Synthesis of 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl with various anions for investigation of ionic liquids

A new synthetic way is described to prepare 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl bearing tetrafluoroborate, hexafluorophosphate or bis(trifluoromethylsulfonylimide) by an anion metathesis of 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide using the corresponding silver salts. 4-Trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl iodide is obtained by the methylation of 4-amino-2,2,6,6-tetramethylpiperidine-1-yloxyl with methyliodide. The new spin probe 4-trimethylammonio-2,2,6,6-tetramethylpiperidine-1-yloxyl bistrifluoromethylsulfonylimide and the spin probes containing tetrafluoroborate or hexafluorophosphate may be useful for an effective investigation of ionic liquids with similar anions.     

Synthesis of 4-sulfonatooxy-2,2,6,6-tetramethylpiperidine-1-yloxyl derivatives for investigation of ionic liquids

Direct sulfonation of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-yloxyl using chlorosulfuric acid trimethylsilylester results in 4-sulfonatooxy-2,2,6,6-tetramethylpiperidine-1-yloxyl in 94% yield that is the basis for the synthesis of potassium 4-sulfonatooxy-2,2,6,6-tetramethylpiperidine-1-yloxyl and sodium 4-sulfonatooxy-2,2,6,6-tetramethylpiperidine-1-yloxyl. These nitroxides can be employed as spin probes to investigate properties of ionic liquids in the molecular domain.     

Synthesis of a new ionic spin probe for investigation of polar and non-polar solvents

A synthesis is described for the new ionic spin probe potassium-(18-crown-6)-4-sulfonatooxy-2,2,6,6-tetramethyl-piperidine-1-yloxyl. This new spin probe shows an improved solubility in both polar and non-polar solvents in comparison with the potassium-4-sulfonatooxy-2,2,6,6-tetramethylpiperidine-1-yloxyl. Furthermore, the solubility of potassium-(18-crown-6)-4-sulfonatooxy-2,2,6,6-tetramethyl-piperidine-1-yloxyl is also improved in ionic liquids relative to the potassium salt comprising no crown ether moiety. The spin probe potassium-(18-crown-6)-4-sulfonatooxy-2,2,6,6-tetramethyl-piperidine-1-yloxyl is highly suitable for investigation of both less polar and highly polar environments.     

2,2,6,6-Tetramethylpiperidine-1-yloxyl bound to the imidazolium ion by an acetamido group for investigation of ionic liquids

New spin probes bearing the 2,2,6,6-tetramethylpiperidine-1-yloxyl covalently bound to the imidazolium ion via a methylene spacer and an amide group are synthesized. If the anion is bis(trifluoromethylsulfonylimide) instead of iodide, the new spin probe has a similar structure as that of an ionic liquid. Nevertheless, the new spin probes are useful tools to investigate ionic liquids.     

ESR spin probes in ionic liquids.

The spin probes 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), and 2,2,6,6-tetramethyl-4-trimethylammoniumpiperidine-1-oxylIodide (CAT-1) are examined in a number of ionic liquids based on substituted imidazolium cations and tetrafluoroborate and hexafluorophosphate anions, respectively. The reorientation correlation times tau(R) of the spin probes in these systems have been determined by complete spectra simulation and, for rapid reortientation, by analysis of the intensities of the hyperfine lines of the electron spin resonance (ESR) spectra. A comparison of the results with those from the model system glycerol/water and selected organic solvents is made. Additions of diamagnetic and paramagnetic ions allow the conclusion that salt effects and spin exchange are present, and that both are superimposed by motional effects. Specific interactions in the ionic liquids, as well as between the spin-probe molecules and the constituents of the ionic liquids are reflected in the spectra of the spin probes, depending on their molecular structure.     

Spin exchange of nitroxyl radicals in H2O and D2O

By means of continuous wave electron spin resonance (cw ESR) in the X and L bands, the spin exchange of series of different concentrations of the spin probes 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), and 4-(trimethylamino)-2,2,6,6-tetramethylpiperidine-1-oxyl iodide (CAT-1) in H(2)O and D(2)O have been examined. The rate constants k(e) of the spin exchange have been determined by complete spectra simulations, as well as directly from hyperfine line broadenings and concentration depending line shifts. The obtained results showed a good agreement. Their respective differences {k(e)(H(2)O) - k(e)(D(2)O)} could be determined for the first time. They reflect the different influence of the solvents on the spin dynamics but confirm the decrease of the reaction rate in D(2)O, caused by the higher degree of order in this liquid. The spectroscopic and kinetic results presented in this paper establish a further kind of isotopic effect.     

Synthesis of 3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl

The reaction of 4-hydroxyimino-2,2,6,6-tetramethyl-3-chloropiperidine-1-oxyl with ammonia results in the formation of 3-amino-4-hydroxyimino-2,2,6,6-tetramethylpiperidine-1-oxyl. Reduction of 3-amino-4-hydroxyimino-2,2,6,6-tetramethylpiperidine-1-oxyl to 3,4-diamino-2,2,6,6-tetramethylpiperidine, protection of the primary amino groups by acylation, followed by oxidation of the secondary amino group to a radical and removal of the acyl protection resulted in the formation of 3,4-diamino-2,2,6,6-tetramethylpiperidine-1-oxyl.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2094–2098, September, 1989.     

Synthesis of 2,2,6,6-Tetramethylpiperidine Derivatives

Diazotization of 4-amino-2,2,6,6-tetramethylpiperidine in acetic or sulfuric acid affords 2,2,6,6- tetramethyl-1,2,3,6-tetrahydropyridine in high yield. Under the same conditions, the corresponding nitroxyl radical transforms into 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl.     

Microstructures and supramolecular structures of butadiene-nitrile rubbers: Paramagnetic-probe study

The chain microstructures and supramolecular structures of butadiene-nitrile rubbers are studied by ESR spectroscopy. On the temperature dependences of the rotational mobility (correlation time τ_c) of paramagnetic probes differing in size (2,2,6,6-tetramethylpiperidine-1-oxyl and 4-benzoate-2,2,6,6-tetramethylpiperidine-1-oxyl), relaxation transitions are observed. It is shown that there is a correlation between the Arrhenius parameters of rotational mobility of radicals and the copolymer composition and that different brands of rubbers differ in microstructure and supramolecular structure.     

Heterospin Copper(II) Catecholate Complex with the TEMPO–Iminopyridine Ligand

Russian Journal of Coordination Chemistry - The heterospin copper(II) complex, ((pyridin-2-ylmethylene)-4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-3,6-di-tert-butylcatecholatocopper(II) (I), is...     

Controlling the extent of spin exchange coupling in 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) biradicals via molecular recognition with cucurbit[n]uril hosts

The binding interactions between two paramagnetic cobaltocenium guests and the hosts cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) were investigated using a combination of electronic absorption, NMR, and electron paramagnetic resonance (EPR) spectroscopies, mass spectrometry, and X-ray crystallography. Guest 1, (4-amido-2,2,6,6-tetramethylpiperidine-1-oxyl)cobaltocenium, forms very stable inclusion complexes with CB7 and CB8. However, CB7 interacts with 1 by including the organometallic cobaltocenium unit, while CB8 engulfs the TEMPO residue. The corresponding equilibrium association constant (K) values are 2.8 ± 0.3 × 10(6) M(-1) for CB7?1 and 2.1 ± 1.0 × 10(8) M(-1) for CB8?1. Biradical guest 2, 1,1'-bis(4-amido-2,2,6,6-tetramethylpiperidine-1-oxyl)cobaltocenium, forms a very stable ternary complex with two CB8 hosts, in which each 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) residue is encircled by a host molecule. The structure of this ternary complex was confirmed in the solid state using single-crystal X-ray diffraction. Binding of the TEMPO side arms by the CB8 hosts gradually decreases the observed level of spin exchange coupling between the two nitroxide groups. In the final 2:1 complex, no spin exchange coupling was observed, but the initial levels of spin exchange coupling could be regenerated in a reversible fashion by adding a competing guest, adamantyltrimethylammonium (AdTMA), to the solution. The binding interactions between 2 and CB7 are similar but the stabilities of the 1:1 and 2:1 complexes are much lower than those of the corresponding CB8 complexes.     

4-Amino-1-oxyl-2,2,6,6-tetramethylpiperidine-3-carboxylic acid (β-TOAC), the first spin-labelled, cyclic, chiral β-amino acid resolved in an enantiomerically pure state

Amination of 3-carboxymethyl-1-oxyl-2,2,6,6-tetramethyl-4-piperidone with (R)-α-methylbenzylamine, NaBH₃CN reduction of the resulting enamine and removal of the chiral auxiliary from the separated diastereoisomers, led to enantiomerically pure (3S,4S) and (3R,4R) methyl 4-amino-1-oxyl-2,2,6,6-tetramethylpiperidine-3-carboxylates.     

Heterocyclic derivatives of long-chain diacetylenic acids

Acyl derivatives of 2-aminopyridine, 2-aminopyrimidine, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl were obtained from long-chain diacetylenic acyl chlorides and the corresponding heterocyclic compounds. Spreading isotherms of monolayers on a water surface show that lengthening of the hydrocarbon chain and replacement of the pyridyl groups in these compounds by the more hydrophilic pyrimidyl groups render the films more condensed. Long-chain acyl derivatives of nitroxyl radicals form monolayers possesing a low collapse pressure. ESR spectra of Langmuir-Blodgett films of these radicals before and after photopolymerization were recorded.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2009–2012, October, 1995.The authors are grateful to S. A. Dzyuba for his help in recording ESR spectra and for helpful discussion.This work was financially supported by the Russian Foundation for Basic Research (Project No. 93-03-04027).     

Polymers having stable radicals. I. Synthesis of nitroxyl polymers from 4-methacryloyl derivatives of 2,2,6,6-tetramethylpiperidine

Polymers having stable nitroxyl free radicals, poly-4-methacryloylamino- and poly-4-methacryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyls, were synthesized from their precursor polymers by oxidizing them in a methanolic solution of hydrogen peroxide. The precursor polymers were prepared by radical polymerization of 4-methacryloyl-amino/oxy-2,2,6,6-tetramethylpiperidines in various solvents. These polymerizations in acetic acid were found to yield polymers of high molecular weight. The copolymers of the precursor monomers with styrene and methyl methacrylate were also prepared as precursor copolymers. These precursor polymers of a piperidine type were converted to the polymers having stable nitroxyl free radicals by the hydrogen peroxide method. In this report, it was assumed that the post-oxidation reaction introduced a nitroxyl group smoothly and quantitatively at room temperature. Elucidations of the stable radical formation and the electron spin behavior of the stable radical polymers were made in terms of elemental analyses, infrared, ultraviolet, and ESR spectroscopy.     

Analysis of electron spin resonance spectra of alkyl spin labels in excised guinea pig dorsal skin, its stratum corneum, delipidized skin and stratum corneum model lipid liposomes

The electron spin resonance (ESR) spectra of alkyl spin labels were observed in the excised guinea pig dorsal skin, its stratum corneum, delipidized skin and stratum corneum model lipid liposomes. The spectrum of 5-doxylstearic acid (5-NS) in the stratum corneum and order parameter obtained from the spectrum, indicated that the spin label was present in highly ordered lipid lamella. On the other hand, the spectrum of methyl ester of 5-NS (5-NMS) and its apparent rotational correlation time calculated from the spectrum, showed only a weakly immobilized component in the stratum corneum as well as in the whole excised skin. The ester spin label seemed to be scarcely present in the rigid lipid lamella, but mainly in the relatively fluid environment. On the other hand, cationic alkyl spin labels showed quite different spectra depending on their alkyl chain lengths. Long-chain 4-(N,N-dimethyl-N,-pentadecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl (CAT-15) seemed to be present in the protein region of the stratum corneum as we recently reported, whereas hydrophilic quaternary ammonium spin label 4-trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyl (CAT-1) seemed to be present in the bulk water of the skin, even in delipidized skin. These findings indicated that the different interaction and different localization of the alkyl spin labels depended on their electronic charge as well as their alkyl chain lengths.     

The rotational mobility of fulleropyrrolineoxyl in toluene solution

The rotational mobility of a stable fullerene-based nitroxyl radical (fulleropyrrolineoxyl) in toluene was studied. The rotational correlation time of fulleropyrrolineoxyl was found to be about eight times longer than that of 4-oxy-2,2,6,6-tetramethylpiperidine-1-oxyl. The activation energy of the rotational motion of both probes was determined and their hydrodynamic radii estimated.     

The nature of sites of absorption of low-molecular-mass compounds by butadiene–acrylonitrile copolymers

The rotational mobilities of the paramagnetic probes TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and BZONO (4-benzoate-2,2,6,6-tetramethylpiperidine-1-oxyl) are studied via EPR spectroscopy and the equilibrium swelling of random and multiblock butadiene–acrylonitrile copolymers of various compositions and stereostructures of butadiene units in n-heptane, methyl acetate, and toluene are studied. The nature of defective regions sorbing low-molecular-mass compounds is ascertained. The rotational mobilities of the probes in defects of various structures are estimated. The sites of sorption are found to be identical in crosslinked and noncrosslinked elastomers. It is shown that the sorption of n-heptane and methyl acetate appears in the same defective regions as those of the TEMPO radical, while the sorption of toluene emerges in sorption sites where the value of free volume is sufficient for the sorption of the bulky radical BZONO. A decay in local molecular mobility in structural defects (“holes”) does not hinder the absorption of lowmolecular- mass compounds if the free volume is sufficient.     

Synthesis and properties of nicotinic acid derivatives containing a 2,2,6,6- tetramethylpiperidine 1-oxyl residue

N¹-(Nicotinoyl)-N²-4-(2,2,6,6-tetramethyl-4-hydroxypiperidine-1-oxyl)hydraxine was obtained by condensation of nicotinoyl hydrazide with 2,2,6,6-tetramethyl-4-oxopiperidine 1-oxyl. Acylation of 2,2,6,6-tetramethyl-4-hydroxypiperidine 1-oxyl with nicotinoyl chloride gives nicotinic acid 2,2,6,6-tetramethyl-1-oxyl 4-piperidyl ester. A spin-labeled analog of nicotinamide was obtained by condensation of nicotinoyl azide with 4-amino-2,2,6,6-tetramethylpiperidine 1-oxyl. The synthesis of 1-N-(-D-ribofuranoside)-3'-N[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)pyridinecarboxamide from 2,2,6,6-tetramethyl-4-nicotinoylaminopiperidine 1-oxyl and 2,3,5-tri-O-benzoyl--D-ribofuranosyl bromide proceeds without damage to the iminoxyl radical. The preparation of the corresponding spin-labeled nucleotide is hindered by destruction of the iminoxyl radical during ion-exchange chromatography.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 352–355, March, 1976.     

Synthesis and structure of redox derivatives of 4-(2-Amino-2-oxoethyl)-2,2,6,6-tetramethylpiperidine-1-yloxyl

According to X-ray diffraction (XRD) analysis and ¹H NMR spectra 2-(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)acetamide, 4-(2-amino-2-oxoethyl)-2,2,6,6-tetramethylpiperidin-1-yloxyl, and 4-(2-amino-2-oxoethyl)-2,2,6,6-tetramethyl-1-oxopiperidinium perchlorate in the crystalline state and in solution possess the chair conformation, equatorial orientation of CH₂C(O)NH₂ group, and differ by the geometry of the N¹ atom of the heterocycle. At growing oxidation state of the piperidine nitrogen atom the pyramidal location of substituents at N¹ in the hydroxyl derivative changes to weakly pyramidal in the piperidinoxyl and turned into planar in the oxoammonium cation. Simultaneously the N¹-O¹ bond shortens transforming from an ordinary (1.451 Å) through a sesquialteral (1.289 Å) into a double (1.189 Å) bond. The insignificant changes in the structure of compounds in the transition piperidinoxyl-oxopiperidinium cation correspond to the low energy of the transition process and result in the ease of the redox-reactions involving this pair.     

Spin-labeled analogs of CMP-NeuAc as NMR probes of the alpha-2,6-sialyltransferase ST6Gal I

Structural data on mammalian proteins are often difficult to obtain by conventional NMR approaches because of an inability to produce samples with uniform isotope labeling in bacterial expression hosts. Proteins with sparse isotope labels can be produced in eukaryotic hosts by using isotope-labeled forms of specific amino acids, but structural analysis then requires information from experiments other than nuclear Overhauser effects. One source of alternate structural information is distance-dependent perturbation of spin relaxation times by nitroxide spin-labeled analogs of natural protein ligands. Here, we introduce spin-labeled analogs of sugar nucleotide donors for sialyltransferases, specifically, CMP-TEMPO (CMP-4-O-[2,2,6,6-tetramethylpiperidine-1-oxyl]) and CMP-4carboxyTEMPO (CMP-4-O-[4-carboxy-2,2,6,6-tetramethylpiperidinine-1-oxyl]). An ability to identify resonances from active site residues and produce distance constraints is illustrated on a (15)N phenylalanine-labeled version of the structurally uncharacterized, alpha-2,6-linked sialyltransferase, ST6Gal I.