Kinetic and equilibrium studies of incorporation of di-sulfonated aluminum phthalocyanine into unilamellar vesicles

• Published in: Biochimica et biophysica acta Vol. 1420; no. 1; pp. 168 - 178
• Main Authors: Maman, Nathalie, Dhami, Suman, Phillips, David, Brault, Daniel
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.08.1999
• Subjects: Biological Transport, Active; Di-sulfonated aluminum phthalocyanine; Dimyristoylphosphatidylcholine; Hydrogen-Ion Concentration; In Vitro Techniques; Indoles - administration & dosage; Indoles - chemistry; Indoles - pharmacokinetics; Kinetics; Lipidic vesicle; Liposomes; Metal coordination; Organometallic Compounds - administration & dosage; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacokinetics; Photodynamic therapy; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacokinetics; Spectrometry, Fluorescence; pH; Metal coordination; Photodynamic therapy; Kinetics; Lipidic vesicle; Di-sulfonated aluminum phthalocyanine
• ISSN: 0005-2736; 0006-3002; 1879-2642
• DOI: 10.1016/S0005-2736(99)00093-0

The interactions of cis-di-sulfonated aluminum phthalocyanine (PcS 2Al) with dimyristoylphosphatidylcholine (DMPC) unilamellar vesicles have been investigated by fluorescence spectroscopy. At pH 7.0, PcS 2Al incorporates into the vesicles with a high affinity constant (2.7×10 6 M −1, in terms of phospholipid concentration). The fluorescence changes following rapid mixing of PcS 2Al with vesicles are biphasic. The first phase is attributed to the entry of PcS 2Al into the vesicles, as deduced from the linear dependence of the rate upon lipid concentration. More surprisingly, this rate is strongly pH dependent with a marked maximum around pH 7.3, a result interpreted in terms of the coordination state of the aluminum ion in aqueous solutions. At this pH, a hydroxide ion neutralizes the residual positive charge of the metal ion that remains unbalanced after coordination by the phthalocyanine cycle. A water molecule is likely to complete the metal coordination sphere. Only this form, PcAl +(OH −)(OH 2), with an uncharged core is quickly incorporated into the vesicles. The protonation of OH − or the deprotonation of the coordinated H 2O leading to a positively or negatively charged core, respectively, account for the observed pH effect. Studies on the effect of cholesterol addition and exchange of PcS 2Al between vesicles and albumin all indicate the absence of transfer of the phthalocyanine between the vesicle hemileaflets, a result expected from the presence of the two negatively charged sulfonated groups at the ring periphery. Instead, the slower kinetic phase is likely due to the movement of the phthalocyanine becoming more buried within the outer leaflet upon the loss of the water molecule coordinated to the aluminum ion.