Experimental electron density and electrostatic potential analysis of zinc(aspirinate) 2 (H 2 O) 2 complex A 3d 10 metal bonding to a drug ligand

International audienceFor the protection against the side effects and the improvement of the pharmacological activity of nonsteroidal antiinflammatory drugs (NSAID's), one alternative way is to design a metal complex of these agents. In this context, we have investigated the electrostatic properties of the zinc-aspirinate dihydrate (Zn[C 9 H 7 O 4 ] 2 (H 2 O) 2 ) complex to characterize and to mimic the activity of this potent pharmaceutical compound. A high-resolution X-ray diffraction experiment at 100 K has been performed on the Zn[C 9 H 7 O 4 ] 2 (H 2 O) 2 complex which crystallizes in the C2/c space group displaying a tetrahedrally coordinated zinc atom. The Hansen-Coppens multipole model was used to derive the experimental electron density to study the chemical bonding and the metal-ligand charge transfer. The investigation of the electron density has revealed that only the Zn 4s orbital participates in the metal-ligand interaction whereas the metal 3d full valence shell remains unperturbated. The κ-model refinement yielded a zinc net charge of +1.3 e with a highly contracted 4s electronic shell. The most positive charge of the aspirinate ligand was found on the acetyl carbon (+0.8 e), in agreement with the previously observed nucleophilic attack on the aspirin drug in the inhibited cyclooxygenase (COX) enzyme channel. The electrostatic potential was calculated from the multipole populations and the net atomic charges derived from the X-ray diffraction data. This fundamental property was carefully analyzed through the 3D isopotential and molecular surface representations to highlight the active sites of the zinc-aspirinate complex