No abstract

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 Mn2+ 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 antimalarial 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.

Stable aqueous fullerene colloidal suspensions (nC(60)) are demonstrated to rely on the [6,6]-closed epoxide derivative of the fullerene (C(60)O) for stability. This derivative is present, though often unrecognized, in small quantities in nearly all C(60) starting materials due to a reaction with air. The low-yield formation of nC(60) from organic solvent solutions results from a preferential partitioning and thus enrichment of C(60)O in the colloidal particles. This partitioning is significantly retarded in the nC(60) synthesis method that does not involve organic solvent solutions: long-term stirring in water. Instead, this method relies on trace levels of ozone in the ambient atmosphere to produce sufficient C(60)O at the surfaces of the nC(60) particles to allow stable suspension in water. Controlled-atmosphere syntheses, deliberate C(60)O enrichment, light scattering measurements, and extraction followed by HPLC analysis and UV-visible absorption spectroscopy support the above model of nC(60) formation and stabilization.

The CXCR4 chemokine receptor is implicated in a number of diseases including HIV infection and cancer development and metastasis. Previous studies have demonstrated that configurationally restricted bis-tetraazamacrocyclic metal complexes are high-affinity CXCR4 antagonists. Here, we present the synthesis of Cu2+ and Zn2+ acetate complexes of six cross-bridged tetraazamacrocycles to mimic their coordination interaction with the aspartate side chains known to bind them to CXCR4. X-ray crystal structures for three new Cu2+ acetate complexes and two new Zn2+ acetate complexes, demonstrate metal-ion dependent differences in the mode of binding the acetate ligand concomitantly with the requisite cis-V configured cross-bridged tetraazamacrocyle. Concurrent density functional theory molecular modelling studies produced an energetic rationale for the unexpected [Zn(OAc)(H2O)]+ coordination motif present in all of the Zn2+ cross-bridged tetraazamacrocycle crystal structures, which differs from the chelating acetate [Zn(OAc)]+ structures of known unbridged and side-bridged tetraazamacrocyclic Zn2+ containing CXCR4 antagonists.

No abstract

No abstract

Ni and Co complexes of cross-bridged vs. unbridged tetraazamacrocycle acetate complexes reveal preferences likely to impact CXCR4 antagonist interactions.

Dichloro(4,4,7,.2]tetradecane)chromium(III) chloride, Dichloro(4,4,7,.2]tetradecane) chromium(III) chloride, and Dichloro (4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2] hexadecane)chromium)(III) chloride have been prepared by the reaction of anhydrous chromium(III) chloride with the appropriate crossbridged tetraazamacrocycle. Aquation of these complexes proved difficult, but Chlorohydroxo(4,4,8,.2]hexadecane)chromium)(III) chloride was synthesized directly from chromium(II) chloride complexation followed by exposure or the reaction to air in the presence of water. The four complexes were characterized by X-ray crystal structure determination. All contain the chromium(III) ion in a distorted octahedral geometry and the macrocycle in the cis-V configuration, as dictated by the ethylene cross-bridge. Further characterization of the hydroxo complex reveals a magnetic moment of μ eff = 3.95 B.M. and electronic absorbtions in acetonitrile at λ max = 583nm (ε = 65.8 L/cm·mol), 431nm (ε = 34.8 L/cm·mol) and 369nm (ε = 17 L/cm·mol).