Configurations of Nickel–Cyclam Antiviral Complexes and Protein Recognition

Abstract

Nickel(II)–xylylbicyclam is a potent anti‐HIV agent and binds strongly to the CXCR4 co‐receptor. We have investigated configurational equilibria of NiII–cyclam derivatives, since these are important for receptor recognition. Crystallographic studies show that both trans and cis configurations are readily formed: [Ni(cyclam)(OAc)2]⋅H2O adopts the trans‐III configuration with axial monodentate acetates, as does [Ni(benzylcyclam)(NO3)2] with axial nitrate ligands, whereas [Ni(benzylcyclam)(OAc)](OAc)⋅2 H2O has an unusual folded cis‐V configuration with NiII coordination to bidentate acetate. UV/Vis and NMR studies show that the octahedral trans‐III configuration slowly converts to square‐planar trans‐I in aqueous solution. For NiII–xylylbicyclam, a mixture of cis‐V and trans‐I configurations was detected in solution. X‐ray diffraction studies showed that crystals of lysozyme soaked in NiII–cyclam or NiII2–xylylbicyclam contain two major binding sites, one involving NiII coordination to Asp101 and hydrophobic interactions between the cyclam ring and Trp62 and Trp63, and the second hydrophobic interactions with Trp123. For NiII–cyclam bound to Asp101, the cis‐V configuration predominates.

CXCR4 chemokine receptor antagonists: nickel(ii) complexes of configurationally restricted macrocycles

“…The four N-donors are planar with further ligands above and below the ring plane to give an octahedral geometry (typical example: NEXQAJ). 30 Our assumption is that a single carboxylate from the peptidic side chain in the CXCR4 protein is bound to our compounds from one side of the ring, due to the steric/topological constraint of including an ethyl bridge, and so these structures were excluded from further analysis. Seventeen structures with bound acetate groups that are not planar were found, comprising fourteen bidentate cis-V structures (including the structure determined by Sadler and co-workers in their study of configuration) 37 and three structures containing monodentate acetate ligands, with two of them including a bound water molecule.…”

Crystal structure and chemical oxidation of the palladium(II) cyclam complex within the cavity of cucurbit[8]uril

“…The cyclam ring in 1 adopts a configuration in which the hydrogens on the nitrogen donor atoms undergo minimal steric clashes (trans-III (S,S,R,R)). It is the most stable configuration both for the free, uncomplexed cyclam and for cyclam complexes [47][48][49]. Only one example of stabilization of uncommon high-energy trans-I (R,S,R,S) and trans-II (R,S,R,R) isomers of the copper(II) cyclam complex as a result of the encapsulation within the CB [8] cavity has been reported recently [27].…”

Artificial Metalloenzymes Constructed From Hierarchically‐Assembled Proteins

“…[102] Other macrocyclic metal complexes of Ni II , Cu II , Zn II , and Gd III bind to other locations within the channels through non-covalent interactions, such as hydrogen bonds and hydrophobic interactions. [105][106][107] Ni and Tezcan constructed a unique protein crystal system by metal-directed protein crystal engineering. This system has large pores that can accommodate large metal complexes.…”