Molecular insights into solubility and crystallization of d-ribose in alcohols: combined experimental and electrostatic potential analysis

d-ribose, a key molecule in energy metabolism with wide applications in pharmaceuticals and functional foods, requires optimized crystallization for industrial production, where solubility is a critical thermodynamic parameter. Existing studies have limitations: narrow temperature ranges for solubility data (20–40 K) and insufficient understanding of how solvents affect solubility mechanisms. This study combines experimental and computational approaches: it measures d-ribose solubility in methanol, ethanol, 2-propanol, and 1-butanol across 293.15–333.15 K, analyzes the data, characterizes crystals formed in ethanol, and explores molecular interactions. Results show solubility follows the order: methanol > ethanol > 2-propanol > 1-butanol, increasing with temperature. Solubility differences correlate with solvent polarity, driven by hydrogen bonding interactions. Ethanol is identified as the optimal crystallization solvent due to moderate solubility, significant temperature sensitivity, and low toxicity. This work provides essential thermodynamic data and molecular insights for optimizing d-ribose production processes, while establishing a predictive framework for understanding functional sugar dissolution in alcoholic solvents.