Carbohydrate-appended tumor targeting iron(III) complexes showing photocytotoxicity in red light.
Glucose-appended photocytotoxic iron(III) complexes of a tridentate Schiff base phenolate ligand [Fe(bpyag)(L)](NO3) (1-3), where bpyag is N,N-bis(2-pyridylmethyl)-2-aminoethyl-β-D-glucopyranoside and H2L is 3-(2-hydroxyphenylimino)-1-phenylbutan-1-one (H2phap) in 1, 3-(2-hydroxyphenylimino)-9-anthrylbutan-1-one (H2anap) in 2, and 3-(2-hydroxyphenylimino)-1-pyrenylbutan-1-one (H2pyap) in 3, were synthesized and characterized. The complex [Fe(dpma)(anap)](NO3) (4), having bis-(2-pyridylmethyl)benzylamine (dpma), in which the glucose moiety of bpyag is substituted by a phenyl group, was used as a control, and the complex [Fe(dpma)(anap)](PF6) (4a) was structurally characterized by X-ray crystallography. The structure shows a FeN4O2 core in a distorted octahedral geometry. The high-spin iron(III) complexes with magnetic moment value of ∼5.9 μB showed a low-energy phenolate-to-Fe(III) charge-transfer (CT) absorption band as a shoulder near 500 nm with a tail extending to 700 nm and an irreversible Fe(III)-Fe(II) redox couple near -0.6 V versus saturated calomel electrode. The complexes are avid binders to calf thymus DNA and showed photocleavage of supercoiled pUC19 DNA in red (647 nm) and green (532 nm) light. Complexes 2 and 3 displayed significant photocytotoxicity in red light, with an IC50 value of ∼20 μM in HeLa and HaCaT cells, and no significant toxicity in dark. The cell death is via an apoptotic pathway, by generation of reactive oxygen species. Preferential internalization of the carbohydrate-appended complexes 2 and 3 was evidenced in HeLa cells as compared to the control complex 4. A 5-fold increase in the cellular uptake was observed for the active complexes in HeLa cells. The photophysical properties of the complexes are rationalized from the density functional theory calculations.
Department of Inorganic and Physical Chemistry, Indian Institute of Science , Bangalore 560012, Karnataka, India.
Uttara
U
Basu
Imran
I
Khan
Akhtar
A
Hussain
Bappaditya
B
Gole
Paturu
P
Kondaiah
Akhil R
AR
Chakravarty
D002241:Carbohydrates / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D004587:Electrophoresis, Agar Gel; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007501:Iron / Q000737:chemistry*; D008027:Light; D018613:Microscopy, Confocal; D011789:Quantum Theory
D002241:Carbohydrates; D056831:Coordination Complexes; D004247:DNA; D007501:Iron