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Accurate acid dissociation constant (pKa) calculation for the sulfachloropyridazine and similar molecules

Authors
  • Carvalho, Fernando Marques1
  • Só, Yuri Alves de Oliveira1
  • Wernik, Alessandra Sofia Kiametis1
  • Silva, Mônica de Abreu2
  • Gargano, Ricardo1
  • 1 Universidade de Brasília, Brasília, DF, Brazil , Brasília (Brazil)
  • 2 Instituto de Federal Goiano, Inhumas, GO, Brazil , Inhumas (Brazil)
Type
Published Article
Journal
Journal of Molecular Modeling
Publisher
Springer-Verlag
Publication Date
Jul 29, 2021
Volume
27
Issue
8
Identifiers
DOI: 10.1007/s00894-021-04851-9
Source
Springer Nature
Keywords
Disciplines
  • VIII Symposium on Electronic Structure and Molecular Dynamics – VIII SeedMol
License
Yellow

Abstract

Accurate calculation of the acid dissociation constant (pKa) has fundamental importance for the description of molecular systems with pharmacological activities. The search for a more appropriate procedure for its determination is always welcome and has aroused increasing interest from the scientific community. In this sense, this work presents a computational study involving the combination of ten DFT functionals (M062X, M06L, B3LYP, BLYP, PBEPBE, BP86, LC-BLYP, SPBE, CAM-B3LYP, LC-PBEPBE) and HF method, eight basis set functions (6-311G, 6-311 + G, 6-311G(d,p), 6-311 + G(d,p), 6-311+ +G(d,p), 6-311(2d,2p), 6-311+ +G(2d,2p), and aug-cc-pVDZ), and three solvation models (SMD, PCM, and CPCM) for an accurate sulfachloropyridazine (SCR) pKa determination. It was found that the smallest deviation (0.02 unit of pKa) between the current study and experimental result was achieved with the BLYP/6-311 + G(d,p)/PCM combination. Therefore, this combination was extended to calculate the pKa of six SCR similar molecules selected through the eletroshape similarity method. For all these molecules, the difference between the obtained results and experimental data ranged between 0.14 and 0.69 units of pKa. This feature suggests that the obtained combination can determine pKa with experimental precision for complexes that are formed by sulfonamide functional group (SO2NHR). Graphical AbstractA computational study involving the combination of different levels of theory, basis sets and solvation models for an accurate sulfanamide pKa determination.

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