Photocytotoxic Copper(II) Complexes with Schiff‐Base Scaffolds for Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a promising and minimally invasive method for the treatment of superficial diseases, and photosensitizers with high phototoxicity indices (defined as (IC )/(IC )) are essential for the development of ideal photosensitizing properties for this technology. Herein, we report a series of photocytotoxic copper(II) complexes [Cu( QYMP)(dppn)] ( QYMP=N,N,O-tridentate Schiff-base derivatives, dppn=benzo[i]dipyrido[3,2-a;2',3'-c]phenazine), the structures of which have been confirmed by mass spectrometry and FTIR spectroscopy. X-ray crystallography revealed that the CuN O core of the [Cu( QYMP)(dppn)](ClO ) complex (3) has a distorted square-pyramidal geometry. Phototoxicity indices of 329 against human squamous cell carcinoma (SCC15) and 296 against basal cell carcinoma (BCC) cell lines have been determined with [Cu( QYMP)(dppn)](ClO ) (4). This can be attributed to the formation of reactive oxygen species, cell apoptosis, and caspase-3 activation, indicating high potential of complex 4 as a photosensitizer candidate in PDT. Thus, copper complexes bearing suitable Schiff-base ligands with a dppn co-ligand may be considered for the design of efficient metal-based anticancer agents for PDT.

Phototherapeutic anticancer strategies with first-row transition metal complexes: a critical review

“…Phototoxic Cu( ii ) complexes with Schiff base ligands were also designed for PDT applications ( Cu-8 ). 124 Cu-8 was quite cytotoxic upon visible light irradiation in human squamous carcinoma cells (SCC15) and in basal carcinoma cells (BCC) and less toxic in the dark. The charge transfer from the phenolate π orbitals to the metal dπ* orbitals is responsible for a visible LMCT absorption band.…”

Palladium(ii) complexes of tetradentate donor–acceptor Schiff base ligands: synthesis and spectral, structural, thermal and NLO properties

“…4 Consequently, Schiff base complexes have raised interest in various fields of research and found applications in many areas, includ ing catalysis, 5 molecular magnetism, 6 spin crossover, 7 sensing, 8 nonlinear optical (NLO) molecular materials, [9][10][11][12] porous 13 and energy materials, 14 as well as for their properties in biologica l, pharmacological and medicinal chemistry. [15][16][17][18][19] In this regard, palladium(II) complexes with Schiff base ligands have been intensively investigated due to their applications in catalysis and in a wide variety of biological reactions. They have indeed been used as homogeneous and heterogeneous catalysts, especially in Suzuki-Miyaura cross coupling reaction, [20][21][22] and as antiviral, anti-fungal, anti-microbial and anti-tumor bioinorganic agents, [23][24][25][26][27][28] respectively.…”

Photodynamic Therapy of Inorganic Complexes for the Treatment of Cancer†

“…Copper is a nontoxic and bioessential element that is vital to the health of all living organisms, and therefore, photochemotherapeutic usage of different copper complexes is an interesting field of research (75,76). The photodynamic activity of copper(II) complexes: [Cu(L 1 )B]ClO 4 and [Cu(L 2 )B]ClO 4 ( where L 1 = 2‐[(pyridin‐2‐yl)methyleneamino]phenol, L 2 = 2‐[(pyridin‐2‐yl)methyleneamino]benzenethiol, and B is 1 H‐imidazo[4,5‐f][1,10]phenanthroline and 1‐(pyren‐2‐yl)‐ 1 H‐imidazo[4,5‐f][1,10]phenanthroline, was studied in a structure–activity relationship (SAR)‐based approach.…”