Photodynamic therapy (PDT) is evolving as an alternative and/or complement to conventional cancer treatment options such as chemotherapy, radiotherapy, and surgery. Being activated by light, one of the key benefits PDT is its selectivity, confining treatment to the tumor area. The porphyrin-based drug Photofrin was the first FDA approved PDT agent and others are in development based on different architectures. For example, our group synthesized the Ru-based complex TLD 1433 that is in Phase II clinical trial. Here, we have synthesized methoxycarbonyl substitution of bipyridine with series of oligothiophene pi-expansive ligands heteroleptic Ru complexes and expect to alter the excited state photophysical properties for efficient PDT. The substitution of electron withdrawing methoxycarbonyl groups tend to afford a smaller HOMO-LUMO gap that will impart longer wavelength absorption and longer excited state lifetimes. The longer wavelength absorption helps to deep tissue penetration and will help to sensitize efficient singlet oxygen (1O2) and increase the singlet state oxygen quantum yields and ultimately lead to increase in photocytotoxicities (EC50 and PI) efficiency in PDT. Herein we explore the theme of pi-expansive methoxycarbonyl polypyridine Ru metal complexes as analogs of TLD1433 from the perspective of synthesis, characterization, and structure-activity relationships.

Synthesis of pi-expansive methoxycarbonyl derivatives of Ru metal polypyridyl complexes for photodynamic therapy applications

ACS Fall 2021

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