Distinct chemical factors in hydrolytic reactions catalyzed by metalloenzymes and metal complexes

Serafim, Leonardo F.; Jayasinghe‐Arachchige, Vindi M.; Wang, Lukun; Rathee, Parth; Yang, Junru; Rai, S. N.; Prabhakar, Rajeev

doi:10.1039/d3cc01380d

Cited by 7 publications

(3 citation statements)

References 232 publications

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“…Since some molecular factors controlling chemical reactions cannot be determined experimentally, computational chemistry provides useful tools to study chemical reactions and predict important thermodynamic and kinetic parameters . One powerful approach in computational chemistry for studying enzymatic reactions is the quantum mechanics/molecular mechanics (QM/MM) method . This technique combines the accuracy of quantum mechanical calculations with the efficiency of molecular mechanics force fields to capture the electronic and structural features of the active site of the enzyme and its surrounding environment.…”

Section: Introductionmentioning

confidence: 99%

“… 22 One powerful approach in computational chemistry for studying enzymatic reactions is the quantum mechanics/molecular mechanics (QM/MM) method. 23 This technique combines the accuracy of quantum mechanical calculations with the efficiency of molecular mechanics force fields to capture the electronic and structural features of the active site of the enzyme and its surrounding environment. In QM/MM calculations, the active site where the reaction occurs is treated quantum mechanically to accurately describe the electronic behavior of the reacting species.…”

Section: Introductionmentioning

confidence: 99%

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Green Enzymatic Synthesis of Geranyl Butyrate: Process Optimization and Mechanistic Insights

Simão Neto,

Sousa Junior,

da Silva Filho

et al. 2024

ACS Omega

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Flavor esters are organic compounds widely used in the food industry to enhance the aroma and taste of products. However, most chemical processes for the production of these flavoring compounds use toxic organic solvents. Some organic solvents derived from petroleum can leave behind residual traces in food products, which may raise concerns about potential health risks and contamination. In this study, we employ Eversa Transform 2.0, a commercial lipase derived from the lipase from Thermomyces lanuginosus, to produce geranyl butyrate in aqueous media. The chemical process was optimized using the Taguchi method, and a conversion of 93% was obtained at the optimal reaction conditions of: 1:5 molar ratio (v/v), 15% biocatalyst load (w/w), at 50 °C, in 6 h. Classic (molecular dynamics) and quantum (density functional theory) simulations unveiled amino acid residues involved in the stabilization of the enzyme−substrate complex. Detailed QM/MM mechanistic studies identified the nucleophilic attack of the deacylation reaction as the rate-limiting step of the entire mechanism, which has a free energy barrier of 14.0 kcal/mol.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Green Enzymatic Synthesis of Geranyl Butyrate: Process Optimization and Mechanistic Insights

Simão Neto,

Sousa Junior,

da Silva Filho

et al. 2024

ACS Omega

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“…The presence of metals catalyzing the hydrolysis of phosphate esters motivated the development of new metallic catalysts capable of cleaving both phosphate esters and DNA itself 4–7 . Thus, metallic compounds of the first transition series, especially copper(II), have been reported in the literature as capable of cleaving PO bonds in different substrates with high hydrolysis rates 8–10 …”

Section: Introductionmentioning

confidence: 99%

Hydrolysis of phosphate diester catalyzed by new mononuclear copper(II) complexes containing selenium ligands

Duarte,

Durigon,

Braga

et al. 2023

J of Physical Organic Chem

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Three new copper(II) mononuclear complexes containing different organoselenium groups (1–3) were synthesized and characterized by the following techniques: elemental analysis, IR and UV‐Vis spectroscopies, electrochemical and conductimetric analysis, and mass spectrometry. Three new complexes, with substituents made in the para position of the aromatic portion of the N,N‐bis(2‐(phenylselanyl)ethyl)amine ligand: p‐OCH3 (1), p‐CH3 (2), and p‐Cl (3), were synthetized to compare with the already published complex (4), with no substituents. The ligand coordinates to the copper(II) center in a tridentate way with Se, N, Se as donor atoms. The hydrolytic activity in phosphate diester cleavage of the complexes was investigated using 2,4‐BDNPP as substrate. The modifications in the ligand are reflected in the difference between the catalytic and activation parameters, where the kcat values follow the order: 4 > 2 > 3 > 1.

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The Cleavage of RNA Model Compounds: The Interplay Between the Nucleophile and the Leaving Group

Koski,

Poijärvi,

Tulisalo

et al. 2024

J of Physical Organic Chem

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Hydrolytic reactions of phosphodiester bonds of RNA have been extensively studied over several decades. Information on the factors that affect the reactivity of phosphodiester bonds in biomolecules is important for the development of new nucleic acid‐related therapeutics. Furthermore, the development of artificial nucleases requires efficient catalytic entities, and rational design of catalysts requires detailed understanding of the catalytic mechanisms. In the present article, we concentrate on the interplay between the nucleophile and leaving group both in the absence and in the presence of metal ion catalysts. The effect of the nucleophile on the reactivity of RNA model compounds has been studied with 2‐hydroxypropyl and uridine 3′‐aryl phosphates as well as with bis‐(p‐nitrophenyl)phosphate as substrates. pH‐rate profiles for three different 2‐hydroxypropyl arylphosphates were compared with those obtained with a uridine 3′‐alkyl and aryl phosphates. The observations are discussed in terms of the relative goodness/poorness of the nucleophile and the leaving group. Metal complex‐dependent reactions were studied in the presence of well‐known and robust CuTerPy and CuBiPy complexes. The results show that CuTerPy and CuBiPy favour different types of phosphodiesters as substrates, depending on the properties of the nucleophile and leaving group, and suggest that the complexes utilize different catalysis mechanisms, which may depend also on the structure of the substrate. The results obtained further the understanding on the basic principles of metal complex‐promoted cleavage of RNA and model compounds, help to assess the relevance of data obtained with model compounds and support the design of artificial enzymes for phosphodiester cleavage.

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Distinct chemical factors in hydrolytic reactions catalyzed by metalloenzymes and metal complexes

Abstract: The selective hydrolysis of the extremely stable phosphoester, peptide and ester bonds of molecules by bio-inspired metal-based catalysts (metallohydrolases) is required in a wide range of biological, biotechnological and industrial applications.

Cited by 7 publications

References 232 publications

Green Enzymatic Synthesis of Geranyl Butyrate: Process Optimization and Mechanistic Insights

Green Enzymatic Synthesis of Geranyl Butyrate: Process Optimization and Mechanistic Insights

Hydrolysis of phosphate diester catalyzed by new mononuclear copper(II) complexes containing selenium ligands

The Cleavage of RNA Model Compounds: The Interplay Between the Nucleophile and the Leaving Group

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