Why Is α- D -Glucose Monomorphic? Insights from Accurate Experimental Charge Density at 90 K

d-glucose is a strategic chemical for agri-food and pharma industries, which are now exploiting an expected increase of 5% in the global investment round from 2020 to 2028. Despite such a broad industrial interest, the reasons behind room-p monomorphism in d-glucose are unclear. The crystal structure of α-d-glucose is provided here with an unprecedented resolution (0.46 Å) by single-crystal X-ray diffraction at T = 90(1) K. Occurrence of anomeric disorder in the α phase, which has not been reported to date, is demonstrated. The topological analysis of the total charge density distribution is also carried out within the framework of Bader's Quantum Theory of Atoms in Molecules, allowing to rank the relative strength of hydrogen bonds in the crystal structure. It is found that most OH···O contacts have a significant covalent character and build up an exceptionally stiff three-dimensional hydrogen bond network. On the one hand, this locks the molecular conformation by hampering the rotational flexibility of the hydroxy substituents. On the other hand, favorable recognition modes, based on the interaction of the charge density distributions of glucose molecules, cooperatively account for the lattice cohesion. A change in the relative orientation of OH groups would affect the crystal cohesion by changing locally the molecular electrostatic potential, V(r).