Engineering Chirality in the Solid State: Co-Crystallization as a Strategy for Chiral Induction and Resolution.

Chirality plays a fundamental role in chemistry, biology, and materials science, where molecular activity and performance often depend on enantiomeric purity. However, most synthetic methods produce racemic mixtures, making efficient strategies for enantioseparation and chiral amplification essential. Among the available approaches, crystallization-based methods offer scalable and mechanistically versatile routes for controlling chirality in the solid state. This review summarizes recent advances in solid-state crystallization strategies for chiral resolution, chirality generation, and enantiomeric amplification. Emphasis is placed on the structural and thermodynamic factors governing the formation of racemic compounds, conglomerates, and solid solutions, and how these phase behaviors influence separation outcomes. Key methodologies including preferential crystallization, attrition-enhanced deracemization, and multicomponent crystallization via diastereomeric salts and chiral co-crystals are discussed to illustrate how rational control of intermolecular interactions and phase equilibria enables effective enantioseparation. Emerging insights into supramolecular symmetry breaking and confinement-driven chiral amplification are also highlighted, demonstrating that solid-state processes can generate or amplify chirality even from achiral precursors. By integrating representative examples with broader conceptual analysis, this review outlines key design principles governing chiral outcomes in crystalline systems and highlights expanding applications of chiral co-crystals in pharmaceuticals and as functional materials, providing a framework for future advances in crystallization-mediated chirality control.