Topology of electron density and electrostatic potential of HIV reverse transcriptase inhibitor zidovudine from high resolution X-ray diffraction and charge density analysis

Iruthayaraj, Ancy and Chinnasamy, Kalaiarasi and Jha, Kunal Kumar and Munshi, Parthapratim and Pavan, Mysore S and Kumaradhas, Poomani (2019) Topology of electron density and electrostatic potential of HIV reverse transcriptase inhibitor zidovudine from high resolution X-ray diffraction and charge density analysis. In: JOURNAL OF MOLECULAR STRUCTURE, 1180 . pp. 683-697.

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Abstract

Azidothymidine (AZT) is a first anti-HIV drug namely Zidovudine used for HIV treatment, which binds to the viral DNA primer and inhibits the HIV reverse transcription. The side effects of this powerful drug are severe and the detailed understanding of its electronic structure helps to design new drugs from the AZT molecule. Present study aims to determine the structure of AZT at electronic level from the experimental charge density analysis as well as the solid state DFT calculations. AZT was crystallized and low temperature high resolution X-ray diffraction intensity data has been measured up to sin (theta/lambda)(max) = 1.1 angstrom(-1) at 100.0 (2) K. The crystal structure of AZT was determined, which reveals the information that the AZT compound crystallizes with two molecules in the asymmetric unit which are conformationally different and linked through strong hydrogen bonding interactions (dimer). The Hirshfeld surface of both molecules shows the locations of weak and strong interactions. Further, a multipole model refinement was carried out using Hansen-Coppens multipole formalism. The experimental topological properties of electron density of AZT molecules were determined and compared with the results of theoretical DFT calculations based on solid state and gas phase studies. The charge density distribution of the two molecules in the asymmetric unit is unequal and shows some difference. The topological properties of O-H center dot center dot center dot O, O-H center dot center dot center dot N, C-H center dot center dot center dot N, H center dot center dot center dot H and azide center dot center dot center dot azide group interactions are also determined. The electrostatic potential (ESP) surface of both AZT molecules in the crystal exhibits high electronegative regions around the O, N atoms and also around the azide group, however, ESP regions of molecules (I) and (II) are not similar. (C) 2018 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Publication:	JOURNAL OF MOLECULAR STRUCTURE
Publisher:	ELSEVIER SCIENCE BV
Additional Information:	Copyright of this article belongs to ELSEVIER SCIENCE BV
Keywords:	Zidovudine; Hirshfeld surface; Experimental charge density; Intermolecular interactions; Electrostatic potential
Department/Centre:	Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	22 Feb 2019 05:29
Last Modified:	22 Feb 2019 05:29
URI:	http://eprints.iisc.ac.in/id/eprint/61801

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