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Journal of Molecular Modeling

, 25:342 | Cite as

Investigation of the reactivity indices for the formation of substituted dinitroanilines and correlations to their dockings on α-tubulin of Plasmodium falciparum

  • Inemesit A. Udofia
  • Taofeek B. Ogunbayo
  • Oluwakemi A. Oloba-Whenu
  • Chukwuemeka IsanborEmail author
  • Ponnadurai Ramasami
Original Paper
  • 37 Downloads

Abstract

The local and global reactivity descriptors of substituted dinitroaniline analogues were investigated using M06-2X/6-31 + G(d,p) method. It was observed that NH2 (m = 3.53 eV; p = 3.70 eV) substituent conveyed the highest nucleophilic character on the benzene ring system than the other groups under study. For the substrates 4-substituted-1-chloro-2,6-dinitrobenzenes, the condensed to atom electrophilicity (\( {\omega}_k^{+} \)) increases in the order COOCH3 > NO2 > F > SO3H > CN > Cl > Br. The para substituted groups with the halogens follow the order of increasing electronegativity, F > Cl > Br. However, the nucleophilicity of the halo substituents of the products increases in the order, F > Br > Cl. Molecular docking simulations using the homology model with the crystallographic structure of zinc-induced bovine tubulin heterodimer (1JFF) as one of the templates reveal that the interactions between the tubulins of Plasmodium falciparum and dinitroaniline analogues are due to H-bonding. In general, the binding interaction is with the following residues: Met137, ARG64, Lys60, Glu183, Val4, His28, Cys171, Tyr224, Asn206, 228, Ile235, and Leu238. The pKas of the residue decrease as the ring activating power of the substituents increases from strongly activating to weakly activating groups. There is no evidence of intra or intermolecular H-bonding between Arg64 and Cys171. Electronegativity (χ) gives a better generic description of the dinitroanilines than any other parameters considered. Short-range hydrophobic interaction contributes to reduced binding affinities of the ligands.

Graphical abstract

Reaction of substituted 2,6-dinitro chlorobenzene with diisopropylamine. Orbital interaction between the substrates and diisopropylamine in the formation of the dinitroanilines

Keywords

Dinitroaniline Nucleophilic aromatic substitution Substituent effects electrophilicity/nucleophilicity index 

Notes

Acknowledgments

We thank the University of Lagos, Nigeria for CRC mini research grant for computational software and equipment.

Supplementary material

894_2019_4169_MOESM1_ESM.docx (81 kb)
ESM 1 (DOCX 80 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of LagosLagosNigeria
  2. 2.Computational Chemistry Group, Department of Chemistry, Faculty of ScienceUniversity of MauritiusRéduitMauritius
  3. 3.Department of Applied ChemistryUniversity of JohannesburgJohannesburgSouth Africa

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