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

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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).

A 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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Acknowledgements

The authors gratefully acknowledge the financial support from the Brazilian Research Councils: CAPES, CNPq, and FAPDF.

Funding

Financial support from the Brazilian agencies: CAPES, FAPDF, and CNPq.

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Authors and Affiliations

  1. Instituto de Física, Universidade de Brasília, Brasília, DF, Brazil

    Fernando Marques Carvalho, Yuri Alves de Oliveira Só, Alessandra Sofia Kiametis Wernik & Ricardo Gargano

  2. Instituto de Federal Goiano, Inhumas, GO, Brazil

    Mônica de Abreu Silva

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  1. Fernando Marques Carvalho
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Correspondence to Fernando Marques Carvalho.

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The online version contains supplementary material available at https://doi.org/10.1007/s00894-021-04851-9.

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All the authors participated in the conception of the study, in the discussion of the obtained results, and in the writing. F. M. C. and Y. A. O. S. performed all the calculations. All the authors read and approved the final version of the manuscript.

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Carvalho, F.M., Só, Y.A.d.O., Wernik, A.S.K. et al. Accurate acid dissociation constant (pKa) calculation for the sulfachloropyridazine and similar molecules. J Mol Model 27, 233 (2021). https://doi.org/10.1007/s00894-021-04851-9

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