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Azithromycin (AZM) is a macrolide-type antibiotic used to prevent and
treat serious infections (mycobacteria or MAC) that significantly inhibit
bacterial growth. Knowledge of the predominant conformation in solution is
of fundamental importance for advancing our understanding of the
intermolecular interactions of AZM with biological targets. We report an
extensive density functional theory (DFT) study of plausible AZM
structures in solution considering implicit and explicit solvent effects.
The best match between the experimental and theoretical nuclear magnetic
resonance (NMR) profiles was used to assign the preferred conformer in
solution, which was supported by the thermodynamic analysis. Among the 15
distinct AZM structures, conformer M14, having a short intramolecular
C6-OH…N H-bond, is predicted to be dominant in water and DMSO solutions.
The results indicated that the X-ray structure backbone is mostly
conserved in solution, showing that large flexible molecules with several
possible conformations may assume a preferential spatial orientation in
solution, which is the molecular structure that ultimately interacts with
biological targets.
42 views reported since publication in 2023.