Abstract:Phosphoesterases hydrolyze the phosphorus oxygen bond of phosphomono-, di- or triesters and are involved in various important biological processes. Carboxylate and/or hydroxido-bridged dizinc(II) sites are a widespread structural motif in this enzyme class. Much effort has been invested to unravel the mechanistic features that provide the enormous rate accelerations observed for enzymatic phosphate ester hydrolysis and much has been learned by using simple low-molecular-weight model systems for the biological … Show more
“…To guide this study, we used the mechanism proposed in the literature for bimetallic PAP as a refence. 32,39 The active center of these enzymes is based on binuclear (HO)-Fe III -(µ-OH)-M II -(H2O) units.…”
Section: Dual Metal Synergistic Degradation Mechanism In Muv-101(fe)mentioning
Heterometallic or mixed-metal Metal-Organic Frameworks (MOFs), incorporating two or more metal ions to the inorganic node of the frameworks, are increasingly gaining importance as a route to produce materials with increasing chemical and functional complexity. Heterometallic MOFs can offer important advantages over their homometallic counterparts to enable targeted modification of the adsorption properties, structural response, electronic structure or chemical reactivity of the framework. This field is still in its infancy likely due to the difficulties of controlling the formation of heterometallic nodes by direct synthesis. This restriction is even more acute in the case of titanium frameworks for which their challenging chemistry renders post-synthetic doping of preformed materials as the only route available. However, this often results in partial or non-homogeneous metal substitution in detriment of the potential benefits of controlling metal distribution at an atomic level toward performance improvement. We report the first family of heterometallic titanium frameworks that can be prepared by direct synthesis from metal precursors and trimesic acid. MUV-101 frameworks [TiM2(µ3-O)(O2CR)6X3] (M = Mg, Fe, Co, Ni; X = H2O, OH -, O 2-) combine mesoporosity with good chemical stability. We use these materials to exemplify the advantages of controlling metal distribution across the framework in heterogeneous catalysis by exploring their activity toward the degradation of a nerve agent simulant of Sarin gas. MUV-101(Fe) is the only pristine MOF capable of catalytic degradation of (diisopropyl-fluorophosphate) DIFP in non-buffered aqueous media without the presence of a basic/nucleophilic co-catalyst. Compared to MUV-101(Fe), other titanium heterometallic and homometallic MOFs as MUV-101(Mg, Co and Ni), MUV-10(Mn), MIL-100(Ti and Fe) or UiO-66(Zr), all display a poorer performance or are poisoned by the degradation products. The catalytic activity of MUV-101(Fe) cannot be explained only by the association of Ti(IV) and Fe(III) but to their synergistic cooperation. Our simulations suggest that the combination of Ti(IV) Lewis acid and Fe(III)-OH Brönsted base sites in this dual metal catalyst leads to a much lower energy barrier for more efficient degradation of DIFP in absence of a base. Overall, this mechanism resembles the activity of the metalloenzyme purple acid phosphatase that displays also bimetallic active sites.
“…To guide this study, we used the mechanism proposed in the literature for bimetallic PAP as a refence. 32,39 The active center of these enzymes is based on binuclear (HO)-Fe III -(µ-OH)-M II -(H2O) units.…”
Section: Dual Metal Synergistic Degradation Mechanism In Muv-101(fe)mentioning
Heterometallic or mixed-metal Metal-Organic Frameworks (MOFs), incorporating two or more metal ions to the inorganic node of the frameworks, are increasingly gaining importance as a route to produce materials with increasing chemical and functional complexity. Heterometallic MOFs can offer important advantages over their homometallic counterparts to enable targeted modification of the adsorption properties, structural response, electronic structure or chemical reactivity of the framework. This field is still in its infancy likely due to the difficulties of controlling the formation of heterometallic nodes by direct synthesis. This restriction is even more acute in the case of titanium frameworks for which their challenging chemistry renders post-synthetic doping of preformed materials as the only route available. However, this often results in partial or non-homogeneous metal substitution in detriment of the potential benefits of controlling metal distribution at an atomic level toward performance improvement. We report the first family of heterometallic titanium frameworks that can be prepared by direct synthesis from metal precursors and trimesic acid. MUV-101 frameworks [TiM2(µ3-O)(O2CR)6X3] (M = Mg, Fe, Co, Ni; X = H2O, OH -, O 2-) combine mesoporosity with good chemical stability. We use these materials to exemplify the advantages of controlling metal distribution across the framework in heterogeneous catalysis by exploring their activity toward the degradation of a nerve agent simulant of Sarin gas. MUV-101(Fe) is the only pristine MOF capable of catalytic degradation of (diisopropyl-fluorophosphate) DIFP in non-buffered aqueous media without the presence of a basic/nucleophilic co-catalyst. Compared to MUV-101(Fe), other titanium heterometallic and homometallic MOFs as MUV-101(Mg, Co and Ni), MUV-10(Mn), MIL-100(Ti and Fe) or UiO-66(Zr), all display a poorer performance or are poisoned by the degradation products. The catalytic activity of MUV-101(Fe) cannot be explained only by the association of Ti(IV) and Fe(III) but to their synergistic cooperation. Our simulations suggest that the combination of Ti(IV) Lewis acid and Fe(III)-OH Brönsted base sites in this dual metal catalyst leads to a much lower energy barrier for more efficient degradation of DIFP in absence of a base. Overall, this mechanism resembles the activity of the metalloenzyme purple acid phosphatase that displays also bimetallic active sites.
“…In the attempt to reproduce the activity, and possibly the proficiency of enzymes, chemists have focused their attention on the creation of artificial nucleases (Morrow et al, 2008; Aiba et al, 2011; Lassila et al, 2011; Lönnberg, 2011; Mancin et al, 2012; Diez-Castellnou et al, 2017a). Despite the significant effort invested in understanding the mechanism of the enzyme catalyzed reaction (Korhonen et al, 2013; Erxleben, 2019) and, therefore, in creating efficient artificial hydrolytic agents, the enzyme reactivity is still unrivaled and several questions remain to be addressed.…”
In this paper, the unusual reactivity of the complex Zn(II)-1,4,7-trimethyl-1, 4,7-triazacyclononane (
2
) in the transesterification of the RNA-model substrate,
HPNP
(
3
), is reported. The dependence of the reactivity (k
2
) with pH does not follow the characteristic bell-shape profile typical of complexes with penta-coordinated metal centers. By the contrary, two reactive species, featuring different deprotonation states, are present, with the tri-aqua complex being more reactive than the mono-hydroxy-diaqua one. Apparently, such a difference arises from the total complex charge which plays an important role in the stability of the transition state/s of the reactions. Relevant insight on the reaction mechanism were hence obtained.
“…A notable illustration is phen-copper(I) complex, [Cu(phen) 2 ] + ( Fig. 6 ), which is the first AMS with ability of DNA cleavage through oxidation of deoxyribose ring [19] . Fig.…”
Section: Amss In Pharma Studiesmentioning
confidence: 99%
“… Fig. 6 The molecular structures of polypyridyl ligands (bpy, phen, and tpy); and [Cu(phen) 2 ] + [19] . …”
Section: Amss In Pharma Studiesmentioning
confidence: 99%
“…Over four decades after the nuclease activity of a Cu(II) complex was reported [16] , the concept of metal complexes as an extremely promising platform in the construction of AMSs is still enjoying a high level of interest as evidenced by many reviews [13] , [14] , [15] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] . Nevertheless, therapeutic potentials of AMSs have not received a substantially deep attention, we therefore try here to highlight the recent progress conducted on the metal complexes employed in mimetic cleavage studies of nucleic acids and shed a light on their potential therapeutic applications.…”
Despite the extensive and rapid discovery of modern drugs for treatment of cancer, microbial infections, and viral illnesses; these diseases are still among major global health concerns. To take inspiration from natural nucleases and also the therapeutic potential of metallopeptide antibiotics such as the bleomycin family, artificial metallonucleases with the ability of promoting DNA/RNA cleavage and eventually affecting cellular biological processes can be introduced as a new class of therapeutic candidates. Metal complexes can be considered as one of the main categories of artificial metalloscissors, which can prompt nucleic acid strand scission. Accordingly, biologists, inorganic chemists, and medicinal inorganic chemists worldwide have been designing, synthesizing and evaluating the biological properties of metal complexes as artificial metalloscissors. In this review, we try to highlight the recent studies conducted on the nuclease-like metalloscissors and their potential therapeutic applications. Under the light of the concurrent Covid-19 pandemic, the human need for new therapeutics was highlighted much more than ever before. The nuclease-like metalloscissors with the potential of RNA cleavage of invading viral pathogens hence deserve prime attention.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
