Metal-O 2 adducts, such as metal-superoxo and -peroxo species, are key intermediates often detected in the catalytic cycles of dioxygen activation by metalloenzymes and biomimetic compounds. The synthesis and spectroscopic characterization of an end-on nickel(II)-superoxo complex with a 14-membered macrocyclic ligand was reported previously. Here we report the isolation, spectroscopic characterization, and high-resolution crystal structure of a mononuclear side-on nickel(III)-peroxo complex with a 12-membered macrocyclic ligand, [Ni(12-TMC)(O 2 )] + (1) 4,7,4,7,. Different from the end-on Ni(II)-superoxo complex, the Ni(III)-peroxo complex is not reactive in electrophilic reactions, but is capable of conducting nucleophilic reactions. The Ni(III)-peroxo complex transfers the bound dioxygen to manganese(II) complexes, thus affording the corresponding nickel(II) and manganese(III)-peroxo complexes. The present results demonstrate the significance of supporting ligands in tuning the geometric and electronic structures and reactivities of metal-O 2 intermediates that have been shown to have biological as well as synthetic usefulness in biomimetic reactions.Metalloenzymes activate dioxygen to carry out a variety of biological reactions including biotransformation of naturally occurring molecules, oxidative metabolism of xenobiotics, and oxidative phosphorylation. One goal in biomimetic research is to understand the mechanistic details of dioxygen activation and oxygenation reactions and the structures of reactive intermediates occurring at the active sites of the metalloenzymes 1 . In the unified mechanism of dioxygen activation, dioxygen first binds to a reduced metal center that forms metal-superoxo and -peroxo intermediates, followed by O-O bond cleavage leading to the formation of high-valent metal-oxo species that are believed to carry out substrate oxidations 1 . Among the metal-oxygen intermediates, mononuclear metal-O 2 adducts, such * Corresponding authors: wwnam@ewha.ac.kr, edward.solomon@stanford.edu. Correspondence and requests for materials should be addressed to W.N. Author contributions: J.C., E.I.S., and W.N. conceived and designed the experiments; J.C., R.S., J.A., S.Y.K., and M.K. performed the experiments; J.C., R.S., J.A., M.K., and T.O. analyzed the data; J.C., R.S., E.I.S., and W.N. co-wrote the paper. 25 . We now report for the first time the synthesis, spectroscopic and electronic properties, and crystal structure of a mononuclear side-on (η 2 ) nickel(III)-peroxo complex stabilized by a 12-membered macrocyclic ligand, [Ni(III)(12-TMC)(O 2 )] + (1) (12-TMC = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane). The reactivities of the Ni(III)-peroxo complex in electrophilic and nucleophilic reactions and peroxo group transfer to other metal complexes have been discussed as well. Results and discussionThe starting nickel complex, [Ni(12-TMC)(CH 3 CN)] 2+ (3), was synthesized and characterized with UV-vis absorption spectroscopy, electrospray ionization mass spectrometry (ESI MS), and X...

The dark side of the Mn: A manganese(III) complex bearing a 13-membered macrocyclic ligand (1, see picture) binds a peroxo ligand in a side-on eta(2) fashion. The reactivity of 1 is influenced by the introduction of anionic ligands trans to the peroxo group. Electronic and structural changes upon trans-ligand binding explain the increased nucleophilicity of the resulting complexes 1-X.

c Silver nanoparticles (AgNPs) are considered to be a potentially useful tool for controlling various pathogens. However, there are concerns about the release of AgNPs into environmental media, as they may generate adverse human health and ecological effects. In this study, we developed and evaluated a novel micrometer-sized magnetic hybrid colloid (MHC) decorated with variously sized AgNPs (AgNP-MHCs). After being applied for disinfection, these particles can be easily recovered from environmental media using their magnetic properties and remain effective for inactivating viral pathogens. We evaluated the efficacy of AgNP-MHCs for inactivating bacteriophage X174, murine norovirus (MNV), and adenovirus serotype 2 (AdV2). These target viruses were exposed to AgNP-MHCs for 1, 3, and 6 h at 25°C and then analyzed by plaque assay and real-time TaqMan PCR. The AgNP-MHCs were exposed to a wide range of pH levels and to tap and surface water to assess their antiviral effects under different environmental conditions. Among the three types of AgNP-MHCs tested, Ag30-MHCs displayed the highest efficacy for inactivating the viruses. The X174 and MNV were reduced by more than 2 log 10 after exposure to 4.6 ؋ 10 9 Ag30-MHCs/ml for 1 h. These results indicated that the AgNP-MHCs could be used to inactivate viral pathogens with minimum chance of potential release into environment. With recent advances in nanotechnology, nanoparticles have been receiving increased attention worldwide in the fields of biotechnology, medicine, and public health (1, 2). Owing to their high surface-to-volume ratio, nano-sized materials, typically ranging from 10 to 500 nm, have unique physicochemical properties compared with those of larger materials (1). The shape and size of nanomaterials can be controlled, and specific functional groups can be conjugated on their surfaces to enable interactions with certain proteins or intracellular uptake (3-5).Silver nanoparticles (AgNPs) have been widely studied as an antimicrobial agent (6). Silver is used in the creation of fine cutlery, for ornamentation, and in therapeutic agents. Silver compounds such as silver sulfadiazine and certain salts have been used as wound care products and as treatments for infectious diseases due to their antimicrobial properties (6, 7). Recent studies have revealed that AgNPs are very effective for inactivating various types of bacteria and viruses (8-11). AgNPs and Ag ϩ ions released from AgNPs interact directly with phosphorus-or sulfur-containing biomolecules, including DNA, RNA, and proteins (12-14). They have also been shown to generate reactive oxygen species (ROS), causing membrane damage in microorganisms (15). The size, shape, and concentration of AgNPs are also important factors that affect their antimicrobial capabilities (8,10,13,16,17).Previous studies have also highlighted several problems when AgNPs are used for controlling pathogens in a water environment. First, existing studies on the effectiveness of AgNPs for inactivating viral pathogens in water are limite...

The morphology of a series of diblock copolymers comprising randomly sulfonated polystyrene (PSS) and polymethylbutylene (PMB) blocks equilibrated with humid air was determined by in situ small-angle neutron scattering (SANS). In-situ SANS data were collected over a wide angular range permitting the determination of the superstructure of the hydrophilic PSS-rich and hydrophobic PMB-rich domains and the substructure within the hydrophilic PSS-rich domains. When the characteristic length of the superstructure is larger than 10 nm, the hydrophilic PSS domains are heterogeneous with periodically arranged watery domains. The scattering signature of the watery domains is very similar to the well-established “ionomer peak”. This peak vanishes when the neutron scattering length density of the water (H2O/D2O mixture) is matched to that of the PSS block. The spacing between watery domains depends only on sulfonation level of the PSS block. When the characteristic length of the superstructure is less than 10 nm, the watery substructure disappears and homogeneous hydrated PSS-rich domains are obtained.

Increased risk of developing endometrial cancers has been observed in women treated with tamoxifen (TAM), a widely used drug for breast cancer therapy and chemoprevention. The carcinogenic effect may be due to genotoxic DNA damage induced by TAM. In fact, TAM-DNA adducts were detected in the endometrium of women treated with this drug. TAM is alpha-hydroxylated by cytochrome P450 3A4 followed by O-sulfonation by hydroxysteroid sulfotransferase, and reacts with guanine residues in DNA, resulting in the formation of alpha-(N2-deoxyguanosinyl)tamoxifen adducts. During this metabolic process, short-lived carbocations are produced at the ethyl moiety of TAM as reactive intermediates. TAM-DNA adducts promote primarily G -->T transversions in mammalian cells. The same mutations have been frequently detected at codon 12 of the K-ras gene in the endometrial tissue of women treated with this drug. TAM-DNA adducts, if not readily repaired, may act as initiators, leading to development of endometrial cancers. The reactivity of TAM metabolites with DNA is inhibited in toremifene, where the hydrogen atom has been replaced by a chlorine atom at the ethyl moiety. Therefore, toremifene may be a safer alternative to TAM. This article describes an overview of the mechanism of TAM-DNA adduct formation, mutagenic events of this adduct, and detection of TAM-DNA adducts in the endometrium of women treated with TAM.

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An increased risk of developing endometrial cancer is observed in breast cancer patients treated with tamoxifen (TAM) and in healthy women undergoing TAM chemoprevention therapy. TAM-DNA adducts were detected in the endometrium of women taking TAM (Shibutani, S., et al. (2000) Carcinogenesis 21, 1461-1467) and are formed primarily through O-sulfonation of alpha-hydroxytamoxifen (alpha-OHTAM). To explore the genotoxicic mechanisms of TAM, TAM was incubated with one of multiple human cytochrome P450 enzymes, i.e., P450 1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, 3A7, 4A11, 4F2, 4F3A, or 4F3B, in a NADPH regenerating system, and the metabolites were identified using HPLC/UV analysis with authentic standards. Among the 18 human P450 enzymes, P450 3A4 generated a significant amount of alpha-OHTAM. When some rat P450 enzymes were examined, P450 3A2 also catalyzed alpha-hydroxylation of TAM. Similarly, human P450 3A4 and rat P450 3A1 and 3A2 converted toremifene (TOR, a chlorinated TAM analogue) to alpha-hydroxytoremifene (alpha-OHTOR). The formation of alpha-OHTAM and alpha-OHTOR by these P450 enzymes was confirmed by tandem mass spectroscopy. Only the P450 3A subfamily enzymes are able to alpha-hydroxylate TAM and TOR. Although the formation of alpha-OHTOR by these enzymes was much higher than that of alpha-OHTAM, TOR is known to be much less genotoxic than TAM. The results support our proposed mechanism that the lower genotoxicity of TOR is due to limited O-sulfonation of alpha-OHTOR by hydroxysteroid sulfotransferases, resulting in the poor formation of DNA adducts (Shibutani, S., et al. (2001) Cancer Res. 61, 3925-3931).