Rotational spectrum of paracetamol

Area of Science:

• Molecular spectroscopy
• Physical chemistry
• Computational chemistry

Background:

• Paracetamol is a widely used analgesic and antipyretic.
• Understanding its molecular structure and conformations is crucial for drug development and pharmacology.
• Previous studies have lacked detailed structural information on isolated paracetamol molecules.

Purpose of the Study:

• To obtain the first rotational spectrum of isolated paracetamol.
• To identify and characterize different conformers of paracetamol in the gas phase.
• To provide experimental data for validating theoretical calculations of paracetamol's structure.

Main Methods:

• Laser ablation of solid paracetamol samples.
• Expansion in a supersonic jet to isolate molecules.
• Fourier transform microwave spectroscopy (FTMW) in the 4-10 GHz range.
• Ab initio quantum chemical calculations for comparison.

Main Results:

• The first rotational spectrum of isolated paracetamol was successfully recorded.
• Four distinct conformers of paracetamol were observed for the first time.
• Two conformers featured a trans peptidic group arrangement, and two featured a cis arrangement.
• Experimental rotational and (14)N quadrupole coupling constants matched theoretical predictions.

Conclusions:

• The study provides the first experimental evidence of multiple paracetamol conformers in isolation.
• The observed conformers offer crucial insights into paracetamol's structural flexibility.
• The findings validate the accuracy of computational methods for predicting molecular structures and properties.