It Takes Three to Tango: The Length of the Oligothiophene Chain Determines the Nature of the Long-Lived Excited State and the Resulting Photocytotoxicity of a Ruthenium(II) Photodrug

TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally-related Ru(II)-imidozo[4,5-f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter- or quaterthiophene changes the nature of the long-lived triplet state from metal-to-ligand charge-transfer to (3)pi pi* character. The addition of the third thiophene thus presents a critical juncture which not only determines the photophysics of the complex but most importantly its capacity for O-1(2) generation and hence the potential of the complex to be used as a photocytotoxic agent.

Automated summary

The study of TLD1433, the first Ru(II) complex tested as a photodynamic therapy agent in a clinical trial, reveals that increasing oligothiophene chain length changes its photophysical properties, especially impacting the generation of O-1(2) and its potential as a photocytotoxic agent, with the addition of a third thiophene playing a critical role.