A compact water-soluble porphyrin bearing an iodoacetamido bioconjugatable site

Abstract

A broad range of applications requires access to porphyrins that are compact, water-soluble, and bioconjugatable. A symmetrically branched hydrocarbon chain (‘swallowtail’) bearing polar end groups imparts high (>10 mM) aqueous solubility upon incorporation at one of the meso positions of a trans-AB-porphyrin. Two such swallowtail-porphyrins (1a, 1b) equipped with a conjugatable group (carboxylic acid, bromophenyl) have been prepared previously. The synthesis of three new water-soluble trans-AB-porphyrins is reported, where each porphyrin bears a diphosphonate-terminated swallowtail group and an amino (2a), acetamido (2b), or iodoacetamido (2c) group. The amine affords considerable versatility for functionalization. The iodoacetamide provides a sulfhydryl-reactive site for bioconjugation. Porphyrins 2a–2c were fully characterized in aqueous solution by ¹H NMR spectroscopy (in D₂O), ESI-MS, static absorption spectroscopy, and static and time-resolved fluorescence spectroscopy. Porphyrins 2a–2c exhibit characteristic porphyrin absorption and emission bands in aqueous solution, with a strong, sharp absorption band in the blue region (∼401 nm) and emission in the red region (∼624, 686 nm). Porphyrin 2b in aqueous phosphate buffer or phosphate-buffered saline solution exhibits a fluorescence quantum yield of ∼0.04 and an excited singlet-state lifetime of ∼11 ns. Collectively, the facile synthesis, amenability to bioconjugation, large spacing between the main absorption and fluorescence features, and long singlet excited-state lifetime make this molecular design quite attractive for a range of biomedical applications.