Thermodynamic Characterization of the Interaction between the Antimicrobial Drug Sulfamethazine and Two Selected Cyclodextrins

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 24; p. 4565
• Main Authors: Mohamed Ameen, Hiba, Kunsági-Máté, Sándor, Bognár, Balázs, Szente, Lajos, Poór, Miklós, Lemli, Beáta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.12.2019; MDPI
• Subjects: Anti-Infective Agents - chemistry; Antibiotics; Antimicrobial agents; Aqueous solutions; beta-Cyclodextrins - chemistry; Biological activity; Calixarenes; Chemists; Computer simulation; Cyclodextrin; Cyclodextrins; Drug Interactions; Freeze drying; Hydrogen; Hydrogen Bonding; Hydrogen-Ion Concentration; Infrared spectroscopy; Models, Molecular; Molecular Structure; NMR; Nuclear magnetic resonance; Organic chemistry; Pharmacology; Physical properties; Solubility; Spectrum analysis; Stoichiometry; Sulfamethazine; Sulfamethazine - chemistry; Supramolecular compounds; Thermodynamics; Vibrations; thermodynamics; host-guest complex; sulfamethazine; zwitterion; cyclodextrin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24244565

Sulfamethazine is a representative member of the sulfonamide antibiotic drugs; it is still used in human and veterinary therapy. The protonation state of this drug affects its aqueous solubility, which can be controlled by its inclusion complexes with native or chemically-modified cyclodextrins. In this work, the temperature-dependent (298-313 K) interaction of sulfamethazine with native and randomly methylated β-cyclodextrins have been investigated at acidic and neutral pH. Surprisingly, the interaction between the neutral and anionic forms of the guest molecule and cyclodextrins with electron rich cavity are thermodynamically more favorable compared to the cationic guest. This property probably due to the enhanced formation of zwitterionic form of sulfamethazine in the hydrophobic cavities of cyclodextrins. Spectroscopic measurements and molecular modeling studies indicated the possible driving forces (hydrophobic interaction, hydrogen bonding, and electrostatic interaction) of the complex formation, and highlighted the importance of the reorganization of the solvent molecules during the entering of the guest molecule into the host's cavity.