Cyanine Dyes

Introduction

Cyanine dyes are highly conjugated, fluorescent molecules with absorption and emission wavelengths in the near infra-red region (700–900 nm). The simplest synthetic route to heptamethine cyanine dyes 1 (so-called because of the seven carbons in the conjugated backbone) was first described by Narayanan and Patonay who heated N-alkylated indolium salts 2 with 2-chloro-1-formyl-3-(hydroxyl methylene) (3) in a Vilsmeier-type reaction.[1] These heptamethine cyanine scaffolds can be readily modified through displacement of the labile chloride group by nucleophiles,[2] [3] [4] resulting in fluorescent molecules with varying quantum yields, extinction coefficients, and fluorescence maxima. Conjugation to biomolecules is achieved through chlorine substitution by 3-(4-hydroxyphenyl) propionic acid.

The resulting cyanine dye has a carboxylic acid moiety which can be coupled to an amine-containing compound via amide-bond formation. Enhanced aqueous solubility is typically achieved through sulfonation of the indole 2. As biological tissue does not absorb strongly within the near infra-red window, cyanine fluorophores are ideal for in vivo optical imaging application,[5] [6] [7] while clinically, indocyanine green has been used for over 25 years in fluorescence angiography and opthalmology (mouse LD₅₀ = 60 mg/kg).[8,9]

Scheme 1 Synthesis of heptamethine cyanine dyes 1

• References

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