Organic molecular crystals produce vivid structural colors that organisms use for communication, camouflage, and thermoregulation. Guanine crystals, in particular, are biominerals that play key optical roles in many organisms. In aqueous solutions, guanine (C₅H₅N₅O) predominantly adopts two tautomeric forms, N9-G (~90%) and N7-G (~10%), which significantly influence its modes of crystallization. The β-anhydrous guanine (β-AG) polymorph is commonly found in biological systems, often appearing as elongated prisms, yet the molecular-level mechanisms underpinning in the growth of guanine crystals remain elusive. In this presentation, we will discuss how that the major tautomer of guanine functions as a self-inhibitor by interfering with solute incorporation at the crystal surface. We synthesized β-AG crystals in both aqueous and organic media and employed in situ atomic force microscopy (AFM) for real-time growth observations at near molecular resolution. Variable-temperature FTIR and density functional theory (DFT) calculations confirmed the significance of tautomeric distributions while in situ AFM and microfluidics confirmed their role in determining the kinetics of crystallization. Moreover, because guanine crystals frequently incorporate related purines such as hypoxanthine, xanthine, and uric acid, we also investigated how these species function as potential modifiers to impact β-AG morphology and growth kinetics. AFM and scanning electron microscopy (SEM) revealed that purine analogues can switch from promoting to inhibiting growth depending on their concentration. Collectively, these findings emphasize the critical influence of tautomerism and molecular modifiers on guanine crystallization, offering deeper insights into biomineralization processes that can be more broadly applicable to other organic tautomers.
