Spectroscopic, molecular docking, and ecotoxicology analyses of the monomer and dimers of 3-aminocyclohexa-2,6-diene-1-sulfonic acid – a theoretical approach

1,3-Cyclohexadienes are an important group of molecules found in natural compounds and their metabolites. In this contribution, optimization, spectral prediction, reactivity, and molecular docking studies of 3-aminocyclohexa-2,6-diene-1-sulfonic acid were performed. The structure was optimized based on the crystallographic structures of cis-(1S)-3-Fluoro-3,5-cyclohexadiene-1,2-diol and 1,1′-(3,5-Cyclohexadiene-1,3-diyl)dibenzene. The most intense transitions in the predicted spectrum were observed at 195, 222, 235, and 324 nm. The molecular orbitals included in these transitions were partially localized on polar groups. The explicit solvent effect was investigated through optimization of structure with one water molecule. The strength of these interactions was assessed by the Natural Bond Orbital Theory and Quantum Theory of Atoms in Molecules. Three different dimer structures were also optimized to obtain the interaction energy for various active positions. The most stable dimer was formed through the interaction of amino and sulfonic groups. The reactivity parameters for three cyclohexadiene were calculated and discussed from the structural point of view. The docking study towards Urokinase Type Plasminogen Activator ( uPa ) proved the importance of various substituents. Once the dimers were used as ligands, the binding energy increased. These results show the possible use of cyclohexadienes as uPa inhibitors. Graphical abstract The optimization of 3-aminocyclohexa-2,6-diene-1-sulfonic acid ( 1 ), cis-(1S)-3-Fluoro-3,5-cyclohexadiene-1,2-diol ( 2 ) and 1,1′-(3,5-Cyclohexadiene-1,3-diyl)dibenzene ( 3 ) compounds was performed at the B3LYP/6-311++G(2df,2p) level of theory. Strong hydrogen bonds were formed with amino and sulfonic groups. The dimer structures proved the importance of intermolecular interactions between polar groups. The docking results towards Urokinase Type Plasminogen Activator ( uPa ) proved the reactivity order determined previously along with the interactions with the amino acids in an active pocket.