Molecular Dynamics studies of the interaction of Zn Phthalocyanines with DMPC bilayer

NOELIA S. GOROD; MARIANA MIRETTI; TOMAS C. TEMPESTI; MARIA TERESA BAUMGARTNER; MARCELO PUIATTI

Encuentro; Enceuentro Virtual de la Sociedad Argentina de Biofísica; 2020; 2020

Sociedad Argentina de Biofísica

Zinc Phthalocyanines (ZnPc) are important agents in Photodynamic Therapy, PDT [1].Their use is favored by some of their properties such as high singlet oxygen generation rate and excitation at wavelengths greater than 630 nm, which allows greater tissue penetration of radiation. However, their poor water solubility and high rate of aggregation in solution discourage their use. To overcome these issues a new generation of agents was developed associating the ZnPc with carriers such as liposomes, polymers, nanoparticles, etc [1].In our group, different ZnPcs loaded in liposomes were successfully employed in PDT against Glioblastome cells [2] and MDR Mycobacterium tuberculosis [3]. In order to deeply understand the mechanism of interaction of different ZnPcs with DMPC liposomes, molecular dynamics studies were carried out.Two methodologies were employed: free simulations and non-equilibriumUmbrella Sampling simulations. Free simulations show that neutral Pcs could enter in the bilayer and stay trapped inside. On the other hand, positively charged Pcs deposit over the bilayer surface, stabilized by the charged polar head of the lipid residues. Free energy profiles built after umbrella sampling simulations help explain these results, showing energy stabilization of the neutral Pcs inside the bilayer. The models also indicate that insertion in the membrane is more favorable that aggregation in water.References:[1] L. P. Roguin, N. Chiarante, M. C. García Vior, J. Marino, Int. J. Biochem. Cell. Biol., 114:105575, 2019.[2] F. N. Velazquez, M. Miretti, M. T. Baumgartner, B. L. Caputto, T. C. Tempesti, and C. G. Prucca. Sci. Rep., 9:3010, 2019.[3] M. Miretti, L. Juri, M. C. Cosiansi, T. C. Tempesti, and M. T. Baumgartner. Chemistry Select, 4:9726?9730, 2019