Interactions of imidazole with water molecules

The investigation started by generating initial configurations through global optimizations using classical potential energy. Then, a suitable functional of density functional theory (DFT) is selected between 20 functionals, including dispersion corrections, by benchmarking to the DLPNO-CCSD(T1)/CBS. The M06L-D3 functional is found to be the most accurate. The structures of the imidazole-water clusters, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>IMZ</mml:mtext> <mml:msub><mml:mrow><mml:mo>(</mml:mo> <mml:msub><mml:mtext>H</mml:mtext> <mml:mn>2</mml:mn></mml:msub> <mml:mtext>O</mml:mtext> <mml:mo>)</mml:mo></mml:mrow> <mml:mi>n</mml:mi></mml:msub> </mml:mrow> </mml:math> , <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>n</mml:mi> <mml:mo>=</mml:mo> <mml:mn>1</mml:mn> <mml:mo>-</mml:mo> <mml:mn>12</mml:mn> <mml:mo>,</mml:mo> <mml:mspace></mml:mspace> <mml:mn>64</mml:mn></mml:mrow> </mml:math> , are then optimized at the M06L-D3/def2-TZVPP level of theory. Hydration free energy and enthalpy are estimated using the cluster continuum solvation model. Calculations are performed using Gaussian 16 and ORCA suite of programs. Quantum theory of atoms in molecules (QTAIM) is performed using the AIMAll program.