Nanoparticle‐Assisted Affinity NMR Spectroscopy: High Sensitivity Detection and Identification of Organic Molecules

Abstract

A simple and effective method for high-sensitivity NMR detection of selected compounds is reported. The method combines 1D NMR diffusion filter experiments and small monolayer-protected nanoparticles as high-affinity receptors. Once bound to the nanoparticles, the diffusion coefficient of the analyte decreases in such way that spectral editing based on diffusion filters can separate its signals from those of other mixture components. Using nanoparticles functionalized with Zn -triazacyclonane complexes, detection and identification of phosphorylated organic molecules can be achieved. Diphenyl phosphate can be detected at 25 micromolar concentration with good selectivity. The selectivity toward organic carboxylates is enhanced at pD=3.75. In these conditions, commercial tablets containing betamethasone phosphate and a large excess of benzoate could be successfully analyzed.

Detection and identification of designer drugs by nanoparticle-based NMR chemosensing

“… 22 Affinity for amphiphilic organic anions can be strongly enhanced by decorating the monolayer with positively charged head-groups. 18 , 23 The accommodation of the hydrophobic portion of the substrate in the alkyl portion of the monolayer and the simultaneous ion-pairing interaction with the head groups grant selectivity and high affinity ( Fig. 1 ).…”

“…In this framework, we recently proposed “nanoparticle-assisted NMR chemosensing” as a general method for direct detection and identification of broad analyte classes. 18 In this approach, monolayer protected gold nanoparticles (MPGNs) act as self-organized receptors. Nanoparticle recognition is then exploited to extract the analyte NMR spectrum from that of the mixture, by use of diffusion-based experiments (DOSY or diffusion filters), 18 a along with magnetization (NOE-pumping) 18b – d or saturation (STD) transfer protocols.…”

Nanoparticle-Assisted Metabolomics

“…Due to their relatively large size, nanoparticles are slowly-diffusing species and dependent on the strengths of their interactions with certain metabolites, and they can differentially slow down the metabolites’ average translational diffusion, which can be used as a “diffusion filter” to separate metabolite signals. Recently, AuNPs functionalized with Zn 2+ -triazacyclonane complexes were applied to detect phosphorylated organic molecules to measure, for example, betamethasone phosphate in commercial drug tablets [ 42 ]. AuNPs with a 2-nm diameter were coated with thiols with different functional groups, which non-covalently interact with small organic molecules and slow down their translational diffusion.…”

Novel Sensing Strategies Based on Monolayer Protected Gold Nanoparticles for the Detection of Metal Ions and Small Molecules

“…In this case, the authors took advantage of the cooperative effect within the ligand shell to bind diamine molecules – with higher affinity than monoamines – thanks to the spontaneous formation of ditopic binding sites on the NP‐surface . In an attempt to decrease the limit of detection of this methodology, the use of highly‐affinity receptors for phosphates – triazacyclononane (TACN)−Zn 2+ complexes – and 1D NMR diffusion filter experiments were implemented . In such approach, diphenyl phosphate was detected at micromolar concentration with good selectivity.…”