Nanostructured AABB Zn (II) Phthalocyanines as Photodynamic Agents for Bacterial Inactivation

Abstract

In this work, the ability of amphiphilic phthalocyanine (Pc) photosensitizers (PS) (Zn(II)Pcs PS1, PS2 and PS3) to assemble into cationic nanoparticles in water and to photo‐inactivate bacterial strains is demonstrated. All the synthesized Zn(II)Pcs exhibit an AABB functionalization pattern, having a binaphthyloxy‐linked bisisoindole (AA) functionalized at the chiral binaphthol core with branched (PS1) or linear (PS2 and PS3) poly‐ammonium chains, and two non‐functionalized isoindole rings (BB). The aggregation behavior and the stability of the nanoparticles formed by the three PS in water is studied by UV‐vis, fluorescence and circular dichroism (CD) spectroscopies, and their shape and size is determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The PS nanoparticles proved efficient in the photoinactivation of S. aureus and E. coli. Although PS2 and PS3 present better photophysical features in their monomeric form (i.e., improved singlet oxygen quantum yield), PS1 is more effective in killing both types of strains, especially the gram‐negative E. coli. This observation may derive from the low stability found for PS1 nanoparticles, which easily disassemble after binding to the bacteria surface, recovering the photophysical properties of the non‐aggregated species.This article is protected by copyright. All rights reserved

Controlling the reactivity of phthalonitriles for the efficient synthesis of chiral phthalocyanines with self-assembly abilities

“…The major drawback of this method is that it usually requires high temperature, which shifts the different equilibria towards the formation of a highly conjugated macrocycle, but does not allow the development of chemoselective conditions that lead to the formation of Pc rings containing different chemical functionalities at the constituent isoindoles in a controlled fashion. Some approaches have been addressed to control the cross-reactivity between different phthalonitrile units, using steric constrictions, 11–15 by preorganization of phthalonitrile units, 16–20 by sequential assembly, 21–26 or even using other types of precursors with complementary reactivity. 27–31 However, controlling the reactivity of the phthalonitriles on the basis of the different electronic characteristics of the substituents that can modify the involved electrophilicity/nucleophilicity is underdeveloped.…”

“…32 One of the outstanding strategies to prepare Pcs with certain chemo- and regiocontrol is the use of bisphthalonitriles linked by constrained binding groups. 16–20 In particular, the introduction of optically active binaphthyl units as bridges deserves special mention since they lead to optically active Pcs thanks to the intrinsic atropisomerism of the binaphthol subunit. 1,17–20,33–35 Binaphthyl-containing Pcs were formerly described by Kobayashi and co-workers, 33 and, since then, several Pcs and related compounds endowed with optically pure binaphthyl cores have been prepared, most of them presenting an unsymmetric functionalization of the Pc core in an AABB pattern (AA coding for the binaphthol-linked diisoindole part) (Fig.…”

“…1). 17–20 Surprisingly, the self-condensation of AA-bisphthalonitriles leading to symmetrically substituted (AA) 2 -Pc derivatives with two bridging binaphthol units (Fig. 1) is rather unfavoured and these types of compounds have been prepared in extremely low yields.…”

“…18 Using this methodology, we have been able to synthesize a variety of derivatives with highly directional amphiphilicity, holding both non-polar aromatic heads and hydrophilic tails located either at the binaphthol or at the periphery of the Pc core. 19,20 These molecules have demonstrated abilities to form chiral nanoparticles in aqueous medium triggered by hydrophobic forces. In particular, the molecules functionalized with cationic residues form homogeneously sized aggregates that perform as nanostructured photosensitizers for the inactivation of bacteria.…”

“…In particular, the molecules functionalized with cationic residues form homogeneously sized aggregates that perform as nanostructured photosensitizers for the inactivation of bacteria. 19,20 On the basis of these results, we have undertaken the preparation of other archetypal chiral amphiphilic Pcs with self-organizing abilities, consisting of a symmetric bis(binaphthol)-(AA) 2 Zn( ii )Pc central core endowed with hydrophilic cationic tails at the binaphthol units ( 1 , Fig. 2), which could lead to nanostructures differing in shape or size with respect to those formed by unsymmetric AABB Pcs.…”