Synthesis of Sterically Shielded Nitroxides Using the Reaction of Nitrones with Alkynylmagnesium Bromides.

Sterically shielded nitroxides, which demonstrate high resistance to bioreduction, are the spin labels of choice for structural studies inside living cells using pulsed EPR and functional MRI and EPRI in vivo. To prepare new sterically shielded nitroxides, a reaction of cyclic nitrones, including various 1-pyrroline-1-oxides, 2,5-dihydroimidazole-3-oxide and 4-imidazole-3-oxide with alkynylmagnesium bromide wereused. The reaction gave corresponding nitroxides with an alkynyl group adjacent to the N-O moiety.

3,4-Unsubstituted 2--Butyl-pyrrolidine-1-oxyls with Hydrophilic Functional Groups in the Side Chains.

Pyrrolidine nitroxides with four bulky alkyl substituents adjacent to N-O group are known for their high resistance to bioreduction. The 3,4-unsubstituted 2--butyl-2-ethylpyrrolidine-1-oxyls were prepared from the corresponding 2--butyl-1-pyrroline-1-oxides via either the addition of ethinylmagnesium bromide with subsequent hydrogenation or via treatment with ethyllithium. The new nitroxides showed excellent stability to reduction with ascorbate with no evidence for additional large hyperfine couplings in the EPR spectra.

The Reactions of 6-(Hydroxymethyl)-2,2-dimethyl-1-azaspiro[4.4]nonanes with Methanesulfonyl Chloride or PPh-CBr.

Activation of a hydroxyl group towards nucleophilic substitution via reaction with methanesulfonyl chloride or PPh-CBr system is a commonly used pathway to various functional derivatives. The reactions of (5(),6())-1-X-6-(hydroxymethyl)-2,2-dimethyl- 1-azaspiro[4.4]nonanes 1- (X = O·; H; OBn, OBz) with MsCl/NR or PPh-CBr were studied.

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition.

Sterically shielded nitroxides of the pyrrolidine series have shown the highest resistance to reduction. Here we report the synthesis of new pyrrolidine nitroxides from 5,5-dialkyl-1-pyrroline -oxides via the introduction of a pent-4-enyl group to the nitrone carbon followed by an intramolecular 1,3-dipolar cycloaddition reaction and isoxazolidine ring opening. The kinetics of reduction of the new nitroxides with ascorbate were studied and compared to those of previously published (1,2,3',4',5',2″)-dispiro[(2-hydroxymethyl)cyclopentan-1,2'-(3',4'-di--butoxy)pyrrolidine-5',1″-(2″-hydroxymethyl)cyclopentane]-1'-oxyl ().

Ultrafine organic aerosol particles inhaled by mice at low doses remain in lungs more than half a year.

Experimental results of the second series of experiments on the penetration of monodisperse polymeric particles, inhaled at low dose by mice, to different organs using direct way of particle registration, based on the ultra-sensitive accelerator mass spectrometer (AMS), are presented. Polystyrene (PS) beads, composed of radiocarbon-labeled styrene, were produced for testing them as model organic aerosols. Mice inhaled C-PS aerosol of 3·10 ultrafine particles per 1 cm for 30 minutes every day during 5 days.