biostudies-literatureHao HNational Institute of General Medical SciencesNIGMS NIH HHS4411-4414https://www.ebi.ac.uk/biostudies/studies/S-EPMC9107076biostudies-literatureUnknown23(11)Lone pair-π (LP-π) interactions between Lewis basic heteroatoms, such as oxygen and sulfur, and electron-deficient π systems are important noncovalent interactions. However, they have seldom been used to control catalyst-substrate interactions in catalysis. We performed density functional theory calculations to investigate the strengths of LP-π interactions between different lone pair donors and cationic π systems, and in different complexation geometries. Energy decomposition analysis calculations indicated that the dominant stabilizing force in LP-π complexes is electrostatic interaction and the electrostatic potential surface of the π system predicts the most favorable site for forming LP-π complexes. Benzotetramisole (BTM) is revealed as a privileged acyl transfer catalyst that promotes LP-π interactions because the positive charge of the acylated BTM is delocalized onto the dihydroimidazole ring, which binds strongly with a variety of oxygen and sulfur lone pair donors.Organic lettersEnergy Decomposition Analysis Reveals the Nature of Lone Pair-π Interactions with Cationic π Systems in Catalytic Acyl Transfer Reactions.PMC9107076R35 GM128779U01 GM125290R35GM128779U01GM125290Qi XLiu PHao HTang WfalseEnergy Decomposition Analysis Reveals the Nature of Lone Pair-π Interactions with Cationic π Systems in Catalytic Acyl Transfer Reactions.Lone pair-π (LP-π) interactions between Lewis basic heteroatoms, such as oxygen and sulfur, and electron-deficient π systems are important noncovalent interactions. However, they have seldom been used to control catalyst-substrate interactions in catalysis. We performed density functional theory calculations to investigate the strengths of LP-π interactions between different lone pair donors and cationic π systems, and in different complexation geometries. Energy decomposition analysis calculations indicated that the dominant stabilizing force in LP-π complexes is electrostatic interaction and the electrostatic potential surface of the π system predicts the most favorable site for forming LP-π complexes. Benzotetramisole (BTM) is revealed as a privileged acyl transfer catalyst that promotes LP-π interactions because the positive charge of the acylated BTM is delocalized onto the dihydroimidazole ring, which binds strongly with a variety of oxygen and sulfur lone pair donors.2021-01-01T00:00:00Z2021 Jun2025-04-22T13:07:35.113Z2025-04-06T00:29:05.091ZS-EPMC91070763401001010.1021/acs.orglett.1c01351