Expansion of the genetic alphabet has long been a high priority in the field of synthetic biology. Such an achievement could enable synthesizing unnatural amino acids and proteins, as well as enhance the capabilities of site-specific labeling. In 2014, in vivo replication of an expanded genetic alphabet was reported for the first time when E.coli successfully incorporated and replicated the unnatural base pair dNaM-d5SICS. The question arises as to whether these unnatural bases are as stable to solar radiation as the natural nucleobases. Using steady-state and time-resolved spectroscopic techniques, we investigated the photophysical properties of dNaM and d5SICS in phosphate buffer and acetonitrile solution. Our results demonstrate that both of these unnatural bases populate long-lived, reactive triplet states in high yield upon UVA excitation. Furthermore, d5SICS is able to generate singlet oxygen with a 42% yield upon 355 nm excitation. The implications of these results in the potential phototoxicity of the unnatural bases to DNA will be discussed. The authors acknowledge the CAREER program of the National Science Foundation (Grant No. CHE-1255084) for financial support.

Potential light-induced risks associated with expanding the genetic alphabet

251st National Meeting (2016)

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