Theoretical investigation of the effects of diverse hydrogen-bonding characteristics on the 17O chemical shielding and electric field gradient tensors within the active sites of MraYAA bound to nucleoside antibiotics capuramycin, carbacaprazamycin, 3′-Hydroxymureidomycin A, and muraymycin D2

This study builds upon our prior researches and seeks to investigate and clarify the influences of various characteristics of hydrogen bonds (H-bonds) and charge transfer (CT) interactions, which were detected within the inhibitor binding pockets (labeled as the QM models I–IV) of MraY_AA–capuramycin, MraY_AA–carbacaprazamycin, MraY_AA–3′-hydroxymureidomycin A, and MraY_AA–muraymycin D2 complexes by QTAIM and NBO analyses from DFT QM/MM MD calculations, on the ¹⁷O chemical shielding (CS) and electric field gradient (EFG) tensors of carboxylate (Oδ), carbonyl (C═O), and hydroxyl (O–H) oxygens in these models. The ¹⁷O CS and EFG tensors of these three types of oxygens in QM models I–IV were calculated at the M06-2X/6-31G** level by including the solvent effects using the polarizable continuum model. From the computed ¹⁷O CS and EFG tensors in these models, it was found that the nuclear shielding, σ_iso, for carboxylate or carbonyl oxygen increases (shielding effect) as the H-bond length decreases and the percentage p-character of n_Oδ/n_C═O lone pair partner in the CT interaction enhances. In contrast, the σ_iso (¹⁷O–H) decreases (deshielding effect) with a reduction in the H-bond length as well as with an enhancement in percentage s-character of the n_OH lone pair/σ*_O–H antibond. By reducing the H-bond length or by increasing p-character of the n_Oδ/n_C═O lone pair, the ¹⁷Oδ/¹⁷O═C quadrupole coupling constant smoothly decreases, while the ¹⁷Oδ/¹⁷O═C asymmetry parameter smoothly increases. Moreover, these calculated parameters are in a good agreement with the experimental values. The information garnered here is valuable particularly for further understanding of empirical correlations between ¹⁷O NMR spectroscopic and H-bonding characteristics in the protein–ligand complexes.