Theoretical Calculation of the NMR Spin−Spin Coupling Constants and the NMR Shifts Allow Distinguishability between the Specific Direct and the Water-Mediated Binding of a Divalent Metal Cation to Guanine

The calculated intermolecular and intramolecular indirect NMR spin−spin coupling constants
and NMR shifts were used for the discrimination between the inner-shell and the outer-shell binding motif
of hydrated divalent cations Mg2+ or Zn2+ with a guanine base. The intermolecular coupling constants
1J(X,O6) and 1J(X,N7) (X = Mg2+, Zn2+) can be unambiguously assigned to the specific inner-shell binding
motif of the hydrated cation either with oxygen O6 or with nitrogen N7 of guanine. The calculated coupling
constants 1J(Mg,O6) and 1J(Zn,O6) were 6.2 and −17.5 Hz, respectively, for the inner-shell complex of
cation directly interacting with oxygen O6 of guanine. For the inner-shell coordination of the cation at nitrogen
N7, the calculated coupling constants 1J(Mg,N7) and 1J(Zn,N7) were 5.6 and −36.5 Hz, respectively. When
the binding of the cation is water-mediated, the coupling constant is zero. To obtain reliable shifts in NMR
parameters, hydrated guanine was utilized as the reference state. The calculated change of NMR spin−spin coupling constants due to the hydration and coordination of the cation with guanine is caused mainly
by the variation of Fermi-contact coupling contribution while the variation of diamagnetic spin−orbit,
paramagnetic spin−orbit, and spin−dipolar coupling contributions is small. The change of s-character of
guanine sigma bonding, sigma antibonding, and lone pair orbitals upon the hydration and cation coordination
(calculated using the Natural Bond Orbital analysis) correlates with the variation of the Fermi-contact term.
The calculated NMR shifts δ(N7) of −15.3 and −12.2 ppm upon the coordination of Mg2+ and Zn2+ ion are
similar to the NMR shift of 19.6 ppm toward the high field measured by Tanaka for N7 of guanine upon the
coordination of the Cd2+ cation (Tanaka, Y.; Kojima, C.; Morita, E. H.; Kasai. Y.; Yamasaki, K.; Ono, A.;
Kainosho, M.; Taira, K. J. Am. Chem. Soc. 2002, 124, 4595−4601). The present data indicate that
measurements of NMR intermolecular coupling constants may be used to discriminate between the specific
inner- and outer-shell binding of divalent cations to nucleobases in DNA and RNA.