A family of 2,4-pyridyl-disubstituted bispidol derivatives bearing methylene carboxylic acid ethyl esters (L-1-L-3), methylene carboxylic acids (L-4 and L-5), or methylenethiophene (L-6) groups were synthesized. In water, all ligands form rigid 1:1 complexes in the presence of Zn(II) in which the bicycle adopts a chair-chair conformation (cis isomer), as observed by H-1 NMR and, in the case of ligand L-1, by an X-ray diffraction crystal structure. Interestingly, addition of Zn(II) ions on ligand L-1 induces a metal-mediated selective hydrolysis of the ethyl esters. This selective hydrolysis was not observed upon addition of other cations such as Na+, Mg+, and Ca2+. Reduction of the central ketone was achieved to prevent ring opening via retro DielsAlder reactions and to afford highly stable and water-soluble ligands (L-4, L-5, L-6). The complexation properties of L-4 and L-6 were studied in solution, with a particular interest for ligand L4. Fast complexation occurs in strongly acidic media (pH = 1), with a high affinity toward Cu(II) (log K-CuL4 = 19.2(3), pCu = 17.0 at pH 7.4, pCu = -log[Cu-free], [Cu] = 1 x 10(-6) M, [L] = 1 x 10(-5) M) and high selectivity versus Co(II), Ni(II), and Zn(II), as shown by the values of the binding constants obtained from potentiometric and spectrophotometric titrations. Reversible redox potential with E-1/2 = -430 mV (vs normal hydrogen electrode) was measured. The complex was found to be fairly inert from acid-assisted dissociation experiments in 5 M HClO4 (t(1/2) = 110 d at 25 degrees C).