We first discuss how the chemical and materials space of energetically efficient catalysis can be explored with computational chemistry. Since reactions for renewable energy catalysis can involve acid–base chemistry and/or ions under aqueous conditions, we then summarize how solvation can be modeled with quantum chemistry schemes using implicit, mixed implicit/explicit, and fully explicit solvation modeling. We will discuss the insights (and limitations) of these solvation models primarily through the scope of understanding CO2 reduction reaction mechanisms, but these will also be applicable for future work elucidating other reaction mechanisms of critical importance for human sustainability such as H2O oxidation and N2 reduction.This article is categorized under: Structure and Mechanism > Reaction Mechanisms and Catalysis

Mitochondrial transcription factor A promotes DNA strand cleavage at abasic sites

In higher eukaryotic cells, mitochondria are essential subcellular organelles for energy production, cell signaling, and the biosynthesis of biomolecules. The mitochondrial DNA (mtDNA) genome is indispensable for mitochondrial function because it encodes protein subunits of the electron transport chain and a full set of transfer and ribosomal RNAs. MtDNA degradation has emerged as an essential quality control measure to maintain mtDNA and to cope with mtDNA damage resulting from endogenous and environmental factors. Among all types of DNA damage known, abasic (AP) sites, sourced from base excision repair and spontaneous base loss, are the most abundant endogenous DNA lesions in cells. In mitochondria, AP sites trigger rapid DNA loss; however, the mechanism and molecular factors involved in the process remain elusive. Herein, we demonstrate that the stability of AP sites is reduced dramatically upon binding to a major mtDNA packaging protein, mitochondrial transcription factor A (TFAM). The half-life of AP lesions within TFAM-DNA complexes is 2 to 3 orders of magnitude shorter than that in free DNA, depending on their position. The TFAM-catalyzed AP-DNA destabilization occurs with nonspecific DNA or mitochondrial light-strand promoter sequence, yielding DNA single-strand breaks and DNA-TFAM cross-links. TFAM-DNA cross-link intermediates prior to the strand scission were also observed upon treating AP-DNA with mitochondrial extracts of human cells. In situ trapping of the reaction intermediates (DNA-TFAM cross-links) revealed that the reaction proceeds via Schiff base chemistry facilitated by lysine residues. Collectively, our data suggest a novel role of TFAM in facilitating the turnover of abasic DNA.

Exceptionally High CO2 Capture in an Amorphous Polymer with Ultramicropores Studied by Positron Annihilation.

A series of amorphous melamine-based polymer networks synthesized by Schiff base chemistry (SNW) were successfully prepared by varying the strut length. The pore structure was analyzed by gas adsorption and positron annihilation methods. Positron lifetime measurements indicate the existence of ultramicropores and also larger mesopores in the SNW materials. The sizes of micropores and mesopores are almost the same in these samples, which are about 0.7 and 16.5 nm, respectively. The relative number of micropores increases in the order of SNW-1 < SNW-2 < SNW-3, while the number of mesopores increases in the reverse order. N2 adsorption/desorption measurements also reveal micropores and mesopores in these materials. However, it gives an underestimation of the micropore volume. Benefiting from the abundant nitrogen content and high microporosity, the SNW materials exhibit exceptionally high CO2 capture ability, which reaches a maximum value of 18.3 wt % in SNW-3 at 273 K and 1 bar, followed by SNW-2 and SNW-1. This order is exactly the same as the order of micropore volume revealed by positron annihilation measurement, suggesting that micropores play a crucial role in the CO2 uptake. Our results show that positron can provide more precise information about the structure of micropores and thus can offer an accurate prediction for the adsorption capacity of complex porous materials.

The effect of base chemistry choice in a generated n‐hexane oxidation model using an automated mechanism generator

AbstractThe present study describes the utilization of a reaction mechanism generator for the development of chemical kinetic models. The aim of the investigation is twofold. The in‐house developed mechanism generator is updated with reaction classes reported in the literature, and the effect of the lower hydrocarbon chemistry, that is, base chemistry, on the generation process is assessed. For this purpose, the algorithm is implemented on two different base chemistry mechanisms, that have previously been validated against a different range of hydrocarbons, that is, the mechanisms of the groups coauthoring the study. n‐Hexane has been used as a modeling target due to its important role in combustion studies as a surrogate for engine and aviation applications. The steps of the generation process are given in detail as this is the first time the current algorithm is utilized. The two generated mechanisms are compared against speciation data, ignition delay times, and flame velocities from the literature. The overall agreement of the generated mechanisms is satisfying; discrepancies exist in the negative temperature coefficient regime. Reaction path analysis and sensitivity analysis were performed, revealing the reactions that cause the different mechanism performance. Among others, the study reveals that the generated schemes pose a fast and adequate alternative to literature mechanisms; it is however evident that the latter may include more detailed reaction paths and are therefore superior in terms of validation.

Coupling of Surface Chemistry and Electric Double Layer at TiO2 Electrochemical Interfaces

Surfaces of metal oxides at working conditions are usually electrified because of the acid-base chemistry. The charged interface compensated with counterions forms the so-called electric double layer. The coupling of surface chemistry and the electric double layer is considered to be crucial but is poorly understood because of the lack of information at the atomistic scale. Here, we used the latest development in density functional theory-based finite-field molecular dynamics simulation to investigate the pH dependence of the Helmholtz capacitance at electrified rutile TiO2(110)-NaCl electrolyte interfaces. It is found that, because of competing forces from surface adsorption and from the electric double layer, water molecules have a stronger structural fluctuation at high pH, and this leads to a much larger capacitance. It is also seen that interfacial proton transfers at low pH increase significantly the capacitance value. These findings elucidate the microscopic origin of the same trend observed in titration experiments.

Evidence-based guidelines for controlling pH in mammalian live-cell culture systems

A fundamental variable in culture medium is its pH, which must be controlled by an appropriately formulated buffering regime, since biological processes are exquisitely sensitive to acid–base chemistry. Although awareness of the importance of pH is fostered early in the training of researchers, there are no consensus guidelines for best practice in managing pH in cell cultures, and reporting standards relating to pH are typically inadequate. Furthermore, many laboratories adopt bespoke approaches to controlling pH, some of which inadvertently produce artefacts that increase noise, compromise reproducibility or lead to the misinterpretation of data. Here, we use real-time measurements of medium pH and intracellular pH under live-cell culture conditions to describe the effects of various buffering regimes, including physiological CO2/HCO3− and non-volatile buffers (e.g. HEPES). We highlight those cases that result in poor control, non-intuitive outcomes and erroneous inferences. To improve data reproducibility, we propose guidelines for controlling pH in culture systems.

General and Greener Synthesis of Diverse Functional Organic Salts through Schiff Base Chemistry

We report a greener and more-general organic method for the synthesis of functional organic salts containing organic anions through a Schiff base reaction between readily available aldehydes and simple aminoguanidinium salts. This reaction is operationally simple, free of metal salts, and forms water as the sole byproduct. The broad scope and good functional-group compatibility of this method permit its use to provide ready access to a library of more than 70 distinct organic salts, including those of heterocyclic anions, complex pharmaceutical anions, and polyanions, which are difficult to obtain through classical inorganic methods. Moreover, choosing different aldehydes and organic anions provides a convenient method for modulating or improving the functional properties of the designed organic salts, such as their melting points, fluorescence, and energetic properties. We therefore expect that this method will open new opportunities for the discovery and functionalization of a wide variety of organic salts and functional materials.

Phenothiazine-Based Hole-Transporting Materials toward Eco-friendly Perovskite Solar Cells

Organic hole-transporting materials (HTMs), AZO-I and AZO-II, were synthesized via Schiff base chemistry by functionalizing a phenothiazine core with triarylamine(s) through azomethine bridges. Substantial enhancements in the power conversion efficiency (PCE = 12.6% and 14% for AZO-I and AZO-II, respectively) and stability (68% or 91% of PCE retained after 60 days for AZO-I or AZO-II, respectively) of perovskite solar cells (PSCs) were achieved when switching from mono- (AZO-I) to disubstituted (AZO-II) HTMs. The extremely low production costs (9 and 12 $/g for AZO-I and AZO-II, respectively), together with the Pd-catalyst-free synthesis, make these materials excellent candidates for low-cost and eco-friendly PSCs.

Acid–Base Chemistry of Porphyrin/Graphene Oxide Complex: Role of Electrostatic Interaction

The acid–base chemistry of cationic 5,10,15,20‐tetrakis(1‐methyl‐4‐pyridinio)porphyrin (TMPyP) and graphene oxide (GO) complex was studied in aqueous solution using absorption and fluorescence spectroscopy. By varying the pH from 0 to 13, we controlled the electrostatic properties of TMPyP and/or GO. The neutrality on GO or negative charge on TMPyP induced the dissociation of the TMPyP/GO complex, indicating that the electrostatic attractive force is indispensable for both forming and preserving the complex. Furthermore, our results suggest that the molecular flattening of the TMPyP in the TMPyP/GO complex is mainly caused by the π–π interaction.