Sunshine model monomer

At this time of year, for those in the Northern hemisphere, at least, thoughts turn to trips to sunny shores and the possibility of undertaking personal dermatological experiments involving solar ultraviolet rays and some subcutaneous photochemistry. However, for Australian researchers, the issue of understanding the chemistry of skin pigments, UV rays, and the formation of melanoma is a much more pressing issue.

Now, Stephen Nighswander-Rempel, Indumathy Mahadevan, Paul Bernhardt, Jessica Butcher, and Paul Meredith of the Centre for Organic Photonics and Electronics, at the University of Queensland, Brisbane, have designed and synthesised a novel indolic compound that can act as a model for the skin pigment eumelanin.

The team's NMR spectroscopy and X-ray diffraction studies reveal new insights into the biochemistry of eumelanin and the relationship between its chemical structure and its function. Ultimately, their work will provide insights into the differences between this pigment and pheomelanin and how they differ in cancerous and non-cancerous skin.

Eumelanin itself is a brown-black polymer of the organic compounds 5,6-dihydroxyindole (DHI), 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and their oxidized forms. It is the most common form of the skin pigment known generally as melanin.

Eumelanin and its coworkers protect us from the harmful effects of ultraviolet light and have a range of unique photochemical properties, as one might expect. Production of the pigment increases when UV-B radiation damages DNA in our skin and leads to the familiar delayed-onset of a suntan.

The mechanism by which the pigment protects us once a tan has formed is thought to be through the absorption of the UV radiation and dissipation of its energy as heat via ultrafast internal conversion, also known as radiationless de-excitation. This reaction allows the pigment to convert almost 100% of the energy of absorbed UV radiation into heat because of the compounds' broad absorbance. Additionally, eumelanin has an extremely low quantum yield and behaves as an antioxidant and free radical-scavenger.

Researchers have debated, for several years, how this relatively unique spectroscopic and chemical behaviour arises.

Most recently, the idea that chemical disorder in the structures of the pigment may be the underlying cause. This, says the Australian team, has been supported by studies on humic compounds from soil that have remarkably similar absorbance, emission and radiative quantum yield properties, which seem to arise through disorder effects. "It seems likely that a variety of macromolecules do form and that this diversity, or disorder, lies at the heart of eumelanin's functionality," the researchers say.

Nighswander-Rempel and colleagues have synthesised N-methyl-5-hydroxy-6-methoxyindole (MHMI) as a stable material, which they explain is highly soluble in a variety of solvents. MHMI forms dimers only through its 4-4' positions, which means that it has a limited number of ways of reacting, a design feature facilitated by the strategic placement of functional groups around the molecule's indole skeleton, the researchers explain. In contrast, the natural pigment monomers, DHI and DHICA, form a range of dimers even under mild conditions and so testing those materials is confounded by this complexity.

The team obtained an XRD crystal structure for their model compound, which the researchers say, shows an intriguing packing arrangement in which four monomers are grouped together in parallel pairs just 3.5 Å apart within each unit cell. They have also recorded optical spectra for this material and observed an absorbance profile with several peaks akin to 5,6-dihydroxyindole (DHI) and N-acetyl-tryptophanamide (NATA). They found that solvent effects alone are apparently not sufficient to influence the quantum yield.

In other words, "MHMI exhibits spectroscopic properties similar to DHICA," the researchers add, "interesting stacking features which shed light on possible eumelanin structural arrangements, and significant solvochromic behaviour." As such, the researchers suggest that their MHMI monomer is an ideal compound for studying the impact of oligomer size on the characteristics of indolic compounds with direct reference to understanding eumelanin and its role in sun protection.

Related links:

Photochem Photobiol, 2008, 23, 620-626
Nighswander-Rempel Page
Article by David Bradley