Role of Tailor-Made Additives in Crystallization from Solution: A Review

Abstract

Additives which share a similar molecular structure with the crystallizing parent molecule are called tailor-made additives (TMAs). The inclusion of well-chosen TMAs often has a significant impact on crystallization behaviors. However, how TMAs affect the solution crystallization has seldom been systematically summarized in recent years. Herein this paper reviews the role of TMAs in solution crystallization. First, the effects and action mechanisms of TMAs on crystal nucleation and growth are discussed, respectively. Next, the applications of TMAs in the regulation of crystal properties including the polymorphism, crystal habit, crystal size, and chirality are introduced. Then the recent progress of molecular simulation in predicting the role of TMAs is discussed. Finally, we analyze the existing problems in this field and give an outlook on the future development. This paper is helpful and useful to readers interested in the use of TMAs to control crystallization and design crystals with desired properties.

Crystal growth and morphology control of needle-shaped organic crystals

“…The influence of additives on nucleation and crystal growth has been studied extensively since the 1960s. [65][66][67][68][69][70] Like solvents, additives can adsorb onto crystal faces and hinder growth perpendicular to the face. According to the classic Cabrera and Vermilyea model, additive molecules integrate into growth sites and block the step advancement.…”

“…72 On the other hand, tailor-made additives can accelerate crystal growth via the step roughening mechanism. 70 To prevent needle growth, a high affinity and high selectivity for the fast growing capping faces is crucial. The effect of solvents and additives on the morphology of urea has been extensively studied.…”

“…72 On the other hand, tailor-made additives can accelerate crystal growth via the step roughening mechanism. 70…”

“…Additives that are structurally related to the crystallizing compound and have a similar size and shape are called tailormade additives. 69,70 Because of the structural similarity, in addition to causing steric hindrance by selectively adsorbing on specific crystal faces, they can irreversibly incorporate into the host lattice and retard crystal growth through lattice distortion. An example is the crystallization of phenytoin in the presence of ester homologues.…”

Mechanistic Insights into the Crystal Habit of d-Xylose in the Presence of Solvents and Additives

“…Controlling parameters such as temperature, solute concentration, cooling rate, and different solvents during crystal growth could also influence crystal habit . Furthermore, the effects of additives on crystal growth mechanisms have been investigated, including surfactants, polymers, and other organic compounds. − While experimental approaches can provide information on crystal habit, finding desirable crystal habits for production often requires significant time and resources. In recent years, computer-aided methods such as molecular simulations and first-principles (FP) simulations have been employed to explain and predict crystal habits, − providing a broader perspective for studying crystal habits at the molecular level.…”