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A new means of accessing N(1)-cyclopropylmethyl-N(11)-ethylnorspermine (CPMENSPM) and the first synthesis of (2R,10S)-N(1)-cyclopropylmethyl-2,10-dihydroxy-N(11)-ethylnorspermine [(2R,10S)-(HO)(2)CPMENSPM] are described. Both of these polyamine analogues are shown to be more active against L1210 murine leukemia cell growth than either N(1),N(11)-diethylnorspermine (DENSPM) or (2R,10R)-N(1),N(11)-diethyl-2,10-dihydroxynorspermine [(2R,10R)-(HO)(2)DENSPM] after 96 h of treatment; the activity was comparable to that of (2S,10S)-N(1),N(11)-diethyl-2,10-dihydroxynorspermine [(2S,10S)-(HO)(2)DENSPM] at 96 h. Both cyclopropyl compounds reduced putrescine and spermidine pools, but less effectively than did DENSPM and its derivatives. Only CPMENSPM, and not (2R,10S)-(HO)(2)CPMENSPM, lowered spermine pools. As with DENSPM and (2R,10R)-(HO)(2)DENSPM, both cyclopropyl analogues diminished ornithine decarboxylase and S-adenosylmethionine decarboxylase activity. Unlike the hydroxylated DENSPM compounds, both cyclopropyl norspermines substantially upregulated spermidine/spermine N(1)-acetyltransferase. The most interesting effect of hydroxylating CPMENSPM is the profound reduction in toxicity compared with that of the parent drug. The same phenomenon had been observed for the DENSPM/(2R,10R)-(HO)(2)DENSPM pair. Thus, hydroxylation of norspermine analogues appears to be a way to maintain the compounds' antiproliferative activity while reducing their toxicity.

In this context, metal nanostructures with localized surface plasmon resonances (LSPRs) have attracted extensive attention. [2] LSPRs can be excited with wide-field normal-incidence illumination, and the optical setup for sensing can be simply constructed based on standard optical microscopes. [3] Periodic plasmonic nanostructures can offer additional advantages, [4] for example, a much narrower resonance linewidth (compared to LSPRs) that is beneficial for measuring a small spectral shift. However, the intense optical fields on the surface of plasmonic nanostructures can result in dissipative loss and lead to heating. Recently, periodic arrays of high-index dielectric nanostructures with collective resonances have been proposed as an alternative. [5-9] However, for periodic arrays of high-index dielectric nanostructures, even with broken inplane symmetry (so-called quasi-BIC; bound states in the continuum), [7,8] the bulk sensitivity (defined as the spectral shift upon the change in the bulk refractive index of the surrounding environment) is much lower than that of plasmonic arrays with the same lattice spacing. The collective lattice resonance stemming from the diffractive coupling in a periodic array of either metal [10-12] or high-index dielectric nanoparticles [13] requires a symmetric refractive-index environment between the bottom substrate and the upper cladding (e.g., aqueous buffers in sensing). [14-17] An asymmetric environment can inhibit long-range coupling between nanoparticles and suppress lattice resonances. In optical sensing, a periodic array of either metal or high-index dielectric nanoparticles is usually fabricated on a transparent substrate and exposed to solutions with different refractive indices. The index-mismatch between widely used quartz substrates (n ≈ 1.5) and aqueous buffers (n ≈ 1.33) can broaden the resonances and deteriorate the bulk sensitivity. [18] Although for sensing in aqueous buffers, one can find fluoropolymer (Cytop) with refractive index close to water to create a symmetric environment, [18,19] it is highly desirable to have a platform that can maintain high-quality resonances when subjected to a relatively large change in the bulk refractive index. (A symmetric refractive-index environment may not be required in a periodic structure with high-quality resonances of quasi-BIC type, for which the bulk sensitivity, however, is not high in the published literature. [7,8]) We recently reported that a hybrid system composed of low-index dielectric pillar arrays on a metal film can support This article reports refractometric sensing using two optical resonances of different types supported by TiO 2 nanopillar arrays on a gold film, which can be exposed to aqueous or organic environments. One lattice resonance, with enhanced electric fields extending into the surrounding environment, can maintain a quality factor Q > 200 when the bulk refractive index of the surrounding environment varies in a large range from 1.33 to 1.58. This lattice resonance exhibits not only sharp trans...

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Traditional thinking has been that hexacoordinate Fe(III) ligands are more effective at preventing iron's interactions with reactive oxygen species, most particularly the Fe(II)-mediated reduction of hydrogen peroxide to the hydroxyl radical (i.e., Fenton chemistry), than are ligands of lower denticity. Thus, a hexacoordinate derivative of the well-characterized tricoordinate ligand (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-thiazolecarboxylic acid [4'-(HO)-DADMDFT], (S,S)-1,11-bis[5-(4-carboxy-4,5-dihydrothiazol-2-yl)-2,4-dihydroxyphenyl]-4,8-dioxaundecane, was designed with the aid of a molecular modeling program and synthesized. Evaluations both in vitro and in vivo were carried out to determine whether there is any advantage, at the level of prevention of Fenton chemistry, radical trapping, or iron clearance, to constructing a desferrithiocin-based hexacoordinate analogue. The hexacoordinate analogue was more effective at preventing the iron-mediated oxidation of ascorbate at low ligand/metal ratios than was its tricoordinate parent and can function as an excellent radical scavenger. At equivalent iron binding doses in the bile duct cannulated rodent, oral administration of the tricoordinate ligand was 3-fold more effective than was po administration of the hexacoordinate derivative. However, sc administration of the hexacoordinate derivative resulted in an efficiency that was 3 times greater than that of the tricoordinate chelator. Unfortunately, the rodent findings were not substantiated in the primates. The hexacoordinate ligand was only about one-half as efficient as its tricoordinate parent when administered sc. Owing to these results, po dosing was not attempted. Thus, there appears to be no overall advantage to coupling two molecules of 4'-(HO)-DADMDFT to afford a hexacoordinate derivative.