Determination of two-photon absorption in nucleobase analogues: a QR-DFT perspective

With the prevalence of fluorescence spectroscopy in biological systems, and the benefits of two-photon absorption techniques, presented here is an assessment of the two-photon accessibility of modern fluorescent nucleobase analogues utilising quadratic response DFT. Due to the complex environment experienced by these nucleobases, the two-photon spectra of each analogue has been assessed in the presence of both [Formula: see text]-stacked and hydrogen-bonding interactions involving the canonical nucleobases. Findings suggest that the [Formula: see text]-stacking environment provides a more significant effect on the spectra of the analogues studies than a hydrogen-bonding environment; analogue structures presenting high two-photon cross-section values for one or more states coincide with polycyclic extensions to preserved canonical base structure, as observed in the qA family of analogues, while analogue structures more closely resembling the structure of the base in question present a much more muted spectra in comparison. Results from this investigation have also allowed for the derivation of a number of design rules for the development of potential, two-photon specific, analogues for future use in both imaging and potential photochemical activation.