Interaction of Metal Complexes with G‐Quadruplexes

Abstract

There is growing evidence that guanine‐rich sequences are ubiquitous in the human genome. They provide DNA with the ability to fold under a topology known as G‐quadruplex (G4), which is distinct from the classical Watson–Crick double helix and characterized by a great polymorphism and dynamics. G4s are found in the promoter region of important oncogenes and in the telomeric region of chromosomes, where they play significant regulatory roles. The stabilization of G4 structures results in the downregulation of oncogenes such as c‐myc, but also inhibits telomerase, which is overexpressed in 85% of the cancer cells, hence contributing to their immortality. Therefore, G4s are now considered a promising target for designing new anticancer drugs. These important therapeutic perspectives have stimulated the development of G4 binders (organic and inorganic), which have grown exponentially during the past decade. The specific recognition of the G4, which is required for cellular applications, is based on the targeting of specific structural features: The upper guanine tetrad that exposes a large aromatic surface to the solvent, specific shape and folding of the loops and grooves. For this purpose, metal complexes proved to be a powerful platform. By combining the effects of the positively charged metal, which can be involved in electrostatic interactions with electronegative regions, and aromatic rings (chelating or not) designed to interact through π‐stacking, strong G4 binders were obtained. The typical versatility of the ligands and complexes synthesis allows for easy screening and, hence, convenient optimization, while offering the possibility to incorporate reactive or fluorescent fragments. Several families of complexes have emerged in the literature, with distinct metal ions and functionalities, which show tight and specific interactions with G4s, while G4s can be also used as scaffold for catalysis. All these aspects are reviewed and discussed in this article after a brief presentation of the main factors determining the G4 folding and the biological implications.

A simple green synthesis of pure and sterling silver nanoparticles via pulsed laser ablation in deionized water: characterization and comparison

“…Metallic NPs can be synthesized by numerous physical and chemical approaches, including chemical reduction, hydrothermal, electrochemical, sol-gel, and metal organic chemical deposition methods [15][16][17]. In contrast to other chemical green synthetic methods, pulsed laser ablation in liquid (PLAL) as an economical, environmentally friendly and versatile physical technique is extensively used to produce metal and alloy NPs with high purity and stability [18].…”