A Gold Nanoparticle Nanonuclease Relying on a Zn(II) Mononuclear Complex

Abstract

Similarly to enzymes,f unctionalized gold nanoparticles efficiently catalyze chemical reactions,hence the term nanozymes.H erein, we present our results showing how surface-passivated gold nanoparticles behave as synthetic nanonucleases,a ble to cleave pBR322 plasmid DNAwith the highest efficiency reported so far for catalysts based on asingle metal ion mechanism. Experimental and computational data indicate that we have been successful in creating acatalytic site precisely mimicking that suggested for natural metallonucleases relying on as ingle metal ion for their activity.I tc omprises one Zn(II) ion to which ap hosphate diester of DNAi s coordinated. Importantly,a si nn ucleic acids-processing enzymes,apositively charged arginine playsakey role by assisting with transition state stabilization and by reducing the pK a of the nucleophilic alcohol of as erine.O ur results also show howd esigning ac atalyst for am odel substrate (bis-pnitrophenylphosphate) may provide wrong indications as for its efficiency when it is tested against the real target (plasmid DNA).

The Mechanism of Cleavage of RNA Phosphodiesters by a Gold Nanoparticle Nanozyme

“…We have observed that this is indeed the case for very challenging substrates such as DNA. [10] Our results show how very subtle changes, in both the catalyst and substrate, may significantly affect the mechanism of metal ion catalyzed cleavage of RNA phosphodiesters.…”

“…However, the binding of the nucleobase to a nearby Zn(II) complex makes it unavailable for cooperating in the cleavage of the substrate. We have shown that phosphate diesters (but not triesters) [23] cleavage by TACN−Zn(II) complexes requires a dinuclear catalytic site [10,12,18,19] . As the concentration of UPNP increases, dinuclear catalytic sites become less and less available and the catalytic performance of the catalyst decreases (downward curvature of the graph of Figure 2A).…”

“…We have shown that phosphate diesters (but not triesters) [23] cleavage by TACNÀ Zn(II) complexes requires a dinuclear catalytic site. [10,12,18,19] As the concentration of UPNP increases, dinuclear catalytic sites become less and less available and the catalytic performance of the catalyst decreases (downward curvature of the graph of Figure 2A). The ability of uridine to bind to the monolayer could be confirmed in inhibition experiments using HPNP as the substrate.…”

“…Indeed, they proved to be rather efficient catalysts for the cleavage of phosphodiesters, including RNA model substrates, and DNA as well. [10] They are self-assembled supramolecular systems in which a cluster of gold atoms is coated with a passivating monolayer, which, for this application, is functionalized with metal ion complexes. [11] For their mode of action, and catalytic efficiency (up to 5-6 orders of magnitude rate acceleration with model substrates) they have been dubbed nanozymes [12] and are among the most efficient catalysts reported so far.…”

Phosphate Triesters Cleavage by Gold Nanozymes

“…We have reported in the past that gold nanoparticles (AuNPs) functionalized with metal ion complexes are powerful catalysts of the cleavage of phosphate diester including DNA. [9][10][11] We thought they were excellent candidates as catalysts for the cleavage of phosphate triesters and nerve agents, in particular. Typically, catalysts developed for this purpose are not tested with the real nerve agents for their toxicity and simulants, far less toxic, are used.…”