(42h) Surprising Effect of Carbon Chain Length on Inducing Ability of Additives: Elusive Form-? of ?-Aminobutyric Acid (GABA) Induced By Sodium Carboxylate Additives

Surprising
Effect of Carbon Chain Length on Inducing Ability of Additives: Elusive Form-II
of gamma-Aminobutyric Acid (GABA) Induced by Sodium Carboxylate Additives

Lingyu
Wang^1,2, Weiwei
Tang^1,2, Junbo Gong^1,2*

¹
National Engineering Research Center of Industry Crystallization Technology,
Tianjin University, Tianjin, China;
² The
Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, Tianjin
University, Tianjin, China

Keywords:
GABA, additives-induced polymorph, carbon chain length, sodium carboxylate

Figure 1. Resulting
polymorphs of GABA obtained in presence of different additives with different
addition amounts (Green balls: Form-I; Red balls: Form-I or Form-II; Blue
balls: Form-II).

Selectively
preparing a desired polymorph in a controlled way is an issue of great concern
for pharmaceutical industry. The introduction of appropriate
additives into crystallization process represents one of important strategies
to achieve polymorphic control. Herein, we developed the strategy of
additives-induced polymorph, realizing the selective crystallization of elusive
Form-II of gamma-aminobutyric acid (GABA), a potent bioactive compound. A
series of sodium carboxylate additives with different carbon chain lengths
(C2-C8) were identified to induce the crystallization of Form-II. It was found
that additive molecules will inhibit the growth of the centrosymmetric Form-I at
two opposite ends thereby precluding it, but they will inhibit the growth of
the polar Form-II at only one end so that it survives. Notably, these sodium
carboxylate additives exhibited distinct inducing ability for Form-II (Figure 1), that is, the
effective critical addition amount required to induce Form-II increases with the increase of carbon
chain length. However,
the sodium formate is an exception and it cannot
induce the Form-II. The difference on the inducing ability of additives was
rationalized based on the competition of attachment and detachment
behavior of additives on growth end of Form-I. When the extent to which the attachment is more favorable
than the detachment is larger, the corresponding additive exhibits better
inhibition effect on Form-I and more
remarkable inducing ability for Form-II.