Acid-base versus structural properties of an aminoglycoside antibiotic--sisomicin: NMR and potentiometric approach.
Aminoglycoside antibiotics constitute a class of the drugs of high interest, whose therapeutic action is based upon the electrostatic interaction with the variety of RNA molecules. The positive charge of these drugs molecules, located at their amino functions, has a prevailing influence on this process. The potentiometry and (1)H NMR spectroscopy are applied hereby to achieve the characteristics of the acid-base properties of particular protonating groups. We found that the pK values of deprotonation processes cover a wide values range 6-9.8. The correlation spectra of sisomicin, both COSY and TOCSY, allowed attributing unambiguously individual signals to the corresponding protons. These spectra involve a lot of the cross-peaks originating from the B and C rings protons, while the analogous signals originating from A rings protons are less numerous. Molecular modeling provided that the methylated amino group of A ring is located too far from the protonated functions of the remaining rings to affect their pK values. The phenomena observed herein are discussed in line of strength of the analogous processes observed for other aminoglycosides. As the result, four types of amino groups consisted within these antibiotics are distinguished.
Krezel
Artur
A
Faculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland.
Szczepanik
Wojciech
W
Swiatek
Magdalena
M
Jezowska-Bojczuk
Małgorzata
M
D000136:Acid-Base Equilibrium; D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011199:Potentiometry / Q000379:methods; D012853:Sisomicin / Q000737:chemistry*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012853:Sisomicin