biostudies-literatureRummel LDeutsche Forschungsgemeinschafte202204393https://www.ebi.ac.uk/biostudies/studies/S-EPMC9401023biostudies-literatureUnknown61(29)We present an experimental and computational study on the conformers of N,N'-diphenylthiourea substituted with different dispersion energy donor (DED) groups. While the unfolded anti-anti conformer is the most relevant for thiourea catalysis, intramolecular noncovalent interactions counterintuitively favor the folded syn-syn conformer, as evident from a combination of low-temperature nuclear magnetic resonance measurements and computations. In order to quantify the noncovalent interactions, we utilized local energy decomposition analysis and symmetry-adapted perturbation theory at the DLPNO-CCSD(T)/def2-TZVPP and sSAPT0/6-311G(d,p) levels of theory. Additionally, we applied a double-mutant cycle to experimentally study the effects of bulky substituents on the equilibria. We determined London dispersion as the key interaction that shifts the equilibria towards the syn-syn conformers. This preference is likely a factor why such thiourea derivatives can be poor catalysts.Angewandte Chemie (International ed. in English)London Dispersion Favors Sterically Hindered Diarylthiourea Conformers in Solution.PMC9401023SPP 1807 (SCHR 597/27-2)Schreiner PRBecker JHausmann HDomanski MHJRummel LfalseLondon Dispersion Favors Sterically Hindered Diarylthiourea Conformers in Solution.We present an experimental and computational study on the conformers of N,N'-diphenylthiourea substituted with different dispersion energy donor (DED) groups. While the unfolded anti-anti conformer is the most relevant for thiourea catalysis, intramolecular noncovalent interactions counterintuitively favor the folded syn-syn conformer, as evident from a combination of low-temperature nuclear magnetic resonance measurements and computations. In order to quantify the noncovalent interactions, we utilized local energy decomposition analysis and symmetry-adapted perturbation theory at the DLPNO-CCSD(T)/def2-TZVPP and sSAPT0/6-311G(d,p) levels of theory. Additionally, we applied a double-mutant cycle to experimentally study the effects of bulky substituents on the equilibria. We determined London dispersion as the key interaction that shifts the equilibria towards the syn-syn conformers. This preference is likely a factor why such thiourea derivatives can be poor catalysts.2022-01-01T00:00:00Z2022 Jul2025-04-04T21:52:13.403Z2025-04-04T21:52:13.403ZS-EPMC94010233554461110.1002/anie.202204393