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

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.