Synthesis, Characterization, and Biological Evaluation of Red-Absorbing Fe(II) Polypyridine Complexes

Johannes Karges,Philippe Goldner,Gilles Gasser

doi:10.3390/inorganics7010004

Abstract

Cancer is known to be one of the major causes of death nowadays. Among others, chemotherapy with cisplatin is a commonly used treatment. Although widely employed, cisplatin is known to cause severe side effects, such as nerve and kidney damage, nausea, vomiting, and bone marrow suppression. Most importantly, a number of cancer tumors are acquiring resistance to cisplatin, limiting its clinical use. There is therefore a need for the discovery of novel anticancer agents. Complementary to chemotherapy, Photodynamic Therapy (PDT) has expanded the range of treatment opportunities of numerous kinds of cancer. Nonetheless, the currently approved PDT photosensitizers (PSs) suffer from major drawbacks, which include poor water solubility or photobleaching, in addition to a slow clearance from the body that causes photosensitivity. Due to these limitations, there is a need for the development of new PDT PSs. To overcome these problems, a lot of research groups around the world are currently focusing their attention towards the development of new metal complexes as PDT PSs. However, most synthesized compounds reported so far show limited use due to their poor absorption in the phototherapeutic window. Herein, we report on the preparation and characterization of three Fe(II) polypyridine complexes (4–6) and evaluate their potential as both anticancer agents and PDT PSs. Very importantly, these compounds are stable in human plasma, photostable upon continuous LED irradiation, and absorb in the red region of the spectrum. We could demonstrate that through additional sulfonic acid groups on the polypyridine ligand being used (bphen: 4,7-diphenyl-1,10-phenanthroline), the water solubility of the complexes could be highly improved, whereas the photophysical properties did not significantly change. One of these complexes (4) shows interesting toxicity, with IC50 values in the low micromolar range in the dark as well as some phototoxicity upon irradiation at 480 and 540 nm against RPE-1 and HeLa cells.

Highlights

Over the last decades, cancer has emerged as one of the deadliest diseases worldwide
We have recently investigated the potential of easy-to-synthesize Cr(III) complexes as Photodynamic Therapy (PDT) PSs [31]
This study demonstrates that a small structural change, like additional sulfonic acid groups at the outer sphere of the complex, completely changes the effect that these compounds have on the cells

Summary

Introduction

Cancer has emerged as one of the deadliest diseases worldwide. A combination of these techniques is most commonly used [1,2]. Cisplatin is still the most commonly used chemotherapeutic drug against cancer, it is responsible for a number of severe side-effects (e.g., nerve and kidney damage, nausea, vomiting, and bone marrow suppression). A number of cancer tumors are acquiring resistance to cisplatin, limiting its clinical use. There is a need for the development of new chemotherapeutic drug candidates.

Methods

Results

Conclusion