DFT and MP2 methods are used to unravel the syn and anti-configurations in the regio-stereoselectivity of carbonyl groups of 5 Fluorouracil paired with HF, CH3OH, H2O, and HCl proton donors. Two configurations of hydrogen-bonded complexes are found: anti-orientated complexes and syn-orientated complexes. The latter are found to be lower in energy than the former when proton donors attack on C=O-1 site, while the contrary is observed when C=O-2 site is attacked by proton donors. In syn-configuration, both C=O-1 and C=O-2 form clusters which are closer in H-bond interaction energies, but C=O-2 is predicted slightly as the preferred interaction site.