Unraveling boric acid interactions with macrocyclic hosts: DFT insights into the key role of hydrogen bonding in complex stabilization

A density functional theory (DFT) investigation was performed to elucidate the interaction mechanisms between boric acid (BA) and various macrocyclic host molecules. The calculated complexation energies were negative, indicating that these interactions are energetically favorable. Structural analyses revealed the formation of hydrogen bonds, particularly between BA and the hosts beta-cyclodextrin (beta-CD), pillar[5]arene (P[5]), and pyrogallol[5]arene (P[5]G). Notably, the hydroxyl groups (OH) of BA played a crucial role in establishing intermolecular hydrogen bonds, which significantly enhanced the stability of the BA/beta-CD and BA/P[5] complexes, as confirmed by natural bond orbital (NBO) and intermolecular Gradient model based on Hirshfeld partition (IGMH) analyses. Furthermore, the calculated HOMO-LUMO energy gaps for the BA/beta-CD, BA/P[5], and BA/P[5]G complexes were found to be larger than those of the individual hosts, indicating a kinetically stable systems. The studied host systems demonstrate potential for enhancing the bioavailability of boric acid and reducing its toxicity through effective host-guest recognition.