10.1002/anie.201902316
Angewandte Chemie International Edition
COMMUNICATION
preference of 3-AuNP. Since simulation suggested a relatively
defined structure of the binding site, we tested other analytes
with a similar structure but different H-bonding pattern abilities
(Figure 6). In the same conditions as before, only 2-hydroxy-
phenylboronic acid was detected by 3-AuNPs with a S/N ratio
(8) comparable to that of salicylate. However, 2-amino-
benzoate was detected with a lower S/N ratio (3), while 2-
methoxy-benzoate was not detected at all (Figure S31-33). 2-
hydroxy-phenylboronic acid was the only guest tested featuring
the same pattern of H-bond acceptor sites of salicylate.
Remarkably, similar differences in the binding of these three
guests to 3-AuNP were suggested by computational docking
studies. These were performed using a representative binding
pocket individuated by MD simulations (Figure 6). After having
confirmed the best docking pose of salicylate in this pocket is
similar to that obtained with MD simulations, we examined the
other potential guests. With 2-hydroxy-phenylboronic acid, we
obtained a pose similar to that of salicylate, with formation of the
Figure 7. A) 1H-NMR subspectrum of sodium salicylate (s) and 4-
hydroxybenzoate (h) 50 M each in H2O/D2O 9:1. B) Water-STD subspectrum
of the same sample in the presence of 1-AuNP. C) Water-STD subspectrum of
the same sample in the presence of 3-AuNP (*: residual AuNP signals).
Conditions: [AuNP] = 7.5 M, carbonate buffer 20 mM, pH = 10, Temperature
= 28 °C, 512 scans, 62 min acquisition time.
recognized
intramolecular
H-bond
network. With
2-
aminobenzoate, the guest orientation was similar but tilted with
respect to salicylate. In contrast, with 2-methoxybenzoate, the
best docked pose was completely different than that of salicylate.
Finally, we sought to use the greater affinity of 3-AuNP to
achieve detection of salicylate at micromolar concentrations. To
this aim, we used the water-STD experiment recently developed
by some of us.[14] Compared to the NOE pumping, water-STD
delivers a much higher sensitivity through the simultaneous
saturation of water and nanoparticles spins at high power.
However, detecting analytes at low concentration also requires
nanoreceptors with sufficient affinity. We analyzed samples
containing the nanoparticles, and salicylate and 4-
hydroxybenzoate both at 50 M concentration in 9:1 H2O/D2O
solutions (Figure 7). Despite this highly sensitive protocol, no
analyte signals were obtained with 1-AuNP. With this
nanoparticle and in these conditions, the fraction of bound
analyte was too small to produce a detectable signal. However,
for 3-AuNP, the sole salicylate signals were present in the
spectrum with a S/N of 3. Hence, the increased affinity of these
nanoparticles for salicylate, combined with a more sensitive
NMR detection protocol, could improve the detection limit 100-
fold.
In conclusion, the results presented in this work demonstrate
the possibility to rationally program the molecular recognition
ability of monolayer-protected nanoparticles. As with protein-
ligand recognition studies,15 we could gradationally mutate the
relevant interacting groups in the nanoparticle coating molecules
in order to tune the affinity of the nanoparticles for salicylate.
The effects of these mutations on affinity and selectivity were
predicted by computational simulations and validated with
experiments.
no. 18883 to M.D.V.). Xiaohuan Sun thanks the China
Scholarship Council for a PhD fellowship (no. 201506870019).
Keywords: rational design • molecular recognition • gold
nanoparticles • NMR sensing
[1]
[2]
J.-M Lehn, Science 1985, 227, 849–856.
U. Drechsler, B. Erdogan, V. M. Rotello, Chem.-Eur. J. 2004, 10, 5570-
5579.
[3]
a) A. K. Boal, V. M. Rotello, J. Am. Chem. Soc. 1999, 121, 4914-4915;
b) A. K. Boal, V. M. Rotello, J. Am. Chem. Soc. 2000, 122, 734-735; c)
G. Fantuzzi, P. Pengo, R. Gomila, P. Ballester, C. A. Hunter, L.
Pasquato, P. Scrimin, Chem. Commun. 2003, 1004-1005; d) X. Liu, Y.
Hu, F. Stellacci, Small 2011, 7, 1961-1966; e) R. Bonomi, A. Cazzolaro,
L. J. Prins, Chem. Commun.2011, 47, 445-447; f) G. Pieters, C.
Pezzato, L. J. Prins, Langmuir 2013, 29, 7180-7185; g) B. Perrone, S.
Springhetti, F. Ramadori, F. Rastrelli, F. Mancin, J. Am. Chem. Soc.
2013, 135, 11768-11771; h) M.-V. Salvia, F. Rarnadori, S. Springhetti,
M. Diez-Castellnou, B. Perrone, F. Rastrelli, F. Mancin, J. Am. Chem.
Soc. 2015, 137, 886-892; i) S. Yapar, M. Oikonomou, A. H. Velders, S.
Kubik, Chem. Commun. 2015, 51, 14247-14250; l) L. Riccardi, L.
Gabrielli, X. Sun, F. De Biasi, F. Rastrelli, F. Mancin, M. De Vivo, Chem
2017, 3, 92-109; m) L- Gabrielli, D. Rosa-Gastaldo, M.-V. Salvia, S.
Springhetti, F. Rastrelli, F. Mancin, Chem. Sci. 2018, 9, 4777-4784.
P. Pengo, S. Polizzi, M. Battagliarin, L. Pasquato, P. Scrimin, J. Mater.
Chem. 2003, 13, 2471-2478.
[4]
[5]
[6]
M. Lucarini, P. Franchi, G. F. Pedulli, C. Gentilini, S. Polizzi, P. Pengo,
P. Scrimin, L. Pasquato, J. Am. Chem. Soc. 2005, 127, 16384-16385.
a) M. Wu, A. M. Vartanian, G. Chong, A. K. Pandiakumar, R. J Hamers,
R. Hernandez, C. J. Murphy, J. Am. Chem. Soc. 2018, in press, DOI:
10.1021/jacs.8b11445; b) T. Kister, D. Monego, P. Mulvaney, A.
Widmer-Cooper, T. Kraus, ACS Nano 2018, 12, 5969-5977; c) K.
Salorinne, S. Malola, O. A. Wong, C. D. Rithner, X. Chen, C. J.
Ackerson, H. Häkkinen, Nat. Commun.2016, 7, 10401; d) P. Possocco,
C. Gentilini, S. Bidoggia, A. Pace, P. Franchi, M. Lucarini, M. Fermeglia,
S. Pricl, L. Pasquato, Acs Nano 2012, 6, 7243-7253.
Acknowledgements
Funded by the Università di Padova P-DiSC (grant #09BIRD
2017-UNIPD, Dipartimento di Scienze Chimiche, to F.M.) and by
the Italian Association for Cancer Research (Investigator Grant
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