561303-73-9Relevant academic research and scientific papers
Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands
Hubin, Timothy J.,Amoyaw, Prince N.-A.,Roewe, Kimberly D.,Simpson, Natalie C.,Maples, Randall D.,Carder Freeman, Tarynn N.,Cain, Amy N.,Le, Justin G.,Archibald, Stephen J.,Khan, Shabana I.,Tekwani, Babu L.,Khan, M.O. Faruk
, p. 3239 - 3244 (2014/06/23)
Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn 2+ complex of this ligand was the most potent with IC50s of 0.127 and 0.157 μM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn2+. Few of the Cu2+ and Fe2+ complexes also showed improvement in activity but Ni2+, Co2+ and Zn2+ complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development.
Synthesis and X-ray crystal structures of iron(II) and manganese(II) complexes of unsubstituted and benzyl substituted cross-bridged tetraazamacrocycles
Hubin, Timothy J.,McCormick, James M.,Collinson, Simon R.,Alcock, Nathaniel W.,Clase, Howard J.,Busch, Daryle H.
, p. 76 - 86 (2008/10/08)
The Mn2+ and Fe2+ complexes of the cross-bridged tetraazamacrocyclic ligands, 4,11-dibenzyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (1), 4,10-dibenzyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane (2), 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (3), and 1,4,7,10-tetraazabicyclo[5.5.2]tetradecane (4) provide new compounds of these elements for fundamental studies and applications. These unsubstituted and benzyl substituted derivatives were prepared for comparison of their structures and properties with the known catalytically active dimethyl cross-bridged ligand complexes, which are especially notable for their exceptional kinetic stabilities and redox activity. The X-ray crystal structures of five complexes demonstrate that the ligands enforce a distorted octahedral geometry on the metals with two cis sites occupied by labile ligands. The Fe2+ complexes of the unsubstitued ligands form μ-oxo dimers upon exposure to air, which have also been structurally characterized. Cyclic voltammetry of the monomeric complexes shows reversible redox processes for the M3+/M2+ couples, which are sensitive to solvent, ring size, and ring substitution.
