Tuning Cu-BTSC redox potential Sample Clauses

Tuning Cu-BTSC redox potential. The redox potential of Cu-BTSC complexes may be altered through chemical modification of the ligand109,110,122. The Cu-BTSC family of complexes therefore possess a range of hypoxia sensitivities. Alkylation at the R1-R4 positions changes the ligand backbone to create a different BTSC species. This renders each BTSC more or less hypoxia selective. For example, Cu-ATSM is alkylated at the R1-R4 positions and is more hypoxia selective than Cu-PTSM, which is alkylated at R1, R3 and R4 positions (figure 1.6). The redox potential of each complex is manipulable by the alkylation at the R1 and R2 positions, which increases the electron donating strength of the ligand110,119. Doing so makes the complex harder to reduce and increases its stability, and thus its hypoxia selectivity. This offers an explanation to the increased hypoxia selectivity of Cu-ATSM compared with Cu-(PTSM)123. Xxxxxx et al., used density functional theory to model Cu-BTSC electron density to better understand the chemical reduction of these complexes119. It was suggested that double alkylation at the R1 and R2 positions of Cu-ATSM protects the complex from electron reduction, such that only the copper ion is reduced, generating a [Cu(I)ATSM]- species. The single R1-R2 alkylation of Cu- PTSM allows the electron reduction of the PTSM complex itself, to generate a [Cu(II)-PTSM]- species. Cu(II)-PTSM]- is less readily oxidised compared with Cu(I)-[ATSM]-, even under normoxic conditions, meaning that it remains as an anion. It is also more prone to protonation, accelerating dissociation and the release of its radiocopper core, even under normoxic conditions. For this reason Cu-PTSM may be utilised as a perfusion tracer as it is trapped in tissue with adequate perfusion124. The [Cu(I)-ATSM]- species is much more stable than [Cu(II)- PTSM]- and therefore resides in the cell for longer, increasing the likelihood that it may interact with molecular oxygen to become reoxidised. When oxygen is eliminated from the environment (i.e. hypoxia) the transiently trapped [Cu(I)-ATSM]- becomes more likely to dissociate. Cu-ATSM is therefore more hypoxia selective than Cu-PTSM. A R1 R2 R3 R3 B C