The photophysics of protonated cytidine and hemiprotonated cytidine base pair: A computational study

Abstract

We here study the effect that a lowering of the pH has on the excited state processes of cytidine and a cytidine/cytidine pair in solution, by integrating time‐dependent density functional theory and CASSCF/CASPT2 calculations, and including solvent by a mixed discrete/continuum model. Our calculations reproduce the effect of protonation at N3 on the steady‐state infrared and absorption spectra of a protonated cytidine (CH+), and predict that an easily accessible non‐radiative deactivation route exists for the spectroscopic state, explaining its sub‐ps lifetime. Indeed, an extremely small energy barrier separates the minimum of the lowest energy bright state from a crossing region with the ground electronic state, reached by out‐of‐plane motion of the hydrogen substituents of the CC double bond, the so‐called ethylenic conical intersection typical of cytidine and other pyrimidine bases. This deactivation route is operative for the two bases forming an hemiprotonated cytidine base pair, [CH·C]+, the building blocks of I‐motif secondary structures, whereas interbase processes play a minor role. N3 protonation disfavors instead the nπ* transitions, associated with the long‐living components of cytidine photoactivated dynamics.

Shedding Light on the Photophysics and Photochemistry of I-Motifs Using Quantum Mechanical Calculations

“…This crossing region, which allowed a fast GS recovery, was separated by a very small energy barrier (<0.1 eV) from CH -min*. This could be reached by the out-of-plane motion of the C5′-H5’ moiety, confirming the indications obtained in our study of hemiprotonated (CH·C) pairs [ 67 ].…”

“…As discussed in detail in ref. [ 67 ], the lowest-energy bright excited state in (CH·C) is a transition localized on the CH base, mostly involving the C5=C6 double bond. In the following, we label this kind of excited state as CH - .…”

Is 1-methylcytosine a faithful model compound for ultrafast deactivation dynamics of cytosine nucleosides in solution?

“…10,41,42 In light of this, 1mCyt might be considered a useful model compound for eliminating the various tautomeric forms (except for the keto form) in the study of the Cyt excited states 44,45 and to reduce the computational cost in the theoretical exploration of the mechanistic details of the dCyd and Cyd deactivation. 2,3 On the other hand, the precise time constants of the S 1 pp* decay from its PES minimum (t 2 ) and the decay of np* (t 3 ) in 1mCyt are noticeably different from those in Cyt, dCyd and Cyd. 2,10 As shown in Table 1, the value of t 2 is B0.76 ps for This journal is © the Owner Societies 2024 1mCyt in water, which is smaller than the time constant of B1.5 ps for Cyt (Fig.…”

“…1 1mCyt is also a model compound used in highlevel quantum mechanical calculations for decreasing the computational cost in analyzing the highly complex excited state potential energy surfaces (PESs) and deactivation dynamics of cytidine (Cyd) and deoxycytidine (dCyd) (Scheme 1). 2,3 There is, however, very limited experimental study regarding excited states of 1mCyt, with only one known investigation using time-resolved IR (TRIR) by Keane et al. 4 This study reported that both 1mCyt and Cyt, after photo-excitation, exhibit ultrafast decay from their light-absorbing pp* state with no significant involvement of the np* natured state.…”

Revealing the excited-state dynamics of cytidine and the role of excited-state proton transfer process

“…2,[11][12][13][14][15] Considering the complexity of DNA structures, it is attractive to study the photochemical and photophysical properties of larger building blocks of DNAs, such as nucleosides, for understanding the photostability of DNAs in a ''bottom to top'' research scheme. Despite a number of theoretical [16][17][18][19][20][21][22][23] and experimental studies 1,[24][25][26][27][28][29][30][31][32][33][34][35] that have been carried out, the deactivation mechanism of Cyd is still a heated debate. Timeresolved IR spectroscopy experiments observed three decay channels with a sub-picosecond (B0.2 ps), a picosecond (B1.5 ps), and a long (tens to hundreds ps) lifetime of Cyd system in aqueous solution.…”