Theoretical insights on the interaction between p-synephrine and Metformin: A DFT, QTAIM and Drug-Likeness investigation

[Display omitted] •Theoretical calculations evaluated using DFT method to locate the interaction sites of P-Synephrine with type 2 diabetes drug Metformin.•QTAIM calculations show promising hydrogen bond energies exhibiting the interaction to be of partial covalent type.•PCM calculation shows the adsorption process is spontaneous, and complexes are soluble in polar solvents.•SWISS ADME analysis depicts that the complexation is orally bio-available. Metformin (MET) known to be an effective drug for type 2 diabetes is interacted with a well known herb P-synephrine (P-SNY) applying density functional theory (DFT) method for combinational drug therapy. Analysis on the geometry and vibrational characteristics confirmed the presence of non-covalent interaction between the hydroxyl and amine groups of herb and drug respectively. The quantum theory of atoms in molecule (QTAIM) is implied to understand the nature of bonds and strength of the interaction. In order to identify the donor, acceptor and further estimate the amount of charges transferred between the herb and drug, natural bond analysis is performed. Furthermore, in order to understand the drug actions, adsorption, distribution, metabolism and excretion (ADME) properties are studied using the SwissADME online tool. The overall study confirms the interaction between MET and P-SNY and additionally these findings can support the experimental community in the design of a new novel hybrid drug combination for the treatment of type 2 diabetes.