Bulk and Surface Conformations in Solid-State Lovastatin: Spectroscopic and Molecular Dynamics Studies

Conformational flexibility in molecules can give rise to a range of functional group terminations at crystal surfaces and dynamic disorder the bulk. In this work, we explore conformational behavior drug molecule lovastatin crystallographically disordered solid through combination computational modeling spectroscopy. Gas-phase periodic quantum-chemical calculations are used study potential energy surface associated with rotatable bonds examine These combined vibrational X-ray photoelectron spectroscopy measurements obtain insight into conformations bulk surface. Our MD simulations show that is driven by cooperative motion butyl on S-butanoate moiety along one crystallographic direction beyond unit cell. The O-H rotate relatively freely between two low-energy conformers gas phase but locked position intermolecular H-bonding interactions crystal, find tentative spectroscopic evidence for second conformer being present We also comment relative utility these different techniques studying molecular conformation highlight possible areas future developments.