Synthesis and antibacterial photosensitizing properties of a novel tricationic subphthalocyanine derivative

Abstract

A novel chloro[2,9,16(2,9,17)-trikis-4-(N-methylpyridyloxy)]subphthalocyaninnato boron(III) iodide (SubOPc3+) has been synthesized by boron trichloride-induced cyclotrimerization of 4-(4-pyridyloxy)phthalonitrile in 1-chloronaphthalene. This approach produced a regioisomers mixture of chloro[2,9,16(2,9,17)-trikis-4-(pyridyloxy)]subphthalocyaninnato boron(III) (SubOPc) with 19% yield. Exhaustive methylation of SubOPc with methyl iodide yielded 92% of tricationic SubOPc3+. The spectroscopic and photodynamic properties of the SubOPc3+ were compared with its homologous non-charged SubOPc and with subphthalocyanine (SubPc). The cationic SubOPc3+ is essentially aggregated in solution of different solvents and it is partially dissolved as monomer in aqueous sodium dodecyl sulfate (SDS) 2% w/v. The photodynamic effect was strongly dependent of the medium, increasing in an appropriated surrounding microenvironment. The photodynamic inactivation produced by these subphthalocyanines was for first time investigated in vitro on a typical Gram-negative bacterium, Escherichia coli. Cationic SubOPc3+ is rapidly bound to E. coli cells reaching a value of ~2 nmol/106 cells after 5 min of incubation with 4 mM of sensitizer in dark. Photosensitized inactivation of E. coli cellular suspensions by SubOPc3+ exhibits a ~2.5 log decrease of cell survival (99.7 % of cellular inactivation), when the cultures are irradiated for 30 min. The growth of E. coli cells was completely arrested when the cultures were exposed to 8 mM of cationic subphthalocyanine and irradiated, whereas a negligible effect was found for the non-charged SubOPc. Also, SubOPc3+ remains a high activity to inactivate E. coli cells immobilized on agar surfaces. Therefore, the reported results indicate that tricationic subphthalocyanines are interesting photosensitizers with useful antibacterial activity.