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Reduction of 2•TARF by NADH, sodium ascorbate and GSH monitored by 1 H and 195 Pt NMR spectroscopy. 1 H NMR signal labelling: ○ Pt-coordinated acetate ligand, • free acetate; 195 Pt NMR signal labelling: ⬣ 2•TARF, ♦ oxaliplatin.
Source publication
In situ activation of Pt(IV) to Pt(II) species is a promising strategy to control anticancer activity and overcome off-target toxicity linked to classic platinum chemotherapeutic agents. Herein, we present the design and synthesis of two new asymmetric Pt(IV) derivatives of cisplatin and oxaliplatin (1·TARF and 2·TARF, respectively) bearing a 2',3'...
Contexts in source publication
Context 1
... reactivity of the two Pt(IV)-TARF complexes was then evaluated using three reducing agents that are present in the cell milieu ( Figure 3, Figure S19 and S20), NADH, sodium ascorbate, and glutathione (GSH). We co-incubated 1•TARF and 2•TARF (1 mM) with such electron donors (4 mM) in an 8% DMF-d7/D2O mixture, and monitored by 1 H NMR the reductive elimination of the axial acetato ligands from the complexes over time (Figure 3). ...
Context 2
... reactivity of the two Pt(IV)-TARF complexes was then evaluated using three reducing agents that are present in the cell milieu ( Figure 3, Figure S19 and S20), NADH, sodium ascorbate, and glutathione (GSH). We co-incubated 1•TARF and 2•TARF (1 mM) with such electron donors (4 mM) in an 8% DMF-d7/D2O mixture, and monitored by 1 H NMR the reductive elimination of the axial acetato ligands from the complexes over time (Figure 3). Both Pt(IV) derivatives instantaneously underwent full conversion with NADH, while ascorbate took approximately 3.5 h to reduce completely 2•TARF and only 45 min in the case of 1·TARF. ...
Context 3
... NMR helped characterize the nature of the Pt-species generated by these activation reactions ( Figure 3, Figure S21). We recorded 195 Pt NMR spectra of 1·TARF and 2·TARF (D2O/DMF-d7, 80/20) treated with 4 equivalents of NADH, observing the disappearance of the Pt(IV) peaks of the prodrugs (1089.6 and 1604.5 ppm respectively) and the appearance of new signals in the Pt(II) region corresponding to cisplatin and oxaliplatin (-2149.2 ...
