Jaana M. H. Pakarinen

Chiral differentiation of some cyclic β-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 β-amino acid enantiomers through ion/molecule reactions

Chiral differentiation of four enantiomeric pairs of β-amino acids, cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclopentanecarboxylic acids (cyclopentane β-amino acids), and cis-(1R,2S)-, cis-(1S,2R)-, trans-(1R,2R)-, and trans-(1S,2S)-2-aminocyclohexanecarboxylic acids (cyclohexane β-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 β-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 β-amino acids, via the kinetic method

Stereochemical differentiation of five diastereomeric pairs of β-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 β-amino acids and cyclopentane β-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 β-amino acids varied from α-amino acids to some β-amino acids. In addition, variation of the metal ion (Cu2+ and Ni2+) 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.

Methyl propionate radical cation

Examination of the reactions of the long-lived (>0.5-s) radical cations of CD3CH2COOCH3 and CH3CH2COOCD3 indicates that the long-lived, nondecomposing methyl propionate radical cation CH3CH2C(O)OCH3+· isomerizes to its enol form CH3CH=C(OH)OCH3+· (ΔHisomerization ≃ −32 kcal/mol) via two different pathways in the gas phase in a Fourier-transform ion cyclotron resonance mass spectrometer. A 1,4-shift of a β-hydrogen of the acid moiety to the carbonyl oxygen yields the distonic ion ·CH2CH2C+ (OH)OCH3 that then rearranges to CH3CH=C(OH)OCH3+· probably by consecutive 1,5- and 1,4-hydrogen shifts. This process is in competition with a 1,4-hydrogen transfer from the alcohol moiety to form another distonic ion, CH3CH2C+(OH)OCH2·, that can undergo a 1,4-hydrogen shift to form CH3CH=C(OH)OCH3+·. Ab initio molecular orbital calculations carried out at the UMP2/6-31G** + ZPVE level of theory show that the two distonic ions lie more than 16 kcal/mol lower in energy than CH3CH2C(O)OCH3+·. Hence, the first step of both rearrangement processes has a great driving force. The 1,4-hydrogen shift that involves the acid moiety is 3 kcal/mol more exothermic (ΔHisomerization=−16 kcal/mol) and is associated with a 4-kcal/mol lower barrier (10 kcal/mol) than the shift that involves the alcohol moiety. Indeed, experimental findings suggest that the hydrogen shift from the acid moiety is likely to be the favored channel.

Differentiation of diastereomeric cyclic β-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 bicyclic diols using metal complexation and collision‐induced dissociation mass spectrometry

Metal complex formation was investigated for di-exo-, di-endo- and trans-2,3- and 2,5-disubstituted trinorbornanediols, and di-exo- and di-endo- 2,3-disubstituted camphanediols using different divalent transition metals (Co(2+), Ni(2+), Cu(2+)) and electrospray ionization quadrupole ion trap mass spectrometry. Many metal-coordinated complex ions were formed for cobalt and nickel: [2M+Met](2+), [3M+Met](2+), [M-H+Met](+), [2M-H+Met](+), [M+MetX](+), [2M+MetX](+) and [3M-H+Co](+), where M is the diol, Met is the metal used and X is the counter ion (acetate, chloride, nitrate). Copper showed the weakest formation of metal complexes with di-exo-2,3-disubstituted trinorbornanediol yielding only the minor singly charged ions [M-H+Cu](+), [2M-H+Cu](+) and [2M+CuX](+). No clear differences were noted for cobalt complex formation, especially for cis-2,3-disubstituted isomers. However, 2,5-disubstituted trinorbornanediols showed moderate diastereomeric differentiation because of the unidentate nature of the sterically more hindered exo-isomer. trans-Isomers gave rise to abundant [3M-H+Co](+) ion products, which may be considered a characteristic ion for bicyclo[221]heptane trans-2,3- and trans-2,5-diols. To differentiate cis-2,3-isomers, the collision-induced dissociation (CID) products for [3M+Co](2+), [M+CoOAc](+), [2M-H+Co](+) and [2M+CoOAc](+) cobalt complexes were investigated. The results of the CID of the monomeric and dimeric metal adduct complexes [M+CoOAc](+) and [2M-H+Co](+) were stereochemically controlled and could be used for stereochemical differentiation of the compounds investigated. In addition, the structures and relative energies of some complex ions were studied using hybrid density functional theory calculations.

Ion‐molecule reactions of 2‐methoxyethanol with some amines, carboxylic acids and amino acids under chemical ionization conditions

2-Methoxyethanol chemical ionization of amines, carboxylic acids and amino acids has been found to produce numerous adduct ions. The most intense adduct ions for amines are [M + H](+) and [M + 77](+), for carboxylic acids [M + 27](+), [M + 59](+) and [M + 77](+), and for amino acids [M + H](+), [M + 13](+), [M + 27](+) and [M + 77](+). Either the adduct ion [M + H](+) or [M + 77](+) was the most abundant ion found for amino acids. The proton affinities of amino acids are noticed to control the formation of the [M + H](+) and [M + 77](+) ions. The relative abundance of [M + 13](+) and [M + 27](+) ions varied for different amino acids being most intense for phenylalanine and aspartic acid. Copyright 1999 John Wiley & Sons, Ltd.