Photoactivated DNA cleavage and anticancer activity of pyrenyl-terpyridine lanthanide complexes

Lanthanide(III) complexes [Ln(R-tpy)(acac)(NO3)2] (Ln = La(III) in 1, 2; Gd(III) in 4, 5) and [Ln(py–tpy)(sacac)(NO3)2] (Ln = La(III), 3; Gd(III), 6), where R-tpy is 4′-phenyl-2,2′:6′,2″-terpyridine (ph–tpy in 1, 4), 4′-(1-pyrenyl)-2,2′:6′,2″-terpyridine (py–tpy in 2, 3, 5 and 6), acac is acetylacetonate and sacac is 4-hydroxy-6-{4-[(β-d-glucopyranoside)oxy]phenyl}hex-3,5-dien-2-onate, were prepared to study their DNA photocleavage activity and photocytotoxicity. Complexes [La(ph-tpy)(acac)(EtOH)(NO3)2] (1a) and [Gd(ph–tpy)(acac)(NO3)2] (4) were characterized by X-ray crystallography. The 1:1 electrolytic complexes bind to calf thymus DNA. The py–tpy complexes cleave pUC19 DNA and exhibit remarkable photocytotoxicity in HeLa cells in UV-A light of 365 nm with apoptotic cell death (IC50: ∼40 nM in light, >200 μM in dark). Confocal microscopy using HeLa cells reveal primarily cytosolic localization of the complexes.

DNA-binding lanthanide(III) pyrenyl-terpyridine complexes show photo-induced DNA cleavage activity and remarkable UV-A light-induced (365 nm) photocytotoxicity in HeLa cells via apoptotic pathway with low dark toxicity.Figure optionsDownload as PowerPoint slideHighlights
► The lanthanide complexes of pyrenyl terpyridine ligand are avid binders to CT DNA.
► The lanthanide terpyridine complexes show photocleavage of DNA in UV-A light of 365 nm.
► The pyrenyl terpyridine lanthanide complexes show remarkable PDT effect in blue light.
► The pyrenyl terpyridine lanthanide complexes show apoptotic cellular damage on photoactivation in blue light.