Crystal structure, DNA crosslinking and photo-induced cytotoxicity of oxovanadium(IV) conjugates of boron-dipyrromethene

Abstract

Cis-dichloro-oxovanadium(IV) complexes [VO(L 1 /L 2)Cl 2 ], where L 1 is N-(4-(5,5-difluoro-1,3,7,9-tetramethyl-5H-4ʎ 4 ,5ʎ 4-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl) methanamine in 1 and L 2 is N-(4-(5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-5H-4ʎ 4 ,5ʎ 4-dipyrrolo[1,2-c:2′,1′f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine in 2) having 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene as boron-dipyrromethene (BODIPY) appended dipicolylamine bases were prepared, characterized and their photocytotoxicity studied. X-ray crystal structure of 1 showed distorted octahedral geometry with a V IV ON 3 Cl 2 core having Cl-V-Cl angle of 91.93(4)°. The complexes showed variable solution conductivity properties. They were non-electrolytes in dry DMF at 25°C but showed 1:1 electrolytic behavior in an aqueous medium due to dissociation of one chloride ligand as evidenced from the mass spectral study. Complexes 1 and 2 showed absorption bands at 500 and 535 nm, respectively. The calf thymus DNA melting study revealed their interaction through DNA crosslinking on exposure to light which was further confirmed from the alkaline agarose gel electrophoresis using plasmid supercoiled pUC19 DNA. Complex 2 showed disruption of the mitochondrial membrane potential in the JC-1 (1,1′,3,3′-tetraethyl-5,5′,6,6′-tetrachloroimidacarbocyanine iodide) assay. The complexes were photocytotoxic in visible light (400-700 nm, power: 10 J cm −2) in cervical cancer HeLa and breast cancer MCF-7 cells. Complex 2 having a photoactive diiodo-boron-dipyrromethene moiety gave a singlet oxygen quantum yield (Φ Δ) value of~0.6. It showed singlet oxygen mediated apoptotic photodynamic therapy activity with remarkably low IC 50 (half maximal inhibitory concentration) value of~0.15 μM. The cis-disposition of chlorides gave a cis-divacant 4-coordinate intermediate structure from the density functional theory (DFT) study thus mimicking the DNA crosslinking property of cisplatin.

Phototherapeutic anticancer strategies with first-row transition metal complexes: a critical review

“…The frontier molecular orbitals of BODIPY are at the origin of the 500 nm absorption bands and lead to generation of 1 O 2 with a quantum yield of approximatively 0.6 in DMSO, causing apoptosis via a type II PDT pathway upon red light (633 nm) irradiation. 38 As it is non-emissive, diiodo derivative ( V-8 ) gave better PDT results than complex V-7 . The heavy iodine atoms favoured spin–orbit coupling, and thus inter-system crossing.…”

Synthesis and structural characterization of oxovanadium(IV) complexes of dimedone derivatives

“…Studies have been focused on its behavior and functions in biological systems, [4] its catalytic and pharmaceutical applications. [5][6][7] The coordination chemistry of vanadium is a topic of interest since its discovery as an essential trace element for certain organisms. Vanadium compounds, especially the coordination chemistry of oxovanadium (IV), have aroused significant interest for several main reasons.…”

“…Studies have been focused on its behavior and functions in biological systems, [ 4 ] its catalytic and pharmaceutical applications. [ 5–7 ]…”

Photodynamic Therapy of Inorganic Complexes for the Treatment of Cancer†

“…Another oxovanadium(IV) complex, [VO(L 2 )Cl 2 ], (where L 2 is N‐(4‐(5,5‐difluoro‐2,8‐diiodo‐1,3,7,9‐tetramethyl‐5H4ʎ4,5ʎ4‐dipyrrolo[1,2‐c:2′,1′‐f][1,3,2]diazaborinin‐10‐yl)benzyl)‐1‐(pyridin‐2‐yl)‐N‐(pyridin‐2‐ylmethyl)methanamine), exhibited mitochondrial membrane disruption by JC‐1 (1,1′,3,3′‐tetraethyl5,5′,6,6′‐tetrachloroimidacarbocyanine iodide) dye assay, in addition to IC 50 values of 0.15 ± 2 µ m and 0.2 ± 0.08 µ m in HeLa cells and MCF‐7 cells, respectively (52). In another study, the PDT activity of the following oxovanadium(IV) complexes was determined: [VO(cat)(L)] and [VO(dopa‐NBD)(L)], (where L is phtpy or stpy), shown in Fig.…”