Mitochondria-Targeting Iron(III) Catecholates for Photoactivated Anticancer Activity under Red Light

Iron(III) catecholates Fe(R-bpa)(R-dopa)Cl] (1, 2) with a triphenylphosphonium (TPP) moiety, where R-bpa is 2-(TPP-N,N-bis((pyridin-2-yl)methyl)ethanamine) chloride (TPPbpa) and R-dopa is 4-{2-(anthracen-9-yl)methylamino]ethyl}benzene-1,2-diol (andopa, 1) or 4-{2-(pyren-1-yl)-methylamino]ethyl}benzene-1,2-diol (pydopa, 2), were synthesized and their photocytotoxicity studied. Complexes 3 and 4 with phenyl-N,N-bis(pyridin-2-yl)methyl]methanamine (phbpa) were used as controls. The catecholate complexes showed an absorption band near 720 nm. The 5e(-) paramagnetic complexes showed a Fe-III/Fe-II irreversible response near -0.45 V and a quasi-reversible catechol/semiquinone couple near 0.5 V versus saturated calomel electrode (SCE) in DMF/0.1 M tetrabutylammonium perchlorate. They showed photocytotoxicity in red/visible light in HeLa, HaCaT, MCF-7, and A549 cells. Complexes 1 and 2 displayed mitochondrial localization, reactive oxygen species (ROS) generation under red light, and apoptotic cell death. Control complexes 3 and 4 exhibited uniform distribution throughout the cell. The complexes showed DNA photocleavage under red light (785 nm), forming hydroxyl radicals as the ROS.

Remarkable photo-induced anticancer activity of vitamin-S6 Schiff base copper(II) complexes of pyridyl bases

Vitamin-B6 (VB6) Schiff base (H2L) copper(II) complexes of pyridyl bases, viz. Cu(bpy)(L)] (1), Cu(phen)(L)] (2) and Cu(dppz)(L)] (3), where bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline and dppz is dipyrido3,2-a:2',3'c]phenazine are synthesized, characterized and their phto-induced anticancer activity studied. The non-electrolytic one electron paramagnetic complexes exhibit a d-d band near 700 nm in DMF. The dppz complex intercalatively binds to calf-thymus DNA with binding constant (K-b) values of similar to 10(6) M-1. This complex exhibits low chemical nuclease activity but excellent DNA photocleavage activity when irradiated with red light of 705 nm forming (OH)-O-center dot radical. It displays remarkable photocytotoxicity in human cervical cancer cells (HeLa) giving IC50 value of 0.9 mu M in visible light (400-700 nm) while being less toxic in darkness (IC50 : 23 mu M). The cellular uptake of the complexes seems to be via VB6 transporting membrane carrier mediated diffusion pathway. Photo-induced cell death follows apoptotic pathway involving photo-generated intracellular reactive oxygen species.

Mitochondrial selectivity and remarkable photocytotoxicity of a ferrocenyl neodymium(III) complex of terpyridine and curcumin in cancer cells

A series of four novel neodymium(III) complexes of the formulation Nd(R-tpy)(O-O)(NO3)(2)] (1-4), where R-tpy is 4'-phenyl-2,2': 6', 2''-terpyridine (Ph-tpy; 1, 2) and 4'-ferrocenyl-2,2': 6', 2''-terpyridine (Fc-tpy; 3, 4); O-O is the conjugate base of acetylacetone (Hacac; 1, 3) or curcumin (Hcurc; 2, 4), are synthesized and characterized. The single crystal structure of 1 shows that the complex is a discrete mononuclear species with the Nd(III) centre in a nine coordinate environment provided by a set of O6N3 donor atoms. Complexes 1 and 3 having the simple acac ligand are prepared as control compounds. Complex 4, possessing an appended ferrocenyl (Fc) and the curcumin moiety, is remarkably photocytotoxic to HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 0.7 mu M and 2.1 mu M while being significantly less toxic to MCF-10A normal cells (IC50 = 34 mu M) and in the dark (IC50 > 50 mu M). The phenyl appended complex 2, lacking a ferrocenyl moiety, is significantly less toxic to both the cell lines when compared with 4. Complexes 1 and 3, lacking the photoactive curcumin moiety, do not show any apparent toxicity both in light and in the dark. The cell death is apoptotic in nature and is mediated by the light-induced formation of reactive oxygen species (ROS). Fluorescence imaging experiment with HeLa cells reveals mitochondrial accumulation of complex 4 within 4 h of incubation. The complexes bind to calf thymus (ct) DNA with moderate affinity giving K-b values in the range of 10(4)-10(5) M-1. The curcumin complexes 2 and 4 cleave plasmid supercoiled DNA to its nicked circular form in visible light via O-1(2) and (OH)-O-center dot pathways. The presence of the ferrocenyl moiety is likely to be responsible for the enhanced cellular uptake and photocytotoxicity of complex 4. Thus, the mitochondria targeting complex 4, being remarkably cytotoxic in light but non-toxic in the dark and to normal cells, is a potential candidate for photochemotherapeutic applications.

Unimpeded permeation of water through biocidal graphene oxide sheets anchored on to 3D porous polyolefinic membranes

3D porous membranes were developed by etching one of the phases (here PEO, polyethylene oxide) from melt-mixed PE/PEO binary blends. Herein, we have systematically discussed the development of these membranes using X-ray micro-computed tomography. The 3D tomograms of the extruded strands and hot-pressed samples revealed a clear picture as to how the morphology develops and coarsens over a function of time during post-processing operations like compression molding. The coarsening of PE/PEO blends was traced using X-ray micro-computed tomography and scanning electron microscopy (SEM) of annealed blends at different times. It is now understood from X-ray micro-computed tomography that by the addition of a compatibilizer (here lightly maleated PE), a stable morphology can be visualized in 3D. In order to anchor biocidal graphene oxide sheets onto these 3D porous membranes, the PE membranes were chemically modified with acid/ethylene diamine treatment to anchor the GO sheets which were further confirmed by Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and surface Raman mapping. The transport properties through the membrane clearly reveal unimpeded permeation of water which suggests that anchoring GO on to the membranes does not clog the pores. Antibacterial studies through the direct contact of bacteria with GO anchored PE membranes resulted in 99% of bacterial inactivation. The possible bacterial inactivation through physical disruption of the bacterial cell wall and/or reactive oxygen species (ROS) is discussed herein. Thus this study opens new avenues in designing polyolefin based antibacterial 3D porous membranes for water purification.