The effect of an extremely bulky carrier ligand, such as N,N,N′,′-tetramethyl-1,2-diaminocycIohexane (Me4DACH, R,R and S,S configurations of the asymmetric carbon atoms of the chelate ring), upon the rate of formation and stability of Me4DACH-PtG2 derivatives has been investigated (G = 9-EtG, 3'-GMP, and 5'-GMP). Of the three possible rotamers, two head-to-tail (ΔHT and ΛHT) and one head-to-head (HH), only the former two are found in solution. The very small difference in H8 chemical shifts between AHT and AHT rotamers indicates that the relationship between the two guanines is very similar in the two conformers which are canted to the same degree but in opposite directions. A smaller interligand steric clash appears to favour the HT rotamer in which the H8 atoms of the guanines are on the same side of pseudo-axial N-Me's with respect to the platinum coordination plane. In the case of 5′-GMP, because of the absence of aminic protons on the carrier ligand, the 5′-phosphate directs its H-bonding potential towards the second ligand in cw-position (the coordinated H2O molecule in the mono adduct, [Me4DACH-Pt(H 2O)(5′-GMP)]+, and the ais-G in the bis-adduct). As a consequence the rotamer in which such an interaction is possible, with the nucleotide keeping its favoured anti conformation, is more stable than expected. In contrast with the behaviour of 5′-GMP, 3′-GMP is found to increase the reactivity of the mono adduct in which the phosphate is directed towards the cis-water molecule and to give a negligible contribution to the stability of the HT rotamer in which the 3′-phosphate is directed towards the cis-nucleotide. © The Royal Society of Chemistry 2003.