The Terthiophene Structural Motif: A Biological Asset or a Simple Ornament?

The clinical advancement of the ruthenium complex [bis(4,4′-dimethyl-2,2′-bipyridin){2-(2,2′:5′,2″-terthiophen-5-yl)imidazo[4,5-f][1,10]phenanthroline}ruthenium]dichloride (TLD-1433) has provided a breath of fresh air to the bioinorganic chemistry of metal-based complexes, especially those developed around Ru(II). The success of TLD-1433 resides in its dual metal–ligand photodynamic therapy mechanism, which allows for the treatment of hypoxic cancer. The presence of α-terthiophene at the periphery of the polypyridyl complex positively modified the photophysical property of the ruthenium complex; however, it is unclear if it possesses other favorable attributes. Considering the tremendous structural and photophysical diversity of terthiophene derivatives (14 isomers), as well as α-terthiophene’s recognized nematocidal activity, the following questions can be asked: What is the main role of α-terthiophene in TLD-1433? Is it to act as a pharmacophoric element, a photo-physical modulator, or a simple structural motif? Can a terthiophene motif be beneficial for other metal-based or organic drugs?