Aryl-Substituted Ruthenium(II) Complexes: A Strategy for Enhanced Photocleavage and Efficient DNA Binding

Abstract

Ruthenium polypyridine complexes have shown promise as agents for photodynamic therapy (PDT) and tools for molecular biology (chromophore-assisted light inactivation). To accomplish these tasks, it is important to have at least target selectivity and great reactive oxygen species (ROS) photogeneration: two properties that are not easily found in the same molecule. To prepare such new agents, we synthesized two new ruthenium complexes that combine an efficient DNA binding moiety (dppz ligand) together with naphthyl-modified (1) and anthracenyl-modified (2) bipyridine as a strong ROS generator bound to a ruthenium complex. The compounds were fully characterized and their photophysical and photochemical properties investigated. Compound 2 showed one of the highest quantum yields for singlet oxygen production ever reported (Φ= 0.96), along with very high DNA binding (log K = 6.78). Such photochemical behavior could be ascribed to the lower triplet state involving the anthracenyl-modified bipyridine, which is associated with easier oxygen quenching. In addition, the compounds exhibited moderate selectivity toward G-quadruplex DNA and binding to the minor groove of DNA, most likely driven by the pendant ligands. Interestingly, they also showed DNA photocleavage activity even upon exposure to a yellow light-emitting diode (LED). Regarding their biological activity, the compounds exhibited an exciting antibacterial action, particularly against Gram-positive bacteria, which was enhanced upon blue LED irradiation. Altogether, these results showed that our strategy succeeded in producing light-triggered DNA binding agents with pharmacological and biotechnological potential.

Ruthenium‐based Photoactive Metalloantibiotics†

“…The antibacterial studies on ruthenium polypyridyl complexes with general formula, [Ru(bpy)(dppz)(L)](PF 6 ) 2 (L = napthyl and anthracyl group attached to a bipyridine ligand), (Fig. 1g and h) shows that these complexes display a stronger antibacterial effect against Gram (+) bacteria when irradiated with blue light compared to when kept in the dark (62). The bactericidal effect was attributed to strong DNA binding and the generation of singlet oxygen leading to DNA damage.…”

Recent Progress in Metal-Based Nanoparticles Mediated Photodynamic Therapy

“…The development of PDT technology can aid in the fight against a range of diseases, such as tumors of the colon and bladder, tumors of the brain and spinal cord, and to develop new methods of treatment of skin in plastic surgery and cosmetology [ 46 , 47 ]. Positive results of treatment of proinflammatory diseases by photodynamic therapy show high efficiency of this method in respect of aerobic, facultative, and obligate anaerobic bacteria, and microscopic fungi [ 48 , 49 ].…”

Is IQG-607 a Potential Metallodrug or Metallopro-Drug With a Defined Molecular Target in Mycobacterium tuberculosis?

“…The modulation of reactivity promoted by metals has also been explored in the design of donors of either nitric oxide or CO, where ruthenium-based compounds have stood out (Tfouni et al, 2012 ; Wright and Wright, 2016 ). Light and electron-transfer triggered processes have been used to generate cytotoxic metal-based compounds with production of reactive oxygen species (ROS), release of NO or CO, and hypoxia-responsive agents (Tfouni et al, 2010 ; Li et al, 2015 ; Pires et al, 2016 ; Romo et al, 2016 ; Sousa et al, 2016 ; Abreu et al, 2017 ; de Sousa et al, 2017 ). Cobalt(III) complexes, for example, have been used to release drugs or agents for imaging under hypoxia conditions, which enables reduction of Co(III) to Co(II).…”