Interdigitated Hydrogen Bonds: Electrophile Activation for Covalent Capture and Fluorescence Turn-On Detection of Cyanide

Hydrogen-bonding promoted covalent
modifications are finding useful
applications in small-molecule chemical synthesis and detection. We
have designed a xanthene-based fluorescent probe 1, in
which tightly held acylguanidine and aldehyde groups engage in multiple
intramolecular hydrogen bonds within the concave side of the molecule.
Such an interdigitated hydrogen bond donor–acceptor (HBD–HBA)
array imposes significant energy barriers (ΔG‡ = 10–16 kcal mol–1)
for internal bond rotations to assist structural preorganization and
effectively polarizes the electrophilic carbonyl group toward a nucleophilic
attack by CN– in aqueous environment. This covalent
modification redirects the de-excitation pathways of the cyanohydrin
adduct 2 to elicit a large (>7-fold) enhancement in
the
fluorescence intensity at λmax = 440 nm. A remarkably
faster (> 60-fold) response kinetics of 1,
relative
to its N-substituted (and therefore “loosely
held”) analogue 9, provided compelling experimental
evidence for the functional role of HBD–HBA interactions in
the “remote” control of chemical reactivity, the electronic
and steric origins of which were investigated by DFT computational
and X-ray crystallographic studies.