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knowledge about the structural components necessary to selec-
tively bind mephedrone has been gained.
Synthesis and characterization protocols are highlighted in
the ESI.† Financial support for this work was provided by the
NSF grant OCE-0963064, NSF GK-12 #0947944 for J. H. Broome’s
graduate studentship, the Winston Churchill Foundation and
Santander Research Grant for K. Kellett’s 12 week travel stipend
to the Wallace lab, and the University of Hertfordshire for
K. Kellett’s graduate studentship. This paper was supported in
part by grants of the European Commission (Drug Prevention
Fig. 4 Normalized fluorescent titration of probe 2 with neat flephedrone
(red lines indicate probe 2 only and the first aliquot) Inset: Plot of and Information Programme 2014-16, contract no. JUST/2013/
flephedrone concentration and the quenching of fluorescence intensity
at 485 nm (acetone, 5 Â 10À6 mol dmÀ3, lex = 410 nm).
DPIP/AG/4823, EU-MADNESS project).
Notes and references
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mephedrone prefers to bind inside the pocket and interact with the
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Even though there were only modest optical changes upon
the binding between probe 2 and mephedrone, the 1H-NMR
spectra showed significant chemical shift changes with the drug
and no changes with caffeine and benzocaine, two common
cutting agents found in mephedrone street samples. Therefore,
we used NMR spectroscopy to evaluate if probe 2 could be used
to detect mephedrone in a simulated ‘street’ sample containing
these two compounds. Therefore, a protocol was developed to
produce the freebase of mephedrone in the presence of benzo-
caine and caffeine. Mephedrone hydrochloride, benzocaine and
caffeine were combined in equal proportions and dissolved in
water. The mixture was then filtered, as caffeine is sparingly
soluble in water compared to benzocaine and mephedrone
hydrochloride. The mephedrone freebase was then liberated
with ammonium hydroxide (pH = 10) and extracted into diethyl
ether. The NMR of this solution showed the presence of all
compounds; however, reduced caffeine and benzocaine signals
were seen relative to mephedrone, which was an advantageous
consequence of the protocol. NMR titration of probe 2 against
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Chem. Commun.
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