Photocytotoxic Oxidovanadium(IV) Complexes of Polypyridyl Ligands Showing DNA‐Cleavage Activity in Near‐IR Light

Abstract

Oxidovanadium(IV) complexes [VO(pyphen)(L)]Cl2 (1, 2) and [VO(pydppz)(L)]Cl2 (3, 4), where L is 1,10‐phenanthroline (phen in 1 and 3) and dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz in 2 and 4) are prepared and characterized. The crystal structure of [VO(pyphen)(phen)](ClO4)2 (1a) shows a six‐coordinate VN5O geometry with a VO2+ moiety in which the polypyridyl ligand binds in a meridional fashion and the phen ligand displays a chelating binding mode with an N‐donor site trans to the oxidovanadyl group. The complexes show a d–d band within 720–750 nm in DMF. The one‐electron paramagnetic complexes are 1:2 electrolytes in DMF. The complexes exhibit an irreversible VIV/VIII redox response near –0.85 V vs. SCE in DMF/0.1 M TBAP. The complexes bind to calf thymus (ct) DNA giving Kb values within 7.5 × 104 to 1.1 × 106 M–1. The complexes show poor chemical nuclease activity in the dark and exhibit significant DNA‐photocleaving activity in near‐IR light of 705 and 785 nm forming ·OH radicals. Complexes 2–4 show remarkable photocytotoxicity in HeLa cancer cells. FACS analysis of the HeLa cells treated with complex 4 shows cell death as highlighted by the sub G1 peak. Propidium iodide staining data indicate apoptosis as the primary mode of cell death.

A journey into the electrochemistry of vanadium compounds

“…[V(atrisph)(OMe)] and [V(atrisph)(acac)] showed vanadium metal-centered redox processes (Table 3, entries 44,45). No stabilization of the V(IV)-phenoxyl radical species has been observed.…”

“…The V(IV) → V(III) couple was observed as an irreversible voltammetric response in the potential range of −0.7 to −1.0 V vs SCE [46]. More detailed information was reported for phenanthroline and phenazine derivatives [45] (Table 1, entries [24][25][26][27].…”

“…the enol form of 2,4-pentanedione N-benzoylhydrazone, and bidentate N-N ligands, bipy and phen [56]. They exhibited an one-electron irreversible oxidation peak in MeCN solution (Table 1, entries 44,45).…”

“…VO 3+ derivatives were prepared with the N-benzoylhydrazones already discussed for VO 2+ complexes, in the presence of the anion of 8-hydroxyquinoline [58]. This set of complexes showed a quasireversible CV response in DCM solution (Table 5, entries [45][46][47][48].…”

“…The cyclic voltammetry of VO(HBdmpz 3 )(FcCO 2 ) at room temperature presented a chemically and electrochemically reversible one-electron oxidation relative to Fe(II) → Fe(III) and a second quasi-reversible one-electron oxidation assigned to the vanadium center (Table 1, entry 23). Different tridentate N-N-N ligands based on polypyridines [45,46], were used to investigate the photocytotoxicity of their oxido-V(IV) complexes. The complexes with pyrenylterpyridine did not show any oxidative cyclic voltammetric response.…”