Separating hydration propensity from hydrogen bond donation in trifluoromethyl ketone warheads
- 1Chemistry, Stanford University Online High School, Redwood City, California, USA
Abstract
Trifluoromethyl ketones populate carbonyl and gem-diol states, but the amount of hydrate present need not report how strongly that hydrate donates a hydrogen bond. We benchmarked 14 trifluoromethyl ketones against a recent colorimetric donor-strength dataset using 198 intended Q-Chem calculations, 181 of which completed normally. In the nine-member aryl subset, experimental hydrate abundance correlated weakly with hydrate-adjusted ln K (r = 0.276), whereas ωB97X-D/def2-TZVPD/SMD parent-relative electronic hydration energies correlated strongly (r = -0.896; ρ = -0.917). Four SMD density-functional profiles were nearly superposable (pairwise r = 0.988-0.999), and local mean C-O distance independently tracked donor strength (r = -0.904). Standardized hydrate-sensor interactions at 1.80 A tracked adjusted ln K (r = -0.683) but not hydrate abundance (r = -0.033). Intramolecular hydrogen bonding stabilized closed hydrate conformers yet weakened external donor interactions. These results separate hydrate population, intrinsic donor strength, and donor accessibility as distinct design variables.
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BibTeX
@misc{tsai2026separating,
title = {{Separating hydration propensity from hydrogen bond donation in trifluoromethyl ketone warheads}},
author = {Aris Tsai},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009702/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009702/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Separating hydration propensity from hydrogen bond donation in trifluoromethyl ketone warheads
AU - Aris Tsai
PY - 2026
DA - 2026/09/30
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009702/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009702/v1
AB - Trifluoromethyl ketones populate carbonyl and gem-diol states, but the amount of hydrate present need not report how strongly that hydrate donates a hydrogen bond. We benchmarked 14 trifluoromethyl ketones against a recent colorimetric donor-strength dataset using 198 intended Q-Chem calculations, 181 of which completed normally. In the nine-member aryl subset, experimental hydrate abundance correlated weakly with hydrate-adjusted ln K (r = 0.276), whereas ωB97X-D/def2-TZVPD/SMD parent-relative electronic hydration energies correlated strongly (r = -0.896; ρ = -0.917). Four SMD density-functional profiles were nearly superposable (pairwise r = 0.988-0.999), and local mean C-O distance independently tracked donor strength (r = -0.904). Standardized hydrate-sensor interactions at 1.80 A tracked adjusted ln K (r = -0.683) but not hydrate abundance (r = -0.033). Intramolecular hydrogen bonding stabilized closed hydrate conformers yet weakened external donor interactions. These results separate hydrate population, intrinsic donor strength, and donor accessibility as distinct design variables.
ER -