Atomic Decomposition Scheme of Noncovalent Interactions Applied to Host–Guest Assemblies

The design of novel stimuli-responsive supramolecular systems based on host-guest chemistry implies a thorough understanding of the noncovalent interactions involved. In this regard, some computational tools enabling the extraction of the noncovalent signatures from local descriptors based on the electron density have been previously proposed. Although very useful to detect the existence of such interactions, these analyses provide only a semi-quantitative description, which represents a limitation. In this work, we present a novel computational tool based on the local atomic descriptor IGM-δ<i>g</i>^inter/At, which is able to decompose the fragment interaction into atomic contributions. Then, the role played by each atom in the formation of the host-guest assembly is quantified by an integrated Δ<i>g</i>^inter/At score. Herein, we apply the IGM-Δ<i>g</i>^inter/At approach to some challenging systems, including multimetallic arrays, buckycatchers, and organic assemblies. These systems exhibit unique structural features that make it difficult to determine the host/guest atoms that contribute the most to the guest encapsulation. Here, the Δ<i>g</i>^inter/At score proves to be an appealing tool to shed light on the guest accommodation on a per-atom basis and could be useful in the rational design of more selective target agents. We strongly believe that this novel approach will be useful for experimental teams devoted to the synthesis of supramolecular systems based on host-guest chemistry.