Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Apr 25;9(21):4777-4784.
doi: 10.1039/c8sc01283k. eCollection 2018 Jun 7.

Detection and Identification of Designer Drugs by Nanoparticle-Based NMR Chemosensing

Affiliations
Free PMC article

Detection and Identification of Designer Drugs by Nanoparticle-Based NMR Chemosensing

Luca Gabrielli et al. Chem Sci. .
Free PMC article

Abstract

Properly designed monolayer-protected nanoparticles (2 nm core diameter) can be used as nanoreceptors for selective detection and identification of phenethylamine derivatives (designer drugs) in water. The molecular recognition mechanism is driven by the combination of electrostatic and hydrophobic interactions within the coating monolayer. Each nanoparticle can bind up to 30-40 analyte molecules. The affinity constants range from 105 to 106 M-1 and are modulated by the hydrophobicity of the aromatic moiety in the substrate. Detection of drug candidates (such as amphetamines and methamphetamines) is performed by using magnetization (NOE) or saturation (STD) transfer NMR experiments. In this way, the NMR spectrum of the drug is isolated from that of the mixture, allowing broad-class multianalyte detection and even identification of unknowns. The introduction of a dimethylsilane moiety in the coating monolayer allows performing STD experiments in complex mixtures. In this way, a detection limit of 30 μM is reached with standard instruments.

Figures

Fig. 1
Fig. 1. Left: recognition of amphiphilic organic ions by MPGNs coated with amphiphilic thiols with complementary charge. Right: chemical structure of representative psychoactive molecules of the 2-phenethylamine (1) family: amphetamine (2), methamphetamine (3), cathinone (4), and MDMA (5) (color code: blue, negative charge; red, positive charge; grey, neutral hydrophilic; green, neutral hydrophobic).
Fig. 2
Fig. 2. Nanoparticle coating thiols and substrates used in this work; substrates colored in red are not luminescent.
Fig. 3
Fig. 3. (a) 1H-NMR spectrum of phenethylamine (7) and S1-AuNP in HEPES buffered D2O; (b) diffusion filter spectrum of the same sample; (c) NOE-pumping spectrum of the same sample (3072 scans, 4 h). (d) NOE-pumping-CPMGz spectrum of the same sample (60 ms CPMGz filter, 3072 scans, 4 h). Conditions: [7] = 2.0 mM, [S1-AuNP] = 15 μM, HEPES buffer 10 mM, and pD = 7.0.
Fig. 4
Fig. 4. 1H-NMR NOE pumping-CPMGz sub-spectra (3072 scans, 4 h) of AuNP-S1 (14 μM in D2O), HEPES buffer (10.0 mM) and different analytes (2 mM): (a)–(k). For 4-nitrophenethylamine (e), the NOE pumping spectrum is shown (same acquisition parameters). For 12 (g) and 15 (h), the signals respectively at 5.92, 5.11 and 1.04 ppm, present in the spectrum, are outside the spectral window shown for clarity (full spectra are reported in Fig. S23†).
Fig. 5
Fig. 5. Plot of the log K vs. log D (pH = 7.4) values relative to the binding of the luminescent analytes 8–13 and 17–19 to S1-AuNP. The lines represent the linear fit of the data (R = 0.885). Red circles report the affinity values estimated for substrates 1, 14 and 15 on the basis of their log D values and the fitting parameters. The error bars reported represent the confidence intervals (3σ) calculated from standard deviations reported in Table 1.
Fig. 6
Fig. 6. DOSY experiment performed on a mixture of phenethylamine (7), tyramine (8) and 4-nitro-phenethylamine (14) in water in the presence of S1-AuNP (32 transients, 64 scans per transient, 2 h). Conditions: [analytes] = 0.5 mM, [AuNP] = 45 μM, HEPES buffer 10 mM, and pD = 7.0. The blue and green bars represent the diffusion coefficients respectively of the nanoparticles and unbound analytes under the experimental conditions used.
Fig. 7
Fig. 7. Graphical representation of binding constants of analytes 10, 11, 18, 19 and S1-, S2-, S3- and S4-AuNPs. Values of association constants and binding sites with their uncertainties are reported in Table S1 in the ESI.
Fig. 8
Fig. 8. (a) 1H-NMR spectrum of N-methylphenethylamine HCl (6, 2 mM), phenylalanine (14, 2 mM) and glucose (20 mM) in D2O. (b) NOE pumping-CPMGz spectrum of the same sample in the presence of S2-AuNP (3072 scans, 4 h). (c) 1H-NMR spectrum of a drug tablet dissolved in D2O. (d) NOE pumping-CPMGz spectrum of the same sample in the presence of S2-AuNP (3072 scans, 4 h). Conditions: [S2-AuNP] = 15 μM, HEPES buffer 10 mM, and pD = 7.0.
Fig. 9
Fig. 9. (a) 1H-NMR subspectrum of phenylalanine (14, 1 mM) and N-methylphenethylamine (6, 50 μM). (b) STD subspectrum of the same mixture in the presence of S4-AuNP (1024 scans, 3 h). (c) Plot of the integrated signal area of the aromatic signals of 6 in the STD spectra vs. [6]; the blue line represents the linear fit of the data (R = 0.995). Conditions: [S4-AuNP] = 15 μM, HEPES buffer 10 mM, and pD = 7.0. The errors in the integral data (800 a.u) were estimated by repeated integrations of the most intense signal at 200 μM and considered constant.

Similar articles

See all similar articles

Cited by 1 article

References

    1. Airuehia E., Walker L. Y., Nittler J. Journal of Child & Adolescent Substance Abuse. 2015;24:186–190.
    1. Underwood E. Science. 2015;347:469–473. - PubMed
    1. European Drug Report, Trends and Developments, EMCDDA, Lisbon, 2017.
    1. Reniero F., Lobo Vicente J., Chassaigne H., Holland M., Tirendi S., Kolar K., Guillou C., JCR Science and Policy Report: Report on characterisation of New Psychoactive Substances (NPS), 2014.
    1. Ambient ionization high resolution mass spectroscopy techniques are also being investigated to obtain direct information on the chemical structure of new compounds, see: Znaleziona J., Ginterová P., Petr J., Ondra P., Válka I., Ševčík J., Chrastina J., Maier V., Anal. Chim. Acta, 2015, 874 , 11 –25 . - PubMed
Feedback