In this Letter, we present Quantum Mechanics/Molecular Mechanics (QM/MM) calculations on molecules containing a 2-deoxycytidine-3'-monophosphate moiety (3'-dCMPH). In particular, we examine the effect that including neighbouring nucleotides at the Molecular Mechanic (MM) level has on the calculated electron affinities and on the energetic barriers of the C3'-O3' bond cleavage. Our results demonstrate that the surrounding nucleotides relocate the excess electron from the pi* orbital of the base to a diffuse phosphate-centred orbital, leading to the formation of a dipole-bound anion state. Both the electron affinities and the activation energy of C3'-O3' bond cleavage are strongly increased. (c) 2009 Elsevier B.V. All rights reserved.