Stereochemical inversion of pillar[5]arene. NMR and DFT studies

Abstract

Pillar[n]arenes, a new class of macrocycles, can be used as drug carriers and as new receptors recognizing biologically important molecules. Investigation of structure and intramolecular mobility of pillar[n]arenes is important for creating pillar[n]arene-based delivery systems with different individual properties. NMR spectroscopy and DFT calculations were used to analyze the conformational dynamics of 4,8,14,18,23,26,28,31,32,35-deca- (carboxymethoxy) - pillar[5]arene and to define the thermodynamic parameters and the reaction paths of stereochemical inversion of pillar[5]arene. The structure and energy of intermediates and transition states were determined in the gas phase and in a water solution. Experimental data show that the energy barrier of stereochemical inversion of pillar[5]arene is about 12 kcal/mol at a temperature of 300 K. DFT calculations overestimate the reaction energetic barrier even with taking into account the solvation effect. The largest barrier is detected for the rotation of the first hydroquinone fragment. Rotating the next fragments requires less energy. Calculations have shown that sequential rotation of neighboring hydroquinone fragments is the most energetically favorable transformation of one enantiomer into another.