The selection of a “perfect tool” for the theoretical determination of acid-base dissociation constants (Ka) is still puzzling. Recently, we developed a user-friendly model exploiting CAM-B3LYP for determining pKa with impressive reliability. Herein, a new challenge is faced, examining a panel of functionals belonging to different rungs of the “Jacob’s ladder” organization, which classifies functionals according to their level of theory. Specifically, meta-generalized gradient approximations (GGAs), hybrid-GGAs, and the more complex range-separated hybrid (RSH)-GGAs were investigated in predicting the pKa of differently substituted carboxylic acids. Therefore, CAM-B3LYP, WB97XD, B3PW91, PBE1PBE, PBEPBE and TPSSTPSS were used, with 6-311G+(d,p) as the basis set and the solvation model based on density (SMD). CAM-B3LYP showed the lowest mean absolute error value (MAE = 0.23) with relatively high processing time. PBE1PBE and B3PW91 provided satisfactory predictions (MAE = 0.34 and 0.38, respectively) with moderate computational time cost, while PBEPBE, TPSSTPSS and WB97XD led to unreliable results (MAE > 1). These findings validate the reliability of our model in predicting carboxylic acids pKa, with MAE well below 0.5 units, using a simplistic theoretical level and a low-cost computational approach.

Pezzola, S., Venanzi, M., Galloni, P., Conte, V., Sabuzi, F. (2024). Towards the “Eldorado” of pKa Determination: A Reliable and Rapid DFT Model. MOLECULES, 29(6) [10.3390/molecules29061255].

Towards the “Eldorado” of pKa Determination: A Reliable and Rapid DFT Model

Pezzola S.;Venanzi M.;Galloni P.;Conte V.
;
Sabuzi F.
2024-01-01

Abstract

The selection of a “perfect tool” for the theoretical determination of acid-base dissociation constants (Ka) is still puzzling. Recently, we developed a user-friendly model exploiting CAM-B3LYP for determining pKa with impressive reliability. Herein, a new challenge is faced, examining a panel of functionals belonging to different rungs of the “Jacob’s ladder” organization, which classifies functionals according to their level of theory. Specifically, meta-generalized gradient approximations (GGAs), hybrid-GGAs, and the more complex range-separated hybrid (RSH)-GGAs were investigated in predicting the pKa of differently substituted carboxylic acids. Therefore, CAM-B3LYP, WB97XD, B3PW91, PBE1PBE, PBEPBE and TPSSTPSS were used, with 6-311G+(d,p) as the basis set and the solvation model based on density (SMD). CAM-B3LYP showed the lowest mean absolute error value (MAE = 0.23) with relatively high processing time. PBE1PBE and B3PW91 provided satisfactory predictions (MAE = 0.34 and 0.38, respectively) with moderate computational time cost, while PBEPBE, TPSSTPSS and WB97XD led to unreliable results (MAE > 1). These findings validate the reliability of our model in predicting carboxylic acids pKa, with MAE well below 0.5 units, using a simplistic theoretical level and a low-cost computational approach.
2024
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore CHIM/06
English
Con Impact Factor ISI
B3PW91
CAM-B3LYP
carboxylic acid
computational pKa
DFT
direct approach
Jacob’s ladder
PBEPBE
PEBE1PBE
pKa
solvation model based on density (SMD)
TPSSTPSS
WB97XD
Pezzola, S., Venanzi, M., Galloni, P., Conte, V., Sabuzi, F. (2024). Towards the “Eldorado” of pKa Determination: A Reliable and Rapid DFT Model. MOLECULES, 29(6) [10.3390/molecules29061255].
Pezzola, S; Venanzi, M; Galloni, P; Conte, V; Sabuzi, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/361903
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