DFT analysis of diclofenac activity and cation type influence on the theoretical parameters of some diclofenac complexes

The twisted structure of diclofenac sodium that is behind the excessively remarkable reactivity of this drug, was investigated by DFT calculations at the B3LYP/6-311G (d) level of theory. The repulsion forces, existing within the molecule because of the simultaneous presence of the acetate moiety as well as the two Cl atoms, created a twisted (74°) diphenylamine structure to yield a preferred orientation. B3LYP/ 6-311G (d) calculations of diclofenac and its complexes, ML2 (L=Ca, Mg, Zn), showed that distortions of the geometric parameters were due to the differing hybridizations depending on the cation type in question. The energy gap values, ΔE, increased in the order Mg>Zn>Ca, pointing out that the energy associated with electron pairing is greatest in the Mg2+ complex, due to the [Ne]3s2 configuration and large charge to radius ratio (3.3) of the metal. The charge density contour plots of the complexes showed the negative charge as condensed around the N atom, indicating a very highly polarized M-N coordinate bond. Both the acid form and sodium salt displayed the typical weak N-H⋯O hydrogen bond association which is absent in the Mg, Ca and Zn complexes. The distance between H and O in all three (3.837 Mg, 3.307 Ca and 4.277 Zn Å) exceeded the possible limit of 3.0 Å.