Bond Synthesis Research Articles

Development of the esterase PestE for amide bond synthesis under aqueous conditions: Enzyme cascades for converting waste PET into tamibarotene.

A growing number of hydrolase enzymes show promiscuous acyltransferase activity, even under aqueous conditions. Here we report, for the first time, the ability of Pyrobaculum calidifontis VA1 esterase (PestE) to catalyse the formation of a wide range of amides in buffer, where the acyl donor forms a significant structural component in the amide product. The reactions occur under mild conditions and can achieve conversions up to 97% in 6 h for formation of N-benzylfuranamide as the model reaction. We demonstrate PestE's potential in enzyme cascades to make amides from waste PET plastic and the conversion of the terephthalic acid product to tamibarotene, a drug with activity against acute leukemia. Rational mutagenesis led to identification of PestE variants F33L_F289A and F33L. F33L_F289A increased conversion of N-benzylfuranamide by 1.2-fold, and F33L gave a 4-fold increase in conversion to tamibarotene.

Development of the esterase PestE for amide bond synthesis under aqueous conditions: Enzyme cascades for converting waste PET into tamibarotene.

A growing number of hydrolase enzymes show promiscuous acyltransferase activity, even under aqueous conditions. Here we report, for the first time, the ability of Pyrobaculum calidifontis VA1 esterase (PestE) to catalyse the formation of a wide range of amides in buffer, where the acyl donor forms a significant structural component in the amide product. The reactions occur under mild conditions and can achieve conversions up to 97% in 6 h for formation of N‐benzylfuranamide as the model reaction. We demonstrate PestE’s potential in enzyme cascades to make amides from waste PET plastic and the conversion of the terephthalic acid product to tamibarotene, a drug with activity against acute leukemia. Rational mutagenesis led to identification of PestE variants F33L_F289A and F33L. F33L_F289A increased conversion of N‐benzylfuranamide by 1.2‐fold, and F33L gave a 4‐fold increase in conversion to tamibarotene.

Single stage bi-substrate transglycosylation reaction for the synthesis of ascorbic acid 2 glucoside using immobilized α-glucosidase

Alpha glucosidases are multifunctional glycoside hydrolases with hydrolysis and transglycosylation ability. It can be utilized for the glycosidic bond synthesis or glycosylation of Ascorbic acid/Vitamin C to its stable analogue, Ascorbic acid 2 glucoside (AA2G), a compound with wide applications in cosmetics and pharma. The application of α-glucosidases for industrial scale transglycosylation is limited due to the low transglycosylation yield of free enzymes. Enzyme immobilization techniques could enable the development of efficient, reusable catalysts. Only a few glycoside hydrolases have been studied in immobilized form for transglycosylation reactions, and α-glucosidases are probably the least explored in this form. Transglycosylation activity of immobilized α-glucosidase from Aspergillus carbonarius BTCF 5 was studied for AA2G synthesis, where different immobilization techniques like calcium alginate encapsulation, adsorption on chitosan beads, covalent cross-linking on magnetic nanoparticles, and cross-linked enzyme aggregates (CLEA) were employed for the immobilization. The immobilization yield of calcium alginate encapsulated enzyme, enzyme immobilized on Fe-MNP support, enzyme immobilized on chitosan beads and as CLEA were 107%, 99%, 46% and 486%, respectively. CLEA was identified as the best immobilization technique for this bi-substrate reaction due to the high immobilization yield and activity retention (30% activity retained after 5 consecutive cycles). Enzyme immobilization increased the transglycosylation activity by 38%, yielding 118 mM AA2G against 72 mM by the free enzyme. This indicates the potential of immobilized α-glucosidase as a catalyst for synthesizing AA2G at an industrial scale.

Synthesis of C-N bonds by nicotinamide-dependent oxidoreductase: an overview.

Compounds containing chiral C-N bonds play a vital role in the composition of biologically active natural products and small pharmaceutical molecules. Therefore, the development of efficient and convenient methods for synthesizing compounds containing chiral C-N bonds is a crucial area of research. Nicotinamide-dependent oxidoreductases (NDOs) emerge as promising biocatalysts for asymmetric synthesis of chiral C-N bonds due to their mild reaction conditions, exceptional stereoselectivity, high atom economy, and environmentally friendly nature. This review aims to present the structural characteristics and catalytic mechanisms of various NDOs, including imine reductases/ketimine reductases, reductive aminases, EneIRED, and amino acid dehydrogenases. Additionally, the review highlights protein engineering strategies employed to modify the stereoselectivity, substrate specificity, and cofactor preference of NDOs. Furthermore, the applications of NDOs in synthesizing essential medicinal chemicals, such as noncanonical amino acids and chiral amine compounds, are extensively examined. Finally, the review outlines future perspectives by addressing challenges and discussing the potential of utilizing NDOs to establish efficient biosynthesis platforms for C-N bond synthesis. In conclusion, NDOs provide an economical, efficient, and environmentally friendly toolbox for asymmetric synthesis of C-N bonds, thus contributing significantly to the field of pharmaceutical chemical development.

Molecular Mechanism of Double-Displacement Retaining β-Kdo Glycosyltransferase WbbB.

Glycosyltransferases (GTs) are pivotal enzymes involved in glycosidic bond synthesis, which can lead to either retention or inversion of the glycosyl moiety's anomeric configuration. However, the catalytic mechanism for retaining GTs remains a subject of controversy. In this study, we employ MD and QM/MM metadynamics to investigate the double-displacement catalytic mechanism of the retaining β-Kdo transferase WbbB. Our findings demonstrate that the nucleophile Asp232 initiates the reaction by attacking the sugar ring containing a carboxylate at the anomeric position, forming a covalent adduct. Subsequently, the adduct undergoes a rotational rearrangement, ensuring proper orientation of the anomeric carbon for the acceptor substrate. In the second step, Glu158 acts as the catalytic base to abstract the proton of the acceptor substrate to complete the transglycosylation reaction. Notably, His265 does not function as the anticipated catalytic acid; instead, it stabilizes the phosphate group through H-bonding interactions. Our simulations support the double-displacement mechanism implicated from the crystallographic studies of WbbB. This mechanism deviates from the common SNi-type and retaining glycoside hydrolase mechanisms, thereby expanding our understanding of GT catalytic mechanisms.

Supramolecular Assembly Frameworks (SAFs): Shaping the Future of Functional Materials.

Supramolecular assembly frameworks (SAFs) represent a new category of porous materials, utilizing non-covalent interactions, setting them apart from metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). This category includes but is not restricted to hydrogen-bonded organic frameworks and supramolecular organic frameworks. SAFs stand out for their outstanding porosity, crystallinity, and stability, alongside unique dissolution-recrystallization dynamics that enable significant structural and functional modifications. Crucially, their non-covalent assembly strategies allow for a balanced manipulation of porosity, symmetry, crystallinity, and dimensions, facilitating the creation of advanced crystalline porous materials unattainable through conventional covalent or coordination bond synthesis. Despite their considerable promise in overcoming several limitations inherent to MOFs and COFs, particularly in terms of solution-processability, SAFs have received relatively little attention in recent literature. This Minireview aims to shed light on standout SAFs, exploring their design principles, synthesis strategies, and characterization methods. It emphasizes their distinctive features and the broad spectrum of potential applications across various domains, aiming to catalyze further development and practical application within the scientific community.

Supramolecular Assembly Frameworks (SAFs): Shaping the Future of Functional Materials

AbstractSupramolecular assembly frameworks (SAFs) represent a new category of porous materials, utilizing non‐covalent interactions, setting them apart from metal–organic frameworks (MOFs) and covalent organic frameworks (COFs). This category includes but is not restricted to hydrogen‐bonded organic frameworks and supramolecular organic frameworks. SAFs stand out for their outstanding porosity, crystallinity, and stability, alongside unique dissolution‐recrystallization dynamics that enable significant structural and functional modifications. Crucially, their non‐covalent assembly strategies allow for a balanced manipulation of porosity, symmetry, crystallinity, and dimensions, facilitating the creation of advanced crystalline porous materials unattainable through conventional covalent or coordination bond synthesis. Despite their considerable promise in overcoming several limitations inherent to MOFs and COFs, particularly in terms of solution‐processability, SAFs have received relatively little attention in recent literature. This Minireview aims to shed light on standout SAFs, exploring their design principles, synthesis strategies, and characterization methods. It emphasizes their distinctive features and the broad spectrum of potential applications across various domains, aiming to catalyze further development and practical application within the scientific community.

New Advances in Covalent Network Polymers via Dynamic Covalent Chemistry.

Covalent network polymers, as materials composed of atoms interconnected by covalent bonds in a continuous network, are known for their thermal and chemical stability. Over the past two decades, these materials have undergone significant transformations, gaining properties such as malleability, environmental responsiveness, recyclability, crystallinity, and customizable porosity, enabled by the development and integration of dynamic covalent chemistry (DCvC). In this review, we explore the innovative realm of covalent network polymers by focusing on the recent advances achieved through the application of DCvC. We start by examining the history and fundamental principles of DCvC, detailing its inception and core concepts and noting its key role in reversible covalent bond formation. Then the reprocessability of covalent network polymers enabled by DCvC is thoroughly discussed, starting from the significant milestones that marked the evolution of these polymers and progressing to their current trends and applications. The influence of DCvC on the crystallinity of covalent network polymers is then reviewed, covering their bond diversity, synthesis techniques, and functionalities. In the concluding section, we address the current challenges faced in the field of covalent network polymers and speculates on potential future directions.

Amino Acid Polymerization on Silica Surfaces.

The polymerization of unactivated amino acids (AAs) is an important topic because of its applications in various fields including industrial medicinal chemistry and prebiotic chemistry. Silica as a promoter for this reaction, is of great interest owing to its large abundance and low cost. The amide/peptide bond synthesis on silica has been largely demonstrated but suffers from a lack of knowledge regarding its reaction mechanism, the key parameters, and surface features that influence AA adsorption and reactivity, the selectivity of the reaction product, the role of water in the reaction, etc. The present review addresses these problems by summarizing experimental and modeling results from the literature and attempts to rationalize some apparent divergences in published results. After briefly presenting the main types of silica surface sites and other relevant macroscopic features, we discuss the different deposition procedures of AAs, whose importance is often neglected. We address the possible AA adsorption mechanisms including covalent grafting and H-bonding and show that they are highly dependent on silanol types and density. We then consider how the adsorption mechanisms determine the occurrence and outcome of AA condensation (formation of cyclic dimers or of long linear chains), and outline some recent results that suggest significant polymerization selectivity in systems containing several AAs, as well as the formation of specific elements of secondary structure in the growing polypeptide chains.

Mechanically Processed Sardinian Wool Promotes C-C Bond Synthesis Under Solvent-Free Conditions

Mechanically Processed Sardinian Wool Promotes C-C Bond Synthesis Under Solvent-Free Conditions

Machine Learning Enables the Prediction of Amide Bond Synthesis Based on Small Datasets

Machine Learning Enables the Prediction of Amide Bond Synthesis Based on Small Datasets

Toward safer and more sustainable by design biocatalytic amide-bond coupling

We describe an exploratory approach to a concept of safer and more sustainable by design in biocatalytic amide bond synthesis.

Deoxyfluorinated amidation and esterification of carboxylic acid by pyridinesulfonyl fluoride.

Amide bond synthesis is one of the most used reactions in medicinal chemistry. We report an amide bond formation reaction through deoxyfluorinated carboxylic acids under mild conditions using 2-pyridinesulfonyl fluoride. The reaction procedure has been used in a one-pot synthesis of amides and esters via in situ generation of acyl fluoride. This one-pot synthetic method provides easy access to amides and esters. Using this method, we have sequentially synthesized a tetrapeptide and calceolarioside-B glycoside derivative with good yields.

Zinc oxide nanoparticles as an efficient antioxidant, photocatalyst, and heterogeneous catalyst in C–P bond synthesis

Zinc oxide nanoparticles (ZnO-NPs) were synthesized using the chemical precipitation technique and characterized through various analytical methods. Powder X-ray diffraction (P-XRD) results confirmed the hexagonal wurtzite phase of the NPs. Fourier-Transform Infrared (FTIR) results showed the presence of characteristic vibrations of ZnO, such as the zinc–oxygen stretching band and the hydroxyl group. UV–Vis spectra established a band gap of 3.2 eV. Energy dispersive X-ray (EDX) identified the elemental composition of the NPs as primarily zinc and oxygen. Atomic force microscopy (AFM) images indicated a distinctive cauliflower-like morphology with an average size of 50 nm. Field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM) provided further insights into the NPs excellent crystalline structure and smooth surface. This study has also evaluated the photocatalytic and antioxidant activities of the ZnO-NPs. The NPs has a good photocatalytic activity for the degradation of textile crystal violet dye. Furthermore, the antioxidant potential of the NPs was assessed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, revealing promising in vitro results. These findings emphasize the multifaceted attributes of ZnO-NPs, making them valuable for a broad spectrum of applications, from catalysis and environmental cleanup to cutting-edge nanotechnology and biomedicine.

Microwave-Assisted Solid Phase Synthesis of Different Peptide Bonds: Recent Advancements

Abstract: Peptides are important as drugs and biologically active molecules. The synthesis of pep-tides has gathered considerable attention in recent years due to their various attractive properties. Conventional peptide synthesis is tedious and requires hazardous reagents and solvents. Micro-wave-assisted solid-phase peptide synthesis has several advantages compared with conventional batch synthesis. Herein, we have discussed various microwave-assisted solid-phase peptide bond synthesis methods developed over the last five years. Peptides are categorized into four groups - small, medium, large, and cyclic based on their length and structural characteristics to make it easier to understand. This review article also discusses the scope and limitations of microwave-assisted solid-phase peptide synthesis.

Guest molecule optimum aggregation hypothesis and optimal concentrations for energy storage from the perspective of hydrate phase change-induced liquid layer

Tetrabutylammonium bromide (TBAB) semi-clathrate hydrate possesses a unique clathrate structure for capturing and sequestering small-molecule gases, such as CH4, H2 and, CO2 and the advantage of phase change energy storage. Elucidating the diversified reactions and determining the optimal phase change characteristics of TBAB hydrate is crucial to discovering and overcoming specific limitations hindering the large-scale applications. In this study, in situ macroscopic visualization, three-dimensional reconstruction via X-ray Computed Tomography, and differential scanning calorimeter measurements were performed to discover, verify, and analyze the distinct characteristics of TBAB hydrate phase change, including phase separation, three-dimensional structure, and thermal effects. The optimal concentration of TBAB hydrate energy storage was found and verified experimentally for the first time. A peculiar liquid layer (liquid-liquid phase separation) caused by hydrate-solution phase separation was observed after multiple formation-dissociation cycles. The liquid layer separated a region that optimized the hydrate phase change. The solutions with different initial concentrations could evolve an optimized phase-change region of the same concentration (37 wt%) via multiple cycles. The region of the same concentration was shown to be the result of optimal aggregation of molecules. In proving the particularity of the concentration in the optimized region, TBAB hydrate dissociation exhibit thermal effects that can be easily ignored (TBAB molecules ionization and ionic bond synthesis), which affected the TBAB hydrate latent heat measurement. Finally, the optimal concentration of TBAB hydrate phase change was determined as 37 ± 1 wt%, and the characteristics of the concentration, including the volume fraction, complete conversion of water molecules and TBAB molecules, and latent heat, were confirmed by the liquid layer. The experimental results obtained for the first time in this study are important guidance for TBAB hydrate in the field of gas capture and energy storage.

Fluorescein isothiocyanate‐tagged boronic acid sensor‐based pH‐dependent discerning tannic acid detection

AbstractBackground and purposeThe distinction of tannic acid (TA) in the presence of other analogues, i.e., gallic acid (GA), dopamine (DA), glucose (Glu), and fructose (Fruc), containing vicinal diols, has long been a significant yet challenging task due to their similar chemical structures and minuscule levels.MethodsHere, the integration of 3‐aminophenyl boronic acid‐modified fluorescein isothiocyanate (3‐APBA‐FITC) for pH‐dependent ultrasensitive and selective detection of TA in wines was proposed. By performing fluorescence signal off and pH‐dependent boronate‐ester bond synthesis, the suggested probe may specifically identify TA.ResultsThe as‐prepared 3‐APBA‐FITC designed probe had shown ultrahigh sensitivity with a limit of detection (LOD) of 0.151 μM. Finally, in detecting TA in artificial wine with a recovery between 92.49‐93.05 % and a relative standard deviation of no more than 2.0 %, the designed strategy has been successfully applied.ConclusionTherefore, the envisaged sensing strategy can be an interesting option for discerning detection of diols containing analytes in food products.

Synthesis and Biological Activity of Novel α-Conotoxins Derived from Endemic Polynesian Cone Snails.

α-Conotoxins are well-known probes for the characterization of the various subtypes of nicotinic acetylcholine receptors (nAChRs). Identifying new α-conotoxins with different pharmacological profiles can provide further insights into the physiological or pathological roles of the numerous nAChR isoforms found at the neuromuscular junction, the central and peripheral nervous systems, and other cells such as immune cells. This study focuses on the synthesis and characterization of two novel α-conotoxins obtained from two species endemic to the Marquesas Islands, namely Conus gauguini and Conus adamsonii. Both species prey on fish, and their venom is considered a rich source of bioactive peptides that can target a wide range of pharmacological receptors in vertebrates. Here, we demonstrate the versatile use of a one-pot disulfide bond synthesis to achieve the α-conotoxin fold [Cys 1-3; 2-4] for GaIA and AdIA, using the 2-nitrobenzyl (NBzl) protecting group of cysteines for effective regioselective oxidation. The potency and selectivity of GaIA and AdIA against rat nicotinic acetylcholine receptors were investigated electrophysiologically and revealed potent inhibitory activities. GaIA was most active at the muscle nAChR (IC50 = 38 nM), whereas AdIA was most potent at the neuronal α6/3 β2β3 subtype (IC50 = 177 nM). Overall, this study contributes to a better understanding of the structure-activity relationships of α-conotoxins, which may help in the design of more selective tools.

Sulfonic Acid‐Functionalized (Bio)Materials as Catalysts for Efficient Amide Bond Synthesis

AbstractSulfonic acid carbon‐(bio)based and natural clays‐based catalysts were prepared and investigated for the first time as heterogeneous catalysts for amide bond synthesis by a Ritter reaction. The different SO3H‐catalysts were screened using benzyl alcohol and acetonitrile as model substrates, and MWCNT‐CSP revealed to be an efficient catalyst, affording the amide in 75 % yield. The practical utility of the catalysts was demonstrated by a diverse range of amides, obtained from alcohols and nitriles, in moderate to good yields. Biomass derived platform alcohols, such as 5‐HMF and furfuryl alcohol, were also tested as potential building blocks for the synthesis of biopolymers. The SO3H‐catalysts revealed to be a highly efficient and environmentally friendly alternative to the conventional acid catalysts commonly used in the Ritter reaction.

Enzyme catalyzes ester bond synthesis and hydrolysis: The key step for sustainable usage of plastics.

Petro-plastic wastes cause serious environmental contamination that require effective solutions. Developing alternatives to petro-plastics and exploring feasible degrading methods are two solving routes. Bio-plastics like polyhydroxyalkanoates (PHAs), polylactic acid (PLA), polycaprolactone (PCL), poly (butylene succinate) (PBS), poly (ethylene furanoate) s (PEFs) and poly (ethylene succinate) (PES) have emerged as promising alternatives. Meanwhile, biodegradation plays important roles in recycling plastics (e.g., bio-plastics PHAs, PLA, PCL, PBS, PEFs and PES) and petro-plastics poly (ethylene terephthalate) (PET) and plasticizers in plastics (e.g., phthalate esters, PAEs). All these bio- and petro-materials show structure similarity by connecting monomers through ester bond. Thus, this review focused on bio-plastics and summarized the sequences and structures of the microbial enzymes catalyzing ester-bond synthesis. Most of these synthetic enzymes belonged to α/β-hydrolases with conserved serine catalytic active site and catalyzed the polymerization of monomers by forming ester bond. For enzymatic plastic degradation, enzymes about PHAs, PBS, PCL, PEFs, PES and PET were discussed, and most of the enzymes also belonged to the α/β hydrolases with a catalytic active residue serine, and nucleophilically attacked the ester bond of substrate to generate the cleavage of plastic backbone. Enzymes hydrolysis of the representative plasticizer PAEs were divided into three types (I, II, and III). Type I enzymes hydrolyzed only one ester-bond of PAEs, type II enzymes catalyzed the ester-bond of mono-ester phthalates, and type III enzymes hydrolyzed di-ester bonds of PAEs. Divergences of catalytic mechanisms among these enzymes were still unclear. This review provided references for producing bio-plastics, and degrading or recycling of bio- and petro-plastics from an enzymatic point of view.