Examination of novel alkoxyamines has demonstrated the pivotal role that the nitroxide plays in mediating the “living” or controlled polymerization of a wide range of vinyl monomers. Surveying a variety of different alkoxyamine structures led to α-hydrido derivatives based on a 2,2,5-trimethyl-4-phenyl-3-azahexane-3-oxy, 1, skeleton which were able to control the polymerization of styrene, acrylate, acrylamide, and acrylonitrile based monomers. For each monomer set, the molecular weight could be controlled from 1000 to 200 000 amu with polydispersities typically 1.05−1.15. Block and random copolymers based on combinations of the above monomers could also be prepared with similar control. In comparison with 2,2,6,6-tetramethylpiperidinoxy (TEMPO), these new systems represent a dramatic increase in the range of monomers that can be polymerized under controlled conditions and overcome many of the limitations associated with nitroxide-mediated “living” free radical procedures. Monomer selection and functional group compatibility now approach those of ATRP-based systems.

ABSTRACT:Nitroxides bearing an a-hydrogen decompose upon heating in a bimolecular reaction. A new mechanism is proposed for the decomposition of t-butylisopropylphenyl nitroxide (TIPNO) involving the formation of a head-to-tail dimer, single electron transfer to form an oxammonium salt, epimerization to the corresponding nitrone, and elimination to form a conjugated oxime. This mechanism may provide insights into designing new nitroxides for use in controlled polymerization.

Copper-free azide-alkyne click chemistry is utilized to covalently modify polyvinyl chloride(PVC). Phthalate plasticizer mimics di(2-ethylhexyl)-1H-triazole-4,5 dicarboxylate (DEHT), di(nbutyl)-1H-1,2,3-triazole-4,5-dicarboxylate (DBT), and dimethyl-1H-triazole-4,5-dicarboxylate(DMT) are covalently attached to PVC. DEHT, DBT, and DMT have similar chemical structures to traditional plasticizers di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and dimethyl phthalate (DMP), but pose no danger of leaching from the polymer matrix and forming small endocrine disrupting chemicals. The synthesis of these covalent plasticizers is expected to be scalable, providing a viable alternative to the use of phthalates, thus mitigating dangers to human health and the environment.

Quantum dot (QD) fluorescence is effectively quenched at low concentration by nitroxides bearing amine or carboxylic acid ligands. The association constants and fluorescence quenching of CdSe QDs with these derivatized nitroxides have been examined using electron paramagnetic resonance (EPR) and fluorescence spectroscopy. The EPR spectra in the non-protic solvent toluene are extremely sensitive to intermolecular and intramolecular hydrogen bonding of the functionalized nitroxides. Fluorescence measurements show that quenching of QD luminescence is nonlinear, with a strong dependence on the distance between the radical and the QD. The quenched fluorescence is restored when the surface-bound nitroxides are converted to hydroxylamines by mild reducing agents, or trapped by carbon radicals to form alkoxyamines. EPR studies indicate that photoreduction of the nitroxide occurs in toluene solution upon photoexcitation at 365 nm. However, photolysis in benzene solution gives no photoreduction, suggesting that photoreduction in toluene is independent of the quenching mechanism. The fluorescence quenching of QDs by nitroxide binding is a reversible process.

Suppression of mitochondrial production of reactive oxygen species is a promising strategy against intrinsic apoptosis typical of degenerative diseases. Stable nitroxide radicals such as 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl (TEMPOL) and its analogs combine several important features, including recycleability, electron acceptance from respiratory complexes, superoxide dismutase mimicry, and radical scavenging. Although successful in antioxidant protection, their effective concentrations are too high for successful in vivo applications. Recently (J Am Chem Soc 127:12460, 2005), we reported that 4-amino 2,2,6,6-tetramethyl-1-piperidinyloxy, covalently conjugated to a five-residue segment of gramicidin S (GS), was integrated into mitochondria and blocked actinomycin D (ActD)-induced superoxide generation and apoptosis. Using a model of ActDinduced apoptosis in mouse embryonic cells, we screened a library of nitroxides to explore structure-activity relationships between their antioxidant/antiapoptotic properties and chemical composition and three-dimensional (3D) structure. High hydrophobicity and effective mitochondrial integration are necessary but not sufficient for high antiapoptotic/antioxidant activity of a nitroxide conjugate. By designing conformationally preorganized peptidyl nitroxide conjugates and characterizing their 3D structure experimentally (circular dichroism and NMR) and theoretically (molecular dynamics), we established that the presence of the ␤-turn/␤-sheet secondary structure is essential for the desired activity. Monte Carlo simulations in model lipid membranes confirmed that the conservation of the D-Phe-Pro reverse turn in hemi-GS analogs ensures the specific positioning of the nitroxide moiety at the mitochondrial membrane interface and maximizes their protective effects. These new insights into the structure-activity relationships of nitroxidepeptide and -peptide isostere conjugates are instrumental for development of new mechanism-based therapeutically effective agents.Poorly controlled and excessive generation of reactive oxygen species (ROS), coupled with their ability to cause oxidative damage to phospholipids, proteins, and DNA, has been associated with the pathogenesis of a number of major human cardiovascular (Ambrosio and Tritto, 1999) and neurodegenerative diseases (Andersen, 2004) as well as cancer (Szatrowski and Nathan, 1991). Not surprisingly, significant efforts have been directed toward the use of radical scavengers and antioxidants in preventive and therapeutic strategies, albeit with limited success. The search for new protective remedies has been focused on molecules combining antioxidant utilities with recycling capacities (Mitchell et al.,

Tetra-n-butylammonium Oxone, readily prepared as a white solid from commercially available Oxone, performs oxidations in anhydrous methylene chloride. Under these conditions, sulfides are oxidized to sulfones in the presence of amines, ketones, esters, carbamates, olefins, and hydroxyl functionalities. Very acid-labile groups such as dimethyl ketals and THP ethers require buffering with anhydrous sodium carbonate. Reactions may be worked up either by direct chromatography of the reaction mixture or by two-phase aqueous extraction. Sulfur-containing amino acid derivatives are also oxidized under these conditions.

The use of 13C NMR shifts in defining halogen regiochemistry or six-membered ring substituent stereochemistry in marine monoterpenes is considered in detail. New additivity parameters and model compound 13C NMR shift data are presented. Structures are proposed for three new red seaweed monoterpenes (3, 4, and 5), and revisions are suggested for four other published structures (6, 7, 8, and 9). Our approach can be extended to certain marine sesquiterpenes such as the chamigrane class. Comparisons between calculated and experimental chamigrane

Low-temperature methods for the preparation of monomeric initiators for use in “living” free radical olefin polymerizations have been developed. Oxidative methods for generating carbon radicals in the presence of nitroxide traps such as TEMPO utilize PbO2 with benzylic, alkyl, or phenylhydrazines or CuCl2 with lithium enolates. Photolytic methods employ [Cp(CO)2Fe]2 with a benzylic bromide, diphenyl disulfide with styrene, or di-tert-butyl peroxide with ethers. The use of di-tert-butyl hyponitrite with ethers generates carbon radicals at 50 °C that are trapped by TEMPO.