Author: Herr Dr. Amoneit
Last saved by: Saritas, Sevim

Location of Caffeic Acid and its Alkyl Esters in Liposomes and Correlation with its Bioactivity
F. Paiva-Martins^1, C. Silva^1, L. Palagi^1, M. Costa^1, S. Losada-Barreiro^1, M. Ferreira^2, P. Gameiro^2, C. Bravo-Díaz^3, J. Fernandes^4, A. Santos-Silva^5
^1CIQUP and ^2REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal. ^3Faculty of Chemistry, Department of Physical-Chemistry, University of Vigo, Vigo, Spain. ^4IBILI and ^5IBMC, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.

The knowledge of the interaction of the antioxidant with lipid membranes is crucial to understand the distribution of these molecules in the body, and to establish relationships between the physico - chemical properties and their biological effects. 
Caffeic acid (CA), a strong radical scavenging molecule, has a hydrophilic nature and therefore has very low diffusion into biomembranes. Therefore, it was our aim to increase the hydrophobicity of CA by synthetizing CA esters with different alkyl chain sizes (C1-C16) [1] and to study the interaction of these esters with a model membrane, using DMPC liposomes, a synthetic phospholipid containing choline. Fluorescence anisotropy of probes and fluorescence quenching studies were used to identify the location of CA and its caffeates in the liposomes [2].  DPH and TMA-DPH were used as fluorescence probes. 
In the studies by fluorescence anisotropy, it was found that caffeates interacted with the interior of the membrane in the same way except for C1, which changed to a lesser extent the anisotropy of the probes. In fluorescence quenching studies the order of interaction with the probe DPH, located inside the liposome, was C8 > C2 > C16 > C1. CA did not change both probes anisotropy and did not show any activity on the fluorescence quenching of the probe DPH proving its more external location.
The protective effects of the same serie of phenolipids with increasing liposolubility against the blood red cell oxidative injury were evaluated. Results showed that caffeates with intermediate alkyl chain (C4 and C8) presented the best protection against the oxidative hemolysis initiated by AAPH.
[1] Menezes, J.C.M.D.S, Kamat, S.P., Cavaleiro, J.A.S, Gaspar, A.garrido, J.,Borges ,F. (2011) J Med Chem, 46, 773-777.
[2] Paiva-Martins, F; Gordon, M. H.; Gameiro, P. (2003), Chem. Phy. Lipids, 124, 26-34.