Electrosynthesis of Verdoheme and Biliverdin Derivatives Following Enzymatic Pathways

• Published in: Journal of the American Chemical Society Vol. 146; no. 23; pp. 15955 - 15964
• Main Authors: Lashgari, Amir, Wang, Xiao, Krause, Jeanette A., Sinha, Soumalya, Jiang, Jianbing “Jimmy”
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 30.05.2024; Amer Chemical Soc
• Subjects: Biliverdine - analogs & derivatives; Biliverdine - chemistry; Biliverdine - metabolism; Chemistry; Chemistry, Multidisciplinary; Electrochemical Techniques; Heme - analogs & derivatives; Heme - chemistry; Heme Oxygenase (Decyclizing) - chemistry; Heme Oxygenase (Decyclizing) - metabolism; Molecular Structure; Physical Sciences; Porphyrins - chemistry; Science & Technology; HEME OXYGENASE; REDUCTION; COMPLEXES; PORPHYRINS; COBALT(II); SPECTRAL PROPERTIES; COUPLED OXIDATION; TETRAPHENYLPORPHYRIN
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.4c02847

Artificial syntheses of biologically active molecules have been fruitful in many bioinspired catalysis applications. Specifically, verdoheme and biliverdin, bearing polypyrrole frameworks, have inspired catalyst designs to address energy and environmental challenges. Despite remarkable progress in benchtop synthesis of verdoheme and biliverdin derivatives, all reported syntheses, starting from metalloporphyrins or inaccessible biliverdin precursors, require multiple steps to achieve the final desired products. Additionally, such synthetic procedures use multiple reactants/redox agents and involve multistep purification/extraction processes that often lower the yield. However, in a single step using atmospheric oxygen, heme oxygenases selectively generate verdoheme or biliverdin from heme. Motivated by such enzymatic pathways, we report a single-step electrosynthesis of verdoheme or biliverdin derivatives from their corresponding meso-aryl-substituted metalloporphyrin precursors. Our electrosynthetic methods have produced a copper-coordinating verdoheme analog in >80% yield at an applied potential of 0.65 V vs ferrocene/ferrocenium in air-exposed acetonitrile solution with a suitable electrolyte. These electrosynthetic routes reached a maximum product yield within 8 h of electrolysis at room temperature. The major products of verdoheme and biliverdin derivatives were isolated, purified, and characterized using electrospray mass spectrometry, absorption spectroscopy, cyclic voltammetry, and nuclear magnetic resonance spectroscopy techniques. Furthermore, X-ray crystallographic data were collected for select cobalt (Co)- and Cu-chelating verdoheme and metal-free biliverdin products. Electrosynthesis routes for the selective modification at the macrocycle ring in a single step are not known yet, and therefore, we believe that this report would advance the scopes of electrosynthesis strategies.