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 ºC, 1 atm CO), using natural amino acid methyl ester derivatives as N-nucleophiles. This optimized methodology led to different families of amphiphilic porphyrins 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 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 our knowledge, this is the first application of a one-step aminocarbonylation reaction for porphyrin functionalization, providing a more straightforward approach compared with traditional multi-step methods.