{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pezzola S"],"funding":["Ministry of Education, Universities and Research"],"pagination":["1255"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10974196"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(6)"],"pubmed_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."],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Towards the \"Eldorado\" of pKa Determination: A Reliable and Rapid DFT Model."],"pmcid":["PMC10974196"],"funding_grant_id":["2022KPK8WM"],"pubmed_authors":["Sabuzi F","Venanzi M","Conte V","Galloni P","Pezzola S"],"additional_accession":[]},"is_claimable":false,"name":"Towards the \"Eldorado\" of pKa Determination: A Reliable and Rapid DFT Model.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-26T11:29:26.862Z","creation":"2025-04-06T13:40:34.792Z"},"accession":"S-EPMC10974196","cross_references":{"pubmed":["38542892"],"doi":["10.3390/molecules29061255"]}}