A ComputationalExploration of Polymorphism and Polytypismin Anhydrous Guanine and Xanthine Biogenic Crystals

Abstract Polymorphism in molecular crystals is often discussed in terms of distinct packing arrangements, yet in many systems, the differences are more subtle and arise from variations in how similar structural motifs are stacked. In this work, we revisit this question for anhydrous guanine (AG) and xanthine (AX), two closely related purine derivatives involved in the optical effects of biogenic crystals found in living organisms, by combining crystal structure prediction with density functional theory calculations. For both compounds, we identify a rich landscape of low-energy structures that are all built from similar hydrogen-bonded molecular layers. We find that the local bonding pattern remains remarkably robust across these structures and that what differentiates some of them is the way these layers are stacked. This leads to a series of closely related structures that are better described as polytypes rather than fundamentally different polymorphs. In xanthine, the two experimentally known forms are found to be nearly degenerate in energy, and many additional structures lie within a few kcal·mol–1 of the global minimum. A similar situation is observed for guanine, although with somewhat stronger intermolecular interactions. Across both systems, electronic properties such as band gaps and refractive indices show only minor variations, reflecting the dominant role of the molecular electronic structure and the limited impact of stacking differences. In addition, we examine the role of tautomerism and show that, although alternative tautomeric forms can lead to more favorable intermolecular interactions, their higher intramolecular energy prevents them from competing with the dominant crystalline phases. Overall, our results provide a consistent picture in which polymorphism in these systems is largely governed by stacking variations of a common structural motif. This highlights the importance of polytypism in molecular crystals and offers a useful framework for understanding and predicting structural diversity in hydrogen-bonded organic solids.