Relationship Between Solid State Structure and Solution Stability of Copper(II) - Hydroxypyridinecarboxylate Complexes

The complementary solid state / solution study of the systematic series of bioactive ligands: 3-hydroxy-1-methyl-4-pyridinecarboxylate (L1), 3-hydroxy-1,2,6-trimethyl-4-pyridinecarboxylate (L2), 4-hydroxy-1-methyl-3-pyridinecarboxylate (L3), 4-hydroxy-1,6-dimethyl-3-pyridinecarboxylate (L4), 4-hydroxy-1-(2-hydroxyethyl)-6-methyl-3-pyridinecarboxylate) (L5) and 4-hydroxy-1-(2-carboxyethyl)-6-methyl-3-pyridinecarboxylate (L6) with copper(II) have been performed in order to design efficient chelating drugs for the treatment of metal overloading conditions. Single crystals of [Cu(L1)2(H2O)].3H2O (1) (monomer) with axial water coordination, [Cu2(L2)4].6H2O (2) and [Cu2(L3)4].4H2O (3) (cyclic dimers) where pyridinolato and carboxylato oxygens, respectively, acts as linkers between adjacent copper complexes, [Cu(L4)2]n.3H2O (4) (1D polymer) and [Cu3(L5)6].18H2O (5) (trimer) constructed by two square-pyramidal and one elongated octahedral Cu(II) complexes have been determined by SXRD. The bidentate coordination mode of the ligands have been found preferentially with cis arrangements in 1 and 2 and trans arrangements in 3-5. The solution speciation and complex stability of aqueous solutions have been studied by pH-dependent electron paramagnetic resonance spectroscopy resulting in the detection of solely monomeric [CuL]+ and [CuL2] complexes. The stability order obtained for the [CuL]+ complexes could be correlated with the deprotonation constants of their hydroxyl group (logβLH) reflecting that the higher acidity increases the complex stability in the order: L2 < L1 ≈ L6 < L4 ≈ L5 < L3. This stability order elucidates the different axial linkers in the cyclic dimers 2 and 3. DFT quantum-chemical calculations support the effect of the electron distribution on the established stability order.