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Stability constants of Cu(II)/indomethacin mononuclear complexes in solution

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Abstract

The stability constants of the non-steroidal anti-inflammatory drug indomethacin mononuclear copper complexes, Cu(Indo)+ and Cu(Indo)2, were calculated by thermodynamic cycles in the frame of density functional theory. The BH&HLYP functional with LANL2DZ and Def2SVP basis set for copper ion and lighter atoms, respectively, were used to perform the search of minimums, and to consider thermal corrections in gas phase. For the minimums found, electronic energies were evaluated by performing single point calculations, using the basis set LANL2TZ+f for copper ion and the 6-311++G(2d,2p) for the rest. To include the continuum contribution to the solvation energy, the solvation model based on density was applied. Cluster/continuum model yields acceptable results in predicting solvation energies of Cu(II) ion and proton with deviations of 4.2 and 4.7 kcal/mol at the worked level of theory. Cluster/continuum calculations of Cu(Indo)+ and Cu(Indo)2 complexes stability constants, reported as logβ, predict 1.65 and − 3.17 in water and 15.9 and 26.7 in ethanol. We also apply the ion-exchange thermodynamic cycle, which aims error cancelation through structural similarity between species in both sides of chemical reactions. Encouraging results are obtained for Cu(Indo)2 stability constant in ethanol, logβ = 16.37, differing just 2.32 units from the experimental value. Structural features and charge distribution, of the species involved in the complexation reaction, are discussed to rationalize the performing of thermodynamic cycles in predicting complexation stability constants.

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Acknowledgements

Raúl Flores acknowledges DGAPA-UNAM for the postdoctoral fellowship. LIR-G acknowledges to CONACyT for the PhD scholarship. The authors gratefully acknowledge the computing time granted by LANCAD and CONACYT on the supercomputer Yoltla/Miztli/Xiuhcoatl at LSVP UAM-Iztapalapa/DGTIC UNAM/CGSTIC CINVESTAV.

Funding

This work was supported by UNAM-PAPIIT IN218118, PIAPI1846-FESC-UNAM and LANCAD-UNAM-DGTIC-058.

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  1. Raúl Flores, Luis I. Reyes-García, Norma Rodríguez-Laguna and Rodolfo Gómez-Balderas have contributed equally to this work.

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  1. Laboratorio de Fisicoquímica Analítica, Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, C.P. 54700, Cuautitlan Izcalli, State of Mexico, Mexico

    Raúl Flores, Luis I. Reyes-García, Norma Rodríguez-Laguna & Rodolfo Gómez-Balderas

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Correspondence to Rodolfo Gómez-Balderas.

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Flores, R., Reyes-García, L.I., Rodríguez-Laguna, N. et al. Stability constants of Cu(II)/indomethacin mononuclear complexes in solution. Theor Chem Acc 137, 125 (2018). https://doi.org/10.1007/s00214-018-2315-z

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