Microhydration of ionized building blocks of DNA/RNA: infrared spectra of pyrimidine $$^{+}$$ + - $$(\hbox {H}_{2}\hbox {O})_{\text {1-3}}$$ ( H 2 O ) 1-3 clusters

THE EUROPEAN PHYSICAL JOURNAL D Eur. Phys. J. D (2021)75:71 https://doi.org/10.1140/epjd/s10053-021-00065-z Regular Article - Clusters and Nanostructures Microhydration of ionized building blocks of DNA/RNA: infrared spectra of pyrimidine+-(H2O)1–3 clusters Kuntal Chatterjee1 and Otto Dopfer1,a 1 Institut für Optik und Atomare Physik, Technische Universität Berlin, Hardenbergstr. 36, 10623 Berlin, Germany Received 28 September 2020 / Accepted 9 December 2020 © The Author(s) 2021 Abstract. 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 massselected microhydrated clusters, Pym+ -Wn (W=H2 O), in the size range 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 Pym+ -Wn predicted by the calculations are characterized by H-bonded structures, in which the H-bonded Wn solvent cluster is attached to the most acidic C4–H proton of 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 Pym+ to Wn , although no proton transfer is observed in the size range n 3. The solvation with protic, dipolar, and hydrophilic W ligands is qualitative different from solvation with aprotic, quadrupolar, and hydrophobic N2 ligands, which strongly prefer interior ion solvation by π stacking interactions. Comparison of Pym+ -W with Pym-W and H+ Pym-W reveals the drastic effect of ionization and protonation on the Pym. . . W interaction. 1 Introduction The structure, stability, and function of almost all biomolecules are strongly governed by their hydration environment, and without hydration these macromolecules often remain inactive [1]. In various cases, the surface water molecules attached to these large biochemical architectures, which are popularly known as biological or interfacial water, are key to their function [2–10]. Such surface water molecules actively participate in charge transport [3,8,10–14] and are crucial for recognition of proteins and drugs through balancing enthalpic and entropic contributions to the overall free energy [15–17]. The molecular picture involving the interaction between these biological water molecules and small building blocks within these large biomolecules often provides information about the function of macromolecules. Mass spectrometry in combination with Supplementary information The online version of this article (https://doi.org/10.1140/epjd/ s10053-021-00065-z) contains supplementary information, which is available to authorized users. a e-mail: (corresponding author) 0123456789().: V,-vol infrared (IR) spectroscopy and computational chemistry is one of the powerful approaches to probe such interactions at the microscopic level [18–34]. Herein, we apply this combined technique to investigate the microhydration network of the pyrimidine cation (Pym+ ). The Pym heterocycle is the primary building block of the uracil, thymine, and cytosine nucleobases, which are fundamental constituents of the genetic materials DNA and RNA [35,36]. Furthermore, most biomolecules occur in various charged states (ionized or (de-)protonated) in the physiological medium. These various charged states strongly influence the nature of the intermolecular forces and thus the solvent binding motifs. In this work, we investigate such interactions between Pym+ and neutral solvent molecules, including the effect of solvent polarity on solvent binding motifs and interaction strengths. In addition to its importance in biophysical phenomena, the Pym· · · water interaction in its various charged states has substantial significance in the area of molecular astrochemistry. For instance, UV irradiation of pyrimidine: H2 O ices results in the formation of nucleobases such as uracil [37–39], which was isolated in different carbonaceous chondrites [40–42]. This is important to understand the enigmatic prebiotic chemistry 123 71 Page 2 of 16 that perhaps leads to the beginning of life on planet earth. We recently reported IR photodissociation (IRPD) spectra of microhydrated structures of protonated Pym, H+ Pym-Wn4 (W=H2 O), which confirmed the exclusive N-protonation of neutral Pym and the preference of polar W for forming NH· · · O type linear ionic hydrogen bonds (H-bonds) [43]. The cluster growth through progressive addition of W ligands occurs via exterior ion solvation that leads to a growing H-bonded Wn network attached to H+ Pym. Although a recent mass spectrometry study showed bimolecular solute-tosolvent proton transfer at n = 4 [44], the IRPD spectra do not show unambiguous evidence for such proton migration up to n = 4, in line with computational data [43]. The same study also reported such a proton transfer in the case of ionized Pym+ -Wn clusters at n = 4 and the preference for internal ion solvation over exterior ion solvation [44]. However, the conclusions were based on density functional theory (DFT) calculations at the M06-2X level combined with mass spectrometric experiments. Such a combined approach is not always reliable in the correct prediction of structures, as has been shown recently for the example of microhydrated clusters of the naphthalene cation [31,45,46]. To this end, we investigate herein the Pym+ -Wn clusters by the much more structure-sensitive IR spectroscopic approach and probe the various ligand binding motifs arising from the increasing number of solvent molecules with the aid of dispersion-corrected DFT calculations at the B3LYP-D3/aug-cc-pVTZ level. Comparison with the previously studied Pym+ -(N2 )n clusters using the same spectroscopic and computational approach [47] illustrates the effect of solvent polarity on the interaction potential with respect to both structure (preferred binding sites and solvation network) and binding energy. We also compare our results for Pym+ -W with the properties of neutral Pym-W [43,48–51] to evaluate the effect of ionization on structure, binding motif, and interaction energy, which is fundamental to comprehend the charge-induced changes arising in solvent binding motifs of biologically relevant molecules. 2 Experimental and theoretical m (...truncated)