Structural features of ATPA and thio-ATPA - Potent and selective gluR5 receptor agonists. Crystal structure determinations and quantum chemical calculations
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ATPA and thio-ATPA are semirigid analogs of the excitatory neurotransmitter (S)-glutamic acid. (S)-ATPA and (S)-thio-ATPA are potent and selective GluR5 receptor agonists. X-ray structure determination of the zwitterions of (RS)-ATPA and (R)-thio-ATPA has been performed. Furthermore, quantum chemical ab initio calculations have been carried out on the tautomeric heterocyclic substructures 4,5-dimethyl-3-isoxazolol and 4,5-dimethyl-3- isothiazolol. Very high level ab initio calculations (including triple-ζ basis set and treatment of electron correlation) are necessary for a consistent theoretical description of the heterocyclic rings of these compounds. Results for the aqueous phase properties (PB-SCRF method, combined with density functional theory) are chemically reasonable and in agreement with experimental data. While the 3-isoxazolol tautomer of the zwitterionic amino acid ATPA predominates in all phases, the 3(2H)-isothiazolone tautomer of the zwitterionic amino acid thio-ATPA predominates in the crystal structure (3:1) and most likely in weakly acidic aqueous solution.
Original language | English |
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Journal | Structural Chemistry |
Volume | 13 |
Issue number | 5-6 |
Pages (from-to) | 479-490 |
Number of pages | 12 |
ISSN | 1040-0400 |
DOIs | |
Publication status | Published - Dec 2002 |
- ab initio calculations, ATPA, GluR5 receptor agonist, tautomerism, Thio-ATPA, X-ray structure
Research areas
ID: 382746703