Cisplatin forms the cis-Pt(NH3)(2)(d(GpG)) intrastrand cross-link with DNA. Recently our experiments showed that the phosphodiester backbone can have a normal (1) or opposite (2) backbone propagation direction, leading to four conformer classes, HH1, HH2, Delta HT1, and Lambda HT2, with the bases in either a head-to-head or head-to-tail orientation. In addition, since each G residue can be syn or anti and the base canting can be left (L) or right (R) handed, 32 variants of this cross-link are conceivable. Reported evidence supported the existence of only the two anti,anti HH1 variants, L in single strands and in cis-Pt(NH3)(2)d(GpG)) and R in duplexes and in the ribo analogue, cis-Pt(NH3)(2)(GpG); in this regard, the latter is an excellent simple model of the DNA lesion. To test such interpretations, we used retro-model adducts (complexes with carrier ligands designed to slow dynamic motion in the d(GpG) cross-link). In retro-model d(Gpc) adducts, anti,syn Delta HT1 L (5'-G anti and 3'-G syn) and anti,anti HH2 R variants have energy comparable to the previously known anti,anti HH1 variants; our work has led to the hypothesis that cis-Pt(NH3)2 adducts may actually be mixtures of conformers exchanging rapidly on the NMR time scale (Marzilli et al. J. Am. Chem. Sec. 1999, 121, 9133-9142). To test this hypothesis, we have now conducted NMR and CD spectroscopic studies of GpG adducts. Retro models containing the Bip (2, 2'-bipiperidine) carrier ligand in two enantiomeric forms, (R,S,S,R)-Bip and (S,R,R,S)Bip (N,C,C, and N chelate ring atoms having the respective R or S configurations), control, respectively, the R and L base canting direction. For low pH (both G N1H's still protonated), (R,S,S,R)-BipPt(GpG) is almost entirely anti,anti HH1 R, but (S,R,R,S)-BipPt(GpG) is a mixture of anti,anti HH1 L and anti,syn Delta HT1 L forms, both new low pH forms for a GpG adduct. This HT variant grew to dominance after similar to 3 d at pH similar to 10 (both G N1's deprotonated). By pH jump experiments, we obtained NMR and deconvoluted CD spectra of both L variants of (S,R,R,S)-BipPt(GpG) at low and high pH. Spectral features of these L variants are present in cis-Pt(NH3)(2)(GpG) spectra, suggesting that the anti,anti HH1 R variant is not exclusively present but that similar to 30% of other variants are present; N1H deprotonation alters the distribution of forms as found also for retro models. The results suggest that the spectroscopic and structural properties for retro models are directly relevant to cisplatin adducts.