Construction of New Potential Reactivators of Phosphonylated Acetylcholinesterase. Substitution of F for H in the Nucleus of Pyridinecarboxaldehyde Oximes.
Abstract
Syn-3-Fluoro-4-pyridinecarboxaldehyde oxime methiodide (3-F-4-PAM), a new potential reactivator of phosphonylated acetylcholinesterase, has been synthesized and characterized by classical organic chemical and structural methods. The pKa of 3-F-4-PAM is 8.18, which represents a lowering of the pKa value of 4-PAM (pKa 8.6) by 0.4 pKa units, due to the electron-withdrawing effect of the F atom. The pKa value of 3-F-4-M equals that of the potent reactivator TMB-4, and thus the reactivator performance of 3-F-4-PAM will constitute a test of the structural parameters of 3-F-4-PAM versus those of TMB-4 as well as those of 2-PAM. In a chemical test relevant to reactivator performance it was found that the Beckman decomposition rate of 3-F-4-PAM-benzoate is accelerated relative to that of 4-PAM-benzoate, also due to the electron-withdrawing effect of the F atom. Systematic comparative studies of the NMR and UV absorption spectra of 2-PAM, 4-PAM, and 3-F-4-PAM were carried out to help build a data base for eventual interpretation of comparative reactivator behavior. Initial chemical synthesis steps toward other F-PAM compounds were also performed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1982
- Accession Number
- ADA176373
Entities
People
- Ernest Kun
- Jerome Mclick
Organizations
- University of California, San Francisco