Selective Displacement of a Scorpionand Triazole Ligand from Metallocyclam Complexes Visualised with NMR Spectroscopy

Abstract

Target-activated metal complexes (TAMCs) -complexes that remain benign until reaching a specific biomolecular target, binding to which then effects structural change that turns on cytotoxicity or other activity -hold considerable allure. The successful development of TAMCs requires analytical methods that allow clear and unequivocal visualisation of changes in the coordination geometry of these systems in solution. Towards this goal, we report an NMR-based method to monitor coordination/de-coordination of a pendant triazole ligand to/ from metallocyclam complexes of zinc(II) and mercury(II). This scorpionand ligand can be displaced from the metal, which remains bound to the macrocyclic ligand, using an appropriate [a]

Scorpiands: Quinquedentate Ligands that Couple the Rigidity of Cyclam and the Flexibility of a Coordinating Side Chain

“…Coordination/de‐coordination of the triazole subunit to/from similar ‘allosteric’ complexes has been investigated and monitored also by different techniques. In a first example, triazole displacement in Hg II and Zn II scorpiate complexes has been induced by the addition of Cl − (Hg II ) and piperidine or citrate (Zn II ) and visualised by monitoring the 1 H NMR resonance of the single triazole C−H proton [50] . Moreover, Todd and Watkinson, using a double‐click procedure, were able to functionalize cyclam with both biotin and a fluorescent subunit (naphthalimide).…”

“…In a first example, triazole displacement in Hg II and Zn II scorpiate complexes has been induced by the addition of Cl À (Hg II ) and piperidine or citrate (Zn II ) and visualised by monitoring the 1 H NMR resonance of the single triazole CÀ H proton. [50] Moreover, Todd and Watkinson, using a double-click procedure, were able to functionalize cyclam with both biotin and a fluorescent subunit (naphthalimide). The corresponding Zn II complex displayed full naphthalimide emission since Zn II , as, a d 10 cation, cannot be involved in any double exchange ET process and, being redox inactive, cannot undergo any eT process with the proximate excited fluorophore.…”

Molecular Switches for any pH: A Systematic Study of the Versatile Coordination Behaviour of Cyclam Scorpionands

“…[38] We are interested in buildings corpionandm olecular switches as the basis of target-activated metal complexes (TAMCs): metal complexes that remain benign andu nreactive until reaching as pecific biomolecular target or microenvironment,w hereupon biomoleculeb inding renders structural and functional change in the complex that switches on cytotoxicity or other desired activity. [23,37,[39][40][41][42] To wards this end, we wished to examine the relative lability of different pendant side-arms within as elf-consistent macrocyclicf ramework. The aims of this work were to develop ad ivergent synthetic strategy that allowsa ccess to aw ide variety of side-arm functionalities, to characterise the coordination properties of the resulting ligands with copper(II) and nickel(II) in the solid state, and to investigate coordination behaviour and pH switching in solution.…”

“…We are interested in building scorpionand molecular switches as the basis of target‐activated metal complexes (TAMCs): metal complexes that remain benign and unreactive until reaching a specific biomolecular target or microenvironment, whereupon biomolecule binding renders structural and functional change in the complex that switches on cytotoxicity or other desired activity . Towards this end, we wished to examine the relative lability of different pendant side‐arms within a self‐consistent macrocyclic framework.…”