Unknown designer drugs can be recognized by self-organized nanoparticle receptors and identified by magnetization transfer NMR.

Nanoparticle-assisted "NMR chemosensing" is an experimental protocol that exploits the selective recognition abilities of nanoparticle receptors to detect and identify small molecules in complex mixtures by nuclear Overhauser effect magnetization transfer. Although the intrinsic sensitivity of the first reported protocols was modest, we have now found that water spins in long-lived association at the nanoparticle monolayer constitute an alternative source of magnetization that can deliver a remarkable boost of sensitivity, especially when combined with saturation transfer experiments. The approach is general and can be applied to analyte− nanoreceptor systems of different compositions. In this work, we provide an account of the new method and we propose a generalized procedure based on a joint water−nanoparticle saturation to further upgrade the sensitivity, which ultimately endows selective analyte detection down to the micromolar range on standard instrumentation.

Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes can cleave phosphate esters and nucleic acids. Remarkably, such synthetic nanonucleases appear to catalyze metal (Zn)-aided hydrolytic reactions of nucleic acids similar to metallonuclease enzymes. To clarify the reaction mechanism of these nanocatalysts, here we have comparatively analyzed two nanonucleases with a >10-fold difference in the catalytic efficiency for the hydrolysis of the 2-hydroxypropyl-4-nitrophenylphosphate (HPNP, a typical RNA model substrate). We have used microsecond-long atomistic simulations, integrated with NMR experiments, to investigate the structure and dynamics of the outer coating monolayer of these nanoparticles, either alone or in complex with HPNP, in solution. We show that the most efficient one is characterized by coating ligands that promote a well-organized monolayer structure, with the formation of solvated bimetallic catalytic sites. Importantly, we have found that these nanoparticles can mimic two-metal-ion enzymes for nucleic acid processing, with Zn ions that promote HPNP binding at the reaction center. Thus, the two-metal-ion-aided hydrolytic strategy of such nanonucleases helps in explaining their catalytic efficiency for substrate hydrolysis, in accordance with the experimental evidence. These mechanistic insights reinforce the parallelism between such functionalized AuNPs and proteins toward the rational design of more efficient catalysts.

Self-assembled gold nanoparticles onto colloidal silica nanoparticles exhibited higher magnetization transfer efficiencies in NMR chemosensing experiments, allowing the detection of analytes as low as 10 μM.

Nanozymes based on TACN AuNPs and FMN photocatalyze the activation of a Pt(iv) prodrug into cisplatin.