Theoretical Characterization of the Hydrogen Bonding Interaction Sites of Mycolactone C Using the ONIOM Method

Abstract

In this work, the ONIOM method, recognized for its effectiveness on large molecules, was used to determine the geometric, energetic, and spectroscopic parameters of hydrogen bond interactions of mycolactone C. Mycolactone C; one of the most virulent forms of toxin, found in Africa and Australia. It has eight (08) oxygen heteroatoms which are all hybridized sp2 and sp3. Using quantum chemistry methods, at the ONIOM level (B3LYP/6-311+G (d, p): AM1), we have determined the preferential binding sites of the hydrogen bonds in the eight mycolactone C oxygen heteroatoms studied. Analysis of the results revealed that the heteroatom O5sp2 is the most suitable site for creating a strong hydrogen bond based on the geometric, energetic (free enthalpy of complexation), and spectroscopic (vibration frequency shifts) parameters. Identifying this O5sp2 heteroatom is a significant step forward in developing a methodology for eradicating the infection and the destructive effects of this toxin.