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 β_LH) 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.