Evaluation of Quantum Chemical Methods and Basis Sets Applied in the Molecular Modeling of Artemisinin

Cleydson B. R. dos Santos, Cleison C. Lobato, Josinete B. Vieira, Davi S. B. Brasil, Alaan U. Brito, Williams J. C. Macêdo, José Carlos T. Carvalho, José C. Pinheiro

Laboratory of Modelling and Computational Chemistry, Federal University of Amapá, Macapá, Brazil.
Laboratory of Theoretical and Computational Chemistry, Institute of Exact and Natural Sciences, Federal University of Pará, Belém, Brazil.
Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Campus Universitário Marcos Zero, Macapá, Brazil.

DOI: 10.4236/cmb.2013.33009                

Abstract

In this paper, we evaluate semiempirical methods (AM1, PM3, and ZINDO), HF and DFT (B3LYP) in different basis sets to determine which method best describes the sign and magnitude of the geometrical parameters of artemisinin in the region of the endoperoxide ring compared to crystallographic data. We also classify these methods using statistical analysis. The results of PCA were based on three main components, explaining 98.0539% of the total variance, for the geometrical parameters C3O13, O1O2C3, O13C12C12a, and O2C3O13C12. The DFT method (B3LYP) corresponded well with the experimental data in the hierarchical cluster analysis (HCA). The experimental and theoretical angles were analyzed by simple linear regression, and statistical parameters (correlation coefficients, significance, and predictability) were evaluated to determine the accuracy of the calculations. The statistical analysis exhibited a good correlation and high predictive power for the DFT (B3LYP) method in the 6-31G** basis set.

Keywords

Artemisinin; Molecular Modeling; Quantum Chemical Methods; Statistical Analysis; B3LYP/6-31G**

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	S. R. Meshnick, C. W. Jefford, G. H. Posner, M. A. Avery and W. Peters, “Second-Generation Antimalarial Endoperoxides,” Parasitology Today, Vol. 12, No. 2, 1996, pp. 79-82. http://dx.doi.org/10.1016/0169-4758(96)80660-0
[2]	D. L. Klayman, “Qinghaosu (Artemisinin): An Antimalarial Drug from China,” Science, Vol. 228, No. 4703, 1985, pp. 1049-1055. http://dx.doi.org/10.1126/science.3887571
[3]	A. A. C. Braga and N. H. Morgon, “Cálculos Teóricos de Afinidades por Próton De N-Alquilaminas Usando o Método Oniom,” Quimica Nova, Vol. 29, No. 2, 2009, pp. 187-193. http://dx.doi.org/10.1590/S0100-40422006000200002
[4]	M. S. Costa, R. Kiralj and M. M. C. Ferreira, “Estudo Teórico da Intera??o Existente Entre a Artemisinina e o Heme,” Quimica Nova, Vol. 30, No. 1, 2007, pp. 25-31. http://dx.doi.org/10.1590/S0100-40422007000100006
[5]	F. H. A. Leite, A. G. Taranto, M. C. Santos Junior, A. Branco, M. T. Araujo and J. W. M. Carneiro, “Search for New Antimalarial Compounds Obtained From Natural Sources by Molecular Modeling,” International Journal of Quantum Chemistry, Vol. 110, No. 11, 2010, pp. 2057-2066.
[6]	F. H. A. Leite, J. W. M.Carneiro, M. T. Araujo, M. Comar Jr. and A. G. Taranto, “Docking Between Natural Peroxides and Heme Group by Parametric Method 6,” International Journal of Quantum Chemistry, Vol. 1012, No. 20, 2012, pp. 3390-3397. http://dx.doi.org/10.1002/qua.24247
[7]	J. C. Pinheiro, R. Kiralj, M. M. C. Ferreira and O. A. S. Romero, “Artemisinin Derivatives with Antimalarial Activity against Plasmodium falciparum Designed with the aid of Quantum Chemical and Partial Least Squares Methods,” QSAR & Combinatorial Science, Vol. 22. No. 8, 2003, pp. 830-842. http://dx.doi.org/10.1002/qsar.200330829
[8]	M. G. G. Cristino, C. C. F. Meneses, M. M. Soeiro, J. E. V. Ferreira, A. F. Figueiredo, J. P. Barbosa, R. C. O. Almeida, J. C. Pinheiro and A. L. R. Pinheiro, “Computational Modeling of Antimalarial 10-Substituted Deoxoartemisinins,” Journal of Theoretical and Computational Chemistry, Vol. 11, No. 2, 2012, pp. 241-263. http://dx.doi.org/10.1142/S0219633612500162
[9]	A. F. Figueiredo, J. E. V. Ferreira, J. P. Barbosa, W. J. C. Macêdo, M. G. G. Cristino, M. S. Lobato, J. C. Pinheiro and R. T. A. Serra, “A Computational Study on Antimalarial Dispiro-1,2,4-Trioxolanes,” Journal of Computational and Theoretical Nanoscience, Vol. 8, No. 9, 2011, pp. 1847-1856. http://dx.doi.org/10.1166/jctn.2011.1892
[10]	J. Q. Araújo, J. W. M. Carneiro, M. T.Araújo, F. H. A. Leite and A. G. Taranto, “Interaction between Artemisinin and Heme. A Density Functional Theory Study of Structures and Interaction Energies,” Bioorganic & Medicinal Chemistry, Vol. 16, No. 9, 2008, pp. 5021-5029. http://dx.doi.org/10.1016/j.bmc.2008.03.033
[11]	GaussView 3.07, Gaussian, Inc.; Pittsburgh, PA, 1997.
[12]	M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople, “Gaussian 03”, Revision C.02; Gaussian, Inc., Wallingford, 2004.
[13]	J. N. Lisgarten, B. S. Potter, C. Bantuzeko and R. A. Palmer, “Structure, Absolute Configuration, and Conformation of the Antimalarial Compound, Artemisinin,” Journal of Chemical Crystallography, Vol. 28, No. 7, 1998, pp. 539-543. http://dx.doi.org/10.1023/A:1023244122450
[14]	F. H. Allen, “The Cambridge Structural Database: A Quarter of a Million Crystal Structures and Rising,” Acta Crystallographica Section B, Vol. 58, No. 01, 2002, pp. 380-388. http://dx.doi.org/10.1107/S0108768102003890
[15]	Pirouette Software, Version 3.01, Infometrix Inc., 2001.
[16]	STATISTICA (Data Analysis Software System); Version 6.1, StatSoft, Inc., 2004. http://www.statsoft.com
[17]	S. O. Silva, M. J. C. Corrêa, H. R. Bitencourt, W. R. Monteiro, J. Lameira, L. S. Santos, G. M. S. P. Guilhon and D. S. B. Brasil, “Density Functional Theory Calculations of the Nuclear Magnetic Resonance Parameters for Two Dihydrochalcones,” Journal of Computational and Theoretical Nanoscience, Vol. 9, No. 7, 2012, pp. 953-956. http://dx.doi.org/10.1166/jctn.2012.2123
[18]	M. M. C. Ferreira, “Multivariate QSAR,” Journal of Brazilian Chemical Society, Vol. 13, No. 6, 2002, pp. 742- 753. http://dx.doi.org/10.1590/S0103-50532002000600004
[19]	A. C. Gaudio and E. Zandonade, “Proposi??o, Valida??o e Análise dos Modelos que Correlacionam Estrutura Química e Atividade Biológica,” Quimica Nova, Vol. 24, No. 5, 2001, pp. 658-671. http://dx.doi.org/10.1590/S0100-40422001000500013
[20]	P. Cimino, P. L. D. Gomez, R. R. Duca and G. Bifulco, “Comparison of Different Theory Models and Basis Sets in the Calculation of 13C NMR Chemical Shifts of Natural Products,” Magnetic Resonance in Chemistry, Vol. 42, No. S1, 2004, pp. S26-S33. http://dx.doi.org/10.1002/mrc.1410
[21]	C. B. R. Santos, J. B. Vieira, A. S. Formigosa, E. V. M. Costa, M. T. Pinheiro, J. O. Silva, W. J. C. Macêdo and J. C. T. Carvalho, “Validation of Computational Methods Applied in Molecular Modeling of Artemisinin with Anti- malarial Activity,” Journal of Computational and Theoretical Nanoscience, Vol. 11, No. 3, 2014, pp. 1-9.
[22]	C. W. Jefford, “Why Artemisinin and Certain Synthetic Peroxides are Potent Antimalarials. Implications for the Mode of Action,” Current Medicinal Chemistry, Vol. 8, No. 15, 2001, pp.1803-1826. http://dx.doi.org/10.2174/0929867013371608
[23]	G. H. Posner, A. J. McRiner, I. H. Paik, S. Sur, K. Borstnik, S. Xie, T. A. Shapiro, A. Alagbala and B. Foster, “Anticancer and Antimalarial Efficacy and Safety of Artemisinin-Derived Trioxane Dimers in Rodents,” Journal of Medicinal Chemistry, Vol. 47, No. 5, 2004, pp. 1299- 1301. http://dx.doi.org/10.1021/jm0303711
[24]	S. Tonmunphean, V. Parasuk and S. Kokpol, “Automated Calculation of Docking of Artemisinin to Heme,” Journal of Molecular Modeling, Vol. 7, No. 4, 2001, pp. 26-33.
[25]	F. J. B. Cardoso, A. F. Figueiredo, M. S. Lobato, R. M. Miranda, R. C. O. Almeida and J. C. Pinheiro, “A Study on Antimalarial Artemisinin Derivatives Using MEP Maps and Multivariate QSAR,” Journal of Molecular Modeling, Vol. 14, No. 1, 2008, pp. 39-48. http://dx.doi.org/10.1007/s00894-007-0249-9
[26]	J. E. V. Ferreira, A. F. Figueiredo, J. P. Barbosa, M. G. G. Cristino, W. J. C. Macêdo, O. P. P. Silva, B. V. Malheiros, R. T. A. Serra and J. C. Pinheiro, “A Study of New Anti-malarial Artemisinins Through Molecular Modeling and Multivariate Analysis,” Journal of the Serbian Chemical Society, Vol. 75, No. 11, 2010, pp. 1533-1548. http://dx.doi.org/10.2298/JSC100126124F
[27]	A. Leach, “Molecular Modelling—Principles and Applications,” 2nd Edition, Pearson Education Limited, Upper Saddle River, 2001.
[28]	W. J. Hehre, “A Guide to Molecular Mechanics and Quantum Chemical Calculations,” Wavefunction, Inc., Irvine, 2003.
[29]	R. S. Mulliken and B. Liu, “Self-Consistent-Field Wave Functions of P2 and PO, and the Role of d Functions in Chemical Bonding and of s-p Hybridization in N2 and P2,” Journal of the American Chemical Society, Vol. 93, No. 25, 1971, pp. 6738-6744. http://dx.doi.org/10.1021/ja00754a004
[30]	I. N. Levine, “Quantum Chemistry,” 4th Edition, Prentice-Hall, New York, 1991.
[31]	M. S. C. Pereira, R. Kiralj and M. M. C. Ferreira, “Theoretical Study of Radical and Neutral Intermediates of Artemisinin Decomposition,” Journal Chemical Information and Modeling, Vol. 48, No. 1, 2008, pp. 85-98. http://dx.doi.org/10.1021/ci700011f
[32]	J. P. Barbosa, J. E. V. Ferreira, A. F. Figueiredo, R. C. O. Almeida, O. P. P. Silva, J. R. C. Carvalho, M. G. G. Cristino, J. C. Pinheiro, J. L. F. Vieira and R. T. A. Serra, “Molecular Modeling and Chemometric Study of Anti- cancer Derivatives of Artemisinin,” Journal of the Serbian Chemical Society, Vol. 76, No. 9, 2011, pp. 1263- 1282. http://dx.doi.org/10.2298/JSC111227111B
[33]	J. R. C. Carvalho, J. E. V. Ferreira, J. P. Barbosa, M. S. Lobato, C. C. F. Meneses, M. M. Soeiro, M. S. Farias, R. C. O. Almeida, K. C. Ventura, J. C. Pinheiro and A. L. R. Pinheiro, “Computational Modeling of Artemisinins with Antileishmanial Activity,” Journal of Computational and Theoretical Nanoscience, Vol. 8, No. 11, 2011, pp. 2193- 2203. http://dx.doi.org/10.1166/jctn.2011.1943
[34]	L. M. Z. G. Passari, P. K. Soares, R. E. Bruns and I. S. Scarminio, “Estatística Aplicada à Química: Dez Dúvidas Comuns,” Quimica Nova, Vol. 34, No 5. 2011, pp. 888-892. http://dx.doi.org/10.1590/S0100-40422011000500028