Molecular Interactions within the Crystal Packing of Busulfan (DNA Cross-Linking Agent) by Hirshfeld Surface Analysis

Author(s): Datla Rajaniverma, Dasari J. Rao*, Shaikh R. Begum, Vishnubolta Seetaramaiah, Yajjala Ramakrishna, Poonam Tondon, Karthick Thangavel*

Journal Name: Current Physical Chemistry

Volume 10 , Issue 3 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Non-Covalent Interactions (NCIs) play a vital role in the chemical process. Certain Experimental and theoretical approaches provide information about the stronger and weaker interactions. In the present work, we have implemented Hirshfeld charges based surface mapping to find the weaker interactions between the molecules of busulfan.

Objective: The main objective of this work is to recognize the non-covalent interactions which are not simply drawn from the experimental and conventional theoretical approach. It aims to provide more insightful information into the crystallographic structure.

Methods: In the present work, we have implemented a Hirshfeld surface mapping which incorporates periodic boundary conditions of the crystalline geometry. Each point of the isosurface is defined by two distances i.e. de, the distance from the point to the nearest atom outside to the surface and di, the distance to the nearest atom inside the surface. Also, for precise identification of intermolecular interactions, mapping by normalized contact distance dnorm is also considered. Fingerprint plot di vs de for various types of interactions were also provided.

Results: The Hirshfeld surface and fingerprint plot show the very weak H···H interactions in addition to the O···H interactions. This enables the visualization of very weak interactions.

Conclusion: This proposed work on Hirschfeld surface analysis accounts for the solidstate environment of the busulfan, crystallographic parameters and packing information. Hence, the interactions obtained for monomer and extended molecular framework in this work are more reliable to study the intermolecular interactions. The 2D finger print plots revealed the predominant O⋅⋅⋅H interactions within the crystal packing. In addition to O⋅⋅⋅H interactions, H⋅⋅⋅H interaction were also identified.

Keywords: 2D finger print plot, busulfan, electron density, hirshfeld surface, solid state calculations, NCI.

Shit, S.; Marschner, C.; Mitra, S. Synthesis, crystal structure, and Hirschfield surface analysis of a new mixed ligand Copper(II) complex. Acta Chim. Slov., 2016, 63(1), 129-137.
[ ] [PMID: 26970797]
Kumar, V.; Jain, G.; Kishor, S.; Ramaniah, L.M. Chemical reactivity analysis of some alkylating drug molecules-A density functional theory approach. Comput. Theor. Chem., 2011, 968, 18-25.
Novak, I.; Kovac, B. On the biological activity of drug molecules: Busulfan and nabumetone. Chem. Phys. Lett., 2010, 498, 240-244.
Ghermani, N.E.; Spasojević-de Biré, A.; Bouhmaida, N.; Ouharzoune, S.; Bouligand, J.; Layre, A.; Gref, R.; Couvreur, P. Molecular reactivity of busulfan through its experimental electrostatic properties in the solid state. Pharm. Res., 2004, 21(4), 598-607.
[ ] [PMID: 15139516]
Karthick, T.; Tandon, P. Computational approaches to find the active binding sites of biological targets against busulfan. J. Mol. Model., 2016, 22(6), 142.
[] [PMID: 27240803]
Buggia, I.; Locatelli, F.; Regazzi, M.B.; Zecca, M. Busulfan. Ann. Pharmacother., 1994, 28(9), 1055-1062.
[] [PMID: 7803883]
Karthick, T.; Tandon, P.; Singh, S.; Agarwal, P.; Srivastava, A. Characterization and intramolecular bonding patterns of busulfan: Experimental and quantum chemical approach. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2017, 173, 390-399.
[] [PMID: 27697721]
Apparao, R.K.; Kaladhar, D. Genomics, proteomics and drug designing approaches on avian leukemia virus. J. Adv. Bio. Info. Applns. Res., 2011, 2, 149-154.
Keshavarz, F.; Alavianmehr, M.M.; Yousefi, R. Molecular dynamics simulation and docking studies on the binding properties of several anticancer drugs to human serum albumin. Mol. Biol. Res. Commun., 2012, 1, 65-73.
Zsila, F.; Bikadi, Z.; Malik, D.; Hari, P.; Pechan, I.; Berces, A.; Hazai, E. Evaluation of drug-human serum albumin binding interactions with support vector machine aided online automated docking. Bioinformatics, 2011, 27(13), 1806-1813.
[ ] [PMID: 21593135]
Baig, T.; Sheikh, H.; Tripathi, P.K. In-silico studies of oncogene protein with anti-cancer drugs. Global J. Biotech. Biochem., 2014, 9, 65-75.
McKenna, R.; Neidle, S.; Kuroda, R.; Fox, B.W. Structures of three DNA cross-linking agents, ethane-1,2-di(methylsulfonate), propane-1,3-di(methylsulfo nate) and n-butane-1,4-di(methylsulfonate). Acta Crystallogr. C, 1989, 45(Pt 2), 311-314.
[ ] [PMID: 2558689]
Turner, M.J.; Mckinnon, J.J.; Wolff, S.K.; Grimwood, D.J.; Spackman, P.R.; Jayatilaka, D.; Spackman, M.A. Crystal Explorer; University of Western Australia: Crawley, Australia, 2017, p. 17.
McKinnon, J.J.; Mitchell, A.S.; Spackman, M.A. Hirshfeld surfaces: A new tool for visualising and exploring molecular crystals.Chemistry, 1998, 4, 2136-2141.
[ 4:11<2136::AID-CHEM2136>3.0.CO;2-G]
Spackman, M.A.; McKinnon, J.J.; Jayatilaka, D. Electrostatic potentials mapped on Hirshfeld surfaces provide direct insight into intermolecular interactions in crystals. CrystEngComm, 2008, 10, 377-388.
Spackman, M.A.; Byrom, P.G. A novel definition of a molecule in a crystal. Chem. Phys. Lett., 1997, 267, 215-220.

open access plus

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 15 November, 2019
Page: [199 - 205]
Pages: 7
DOI: 10.2174/1877946809666191115120147

Article Metrics

PDF: 33