Proton-transfer dictated supramolecular hydrogen bonded architecture in cytosine with substituted carboxylic acid coformers: Experimental and theoretical investigation by density functional approximations, DLPNO-CCSD(T)-F12, and G0W0 calculations

The nucleobase cytosine has been utilized for co-crystallization with three coformers (gallic acid, aspirin, and thiazole-4-carboxylic acid) by the solvent grinding method. The resulting salts CYT-GAL, CYT-SAL, and CYT-TCA were characterized by the single-crystal x-ray diffraction technique. Structural analysis reveals that the salts are stabilized by N-H⋯O and N-H⋯N hydrogen bonds (HBs). Protonation of cytosine (N3) leads to the formation of R22(8) ring sets, which violates the Watson-Crick pair formation. Furthermore, all the features of these salts were confirmed by PXRD, TGA, NMR, and FTIR. HOMO-LUMO gaps were benchmarked using 65 DFAs against the HF/VTZ-F12 HOMO-LUMO gaps because DLPNO-CCSD(T)-F12, such as MP2, retains the HF orbitals and does not alter orbital energies. HOMO-LUMO gaps obtained at this level are the same as the HF/VTZ-F12 HOMO-LUMO gaps. Range-separated double-hybrid DFAs (RSX-QIDH, SCS-RSX-QIDH, and SOS-RSX-QIDH) showed the best agreement with these gaps. G0W0 calculations using several DFAs and HF starting points were additionally performed to assess their reliability for predicting these gaps. Bonding analysis using quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI), natural bond orbital, and molecular electrostatic potential was carried out at the DSD-PBEP86-D3BJ/def2-TZVP level of theory, validated against seven additional DFAs. QTAIM reveals that CYT-GAL is stabilized by N-H⋯O intermolecular HBs, CYT-SAL is stabilized by a partially covalent O-H⋯O intramolecular HB (delocalization index 0.1128), and CYT-TCA is stabilized by weaker van der Waals interactions (C⋯C, C⋯N, and S⋯N). Furthermore, NCI analysis reveals new interactions, including intramolecular HBs of type O-H⋯O and H⋯O interactions in CYT-GAL, a new H⋯O interaction in the case of CYT-SAL, and a new C⋯C interaction in the case of CYT-TCA.