Iron(III) salicylates of dipicolylamine bases showing photo-induced anticancer activity and cytosolic localization

An iron(III) salicylate having a dipicolylamine base (andpa) with a photoactive anthracenyl moiety is prepared, characterized, and studied for its photo-induced anticancer activity and cellular localization in HeLa and MCF-7 cells. Its phenyl analogue is structurally characterized by X-ray crystallography. The complex has a ternary structure in which the dipicolylamine ligand and salicylic acid in dianionic form (sal) display respective tridentate and bidentate mode of coordination in Fe(sal)(phdpa)Cl] (1). Complex Fe(sal)(andpa)Cl] (2) having a pendant anthracenyl moiety shows significant photocytotoxicity in visible light (400-700 nm) giving IC50 values of 8.6 +/- 0.7 and 3.4 +/- 0.9 mu M in HeLa and MCF-7 cells, while being essentially nontoxic in the dark (IC50 > 100 mu M). The complex shows cytosolic localization in the cancer cells. Formation of hydroxyl radicals ((OH)-O-center dot) as the reactive oxygen species is evidenced from the pUC19 DNA photocleavage studies. (C) 2015 Elsevier Ltd. All rights reserved.

The mycobacterial iron-dependent regulator IdeR induces ferritin (bfrB) by alleviating Lsr2 repression

Emerging evidence indicates that precise regulation of iron (Fe) metabolism and maintenance of Fe homeostasis in Mycobacterium tuberculosis (Mtb) are essential for its survival and proliferation in the host. IdeR is a central transcriptional regulator of Mtb genes involved in Fe metabolism. While it is well understood how IdeR functions as a repressor, how it induces transcription of a subset of its targets is still unclear. We investigated the molecular mechanism of IdeR-mediated positive regulation of bfrB, the gene encoding the major Fe-storage protein of Mtb. We found that bfrB induction by Fe required direct interaction of IdeR with a DNA sequence containing four tandem IdeR-binding boxes located upstream of the bfrB promoter. Results of in vivo and in vitro transcription assays identified a direct repressor of bfrB, the histone-like protein Lsr2. IdeR counteracted Lsr2-mediated repression in vitro, suggesting that IdeR induces bfrB transcription by antagonizing the repressor activity of Lsr2. Together, these results elucidate the main mechanism of bfrB positive regulation by IdeR and identify Lsr2 as a new factor contributing to Fe homeostasis in mycobacteria.

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.

Stabilization of a Tetrahedral (Mn5+O4) Chromophore in Ternary Barium Oxides as a Strategy toward Development of New Turquoise/Green-Colored Pigments

An experimental investigation of the stabilization of the turquoise-colored chrornophore (Mn5+O4) in various oxide hosts, viz., A(3)(VO4)(2) (A = Ba, Sr, Ca), YVO4, and Ba2MO4 (M = Ti, Si), has been carried out. The results reveal that substitution of Mn5+O4 occurs in Ba-3(VO4)(2) forming the entire solid solution series Ba-3(V1-x MnxO4)(2) (0 < x <= 1.0), while with the corresponding strontium derivative, only up to about 10% of Mn5+O4 substitution is possible. Ca-3(VO4)(2) and YVO4 do not stabilize Mn5+O4 at all. With Ba2MO4 (M = Ti, Si), we could prepare only partially substituted materials, Ba2M1-xMn5+O4+x/2 for x up to 0.15, that are turquoise-colored. We rationalize the results that a large stabilization of the O 2p-valence band states occurs in the presence of the electropositive barium that renders the Mn5+ oxidation state accessible in oxoanion compounds containing PO43-, VO43-, etc. By way of proof-of-concept, we synthesized new turquoise-colored Mn5+O4 materials, Ba-5(BO3)(MnO4)(2)Cl and Ba-5(BO3)(PO4)(MnO4)Cl, based on the apatite-Ba-5(PO4)(3)Cl-structure.