To understand the effects of D-U base-pairing on the photodestruction of U, we analyze both U and D-U potential energy surfaces in the ground and excited state. As a photoreactive path, we are here focusing on the cyclodimerization (formation of CPD). We will not discuss the U photohydration reaction, as this is known to be reversible and with negligible yields at pH > ∼ 6, nor other less relevant addictions. A combination of two coordinates is known to be relevant for the formation of U CPDs, namely the one involving C5 and C6 intra-stack coordinates. We have decided to approach our computational investigation by probing the shape of the potential energy surface with respect to these two coordinates as well as searching possible conical intersections (CI), typically involved in such photochemical pathways. We only focus here on the face-to-face arrangements of uracil dimers since it has been recently suggested to be the largely dominating photoreactive reactive channel for CPD. We have defined two coordinates d(C5C6') and d(C6C5'), shortly dCC1 and dCC2, respectively. We have built potential energy surfaces (PESs) in a vacuum, for both the case of two U stacking (UU) and two U stacking with a D forming hydrogen bonds with one of the U molecules (D:UU) -as inspired by the D-U anhyd crystal structure. Such constructed ground state DFT relaxed PES at DFT-ωB97XD level of theory, as well as relaxed S 1 TD-DFT relaxed PES (same functional) are reported in Figure and Figure .