Aqueous Solubilization of Hydrophobic Tetrapyrrole Macrocycles by Attachment to an Amphiphilic Single-Chain Nanoparticle (SCNP)

Solubilization of hydrophobic tetrapyrrole macrocycles and other fluorophores in aqueous solution has been achieved by covalent attachment to the terminus of an amphiphilic polymer, thereby affording a single-fluorophore–single-chain nanoparticle (SCNP). The polymer is a heterotelechelic random polyacrylate/polyacrylamide copolymer bearing hydrophobic and hydrophilic pendant chains. NMR and analytical SEC studies reveal that the polymer has an extended morphology in organic solvents but a folded unimeric morphology (~13 nm hydrodynamic diameter) in 1 M NaCl aqueous solution. Six hydrophobic organic fluorophores (coumarin, perylene, two chlorins, two phthalocyanines) have been synthesized with a conjugatable tether. Covalent conjugation of the fluorophore–maleimide to the polymer terminus via thiol–maleimide reaction afforded the single-fluorophore–SCNP with excellent aqueous solubility, retained spectral features, and fluorescence quantum yield value comparable with the respective hydrophobic benchmark in toluene. This single-fluorophore–single-polymer strategy simplifies the challenging and often idiosyncratic syntheses of water-soluble tetrapyrrole macrocycles by using the polymer as a general aqueous solubilization package, and in so doing opens up opportunities for the application of hydrophobic fluorophores in the life sciences.