Platinum Drugs, Nucleotides and DNA : The Role of Interligand Interactions - Metal Complex-DNA Interactions - page 141

pointing toward the cis G ('6-out' canting). The base with O6 on the same side of
the coordination plane as the N-CH 2 X group of the cis amine (X = H or R for
Me 2 dab and bip ligands, respectively) had a downfi eld H8 signal (HH d ), 76 - 78,82,104
indicative of an H8 pointing away from the cis G (no canting or ' 6 - in ' canting). Dif-
ferently from HH, in HT conformers the two bases are equivalent and the H8 of
each G is on the same side of the coordination plane as the six-membered ring of
the cis G. Under these circumstances the shielding effect of the cis G is expected
to be signifi cant even for no canting or moderate '6-in' canting of the two
nucleobases.

5.2 Internucleotide Interactions

5.2.1 Dipole - Dipole Interaction Between cis Guanines

The major HT conformer found in Me 2 dab and bip - PtG 2 adducts has G O6 located
on the opposite side of the coordination plane from the cis amine N - H. 78,104 The
favoured form could not participate in a G O6/NH cis amine hydrogen bond, reveal-
ing that such an H-bonding might not be so important (Figure 5.7). 100,104,114
The most plausible explanation for this behaviour is that stabilization of the
HT conformers stems from dipole-dipole interactions between cis bases, and that
this interaction is stronger for G bases having the six-membered ring of each
guanine leaning towards the cis G ( ' 6 - in ' canting). The ' 6 - in ' canting, however,
will bring the H8 of each guanine close to the cis amine and, if an N-Me substitu-
ent is on the same side of the platinum coordination plane as the H8, an unfa-
vourable interaction between the two groups will limit the degree of '6-in' canting
and the stability of the conformer. This is the case for 'minor' HT conformers
depicted in Figure 5.7. It is noteworthy that, in X-ray structures of HT conformers
of cis - A 2 PtG 2 complexes, much greater '6-in' canting can be found when the H8 of
each guanine is on the same side of the platinum coordination plane as an N-H of
the cis amine 115,116 than when it is on the side of an N-Me of the cis amine. 117,118
A '6-in' canting of ca. 20 ° (deviation from the guanine plane orthogonal to the
coordination plane) will bring the electron-rich O6 atom of each guanine closer to
the electron-defi cient H8 atom of the cis base. Moreover, greater canting also
reduces the dihedral angle between the planes of the two guanines (for a canting
angle of 10 ° , 20 ° , 30 ° and 40 ° the dihedral angle is found to be 82 ° , 74 ° , 66 ° and
56 °, respectively) and possibly increases internucleotide stacking interactions.

5.2.2 Repulsion Between O 6 Groups of cis Guanines

In Me 2 dab and bip-PtG 2 HH conformers, there is a large dispersion of H8 chemical
shifts ( 1 ppm) that stems from a combination of electronic and steric effects. Elec-

trostatic repulsion between electron-rich O6 atoms of cis Gs will tend to place the
six - membered rings farther apart. 119 The stereochemistry of the Me 2 dab and bip

∼