The Synthesis and Structure of Encapsulating Ligands: Properties of Bicyclic Hexamines

Abstract

Template syntheses based on tris (ethane-1,2-diamine)cobalt(III) lead to cobalt(III) complexes of cage hexamines of the ' sarcophagine ' type ( sarcophagine = sar = 3,6,10,13,16,19- hexaazabicyclo [6.6.6] icosane ) rapidly and in high yield. Reduction of these species to their cobalt(II) forms enables the ligands to be removed in concentrated acids at elevated temperatures, and in hot aqueous solutions containing excess cyanide ion. The free sarcophagine and 1,8-diaminosarcophagine [(NH2)2sar or diamsar] ligands are strong bases, accepting up to four and five protons, respectively, in aqueous solution. In chloride medium, I = 1.0, at 298 K, pK1 = 11.95, pK2 = 10.33, pK3 = 7.17, pK4 ≈ 0 for sarcophagine , and pK1 = 11.44, pK2 = 9.64, pK3 = 6.49, pK4 = 5.48, pK5 ≈ 0 for diaminosarcophagine , with very similar values being found for triflate medium. Crystal structure determinations for both free bases, the chloride, sulfate, perchlorate and nitrate salts of diamsar , the complex of zinc chloride with sar, and the magnesium nitrate complex with diamsar show remarkably small variations in the cavity defined by the bicyclic ligands, though relatively subtle bond length and bond angle changes can be rationalized in terms of the effects of proton and metal ion binding. Exhaustive methylation of sarcophagine produces the highly lipophilic, hexatertiary base hexamethylsarcophagine , which, in the solid state, adopts quite different conformations and nitrogen-atom configurations to those of sar itself. All the ligands rapidly form metal ion complexes of generally exceptional kinetic and thermodynamic stability.

Kinetic Inertness and Electrochemical Behavior of Copper(II) Tetraazamacrocyclic Complexes: Possible Implications for in Vivo Stability

“…[8,10] Neither Cu-CB-Cyclam nor Cu-CB-DO2A showed comparable inertness to Cu-CB-TE2A, suggesting that both the carboxymethyl pendant arms and the bicyclo[6.6.2] cross-bridged cyclam backbone are essential for Cu-CB-TE2A's exceptional robustness. Sargeson and co-workers have reported encapsulated Cu II complexes of hexaaza cage ligands which are also extremely inert to acid decomplexation, [11,12] although direct comparisons with Cu-CB- TE2A have not yet been made.…”

Copper(II) Complexes of a Hexadentate Mixed‐Donor N3S3 Macrobicyclic Cage: Facile Rearrangements and Interconversions

“…Complete removal of Co from sar-derived cages can only be achieved after reduction to the less stable and more labile Co II form, followed by either complexation with cyanide or protonation of the free ligand. [25] In less constrained macromonocyclic Co III complexes, equilibrium and mechanistic information has been obtained identifying both ligand substitution plus amine and thioether inversion reactions. [26,27] The copper(II) chemistry of cage ligands is distinct from other transition metals due to its extreme lability and unusual coordination geometries.…”

Amyloid-β Peptide Aβ3pE-42 Induces Lipid Peroxidation, Membrane Permeabilization, and Calcium Influx in Neurons

“…Thioflavin-T, coumarin-3-carboxylic acid (3-CCA), butylated hydroxytoluene, bovine serum albumin, and paraformaldehyde were purchased from Sigma. Diamsar (1,8-diaminosarcophagine) was synthesized as reported previously (40).…”