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.

Tetracyclic bisaminals formed by condensation of tetraazamacrocycles and glyoxal have rarely been utilized as ligands for transition metal ions. Five novel Cu²⁺ complexes are presented to expand this set. Glyoxal derivatives of pyruvic aldehyde and butanedione were expected to further rigidify the bisaminal skeleton because of the steric requirements of the methyl groups, while the previously unutilized homocyclam was expected to increase flexibility due to the presence of a seven-membered ring. Additionally, a nitrato complex was prepared to examine the effect of more bulky monodentate ligands on the bisaminal framework. The new complexes showed similar four-coordination of Cu²⁺, but with significant changes in coordination geometry caused by substitution of the glyoxal bridge by one or two methyl groups. The homocyclam derivative produced a completely different coordination mode due to the flexibility of the larger macrocycle ring. Both structural and electronic properties were affected by the use of nitrato in place of the typical chlorido monodentate ligands. Overall, the electronic properties (magnetic moment, electronic spectra, and cyclic voltammetry) were only subtly affected. However, larger changes were observed when the larger homocyclam macrocycle was used or the nitrato anion was used in place of the chlorido ligand to complete the coordination. Additionally, the recently published geometric index τ_δ was evaluated by using this series of closely related Cu²⁺ complexes.

Gallium-68 has the potential to become the technetium-99m of positron emission tomography with ideal decay characteristics and a long-lived parent isotope for generator production. The work in the area of ⁶⁸Ga is focused on two key areas: (1) synthesis of a library of bifunctional chelators, which can be quickly radiolabelled to form kinetically inert complexes under mild conditions compatible with biomolecules and (2) development of radiosynthetic methodologies for clinical use and to facilitate radiolabelling of a wide range of chelators under mild conditions. Recent advances in these areas, with particular focus on the past 3 years, are covered herein.