Chiral discrimination of ß-3-homo-amino acids using the kinetic method.

Chiral discrimination of seven enantiomeric pairs of ß-3-homo-amino acids was studied by using the kinetic method and trimeric metal-bound complexes, with natural and unnatural α-amino acids as chiral reference compounds and divalent metal ions (Cu(2+) and Ni(2+) ) as the center ions. The ß-3-homo-amino acids were selected for this study because, first of all, chiral discrimination of ß-amino acids has not been extensively studied by mass spectrometry. Moreover, these ß-3-homo-amino acids studied have different aromatic side chains. Thus, the emphasis was to study the effect of the side chain (electron density of the phenyl ring, as well as the difference between phenyl and benzyl side chains) for the chiral discrimination. The results showed that by the proper choice of a metal ion and a chiral reference compound, all seven enantiomeric pairs of ß-3-homo-amino acids could be differentiated. Moreover, it was noted that the ß-3-homo-amino acids with benzyl side chains provided higher enantioselectivity than the corresponding phenyl ones. However, increasing or decreasing the electron density of the aromatic ring by different substituents in both the phenyl and benzyl side chains had practically no role for chiral discrimination of ß-3-homo-amino acids studied. When copper was used as the central metal, the phenyl side chain containing reference molecules (S)-2-amino-2-phenylacetic acid (L-Phg) and (S)-2-amino-2-(4-hydroxyphenyl)-acetic acid (L-4'-OHPhg) gave rise to an additional copper-reduced dimeric fragment ion, [Cu(I) (ref)(A)](+) . The inclusion of this ion improved noticeably the enantioselectivity values obtained.

Chiral differentiation of some cyclic beta-amino acids by kinetic and fixed ligand methods.

Differentiation of beta-amino acid enantiomers with two chiral centres was investigated by kinetic method with trimeric metal-bound complexes. Four enantiomeric pairs of beta-amino acids were studied: cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)- and trans-(1S,2S)-2-aminocyclopentanecarboxylic acids (cyclopentane beta-amino acids), and cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclohexanecarboxylic acids (cyclohexane beta-amino acids). The results showed that the choice of metal ion (Cu(2+), Ni(2+)) and chiral reference compound (alpha- and beta-amino acids) had an effect on the enantioselectivity. Especially, aromaticity of the reference compound was noted to enhance the enantioselectivity. The fixed-ligand kinetic method, a modification of the kinetic method, was then applied to the same beta-amino acids, with dipeptides used as fixed ligands. With this method, dipeptide containing an aromatic side chain enhanced the enantioselectivity.

Chiral differentiation of some cyclopentane and cyclohexane beta-amino acid enantiomers through ion/molecule reactions.

Chiral differentiation of four enantiomeric pairs of beta-amino acids, cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclopentanecarboxylic acids (cyclopentane beta-amino acids), and cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclohexanecarboxylic acids (cyclohexane beta-amino acids) was performed successfully by using host-guest complexes and ion/molecule reactions. The experiments were conducted by using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The effect of a chiral host molecule was tested by using three different host compounds; (+)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid, (-)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid, and beta-cyclodextrin. This is the first time that small enantiomeric pairs with two chiral centers have been differentiated using ion/molecule reactions and host-guest complexes.

Diastereochemical differentiation of some cyclic and bicyclic beta-amino acids, via the kinetic method.

Stereochemical differentiation of five diastereomeric pairs of beta-amino acids, di-endo- and di-exo-2,3-disubstituted norbornane and norbornene amino acids, cis- and trans-2-aminocyclohexane-, 2-amino-4-cyclohexene-, and 2-aminocyclopentanecarboxylic acids, was investigated via the kinetic method with metal-bound trimeric complexes. This is the first time that diastereomers (di-endo/di-exo and cis/trans) have been differentiated with metal-bound trimeric complexes and the kinetic method. Moreover, determination of diastereochemical excess by the kinetic method was applied to norbornane beta-amino acids and cyclopentane beta-amino acids. Experiments showed that a remarkable differentiation of the studied diastereomers was achieved. It was observed that better selectivity values correlated to more rigid structures. The reference compounds for the studied beta-amino acids varied from alpha-amino acids to some beta-amino acids. In addition, variation of the metal ion (Cu(2+) and Ni(2+)) had some role in the selectivity values obtained. Ab initio and hybrid density functional theory calculations were performed to clarify the results obtained by mass spectrometry.

Differentiation of diastereomeric cyclic beta-amino acids by varying the neutral reagent in ion/molecule reactions studied by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

Stereochemical differentiation of diasteromeric pairs of cis- and trans-2-aminocyclohexane-, -2-amino-4-cyclohexene-, and -2-aminocyclopentanecarboxylic acids was investigated with host-guest complexes where tetraethyl resorcarene was the host molecule. Diastereoselectivity was evaluated by ion/molecule reactions and collision-induced dissociation with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS). The effect of varying the neutral reagent (n-propylamine, i-propylamine, diethylamine, and triethylamine) in ion/molecule reactions was evaluated. Both steric interactions and proton affinity of the neutral reagents influenced the reaction rates. High proton affinity of the neutral reagent apparently had a twofold effect. If the proton affinity of the neutral reagent was too high, the reaction tended to become too exothermic and part of the host-guest complex decomposed instead of transforming to a new host-guest complex, effecting a decrease in the reaction rate. The remaining portion of the host-guest complexes meanwhile reacted very fast with the neutral reagent due to high proton affinity causing an increase in the reaction rate. n-Propylamine and i-propylamine proved to be the best neutral reagents, providing clear diastereoselectivity for beta-amino acids in ion/molecule reactions. Interestingly, diastereoselectivity was better for flexible cyclohexane beta-amino acids (2 and 3) than for more rigid cyclopentane beta-amino acids (6 and 7). The results of ab initio and hybrid density functional theory calculations on the structures of the host-guest complexes of saturated beta-amino acids were in good agreement with the experimental results.

Diastereochemical differentiation of beta-amino acids using host-guest complexes studied by Fourier transform ion cyclotron resonance mass spectrometry.

Host-guest complexes where tetraethyl resorcarene was the host molecule were used to study the stereoselectivity of diasteromeric pairs of di-endo- and di-exo-2,3-disubstituted norbornane and norbornene amino acids by ion-molecule reactions and collision-induced dissociation with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). Both methods showed stereoselectivity for the diastereomeric pairs. Particularly high selectivity was achieved for di-endo- and di-exo-2,3-disubstituted norbornane amino acids with ion-molecule reactions. Also, ab initio and hybrid density functional theory calculations were performed to study the different structures of the host-guest complexes. Hydrogen bonding was crucial for the calculated lowest energy structures, and sterical considerations satisfactorily explained the ion-molecule reaction results.