Charge density and electrostatic potential analyses in paracetamol.

Area of Science:

• Crystallography
• Quantum Chemistry
• Materials Science

Background:

• Paracetamol is a widely used analgesic and antipyretic.
• Understanding its electronic structure is crucial for its biological activity and crystal engineering.
• Previous studies have explored paracetamol's properties, but a detailed analysis of its electron density and electrostatic potential in the solid state is needed.

Purpose of the Study:

• To derive and analyze the experimental electron density of monoclinic paracetamol at 100 K.
• To investigate the topological features of the electron density and electrostatic potential.
• To calculate atomic charges, electrostatic forces, and interaction energies within the crystal lattice.

Main Methods:

• High-resolution X-ray diffraction at 100 K.
• Hansen-Coppens multipole modeling for electron density refinement.
• Analysis of electron density and electrostatic potential topology.
• Calculation of atomic charges using numerical integration and the divergence theorem.
• Estimation of electrostatic forces via the Maxwell stress tensor.
• Calculation of dimer interaction energies.

Main Results:

• The electron density of monoclinic paracetamol was successfully refined.
• The nitrogen atom showed the highest charge magnitude (-1.2 e), consistent with its nucleophilic behavior in biological systems.
• Atomic charges, electrostatic forces, and dimer interaction energies were quantified.
• Topological analysis provided insights into intermolecular interactions.

Conclusions:

• The detailed electron density analysis provides a fundamental understanding of paracetamol's electronic structure in the solid state.
• The findings correlate the molecular charge distribution with its known biological activity.
• This study offers valuable data for computational modeling and the design of new paracetamol-based materials.