Additive‐Induced Selective Crystallization of the Elusive Form‐II of γ‐Aminobutyric Acid

Abstract

The impact of two structural factors of sodium carboxylate additives on their ability to induce the selective crystallization of g-aminobutyric acid (GABA) Form-II was investigated, namely, the number of -COOgroups and the types of R groups (chain alkyl, cyclic alkyl, or phenyl). It was found that the increase of -COOgroups caused the additives lose their inducing ability. This may be attributed to the fact that the increment of hydrophilic -COOgroups results in enhanced solvation and steric effect of additives, which makes additives unable to interact with GABA effectively. Additives with different R groups all can induce Form-II but they exhibited varying inducing abilities. This could be due to the distinct results of competition between the attachment and detachment of different additives on the GABA growth end.

Selective Crystallization of l-Histidine Metastable Polymorphs: The Role and Mechanism of Additives

“…A large number of studies ,− have proved that it is a promising method to regulate polymorphs by additives. In this work, a series of TMAs were chosen to explore their impact on the polymorphic outcome of l -histidine.…”

“…In contrast, the growth of form A, with –COO – groups exposed on both the + a and − a sides, experiences inhibition on both sides of the a -axis. Consequently, form A is more seriously inhibited than form B. − , Thus, it can be inferred that when l -valine reaches a certain concentration, only form B will crystallize. This is one reason l -valine selectively crystallizes l -histidine from form B.…”

GABA-Controlled Synthesis of the Metastable Polymorphic Form and Crystallization Behavior with a Chiral Malic Acid

“…Confirming this assumption, the group of Gong produced form II of GABA by using carboxylate additives. They figured out that the size of the acetate is critical for an effective crystallization of form II. , Thereby, the acetate acts as a cap on the additive . As a consequence, both the pH and the nature of the carboxylic acid play a crucial role in the selective synthesis of form II.…”

“…In 2019, however, a novel synthesis route to form II via additives was submitted by the group of Gong, which is describing a simple synthesis of the form II. 20,21 An overview is given in Table 1.…”

“…The group also states that the metastable form will start losing its biological activity within an hour and several days, which is attributing to its thermodynamically favored relaxation to form I. , For many years, apart from sublimation and subsequent deposition, no polymorphic transition from GABA form I to GABA form II has been identified. In 2019, however, a novel synthesis route to form II via additives was submitted by the group of Gong, which is describing a simple synthesis of the form II. , An overview is given in Table .…”