Catalysis Of Ester Hydrolysis Research Articles

Ecofriendly Synthesis of Ribociclib Intermediate Using Regioselective Hydrodechlorination and DMAP Catalyzed Ester Hydrolysis

Ecofriendly Synthesis of Ribociclib Intermediate Using Regioselective Hydrodechlorination and DMAP Catalyzed Ester Hydrolysis

Syntheses of benzhydryl 2-propanoyl-functionalized trithiocarbonates and its use as chain transfer agents in the RAFT polymerization of styrene

Abstract The preparation of three new benzhydryl 2-propanoyl-functionalized trithiocarbonate RAFT agents, benzhydryl 2-(ethylsulfanylthiocarbonylsulfanyl)propanoate, benzhydryl 2-(butylsulfanylthiocarbonylsulfanyl)propanoate, benzhydryl 2-(dodecylsulfanylthiocarbonylsulfanyl)propanoate is described. The RAFT polymerization of styrene, mediated by the appropriate benzhydryl 2-(alkylsulfanylthiocarbonylsulfanyl)propanoate as the chain transfer agent, with AIBN as initiator at 70 0C, proceeds via reversible-deactivation radical polymerization processes to produce the corresponding α-benzhydryl 2-propanoyl polystyrene derivative, with the benzhydryl ester group introduced at the α-terminus of the polymer chain. Polymerization kinetics measurements show that each RAFT polymerization reaction follows first order rate kinetics with respect to percentage monomer consumption and the number average molecular weights of the functionalized polymers increase linearly with the percentage monomer conversion to produce functionalized polymers with narrow molecular weight distributions. The percentage monomer conversion with time for each polymerization reaction was monitored by 1H NMR spectroscopy by evaluating the consumption of styrene with respect to polymerization time. Post-RAFT polymerization chain end modification of α-benzhydryl 2-propanoyl-functionalized polystyrene by the acid catalyzed ester hydrolysis reactions with concentrated sulfuric acid afforded the corresponding α-carboxyl functionalized polystyrene derivative, with the retention of the thiocarbonylthio moiety at the ω-terminus of the polymer chain. The benzhydryl 2-propanoyl-functionalized trithiocarbonate chain transfer agents and the different functionalized polystyrene derivatives were characterized by 1H NMR, 13C NMR and FTIR spectroscopy, size exclusion chromatography, thin layer chromatography and mass spectrometry measurements.

Conjugating Catalytic Polyproline Fragments with a Self-Assembling Peptide Produces Efficient Artificial Hydrolases

A polyproline fragment containing a catalytic dyad of His-His or Ser-His was coupled with a self-assembling peptide MAX1 to design new hydrolases (H2H5 and H2S5) for catalyzing ester hydrolysis. Circular dichroism measurements indicated that the peptides change their conformation from randomcoils to β-sheets when pH increases from 5 to 10. IR spectra also displayed the vibration modes corresponding to their β-structures at pH 9.0. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) measurements showed that in solution, the designed peptides self-assemble into network fibrils having a significantly increased catalytic efficiency on ester hydrolysis. On p-nitrophenyl acetate (p-NPA) substrate, the designed peptides exhibit high catalytic efficiency at pH 9.0 (kcat/KM = 12.1 M-1 s-1 for H2H5, 13.3 M-1 s-1 for H2S5), and their efficiency is even better at pH 10.0 (kcat/KM = 24.3 M-1 s-1 for H2H5, 99.4 M-1 s-1 for H2S5). Additionally, H2H5 and H2S5 also display good activity on catalyzing the hydrolysis of p-nitrophenyl-(2-phenyl)-propanoate (p-NPP) and p-nitrophenyl methoxyacetate (p-NPMA). Combining the polyproline-based catalytic scaffold with a self-assembling peptide generates an efficient hydrolase, providing a new design for effective artificial enzymes.

Sulfonatocalixarene Counterion Exchange Binding Model in Action: Metal‐Ion Catalysis Through Host‐Guest Complexation

Abstractp‐Sulfonatocalixarene water soluble macrocyclic host receptors are known to form cooperative ternary complexes with complementary organic guest and metal cations. This property may be explored to enhance the interaction of weak nitrogen ligands with metal cations in a confined space showing some resemblance to metal‐containing enzymes. However, the best of our knowledge, catalytic potential of this property remains unexplored. In this work the Ni2+ catalyzed hydrolysis of a picolinate ester (2,4‐dinitrophenyl picolinate, 1) was used as a model reaction to evaluate the effect of sulfonatocalixarene macrocycles in the kinetics of this reaction. The results show that the host molecules promote the reaction through simultaneous complexation of the metal cation and the substrate and, in the case of the larger calixarenes containing more basic phenol groups, substantially higher rate enhancements are observed owing to additional assistance provided by base/nucleophilic catalysis. However, due the ionic nature of these receptors auto‐inhibition of the reaction is observed at higher concentrations due counterion (Na+) binding that competes with the catalytically active Ni2+ ‐complexes.

De Novo Designed α-Helical Coiled-Coil Peptides as Scaffolds for Chemical Reactions.

Coiled coils (CCs) are well-understood protein-folding motifs. They appear in a variety of oligomer states and as homo- and heteromeric assemblies. This versatility and the general accessibility by de novo design makes them ideal building blocks for synthetic biology. This Minireview highlights the efforts being made in designing small peptide catalysts or reaction templates based on the CC scaffold. The first reports described autocatalysis or mediation of peptide ligation based on CC recognition. Over the years, the designs became more advanced, catalyzing ester hydrolysis, acyl transfer and redox reactions with partial enzyme-like reactivity. Due to the ability to control CC assembly, and, in heterodimeric systems, the association and dissociation, the CC motif has become a common peptide tag in chemical biology.

Characterization and application of chemical-resistant polyurethane-based enzyme and whole cell compartments

This study presents the preparation and physical-chemical characterization of chemical resistant polyurethane-based compartments for biocatalytic application. The artificial compartments were prepared from an emulsion of polymer precursor and an aqueous phase that includes a biocatalytic reaction system. After curing, highly dispersed aqueous domains were obtained, which still contain the entire biocatalytic reaction system and remain fixed in the solid polymer preparation. The tensile and compression behavior of the prepared polymeric material is not significantly affected by the incorporation and facilitates excellent stability against various organic solvents and acid solutions. Thereby, the compartments can be used not only for enantioselective alcohol-dehydrogenase catalyzed reduction but also for a whole cell catalyzed hydrolysis of esters. Moreover, the compartmented whole-cell system was considerably stable to allow multiple reuses without a noticeable loss of catalytic activity of the incorporated whole cell catalytic reaction system.

Exploration of Intrinsic Lipase‐Like Activity of Zirconium‐Based Metal‐Organic Frameworks

To overcome the disadvantages of natural enzymes, artificial enzyme mimics attracted increasing attention of researchers. Metal‐organic frameworks (MOFs) are expected as one of the most appropriate candidates for artificial enzyme mimics. In this work, we demonstrate that the zirconium‐based MOF material UiO‐66 and its analogues possess intrinsic lipase‐like activity and can efficiently catalyze ester hydrolysis, transesterification and esterification reactions. Furthermore, the UiO‐66(NH2) exhibits much higher catalytic activity than that of UiO‐66, which can be attributed to the synergy effect between the zirconium cluster centres and the amino moieties during the catalytic cycle.

Asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680

The asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to the requisite (E)-α,β-unsaturated ester followed by in situ enolate oxidation with (−)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti-α-hydroxy-β-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn-α-hydroxy-β-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO3-mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn-α-hydroxy-β-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti-α-hydroxy-β-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric α-hydroxy-β-amino acids.

Catalytic Promiscuity of Ancestral Esterases and Hydroxynitrile Lyases.

Catalytic promiscuity is a useful, but accidental, enzyme property, so finding catalytically promiscuous enzymes in nature is inefficient. Some ancestral enzymes were branch points in the evolution of new enzymes and are hypothesized to have been promiscuous. To test the hypothesis that ancestral enzymes were more promiscuous than their modern descendants, we reconstructed ancestral enzymes at four branch points in the divergence hydroxynitrile lyases (HNL's) from esterases ∼ 100 million years ago. Both enzyme types are α/β-hydrolase-fold enzymes and have the same catalytic triad, but differ in reaction type and mechanism. Esterases catalyze hydrolysis via an acyl enzyme intermediate, while lyases catalyze an elimination without an intermediate. Screening ancestral enzymes and their modern descendants with six esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P < 0.01). Ancestral esterases were more likely to catalyze a lyase reaction than modern esterases, and the ancestral HNL was more likely to catalyze ester hydrolysis than modern HNL's. One ancestral enzyme (HNL1) along the path from esterase to hydroxynitrile lyases was especially promiscuous and catalyzed both hydrolysis and lyase reactions with many substrates. A broader screen tested mechanistically related reactions that were not selected for by evolution: decarboxylation, Michael addition, γ-lactam hydrolysis and 1,5-diketone hydrolysis. The ancestral enzymes were more promiscuous than their modern descendants (P = 0.04). Thus, these reconstructed ancestral enzymes are catalytically promiscuous, but HNL1 is especially so.

Self-assembled Peptide nanofibers designed as biological enzymes for catalyzing ester hydrolysis.

The structural arrangement of amino acid residues in a native enzyme provides a blueprint for the design of artificial enzymes. One challenge of mimicking the catalytic center of a native enzyme is how to arrange the essential amino acid residues in an appropriate position. In this study, we designed an artificial hydrolase via self-assembly of short peptides to catalyze ester hydrolysis. When the assembled hydrolase catalytic sites were embedded in a matrix of peptide nanofibers, they exhibited much higher catalytic efficiency than the peptide nanofibers without the catalytic sites, suggesting that this well-ordered nanostructure is an attractive scaffold for developing new artificial enzymes. Furthermore, the cytotoxicity of the assembled hydrolase was evaluated with human cells, and the novel artificial biological enzyme showed excellent biocompatibility.

Influence of the position of the substituent on the efficiency of lipase-mediated resolutions of 3-aryl alkanoic acids

Hydrolase-catalysed kinetic resolutions to provide enantioenriched α-substituted 3-aryl alkanoic acids are described. (S)-2-Methyl-3-phenylpropanoic acid (S)-1a was prepared in 96% ee by Pseudomonas fluorescens catalysed ester hydrolysis, while, Candida antarctica lipase B (immob) resolved the α-ethyl substituted 3-arylalkanoic acid (R)-1b in 82% ee. The influence of the position of the substituent relative to the ester site on the efficiency and enantioselectivity of the biotransformation is also explored; the same lipases were found to resolve both the α- and β-substituted alkanoic acids. Furthermore, the steric effect of substituents at the C2 stereogenic centre relative to that for their C3 substituted counterparts on the efficiency and stereoselectivity is discussed.

Degradation Behaviour of Thin Polymer Films of Poly(Amide Ester) Hydrogel Using Quartz Crystal Microbalance

Quartz Crystal Microbalance (QCM) has been typically used as a mass sensor in the study of monolayer and multilayer depositions and dissolution, mass transport in polymer films on electrodes, corrosion processes at electrodes and mass changes caused by protein adsorption at electrodes. Thin films of an aromatic poly (amide ester) hydrogel with hydrolyzable cross links were prepared in-situ on a gold-coated quartz crystal which is the transducing element of a Quartz Crystal Microbalance (QCM). Here we report the synthesis and degradation behavior of an aromatic poly (amide ester) hydrogel with hydrolyzable cross links using QCM. Degradation of the hydrogel films was found to proceed with Δf increment, indicating mass decrease and is in line with the theory proposed by Sauerbrey. Films with a higher cross-link density underwent partial degradation with swelling; and are depicted as a decrease in the Δf values with time. Deviation from the general base catalysis of ester hydrolysis was observed at higher base concentration due to the biphasic environment of the hydrolysis reaction.

Enzyme and acid catalyzed degradation of PEG45-b-PBO0,6,9-b-PCL60 micelles: Increased hydrolytic stability by engineering the hydrophilic–hydrophobic interface

Acid and Pseudomonas (P.) cepacia lipase catalyzed ester hydrolysis were evaluated for block copolymer micelles generated from low polydispersity PEG45-b-PBOn-b-PCL60 (n = 0, 6, 9). Moving the hydrophilic–hydrophobic junction away from the PCL micelle core–water interface by inserting a short hydrophobic non-hydrolyzable PBO segment between the PEG and PCL blocks was studied as a strategy for tuning the micelle hydrolytic stability. 1H NMR was applied in evaluating the micelle and solution compositions and to determine kinetic parameters. Acid and lipase catalyzed micelle hydrolysis proceed by distinctly different routes. Micelles from the triblock copolymers PEG45-b-PBOn-b-PCL60 (n = 6, 9) are observed to react substantially slower and persist intact longer in the presence of both strong acids and lipase enzymes than micelles of the parent diblock copolymer (PEG45-b-PCL60).

Ester hydrolysis by a histidine-containing cavitein

We have used a template-assembled synthetic protein (TASP) to investigate catalytic function in ester hydrolysis. A histidine-containing cavitein has been found to catalyze ester hydrolysis with a rate increase of 18 times that of background.

Effect of co‐solvent addition on the reaction kinetics of the lipase‐catalyzed resolution of ibuprofen ester

AbstractBACKGROUND: The addition of co‐solvent is not limited to enhancing the catalytic rate, it could also assist in situ racemization in the dynamic kinetic resolution of racemic compounds by increasing the reactivity of the base catalyst employed. In the current work, reaction media with the presence of DMSO were investigated in Candida rugosa lipase (EC 3.1.1.3)‐catalyzed hydrolysis of ibuprofen ester that focuses on the thermodynamic effect, reaction stability and implication for the kinetic parameters.RESULTS: The introduction of 2% DMSO increased the reaction rate, conversion, and enantioselectivity of the Candida rugosa lipase‐mediated resolution. However, the performance of the particular enzymatic reaction was reduced when a higher DMSO concentration was added. At lower reaction temperatures, the medium with 2% DMSO exhibited an increase in enantioselectivity, which was attributed to a higher activation energy difference between the fast‐ and slow‐reacting enantiomers compared with the water‐isooctane medium. Additionally, the presence of DMSO had a significant effect on the kinetic parameters, shown by a lower value of Michaelis constant compared with that of a normal reaction without DMSO, which resulted in a fast reaction rate. Finally, inhibition due to the uncompetitive substrate inhibitor was reduced, while the non‐competitive product inhibitor consequently increased.CONCLUSION: This work has demonstrated that only 2% of DMSO can be tolerated by the free Candida rugosa lipase in the resolution of ibuprofen ester. However, it is still able to give significant positive effects on the hydrolysis rate, kinetic parameters and enantioselectivity as well as reaction stability. © 2012 Society of Chemical Industry

A Study on the Different Methods of Preparation of Lutein from Supercritical Fluid Processed Lutein Esters

Lutein is a dietary oxycarotenoid which is found to reduce the risks of Age-related Macular Degeneration (AMD). Supercritical fluid extraction of lutein esters from marigold petals was carried out and was found to be much effective than conventional solvent extraction. The saponification of pre-concentrated lutein esters to produce free lutein was studied which showed a composition of about 88% total carotenoids (UV-VIS spectrophotometry) and 90.7% lutein (HPLC). The lipase catalyzed hydrolysis of lutein esters in conventional medium was investigated. The optimal temperature, pH, enzyme concentration and water activity were found to be 50°C, 7, 15% and 0.33 respectively and the activity loss of lipase was about 25% after 8 times re-use at 50°C for 12 days. However, the lipase catalyzed hydrolysis of lutein esters in conventional media resulted in poor conversions (38.7%).

Peptide dendrimer enzyme models for ester hydrolysis and aldolization prepared by convergent thioether ligation

Peptide dendrimers with multiple histidines or N-terminal prolines efficiently catalyze ester hydrolysis or aldol reactions in aqueous medium. Part of the catalytic proficiency of these dendritic enzyme models stems from multivalency effects observed in G2, G3 and G4 dendrimers displaying multiple catalytic groups in their branches. To study multivalency in higher generation systems, G4, G5 and G6 peptide dendrimers were prepared by a convergent assembly. Thus, peptide dendrimers bearing four or eight chloroacetyl groups at their N-termini underwent multiple thioether ligation with G2 and G3 peptide dendrimers with a cysteine residue at their focal point, to give G4, G5 and G6 dendrimers containing up to 341 amino acids, including multiple histidines or N-terminal prolines. While the efficiency of the esterase catalysts was comparable to that of their lower generation analogs, a remarkable reactivity increase was observed in G5 and G6 aldolase dendrimers.

ChemInform Abstract: Synthesis of Optically Active Cyclohexenol Derivatives via Enzyme Catalyzed Ester Hydrolysis of 4-Acetoxy-3-methyl-2-cyclohexenone.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A new Zn2+ chemosensor based on functionalized 8-hydroxylquinoline

Abstract A new fluorescent Zn2+ chemosensor (3) based on functionalized 8-hydroxylquinoline has been synthesized and characterized. Compound 3 shows weak fluorescence in CH3CN–HEPES buffer solution (50 mM, pH 7.2 v/v = 1:9), but the fluorescence is significantly enhanced upon binding to Zn2+ through a zinc(II)-catalyzed ester hydrolysis reaction to form a highly emissive zinc(II) complex. This suggests that 3 can be served as a typical “switch–on” chemosensor with high selectivity for Zn2+ over other metal ions.

Switching from an Esterase to a Hydroxynitrile Lyase Mechanism Requires Only Two Amino Acid Substitutions

The alpha/beta hydrolase superfamily contains mainly esterases, which catalyze hydrolysis, but also includes hydroxynitrile lyases, which catalyze addition of cyanide to aldehydes, a carbon-carbon bond formation. Here, we convert a plant esterase, SABP2, into a hydroxynitrile lyase using just two amino acid substitutions. Variant SABP2-G12T-M239K lost the ability to catalyze ester hydrolysis (<0.9 mU/mg) and gained the ability to catalyze the release of cyanide from mandelonitrile (20 mU/mg, k(cat)/K(M) = 70 min(-1)M(-1)). This variant also catalyzed the reverse reaction, formation of mandelonitrile with low enantioselectivity: 20% ee (S), E = 1.5. The specificity constant for the lysis of mandelontrile is 13,000-fold faster than the uncatalyzed reaction and only 1300-fold less efficient (k(cat/)K(M)) than hydroxynitrile lyase from rubber tree.