Abstract
Theoretical studies based on the density functional theory (DFT) have been performed to study structural and vibrational properties of the free base, cationic, and hydrochloride species of narcotic tramadol agent in the gas phase and aqueous solution. In both media, B3LYP/6-31G* calculations were used while in solution, the self-consistent reaction field (SCRF) method together with the integral equation formalism variant polarised continuum (IEFPCM) and universal solvation model density (SMD) models have been employed because these models consider the solvent effects. The vibrational studies have revealed that the species cationic is present in the solid phase because the most intense band predicted for the hydrochloride in infrared and Raman spectra is not observed in the experimental spectra. The harmonic force fields, together with the normal internal coordinates and scaling factors, have allowed the complete vibrational assignments of 126, 129, and 132 vibration modes expected for the free base, cationic, and hydrochloride species, respectively, by using the SQMFF methodology. The cationic species evidence the most negative solvation energy and higher hydration in solution in agreement with its lower stability, while the hydrochloride species is the most reactive in solution. MK charges and NBO and AIM studies support cationic species' instability due to the positive charge on N atom. Comparisons of the experimental UV spectrum of hydrochloride tramadol with the predicted for the three species suggest that the free base, cationic, and hydrochloride species can be present in solution. Comparisons of predicted infrared, Raman, 1H, and 13C NMR and electronic spectra for the free base, cationic, and hydrochloride species of tramadol with the corresponding experimental ones have evidenced reasonable correlations for the cationic species showing that this species present in the solid phase and in solution.
Highlights
In pharmacology, the hydrochloride species are highly used as medicaments because these structural forms allow the oral bioavailability of drugs as bioactive molecules and their incorporation quickly as therapeutic agents, as mentioned by Veber et al [1]
Three species of narcotic tramadol agent's theoretical structures were studied in the gas phase and aqueous solution by using the functional hybrid B3LYP with the 6-31G* basis set
Comparisons of predicted infrared, Raman, 1H, and 13C NMR and electronic spectra for the free base, cationic, and hydrochloride species of tramadol with the corresponding experimental ones have evidenced reasonable correlations for the cationic species showing that this species present in the solid phase and in solution
Summary
The hydrochloride species are highly used as medicaments because these structural forms allow the oral bioavailability of drugs as bioactive molecules and their incorporation quickly as therapeutic agents, as mentioned by Veber et al [1]. The free base, cationic, and hydrochloride forms of narcotic tramadol were studied from a theoretical point of view combining DFT calculations with experimental available infrared, Raman, 1H- and 13C-NMR and ultraviolet spectra in order to predict structural, electronic, topological and vibrational properties of its three forms [24]. Complete vibrational assignments of those three forms of tramadol were performed by using the B3LYP/6-31G* method [25,26] with the scaled quantum mechanical force fields (SQMFF) methodology, normal internal coordinates, transferable scaling factors, and the Molvib program [27-29]. The three forms of tramadol have the N(CH3)2·group in its structures, as in antihistaminic promethazine and diphenydramine agents [10,15], while in some alkaloids an only N-CH3 group is found [8-11,16] These N-CH3 groups' presence plays a very important role in the chemical properties and biological activities of these pharmacological species. The 1H and 13C NMR and electronic spectra were predicted in aqueous solution by using the gauge‐including atomic orbital (GIAO) method and the Time-dependent DFT calculations (TD-DFT) by using the same level of theory [35,47]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
