Zinc(ii) complexes of constrained antiviral macrocycles?

Dalton Transactions Pub Date: 2012-04-02 DOI: 10.1039/C2DT30140G

Abstract

The configurations of metallocyclams are of interest in relation to protein recognition and anti-HIV activity. We have synthesised four novel zinc(II) complexes with hexyl-Me2-cyclam (HMC; 3,14-dimethyl-2,6,13,17-tetraazatricyclo(16.4.0.07,12)docosane), 1, and naphthyl-hexyl-Me2-cyclam (NHMC; 2,13-bis(1-naphthylmethyl)-5,16-dimethyl-2,6,13,17-tetraazatricyclo(16.4.0.07,12)docosane), 2, as ligands. X-ray crystallographic data for Zn(II)–HMC diacetate, 3 show that zinc is six-coordinate in a distorted octahedral environment bound to four equatorial N atoms from the macrocycle and two axial acetato O atoms. The 14-membered metallo-macrocycle adopts a trans-III (RRSS) configuration with two six-membered rings in chair forms and two five-membered rings in gauche forms. In the chlorido Zn(II)–HMC complex 5, zinc appears to be 5-coordinate with square-pyramidal geometry. Interestingly, the chlorido Zn(II)–NHMC complex 6 crystallised in a trans-I configuration containing 4-coordinate tetrahedral zinc bound to three cyclam ring N atoms, a possible model for intermediates formed during the uptake and release of metals by cyclams. The ligand 1 and the zinc complex 3 were active towards viral strains HIV-1 (IIIB) (IC50 values of 10.51 ± 0.23 and 3.50 ± 0.33 μM, respectively), and HIV-2 (ROD) (IC50 values of 133.78 ± 14.10 and >110.67 μM, respectively). 2D [1H, 13C] and [1H, 15N] NMR spectroscopic studies suggested that the types of configurational isomers present in solution depend on the axial ligand.

Graphical abstract: Zinc(ii) complexes of constrained antiviral macrocycles
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