Unlocking New Porphyrin Aminoacid Bioconjugates with a Pd-Catalyzed Carboxamide Synthesis

Abstract

This study introduces a novel approach for the one-step preparation of carboxamide porphyrin-amino acid bioconjugates via palladium/xantphos-catalyzed aminocarbonylation of 5,15-dibromo-10,20-diphenylporphyrin and 5,10,15,20-tetrakis(4-bromophenyl)porphyrin, under relatively mild conditions (70–100 °C, 1 atm CO), using natural amino acid methyl ester derivatives as N-nucleophiles. This optimized methodology leads to different families of amphiphilic porphyrin bioconjugates containing between one and four amino acids through carboxamide bonds, with isolated yields up to 71%. The resulting porphyrin-amino acid conjugates incorporate glycine, alanine, phenylalanine, and valine, offering tunable molecular weights and functional properties tailored to diverse applications. Comprehensive characterization using proton nuclear magnetic resonance (¹H-NMR), UV-Visible absorption, fluorescence spectroscopy, and singlet oxygen quantum yields highlights the potential of these conjugates as photosensitizers for photodynamic therapy and microbial inactivation. To the best of one's knowledge, this is the first application of a one-step aminocarbonylation reaction for porphyrin functionalization, providing a more straightforward approach compared with traditional multistep methods.