Toward Photoactivatable Copper(I) Anticancer Agents: Heteroleptic Cu(I) Complexes with Functionalized Dipyridylamine Ligands

In this study, we report the synthesis and characterization of three Cu(I) complexes bearing functionalized dipyridylamine ligands and DPEphos. Structural analysis confirms a distorted tetrahedral coordination environment around the metal center. Photophysical studies in DMSO show similar absorption profiles (λabs ≈ 341–343 nm) with ligand-centered and MLCT transitions, while emission spans the visible region (λemi = 410–483 nm) and is strongly influenced by ligand substitution, with the CF3 derivative displaying a marked red shift. Emission is insensitive to oxygen and exhibits short lifetimes (τ ≈ 14.9–15.3 ns), suggesting short-lived 1MLCT excited states. Biological evaluation in A375 melanoma cells reveals that all complexes exhibit low-micromolar cytotoxicity under dark conditions (IC50 = 3.33–4.92 μM). Notably, only the CF3-substituted complex shows a significant light-induced enhancement of activity upon irradiation at 390 nm (IC50 = 1.18 μM), indicating photoactivation.