Synthesis of Optically Pure Cyclometalated Iridium(III) Complex‐Peptide Hybrids and Their Anticancer Activity

Abstract

We report on the synthesis of optically pure cyclometalated iridium(III) complex‐peptide hybrids as amphiphilic peptide conjugates (IPH‐ACs) from Δ‐ and Λ‐Ir(tpyCO2H)3 (tpy: 2‐(4’‐tolyl)pyridine) by optical resolution via diastereomeric intermediates conjugated with the chiral alcohol, (1R,2R)‐2‐aminocyclohexanol ((R,R)‐11). Spectroscopic spectra of the optically pure IPH‐ACs that were prepared from Δ‐ and Λ‐Ir(tpyCO2H)3 are reported. It was found that both optically pure IPH‐ACs induce paraptotic cell death in Jurkat cells and the EC50 values were evaluated by MTT assays. We also performed TEM analyses of Jurkat cells treated with Λ‐13 to observe morphological changes that occurred, and cytoplasmic vacuolization, a characteristic feature of paraptosis, was observed. The intracellular uptake of IPH‐ACs by the cells measured by ICP‐MS (inductively coupled plasma‐mass spectrometry) was higher for the Λ‐forms and the EC50 values of the Λ‐forms were slightly lower than those of the Δ‐IPH‐ACs. The intrinsic cytotoxicity of the IPH‐ACs, taking into account the fact that the intracellular uptake and the intrinsic cytotoxicity is almost equal for the Δ‐ and Λ‐forms, suggests that the difference in cytotoxicity against Jurkat cells is due to the selectivity in the intracellular uptake of each stereoisomer.