Correcting long-range electrostatic interactions in multiple hydrogen-bonded systems by experimental electron density

Supramolecular polymers have attracted considerable attention owing to their potential applications in biomedicine, molecular machines, sensing, and self-healing materials. Precise evaluation of hydrogen-bond energies is crucial for the rational design of these materials. Here, the experimental electron densities (EEDs) of three representative quadruple hydrogen-bonded dimers, ureidopyrimidinone (DDAA, DADA. D: donor; A: acceptor) and ureidotriazine (DADA), are investigated using high-resolution single-crystal X-ray diffraction. Comparative energy decomposition analyses (EDA) of the experimental and theoretical electron densities are performed. The total interaction energies from the EDA of EEDs are in good agreement with the experimentally determined binding constants, correcting the discrepancies observed in theoretical EDA and in the typical secondary electrostatic interaction model. Our results confirm the pivotal role of long-range electrostatic interactions in governing multiple hydrogen-bonded systems, and the EDA-EED approach provides a benchmark for theoretical methods that accurately describe long-range electrostatic interactions, which are fundamentally important for the development of supramolecular systems.