Virginia Tech
Quantitative structure activity relationships of monoamine oxidase catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs
Abstract
dc:description.abstractStudies into the quantitative structure act! Vlty relationships of rate s of I-methyl-4-phenyl-l,2,3,6-tetrahydropyridine oxidation catalyzed by monoamine oxidases A and B were performed to elucidate active site substrate conformation and oxidation mechanisms. Plotting experimental kinetic activity against molecular properties obtained by experiment and by computational chemistry methods demonstrated correlations with lipophilic, steric, and electronic factors. Compounds studied were 4-aryloxy analogs, 4- aromatic heterocycle analogs, and 4-phenyl analogs. The conformer with phenyl ring to tetrahydropyridine dihedral angles similar to a low energy conformer of I-methyl-4-(2'-methyl-phenyl)-1,2,3,6- tetrahydropyridine is the most active conformer. Results indicate that rate limiting single electron transfer mechanisms are more viable than hydrogen atom abstraction mechanisms. Results indicate that binding or dissociation is the rate limiting step for aryloxy-analog oxidation catalyzed by monoamine oxidase B whereas the catalytic event itself is the rate limiting step for the other analogs. Several equations were developed to describe quantitative structure activity relationships of oxidation rates.
Degree
thesis:*- Name thesis:degree_name
- Master of Science
- Level thesis:degree_level
- masters
- Discipline thesis:degree_discipline
- Chemistry
- Department dc:contributor.department
- Chemistry
- Grantor dc:publisher
- Virginia Tech
- Year dc:date.issued
- 1996
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Harris, Dana N.
- Chair dc:contributor.committeechair
-
- Castagnoli, Neal Jr.
- Committee members dc:contributor.committeemember
-
- Tanko, James M.
- Bevan, David R.
- Bell, Harold M.
Subjects
dc:subject × 4Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
- Language dc:language.iso
- en
Identifiers
dc:identifier.*- Dc Identifier Other
- etd-08252008-162914
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/44451