The Effect and Counter-Effect of Impurities on Crystallization of an Agrochemical Active Ingredient: Stereochemical Rationalization and Nanoscale Crystal Growth Visualization

The molecular mechanisms underpinning the effects of impurities (reaction byproduct) on the crystallization of N-phosphonomethyl glycine (PMG), a common herbicide, are presented. The impurities, iminobismethylene phosphonic acid (IMPA) and amino methyl phosphonic acid (AMPA), were incorporated into PMG crystals by selectively adsorbing onto the (100) face, and subsequently, caused major reduction in the growth rate of this face of the crystal. In contrast, the impurity N-phosphonomethyl imino diacetic acid (PIDA), with a lower binding affinity to PMG crystals, did not affect the crystal habit significantly. These experimental results are rationalized based on stereospecific interaction of the impurities with the PMG crystal and binding energy calculations. Interestingly, when PIDA is present along with IMPA or AMPA in the crystallizing solution, it produced a beneficial effect by counteracting the habit-modifying effects of the other two impurities. In situ monitoring of crystal growth from pure and impure supersaturated aqueous solution using an atomic force microscope revealed that IMPA slowed down the propagation of steps on the (100) surface of PMG crystal and, in contrast, PIDA accelerated the propagation of steps on the crystal surface. On the basis of these observations, it is surmised that interaction of PIDA at the kink sites on the crystal surface reduced the step free energy and, in turn, led to resurrection of crystal growth from the inhibitory effect of IMPA.