Development of a near infrared fluorescence labeling reagent: Synthesis of indole-functionalized indocyanine green derivatives

We have demonstrated a facile synthesis of functionalized indocyanine green (ICG) derivatives. Heteroatom-substituted indolenine was synthesized via S _NAr reaction of 5-chloro-2,4-di-nitroanisole with 1,2-dimethyl-1-propenyl trimethylsilyl ether followed by reduction of the nitro groups. After the introduction of hydrophilic butanesulfonate moieties, homo- and heterocondensations with glutaconaldehyde dianilide provided symmetrical and unsymmetrical ICG derivatives, which exhibit near infrared (NIR) absorption and fluorescence emission similar to those of ICG. NIR fluorescence labeling reagent was synthesized using the amino group in the ICG derivative. The 1,3-dipolar cycloaddition with benzyl azide was performed utilizing copper nanoparticles toward a versatile method for the synthesis of NIR molecular imaging probes.