Quantum Chemical NMR Spectroscopic Structural Analysis in Solution: The Investigation of 3-Indoleacetic Acid Dimer Formation in Chloroform and DMSO Solution

We present a DFT-PCM NMR study of 3-indoleacetic acid (3-IAA), used as a working example, including explicit solvent molecules, named PCM-nCHCl₃, PCM-nDMSO (n = 0, 2, 4, 8, 14, 20, and 25), to investigate the dimer formation in solution. Apart from well-known cyclic (I) and open (II) acetic acid (AA) dimers, two new structures were located on DFT-PCM potential energy surface (PES) for 3-IAA named quasicyclic A (III) and quasicyclic B (IV), the last one having N–H…O hydrogen bond (instead of O–H…O). In addition, four other structures having π–π type interactions named V, VI, VII, and VIII were also obtained completing the sample on the PES. Our theoretical results and experimental ¹H NMR data (CDCl₃) strongly indicate that 3-IAA should exist in a quasicyclic form (III) in a chloroform solution different from AA. Solute–solvent interactions play a key role in O–H and N–H chemical shifts. The strong H-bond formation between the S=O and O–H and N–H groups produces large chemical shift value THAT masquerades the identification of dimer formation in DMSO solution based on ¹H NMR chemical shift changes. However, analysis of ¹³C NMR and relative energy DFT-PCM-nDMSO results strongly indicate the presence of parallel ring interacting dimer having OH…benzene ring bond (VI). There can be a competition between solute–solute and solute–solvent interactions, and polar DMSO solvent can break the quasicyclic dimers (III and IV) intermolecular O–H…O and N–H…O bonds yielding two solvated monomeric species hydrogen bonded to O=S(CH₃)₂ groups, what may take place for other organic molecules in solution. However, it did not happen for the π–π interacting dimers and structure VI survived in DMSO solution.