Destabilizing effect of a fluorouracil extra base in a hybrid RNA duplex compared with bromo and chloro analogues

In the presence of cobalt, rhodium or iridium hexammine salts, the RNA/DNA hybrid r-GCUUCGGC-d^XU (with X = F, Cl or Br) crystallizes as a double-stranded helix with four consec­utive G–U and C–U mismatches. The deoxy chloro- and bromouracil derivatives are isomorphous, space group C2, unit-cell parameters a = 53.80, b = 19.40, c = 50.31 Å, β = 109.9°, with the same infinite helix arrangement in the packing along the c axis with one extra DNA halogenouracil base included in the stacking. However, the fluorouracil derivative, with unit-cell parameters a = 53.75, b = 19.40, c = 45.84 Å, β = 105.7°, is not isomorphous. The corresponding extra DNA base d^FU of the second strand is ejected out of the helical stack, leading to a shortening of the c axis. The specific destabilization of the fluorouracil for the duplex building is analyzed in terms of the polarization effect of the halogen atom attached to the 3′-­terminal base that modulates its interactions.