Dominant non-covalent forces in diphenhydramine-8-chlorotheophylline supramolecular assembly

In this study, by applying the principles of the quantum mechanical method, we studied the molecular-level interactions present between two common drugs, namely CTP and DPH, using M062X/cc-pVDZ theory. The interactions were studied at six different sites, thus giving rise to six CTP-DPH complexes using modern computational tools. The binding energies of complexes A–F were calculated, and it was shown that the complex formation is thermodynamically favorable. Natural Bond Orbital (NBO) analysis throws light on the inter- and intramolecular interactions present in the complex. To get a detailed idea of the type of interaction, along with its strength, tools such as Quantum Theory of Atoms in Molecules (QTAIM), reduced density gradient approach (NCI-RDG) and Interaction Region Indicator (IRI) were used. The QTAIM parameters, along with the NCI and IRI results, show the presence of weaker interactions such as hydrogen bonds, van der Waals interactions. Focus was also given to analyzing the decomposition of total energy into different components using LED analysis based on DLPNO-CCSD(T) level of theory. The Local Energy Decomposition (LED) analysis goes very well with the binding energy values. The results obtained show that complex F has the highest stability among all the complexes. Also, the results calculated using different methods are consistent, supporting the dominance of weak dispersive forces. Thus, this study gives valuable information related to the interactions between these two drugs, such as their biocompatibility, complexity in pharmaceutical applications.