Crosswise Phthalocyanines with Collinear Functionalization: New Paradigmatic Derivatives for Efficient Singlet Oxygen Photosensitization

Abstract

We describe here the preparation of a series of trans‐ABAB Zn(II) phthalocyanines (ZnPcs, which combine several interesting features. First, these compounds present high solubility and hindered aggregation, due to the functionalization of two facing isoindole constituents (B) of the ZnPc with bis(trifluoromethylphenyl) units. Second, the other two isoindoles (A) bear extra‐annulated phthalimide units containing different substituents in the nitrogen positions, this feature results in a collinear arrangement of a variety of functional groups. Some of these collinearly functionalized ZnPcs are interesting building blocks for constructing either homo‐ or heteroarrays containing ZnPc units. Furthermore, the amphiphilic nature of some members of the series renders them interesting candidates for photosensitization of singlet oxygen. Photophysical studies on a model compound of the series have shown that these molecules are efficient singlet oxygen photosensitizers in both polar and apolar media, with 1O2 quantum yields (φΔ) as high as 0.74.

Boosting the singlet oxygen photosensitization abilities of Zn(ii) phthalocyanines through functionalization with bulky fluorinated substituents

“…11 However, an important shortcoming of ZnPcs is that they cannot circumvent the π-π stacking issues by covalent axial functionalization. In this regard, our research group has recently described a new strategy to prepare ZnPcs showing both hindered aggregation and water solubility, that is, by introducing two types of peripheral substituents in the Pc in a crosswise, ABAB architecture 12,13 (A and B coding for the two differently functionalized isoindole constituents). First, - interaction in aggregates is eluded by endowing two facing isoindoles (B) of the ZnPc with bulky bis(trifluoromethyl)phenyl units, and the other two isoindoles (A) can provide the necessary watersolubility if they are properly functionalized with hydrophilic substituents.…”

Phthalocyanin‐Synthese: vom Ursprung zu aktuellen Trends

“…Das System liefert ZnPcs mit nichtaggregierenden Eigenschaftengrundlegend für die Verwendung als Photosensibilisatoren zur Produktion von Singulett-Sauerstoff in therapeutischen Anwendungen, etwa bei Krebs und bakteriellen Infektionen. 11) Niedrigsymmetrische Phthalocyanine lassen sich auch mit einer programmierten Synthesestrategie herstellen. Diese umfasst Vorauswahl und Konjugation von vier Phthalonitrilvorstufen sowie eine anschließende basengeförderte intramolekulare Cyclisierung in Gegenwart eines Metalltemplats (Abbildung 4).…”

Assessing Amphiphilic ABAB Zn(II) Phthalocyanines with Enhanced Photosensitization Abilities in In Vitro Photodynamic Therapy Studies Against Cancer

“…In this context, the choice of adequate substituents is decisive to achieve solubility in aqueous media and hinder their aggregation. Hydrophilic groups can be introduced to reach water solubility [5], whereas aggregation can be reduced or avoided by the introduction of bulky substituents in the Pc [6]. Among the different metallic Pcs used for PDT, Zn(II)Pcs stand out as one of the most promising, as they present high efficiencies in the generation of and hinder their aggregation.…”

“…Among the different metallic Pcs used for PDT, Zn(II)Pcs stand out as one of the most promising, as they present high efficiencies in the generation of and hinder their aggregation. Hydrophilic groups can be introduced to reach water solubility [5], whereas aggregation can be reduced or avoided by the introduction of bulky substituents in the Pc [6]. Among the different metallic Pcs used for PDT, Zn(II)Pcs stand out as one of the most promising, as they present high efficiencies in the generation of 1 O2 [7][8][9][10].…”

“…Among the different metallic Pcs used for PDT, Zn(II)Pcs stand out as one of the most promising, as they present high efficiencies in the generation of 1 O2 [7][8][9][10]. Recently, our research group has described new paradigmatic ABAB Zn(II)Pcs (with A and B coding for differently functionalized isoindole constituents) that show both hindered aggregation and notably high 1 O2 quantum yield (ΦΔ) values, featuring also chemical flexibility to incorporate additional functionalization that affords, for instance, water solubility [6]. For that purpose, a bulky phthalonitrile precursor endowed with bis(trifluoromethyl)phenyl units is used to avoid aggregation in the target ABAB Zn(II)Pc, but also to hamper its self-condensation, and thus force its cross-condensation with other phthalonitrile [11], which can be functionalized with hydrophilic groups.…”