PubMed Health⌕ Search

Biomedical subjects

M F Otto

Publications and source records attributed to M F Otto.

3 recordsLinked to original sources

Classical and quantum Hamiltonian ratchets.

We explain the mechanism leading to directed chaotic transport in Hamiltonian systems with spatial and temporal periodicity. We show that a mixed phase space comprising both regular and chaotic motion is required and we derive a classical sum rule which allows one to predict the chaotic transport velocity from properties of regular phase-space components. Transport in quantum Hamiltonian ratchets arises by the same mechanism as long as uncertainty allows one to resolve the classical phase-space structure. We derive a quantum sum rule analogous to the classical one, based on the relation between quantum transport and band structure.

Journal Article↗

Spontaneous and oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates.

Methamidophos (CH3O(NH2)P(O)SCH3) and phosphoramidates, with the general structure RO(NH2)P(O)OC6H4-p-NO2, in which R = C2H5, C1CH2CH2, FCH2CH2 and F3CCH2, as well as (NH2)2P(O)OC6H4-p-NO2 were synthesized to investigate the relationship between the rates of inhibition and of spontaneous reactivation of AChE inhibited by these organophosphates and their potential as prophylactics against nerve agent poisoning. The phosphoramidates inhibit electric eel acetylcholinesterase (EEAChE), the bimolecular inhibition rate constants ranging from 5 x 10(4) to 3 x 10(6) M-1.min-1 at pH 7.5, 25 degrees C. The inhibited enzymes reactivate spontaneously, with half-lives ranging from 1.3 to 15 h at pH 7.5, 25 degrees C. These half-lives increase 2-4 fold when the temperature is raised to 37 degrees C. Reactivation is accelerated by micromolar concentrations of oximes such as obidoxime and HI-6. Aging of the inhibited enzymes was not observed. Nevertheless, reactivation appears to be incomplete for some of the inhibited enzymes. The title compounds seem promising as prophylactic agents against nerve agent intoxication.

Acetylcholinesterase↗

Stabilization and gas chromatographic analysis of the four stereoisomers of 1,2,2-trimethylpropyl methylphosphonofluoridate (soman) in rat blood.

A method for the stabilization and gas chromatographic analysis of the four stereoisomers of C(+/-)P(+/-)-1,2,2-trimethylpropyl methylphosphonofluoridate (C(+/-)P(+/-)-soman) in rat blood samples is described. Satisfactory stabilization of all four stereoisomers is obtained by (i) acidification of the blood sample to pH 4.2 at 0 degrees C, to stabilize the C(+/-)P(+) isomers, (ii) addition of aluminum ions (2.5 mM) for complexation of fluoride ions, which prevents regeneration of C(+/-)P(-)-soman by free fluoride ions from soman-inhibited aliesterase, and (iii) addition of 2,2-dimethylpropyl methylphosphonofluoridate in order to occupy covalent binding sites for C(+/-)P(-)-soman. The stereoisomers of soman and internal standard are extracted from the blood-stabilizing buffer mixture with a Sep-Pak C18 cartridge and are subsequently eluted with ethyl acetate with overall extraction recoveries of 52 +/- 8%. The four soman stereoisomers are resolved and analyzed on a wide-bore capillary Chirasil Val column, synthesized, and coated in house, which also resolves the internal standard C(+/-)P(+/-)-1,2,2-[U-2H]trimethylpropyl methylphosphonofluoridate from C(+/-)P(+/-)-soman. Alternatively, the gas chromatographic analysis can be performed on a wide-bore capillary Chirasil Val column, identical with the commercially available Chirasil Val column, when combined in series with a Carbowax 20M column. This system resolves the four stereoisomers of soman and the internal standard C(-)P(+)-1,2,2-trimethylpropyl [U-2H]methylphosphonofluoridate. Using an alkali flame ionization detector, the detection limit of our procedure is ca. 250 pg soman isomer/blood sample.

Animals↗