Nucleation control, separation and bulk growth of metastable α-l-glutamic acid single crystals in the presence of l-tyrosine

The nucleation control and separation of the metastable α-l-glutamic acid polymorph from aqueous solution was successfully carried out in the presence of the selective additive l-tyrosine. The influence of different additive concentrations on the solubility, pH and nucleation time of l-glutamic acid polymorphs was revealed. It is found that below a critical level of concentration (<0.07 g/100 ml), the incorporated additive suppresses the nucleation of the commonly occurring stable β-polymorph effectively and promotes the nucleation of rarely occurring metastable α polymorph. Above the critical level, the additive suppresses completely the nucleation of both α- and β-polymorphs in the solution. For the first time, a bulk single crystal measuring size of 20×11×8 mm3 of the metastable α-l-glutamic acid was successfully grown from aqueous solution in the presence of an optimized concentration of l-tyrosine by the slow cooling method with the reversible seed rotation technique. Morphology of the grown crystals was revealed in accordance with equilibrium morphology. X-ray powder diffraction and single crystal structural refinement studies reveal that the incorporated additive molecules do not alter or enter into the crystal lattices but plays their inhibitory role only by just making their presence in the solution.

► Effect of l-tyrosine on the nucleation of l-glutamic acid polymorphs is revealed.
► Separation of α nucleation is achieved by suppressing β-nucleation in the solution.
► We report first time the critical concentration of l-tyrosine which yields only α.
► Above critical level of l-tyrosine, the solution yields neither α- nor β-nucleation.
► l-tyrosine plays its inhibitory role without entering into the crystal lattice.