The high-spin dichloro Mn 2+ and Fe 2+ complexes of 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (1) and 4, 10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane (2) provide durable new compounds of these elements for important fundamental studies and applications. The compounds are especially noteable for their exceptional kinetic stabilities and redox activity. The X-ray crystal structures of all four complexes demonstrate that the ligands enforce a distorted octahedral geometry on the metals with two cis sites occupied by labile chloride ligands. Magnetic measurements reveal that all are high spin with typical magnetic moments. Cyclic voltammetry of the complexes shows reversible redox processes at +0.110 and +0.038 V (versus SHE) for the Fe 3+ /Fe 2+ couples of Fe(1)Cl 2 and Fe(2)Cl 2 , respectively, while the Mn 3+ /Mn 2+ and Mn 4+ /Mn 3+ couples were observed at +0.585 and +1.343 V, and +0.466 and +1.232 V for the complexes Mn(1)Cl 2 and Mn(2)Cl 2 , respectively. Mn 2+ (1) was found to react with H 2 O 2 and other oxidizing agents to produce the Mn 4+ (1) complex. The catalytic efficacy of Mn 4+ (1) in aqueous solution has been assessed in the epoxidation reaction of carbamazepine and hydrogen abstraction reaction with 1,4-cyclohexadiene. The complex has been found to be a selective catalyst, exhibiting moderate catalytic activity in oxygen transfer, but significantly more effective catalytic activity in hydrogen abstraction reactions.

No abstract

No abstract

No abstract

A family of Mn3+ and Fe3+ complexes of 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (1) and 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane (2) has been prepared by the chemical oxidation of the divalent manganese and iron analogues. The ligands are ethylene cross-bridged tetraazamacrocycles derived from cylam and cyclen, respectively. The synthesis and characterization of these complexes, including X-ray crystal structure determinations, are described. The structural evidence demonstrates that the tetradentate ligands enforce distorted octahedral geometries on the metal ions, with two cis sites occupied by labile ligands. Magnetic measurements reveal that the complexes are high spin with typical magnetic moments. Cyclic voltammetry shows reversible redox processes for the Fe3+/Fe2+ couples of the iron(III) complexes, while Mn3+/Mn2+ and Mn4+/Mn3+ couples were observed for the complexes with manganese(III). The manganese chemistry of 1 was studied in depth. The dichloro manganese(III) cation of 1 undergoes facile ligand substitution reactions at the labile, monodentate sites, for example substituting azide for chloride ligands. Air oxidation of the dichloro complex of Mn (1)2+ in basic solution does not give the expected mu-oxo dimeric product common to manganese. Instead, an unusual manganese(III)-OH complex has been isolated from this reaction and structurally characterized. A similar reaction under slightly different conditions gives a putative MnIII(OH)2 complex that metathesizes to MnIII(OMe)2 upon recrystallization from methanol.

A zinc(II) containing configurationally restricted analogue of bismacrocyclic cyclam-type CXCR4 chemokine receptor antagonists has been synthesized and shown to adopt only one configuration in solution. The single crystal X-ray structure reveals favorable binding to acetate via a bidentate chelation that can be related to the proposed interaction with aspartate on the receptor protein surface. The zinc(II) complex is highly active against HIV infection in vitro. AMD3100 (the octa HCl salt of 1-1′-[1,4-phenylenebis-(methylene)]-bis(1,4,8,11-tetraazacyclotetradecane)), Figure 1c, is a drug that interacts with a cell surface protein (CXCR4) via hydrogen bonding interactions or more effectively as the metal complex via coordinate bonds with aspartate residues. 1 On metal complex formation, the tetra-aza macrocyclic rings in AMD3100 show multiple configurations in solution. 2 Configurationally fixed analogues would have the advantage of presenting only one configuration in solution for coordinate bond formation on binding to the protein. Our study aims to produce a series of configurationally fixed complexes and show the key importance of the coordination interaction for drug binding. We also wish to validate the general strategy of configurational fixing as a route to improve the activity of metal-containing drugs.The CXCR4 chemokine receptor is a seven-helix transmembrane G-protein coupled receptor with multiple critical functions in both normal and pathological physiology. It is a member of the family of 18 recognized chemokine receptors and has a sole natural ligand (CXCL12). 3 Synthetic small molecule antagonists exist, including AMD3100, and have been shown to have both a high binding specificity and an effective inhibitory action against a number of disease states. 4,5 For example, in vitro assays show that AMD3100 inhibits infection by the human immunodeficiency virus (HIV-1 and HIV-2) at micromolar concentrations. 6 It has been demonstrated that formation of metal complexes and aza-macrocyclic ring configuration may have major effects on AMD3100-protein interactions. 1,2,[7][8][9] In particular, it has been suggested that zinc(II) could play a key role in the biological activity of the bicyclam derivatives. 10,11 In an attempt to rationalize the effects of cyclam configuration and to produce new specific antagonists for CXCR4, we have successfully synthesized a configurationally fixed bismacrocyclic compound and its zinc(II) complex. The solution and solid-state properties of the zinc(II) complex were investigated via high field NMR (800 MHz) and X-ray crystallography. The inhibitory effect on infection by HIV-1 and HIV-2 in MT-4 cells is also presented for both the chelator, 4 ((5-5′-[1,4-phenylenebis(methylene)]-bis (1,5,8,12-tetraazabicyclo[10.2.2]hexadecane)), and the complex Zn 2 4(OAc) 4 .There are six possible configurations that a cyclam ring can adopt on complexation to a metal ion, as defined by Bosnich and co-workers and shown in Figure 1b, where trans-III is generally the most thermodyn...

No abstract

No abstract