Gold nanoparticles passivated with organic molecules can be functionalized to produce nanodevices with unique properties and applications, e.g. in nanomedicine and diagnostics, chemosensing and even catalysis. The artificial enzymes, hence the term nanozymes, mimic an enzyme catalytic site by placing together several functions supposed to cooperate in the catalytic process (for instance two metal complexes, a metal complex and a cationic group. 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.<br/>For instance, we have reported that gold nanoparticles (AuNPs) passivated with thiols functionalized with 1,4,7-triazacyclonane (TACN) complexed with Zn(II) are among the most efficient catalysts for the cleavage of the RNA-model substrate 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) in physiological conditions.<sup> </sup>In this case, nanocatalysis is facilitated by catalytic Zn(II) ions on the surface of AuNPs, that is reminiscent of metal-dependent nucleases that cleave phosphodiester bonds of nucleic acids via the two-metal-ion mechanism. Interestingly, the reactivity was influenced greatly by a simple modification of the linker. More recently, we have engineered the passivating monolayer of small gold clusters with short peptides and a Zn(II) complex being able to cleave pBR322 plasmid DNA with high efficiency.<br/>The fundamental nanozyme’s behavior at the level of the outer coating monolayer remains however poorly understood that limits our ability to rationally design more efficient nanodevices. To address this, we have used a microsecond long atomistic simulations, flanked by NMR experiments, to understand the structure and dynamics of the outer coating monolayers of these nanonucleases, either alone and in complex with substrates, in solution.The simulations provided high-resolution structural and dynamical picture of self-organization of coating monolayers impacting the formation of pre-catalytic complexes.

Metal-dependent catalysis of nucleic acid processing nanozymes: First steps toward computational nanoenzymology

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.