Chiral Ligand Exchange Chromatography: Separation of Enantiomeric Mixtures of Underivatized α-Amino Acids under UV Detection

Abstract

) em água ou em água/ metanol. A utilização de água/metanol leva a uma grande diminuição dos tempos de retenção dos α-amino ácidos mais hidrofóbicos, preservando a separação enantiomérica. O pH precisa ser alto o bastante para permitir a presença de grupos -NH 2 livres, o que torna a complexação com Cu(II) mais fácil. α-Amino ácidos conformacionalmente mais restritos, como a L-prolina e a L-hidroxiprolina, conduziram a separações enantioméricas menores. A formação de complexos pseudo-homoquirais e pseudo-heteroquirais, por troca de ligantes, que é cinética e termodinamicamente controlada, desempenha um papel fundamental para a separação enantiomérica desejada. Esta metodologia simples e barata pode ser usada em qualquer laboratório envolvido em síntese de α-amino ácidos.Enantiomeric mixtures of alanine, serine, threonine, valine, methionine, leucine and norleucine were resolved in ligand exchange reversed phase HPLC (reproducibly), by using L-proline, L-) and Cu(CH 3 COO) 2 (1 mmol L -1 ) in water or in water/methanol. The latter mobile phase greatly decreased the retention time of the more hydrophobic α-amino acids, preserving enantioseparation. pH must be high enough to allow the presence of free -NH 2 groups in order to make the complexation with Cu(II) easier. The more restricted conformation of L-proline and L-hydroxyproline led to lower enantioseparations. The ligand exchange formation of pseudo-homochiral and pseudo-heterochiral complexes, thermodynamically and kinetically controlled, plays a fundamental role for the desired enantiomeric chromatographic separation. This simple and inexpensive methodology can be used routinely by any laboratory involved in α-amino acid synthesis.

Supramolecular Complex of 2-Hydroxypropyl-β-cyclodextrin with d- and l-tryptophan

“…We have also determined that the complexes occurred in the solid state, with two points of interaction: one superficial, with H-bonds between Tryptophan's NH 3 þ group and cyclodextrin OH groups; and another interaction between the indole moiety and CD cavity. This work represents a part of our continuous work on understanding interactions between chiral compounds [22] and can better clarify the thermodynamics associated with such interactions. …”

Elucidation of chiral Recognition mechanism of alpha-amino acids using ligand exchange high performance liquid chromatography

“…This model was exposed in our previous work of chiral recognition. 14 In order to examine what configuration is thermodynamically favored, we have carried out theoretical studies with the two possible homochiral complex structures.…”

“…3,4 Based on the ligand exchange principle, chiral resolution is possible due to the transient formation of a pair of diastereomers, pseudo-homochiral and pseudo-heterochiral complexes, with different chemical properties and consequently different retentivities in the mobile phase. [5][6][7][8][9][10][11][12][13] Our previous publication 14 reported the successful study of three chiral selectors: L-proline, L-hydroxyproline and N,N-dimethyl-L-phenylalanine combined with Cu(II) ion in the mobile phase for the enantioseparations of some α-amino acids, with the elution order of D followed by L, using RP (Reversed Phase)-HPLC. In order to determine the preferable configuration of the diastereoisomeric complex (Figure 1), it was carried out for both isomers a theoretical study of structure optimization and infrared spectra simulation in the 100-600 cm -1 range, which corresponds to the bands assigned as metal-ligand vibrations.…”

Interfaces com a indústria

“…Em paralelo, visando baratear custos analíticos desenvolveram-se processos cromatográficos de separação usando ligantes quirais 86 . A idéia por trás desta separação é da formação transiente de complexos pseudohomo-e pseudoheteroquirais, obtidos via troca de ligantes, que podem apresentar diferentes retentividades em cromatografia líquida de alta eficiência (CLAE) em fase reversa 87 ( Figuras 32 e 33). …”