| People involved: | Villy Sundström, Alice Corani, Amal El Nahhas |
| Former members: | Magdalena Gauden, Jenny Eliasson, Annemarie Huijser |
This project is related to the following Fields, Subjects and Techniques:
The rate of malignant melanoma (a deathly form of skin cancer) under populations of European origin is since the 1970s doubling every 10 to 20 years. This is likely due to increased sun exposure and a poor natural protection by melanin pigments in the skin. On the other hand leads a shortage of UV-exposure to lack of vitamin D and accompanying medical problems. Remarkably, populations with darker skin containing more eumelanin instead of pheomelanin are far less vulnerable to malignant melanoma! This suggests a photoprotective function for eumelanin, while pheomelanin is thought to even be phototoxic.[1-4] Mechanistic information on underlying UV-induced processes is however largely lacking.
Eumelanin is a highly heterogeneous macromolecule based on 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), while pheomelanin is based on benzothiazine and benzothiazole derivatives (see Figure 1).[5-7] Earlier studies reported in literature have been strongly complicated by the highly heterogeneous structure of both pigments, and the lack of knowledge even on the building blocks. No assignments to specific processes occuring in a well-defined part of the pigment have been possible to make.
We want to achieve detailed insight into the photophysics and -chemistry of eumelanin and pheomelanin by starting with the smallest monomeric building blocks and utilizing this knowledge to analyze well-defined systems with increasing complexity and ultimately the full pigment. In this way the relationship between structure and functionality will be established. In addition, we are studying possibilities to control and manipulate UV-induced processes, providing the basis of a skin-type dedicated prevention of skin cancer.
DHICA
We have recently studied the UV-dissipative mechanisms in relevant states of eumelanin building block DHICA by ultrafast time-resolved fluorescence spectroscopy. Excitation of the carboxylate anion leads to dual fluorescence. The band peaking at 378 nm is caused by emission from the excited initial geometry. The second band around 450 nm is due to a complex formed between the anion and specific buffer components. In the absence of complex formation, the anion solely decays non-radiatively or by emission with a lifetime of about 2.1 ns. Excitation of the neutral carboxylic acid state, on the other hand, leads to weak emission around 427 nm with a short lifetime of 240 ps. Isotope studies show that this emission originates from a zwitterionic state formed upon excitation of the neutral state by sub-ps excited state intramolecular proton transfer (ESIPT) from the carboxylic acid group towards the indole nitrogen (see Figure 2).[8] Ongoing studies show that similar processes also occur in larger complexes, suggesting ESIPT is a build-in photoprotective mechanism in epidermal eumelanin.
DHICA oligomers
We are right now also studying the excited state dynamics of DHICA oligomers. [9]
Indole-2-carboxylic acid and 5-hydroxyindole-2-carboxylic acid
We have also investigated the role of the hydroxyl groups by joint computational and experimental studies on indole-2-carboxylic acid and 5-hydroxyindole-2-carboxylic acid. [10,11]
DHI
The UV-induced reaction mechanisms in the other eumelanin building block, DHI, appear to strongly depend on the excitation wavelength, as shown in Figure 3. [11]
DHI-based oligomers and eumelanin
We have recently also studied the UV-induced mechanisms in DHI-based dimers and synthetic eumelanin, the latter solubilized by using polyvinylalcohol (PVA). [12,13]
* Dr. Alessandro Pezzella and Prof. Marco d'Ischia, University of Naples, Italy (synthesis model pigments).
* Dr. Michal F. Rode and Prof. Andrzej L. Sobolewski, Institute of Physics and Academy of Sciences in Warsaw, Poland (Quantum-chemical calculations).
* Jonas K. Hannestad and Prof. Bo Albinsson, Chalmers University, Goteborg, Sweden.
* Dr. Sophie Canton, Lund University, Sweden (X-ray Absorption spectroscopy).
1. Harsanyi, Z. P.; Post, P. W.; Jeannie, P.; Brinkmann, P.; Chedekel, M. R.; Deibel, R. M., Experientia 1980, 36, 291.
2. Takeuchi, S.; Zhang, W.; Wakamatsu, K.; Ito, S.; Hearing, V.; Kraemer, K.; Brash, D., Proc. Natl. Acad. Sci. 2004, 101 (42), 15076.
3. Elwood, J.; Whitehead, S.; Davison, J.; Stewart, M.; Galt, M., Int. J. Epidem. 1990, 19, 801.
4. Bliss, J.; Ford, D.; Swerdlow, A.; Armstrong, B.; Cristofolini, M.; Elwood, J.; Green, A.; Holly, E.; Mack, T.;Mackie, R.; Osterlind, A.; Walter, S.; Peto, J.; Easton, D., Int. J. Cancer 1995, 62, 367.
5. Di Donato, P.; Napolitano, A.; Prota, G., Biochim. Biophys. Acta 2002, 1571 (2), 157.
6. Tesema, Y. T.; Pham, D. M.; Franz, K. J., Inorg. Chem. 2008, 47 (3), 1087.
7. Nighswander-Rempel, S. P., Biopolymers 2006, 82 (6), 631.
8. Huijser, A.; Pezzella, A.; Hannestad, J.K.;Panzella, L.;Napolitano, A.;d'Ischia, M.; Sundstrom, V., ChemPhysChem 2010, 11, 2424.
9. Huijser, A.; Pezzella, A.; d'Ischia, M.; Corani, A.; Sundstrom, V.; manuscript in preparation.
10. Huijser, A.; Rode, M.F.;Sobolewski, A.L.; Sundstrom, V., PhysChemChemPhys, 2011, submitted.
11. Huijser, A.; Pezzella, A.; Sundstrom, V., PhysChemChemPhys, 2011, 13, 9119.
12. Pezzella, A.; Ambrogi, V.; Arzillo, M.; Napolitano, A.;Carfagna, C.;d'Ischia, M., Photochemistry and Photobiology, 2010, 86, 533.
13. Pezzella, A.; Huijser, A.; Corani, A.; d'Ischia, M. Sundstrom, V., manuscript in preparation.