Letters to the Editor Cite This: Chem. Res. Toxicol. 2018, 31, 639−640
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Addendum: Solvation Energies of Butylparaben, Benzo[a]pyrene diol epoxide, Perfluorooctanesulfonic acid, and DEHP in Complex with DNA Bases
Chem. Res. Toxicol. 2018.31:639-640. Downloaded from pubs.acs.org by ST FRANCIS XAVIER UNIV on 08/20/18. For personal use only.
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bonding energy indicates that butylparaben may be as critical as indicated by various studies suggesting endocrine effects6−9 and thus propose a ban of usage in hygienic products and consumer products. The PFOS molecule however appears more difficult to correlate to empirical findings, as PFOS has a negative charge at physiological conditions, and given the restrictions of the ANTECHAMBER10 package used in the original study,1 this charge was not possible to include. Studies on PFOS− may therefore be important for future approaches by computational toxicology and are encouraged to bring more knowledge on the mechanism of this elusive pollutant. As for DEHP, its interaction is the weakest of the four given compounds, however, favorable indeed, and also indicates that DEHP may have an interfering role on DNA under a physiological environment, and at least pose a threat to the cellular system. Ultimately, the calculations provide a rectification of the overemphasized energies that benzo[a]pyrene diol epoxide assumed in the absence of the quantum chemical solvent model in the original study1 and show that these energies, occurring in vacuum only, are not as strong as originally published and are instead in the same threshold of bonding strength as the other compounds DEHP, PFOS, and BPRB. In conclusion, the results suggest that DEHP, PRB, and BAP have similar intercalation energies; however, as BPRB and DEHP do not possess chemical reactivity to form adducts, only BAP poses an eminent carcinogenic potential. The potential of the three tested compounds, DEHP, PFOS, and BPRB to bind to the DNA noncovalently is therefore concluded to be significant and equal to benzo[a]pyrene diol epoxide; however, accounting for the molecular dynamics simulations in the original study,1 the three compounds BPRB, DEHP, and PFOS do not appear to be attracted by long-range interactions to the DNA with equal strength as the positive control BAP and tend indeed to remain outside the binding surface of the DNA in four out of five cases compared to BAP, which binds more frequently to the DNA surface forming multiple bonding complexes (3 out of 5). This may explain the known affinity that BAP has for the DNA in general and show therefore that BAP, DEHP, and PFOS display a reduced affinity to interact with a generic DNA fragment by long-range interactions.
ear Editor, the bonding mechanisms between DEHP, PFOS, butylparaben, and benzo[a]pyrene with a DNA fragment were recently published1 and showed intriguing mechanisms of complex formation between these priority pollutants and the gene core fragment of the p53 suppressor. The mechanisms were analyzed at the electronic level and important bonding data, including solvent model by molecular dynamics simulation and quantum chemical energies of electronic interaction between the pollutants and the DNA, were derived. This study did however not include the effect of the solvent on the electronic landscape of the molecules, which is the ultimate description of whether an interaction is truly favored by the ubiquitous solvent phase of water, which participates in all cellular and biomolecular mechanisms and reactions and which governs the structures of all biomolecules2. It is for this reason that we wish to submit this addendum, which finally defines the true energies of interaction of the published complexes,1 which includes the SMD solvation model.3 The calculations show that all complexes form under favorable energies when the SMD quantum chemical solvent model is included, and hence, the necessary confirmation of the favorable effects of solvent on the potential energy landscape is made for these geometries. Table 1 shows the bonding energies of the published Table 1. Accurate Bonding Energies of Published Complexes1 Using SMD Quantum Chemical Solvent Model single point energy (E) Bap1 Bap2 Bap3 DEHP PFOS PRB
complex
DNA
molecule
Ebind (kJ/mol)
−2378.91 −2570.92 −2760.74 −2734.22 −4466.66 −4326.96
−1382.30 −1574.31 −1764.13 −1495.37 −1839.37 −3673.40
−996.57 −996.57 −996.57 −1238.82 −2627.25 −653.52
−91.10 −118.75 −94.76 −74.35 −95.97 −103.46
complexes,1 which are here derived using the procedure using Gaussian16 A.03 package,4 where the geometries of complexes were optimized at B3LYP-D3(BJ)/6-311G*5 level under SMD-solvation model and a single point energy was derived to generate the energies. The results conclude that all complexes form with favorable solvated electronic energies and therefore bind selectively to the DNA in a favorable manner. Most intriguingly, butylparaben exerts a bonding strength to the DNA that is similar in magnitude to the bonding strength that benzo[a]pyrene diol epoxide displays at intercalation. This particular feature may indicate that butylparaben, which is banned in several countries, encompasses a bonding mode to the DNA that may interfere with the DNA mechanisms; however, this must be confirmed by empirical studies. Nevertheless, a similar © 2018 American Chemical Society
Sergio Manzetti*,†,‡ Tian Lu§ †
Uppsala University, Department of Cellular and Molecular Biology, Husargatan 3, SE-75124 Uppsala, Sweden ‡ Fjordforsk AS, Bygdavegen 155, 6894 Vangsnes, Norway § Beijing Kein Research Center for Natural Sciences, Beijing 100022, P. R. China Published: August 6, 2018 639
DOI: 10.1021/acs.chemrestox.8b00180 Chem. Res. Toxicol. 2018, 31, 639−640
Chemical Research in Toxicology
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Letters to the Editor
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Sergio Manzetti: 0000-0003-4240-513X
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REFERENCES
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DOI: 10.1021/acs.chemrestox.8b00180 Chem. Res. Toxicol. 2018, 31, 639−640
