The chirality selectivity in the uptake of platinum (II) complexes with 1,2-cyclohexanediamine isomers as carrier ligand by human erythrocytes.

Abstract

The uptake kinetics of cisplatin analogs of 1,2-cyclohexanediamine(dach) isomers with various leaving groups, by human erythrocytes in plasma isotonic buffer, were studied. The experimental results showed that the uptake rate constants (k values) decrease with the change of leaving group in the sequence: chloride (Cl) > squaric acid (SA) > oxalate (OX) > demethylcantharic acid (DA), with the same dach isomer as carrier group. It is noteworthy that for the platinum (II) complexes with the same leaving group, the k values always reduce as: 1R, 2R-dach > 1R, 2S-dach > 1S, 2S-dach. This result reflects the chirality selectivity. No differences in reactivity to protein thiols and effects on membrane permeability were found for the R,R-, R,S-, S,S-isomeric complexes. It is proposed that the chirality selectivity in uptake is due to the recognition of the chirality of the platinum complexes by the erythrocyte membrane. The interactions between the chiral platinum complexes and the head groups of the membrane phospholipid molecules are probably involved.