**4. Concluding Remarks**

The mixture of 9-ethyladenine and oxalic acid have, surprisingly, resulted in the most productive nucleobase or derivative up to the authors' knowledge. For most of the studied nucleobases or their derivatives found in the literature (adenine, n-benzyladenine, caffeine, theobromine, theophylline or even lamivudine), the salt/cocrystal in a 2:1 ratio is the most common solid form. In this work, we have described up to six different multicomponent solids including two molar ratios and anhydrous/solvated forms using mechanochemistry, slurry or crystallization experiments. Once again, it reflects the importance of the combination of all these techniques as complementary tools besides to computational methods to fully understand the solid state landscape of multicomponent pharmaceutical solids for a determined API or model compound.

The obtained solids have been characterized and the crystal structures for the two anhydrous forms have been solved. The H-bonding networks observed in the solidstate of both compounds have been analyzed using DFT calculations combined with the QTAIM methodology. The energy of each individual H-bond has been computed, showing the relevance of the *R*<sup>2</sup> 2(10) centrosymmetric dimer in **1**. The dissociation energies of the charge assisted H-bonds (N1+–H···O) are similar in both compounds, which are the strongest H-bonds (~7 kcal/mol) formed in the solid state. The QTAIM analysis also evidences the relevance of CH···O interactions (up to 2.4 kcal/mol) as ancillary interactions in both compounds.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/article/ 10.3390/cryst12010089/s1, Experimental methods for solution syntheses and grinding screening. Figure S1: TGA-DSC traces of 9-ethyladenine-oxalic acid (1:1) salt (1). Figures S2: TGA-DSC traces of 9-ethyladenine-oxalic acid (2:1) salt (3). Figure S3: TGA-DSC traces of 9-ethyladenine-oxalic acid hydrated (1:1) salt (2). Figure S4: TGA-DSC traces of 9-ethyladenine-oxalic acid hydrated salt (4). Figures S5: TGA-DSC traces of 9-ethyladenine-oxalic acid hydrated (1:1) salt (5). Figure S6: TGA-DSC traces of 9-ethyladenine-oxalic acid hydrated (1:1) hydrated salt (6). Figure S7: Ortep images of compounds (a) 1 and (b) 3. Table S1: Hydrogen bond details for 9-ethyladenine-oxalic acid (1:1) salt (1). Table S2: Hydrogen bond details for 9-ethyladenine-oxalic acid (2:1) salt (3). Figure S8: Diffractograms of initial and undissolved solids for compounds 9ETADE-OXA (2:1) (3), 9ETADE- OXA (1:1) (1) and 9ETADE-SUC (1:1) salt. Figure S9: PXRD patterns of the anhydrous 9ETADE-OXA salts under different temperature and relative humidity conditions.

**Author Contributions:** M.B.-O. prepared 9-ethyladenine. M.B. designed the experiments, characterized the samples and obtained the single crystals. M.B.-O. performed the data collection and the resolution of the crystal structures. A.F. performed the D.F.T. study. M.B., A.F. and E.M. designed the concept. E.M. supervised the work. All authors wrote and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** M.B. and E.M. are grateful to the Severo Ochoa FunFuture project (MICINN, CEX2019- 917S) and Generalitat de Catalunya (2017SGR1687). M.B.-O. thanks the Vice-Rector for Research and International Relations of the University of the Balearic Islands for the financial support in setting up the single-crystal X-ray diffraction facility. A.F. thanks the MICIU/AEI from Spain for financial support (Projects CTQ2017-85821-R and PID2020-115637GB-I00, Feder funds).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We thank R. Frontera from the Centre de Tecnologies de la Informació (CTI) at the UIB for computational facilities. The authors also thank the powder diffraction and thermal analysis services from the ICMAB.

**Conflicts of Interest:** The authors declare no conflict of interest.
