VCD spectroscopy reveals that a water molecule determines the conformation of azithromycin in solution†

We report the IR and VCD spectra of azithromycin, a macrolide antibiotic with a total of 18 stereogenic centers. The computational analysis of the spectra reveals that a single water molecule has to be considered in the conformational search. Its key role is the stabilization of an extended hydrogen bonding network and an otherwise unstable conformation that determines the VCD spectral signatures.

Automated summary

In this study, the IR and VCD spectra of azithromycin were reported, with computational analysis revealing the importance of a single water molecule in stabilizing the hydrogen bonding network and determining the VCD spectral signatures. The presence of this water molecule was essential for understanding the conformational dynamics of azithromycin.