From advancing precision medicine and examining how nail fungus affects various sports to investigating multilingual hearing behavior in noisy environ...

We are hiring! Job Position at CWRU, College of Arts and Sciences Pre-Award Grant Administrator Job Description POSITION OBJECTIVE Working in conjunction with the Associate and Assistant Dean for ...

Alloxazine photosensitizers, molecularly engineered through sugar conjugation and methoxy substitution to enhance solubility, photodynamic potency, and fluorescence, enable image-guided photodynamic ...

The photostability of DNA and RNA bases to ultraviolet radiation is essential to life, as evidenced by their ability to dissipate excess electronic energy via u

Nucleoside analogs simultaneously exhibiting high fluorescence quantum yields and efficient triplet state population are rare. Such multifunctional nucleosides represent a crucial advancement for cell imaging-assisted photodynamic therapy relying on heavy-atom-free photosensitizers and hold additional promises as inhibitors of cancer cell proliferation. This study investigates the photophysical, electronic structure, excited state dynamics, and skin cancer cell photodynamic and inhibitory properties of 5-(5-phenylthiophen-2-yl)-6-azauridine (PTAU). PTAU absorbs up to 425 nm and demonstrates dual photophysical characteristics, with fluorescence and singlet oxygen quantum yields of 43 ± 1% and 52 ± 2% in acetonitrile and 12 ± 1% and 33 ± 2% in aqueous buffer, respectively. Time-resolved absorption and fluorescence spectroscopy, complemented by quantum chemical calculations, reveal the existence of two rotameric species of PTAU in solution. Both rotamers exhibit nanosecond-scale fluorescence and intersystem crossing lifetimes, as well as microsecond-scale triplet decay lifetimes. When applied to B16F10 murine melanoma cells, PTAU localizes mostly in the cytoplasm, primarily in mitochondria, and demonstrates moderate photodynamic activity, achieving IC50 values of 125 ± 5 μM and 80 ± 3 μM at photoactivation doses of 7.5 J cm–2 and 25 J cm–2, respectively, while exhibiting no cytotoxicity in the dark. Notably, PTAU also inhibits the cell proliferation of B16F10 murine melanoma and A431 human epidermoid carcinoma by more than 95% at a concentration of 250 μM in the dark. Therefore, this proof-of-concept study reveals PTAU as the first example of a nucleoside analog with potential multifunctional applications, including photodynamic action, bioimaging, and the inhibition of skin cancer cell proliferation. These findings pave the way for further developing next-generation modified 6-azauridine analogs absorbing visible to near-infrared light for their use as cell imaging-assisted PDT agents and cancer cell inhibitors, targeting potential deep-tissue cancer treatment.

Synthetic biology aims to expand the genetic code by increasing cellular information storage and retrieval. A recent advance is the dTAT1-dNaM unnatural base pair, which is more photo- and thermostable than dTPT3-dNaM while maintaining high efficiency and fidelity in vitro and in vivo. However, the photophysics and cytotoxicity behavior of dTAT1 under UV light have not been investigated. We demonstrate that dTAT1 populates the triplet state upon 390 nm excitation but exhibits minimal cytotoxicity in cells. Analysis of reactive oxygen species indicates that dTAT1 produces a low singlet oxygen quantum yield of 17% while it generates superoxide, a less harmful reactive oxygen species. Its triplet lifetime is 2.7 times shorter than that of dTPT3, contributing to its lower photocytotoxicity. These findings highlight the potential of dTAT1 for safe genetic code expansion and therapeutic applications, providing valuable insights for designing next-generation unnatural nucleosides with minimal impact on cellular health.

This review provides focused coverage of the photophysical properties of noncanonical and synthetic nucleobases reported over the past decade. It emphasizes key research findings and physical insights...