Mixed-Valent Molecular Triple Deckers.

Two phenothiazine (PTZ) moieties were connected via naphthalene spacers to a central arene to result in stacked PTZ-arene-PTZ structure elements. Benzene and tetramethoxybenzene units served as central arenes mediating electronic communication between the two PTZ units. Based on cyclic voltammetry, UV/Vis-NIR absorption, EPR spectroscopy, and computational studies, the one-electron oxidized forms of the resulting compounds behave as class II organic mixed-valence species in which the unpaired electron is partially delocalized over both PTZ units. The barrier for intramolecular electron transfer depends on the nature of the central arene sandwiched between the two PTZ moieties. These are the first examples of rigid organic mixed-valent triple-decker compounds with possible electron-transfer pathways directly across a stacked structure, and they illustrate the potential of oligo-naphthalene building blocks for long-range electron transfer and a future molecular electronics technology.

Nanoparticle-based highly sensitive MRI contrast agents with enhanced relaxivity in reductive milieu.

Current magnetic resonance imaging (MRI) contrast agents often produce insufficient contrast for diagnosis of early disease stages, and do not sense their biochemical environments. Herein, we report a highly sensitive nanoparticle-based MRI probe with r1 relaxivity up to 51.7 ± 1.2 mM(-1) s(-1) (3T). Nanoparticles were co-assembled from Gd(3+) complexed to heparin-poly(dimethylsiloxane) copolymer, and a reduction-sensitive amphiphilic peptide serving to induce responsiveness to environmental changes. The release of the peptide components leads to a r1 relaxivity increase under reducing conditions and increases the MRI contrast. In addition, this MRI probe has several advantages, such as a low cellular uptake, no apparent cellular toxicity (tested up to 1 mM Gd(3+)), absence of an anticoagulation property, and a high shelf stability (no increase in free Gd(3+) over 7 months). Thus, this highly sensitive T1 MRI contrast nanoparticle system represents a promising probe for early diagnosis through possible accumulation and contrast enhancement within reductive extracellular tumour tissue.

New concepts to fight oxidative stress: nanosized three-dimensional supramolecular antioxidant assemblies.

INTRODUCTION: Misregulation of reactive oxygen species and reactive nitrogen species by the body's antioxidant system results in oxidative stress, which is known to be associated with aging, and involved in various pathologies including cancer, neurodegenerative and cardiovascular diseases. A large variety of low-molecular-weight (LMW) antioxidant compounds and antioxidant enzymes have been proposed to alleviate oxidative stress, but their therapeutic efficacy is limited by their solubility, stability or bioavailability. In this respect, nanoscience-based systems are expected to provide more efficient mitigation of oxidative stress. AREAS COVERED: The main nanoscience-based three-dimensional (3D) supramolecular assemblies, decorated with, or entrapping antioxidant compounds, or which possess intrinsic antioxidant activity are discussed and illustrated with recent examples. Assemblies with different architectures and sizes in the nanometer range serve: i) to deliver LMW antioxidant compounds or enzymes; ii) as antioxidant systems due to their intrinsic activity; and recently iii) to provide a confined space where catalytic antioxidant reactions take place in situ (nanoreactors and artificial organelles). A few insights into the role of antioxidants in mitigating oxidative stress caused by therapeutic compounds or drug carriers are also discussed. EXPERT OPINION: Several challenges must still be overcome in the development of 3D supramolecular assemblies to efficiently fight oxidative stress. First, an improvement of the assemblies' properties and stability in biological conditions has to be addressed. Second, new systems based on the combination of biomolecules or mimics in supramolecular assemblies should provide multifunctionality, stimuli-responsiveness and targeting properties for a more efficient therapeutic effect. Third, comparative studies are necessary to evaluate these systems in a standardized manner both in vitro and in vivo.