Conformational Mobility and Efficiency in Supramolecular Catalysis. A Computational Approach to Evaluate the Performances of Enzyme Mimics

Salvio, Riccardo; D’Abramo, Marco

doi:10.1002/ejoc.202001022

Cited by 11 publications

(7 citation statements)

References 70 publications

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“…Gromacs topologies of the investigated molecules were generated with Automated Topology Builder version 3.0. The other configurations of the Molecular Dynamic simulation were set up as previously reported [14] . The determination of the distances between the active units described in the main text was performed with the command mindist.…”

Section: Methodsmentioning

confidence: 99%

“…The other configurations of the Molecular Dynamic simulation were set up as previously reported. [14] The determination of the distances between the active units described in the main text was performed with the command mindist.…”

Section: Conflict Of Interestmentioning

confidence: 99%

“…However, it is necessary to avoid an exceedingly rigid structure as significant catalytic activity and cooperativity always arises from a good compromise between preorganization and flexibility. [14][15][16] Given the importance of phosphodiester bonds in living organisms and their reluctance to undergo spontaneous hydrolysis, [17,18] a number of researchers developed enzyme mimics able to efficiently cleave DNA, RNA and their model compounds. [1,15,[19][20][21][22][23][24][25][26][27][28][29] In most of these artificial phosphodiesterases metal cations are employed as active functions, with the role of Lewis acid activators, binding sites, nucleophile carriers and promoters of leaving group departure.…”

Section: Introductionmentioning

confidence: 99%

“…In these systems the active functional groups are kept close to each other, through covalent bonds, in order to guarantee the best cooperativity. However, it is necessary to avoid an exceedingly rigid structure as significant catalytic activity and cooperativity always arises from a good compromise between preorganization and flexibility [14–16] …”

Section: Introductionmentioning

confidence: 99%

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Intra‐ and Intermolecular Cooperativity in the Catalytic Activity of Phosphodiester Cleavage by Self‐Assembled Systems Based on Guanidinylated Calix[4]arenes

Lisi

Vezzoni

Casnati

et al. 2023

Chemistry A European J

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The calix[4]arene scaffold, blocked in the cone conformation through alkylation with long alkyl chains, and decorated at the upper rim with four guanidine or arginine units, effectively catalyzes the cleavage of the phosphodiester bond of DNA and RNA model compounds in water. An exhaustive kinetic investigation unequivocally points to the existence of spontaneous aggregation phenomena, driven by hydrophobic effect, occurring at different critical concentrations that depend on the identity of the compound. A pronounced superiority of the assembled structures compared with the monomers in solution was observed. Moreover, the catalytically active units, clustered on the macrocyclic tetrafunctional scaffold, were proved to efficiently cooperate in the catalytic mechanism and result in improved reaction rates compared to those of the monofunctional model compounds. The kinetic analysis is also integrated and corroborated with further experiments based on fluorescence spectroscopy and light scattering. The advantage of the supramolecular assemblies based on tetrafunctional calixarenes leads to believe that the active units can cooperate not only intramolecularly but also intermolecularly. The molecules in the aggregates can probably mold, flex and rearrange but, at the same time, keep an ordered structure that favors phosphodiester bond cleavage. This dynamic preorganization can allow the catalytic units to reach a better fitting with the substrates and perform a superior catalytic activity.

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Section: Methodsmentioning

confidence: 99%

Section: Conflict Of Interestmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intra‐ and Intermolecular Cooperativity in the Catalytic Activity of Phosphodiester Cleavage by Self‐Assembled Systems Based on Guanidinylated Calix[4]arenes

Lisi

Vezzoni

Casnati

et al. 2023

Chemistry A European J

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“…[27][28][29] In the last years, our group designed and developed a series of supramolecular artificial phosphodiesterases inspired by Nature and based on guanidinium units. [7,18,30,31] These units can synergically operate either by themselves and in conjunction with other active units. [8,10,[32][33][34] The combined action of the functional groups may decrease the activation energy of a reaction of a much greater extent than that exerted by a single unit individually.…”

Section: Introductionmentioning

confidence: 99%

Enzyme Mimics Based on Guanidinocalix[4]arene/ Nanodiamond Hybrid Systems with Phosphodiesterase Activity

Vezzoni,

Casnati,

Orlanducci

et al. 2024

ChemCatChem

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Diamond nanoparticles are an extremely promising class of carbon‐based nanomaterials. Because of their versatility, they have an interest in a large variety of applications, however, their use in the fabrication of enzyme mimics was not previously investigated. In this study, we realized hybrid systems based on guanidinium derivatives and diamond nanoparticles by simple adsorption of the organic material on their surface. The guanidinium derivatives chosen for this study are calix[4]arenes, blocked in the cone conformation via functionalization at the lower rim with alkyl chains, and decorated with guanidinium or arginine units at the upper rim. The corresponding monofunctional counterparts were also investigated as model compounds. These materials were characterized with different experimental techniques, i.e. thermogravimetric analysis, dynamic light scattering, ζ‐potential measurements and IR/Raman spectroscopy. Their catalytic properties in the cleavage phosphodiesters were investigated by an in‐depth kinetic analysis. The whole experimental picture points to conclude that these compounds are stably adsorbed onto the nanodiamonds surface and are active in the transesterification reaction of the RNA model compound 2‐hydroxypropyl p‐nitrophenyl phosphate in water, with a notable advantage over their catalytic performances at the same concentration in solution.

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Unveiling the Cleavage Mechanism of an RNA Model Compound on the whole pH Scale: Computations Meet Experiments in the Determination of Reaction Rates

Nardi,

Olivieri,

D'Abramo

et al. 2024

ChemPhysChem

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The knowledge of the mechanism of reactions occurring in solution is a primary research line both in the context of theoretical‐computational chemistry and in the field of organic and bio‐organic chemistry. Given the importance of the hydrolysis of nucleic acids in life‐related phenomena, here we present a combined experimental and computational study on the cleavage of an RNA model compound. This phosphodiester features a cleavage rate strictly dependent on the pH with three different dependence domains. Such experimental evidence, highlighted by an in‐depth kinetic investigation, unequivocally suggests a change in the reaction mechanism along the pH scale. In order to interpret the data and to explain the experimental behavior, we have applied a theoretical‐computational procedure, involving a hybrid quantum/classical approach, able to model chemical reactions in complex environments, i.e. in solution. This study turns out to quantitatively reproduce the experimental data with accuracy and, in addition, provides useful mechanistic insight into the transesterification process of the investigated compound. The study indicates that the cleavage can occur through an ANDN, an AN+DN, and a DNAN mechanism depending on the pH values.

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Conformational Mobility and Efficiency in Supramolecular Catalysis. A Computational Approach to Evaluate the Performances of Enzyme Mimics

Cited by 11 publications

References 70 publications

Intra‐ and Intermolecular Cooperativity in the Catalytic Activity of Phosphodiester Cleavage by Self‐Assembled Systems Based on Guanidinylated Calix[4]arenes

Intra‐ and Intermolecular Cooperativity in the Catalytic Activity of Phosphodiester Cleavage by Self‐Assembled Systems Based on Guanidinylated Calix[4]arenes

Enzyme Mimics Based on Guanidinocalix[4]arene/ Nanodiamond Hybrid Systems with Phosphodiesterase Activity

Unveiling the Cleavage Mechanism of an RNA Model Compound on the whole pH Scale: Computations Meet Experiments in the Determination of Reaction Rates

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