Density functional theory calculation of lipophilicity for organophosphate type pesticides

Filip Ž. Vlahović, Saša Ivanović, Matija Zlatar, Maja Gruden


Density functional method with continuum solvation model is used for calculation of partition coefficient log KOW and determination of lipophilicity of 22 most frequently used organophosphate type pesticides. Excellent agreement with experimental data is obtained using three different density functional approximations (one local, one general gradient and one hybrid), and our result highlights DFT as a reliable and trustworthy method for calculation and of lipophilicity for this important class of molecules. Furthermore, calculated lipophilicity results are associated with experimentally determined LD50 and LC50 values, showing that the most toxic pesticides are these with transient characteristics (medium lipophilicity), although this concussion must be taken with a caution due to the many factors influencing the ingestion and action of a certain substance in the body beside lipophilicity.


DFT; lipophilicity; organophosphate pesticides; toxicity; partition coefficient


B. Eskenazi, A. R. Marks, A. Bradman, K. Harley, D. B. Barr, C. Johnson, N. Morga, N. P. Jewell, Environ. Health Perspect. 115 (2007) 792

M. Balali-Mood, M. Abdollahi, Basic and Clinical Toxicology of Organophosphorus Compounds, Springer, London, 2013

World Health Report, World Health Organization, Geneva, 2004

M. Eddleston, M. R. Phillips, Br. Med. J. 328 (2004) 42

C. H. S. Rao, V. Venkateswarlu, T. Surender, M. Eddleston, N. A. Buckley, Trop. Med. Int. Health 10 (2005) 581

M. Eddleston, QJM: Int. J. Med. 93 (2000) 715

P. D. Leeson, B. Springthorpe, Nat. Rev. Drug. Discov. 6 (2007) 881

L. Karalliedde, S. Feldman, J. Henry, T. Marrs, Organophosphates and Health, Imperial College Press, London, 2001

R. F. Ribeiro, A. V. Marenich, C. J. Cramer, D. G. Truhlar, Phys. Chem. Chem. Phys. 13 (2011) 10908

A. Jalan, R. W. Ashcraft, R. H. West, W. H. Green, Annu. Rep. Prog. Chem., Sect. C: Phys. Chem. 106 (2010) 211

C. Giaginis, A. Tsantili‐Kakoulidou, J. Liq. Chromatogr. Relat. Technol. 31 (2007) 79

K. Valkó, J. Chromatogr., A 1037 (2004) 299

A. Tsantili-Kakoulidou, Encyclopedia of Chromatography, 2nd ed., CRC Press, Boca Raton, FL, 2005, p. 993

S. Balaz, Chem. Rev. 109 (2009) 1793

J. Sangster, Octanol-Water Partition Coefficients: Fundamentals and Physical Chemistry, Wiley, New York, 1997

C. Giaginis, A. Tsantili-Kakoulidou, J. Pharm. Sci. 97 (2008) 2984

S. Aurijit, E. K. Glen, Curr. Top. Med. Chem. 10 (2010) 67

N. Bodor, P. Buchwald, Adv. Drug Deliv. Rev. 36 (1999) 229

M. Michalík, V. Lukeš, Acta Chim. Slov. 9 (2016) 89

C. J. Cramer, D. G. Truhlar, Chem. Rev. 99 (1999) 2161

J. Tomasi, M. Persico, Chem. Rev. 94 (1994) 2027

A. V. Marenich, C. J. Cramer, D. G. Truhlar, J. Phys. Chem., B 113 (2009) 6378

J. Tomasi, B. Mennucci, R. Cammi, Chem. Rev. 105 (2005) 2999

C. J. Cramer, D. G. Truhlar, Acc. Chem. Res. 41 (2008) 760

K. S. A. M. Shweshein, F. Andric, A. Radoicic, M. Zlatar, M. Gruden-Pavlovic, Z. Tesic, D. Milojkovic-Opsenica, Sci. World J. 2014 (2014) 10

M. Remko, M. Swart, F. M. Bickelhaupt, Bioorg. Med. Chem. 14 (2006) 1715

C. C. R. Sutton, G. V. Franks, G. da Silva, J. Phys. Chem., B 116 (2012) 11999

E. L. M. Miguel, P. L. Silva, J. R. Pliego, J. Phys. Chem., B 118 (2014) 5730

M.-H. Baik, R. A. Friesner, J. Phys. Chem., A 106 (2002) 7407

R. E. Skyner, J. L. McDonagh, C. R. Groom, T. van Mourik, J. B. O. Mitchell, Phys. Chem. Chem. Phys. 17 (2015) 6174

M. Kolář, J. Fanfrlík, M. Lepšík, F. Forti, F. J. Luque, P. Hobza, J. Phys. Chem., B 117 (2013) 5950

M. J. Frisch, G. W. Trucks, H. B. Schlegel, Gaussian 09, Revision D.02, 2016

J. P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett. 77 (1996) 3865

J. P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett. 78 (1997) 1396

Y. Zhao, D. G. Truhlar, J. Chem. Phys. 125 (2006) 194101

Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 120 (2008) 215

P. C. Hariharan, J. A. Pople, Theor. Chim. Acta 28 (1973) 213

R. F. Ribeiro, A. V. Marenich, C. J. Cramer, D. G. Truhlar, J. Phys. Chem., B 115 (2011) 14556

Y. C. Martin, J. Med. Chem. 39 (1996) 1189

J. Sangster, J. Phys. Chem. Ref. Data 18 (1989) 1111

C. T. Garten, J. R. Trabalka, Environ. Sci. Technol. 17 (1983) 590

B. T. Bowman, W. W. Sans, J. Environ. Sci. Health, B 18 (1983) 667

P. Pernot, B. Civalleri, D. Presti and A. Savin, J. Phys. Chem., A 119 (2015) 5288

N. Bodor, P. Buchwald, Retrometabolic Drug Design and Targeting, Wiley, New York, 2012

P. Keen, in Concepts in Biochemical Pharmacology: Part 1, B. B. Brodie, J. R. Gillette, H. S. Ackerman, Eds., Springer, Heidelberg, 1971, p. 213

L. Shargel, A. Yu, S. Wu-Pong, Applied Biopharmaceutics & Pharmacokinetics, 6th ed., McGraw-Hill Education, New York, 2012.


Copyright (c) 2017 J. Serb. Chem. Soc.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

IMPACT FACTOR 0.828 (140 of 172 journals)
5 Year Impact Factor 0.917 (140 of 172 journals)