Theoretical and Raman Spectroscopic Studies of the Conformational Changes of Thyroxine Induced by Interactions with DMPC Phospholipids

A. PETRUK; FARIAS, R.; ROSA MARIA SUSANA ALVAREZ

Rosario, Santa Fe

Congreso; XXXV Reunión Anual de la Sociedad Argentina de Biofísica; 2006

Theory and modeling of biological systems  Theoretical and Raman Spectroscopic Studies of the Conformational Changes of Thyroxine Induced by Interactions with DMPC Phospholipids Ariel A. Petruka, Ricardo N. Faríasb, Rosa María S. Álvareza,b aInstituto de Química Física,Fac.de Bioqca., Qca. y Fcia., UNT, San Lorenzo 456, Tucumán 4000 bINSIBIO, Inst. Sup. Inv. Biológicas, Chacabuco 461, Tucumán 4000 mysuko@fbqf.unt.edu.ar During the last years we have been interested in studying by vibrational spectroscopy structural changes of thyroid hormones T2, T3 and T4 induced by interactions with membrane phospholipids. Relevant Raman vibrational bands of L-T3 and L-T4 have resulted to be sensitive spectral markers for monitoring conformational changes of the hormones after insertion into phosphatidylcholine lipids (PC). The different molecular structures that these hormones can adopt were associated with the rotational energy that governs the mutual orientations between the both aromatic rings, as well as with the steric demands according to the geometries and sizes that thyroxine and its analogues present. The study of the hormones upon lipid interactions becomes more interesting if the hormones are inserted in media showing different lipid fluidity. Thus, the present study focuses on the vibrational behaviour of L-T4 and its complex formation with dimyristoyl-phosphatidylcholine (DMPC) in liquid-crystalline state at two different temperatures. The spectral differences are compared with those previously obtained for the hormone upon interaction with PC. Quantum chemical calculations of energies and molecular geometry optimisations allow interpretations related to structural changes experienced by the hormone according to the lipid environment. The theoretical calculations were performed  using the ONIOM method included in the Gaussian 03 program package. Vibrational frequencies estimations for the hormone upon DMPC interaction facilitated the interpretation of the experimentally observed shifts. In this way, we continue the analysis on a molecular level of the interactions between thyroid hormones and phospholipids with different fluidity, which results in a combined experimental and theoretical approach and whose goal is to contribute to the understanding the specific hormone-membrane interactions in more detail.