Design and Synthesis of Cellulose Derivatives with Antioxidant Activity Sonia Trombino, Roberta Cassano, * Ermelinda Bloise, Rita Muzzalupo, Sonia Leta, Francesco Puoci, Nevio Picci Introduction Free radicals are very reactive species that are generated in living organisms in a variety of metabolic processes and in much larger amounts during chronic or acute diseases. They have an important role in the immune system of the organism, and they also act as signal molecules to regulate cellular processes through subtle changes in redox balance. Therefore, in biological systems it is very important to maintain a balance between the formation and the removal of these species. Excess amounts of free radicals can cause cell disruption and death by reacting with important cellular components, such as nucleic acids, membrane lipids, or proteins, and mediate a wide range of diseases and conditions such as artherosclerosis, [1] inflam- mation, [2] carcinogenesis, [3] rheumatoid arthritis, [4] cata- racts, [5] asthma, [6] Parkinson’s disease [7–9] and diabetes. [10] Antioxidants are compounds that are able to protect the human body against damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS), generated regularly in living systems as a result of normal organ functions, or as a result of excess oxidative stress. The natural antioxidant systems of a living organism must be continuously maintained and replenished because anti- oxidants are largely a preferred target for free radicals. The efficiency of the natural antioxidant systems is often Full Paper In this study we report the synthesis and characterisation of cellulose ferulate, lipoate and a-tocopherulate, and their ability to inhibit lipid peroxidation in rat-liver microsomal membranes, induced in vitro by two different sources of free radicals: tert-butyl hydroperoxide and 2,2 0 -azobis-(2-amidinopropane). We also compared the antioxidant efficiency of the ferulate derivatives obtained through two different synthetic runs, and of a tocopheru- late derivative prepared from 6- carboxycellulose. This study showed that the designed systems, preser- ving the antioxidant activity of the free substrates, are more effective in protecting from tert-butyl hydro- peroxide than from 2,2 0 -azobis- (2-amidinopropane). Moreover, the cellulose ferulate with the higher degree of substitution acted as the best antioxidant. S. Trombino, R. Cassano, E. Bloise, R. Muzzalupo, S. Leta, F. Puoci, N. Picci Department of Pharmaceutical Sciences, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy Fax: þ39 0984493163; E-mail: roberta.cassano@unical.it 86 Macromol. Biosci. 2008, 8, 86–95 ß 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim DOI: 10.1002/mabi.200700110