Synthesis, X-ray crystallographic, spectroscopic investigation and cleavage studies of HPNP by simple bispyridyl iron, copper, cobalt, nickel and zinc complexes as artificial nucleases

Abstract

The ligand N, N-bis[[6-(hydroxymethyl)pyridine-2-yl]methyl]- p-tosylamide ( L) and its Fe(II), Co(II), Ni(II), Cu(I), Cu(II) and Zn(II) complexes were synthesised as potential catalysts for the hydrolysis of phosphate diesters such as 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) and mRNA. The ligand and its complexes were characterised by X-ray crystallography, IR, fluorescence and absorption spectroscopy and ESMS. The X-ray structures of L · Fe(II), [L 1 Fe 1 ], L · Co(II) [L 1 Co 1 ], L · Ni(II) [L 1 Ni 1 ] and L · Zn(II) [L 1 Zn 1 ] showed that there were structurally similar complexes consisting of an octahedral geometry where the metal ion was coordinated to the nitrogens of the two pyridines and to the two hydroxy groups in a square planar arrangement with two CH 3CN molecules capping the two vacant coordination sites. The L · Cu(II) however was obtained as a symmetrical dimer [L 2 Cu 2 ] from Cu(I). The recognition (complexation) of the in situ complex L · Cu(I) (which gave L · Cu(II) upon oxidation in air) and L · Zn(II) were also investigated by monitoring the changes in the 1H NMR spectrum upon titration with Cu(I) and Zn(II) salts. The L · Zn(II) complex was also strongly fluorescent, with a fluorescence enhancement of ca. 200 upon the addition of 1 eq. of ZnClO 4. All the compounds hydrolytically cleaved HPNP at pH 7.4 and 37.4 °C, but to different degrees, with L · Cu(II) and L · Zn(II) being most efficient in promoting transesterification of HPNP.