Relationship between Solid State Structure and Solution Stability of Copper(II) – Hydroxypyridinecarboxylate Complexes

Nóra V. May, G. Tamás Gál, Zsolt Szentendrei, László Korecz, Zoltán May, Maria Grazia Ferlin, Annalisa Dean, Petra Bombicz and Valerio B. Di Marco

New J. Chem., 2019,43, 10699-10710


The complementary solid state/solution studies 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, act as linkers between adjacent copper complexes, [Cu(L4)2]n·3H2O (4) (1D polymer) and [Cu3(L5)6]·18H2O (5) (trimer), constructed using two square-pyramidal and one elongated octahedral Cu(II) complexes have been determined by SXRD. The bidentate coordination mode of the ligands has 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 (log βLH) 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.

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