A Heme‐Acquisition Protein Reconstructed with a Cobalt 5‐Oxaporphyrinium Cation and Its Growth‐Inhibition Activity Toward Multidrug‐Resistant Pseudomonas aeruginosa

Abstract

Using artificial hemes for the reconstruction of natural heme proteins represents a fascinating approach to enhance the bioactivity of the latter. We report the synthesis of various metal 5-oxaporphyrinium cations as cofactors, and a cobalt 5-oxaporphyrinium cation was successfully incorporated into the heme-acquisition protein (HasA) secreted by Pseudomonas aeruginosa. We hypothesize that the oxaporphyrinium cation strongly binds to the HasA-specific outer membrane receptor (HasR) due to its cationic charge, which prevents the subsequent acquisition of heme. In fact, the reconstructed HasA inhibited the growth of Pseudomonas aeruginosa and even of multidrug-resistant P. aeruginosa.

Photodynamic Antimicrobial Activity of a Novel 5,10,15,20-Tetrakis (4-Ethylphenyl) Porphyrin against Clinically Important Bacteria

“…The antimicrobial activity of porphyrins is frequently attributed to their chemical properties, such as their ability to transfer electrons, catalyze the reactions of some enzymes (peroxidases, catalases, and oxidases), absorb photons and produce ROS, and break down the lipids in cell membranes [ 45 ]. However, one inhibition mechanism of bacterial growth that has been little studied to date is the binding of porphyrins to hemoproteins, where the resulting malfunction of these proteins affects bacterial metabolism [ 47 , 48 ]. This inhibition mechanism should be studied very carefully because there are very similar metabolic pathways in bacteria and mammals that require the intervention of heme groups, which suggests a possible cytotoxic effect in eukaryotes.…”

Electrosynthesis of Verdoheme and Biliverdin Derivatives Following Enzymatic Pathways

“…To investigate the similar properties in the metal-free verdoheme compound bearing phenyl groups at the meso positions of the 5-oxaporphyrin ring, H 2 PhOxa (Figure S11) and CuPhOx-aTFSI, we carried out TD-DFT calculations that elucidated ground and excited state positions for NH cis/trans configurations of H 2 PhOxa macrocycle and CuPhOxaTFSI. These included both NH isomeric forms of H 2 PhOxa due to two distinct NH tautomeric states within the macrocycle, as reported by Shinokubo et al 11,34 Energy-level analysis assessed ground (S 0 ) and excited (S 1 , S 2 , and S 3 ) states, showing good correlation with experimental data. Results including HOMO and LUMO molecular orbitals (MOs) are tabulated (Table S2) and graphically presented (Figure S12).…”

“…Shinokubo et al reported CV data of OEOxaPor (Figure S11) and its corresponding metal complexes, MOEOxaPor, M = Ag, Co, Ni, and Zn (Table S1). 11,34 According to their studies, the first reduction peak (E red 1 ) of MOEOxaPor shows up between −0.66 and −0.91 V vs Fc/Fc + regardless of the metal center. It is worth noting that metal-free OEOxaPor also exhibits the E red 1 within a similar potential range (Table S1), suggesting that the metal center has minimal influence on the first reduction of the MOEOxaPor complexes.…”

Pyrrolylmethylene Appended Corrorin: Peripheral Coordination and Transformation to Pyridyl Incorporated Hemiporphycene Analogue

“…Porphyrins, the so-called “pigments of life”, are extensively studied because of their unique structures and properties . Based on the porphyrin macrocycle, the structures and functions could be further extended by developing various porphyrinoids . In this respect, porphyrin isomers have been synthesized by changing the linking modes between the pyrrolic units.…”