Synthesis and Spectral Properties of 6'-Triazolyl-Dihydroxanthene-Hemicyanine Fused Near-Infrared Dyes

We describe the synthesis of a range of 6’-triazolyl-dihydroxanthene-hemicyanine (DHX-hemicyanine) fused dyes through an effective copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction, with the dual aim of providing molecular diversity and fine tuning spectral properties of these near-infrared (NIR)-active materials. This was implemented by reacting 16 different aliphatic and aromatic azides with a terminal alkynyl-based-DHX-hemicyanine hybrid scaffold prepared in four steps and 35% overall yield from 4-bromosalicylaldehyde. The resulting triazole derivatives have been fully characterized and their optical properties determined both in organic solvents and simulated physiological conditions (phosphate buffered saline containing 5% of bovine serum albumin protein). This systematic study is a first important step towards the development of NIR-I fluorogenic "click-on" dyes or related photoactive agents for light-based diagnostic and/or therapeutic applications.