Development of a Near Infrared Fluorescence Labeling Reagent: Synthesis of Indole-Functionalized Indocyanine Green Derivatives

Abstract

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-di­nitroanisole 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.

Key words

cycloaddition - indoles - nucleophilic aromatic substitution - indocyanine green - near infrared fluorescence

References and Notes

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17

RajanBabu et al. reported α-nitroarylation by aromatic nucleophilic substitution with silyl enol ethers was performed using TASF in THF-MeCN at rather lower temperatures such as -60 ˚C. See ref. 16.

20

Synthesis of 5-amino-1-δ-sulfobutyl-2,3,3-trimethyl-(3H)-indolenine and its cyanine derivatives was reported in ref. 11b.

21

Compound 3c was prepared from 1,1,2-trimethyl-(1H)-benz[e]indole and 1,4-butane sultone according to standard methods.