An inner salt derivative of Thioflavin T designed for live-cell imaging of mitochondrial G-quadruplexes

Mitochondrial G-quadruplex structure is an important element for regulating mitochondrial function and is expected to be a potential target for the treatment of some major diseases. Currently, compounds that can track mitochondrial G-quadruplexes are still limited, making it difficult to investigate their functional mechanisms in depth. In this study, a new compound named ThT-S was prepared through structural modification of Thioflavin T (ThT). ThT-S not only has higher selectivity for G-quadruplex structure, but also can rapidly enter mitochondria in live cells with high specificity. ThT-S also has the advantages of good optical stability and low cytotoxicity. These properties make ThT-S a promising sensor for mitochondrial G-quadruplex studies. This study also provides new insights into the structural design of mitochondrial G-quadruplex-targeting compounds. • A new ThT derivative named ThT-S has been designed. • ThT-S has higher selectivity for G-quadruplex structure. • ThT-S is highly targeted to mitochondria and stains rapidly. • ThT-S can be used for in situ imaging of mitochondrial G-quadruplexes.