Aromatic isocyanides have gained a lot of attention lately as promising antifungal
and anticancer drugs, as well as high-performance fluorescent analytical probes for
the detection of toxic metals, such as mercury, even in vivo. Since this topic is
relatively new and aromatic isocyanides possess unique photophysical properties, the
understanding of structure–behavior relationships and the preparation of novel potentially
biologically active derivatives are of paramount importance. Here, we report the photophysical
characterization of 1,5-diisocyanonaphthalene (DIN) backed by quantum chemical calculations.
It was discovered that DIN undergoes hydrolysis in certain solvents in the presence
of oxonium ions. By the careful control of the reaction conditions for the first time,
the nonsymmetric product 1-formamido-5-isocyanonaphthalene (ICNF) could be prepared.
Contrary to expectations, the monoformamido derivative showed a significant solvatochromic
behavior with a ~50 nm range from hexane to water. This behavior was explained by
the enhanced H-bond-forming ability of the formamide group. The significance of the
hydrolysis reaction is that the isocyano group is converted to formamide in living
organisms. Therefore, ICNF could be a potential drug (for example, antifungal) and
the reaction can be used as a model for the preparation of other nonsymmetric formamido–isocyanoarenes.
In contrast to its relative 1-amino-5-iscyanonaphthalene (ICAN), ICNF is highly fluorescent
in water, enabling the development of a fluorescent turnoff probe.
