Analysis of the Structures, Electronic, and Spectroscopic Properties of Piperidine-Based Analgesic Drugs Carfentanil and Acetylfentanyl

The geometrical molecular structures, atomic charges, frontier molecular orbitals, and UV–visible electronic data of analgesic drugs carfentanil and acetylfentanyl were computed using quantum chemical code. In addition, NMR (1H and 13C) chemical shifts, harmonic vibrational wavenumbers, and the corresponding vibrational assignments were proposed on the basis of potential energy distribution. The calculations were carried out at Becke-3-Lee–Yang–Parr (B3LYP) functional with density functional theory (DFT) and time-dependent density functional theory (TD-DFT) using the 6–311 +  + G(d,p) basis set. The piperidine rings of the two molecules adopt a more stable chair conformation of a six-membered ring structure with slight distortion at the point of substitution. This shows that the piperidine moiety of the carfentanil and acetylfentanyl have similar geometric parameters and thus support the hypothesis that the piperidine ring in these molecules is the primary structural feature that is responsible for their analgesic activities. In addition, the introduction of the carbomethoxy (-COCH3) group into the piperidine ring of fentanyl has little or no effect on the electronic properties of this class of molecules. The theoretical results were successfully compared with similar piperidine-based analgesic drugs fentanyl and available experimental data. This research gives precise and invaluable information that will help in the structural elucidation of analogs of fentanyl that could be used in the development of analytical methods for the accurate and reliable detection and monitoring of these important molecules.