Abstract
•Metformin’s interaction with solvent molecules was investigated.•Implicit solvation showed extensive solvation energy with the SMD model.•Local energy decomposition give insight to the nature of the interactions.•NBO and AIM studies support LED.•Solvent dynamics was investigated using ab initio molecular dynamics.
Metformin, brand nameGlucophage, is a medication used to regulate blood sugar levels in patients who have Type 2 diabetes. This drug has been in use for decades, and the main aim of this manuscript is to find how the drug interacts with a solvent system (water) using theoretical tools. We used PBE0-D3/def2-TZVP method for optimizations and other calculations and LED and AIMD PBE0-D3/def2-TZVP and DLPNO-CCSD(T) levels. There are five different possible locations of binding between metformin and water. Qualitative analysis of the non-covalent interactions showed hydrogen bonding interaction between them, which is confirmed by NBO and AIM studies. Local energy decomposition studies dissected the NCI quantitatively into different components. In the AIMD assay, the velocity of all atom's boundaries of metformin with solvent molecules simulations were calculated depending on time. The implicit solvation assay also shows the same result as LED and AIMD.