The Red Color of Life Transformed – Synthetic Advances and Emerging Applications of Protoporphyrin IX in Chemical Biology

Abstract

Protoporphyrin IX (PPIX) is the porphyrin scaffold of heme b, a ubiquitous prosthetic group of proteins responsible for oxygen binding (hemoglobin, myoglobin), electron transfer (cytochrome c) and catalysis (cytochrome P450, catalases, peroxidases). PPIX and its metallated derivatives frequently find application as therapeutic agents, imaging tools, catalysts, sensors and in light harvesting. The vast toolkit of accessible porphyrin functionalization reactions enables easy synthetic modification of PPIX to meet the requirements for its multiple uses. In the past few years, particular interest has arisen in exploiting the interaction of PPIX and its synthetic derivatives with biomolecules such as DNA and heme‐binding proteins to evolve molecular devices with new functions as well as to uncover potential therapeutic toeholds. This review strives to shine a light on the most recent developments in the synthetic chemistry of PPIX and its uses in selected fields of chemical biology.

A Coumarin–Porphyrin FRET Break-Apart Probe for Heme Oxygenase-1

“…Another route of functionalization is through amide coupling methodologies of one (or both) of the propionic acid residues . Such reactivity has been summarized in an excellent review by Senge and Sitte . However, it still remains a major challenge to functionalize the α- meso -position of PPIX selectively, as each of the four inequivalent meso -positions have an almost identical reactivity leading to a mixture of species that are difficult to separate. , …”

Learning from Nature: Bioinspired Chlorin-Based Photosensitizers Immobilized on Carbon Materials for Combined Photodynamic and Photothermal Therapy

“…These tetrapyrrolic macrocycle types are commonly found in nature and provide a key biochemical role in many natural processes. An example of porphyrin in biological processes is the heme present in cytochrome P-450 monooxygenase enzymes [ 60 ], hemoglobin, and myoglobin for the transport and storage of O 2 [ 61 ]. Chlorophyll is responsible for the green color of plants, algae, and cyanobacteria, and bacteriochlorophyll a , a bacteriochlorin derivative, is involved in photosynthesis in some bacteria.…”

Main Strategies for the Synthesis of meso-Arylporphyrins

“…Therefore, it seems reason­able to isolate bioporphyrins of the chlorophyll and heme groups from natural sources such as plants, algae, and animal blood and, if necessary, to modify them [ 22 , 23 ]. Methods for the isolation of tetrapyrroles from plant and animal raw materials and their purpose­ful modification have been widely developed, and the variety of methodological approaches for their prepara­tion from various sources can be the subject of a sepa­rate review [ 24 – 27 ].…”