Stabilization of zwitterions in solution: GABA analogues.

• Abstract: The solution-phase structures of a number of conformationally restricted gamma-aminobutyric acid (GABA) analogues are investigated at the MP2/6-31+G* level of theory, using both explicit water molecules and the conductor-like screening solvation model (COSMO) to model solvation. GABA analogues constrained in a cis conformation by either a double bond or cyclopropane ring have the potential to attain either folded, intramolecularly hydrogen-bonded, or partially folded conformations in solution. Systems constrained in a cis conformation by a cyclopentane or cyclopentene ring are more conformationally restricted and exist only in a folded, intramolecularly hydrogen-bonded form. GABA analogues constrained in a trans conformation by either a double bond or cyclopropane ring have the potential to adopt either partially folded or fully extended conformations in solution. Due to a lack of conformational flexibility, analogues that are constrained in a trans conformation by a cyclopentane or cyclopentene ring attain only partially folded conformations. Like GABA, conformationally flexible GABA analogues possess a large number of stable rotamers, and may exist in any or all of these conformations in aqueous solution. The structures of these analogues provide an essential foundation for subsequent structure-activity analysis of ligand binding at GABA receptors and transporters. This work is therefore expected to facilitate the design and development of new biologically active GABA analogues to treat GABA-related neurological disorders.
• Authors: Deborah L Crittenden, Mary Chebib, Meredith J T Jordan (Affiliation: School of Chemistry, University of Sydney, NSW, Australia 2006.)
• Journal: The journal of physical chemistry. A (J Phys Chem A) Vol. 109 Issue 18 Pg. 4195-201 (May 12 2005) ISSN: 1089-5639 [Print] United States
• PMID: 16833745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ions
• Solutions
• gamma-Aminobutyric Acid

Topics

• Ions (chemistry)
• Solutions
• gamma-Aminobutyric Acid (analogs & derivatives, chemistry)