title: Photodynamic efficiency of cationic meso-porphyrins at lipid bilayers: insights from molecular dynamics simulations.
abstract: Porphyrin derivatives have applications as photoactive drugs in photodynamic therapy. However, little is known about their interactions with phospholipid membranes at the molecular level. We employed molecular dynamics simulations to model the binding between a series of cationic meso-(N-methyl-4-pyridinium)phenylporphyrins and anionic phosphatidylglycerol lipid bilayers. This was done in the presence of molecular oxygen within the membrane. The ability of various porphyrins to cause photodamage was quantified in terms of their immersion depth and degree of exposition to a higher oxygen concentration inside the membrane. Simulations showed that the photodynamic efficiency could be improved as the number of hydrophobic phenyl substituents attached to the porphyrinic ring increased. In the specific case of porphyrins containing two hydrophobic and two charged substituents, the cis isomer was significantly more efficient than the trans. These results correlate well with previous experimental observations. They highlight the importance of both the total charge and amphiphilicity of the photosensitizer for its performance in photodynamic therapy.
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia 166, CEP 09210-170, Santo André (SP), Brazil. rodrigo.cordeiro@ufabc.edu.br
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Cordeiro
authors.forename: Ronei
authors.initials: R
authors.lastname: Miotto
authors.forename: Maurício S
authors.initials: MS
authors.lastname: Baptista
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D014867:Water / Q000737:chemistry
chemical_list: D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; D017319:Photosensitizing Agents; D011166:Porphyrins; D011726:Pyridinium Compounds; C090734:bis(N-methyl-4-dipyridiniumyl)diphenylporphyrin; D014867:Water