Carbonic Anhydrase Activity Research Articles

Discovery of the First-in-Class Dual TSPO/Carbonic Anhydrase Modulators with Promising Neurotrophic Activity.

In searching for putative new therapeutic strategies to treat neurodegenerative diseases, the mitochondrial 18 kDa translocator protein (TSPO) and cerebral isoforms of carbonic anhydrase (CA) were exploited as potential targets. Based on the structures of a class of highly affine and selective TSPO ligands and a class of CA activators, both developed by us in recent years, a small library of 2-phenylindole-based dual TSPO/CA modulators was developed, able to bind TSPO and activate CA VII in the low micromolar/submicromolar range. The interaction with the two targets was corroborated by computational studies. Biological investigation on human microglia C20 cells identified derivative 3 as a promising lead compound worthy of future optimization due to its (i) lack of cytotoxicity, (ii) ability to stimulate TSPO steroidogenic function and activate CA VII, and (iii) ability to effectively upregulate gene expression of the brain-derived neurotrophic factor.

Unveiling tomorrow: Carbonic anhydrase activators and inhibitors pioneering new frontiers in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder and a principal basis of dementia in the elderly population globally. Recently, human carbonic anhydrases (hCAs, EC 4.2.1.1) were demonstrated as possible new targets for treating AD. hCAs are vital for maintaining pH balance and performing other physiological processes as they catalyze the reversible hydration of carbon dioxide to bicarbonate and a proton. Current research indicates that hCA plays a role in brain functions critical for transmitting neural signals. Activation of carbonic anhydrase (CA) has emerged as a promising avenue in addressing memory loss and cognitive issues. Conversely, the exploration of CA inhibition represents a novel frontier in this field. By enhancing glial fitness and cerebrovascular health and blocking amyloid-β (Aβ)-induced mitochondrial dysfunction pathways, cytochrome C (CytC) release, caspase 9 activation, and H2O2 generation in neurons, CA inhibitors improve cognition and lessen the pathology caused by Aβ. Recent research has pushed hCAs into the spotlight as critical players in AD pathogenesis and precise therapeutic targets. The captivating dilemma of choosing between hCA inhibitors and activators looms large, as inhibitors reduce Aβ aggregation and improve cerebral blood flow, while activators enhance cerebrovascular functions and restore pH balance. The current review sheds light on the clinical evidence for hCAs and the roles of inhibitors and activators in AD. Additionally, this review offers a fascinating outlook on the data that may aid medicinal chemists in designing and developing new leads that are more effective and selective for upcoming in vitro and in vivo studies, allowing for the discovery and introduction of novel drug candidates for the treatment of AD to the market and into the clinical pipeline.

Carbonic anhydrase activity and metabolite variation of different microalgae species at alkaline pHs

A significant increase in atmospheric greenhouse gases over the last century has led to the development of several methods and technologies to remove carbon dioxide (CO2). Microorganisms produce carbonate minerals through the natural mineralization of CO2; however, the feasibility of this process remains in research. This work aimed to study the cultivation of different microalgae under alkaline pH to maintain their potential for carbon mitigation. According to the results, the highest carbonic anhydrase activity has been reached (4.64 mg/g) for Chlamydomonas reinhardtii at a pH of 10. C. reinhardtii, at a pH of 9.5, yielded the highest chlorophyll content (23.58 mg/g), while Spirulina at a pH of 8.5 produced the highest biomass (882.9 mg/L). Also, a positive correlation existed between pH and lipid content for C. reinhardtii. Spirulina, however, exhibits the opposite effect. According to a principal component analysis, there is an opposite relationship between pH and carbonic anhydrase (CA) activity for C. reinhardtii and filamentous-type cyanobacteria from Salda Lake. The following order of the suitability of the microalgae species for high carbon capture is determined by the Analytic hierarchy process method: Spirulina>C. reinhardtii > Chlorella vulgaris > Coccus-type cyanobacteria > Filamentous-type cyanobacteria from Salda Lake. Additionally, this study provided important results regarding the cyanobacteria species isolated from an alkaline lake, Lake Salda. This would contribute to future studies of carbon capture and carbon mitigation mechanisms.

Design, synthesis of antipyrine-based Schiff bases and investigation of their cholinesterase and carbonic anhydrase activities by in vitro and in silico approaches

In this study, a series of antipyrine-based Schiff bases (1-10) was designed, synthesized, and evaluated as potential inhibitors of various metabolic enzymes, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human erythrocyte carbonic anhydrase I and II (hCA I and hCA II). The target molecules were characterized by UV-Vis, FT-IR, 1H NMR, 13CNMR, LC-HRMS, and elemental analysis. All tested derivatives demonstrated low nanomolar inhibition with Ki values of in the range of 20.58 ± 0.35 to 53.11 ± 1.02 nM against AChE, 21.84 ± 0.40 to 54.41 ± 1.05 nM against BChE, 27.45 ± 0.41 to 48.22 ± 0.91 nM against cytosolic hCA I isoform associated with epilepsy, and 6.02 ± 0.11 to 29.32 ± 0.54 nM against cytosolic hCA II isoform associated with glaucoma. In general, most these molecules, except for a few, inhibited these enzymes more than acetazolamide (AZA) and neostigmine. Among them, compounds 5, 7, 8, and 9 showed the best inhibitory activities against AChE, BChE, hCA I, and hCA II, respectively. Docking results were calculated for the compounds that showed the best inhibitory activity against these enzymes and for reference compounds. Based on the molecular docking results, they were determined to have high binding energies, including hydrogen bonds, electrostatic interactions, and hydrophobic interactions. Absorption, distribution, metabolism, and excretion (ADME) parameters determined that all the synthesized pyrazolone ring-bearing Schif base derivatives (1-10) have the expected physicochemical properties in terms of drug-likeness and can be evaluated as orally active potential. Properties such as the electrophilicity index and chemical hardness were also investigated by density functional theory (DFT) at the B3LYP/6-311G** level of theory.

Novel three-stage microalgal cultivation system for lipid production utilizing nutrients derived from refinery waste

The pollution and transformation of refineries are receiving increasing attention. The carbonic anhydrase in Tetradesmus obliquus was found exhibiting a hysteresis phenomenon in response to periodic changes in the composition of external carbon sources, with a surge in inorganic carbon concentration stressing the carbonic anhydrase activity to increase by 6–9 times. On this basis, a novel three-stage culture system of T. obliquus was proposed, which mainly uses refinery waste as the nutrients. By controlling the nutrient content in the environment, especially the composition of carbon sources, microalgae could sequentially complete rapid biomass accumulation, efficient inorganic carbon assimilation, and oil production. Compared to a single-environment culture system, the biomass yield increased by 1.34 times, the oil content increased by more than 6%, and the oil productivity increased by 2.08 times. Above findings may lay a partial theoretical foundation for the future evolution of traditional refineries towards “fossil–algal-biomass” hybrid refineries.

Response of nitrifiers to gradually increasing pH conditions in a membrane nitrification bioreactor: Microbial dynamics and alkali-resistant mechanism

Nitrification and nitrifiers are pH-sensitive especially under the alkaline environment in the activated sludge system. However, it is unclear how nitrifiers and nitrification respond to long-term alkaline environment. This study employed a continuous flow membrane nitrification bioreactor to investigate the dynamics of nitrification efficiency and microbial community adaptation under a 320-day alkaline operation. Results showed that activated sludge adapted remarkably to a progressive increase in pH from 7.5 to 10.0, achieving robust nitrification with average ammonia removal efficiencies of 96.6 ± 2.2%. Subsequently, an integrated alkali-resistant mechanism of nitrifiers was proposed. Specifically, under the long-term operation of pH 10.0, certain bacteria secreted enhanced extracellular acidic polysaccharides (i.e., up to 10.95 ± 0.27 mg·g−1 MLVSS in soluble extracellular polymeric substances (EPS)) and acidic organic compounds (e.g., humic acids increased by 1.47-fold in tightly bounded EPS) to neutralize external alkalinity. Moreover, significant enrichments in both the ammonia oxidizing bacteria Nitrosomonas (by 1.3%) and the nitrite oxidizing bacteria Nitrospira (by 5.4%) were observed in a 170-day operation of pH 10.0 condition. Meanwhile, norank_f__JG30-KF-CM45 (2.0%) and Rhodobacter (0.9%) also contributed to ammonia removal at pH 10.0. On the cellular-level, bacteria enabled to maintain intracellular pH stabilization primarily through cation/proton antiporters, evidenced by significant increases in NhaA, TrkA and KefB activities by 98.0%, 151.7% and 115.2%, respectively. A 43.1% increase in carbonic anhydrase activity also facilitated consumption of aqueous OH− ions through biomineralization, leading to CaCO3 deposition on microbial surface. These findings further enhanced understandings of physiological adaptation of nitrifiers in the long-term alkaline activated sludge system.

The physiological significance of plasma-accessible carbonic anhydrase in the respiratory systems of fishes.

Carbonic anhydrase (CA) activity is ubiquitously found in all vertebrate species, tissues and cellular compartments. Most species have plasma-accessible CA (paCA) isoforms at the respiratory surfaces, where the enzyme catalyzes the conversion of plasma bicarbonate to carbon dioxide (CO2) that can be excreted by diffusion. A notable exception are the teleost fishes that appear to lack paCA at their gills. The present review: (i) recapitulates the significance of CA activity and distribution in vertebrates; (ii) summarizes the current evidence for the presence or absence of paCA at the gills of fishes, from the basal cyclostomes to the derived teleosts and extremophiles such as the Antarctic icefishes; (iii) explores the contribution of paCA to organismal CO2 excretion in fishes; and (iv) the functional significance of its absence at the gills, for the specialized system of O2 transport in most teleosts; (v) outlines the multiplicity and isoform distribution of membrane-associated CAs in fishes and methodologies to determine their plasma-accessible orientation; and (vi) sketches a tentative time line for the evolutionary dynamics of branchial paCA distribution in the major groups of fishes. Finally, this review highlights current gaps in the knowledge on branchial paCA function and provides recommendations for future work.

Enhanced Recognition Memory through Dual Modulation of Brain Carbonic Anhydrases and Cholinesterases.

This study introduces a novel multitargeting strategy that combines carbonic anhydrase (CA) activators and cholinesterase (ChE) inhibitors to enhance cognitive functions. A series of tacrine-based derivatives with amine/amino acid moieties were synthesized and evaluated for their dual activity on brain CA isoforms and ChEs (AChE and BChE). Several derivatives, notably compounds 26, 30, 34, and 40, demonstrated potent CA activation, particularly of hCA II and VII, and strong ChE inhibition with subnanomolar to low nanomolar IC50 values. In vivo studies using a mouse model of social recognition memory showed that these derivatives significantly improved memory consolidation at doses 10-100 times lower than the reference compounds (either alone or in combination). Molecular modeling and ADMET predictions elucidated the compound binding modes and confirmed favorable pharmacokinetic and safety profiles. The findings suggest that dual modulation of CA and ChE activities is a promising strategy for treating cognitive deficits associated with neurodegenerative and psychiatric disorders.

Comparative study of stability and activity of wild-type and mutant human carbonic anhydrase II enzymes using molecular dynamics and docking simulations

The human carbonic anhydrase II (HCA II) enzyme is a cytosolic protein that catalyzes the reversible hydration of carbon dioxide (CO2). Considering the critical role of the HCA II and the effects of some mutations on the activity and stability of the enzyme in humans, several computational methods are used to study the structure and dynamics of the wild-type and the mutant enzymes with three ligands, CO2, 4-nitrophenyl acetate and acetazolamide. Our results of MD simulation of a wild-type enzyme with 4-nitrophenyl acetate show that it created essential effects on the fluctuation of this enzyme and made it more unstable and less compact than the same enzyme without ligand. In the MD of the mutant enzyme with 4-nitrophenyl acetate ligand, no significant difference is observed between with and without ligand. The affinity of the wild-type enzyme to the 4-nitrophenyl acetate is notably higher than the mutant enzyme with the same ligand. Furthermore, results showed that wild-type and mutant enzymes with CO2 are more favorable in stability and flexibility than the same enzymes without ligand. The MD results of wild-type with acetazolamide indicate instability compare without ligand, but in MD of mutant enzyme with acetazolamide show that it more stable and compact than the same enzyme without ligand. Finally, Comparing protein trajectories to assess the impact of ligands on the stability and activity of HCA II enzymes can have medical applications and can in the engineering and design of new variants of carbonic anhydrase enzyme.

Structure based exploration of mitochondrial alpha carbonic anhydrase inhibitors as potential leads for anti-obesity drug development.

Obesity has emerged as a major health challenge globally in the last two decades. Dysregulated fatty acid metabolism and de novo lipogenesis are prime causes for obesity development which ultimately trigger other co-morbid pathological conditions thereby risking life longevity. Fatty acid metabolism and de novo lipogenesis involve several biochemical steps both in cytosol and mitochondria. Reportedly, the high catalytically active mitochondrial carbonic anhydrases (CAVA/CAVB) regulate the intercellular depot of bicarbonate ions and catalyze the rapid carboxylation of pyruvate and acetyl-co-A to acetyl-co-A and malonate respectively, which are the precursors of fatty acid synthesis and lipogenesis. Several in vitro and in vivo investigations indicate inhibition of mitochondrial carbonic anhydrase isoforms interfere in the functioning of pyruvate, fatty acid and succinate pathways. Targeting of mitochondrial carbonic anhydrase isoforms (CAVA/CAVB) could thereby modulate gluconeogenetic as well as lipogenetic pathways and pave way for designing of novel leads in the development pipeline of anti-obesity medications. The present review unveils a diverse chemical space including synthetic sulphonamides, sulphamates, sulfamides and many natural bioactive molecules which selectively inhibit the mitochondrial isoform CAVA/CAVB with an emphasis on major state-of-art drug design strategies. More than 60% similarity in the structural framework of the carbonic anhydrase isoforms has converged the drug design methods towards the development of isoform selective chemotypes. While the benzene sulphonamide derivatives selectively inhibit CAVA/CAVB in low nanomolar ranges depending on the substitutions on the phenyl ring, the sulpamates and sulpamides potently inhibit CAVB. The virtual screening and drug repurposing methods have also explored many non-sulphonamide chemical scaffolds which can potently inhibit CAVA. The review could pave way for the development of novel and effective anti-obesity drugs which can modulate the energy metabolism.

Preparation and characterization of chitosan nanoparticles with extracts of Rheum ribes, evaluation of biological activities of extracts and extract loaded nanoparticles

The biological activities of different parts of the Rheum ribes plant were evaluated comparatively. Extracts showing strong biological activity were identified and it was determined which of the extract-loaded nanoparticles showed stronger activity. Cytotoxic activity of R. ribes extracts was calculated on glial (C6) and fibroblast (NIH 3T3) cells using XTT assay. Spectrophotometry was used to evaluate the impact of these compounds on the enzyme activities of human carbonic anhydrase I and II (hCA I and hCA II). The findings showed that chitosan NPs with extracts loaded on them have a lower IC50 value and more cytotoxic activity in C6 cells than chitosan NPs with only extracts. R. ribes young shoots ultrasonic methanol extract (RYU) was shown to have the strongest antiproliferative efficacy against C6 cells. Results showed that RYU and ultrasonic methanol extract of R. ribes radix (RRU) were determined as the best carbonic anhydrase inhibitors. According to results of particle size, encapsulation efficiency, and release studies of chitosan NPs, it has been observed that they are suitable for application. At a concentration of 10 µg/mL, it was found that none of the R. ribes extracts exhibited cytotoxic action toward the NIH 3T3 cell line. According to results of particle size, encapsulation efficiency, and release studies of chitosan NPs, it has been observed that they are suitable for application. It was observed that none of the extracts of R. ribes at a concentration of 10 µg/mL showed cytotoxic activity in the NIH 3T3 cell line.

Interaction of Micro- and Nanoplastics with Enzymes: The Case of Carbonic Anhydrase.

Microplastics (MPs) and nanoplastics (NPs) have emerged as significant environmental pollutants with potential detrimental effects on ecosystems and human health. Several studies indicate their interaction with enzymes; this topic represents a multifaceted research field encompassing several areas of interest from the toxicological and ecotoxicological impact of MPs and NPs on humans and wildlife to the biodegradation of plastics by microbial enzymes. This review aims to provide a critical analysis of the state-of-the-art knowledge of the interaction of MPs and NPs on the enzyme carbonic anhydrase (CA), providing recent insights, analyzing the knowledge gaps in the field, and drawing future perspectives of the research and its application. CA is a widespread and crucial enzyme in various organisms; it is critical for various physiological processes in animals, plants, and bacteria. It catalyzes the reversible hydration of CO2, which is essential for respiration, acid-base balance, pH homeostasis, ion transport, calcification, and photosynthesis. Studies demonstrate that MPs and NPs can inhibit CA activity with mechanisms including adsorption to the enzyme surface and subsequent conformational changes. In vitro and in silico studies highlight the role of electrostatic and hydrophobic interactions in these processes. In vivo studies present mixed results, which are influenced by factors like particle type, size, concentration, and organism type. Moreover, the potentiality of the esterase activity of CA for plastic degradation is discussed. The complexity of the interaction between CA and MPs/NPs underscores the need for further research to fully understand the ecological and health impacts of MPs and NPs on CA activity and expression and glimpses of the potentiality and perspectives in this field.

Investigating Active Site Binding of Ligands to High and Low Activity Carbonic Anhydrase Enzymes Using Native Mass Spectrometry.

Carbonic anhydrases (CAs) are a family of enzymes that play an important pH regulatory role in health and disease. While different CA isozymes have a high degree of structural similarity, they have variable enzymatic activity, with CA III being the least active and having less than 1% of the activity of CA II, the most active. Furthermore, ligand binding studies for CA III are limited, and a resulting lack of chemical probes impedes understanding of this CA isozyme in comparison to other CA family members where studies are abundant. Therefore, we employed native mass spectrometry (nMS), also known as intact mass spectrometry, to assess ligand binding to CA II and CA III and discovered two novel compounds that for the first time display strong binding to CA III. We present a new data visualization and quantification tool developed to display native mass spectra as an intuitive stacked heat map representation for rapidly interpreting the results of ligand-protein binding from nMS screening.

Assessing the potential of a genetically modified Parachlorella kessleri-I with low CO2 inducible proteins for enhanced biomass and biofuel productivity

The biological process is one of the promising approaches for CO2 capture and storage. Recently, biological sequestration using microalgae has gained much interest due to its capability to utilize CO2 as a carbon source to generate valorizable biomass. This algal biomass further can be used as a feedstock for bioenergy and different value-added products. Here, we have heterogeneously overexpressed the low CO2 inducible proteins (LCIA & LCIB) from Chlamydomonas reinhardtii in the marine alga Parachlorella kessleri-I. Incorporation of these two genes boosted the endogenous CCM leading to a hybrid system and improved overall carbon acquisition. The combination of these CCM proteins enhanced the supply of inorganic carbon to RuBisCO with positive effects on growth and biomass productivity. Biochemical analyses revealed that the hybrid CCM in P. kessleri-I was characterised by 2- fold higher carbonic anhydrase activity, increased starch, and 2X more lipid yield in comparison to wild type (WT) strain. Moreover, the semi-continuous cultivation of GM strain with supply of 1 % CO2 led to around 60 % rise in the overall biomass productivity. These traits also persisted in scale-up studies leading to 2X more biomass productivity in the GM strain than WT in 100 L PBR. A comparative life-cycle assessment underlines the sustainability of the process of carbon capture and both biofuel and biochar production from P. kessleri-I with a hybrid CCM.

Enhancing Photosynthesis and Plant Productivity through Genetic Modification.

Enhancing crop photosynthesis through genetic engineering technologies offers numerous opportunities to increase plant productivity. Key approaches include optimizing light utilization, increasing cytochrome b6f complex levels, and improving carbon fixation. Modifications to Rubisco and the photosynthetic electron transport chain are central to these strategies. Introducing alternative photorespiratory pathways and enhancing carbonic anhydrase activity can further increase the internal CO2 concentration, thereby improving photosynthetic efficiency. The efficient translocation of photosynthetically produced sugars, which are managed by sucrose transporters, is also critical for plant growth. Additionally, incorporating genes from C4 plants, such as phosphoenolpyruvate carboxylase and NADP-malic enzymes, enhances the CO2 concentration around Rubisco, reducing photorespiration. Targeting microRNAs and transcription factors is vital for increasing photosynthesis and plant productivity, especially under stress conditions. This review highlights potential biological targets, the genetic modifications of which are aimed at improving photosynthesis and increasing plant productivity, thereby determining key areas for future research and development.

Carbonic anhydrase encapsulation using bamboo cellulose scaffolds for efficient CO2 capture and conversion

Utilizing carbonic anhydrase (CA) to catalyze CO2 hydration offers a sustainable and potent approach for carbon capture and utilization. To enhance CA's reusability and stability for successful industrial applications, enzyme immobilization is essential. In this study, delignified bamboo cellulose served as a renewable porous scaffold for immobilizing CA through oxidation-induced cellulose aldehydation followed by Schiff base linkage. The catalytic performance of the resulting immobilized CA was evaluated using both p-NPA hydrolysis and CO2 hydration models. Compared to free CA, immobilization onto the bamboo scaffold increased CA's optimal temperature and pH to approximately 45 °C and 9.0, respectively. Post-immobilization, CA activity demonstrated effective retention (>60 %), with larger scaffold sizes (i.e., 8 mm diameter and 5 mm height) positively impacting this aspect, even surpassing the activity of free CA. Furthermore, immobilized CA exhibited sustained reusability and high stability under thermal treatment and pH fluctuation, retaining >80 % activity even after 5 catalytic cycles. When introduced to microalgae culture, the immobilized CA improved biomass production by ∼16 %, accompanied by enhanced synthesis of essential biomolecules in microalgae. Collectively, the facile and green construction of immobilized CA onto bamboo cellulose block demonstrates great potential for the development of various CA-catalyzed CO2 conversion and utilization technologies.

Genetically engineered whole-cell biocatalyst for efficient CO2 capture by cell surface display of carbonic anhydrase from Bacillus cereus GLRT202 on Escherichia coli

CO2 sequestration is important for reducing greenhouse effects. Carbonic anhydrase (CA) from bacteria has a promising role because it can be modified by genetic techniques and bioengineering. In this study, the CA from B. cereus GLRT202 (Bc-CA) was genetically engineered and anchored on the surface of E. coli by using the N-domain of the ice nucleation protein from P. syringae (INPN). Both surface-displayed and cytosolic Bc-CA yielded high expression levels of CA when induced with 0.5 mM IPTG. It exhibited no adverse influence on the host cell growth. Additionally, surface-displayed Bc-CA enhanced its stability and specificity compared to cytosolic expressed Bc-CA. The CA activity of whole-cell surface-displayed cells was 1.66-fold higher (5.19 U/mL) than that of the cytosolic form. Besides the advantages of higher activity, the whole-cell displaying CA was comparatively stable, with better storage (at 4 ℃) and resting culture stability (at 37 ℃). The whole-cell biocatalyst induced the calcite precipitation, which indicated that the cell facilitated the CO2 capture. XRD, FTIR, and FESEM characterized calcite precipitates thus obtained. This study demonstrates that Bc-CA can be correctly expressed on the E. coli surface through fusion with the INPN. This leads to an effective whole-cell biocatalyst with enhanced stability and specificity of the enzyme for efficient CO2 capture applications.

Biologically driven isotope fractionation in ultrastructurally different shell portions of freshwater pearl mussels (Margaritifera margaritifera): Implications for stream water δ18O reconstructions

AbstractOxygen isotopes in stream water can serve as natural tracers of watershed dynamics. Freshwater pearl mussels provide δ18Owater estimates that overcome temporal and spatial limitations of instrumental records. The reliability of shell‐based δ18Owater reconstructions depends on understanding which shell layer biomineralizes closer to oxygen isotopic equilibrium with ambient water. To determine this, both the (outer) prismatic and (inner) nacreous sublayers of the outer shell layer were sampled. Over 2500 isotope values were obtained from shells collected from the Our River (Luxembourg) and from mussels cultured in tanks at constant temperature and monitored δ18Owater. Calculated δ18Owater from the prismatic portion was in excellent agreement with monitored δ18Owater, while δ18Oshell of the nacreous portion was systematically offset by +0.43‰, overestimating δ18Owater by +0.53‰. Although shell portions were formed simultaneously from the same extrapallial fluid, they underwent different fractionation mechanisms, presumably due to differences in carbonic anhydrase activity catalyzing mineralization processes.

Zinc-based organophyllosilicate nanosheets as novel carbonic anhydrase-like nanozyme for efficient CO2 fixation

The unparalleled catalytic activity of carbonic anhydrases (CAs) towards CO2 hydrolysis can potentially contribute to carbon capture, utilization, and storage technology aimed at global decarbonization; however, the high cost and low stability of CAs significantly limit their practical applications. Recently, the development of robust and effective nanozymes with CA-mimicking activity has been proposed as a promising solution to this challenge. Herein, a novel zinc-based organophyllosilicate (ZnAC) nanozyme with CA-like catalytic activity was synthesized by a facile one-pot sol–gel method for the first time, leading to a Zn-O coordination structure that mimicked the catalytic center fragments of natural CAs, with surface amino groups acting as the affinity sites and proton shuttles. The synergistic effect of the two components on the open surface of the layered structure resulted in excellent CA-like activity with a Michaelis–Menten constant (Km) of 4.071 mM, maximum velocity (Vmax) of 0.220 mM/s, and turnover number (kcat) of 11.213 /s at 25 °C and pH=7.5, which were superior to those of most previously reported CA-like nanozymes. The catalytic performance of ZnAC significantly improved with increasing pH and temperature; furthermore, ZnAC exhibited excellent stability, maintaining high catalytic activity after the exposure to extreme temperatures or pH values, eight reaction cycles, and 30 d of storage. Additionally, ZnAC significantly increased the rate of CO2 hydration and the extent of CO2 mineralization and precipitation. This work proposes a new strategy for designing and constructing efficient CA-like nanozymes, providing valuable insights into the structure–activity relationship and new perspectives for the implementation of CO2 fixation.

New Thiazole Derivatives: Carbonic Anhydrase I–II and Cholinesterase Inhibition Profiles, Molecular Docking Studies

AbstractThiosemicarbazone derivative was obtained by the addition of thiosemicarbazide to 5‐nitro‐thiophene‐2‐carbaldehyde. The addition–cyclization of the 2‐bromoacetophenone derivative to thiosemicarbazone derivative gave the new thiazole derivatives (2 a‐k). Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), antioxidant, and human carbonic anhydrase (hCA) I and II isoform inhibitory activities of the thiazole derivatives 2 a‐k were investigated. The effects of thiazole derivatives on carbonic anhydrase I and II (hCA I–II) isoenzymes were examined in vitro using the esterase method. IC50 values for enzyme inhibition were found to be 2.661–22.712 μM for hCA I and 5.372–26.813 μM for hCA II. All derivatives reduced the activities of carbonic anhydrase I and II isoenzymes and were new potential inhibitor molecule candidates. These compounds were found to have minimal effects on AChE and BChE. The antioxidant properties of the target compounds were determined using DPPH and ferric ion‐chelating assays. In particular, compounds 2 k and 2 h had the highest antioxidant effect in the series with IC50 values of 30.11±0.008 μM and 30.21±0.006 μM, respectively. ADMET properties of the compounds found to be effective were evaluated and their interactions with the enzyme were determined by molecular docking.