research papers 982 https://doi.org/10.1107/S2053229620012589 Acta Cryst. (2020). C76, 982–991 Received 28 August 2020 Accepted 15 September 2020 Edited by P. Fanwick, Purdue University, USA Keywords: cation– interaction; Altretamine; DFT; AIM; NBO; hexamethylmelamine; crystal structure; anticancer drug; computational chemistry. Supporting information: this article has supporting information at journals.iucr.org/c The effect of cation–p interactions on the stability and electronic properties of anticancer drug Altretamine: a theoretical study Fahimeh Alirezapour* and Azadeh Khanmohammadi Department of Chemistry, Payame Noor University, PO Box 19395-3697 Tehran, Iran. *Correspondence e-mail: fahimehalirezapour@yahoo.com The present work utilizes density functional theory (DFT) calculations to study the influence of cation– interactions on the electronic properties of the complexes formed by Altretamine [2,4,6-tris(dimethylamino)-1,3,5-triazine], an anticancer drug, with mono- and divalent (Li + , Na + ,K + , Be 2+ , Mg 2+ and Ca 2+ ) metal cations. The structures were optimized with the M06-2X method and the 6-311++G(d,p) basis set in the gas phase and in solution. The theory of ‘Atoms in Molecules’ (AIM) was applied to study the nature of the interactions by calculating the electron density (r) and its Laplacian at the bond critical points. The charge-transfer process during complexation was evaluated using natural bond orbital (NBO) analysis. The results of DFT calculations demonstrate that the strongest/weakest interactions belong to Be 2+ /K + complexes. There are good correlations between the achieved densities and the amounts of charge transfer with the interaction energies. Finally, the stability and reactivity of the cation– interactions can be determined by quantum chemical computation based on the molecular orbital (MO) theory. 1. Introduction The development of anticancer drugs began four decades ago with the unexpected discovery of the antitumour activity of drugs and their successful use in the behaviour of various cancer cells (Spiegel & Magistrato, 2006; Deepa et al., 2012). Altretamine (trade name Hexalen) is an anticancer chemo- therapeutic drug that works by reducing or stopping the growth of cancer cells (Keldsen et al., 2003). It is known chemically as hexamethylmelamine, which has the empirical formula C 9 H 18 N 6 . Altretamine (ALT) belongs to the group of pharmaceuticals called antineoplastics (Damia & D’Incalci, 1995). In fact, ALT is a novel synthetic cytotoxic antineoplastic s-triazine derivative. This drug is cell cycle nonspecific and works by damaging DNA (Lemke & Williams, 2008). ALT has been shown to be effective for some ovarian tumours resistant to classical alkylating agents (Keldsen et al., 2003; Chan, 2004). The antitumour activity of ALT is attributed to the N-methyl moieties and has the advantage of less toxicity with respect to other drugs (Damia & D’Incalci, 1995; Malik, 2001). A number of experimental methods based on gas–liquid chro- matography with nitrogen-sensitive detection and mass spec- trometery (Morimoto et al. , 1980; Hulshoff et al. , 1980; D’Incalci et al., 1979; Gescher et al., 1980; Klippert et al., 1983) have been applied for the analysis of ALT. The importance of noncovalent interactions in chemistry cannot be underestimated. These interactions (hydrogen bonding, -stacking, cation–, etc.) are important in molecular biology, drug design and supramolecular chemistry (Waters, ISSN 2053-2296 # 2020 International Union of Crystallography