Electrochemical Characterization of Central Action Tricyclic Drugs by Voltammetric Techniques and Density Functional Theory Calculations

Abstract

This work details the study of the redox behavior of the drugs cyclobenzaprine (CBP), amitriptyline (AMP) and nortriptyline (NOR) through voltammetric methods and computational chemistry. Results obtained in this study show that the amine moiety of each compound is more likely to undergo oxidation at 1a at Ep1a ≈ 0.69, 0.79, 0.93 V (vs. Ag/AgCl/KClsat) for CBP, AMP and NOR, respectively. Moreover, CBP presented a second peak, 2a at Ep2a ≈ 0.98 V (vs. Ag/AgCl/KClsat) at pH 7.0. Furthermore, the electronic structure calculation results corroborate the electrochemical assays regarding the HOMO energies of the lowest energy conformers of each molecule. The mechanism for each anodic process is proposed according to electroanalytical and computational chemistry findings, which show evidence that the methods herein employed may be a valuable alternative to study the redox behavior of structurally similar drugs.

Redox Behavior of Central-Acting Opioid Tramadol and Its Possible Role in Oxidative Stress

“…The quantum chemistry calculations by EHM showcased that, in the model, HOMO-0 was rendered around the tertiary amine of the DMC moiety, while HOMO-1 and LUMO-0 were rendered in the aromatic benzene ring, being the methoxyl moiety also encompassed in HOMO-1 rendering (Figure 3). Owing to previous reports, wherein is showcased the correlation of HOMO and LUMO renderings and energy gaps to possible oxidation sites in molecules [13,14,23], we therefore suggest that the aforementioned regions are the most thermodynamically feasible to undergo redox reactions.…”

“…An interesting feature was that in HOMO-1, the rendering of the electric orbital also encompassed the methoxyl moiety (Figure 3D). Considering that smaller energy gaps favor the occurrence redox processes [13], therefore, HOMO-n and LUMO-n can be correlated to the thermodynamic feasibility of oxidation or reduction [14]. In this sense, HOMO-0 and HOMO-1 might be associated with oxidative processes underwent by TRA, while LUMO-0 can be correlated to reduction.…”

“…Among the several tools which are used to investigate the physicochemical features of compounds are electrochemistry and theoretical chemistry [9,10]. These approaches allow researchers to gather information regarding the thermodynamics of compounds in several energy levels and reaction coordinates, thence shedding light on the feasibility of chemical transformations such as redox processes [11]. Moreover, reactional kinetics can also be investigated through these tools, thereby allowing a comprehensive study of the physicochemical behavior of compounds.…”

“…Nonetheless, several authors employed the electroanalytical approach of voltammetry to study the redox properties of drugs, as well as to correlate the results of ab initio quantum chemistry calculations based on density functional theory [12,13], or semi-empirical approaches consisting of Hartree-Fock formalism such as extended Hückel method (EHM) [14] to better understand the thermodynamics and kinetics involved in oxidation and reduction reactions, as well as to draw interpretations of how chemical compounds might scavenge ROS or promote their formation.…”

Thermodynamics and Kinetics ofCamellia sinensisExtracts and Constituents: An Untamed Antioxidant Potential

“…In this sense, all these molecules could undergo redox reactions due to their easily excitable electrons in the conjugated aromatic systems (flavonoids) and single aromatic ring (gallic acid and caffeine) [25]. Notwithstanding, this interpretation is further corroborated by experimental data as well as by the evaluation of their energy gap (ΔE) in comparison to that of other known antioxidants such as alpha-tocopherol, which showcase ΔE of 10.2011 eV when analyzed under the same method [25,26,28,29]. Table 3 showcases the ΔE of major C. sinensis constituents.…”