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Major advance in research on melanin, the pigment that colours skin, eyes, and hair

Published: 10 April 2023

For the first time, scientists produce an organic molecule that mimics melanin’s essential properties

In a study , a multidisciplinary, international team of scientists at Ď㽶ĘÓƵ, The Ohio State University, and the University of Girona announced that they had succeeded in synthesizing a melanin model compound. This breakthrough sheds new light on melanin’s structure and the unusual properties that enable it to protect organisms from the damaging effects of ultraviolet radiation.

A research question that goes back centuries

Melanin pigments, which give colour to skin, eyes, and hair, have been studied for over four centuries. Scientists have long known that melanin derives from the simple amino acid L-tyrosine and that it protects organisms from the sun's harmful rays and supports vision, hearing, and the immune system. Yet its chemical structure at the atomic level has remained enigmatic.

Just as DNA is made up of building blocks in the form of nucleotides and proteins are made up of building blocks in the form of amino acids, so too is melanin made up of building blocks. The difference is that no one yet knows what those building blocks are.

“It is remarkable that in 2023, we still don’t know the fundamental constituents of the substance that gives us our skin colour,” said Jean-Philip Lumb, Professor of Chemistry at McGill and one of the lead authors of the study. “Our objective is to gain clear insight into what atoms make up melanin and how they are arranged so that we can understand the source of melanin’s functional properties.”

Toward a melanin-derived sunscreen

Scientists have long endeavored to study a highly reactive component of melanin, known as indolequinone (IQ), to better understand how it gives rise to melanin’s functional properties. In the current study, the researchers created a shielded version of IQ that was stable enough for detailed spectroscopic studies. Together with of The Ohio State University and of the University of Girona, the team investigated IQ’s optical and electronic properties and discovered that IQ exhibited intriguing sun-screening qualities that the researchers had not anticipated.

Previous attempts to create melanin model compounds have all resulted in molecules that absorb light but then release the captured energy by emitting a photon. But this is precisely what sunscreen tries to prevent. Instead, chemical sunscreens convert UV light into heat before it can penetrate the skin and damage DNA. To the researchers’ surprise, these sun-screening properties were what they found when they studied IQ. “When we made this molecule, we anticipated that it would be like all other quinones that had been previously studied and that it would absorb and then emit light,” Lumb said. “But we found that this deceptively simple molecule does something extraordinary: it takes all of the energy that it absorbs from light and converts it into heat."

That was not the only unexpected feature the researchers identified in the melanin model compound. Effective chemical sunscreens should be “broad-spectrum”: they should absorb and convert light from across the entire visible light spectrum. The researchers found that IQ absorbs all wavelengths from 200 to 1000 nanometers, from ultraviolet to infrared. “While other molecules exhibit broad-spectrum absorption, none of them are as small as IQ,” said Lumb. “This has practical benefits because the number of atoms needed to arrive at this particular function is fewer than anything reported up to now."

Interdisciplinary collaboration across three countries

The findings result from a collaboration between Lumb, a synthetic organic chemist at Ď㽶ĘÓƵ, Kohler, a laser spectroscopist at The Ohio State University, and Blancafort, a theoretical chemist at the University of Girona, Spain. Each collaborator made essential contributions to the project: McGill researchers created the compounds and sent them to Ohio State for spectroscopic studies, which were in turn shared with the University of Girona for computational analysis.

Even though all three PIs are chemists studying distinct aspects of melanin, Lumb said they approached the challenge of understanding melanin differently. “Even though we all work on the same problem, our approaches are acutely different and complementary. One of the challenges was to create a shared language around melanin that we could all use to take this project forward.”

The collaboration, formed in the middle of the pandemic, is only getting started. “There is still much ambiguity around what creates pigmentation, and we are excited about the future of our approach,” Lumb said. “These fundamental questions surrounding pigmentation are difficult to solve but are at the heart of human curiosity.”

About the study

by Xueqing Wang, Lilia Kinziabulatova, Marco Bortoli, Anju Manickoth, Marisa A. Barilla, Haiyan Huang, Lluís Blancafort, Bern Kohler, and Jean-Philip Lumb was published in Nature Chemistry. The research was supported by the Natural Sciences and Engineering Research Council of Canada, the Ohio Eminent Scholar funds, the Ministerio de Ciencia e Innovación, Secretaria d’Universitats de Recerca, and the European Social Fund.

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