Effect of additives on the preferential crystallization of L-asparagine monohydrate

Abstract

Preferential Crystallization (PC) is a popular process to separate enantiomers, however the nucleation and growth of the counter enantiomer during the process can compromise the enantiopurity of the final crystalline product. This research investigates the use of additives to inhibit the nucleation and growth of the counter enantiomer. In this study, we use Lasparagine monohydrate (L-Asn•H2O) as the preferred enantiomer in crystallization from DLAsn•H2O solutions. Additives include both pure enantiomers of several related amino acid species. This allows investigation of differences in inhibition caused by additives that are of the same chirality and different chirality as the preferred enantiomer. The additives had no discernible effect on the solubility but had a small effect on the metastable limit, with additives tending to slightly widen the metastable zone but also make the zone widths more

Particle Size Distributions and Performance of Preferential Crystallization of L‐Asparagine·H2O with Tailor‐Made Additives

“…The growth rate of L‐ Asn·H 2 O from DL‐ Asn·H 2 O with D‐ Glu and D‐ Asp is very low when compared to DL‐ Asn·H 2 O without any additives because of the inhibition of D‐ Glu and D‐ Asp on the crystal growth of L‐ Asn·H 2 O. The inhibition due to D‐ Asp is stronger than the inhibition due to D‐ Glu, and this agrees with the results of our previous study which investigated the effects of these additives on the single‐crystal growth rates of L‐ Asn·H 2 O .…”

“…The rule of reversal states that, in the PC process, a chiral additive should inhibit the solute species having the same chirality, but in this case the additive also inhibits the enantiomorph of the opposite chirality. However, D‐ Asp has a stronger inhibiting effect on the crystal growth of D‐ Asn·H 2 O, as discussed in our previous study .…”

“…The aim of the current study is to determine whether the use of tailor‐made chiral additives can increase the time during which the preferred enantiomorph can be crystallized without crystallization of the counter‐enantiomorph, thus increasing the yield and enantiopurity of the crystal product in PC. Previously, we have studied the effects of additives on the solubility, the metastable zone width, and the growth rate in the PC process , but the effect of the additives on the particle size distribution has not yet been studied. Therefore, this study investigates the effects of D‐ aspartic acid ( D‐ Asp) and D‐ glutamic acid ( D‐ Glu) on the yield and particle size distribution in PC of L‐ Asn·H 2 O from DL‐ Asn·H 2 O, also determining the crystal growth rates of L‐ Asn·H 2 O in the PC experiments.…”

“…The rate of L-AsnÁH 2 O crystallization from the DL-AsnÁH 2 O solutions appears to decrease slightly when D-Glu and D-Asp are used as additives, although the change is small compared to the experimental accuracy of the determination. A decrease in the rate of crystallization of L-AsnÁH 2 O could occur because these D-amino acid additives decrease not only the crystal growth rate of D-AsnÁH 2 O but also the crystal growth rate of L-AsnÁH 2 O, even though there is a difference in the absolute configuration of the solute and the additive[13].Theconcentration of D-AsnÁH 2 O from the PC of L-AsnÁH 2 O from DL-AsnÁH 2 O with D-Glu and D-Asp as additives is shown in Fig. 2.…”

Phase equilibria and their applications

“…Even if from an energetic point of view, both enantiomers have the same probability to crystallize, additives can be used to change the crystallization kinetics allowing only a single enantiomer to crystallize demonstrating a delicate interplay between thermodynamic equilibrium requirements and the kinetics of crystallization [32].…”