Structures, Reactivities and Vibrational Study of Species Derived from the Adrenergic Α 2 Receptor Agonist Guanfacine Agent

Abstract

In the present work, eight different species of adrenergic α 2 receptor agonist guanfacine have been theoretically studied in gas phase and in aqueous solution combining hybrid B3LYP/6- 31G* calculations with the Scaled Mechanical Quantum Force Field (SQMFF) methodology and the experimental available infrared and Raman spectra in order to perform their complete vibrational assignments. Hence, the different structures of three tautomeric forms of free base (A, B and C), two cationic (E and G), one anionic (D) and two hydrochloride (F and H) species of that antihypertensive agent were optimized in solution with the Integral Equation F variant Polarised Continuum Method (IEFPCM) and the universal solvation model. The anionic species of guanfacine presents the higher corrected solvation energy with valor of -301,60 kJ/mol, slightly lower than the corresponding to scopolamine alkaloid (-310.34 J/mol) and higher than the corresponding to cocaine alkaloid (-255.24 J/mol). The studies of the frontier orbitals have evidenced that in gas phase, the anionic D species is the most reactive while in solution the hydrochloride H species is the most reactive together with the anionic species. High global nucleophilicity (E) and electrophilicity indexes (ω) values have evidenced both cationic species E and G while the lower values of both indexes are predicted for the anionic D species in both media. In addition, the harmonic force fields, force constants and the complete vibrational assignments for the 63, 66, 69 and 72 vibration normal modes expected for the anionic, free bases, cationic and hydrochloride species of guanfacine are respectively reported for first time.