Microhydration Structures of Protonated Oxazole

The initial microhydration structures of the protonated pharmaceutical building block oxazole (Ox), H⁺Ox-W_n≤4, are determined by infrared photodissociation (IRPD) spectroscopy combined with quantum chemical dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ). Protonation of Ox, achieved by chemical ionization in a H₂-containing plasma, occurs at the most basic N atom. The analysis of systematic shifts of the NH and OH stretch vibrations as a function of the cluster size provides a clear picture for the preferred cluster growth in H⁺Ox-W_n. For n = 1–3, the IRPD spectra are dominated by a single isomer, and microhydration of H⁺Ox with hydrophilic protic W ligands occurs by attachment of a hydrogen-bonded (H-bonded) W_n solvent cluster to the acidic NH group via an NH···O H-bond. Such H-bonded networks are stabilized by strong cooperativity effects. This is in contrast to previously studied hydrophobic ligands, which prefer interior ion solvation. The strength of the NH···O ionic H-bond increases with the degree of hydration because of the increasing proton affinity (PA) of the W_n cluster. At n = 4, proton-transferred structures of the type Ox-H⁺W_n become energetically competitive with H⁺Ox-W_n structures, because differences in solvation energies can compensate for the differences in the PAs, and barrierless proton transfer from H⁺Ox to the W_n solvent subcluster becomes feasible. Indeed, the IRPD spectrum of the n = 4 cluster is more complex suggesting the presence of more than one isomer, although it lacks unequivocal evidence for the predicted intracluster proton transfer.