Aqueous solubilization of hydrophobic tetrapyrrole macrocycles by attachment to an amphiphilic single-chain nanoparticle (SCNP)

Abstract

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 groups. The polymer has a folded unimeric morphology (∼13 nm hydrodynamic diameter) in 1 M NaCl aqueous solution as indicated by dynamic light-scattering spectroscopy. Five hydrophobic organic fluorophores (coumarin, perylene, two chlorins, one phthalocyanine) have been synthesized with a conjugatable tether. Covalent conjugation of the fluorophore–maleimide to the polymer terminus via thiol–maleimide reaction was carried out in DMF. The resulting fluorophore–SCNP in 1 M NaCl aqueous solution exhibited spectral features and fluorescence quantum yield comparable to those of the respective hydrophobic benchmark in toluene. This single-fluorophore–single-polymer strategy bypasses 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.