Photocytotoxic Activity of Copper(II) and Zinc(II) Complexes of Curcumin and (Acridinyl)dipyridophenazine

Abstract Copper(II) and zinc(II) β‐diketonates of N,N‐donor ligands, viz . [Cu(dppz)(cur)](NO 3 ) ( 1 ), [Cu(acdppz)(cur)](NO 3 ) ( 2 ), [Cu(acdppz)(acac)](NO 3 ) ( 3 ), [Zn(dppz)(cur)](NO 3 ) ( 4 ) and [Zn(acdppz)(cur)](NO 3 ) ( 5 ), where dppz is dipyrido[3,2‐a:2’,3’‐c]phenazine, acdppz is 11‐(9‐acridinyl)dipyrido[3,2‐ a :2 ’, 3 ’ ‐ c ]phenazine, cur and acac are mono‐deprotonated curcumin (Hcur) and acetyl acetone (Hacac), were synthesized, characterized and their photocytotoxicity studied. An analogue of complex 3 , viz . [Cu(acdppz)(acac)(H 2 O)]Cl 1/2 (NO 3 ) 1/2 ( 3 a ), structurally characterized by X‐ray crystallography, has a cationic complex in square‐pyramidal geometry with CuN 2 O 3 core with an axial aqua ligand. Complexes 1 , 2 , 4 and 5 displayed emission at ∼520 nm (λ exc : 430 nm) in dimethyl sulfoxide (DMSO) giving a fluorescence quantum yield value within 0.01‐0.06. The complexes, in contrast to free curcumin, were fairly stable in cellular media up to 36 h, with no apparent degradation of the bound curcumin. The complexes were photocytotoxic (IC 50 : 0.3 ‐ 4.5 μM) in human cervical cancer (HeLa), breast cancer (MCF‐7) and liver cancer (HepG2) cells. The apoptotic cell death is due to reactive oxygen species formation. Complexes 2 and 5 showed significant uptake in HeLa cells, localizing predominantly in the cytoplasm. Mechanistic data from the pUC19 DNA photocleavage study suggest involvement of acridine and curcumin in photo‐generation of singlet oxygen and hydroxyl radicals as the ROS in light of 400–700 nm.