Structural polymorphism and Raman conformation markers of cyclic deoxytriadenylic acid

X-ray analysis of two different trigonal crystal forms (space groups R32 and P3) of cyclic deoxytriadenylic acid [c(dAp)₃] indicates for each an asymmetric unit consisting of two conformationally similar c(dAp)₃ molecules. Raman spectroscopy supports the X-ray interpretation for the R32 crystal, but identifies another c(dAp)₃ conformation not revealed in the P3 X-ray structure. The results for the P3 crystal can be explained if an additional c(dAp)₃ conformer is present but not sufficiently ordered within the lattice to contribute to X-ray diffraction. The Raman signature of aqueous c(dAp)₃, which differs from signatures of both the R32 and P3 crystals, exhibits backbone markers similar to those of thermally denatured DNA and indicates that c(dAp)₃ molecules in solution populate a wider range of phosphoester ring conformations than in R32 and P3 crystals. Thus, polymorphism is observed for both crystal and solution structures of c(dAp)₃. The results imply a highly flexible phosphoester ring that may be relevant to the function of cyclic oligonucleotides as biological effecters. A novel Raman marker at 821 cm^-1 is demonstrated as diagnostic of phosphoester torsions α and ζ in the gauche⁺ range. Specific Raman markers are also identified for the S type (C2'-endo) deoxyadenosine conformations that occur in R32 and P3 crystal structures of c(dAp)₃.