Molecular Interactions of a Zinc(II) Macrocycle towards Carboxylate Ligands

Abstract

Cyclam and its derivatives attract great interests due to their highly potent and selective anti-HIV activity by specifically blocking the co-receptor CXCR4. Particularly, the xylyl-bicyclam known as AMD3100 has recently been on clinical trials for the treatment of AIDS. The aspartate residues (Asp 171 and Asp 262) having carboxylate groups of the CXCR4 co-receptor have been understood to participate in the recognition of cyclams. The antiviral activity is greatly enhanced by metal complexation, especially zinc(II) ion, to macrocycles. It is believed that the metal ions of the zinc(II) complexes preferentially recognize the aspartates of the CXCR4 co-receptor by coordination. Therefore, the better knowledge of interactions between zinc(II) macrocycles and carboxylates is crucial for the improved design and development of more effective antiHIV agents. In this context, we have made an effort to expand upon the examples of carboxylato zinc(II) macrocycles to elucidate the nature of interactions between zinc(II) macrocycles and carboxylates. Herein, we report the synthesis, structure and properties of a new carboxylato zinc(II) complex Zn(L)(apc)2 (1) (L = 5,16-dimethyl-2,6,13,17tetraazatricyclo[16.4.0.0]docosane, apc = 3-amino-2pyrazinecarboxylate) in which the macrocycle L has a close resemblance to a cyclam. Experimental Section