Nanoscale supramolecular probes for the naked-eye detection of illicit drugs

The identification of psychoactive substances, in particular of designer drugs, on the site of their discovery is crucial to contrast the diffusion of drugs of abuse. We report here the first example of a nanoscale colorimetric probe, based on the nanoconfinement of a tricyclic dye and the target analytes in the cavity of cucurbit[8]uril. The probe selectively responds to N-(2methoxybenzyl)phenethylamines, with a limit of detection of 3 \u3bcM. The sensing system can be deposited on paper, thus obtaining a colorimetric strip test capable of discriminating illegal drugs from other substances of common use

Duplexvs.folding: tuning the self-assembly of synthetic recognition-encoded aniline oligomers

One of the challenges in the realization of synthetic oligomers capable of sequence-selective duplex formation is intramolecular folding interaction between complementary recognition units. To assess whether complementary hetero-oligomers can assemble into high fidelity duplex structures, the competing folding equilibria must be carefully considered. A family of recognition-encoded aniline oligomers were assembledviareductive amination of dianiline linkers and dialdehyde monomers, which were equipped with either a 2-trifluoromethylphenol or a phosphine oxide H-bond recognition unit. To test the possibility of 1,2-folding in mixed sequence oligomers, the self-assembly properties of the homo- and hetero-dimers were characterised by19F and1H NMR titration and dilution experiments in toluene and in chloroform. Three different systems were investigated with variations in the steric bulk around the H-bond acceptor unit and the length of the dianiline linker. For two systems, the hetero-dimers folded with intramolecular H-bonding in the monomeric state, reducing stability of the intermolecular duplex by two to three orders of magnitude compared with the corresponding homo-oligomers. However, the use of a long rigid linker as the backbone connecting two monomer units successfully prevents 1,2-folding and leads to the formation of a stable mixed sequence duplex in toluene

Hybrid nanoreceptors for high sensitivity detection of small molecules by NMR chemosensing

“Nanoparticle-assisted NMR chemosensing” combines magnetization transfer NMR techniques with the recognition abilities of gold nanoparticles (AuNPs) to isolate the NMR spectrum of relevant organic species in mixtures. The efficiency of the magnetization transfer is crucial to set the detection limit of the technique. To this aim, a second generation of nanoreceptors obtained by the self-organization of 2 nm AuNPs onto the surface of bigger silica nanoparticles shows better magnetization transfer performances, allowing the detection of analytes in water down to 10 μM concentration using standard instrumentation

Nanoparticle-Assisted NMR Spectroscopy: Enhanced Detection of Analytes by Water-Mediated Saturation Transfer

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

Selective NMR detection of N-methylated amines using cavitand-decorated silica nanoparticles as receptors

We report a strategy for the realization of NMR chemosensors based on the spontaneous self-assembly of lower rim pyridinium-functionalized tetraphopshonate cavitands on commercial silica nanoparticles. These nanohybrids enable the selective detection of physiologically relevant N-methylated amines, with a limit of detection of 31 mu M, via STD-based NMR experiments, achieving for the first time fine structural selectivity in nanoparticle-assisted NMR chemosensing

Toward supramolecular nanozymes for the photocatalytic activation of Pt(iv) anticancer prodrugs

A supramolecular nanozyme for the photocatalytic conversion of a Pt(iv) anticancer complex to cisplatin is described herein. We employed 1.9 nm Au nanoparticles decorated with thiol ligands bearing a TACN (1,4,7-triazacyclononane) headgroup to encapsulate FMN (riboflavin-5\u2032-phosphate). In the presence of an electron donor, flavin-loaded nanoparticles photocatalyzed the reductive activation of the prodrug cis,cis,trans-[Pt(NH3)2(Cl2)(O2CCH2CH2COOH)2] to cisplatin, achieving turnover frequency values of 7.4 min-1

On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes

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

Molecular Mechanisms Underlying Detection Sensitivity in Nanoparticle-Assisted NMR Chemosensing

Nanoparticle-assisted nuclear magnetic resonance (NMR)chemosensingexploits monolayer-protected nanoparticles as supramolecular hoststo detect small molecules in complex mixtures via nuclear Overhausereffect experiments with detection limits down to the micromolar range.Still, the structure-sensitivity relationships at the basisof such detection limits are little understood. In this work, we integrateNMR spectroscopy and atomistic molecular dynamics simulations to examinethe covariates that affect the sensitivity of different NMR chemosensingexperiments [saturation transfer difference (STD), water STD, andhigh-power water-mediated STD]. Our results show that the intensityof the observed signals correlates with the number and duration ofthe spin-spin interactions between the analytes and the nanoparticlesand/or between the analytes and the nanoparticles' solvationmolecules. In turn, these parameters depend on the location and dynamicsof each analyte inside the monolayer. This insight will eventuallyfacilitate the tailoring of experimental and computational setupsto the analyte's chemistry, making NMR chemosensing an evenmore effective technique in practical use