Factors Controlling Metal-Ion Selectivity in the Binding Sites of Calcium-Binding Proteins. The Metal-Binding Properties of Amide Donors. A Crystallographic and Thermodynamic Study

The metal-ion complexing properties of the ligand EDTAM
(ethylenediamine-N,N,N‘,N‘-tetraacetamide)
are investigated as a model for the role of amide oxygen donors in the binding
sites of Ca-binding proteins. The structures of the complexes
[Ca(EDTAM)NO3]NO3 (1),
[La(EDTAM)(H2O)4](NO3)3·H2O
(2), and [Cd(EDTAM)(NO3)]NO3
(3) are reported:  1 monoclinic,
P21/c, a = 10.853(2)
Å, b = 12.893(3) Å, c
= 13.407(3) Å, β = 103.28(3)°, Z
= 4, R = 0.0281; 2 triclinic,
P1̄, a = 8.695(2)
Å, b = 9.960(2) Å, c
= 16.136(3) Å, α = 95.57(3)°, β =
94.84(3)°, γ = 98.72(3)°, Z = 2,
R = 0.0394; 3 monoclinic,
P21/c, a = 10.767(2)
Å, b = 12.952(2) Å, c
= 13.273(2) Å, β = 103.572(3)°, Z
= 4, R = 0.0167. Compounds 1 and
3 are isostructural, and the EDTAM binds to the metal ion
through its two N-donors and four O-donors from the amide groups. Ca(II) in
1 is 8-coordinate with a chelating NO3-
group, while Cd(II) in 3 may possibly be 7-coordinate, with an
asymmetrically coordinated NO3- that is best regarded as
unidentate. The La(III) in 2 is coordinated to the EDTAM in a
manner similar to that of 1 and 3, but it is
10-coordinate with four water molecules coordinated to the La(III). The
formation constants (log K1) for complexes of a
variety of metal ions with EDTAM are reported in 0.1 M NaNO3 at 25.0
± 0.1 °C. These are compared to the log
K1 values for en (ethylenediamine) and THPED
(N,N,N‘,N‘-tetrakis(2-hydroxypropyl)-ethylenediamine).
For large metal ions, such as Ca2+ or La3+, log
K1 increases strongly when the four acetamide
groups are added to en to give EDTAM, whereas for a small metal ion, such as
Mg2+, this increase is small. The log
K1 values for EDTAM compared to THPED suggest
that the amide oxygen is a much stronger base than the alcoholic oxygen.
Structures of binding sites in 40 Ca-binding proteins are examined. It is shown
that the Ca−OC bond angles involving coordinated amides in these sites
are large, commonly being in the 150−180° range. This is discussed in
terms of the idea that for purely ionic bonding the
M−OC bond angle will approach 180°, while for covalent
bonding the angle should be closer to 120°. How this fact might be used by
the proteins to control selectivity for different metal ions is discussed.