Monatsh Chem 139, 1513–1518 (2008) DOI 10.1007/s00706-008-0940-2 Printed in The Netherlands On synthesis and properties of hypericin-porphyrin hybrids Stefan Aigner, Heinz Falk Institute of Organic Chemistry, Linz, Austria Received 21 March 2008; Accepted 31 March 2008; Published online 9 June 2008 # Springer-Verlag 2008 Abstract Two diastereomeric tetraphenylporphyrinyl- !-hypericinyl-ethylenes were prepared and their properties investigated. The (Z)-diastereomer dis- played an even higher photosensitization of singlet oxygen and=or reactive oxygen species than hyperi- cin, whereas the (E)-configured derivative showed a somewhat weaker effect. Accordingly, hybridization of hypericin and porphyrin chromophores seems to be a promising target for the development of novel sen- sitizers for photodynamic therapy. Keywords Hypericin; Porphyrin; Singlet oxygen; Reactive oxidative species; Absorption. Introduction Hypericin (1) on the one side and derivatives of por- phyrin (2), among them the celebrated Photofrin + , on the other side, are on the forefront of sensitizers used in photodynamic therapy [1–3]. In both areas numerous investigations have been dedicated to im- prove these photosensitizers by appropriate deriva- tization to yield higher-generation agents. Among such studies hybridization of different chromo- phores or pharmacophores is a promising avenue [4]. Thus, we set out to explore the hybridization of hypericin with porphyrin to unite the intense long-wavelength absorption of hypericin with the very weakly absorbing, but highly tumor-targeting properties of porphyrins [5]. With respect to the hypericin moiety the methyl groups have proven hitherto to be ideally suited to serve as ‘‘anchors’’ for substitution because the photophysical proper- ties of the hypericin chromophore remain more or less untouched by such derivatizations [2]. With respect to the porphyrin moiety we chose a most easily accessible precursor system, namely a meso- tetraphenylporphyrin substituted at position 4 of one of the phenyl rings as e.g., with an amino or alde- hyde group [6, 7]. Two strategies were followed: first, the direct attachment of the meso-tetraphenyl- porphyrin moiety to the methyl carbon atom of the hypericin core, and second, hybridization of the two chromophores via a linker durable against hydrolyt- ic cleavage. Formulae 1 Correspondence: Heinz Falk, Department of Organic Chem- istry, Johannes Kepler University Linz, 4040 Linz, Austria, Europe. E-mail: heinz.falk@jku.at