New Corrole Analogues: Isocorroles and Azulicorrole

Abstract

Porphyrinoids are a family of molecules, which consist of large ring structures or macrocycles. One of the oldest, and most important, of the porphyrinoids is the biological molecule called porphyrin. Since the dawn of life, porphyrins have orchestrated photosynthesis and oxygen respiration, two of the most important energy-generating processes in nature. In addition to porphyrins, other porphyrinoids like chlorophylls, corrin, and F430 play major roles in biology. In the laboratory, on the other hand, synthetic chemists have access to a vastly wider array of porphyrin-type molecules, with correspondingly diverse potential applications.<p>

<p>At the heart of porphyrinoid chemistry is a process called “the pyrrole-aldehyde condensation”, which allow chemists to synthesize a variety of porphyrinoids in a simple and facile manner. The pyrrole-aldehyde condensation is essentially a self-assembly process, in which two different types of molecules, pyrrole and aldehyde, assemble to chains that either cyclize spontaneously or by the action of oxidizing chemicals, to form the porphyrinoid macrocycles. Chains of different lengths naturally result in different porphyrinoids, but certain additives may be used to produce different porphyrinoids from the same chain. Moreover, once a porphyrinoid is made, facile synthetic methods exist that allow their transformation to yet another porphyrinoid. Overall, the pyrrole-aldehyde condensation is an impressive tool-box with which chemists may choose to make one of a large array of different porphyrinoids. <p>

<p>Simon Larsen’s doctoral thesis work carried out in the inorganic and materials chemistry group of Professor Abhik Ghosh at UiT details the synthesis of new porphyrinoids using pyrrole-aldehyde condensation. Corrole, a prominent member of the porphyrinoid family, is prepared in a two-step process where first pyrrole and aldehyde assemble to a chain of four pyrroles and three aldehydes, before an oxidizing chemical cyclizes the chain to form the finished corrole. Larsen discovered that adding a third molecule, called azulene, to the first step of the corrole synthesis, caused it to replace one of the pyrrole units of the chain, resulting in the new macrocycle azulicorrole upon cyclization. Larsen also discovered a new synthesis of another kind of porphyrinoid called isocorrole, which he prepared in one step from corroles. Importantly, his protocol holds considerable promise as a new and important synthetic method, since it proceeds almost instantaneously, for all intents and purposes.<p>

<p>In addition to their prominent role in nature, porphyrins are also ubiquitous in the human body, for better or for worse. Porphyria is a group of diseases, in which porphyrins accumulate in various tissues of the body. Exposure to sunlight transforms the porphyrins to dangerous toxins, and the worst forms of the disease, left untreated, can enact the kind of hideous disfigurement we through popular culture have come to identify with the undead. Indeed, victims of porphyria may have led to the idea of vampires and werewolves in ancient folklore. While searching for a cure for porphyria, in the mid-20th century scientists came to realize that the photoactivated toxicity of porphyrins might be a tool for medicine, and as a result, photodynamic therapy was born. In photodynamic therapy, molecules called photosensitizers destroy malignant tissue, simply by shining light on them. For photodynamic therapy to be effective inside the human body, the photosensitizer must absorb light at wavelengths that pass through the skin, an area of the electromagnetic spectrum referred to as the near-IR region. A key feature of the above-mentioned compounds is that they absorb strongly in the near-IR region, suggesting that they have considerable potential as photosensitizers in photodynamic therapy.