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Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+-doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages. Both the photoNORM [Mn(NO)dpaqNO2 ]BPh4(dpaqNO2 = 2-[N,N-bis(pyridin-2-yl-methyl)]-amino-N'-5-nitro-quinolin-8-yl-acetamido) and the Nd-UCNPs are activated by tissue-penetrating near-infrared (NIR) light at ∼800 nm. Thus, simultaneous therapeutic NO delivery and photoluminescence (PL) imaging can be achieved with a NIR diode laser source. The loaded microparticles are non-toxic to their macrophage hosts in the absence of light. The microparticle-carrying macrophages deeply penetrate into NIH-3T3/4T1 tumor spheroid models, and when the infiltrated spheroids are irradiated with NIR light, NO is released in quantifiable amounts while emission from the Nd-UCNPs provides images of microparticle location. Furthermore, varying the intensity of the NIR excitation allows photochemical control over NO release. Low doses reduce levels of hypoxia inducible factor 1 alpha (HIF-1α) in the tumor cells, while high doses are cytotoxic. The use of macrophages to carry microparticles with a NIR photo-activated theranostic payload into a tumor overcomes challenges often faced with therapeutic administration of NO and offers the potential of multiple treatment strategies with a single system.

The relationship between the spin state and the reactivity with O2 of a series of the chlorocatecholatoiron(III) complexes is investigated. The study revealed that the low-spin complex has a lower reactivity with O2 than high-spin analogue, despite higher semiquinonate character in the low-spin state than in the high-spin state.

The bis(mu-oxo)dimanganese(III,III) complex [Mn(super II)(sub 2)(mu-oxo)2(TPA)2](super 2+) exhibits a high catechol oxidase activity. The reaction is very unique because the aerobic oxidation of catechols are catalyzed by a manganese complex through mononuclear Mn(II)-SQ and bis(mu-oxo-dimanganese(III,III) complexes.

Dicopper complexes [Cu2(μ-OH)(Ln)](ClO4)2 [n = 1 (1) and 2 (2)] with a novel phenanthrene amide-tether ligand conjugate (HL1) and the original p-cresol-2,6-bis(amidecyclen) (HL2) were synthesized. A phenanthrene unit of 1 enhances the DNA-binding by 9-fold, enabling 1 to convert supercoiled plasmid DNA with H2O2 to a linear one in a 9.3-fold higher yield than 2. 1 reacts with H2O2 to form the μ-1,1-hydroperoxodicopper(II) complex 3 as the active species. The IC50 values of 1 against cancer cells of the lung and pancreas are 23.8 and 18.4 μM, respectively, 12-fold more toxic than the 284 and 241 μM of 2. Confocal microscopy, fluorescence-activated cell sorting, and caspase activity assays using HeLa cells revealed that 1 induces mitochondrial apoptosis. A DNA-targeting phenanthrene unit of 1 enhances the cancer-cell-selective toxicity via mitochondrial apoptosis. [ABSTRACT FROM AUTHOR]

A study illustrates how the modification of heme-propionates improves the peroxidase activity of reconstituted myoglobin for small molecule substrates, which led to the engineering of a new binding domain on the myoglobin surface. The existing chemical mutation of the prosthetic group will function as a new strategy for synthesizing novel catalysts with tailored properties. Experimental methods and findings are presented.

Research was conducted to evaluate artificial protein-protein complexation between the cytochrome c and a reconstituted myoglobin. In this study, novel myoglobins were developed by inserting artificial prosthetic porphyrins into apomyglobin. Results show that an effective recognition domain can be formed from the artificial functional groups bound to the terminal of porphyrin in the reconstituted myoglobin.

The synthesis and characterization of several new Cu(II)-ACC (1-aminocyclopropane carboxylic acid) complexes, [Cu(ACC)(1,10-phenanthroline)](Cl[O.sub.4]) and [Cu(ACC)(2-picolylamine)](Cl[O.sub.4]) is presented. The results from density functional theory calculations provide insight into the Cu(I)-OOH as a possible active species for the conversion of ACC into ethylene.