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).

Proving Cooperativity of a Catalytic Reaction by Means of Nanoscale Geometry: The Case of Click Reaction

“…However, in this system, determination of cooperativity involving two Zn­(II) centers was problematic because all reactants were anionic whereas the NPs were positively charged, their charge increasing with proportion of coordinated zinc cations (each contributing +2 charge versus +1 for the uncoordinated, protonated azacrowns). Because it is now known that catalytic reaction rates for charged substrates are sensitive to nanoparticle’s electrostatic potential, ,,,− ,− the increase in the rate of transphosphorylation could be attributed either to cooperativity or to the more positively charged NPs’ increasing local concentration of negatively charged reactants.…”

“…In a broader context, the advantage of this method is that it could be used to prove or disprove cooperativityfor various types of catalytic complexesbased on the kinetic trends alone, without recourse to detailed mechanistic knowledge. On balance, it requires the attachment of catalytic units to NPs, which, however, is typically straightforward − and significantly less complex than the synthesis (or isolation) of “pre-organized” multicenter complexes.…”

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

“…vi) Conjugation of metal complexes with bioactive molecules such as peptides, nucleotides, and vitamins as well as DNA binders to recognize specific targets and promote highly efficient catalytic reaction [92] , [93] , [94] , [95] , [96] , [97] , [98] , [99] . vii) Nanoformulation of metal complexes with nanoparticles (nano-nucleases) to obtain cooperative systems with enhanced nuclease-like activity [41] , [90] , [100] , [101] , [102] , [103] , [104] , [105] , [106] , [107] .…”

Mechanistic Insight into the Phosphodiester Bond Hydrolysis of Nanozymes

“…[7][8][9][10] These multivalent systems having several copies of catalytically active functional groups do not only induce the cooperation of the reactive functions towards the acceleration of the cleavage process, but also allow many catalytic events to occur simultaneously. [11,12] For instance, we have reported that 1.6 nm diameter gold cores coated with a monolayer of thiols bearing Zn(II)chelating 1,4,7-triazacyclonane (TACN) moiety are among the most efficient catalysts for the phosphodiester bond cleavage [13,14] The nanocatalysis is always facilitated by catalytic Zn(II) ions on the surface of AuNPs, that is reminiscent of metaldependent nucleases. However, the fundamental nanozyme's behaviour at the level of the outer coating monolayer remains poorly understood.…”

“…[15,16] We have also shown that AuNPs can form pre-catalytic complexes with DNA, in solution. [14] In this context, we used µs-long atomistic simulations, flanked with NMR experiments, to further dissect the mechanistic origins of the catalytic power of nanonucleases. Our new comparative study focused on two structurally similar AuNPs with a significantly different activity.…”