Hydration of biomolecules is an important physiological process that governs their structure, stability, and function. Herein, we probe the microhydration structure of cationic pyrimidine (Pym), a common building block of DNA/RNA bases, by infrared photodissociation spectroscopy (IRPD) of mass-selected microhydrated clusters, $$\hbox {Pym}^{+}$$
Pym
+
-$$\hbox {W}_{n}$$
W
n
(W=$$\hbox {H}_{2}\hbox {O}$$
H
2
O
), in the size range $$n=1$$
n
=
1
–3. The IRPD spectra recorded in the OH and CH stretch range are sensitive to the evolution of the hydration network. Analysis with density functional theory calculations at the dispersion-corrected B3LYP-D3/aug-cc-pVTZ level provides a consistent picture of the most stable structures and their energetic and vibrational properties. The global minima of $$\hbox {Pym}^{+}$$
Pym
+
-$$\hbox {W}_{n}$$
W
n
predicted by the calculations are characterized by H-bonded structures, in which the H-bonded $$\hbox {W}_{n}$$
W
n
solvent cluster is attached to the most acidic C4–H proton of $$\hbox {Pym}^{+}$$
Pym
+
via a single CH...O ionic H-bond. These isomers are identified as predominant carrier of the IRPD spectra, although less stable local minima provide minor contributions. In general, the formation of the H-bonded solvent network (exterior ion solvation) is energetically preferred to less stable structures with interior ion solvation because of cooperative nonadditive three-body polarization effects. Progressive hydration activates the C4–H bond, along with increasing charge transfer from $$\hbox {Pym}^{+}$$
Pym
+
to $$\hbox {W}_{n}$$
W
n
, although no proton transfer is observed in the size range $$n\leqslant $$
n
⩽
3. The solvation with protic, dipolar, and hydrophilic W ligands is qualitative different from solvation with aprotic, quadrupolar, and hydrophobic $$\hbox {N}_{2}$$
N
2
ligands, which strongly prefer interior ion solvation by $$\uppi $$
π
stacking interactions. Comparison of $$\hbox {Pym}^{+}$$
Pym
+
-W with Pym-W and $$\hbox {H}^{+}$$
H
+
Pym-W reveals the drastic effect of ionization and protonation on the Pym...W interaction.
Graphic Abstract
