Structural study of benzidamine salicylate in the solid state and in solution

Area of Science:

• Analytical Chemistry
• Solid-State Chemistry
• Medicinal Chemistry

Background:

• Benzidamine salicylate (Benzasal) is an analgesic and anti-inflammatory compound.
• Understanding its molecular structure and interactions is key to its pharmaceutical properties.

Purpose of the Study:

• To characterize the vibrational (IR, Raman) and NMR spectra of benzidamine salicylate.
• To determine the crystal structure of benzidamine salicylate using X-ray diffraction.
• To elucidate the intermolecular and intramolecular interactions in benzidamine salicylate.

Main Methods:

• Infrared (IR) spectroscopy
• Raman spectroscopy
• Proton (1H) and Carbon-13 (13C) Nuclear Magnetic Resonance (NMR) spectroscopy
• X-ray diffraction analysis

Main Results:

• Spectroscopic data for benzidamine, benzidamine hydrochloride, and salicylic acid were obtained for comparison.
• The crystal structure revealed significant intermolecular N(+)H...O(-)...-C hydrogen bonds between benzidamine and salicylate ions.
• These hydrogen bonds, with distances of 2.658 A and 3.228 A, were observed to persist in CDCl3 solution.
• A strong intramolecular hydrogen bond within the salicylate anion was also identified in both solid and solution states.

Conclusions:

• The study provides a comprehensive characterization of benzidamine salicylate's structure and bonding.
• Hydrogen bonding plays a critical role in the solid-state and solution behavior of benzidamine salicylate.
• These findings contribute to a deeper understanding of the structure-activity relationship for this analgesic and anti-inflammatory agent.