Crystal Growth Impedance from Slow Conformer Interconversion in Bulk Solution

Small molecules often exhibit multiple metastable conformers in solution while their crystal structures incorporate only one of the conformers. Several studies have hypothesized that slow conformer interconversion could impede the kinetics of crystal growth. This study develops coupled species and population balances to model the kinetics of conformer interconversion and crystal growth in a mixed suspension mixed product removal crystallizer at steady-state. To isolate the effects of slow interconversion, we develop, nondimensionalize, and solve two models. One model includes finite interconversion rates and the other "control"model assumes rapid interconversion such that the conformers are at equilibrium with each other in solution. Finally, we develop and analyze a version of the model in which the incorrect conformer can block sites for attachment of the growth conformer. The models show that slow interconversion causes unequal supersaturations of the two conformers in solution and reduces the total crystal volume fraction in solution, but does not alter the crystal size distribution.