(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, 115%;font-family:" times new roman>Weiwei
Tang^1,2, Junbo Gong^1,2*

¹
National Engineering Research Center of Industry Crystallization Technology,
Tianjin University, Tianjin, China;
² 12.0pt;line-height:115%;font-family:" times new roman>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

text-align:center;text-indent:10.05pt;line-height:normal">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).

text-align:center;text-indent:10.0pt;line-height:normal"> 

line-height:normal">Selectively
preparing a desired polymorph in a controlled way is an issue of great concern
for pharmaceutical industry. The font-family:" times new roman>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 " times new roman> font-family:" times new roman>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) font-family:" times new roman>, 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- font-family:" times new roman>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 font-family:" times new roman>which the attachment is more favorable
than the detachment is larger, the corresponding additive exhibits better
inhibition effect on Form- font-family:" times new roman>I and more
remarkable inducing ability for Form- font-family:" times new roman>II.