d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.

The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in the hippocampus, cortex, and blood samples from NIH Swiss mice are reported. Perfused brain tissues were analyzed for the first time, thereby eliminating artifacts due to endogenous blood, and decreased the mouse-to-mouse variability in amino acid levels. Total amino acid levels (l- plus d-enantiomers) in brain tissue are up to 10 times higher than in blood. However, all measured d-amino acid levels in brain tissue are typically ∼10 to 2000 times higher than blood levels. There was a 13% reduction in almost all measured d-amino acid levels in the cortex compared to those in the hippocampus. There is an approximate inverse relationship between the prevalence of an amino acid and the percentage of its d-enantiomeric form. Interestingly, glutamic acid, unlike all other amino acids, had no quantifiable level of its d-antipode. The bioneurological reason for the unique and conspicuous absence/removal of this d-amino acid is yet unknown. However, results suggest that d-glutamate metabolism is likely a unidirectional process and not a cycle, as per the l-glutamate/glutamine cycle. The results suggest that there might be unreported d-amino acid racemases in mammalian brains. The regulation and function of specific other d-amino acids are discussed.

Enantiomeric separations of chiral sulfonic and phosphoric acids with barium-doped cyclofructan selectors via an ion interaction mechanism.

New cyclofructan-6 (CF6)-based chiral stationary phases (CSPs) bind barium cations. As a result, the barium-complexed CSPs exhibit enantioselectivity toward 16 chiral phosphoric and sulfonic acids in the polar organic mode (e.g., methanol or ethanol mobile phase containing a barium salt additive). Retention is predominantly governed by a strong ionic interaction between the analyte and the complexed barium cation as well as hydrogen bonding with the cyclofructan macrocycle. The log k versus log [X], where [X] = the concentration of the barium counteranion, plots for LARIHC-CF6-P were linear with negative slopes demonstrating typical anion exchange behavior. The nature of the barium counteranion also was investigated (acetate, methanesulfonate, trifluoroacetate, and perchlorate), and the apparent elution strength was found to be acetate > methanesulfonate > trifluoroacetate > perchlorate. A theory based upon a double layer model was proposed wherein kosmotropic anions are selectively adsorbed to the cyclofructan macrocycle and attenuate the effect of the barium cation. van't Hoff studies for two analytes were conducted on the LARIHC-CF6-P for three of the barium salts (acetate, trifluoroacetate, and perchlorate), and the thermodynamic parameters governing retention and enantioselectivity are discussed. Interestingly, for the entropically driven separations, enantiomeric selectivity can increase at higher temperatures, even with decreasing retention.