Carbonic Anhydride Research Articles

Effect of Brønsted Acids on the Activation of Mixed Anhydride/Mixed Carbonic Anhydride and C-Terminal-Free N-Methylated Peptide Synthesis in a Micro-Flow Reactor.

Amidations employing mixed (carbonic) anhydrides have long been favoured in peptide synthesis because of their cost-effectiveness and less waste generation. Despite their long history, no study has compared the effects of additives on the activation of mixed anhydrides and carbonic anhydrides. In this study, we investigated the amidation of mixed (carbonic) anhydride in the presence of a base and/or Brønsted acids. The use of NMI⋅HCl significantly improved the conversion of the mixed carbonic anhydride, while expediting nucleophilic attacks on the desired carbonyl group. In contrast, in the case of mixed anhydrides, neither the conversion nor the desired nucleophilic attack improved significantly. We developed a C-terminus-free N-methylated peptide synthesis method using mixed carbonic anhydrides in a micro-flow reactor. Fourteen N-alkylated peptides were synthesized in moderate to high yields (55-99 %) without severe racemization (<1 %). Additionally, a significant enhancement in the amidation between mixed carbonic anhydrides and bis-TMS-protected N-methyl amino acids with the inclusion of NMI⋅HCl was observed for the first time. In addition, we observed unexpected C-terminal epimerization of the C-terminus-free N-methyl peptides.

Synthesis of Thermoresponsive, Catechol-Rich Poly(ethylene glycol) Brush Polymers for Attenuating Cellular Oxidative Stress.

Herein, we report a platform to integrate customizable quantities of catechol units into polymers by reacting caffeic acid carbonic anhydride with polymers having pendant amine groups. Brush poly(ethylene glycol)-caffeamide (PEG-CAF) copolymers based on oligo(ethylene glycol)methyl ether methacrylate (OEGMA500) were obtained with a catechol content of approximately 30, 40, and 50 mol % (vs OEGMA content). Owing to the hydrophobicity of the introduced CAF groups, the catechol copolymers exhibited cloud points in the range of 23-46 °C and were used to fabricate thermoresponsive FeIII metal-phenolic network capsules. Polymers with the highest CAF content (50 mol %) proved most effective for attenuating reactive oxygen species levels in vitro, in co-cultured fibroblasts, and breast cancer cells, even in the presence of an exogenous oxidant source. The reported approach to synthesize customizable catechol materials could be generalized to other amine-functional polymers, with potential biomedical applications such as adhesives or stimuli-responsive drug delivery systems.

Mathematical Equations of Thermodynamic Probability of Thermal Decomposition of Ammonia

Annotation: Technical solutions have been developed to create a technology for obtaining calcium cyanamide from lime, carbonate anhydride and industrial ammonia. A technological scheme for obtaining nitrogen fertilizer and an effective defoliant - calcium cyanamide has been developed and the optimal technological parameters of the process at the pilot plant an experimental batch of calcium cyanamide was produced. Keywords: Carbon dioxide, ammonia, expander gas, calcium cyanamide, off-gases.

Isolation and structural characterization of stable carbamic–carbonic anhydrides: an experimental and computational study

Beyond intermediates: isolation, chemical characterization, and computational studies of the first examples of stable carbamic–carbonic anhydrides.

Synthesis of Customizable Macromolecular Conjugates as Building Blocks for Engineering Metal–Phenolic Network Capsules with Tailorable Properties

Metal–phenolic networks (MPNs), formed through coordination bonding between phenolic molecules and metal ions, are a promising class of materials for engineering particle systems for diverse applications. However, the properties of such MPNs are inherently restricted due to the finite properties of naturally occurring phenolic molecules. Herein, we report a simple and robust approach to incorporate phenolic moieties into polymers, thereby providing customizable phenolic ligand building blocks that can be used to assemble capsules with a range of tailorable properties. The phenolic ligand building blocks were synthesized via carbonic anhydride coupling to terminal amines, a conjugation approach typically used for peptide coupling but applied herein for functionalizing polymers. The chemistry enabled optimized end-group purity, thus affording a robust and efficient strategy to generate a library of macromolecular poly(ethylene glycol) (PEG) catechol building blocks with different architectures (i.e., 2-, 4-, and 8-arm) and molecular weights (from 2.5 to 20 kDa). The resulting phenolic building blocks were applied to fabricate capsules with shell thickness, permeability, and cell association properties that were controlled via the variation of the macromolecular catechol architecture and molecular weight. Specifically, the shell thickness was varied more than 19-fold (i.e., between ∼9 and 169 nm) by judicious selection of the polymer molecular weight, arm number, and template. Similarly, the permeability of the resulting MPN capsules to 500 kDa dextran was tuned from >90 to <5% by varying the number of arms in the polymer structure while maintaining a constant PEG Mn-to-catechol group ratio. Furthermore, the cell association was reduced by a factor of 2.5 by employing 20 kDa 8-arm PEG instead of 2.5 kDa 2-arm PEG during film assembly. These results demonstrate that the applied macromolecular conjugation approach can be used to customize particle properties, potentially facilitating applications in therapeutic delivery, imaging, separations, and catalysis.

N-Methylated Peptide Synthesis via Generation of an Acyl N-Methylimidazolium Cation Accelerated by a Brønsted Acid.

The development of a robust amide-bond formation remains a critical aspect of N-methylated peptide synthesis. In this study, we synthesized a variety of dipeptides in high yields, without severe racemization, from equivalent amounts of amino acids. Highly reactive N-methylimidazolium cation species were generated in situ to accelerate the amidation. The key to success was the addition of a strong Brønsted acid. The developed amidation enabled the synthesis of a bulky peptide with a higher yield in a shorter amount of time compared with the results of conventional amidation. In addition, the amidation can be performed by using either a microflow reactor or a conventional flask. The first total synthesis of naturally occurring bulky N-methylated peptides, pterulamides I-IV, was achieved. Based on experimental results and theoretical calculations, we speculated that a Brønsted acid would accelerate the rate-limiting generation of acyl imidazolium cations from mixed carbonic anhydrides.

N‐Methylated Peptide Synthesis via Generation of an Acyl N‐Methylimidazolium Cation Accelerated by a Brønsted Acid

AbstractThe development of a robust amide‐bond formation remains a critical aspect of N‐methylated peptide synthesis. In this study, we synthesized a variety of dipeptides in high yields, without severe racemization, from equivalent amounts of amino acids. Highly reactive N‐methylimidazolium cation species were generated in situ to accelerate the amidation. The key to success was the addition of a strong Brønsted acid. The developed amidation enabled the synthesis of a bulky peptide with a higher yield in a shorter amount of time compared with the results of conventional amidation. In addition, the amidation can be performed by using either a microflow reactor or a conventional flask. The first total synthesis of naturally occurring bulky N‐methylated peptides, pterulamides I–IV, was achieved. Based on experimental results and theoretical calculations, we speculated that a Brønsted acid would accelerate the rate‐limiting generation of acyl imidazolium cations from mixed carbonic anhydrides.

Protection and Activation of Hydroxycinnamic Acids in Water

AbstractHydroxycinnamic acids such as p‐coumaric, ferulic, sinapic and caffeic acids were protected as carbonates and activated as mixed carbonic anhydrides in water at RT by adding a base and isobutyl chloroformate. These anhydrides were used for amine and C‐protected α‐amino acid acylation to give O‐carbonate protected phenolic amides. Acylation of free α‐amino acids was performed in acetone‐water in high yields producing the O‐carbonate protected N‐hydroxycinnamoyl‐α‐amino acids. Pure derivatives were obtained in many cases directly by crystallization. Free phenolic compounds were rapidly obtained by carbonate deprotection with piperidine. The method offers a novel route for amide bond formation in water and the direct functionalization of hydroxycinnamic acid families with free α‐amino acids, providing a facile preparation of precious natural bioactive derivatives.

Analytical method development and validation for the determination of Brinzolamide by RP-HPLC

Brinzolamide is inhibitor of carbonic anhydride and is highly specific and non-competitive. The aim of the present study is to develop a simple, precise, accurate, sensitive RP-HPLC method for the determination of bulk drug. The objective of the method validation is to demonstrate whether the method was suited for the intended purpose. The method was validated as per the ICH guidelines. The method was validated for linearity, precision (repeatability, intermediate precision), accuracy, specificity, robustness, ruggedness, limit of detection and limit of quantification. Cosmosil (4.6X250mm, 5 μ) column was used for separation. The selected wavelength for Brinzolamide was 254 nm. The mobile phase consists of Acetonitrile: Potassium dihydrogen phosphate buffer (40:60). Flow rate was delivered at 1.0 mL/min. Appropriate dilutions of standard stock solutions were prepared to get desired concentrations in the range of 100-500 mcg/ml. The equation od standard curve was y = 441.8x + 1132 and R2 = 0.998. The RT obtained was 6.6167 minutes.&#x0D; Keywords: Brinzolamide, UV spectroscopy, RP-HPLC, ICH

Peptide-Chain Elongation Using Unprotected Amino Acids in a Micro-Flow Reactor.

Conventional peptide synthesis requires a deprotection step after each amidation step, which decreases synthetic efficiency. Therefore, peptide synthesis using unprotected amino acids is considered an ideal approach. Here, we report peptide chain elongation using unprotected amino acids via a mixed carbonic anhydride. Micro-flow technology enabled rapid mixing of an organic layer containing a protected amino acid or dipeptide and an aqueous layer containing an unprotected amino acid or dipeptide to accelerate the desired amidation, and this approach successfully suppressed undesired racemization/epimerization (≤0.4 %). Various di-, tri-, and tetra-peptides were obtained in good to high yields. This is the first report on peptide chain elongation that proceeds without severe racemization from unprotected amino acids using inexpensive, nonexplosive, less wasteful, and less toxic reagents.

Novel zinc compound with thiosemicarbazone of glyoxylic acid: Synthesis, crystal structure, and bioactivity properties

Reaction of zinc nitrate with thiosemicarbazone of glyoxylic acid (H2GAT) leads to the formation of the new complex that have been characterized by spectroscopic methods. Crystal structure of the compound Zn3C18H34N18O17S6 (1) was determined using single crystal X-ray diffraction methods. Single crystal X-ray measurements showed that the complex crystallized in a triclinic system with the space group P-1. The structure of complex 1 presents distorted octahedral geometry around the zinc ion centre. In the crystal structure, Zn(II) ion is coordinated by two nitrogen, two oxygen and two sulfur atoms from two different thiosemicarbazone of glyoxylic acid and two oxygen atoms from two different water molecules. Thermogravimetry shows four steps of decomposition in the temperature range 225–990 °C. This complex was an inhibitor of butyrylcholinesterase (BChE), cytosolic carbonic anhydride I and II isoforms (hCA I and II) and acetylcholinesterase (AChE) enzymes for complex 1 with Ki values of 0.95 ± 0.10 μM for hCA I, 1.54 ± 0.24 μM for hCA II, 25.98 ± 2.44 μM for BChE, 166.21 ± 13.63 μM for α-glycosidase and 18.53 ± 1.36 μM for AChE, respectively.

Mechanism and kinetics of the oxidation of dimethyl carbonate by hydroxyl radical in the atmosphere.

The mechanism and kinetics for the reaction of dimethyl carbonate (DMC) with OH radical have been studied by using quantum chemical methods. Four reaction pathways were identified for the initial reaction. In the first two pathways, hydrogen atom abstraction is taking place and alkyl radical intermediate is formed with the energy barrier of 6.4 and 7.9kcal/mol. In the third pathway, OH addition reaction to the carbonyl carbon (C2) atom of DMC and intermediate, I2, is formed with an energy barrier of 11.9kcal/mol. In the fourth pathway, along with CH3O●, methyl hydrogen carbonate is formed. For this C-O bond breaking and O-H addition reaction, the energy barrier is 27kcal/mol. The calculated enthalpy and Gibbs energy values show that the studied initial reactions are exothermic and exoergic except the OH addition reaction. For the initial reactions, the rate constants were calculated by using canonical variational transition state theory (CVT) with small curvature tunneling (SCT) correction over the temperature range of 278-1200K. At 298K, the calculated rate coefficient for the in-plane and out-of-plane hydrogen atom abstraction reaction pathway is 2.30 × 10-13 and 0.02 × 10-13cm3molecule-1s-1. Further, the reaction between alkyl radical intermediate formed from the first pathway and O2 is studied. The reaction of alkyl peroxy radical intermediate with atmospheric oxidants, HO2, NO, and NO2 is also studied. It was found that the formic (methyl carbonic) anhydride is the end product formed from the atmospheric oxidation and secondary reactions of DMC.

Cover Picture: Anionic Copolymerization of Carbonyl Sulfide with Epoxides via Alkali Metal Alkoxides (Chin. J. Chem. 7/2018)

The cover picture shows a protocol of an anionic copolymerization of carbonyl sulfide (COS) with epoxides via alkali metal alkoxides. COS is an analogue of carbon dioxide (CO2), and can be converted to CO2 via the carbonic anhydride enzymes widely existing in nature. It causes acid rain, ozonosphere damage and haze by a series of photochemical reactions. Very simple and low‐cost alkali metal alkoxides are shown as effective catalysts, affording highly transparent poly(monothiocarbonate)s with 100% alternating degree, &gt;99% tail‐to‐head (T‐H) content, high number‐average molecular weights with narrow molecular weight distributions. This is an environment‐friendly and atom‐economic process for making sulfur‐containing polymers. More details are discussed in the article by Zhang et al. on page 625–629. image

Amino Acids as Building Blocks for Carbonic Anhydrase Inhibitors.

Carbonic anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life, classified into seven genetically different families (α–θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3−) and protons (H+). Fifteen isoforms of human CA (hCA I–XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) have been used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

Anionic Copolymerization of Carbonyl Sulfide with Epoxides via Alkali Metal Alkoxides

AbstractCarbonyl sulfide (COS), an analogue of carbon dioxide (CO2), can be converted to CO2 via the carbonic anhydride enzymes widely existing in nature. COS is an ideal monomer for making poly(monothiocarbonate)s, which are difficult to synthesize by traditional methods. Herein, for the first time, we describe an anionic copolymerization of COS with epoxides using alkali metal alkoxides as the catalysts (initiators), affording poly(monothiocarbonate)s with 100% alternating degree, &gt;99% tail‐to‐head (T‐H) content, high number‐average molecular weights (Mns, up to 90.3 kg/mol) with narrow molecular weight distributions (Đ=Mw/Mn, 1.05—1.31 for COS/propylene oxide copolymers) under solvent‐free and mild conditions. Oxygen‐sulfur exchange reaction (O/S ER), which can result in the production of contaminated dithiocarbonate and carbonate units in the main chain, was nearly completely depressed at 0 oC. In addition, in contrast to previously reported salen chromium (iron) complexes that required multiple synthetic steps, this work provides simple, low‐cost, and effective catalysts for making colorless sulfur‐containing polymers.

HCAII-inspired catalysts for making carbon dioxide-based copolymers: The role of metal-hydroxide bond

The general characteristics of the active center of the catalysts (including zinc-cobalt(III) double metal cyanide complex [Zn-Co(III) DMCC]) for the copolymerization reaction of carbon dioxide (CO2) with epoxide are summarized. By comparing the active center, catalytic performance of the Zn-Co(III) DMCC (and other catalysts) with HCAII enzyme in the organism for activating CO2 (COS and CS2), we proposed that the metal-hydroxide bond (M-OH), which is the real catalytic center of human carbonic anhydride II (HCAII), is also the catalytic (initiating) center for the copolymerization. It accelerates the copolymerization and forms a closed catalytic cycle through the chain transfer reaction to water (and thus strictly meets the definition of the catalyst). In addition, the metal-hydroxide bond catalysis could well explain the oxygen/sulfur exchange reaction (O/S ER) in metal (Zn, Cr)-catalyzed copolymerization of COS (and CS2) with epoxides. Therefore, it is very promising to learn from HCAII enzyme to develop biomimetic catalyst for highly active CO2/epoxide copolymerization in a well-controlled manner under mild conditions.

Adsorption of CO2 on a confined fluidized bed of pelletized 13X zeolite

The paper presents the results of an investigation into CO2 adsorption by a fluidized bed of pellets of 13X zeolite. The experiments compare the performance of a confined and that of a conventional fluidized bed using the same apparatus at ambient temperature and pressure. The effect of CO2 concentration in the inlet air stream, superficial gas velocity and particle size of the fluidized sorbent is analysed with reference to gas streams in which the fraction of carbon anhydride is that typical of a flue gas. The effectiveness of CO2 adsorption is assessed in terms of moles of CO2 adsorbed per unit mass of sorbent, breakthrough time and fraction of bed utilized at the breakpoint. Along with the increase of the adsorbed mass of CO2, it is found that the increment of the breakthrough time is roughly equal to 70%, while the increase of the fraction of bed utilized is always about 30%. Furthermore, in the confined fluidized bed the increase of temperature associated to adsorption is more limited and can be controlled by regulating the superficial gas velocity.The results obtained demonstrate that confined fluidization improves the efficiency of the adsorption process thus constituting a valid alternative to the conventional technique.

Designer Anhydride Clears the Path for Alkoxycarbonylations in Catellani Reactions

In this issue of Chem , Dong and colleagues show that an engineered mixed carboxylate carbonate anhydride serves as an electrophilic trap in palladium/norbornene-catalyzed double functionalization of aryl iodides, enabling the introduction of the synthetically valuable carboxylate moiety in the ortho -position.

One for Many: A Universal Reagent for Acylation Processes

AbstractThis work describes acylation reactions facilitated by a type of heterocycle‐based acyl transfer agent, 2‐acyloxypyridazinone. Reactions of 2‐acyloxypyridazinone with carboxylic acids yield mixed carbonic anhydride intermediates, which are reactive and could be coupled with a wide range of substrates including acids, amines, alcohols, and thiols. The wide substrate scope, ease of operation (no additive or catalyst), storage and handling stability, and atom‐efficiency from recycling the heterocycle carrier make the reported acylating agent attractive for acylation‐based coupling reactions.magnified image

The use of elements of the Stewart model (Strong Ion Approach) for the diagnostics of respiratory acidosis on the basis of the calculation of a value of a modified anion gap (AGm) in brachycephalic dogs.

Apart from the HH equation, the acid-base balance of an organism is also described by the Stewart model, which assumes that the proper insight into the ABB of the organism is given by an analysis of: pCO2, the difference of concentrations of strong cations and anions in the blood serum - SID, and the total concentration of nonvolatile weak acids - Acid total. The notion of an anion gap (AG), or the apparent lack of ions, is closely related to the acid-base balance described according to the HH equation. Its value mainly consists of negatively charged proteins, phosphates, and sulphates in blood. In the human medicine, a modified anion gap is used, which, including the concentration of the protein buffer of blood, is, in fact, the combination of the apparent lack of ions derived from the classic model and the Stewart model. In brachycephalic dogs, respiratory acidosis often occurs, which is caused by an overgrowth of the soft palate, making it impossible for a free air flow and causing an increase in pCO2--carbonic acid anhydride The aim of the present paper was an attempt to answer the question whether, in the case of systemic respiratory acidosis, changes in the concentration of buffering ions can also be seen. The study was carried out on 60 adult dogs of boxer breed in which, on the basis of the results of endoscopic examination, a strong overgrowth of the soft palate requiring a surgical correction was found. For each dog, the value of the anion gap before and after the palate correction procedure was calculated according to the following equation: AG = ([Na+ mmol/l] + [K+ mmol/l])--([Cl- mmol/l]+ [HCO3- mmol/l]) as well as the value of the modified AG--according to the following equation: AGm = calculated AG + 2.5 x (albumins(r)--albumins(d)). The values of AG calculated for the dogs before and after the procedure fell within the limits of the reference values and did not differ significantly whereas the values of AGm calculated for the dogs before and after the procedure differed from each other significantly. 1) On the basis of the values of AGm obtained it should be stated that in spite of finding respiratory acidosis in the examined dogs, changes in ion concentration can also be seen, which, according to the Stewart theory, compensate metabolic ABB disorders 2) In spite of the fact that all the values used for calculation of AGm were within the limits of reference values, the values of AGm in dogs before and after the soft palate correction procedure differed from each other significantly, which proves high sensitivity and usefulness of the AGm calculation as a diagnostic method.