[Show abstract][Hide abstract] ABSTRACT: IUCr Journals CRYSTALLOGRAPHY JOURNALS ONLINE This open-access article is distributed under the terms of the Creative Commons Attribution Licence http://creativecommons.org/licenses/by/2.0/uk/legalcode, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. Acta Cryst. (2014). E70, 148–152 Prior et al. · [CrCl 2 (C 12 H 26 N 4)]PF 6 and [CrCl 2 (C 14 H 30 N 4)]PF 6
[Show abstract][Hide abstract] 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 Mn(2+) complex of this ligand was the most potent with IC50s of 0.127 and 0.157μM 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 Mn(2+). Few of the Cu(2+) and Fe(2+) complexes also showed improvement in activity but Ni(2+), Co(2+) and Zn(2+) complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development.
[Show abstract][Hide abstract] ABSTRACT: Tetraazamacrocyclic complexes of transition metals provide useful units for incorporating multiple coordination interactions into a single protein binding molecule. They can be designed with available sites for protein interactions via donor atom-containing amino acid side chains or labile ligands, such as H(2)O, allowing facile exchange. Three configurationally restricted nickel(ii) cyclam complexes with either one or two macrocyclic rings were synthesised and their ability to abrogate the CXCR4 chemokine receptor signalling process was assessed (IC(50) = 8320, 194 and 14 nM). Analogues were characterised crystallographically to determine the geometric parameters of the acetate binding as a model for aspartate. The most active nickel(ii) compound was tested in several anti-HIV assays against representative viral strains showing highly potent EC(50) values down to 13 nM against CXCR4 using viruses, with no observed cytotoxicity (CC(50) > 125 μM).
[Show abstract][Hide abstract] ABSTRACT: Covalently linked azamacrocycles have been known for several decades, but only a modest number of these ligands and their complexes had been described prior to 2000. Since that time, a number of new synthetic methods for their preparation have been discovered, yielding a growing collection of these interesting ligands. Additionally, the number of uses to which these ligands and their metal complexes have been applied has expanded. In this review, the important synthetic methods yielding linked azamacrocycles will be outlined, and their applications will be discussed.
[Show abstract][Hide abstract] ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
[Show abstract][Hide abstract] ABSTRACT: Dichloro(4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane)chromium(III) chloride, Dichloro(4,10-dibenzyl-1,4,7,10-tetraazabicyclo[5.5.2]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 cross-bridged tetraazamacrocycle. Aquation of these complexes proved difficult, but Chlorohydroxo(4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]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 mu(eff) = 3.95 B.M. and electronic absorbtions in acetonitrile at lambda(max) = 583nm (epsilon = 65.8 L/cm.mol), 431nm (epsilon = 34.8 L/cm.mol) and 369nm (epsilon = 17 L/cm.mol).
[Show abstract][Hide abstract] ABSTRACT: A new copper(II) containing bis-macrocyclic CXCR4 chemokine receptor antagonist is shown to have improved binding properties to the receptor protein in comparison to the drug AMD3100 (Plerixafor, Mozobil). The interaction of the metallodrug has been optimized by using ultrarigid chelator units that offer an equatorial site for coordination to the amino acid side chains of the protein. Binding competition assays with anti-CXCR4 antibodies show that the new compound stays bound longer and it has improved anti-HIV potency in vitro (EC(50) = 4.3 nM). X-ray structural studies using acetate as a model for carboxylate amino acid side chains indicate the nature of the coordination interaction.
Journal of the American Chemical Society 03/2009; 131(10):3416-7. · 10.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pyrazine-containing ligands 1 (pyrazine-2-carboxylic acid (pyridine-2-ylmethyl)-amide) and 2 (pyrazine-2,5-dicarboxylic acid bis-[(pyridine-2-ylmethyl)-amide]) have been synthesized and characterized in order to probe their ability to form polynuclear transition metal complexes. A mixed oxidation state Co3+–Co2+–Co3+ complex with deprotonated ligand 1, [Co(1−)2Co(H2O)2Cl2Co(1−)2]Cl2, has been obtained and characterized by X-ray crystal structure determination. The central octahedral cobalt(II) ion in the complex is coordinated by one pyrazine nitrogen from each of the surrounding octahedral cobalt(III), ions which are meridianally coordinated by two of the ligands 1−. Key aspects of both ligands are their rigid meridianal coordination, coupled with the pyrazine core, which demands coordination of metal ions on opposite sides of the ligand strand.
[Show abstract][Hide abstract] ABSTRACT: The title compound, [FeCl2(C12H26N4)]PF6, is the first mononuclear Fe3+ complex of an ethylene cross-bridged tetraaza-macrocycle to be structurally characterized. Comparison with the mononuclear Fe2+ complex of the same ligand shows that the smaller Fe3+ ion is more fully encapsulated by the cavity of the bicyclic ligand. Comparison with the mu-oxo dinuclear complex of an unsubstituted ligand of the same size demonstrates that the methyl groups of 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane prevent dimerization upon oxidation of the metal centre. Nax -Fe3+ -Nax bond angles (ax is axial), and thus the degree of encapsulation by the ligand, are quite different between the mononuclear and dinuclear mu-oxo species, which is probably the consequence of steric considerations.
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Medicinal Chemistry 11/2006; 49(21):6162-5. · 5.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CCXCR4 belongs to the superfamily of seven transmembrane G-protein-
coupled receptors that transduce signals via heterotrimeric
G-proteins. CXCR4 and its ligand CXCL12 are widely expressed in
normal tissues and play a fundamental role in many processes including
fetal development and trafficking of naı¨ve lymphocytes. CXCR4
receptor has been determined to act as a co-receptor for HIV-1 and
HIV-2 (X4) strains, and thus is a potential therapeutic target.
Bis-azamacrocycles (BAZ) such as AMD3100 have been identified as
potent inhibitors of HIV replication and CXCL12 by interacting with
Asp171 and Asp262 of CXCR4. Incorporation of transition metals to
AMD3100 increases the antiviral potency up to 36-fold. A series of
configurationally restricted BAZ with an ethylene moiety were prepared
which show improved binding properties to AMD3100. Configurationally
restricted BAZ were evaluated for binding potency to
CXCR4 by their ability to block the binding of CXCR4 specific mAbs.
Configurationally restricted BAZ inhibited all mAbs more effectively
than metal complexes of AMD3100. These configurationally restricted
BAZ are attractive drug candidates for therapeutic intervention in
which CXCR4 is critically involved.
[Show abstract][Hide abstract] ABSTRACT: An unusual copper(ii) complex of a highly rigid and bulky ligand (a macrocycle-glyoxal condensate) has been synthesized and investigated via DFT calculations and structural characterisation.
Chemical Communications 09/2004; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The cobalt(III) complexes of 4,11-diacetato-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (1), [Co(1)]PF 6 , and 4,11-diacetamido-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (2), [Co(2)][PF 6 ] 3 , have been synthesized and characterized. The crystal structure of [Co(1)]PF 6 consists of an octahedral cobalt(III) cation coordinated to all four ligand nitrogen donors in the macrobicycleÕs cavity, as well as to the deprotonated carboxylate oxygen atoms of both pendant arms. Analytical and spectroscopic data indicates that the ligand in [Co(2)][PF 6 ] 3 is not deprotonated, suggesting coordination through the amide carbonyl oxygens. Study of the electronic spectra of these novel complexes and comparison with data from related cobalt(III) complexes characterizes the ligands as strong field with D 0 ¼ 24; 040 and D 0 ¼ 24; 250 cm À1 for 1 and 2, respectively. Cyclic voltammograms were obtained for both complexes with large variations observed due to the differences in ligand charge and coordination. Ó 2003 Published by Elsevier B.V.
[Show abstract][Hide abstract] ABSTRACT: New copper(II) and zinc(II) complexes of cross-bridged tetraazamacrocyclic ligands derived from 1,4,8,11-tetraazacyclotetrade-cane (cyclam), 1,4,7,10-tetraazacyclotridecane (aneN4), and 1,4,7,10-tetraazacyclododecane (cyclen) have been synthesized. The X-ray crystal structures of the two cyclen-derived complexes have been determined and show both metal ions to be in distorted octahedral environments with the ligand in a cis -folded conformation. The bridged-ligand complexes are remarkably stable kinetically under harsh acidic conditions, as seen from their dissociation reactions. The electrochemical and spectroscopic properties of the Cu 2' complexes have also been investigated. # 2003 Elsevier Science B.V. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: The Mn 2' and Fe 2' complexes of the cross-bridged tetraazamacrocyclic ligands, 4,11-dibenzyl-1,4,8,11-tetraazabicy-clo[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 Fe 2' complexes of the unsubstitued ligands form m-oxo dimers upon exposure to air, which have also been structurally characterized. Cyclic voltammetry of the monomeric complexes shows reversible redox processes for the M 3' /M 2' couples, which are sensitive to solvent, ring size, and ring substitution. # 2002 Elsevier Science B.V. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Bridging superstructures added to small azamacrocycles, through the accompanying additional topological constraint, enhance the characteristic that makes azamacrocycles indispensable ligands for transition metal coordination including biomimetic chemistry: high complex stability. This review begins by briefly revisiting the coordination chemistry concepts leading to this advantage over less topologically complex ligands. Then, it details the approaches used to synthesize such bridged azamacrocycles, including direct organic synthesis, the use of templates, protection/deprotection chemistry, and various condensation reactions. The example of a specific ligand type and its transition metal complexes, which are useful for biomimetic applications, illustrates the potential of the field and lead to some general conclusions.
[Show abstract][Hide abstract] ABSTRACT: Novel Cu(II) complexes CuLCl(2) (L = 1-4) have been synthesized containing the metal bound to a well-known type of tetracyclic bisaminal formed from the condensation of glyoxal and tetraazamacrocycles (1 = cyclam-glyoxal condensate, 2 = aneN4-glyoxal condensate, 3 = cyclen-glyoxal condensate, 4 = isocyclam-glyoxal condensate). The four-coordinate complexes were characterized by X-ray crystallography, electronic spectroscopy, solid-state magnetic moments, and electron spin resonance spectroscopy. The tetracyclic bisaminals, although having four potential donor atoms, are bound in a cis-bidentate fashion to Cu(II) with two additional cis-chloride donors. The ligands take up folded conformations, and with the exception of ligand 4, only nonadjacent nitrogen atoms coordinate. As expected, ligand 2 in Cu(2)Cl(2) has a folded structure similar to those of the previously characterized 1 and 3. The conformation of 4 in the complex Cu(4)Cl(2) differs from 1-3 in that three nitrogens direct their lone pairs to one side of the folded tetracycle, with adjacent nitrogen atoms coordinated to Cu(II). This difference is probably caused by the presence of the more flexible seven-membered ring rather than the five- to six-membered rings in 1-3. Air oxidation of Cu(I) in the presence of 1 or 3 results in bis(mu-hydroxo) dimers as characterized by X-ray crystal structures, suggesting dioxygen binding, followed by O-O bond splitting to give the Cu(2)O(2) diamond core.