RESEARCH ARTICLE Quantitative Analysis of Intermolecular Interactions in 7-Hydroxy-4-methyl-2H-chromen-2-one and Its Hydrate Piyush Panini • K. N. Venugopala • B. Odhav • Deepak Chopra Published online: 9 March 2014 Ó The National Academy of Sciences, India 2014 Abstract The determination of the crystal and molecular structure of organic compounds has contributed immensely towards the area of crystal engineering. This contributes towards the understanding of the molecular geometry and the different intermolecular interactions which control crystal packing. An approach which quantifies the ener- getics associated with the formation of different ‘‘molec- ular pairs’’ is of importance to recognize the hierarchy of intermolecular interactions present in the crystal. We intend to explore different computational tools which contribute towards the field of crystal engineering. In this regard, the crystal structure of 7-hydroxy-4-methyl-2H- chromen-2-one and its hydrate were re-determined and their crystal packing were analyzed in terms of the inter- action energy of different intermolecular interactions, cal- culated by PIXEL method, contributing towards the stabilization of the crystal packing. The system is so cho- sen such that it allows the analysis of weak interactions like C–HO, C–Hp, pp, lpp etc. in the presence of strong O–HO hydrogen bonds and also allows for a systematic exploration of the effect of solvent (water in the present case) on the crystal packing. The calculation of the lattice energy reveals that the anhydrous form is 7 kcal/mol more stable than the corresponding hydrate. The major stabilization towards the crystal packing were observed to come from strong O–HO=C hydrogen bonds (9 kcal/ mol) in case of the anhydrous form while in case of its hydrate, water acts as both an acceptor and a donor of the hydrogen bonds, the interaction energy ranging from 5 to 9 kcal/mol. The weak C–HO hydrogen bond were found to be the second highest contributor (I.E = 3.5–5.5 kcal/ mol) towards the stabilization of the packing in both the crystal structures. The main differences in the crystal packing were observed in the presence of weaker interac- tions in their crystal packing. The weak C–Hp, O(lp)C=O interactions were observed in the crystal packing of the anhydrous form while the pp, O(lp)p interactions stabilize the crystal packing in case of its hydrate. This phenomenon were further well supported by the analysis of the Hirshfeld surfaces mapped with differ- ent properties, 2D-fingerprint plots, electrostatic potential mapped on the Hirshfeld surface and electron density iso- surface (calculated by ab initio calculation at DFT-D3/ B97-D) at both solid state and optimized geometry. Keywords Coumarin  Hirshfeld  PIXEL  Molecular pairs  Intermolecular interactions Introduction Coumarin derivatives are found to exhibit a wide range of biological activities such as anticoagulant, anti-inflamma- tory, anti-carcinogenic, antioxidant and antibiotic activities [1–6]. It is used as an inhibitor for protein tyrosine phosphatase 1B, acetyl cholinesterase and monoamine oxidase [7–9]. In addition, the 2H-chromen-2-one deriva- tives have also received attention in the area of dye and pigment industries as it is useful in the production of fluorescent materials [10]. The related derivatives of these class of compounds are also widely explored in the area of P. Panini  D. Chopra (&) Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Indore By-pass Road, Bhauri, Bhopal 462066, Madhya Pradesh, India e-mail: dchopra@iiserb.ac.in K. N. Venugopala  B. Odhav Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa 123 Proc. Natl. Acad. Sci., India, Sect. A Phys. Sci. (April–June 2014) 84(2):281–295 DOI 10.1007/s40010-014-0143-7