Optically Active Oligomer Units in Aggregates of a Highly Unsaturated, Optically Inactive Carotenoid Phospholipid Bente Jeanette Foss, [a] Hans-Richard Sliwka,* [a] Vassilia Partali, [a] Christian Kçpsel, [b] Bernhard Mayer, [b] Hans-Dieter Martin,* [b] Ferenc Zsila, [c] Zsolt Bikadi, [c] and Miklos Simonyi* [c] Introduction The chiroptical properties of glycerolipids have been rarely investigated, while the two other groups of vital biomole- cules, carbohydrates and proteins with their well-established exclusive building blocks of d-sugars and l-amino acids, have received a lot of attention. Despite the fact that the biosynthesis of lipids also results in only one specific enan- tiomer, a chiral, functional discrimination of enantiomeric lipids has rarely been found. Membranes consist of pure phospholipid enantiomers, but with respect to penetration and other physical properties, phosphocholines behave as achiral molecules. [1–3] It was only recently that a decisive enantiomeric interaction between odorants and lipids was detected in the olfactoric system. [4] Another reason for ne- glecting chiroptical investigations of glycerolipids is their in- visibility. (Phospho)lipids show notoriously low or no specif- ic rotations, likewise, electronic optical activity (EOA) is weak or absent due to the lack of chromophores. [5] The few natural chromophoric lipids contain ajenoic acids C12:5, C14:5 in triglycerides [6] and parinaric acid C18:4 in phophatidylcholines. [7] The circular dichroism (CD), or fluo- rescence-detected CD (FDCD), of these lipids has not yet been measured, nor have chiral lipids been prepared from synthetic conjugated tetraenic fatty acids. [8] The acyl chains in these unsaturated lipids are only partly accessible by EOA spectroscopy. In various attempts to introduce chro- mophores, phospholipids with stilbene, biphenyl, terphenyl, and azobenzene fatty acids have been synthesized. [9–11] Like- wise, a glycerophosphatidylcholine enantiomer with styryl- thiophene acyl groups was synthesized, which was devoid of optical activity. [12] Undoubtedly, the mentioned lipids con- tain rather xenobiotic acyl groups and are, therefore, differ- ent from lipids of naturally occurring fatty acids. For historical reasons optical activity is restricted to wave- lengths from 200–800 nm. Although the accessible chiropti- cal spectral range has successively been extended to both lower and higher wavelengths, enantiomers continue to be defined as “optically inactive” when no signal in the classical wavelength scale is detected. Thus, the highly unsaturated carotenoylphospholipid (R)-5 (in MeOH), which does not exhibit EOA in the usual accessible range of the dichro- graph, (see Figure 1a, c), is considered optically inactive. Abstract: Enantiomers of glycerophos- pholipids show low or no optical activi- ty. Accordingly, optical activity was not observed with the R enantiomer of a highly unsaturated carotenoyl lyso- phospholipid in solution. In spite of this, strong Cotton effects are detected in water. The amphiphilic carotenoid– phospholipid monomers associate to form aggregates, whose optical activity is attributed to oligomeric entities. These small helical assemblies cannot exist independently. Yet, the calculated octamer represents the simplest repeat- ing primary unit that sufficiently ex- presses the absorption properties and supramolecular optical activity. Keywords: carotenoids · helical structures · molecular modeling · phospholipids [a] B.J. Foss, H.-R. Sliwka, V. Partali Norges Teknisk Naturvitenskapelige Universitet (NTNU) Institutt for Kjemi 7491 Trondheim (Norway) Fax: (+ 47) 73-59-6255 E-mail : hrs@nvg.ntnu.no [b] C. Kçpsel, B. Mayer, H.-D. Martin Institut für Organische Chemie und Makromolelulare Chemie Heinrich-Heine-Universität, 40225 Düsseldorf (Germany) Fax: (+ 49) 211-81-14324 E-mail: martin@uni-duesseldorf.de [c] F. Zsila, Z. Bikadi, M. Simonyi Department of Bioorganic Chemistry, Chemical Research Center 1525 Budapest (Hungary) Fax: (+ 361) 325-9188 E-mail: msimonyi@chemres.hu Chem. Eur. J. 2005, 11, 4103 – 4108 DOI: 10.1002/chem.200401191  2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4103 FULL PAPER