Photodynamic Applications of New Imidazo[4,5‐f][1,10]phenanthroline Oxidovanadium(IV) Complexes: Synthesis, Photochemical, and Cytotoxic Evaluation

Abstract

Four oxidovanadium (IV) complexes of 1H-imidazo[4,5-f][1,10] phenanthroline analogues with the general formula [VO(L) 2 ] (acac) 2 (1-4) were synthesized and characterized, and their invitro photodynamic activity was evaluated. The complexes showed broad, low-intensity d-d bands at wavelengths from 635 nm to 775 nm in aqueous DMSO. The 1-(pyren-2-yl)-1Himidazo[4,5-f][1,10]phenanthroline oxidovanadium(IV) complex (4) exhibited remarkable photocytotoxicity in HaCaT cells, and cellular apoptosis was confirmed in an AO/EB dual-staining assay. The IC 50 of complex 4 was 8.2 μM under visible light (400-700 nm), but it was less toxic in dark (IC 50 ∼ 70 μM). None of the complexes were less toxic to immortalized lung epithelial cells (IC 50 > 50 μM), which suggested their activity was target-specific. Annexin V-FITC/PI assays performed with 2',7'-dichlorofluorescein diacetate indicated that apoptosis induced by the photoactivated complexes was due primarily to the intracellular generation of singlet oxygen (1 O 2), a reactive oxygen species. Photophysical studies and time-dependent density functional theory (TD-DFT) calculations suggested that the lowest triplet excited states of the complexes were long-lived and facilitated effective intersystem crossing, resulting in the efficient generation of 1 O 2 with good quantum yields (0.49). The remarkable photocytotoxicity of complex 4 indicates that it is promising for the development of next-generation oxidovanadium(IV)-based photochemotherapeutic agents.

Impact of the Anthryl Linking Mode on the Photophysics and Excited-State Dynamics of Re(I) Complexes [ReCl(CO)3(4′-An-terpy-κ2N)]

“…Reacting with 1 O 2 , diphenylisobenzofuran forms endoperoxide, which spontaneously decomposes to 1,2-dibenzoylbenzene. 49 , 86 − 88 As shown in Figure 9 , both complexes 1 and 2 exhibit singlet oxygen sensitizing ability. The insignificantly enhanced singlet oxygen sensitizing ability of 2 (Φ ΔO 2 = 0.45) in relation to 1 (Φ ΔO 2 = 0.42) correlates with its longer triplet excited-state lifetime in DMSO at room temperature ( Table 2 ).…”

“…The ability of Re­(I) complexes for photosensitized generation of singlet oxygen was examined by an indirect method with the use of diphenylisobenzofuran (DPBF), which is highly sensitive to 1 O 2 . Reacting with 1 O 2 , diphenylisobenzofuran forms endoperoxide, which spontaneously decomposes to 1,2-dibenzoylbenzene. ,− As shown in Figure , both complexes 1 and 2 exhibit singlet oxygen sensitizing ability. The insignificantly enhanced singlet oxygen sensitizing ability of 2 (Φ ΔO 2 = 0.45) in relation to 1 (Φ ΔO 2 = 0.42) correlates with its longer triplet excited-state lifetime in DMSO at room temperature (Table ).…”

Pyrenyl-Substituted Imidazo[4,5-f][1,10]phenanthroline Rhenium(I) Complexes with Record-High Triplet Excited-State Lifetimes at Room Temperature: Steric Control of Photoinduced Processes in Bichromophoric Systems

“…The efficiency of Re­(I) complexes in the generation of singlet oxygen was evaluated by an indirect method using [Ru­(bipy) 3 ]­(PF 6 ) 2 as the reference standard and 1,3-diphenylisobenzofuran (DPBF) as the singlet oxygen scavenger. The latter one is highly reactive toward 1 O 2 , forming endoperoxide, which spontaneously decomposes to 1,2-dibenzoylbenzene. − The progress of photo-oxidation of DPBF in the presence of Re­(I) complexes and [Ru­(bipy) 3 ]­(PF 6 ) 2 was monitored by the gradual decrease in the absorption of DPBF at 417 nm (Figure S33) and quantitatively compared by plotting A / A 0 against the irradiation time (Figure ).…”

In Vitro and In Vivo Biological Activities of Dipicolinate Oxovanadium(IV) Complexes

“…Vanadium compounds have been widely investigated due to a broad application in catalysis − and a wide range of pharmacological properties. − In the area of medicinal applications, the exploration of vanadium-based compounds has been focused on their insulin-mimetic properties, − ,− anticancer activities, − ,− antibacterial action, ,,,− and effects on enzymes. ,,, In particular, bis(ethylmaltolato)oxidovanadium(IV) (BEOV) entered the phase IIa clinical trials as an antidiabetic agent and its improved pharmacokinetics relative to vanadyl sulfate was evidenced. − Vanadocene dichloride, (η 5 -C 5 H 5 ) 2 VCl 2 (C 5 H 5 = cyclopentadienyl), was demonstrated to have antitumor effects on a wide spectrum of cancer cells, including testicular cancer, leukemia, breast cancer, glioblastoma, and colon cancer. − ,− Among oxidovanadium(IV) derivatives, special attention has been devoted to bis(4,7-dimethyl-1,10-phenanthroline)-sulfatooxidovanadium(IV) (Metvan), which was found to induce apoptosis in leukemia, multiple myeloma, and solid tumors such as breast, prostate, testis, and glioblasto...…”