1 São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, SP, 19806-900, Brazil; Department of Chemistry and Biochemistry and Centre for NanoScience Research, Concordia University, Montreal, Canada.
2 São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, SP, 19806-900, Brazil; São Carlos Institute of Physics, University of São Paulo (USP), CP 369, São Carlos, SP, 13566-590, Brazil.
3 São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, SP, 19806-900, Brazil.
4 Department of Chemistry, State University of Maringá, Maringá, PR, Brazil.
5 Department of Chemistry and Biochemistry and Centre for NanoScience Research, Concordia University, Montreal, Canada.
6 São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, SP, 19806-900, Brazil. Electronic address: pedro.aoki@unesp

Cell membranes are the first barriers for drug binding and key for the action of photosensitizers (PS). Herein, we report on the incorporation of the PS hypericin into Langmuir monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), to represent eukaryotic cell membranes, and 1,2-dioleoyl-sn-glycero-3-phospho(1'-rac-glycerol) (DOPG), mimic bacterial membranes. Surface pressure (p) vs mean molecular area (A) isotherms showed a high degree of interaction (binding, penetration and relative solubilization) of hypericin into DPPC and DOPC monolayers. On the other hand, electrostatic repulsions govern the interactions with DOPG and DOPS, favoring hypericin self-aggregation, as visualized by Brewster angle microscopy (BAM). Indeed, the larger domains in BAM were consistent with the greater expansion of DOPG monolayers with incorporated hypericin, owing to stronger electrostatic repulsions. In contrast to DPPC, light-irradiation of DOPC monolayers containing hypericin induced loss of material due to hydrocarbon chain cleavage triggered by contact-dependent reactions between excited states of hypericin and chain unsaturations. The mild effects noted for both irradiated DOPS and DOPG monolayers are attributed to hypericin self-aggregation, which may have decreased the singlet oxygen quantum yield (F¹O₂) via self-quenching, despite the increased instability induced in the monolayers.