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(x)U (with X = F, Cl or Br) crystallizes as a double-str anded helix with four consecutive G-U and C-U mismatches. The deoxy chloro- and bromouracil derivatives are isomorphous, space group C2, unit-cell par ameters a = 53.80, b = 19.40, c = 50.31 Angstrom, beta = 109.9 degrees, wit h the same infinite helix arrangement in the packing along the c axis with one extra DNA halogenouracil base included in the stacking. However, the fl uorouracil derivative, with unit-cell parameters a = 53.75, b = 19.40, c = 45.84 Angstrom, beta = 105.7 degrees, is not isomorphous. The corresponding extra DNA base d(F)U of the second strand is ejected out of the helical st ack, leading to a shortening of the c axis. The specific destabilization of the fluorouracil for the duplex building is analyzed in terms of the polar ization effect of the halogen atom attached to the 3'-terminal base that mo dulates its interactions.