Coordination pattern, solution structure and DNA damage studies of the copper(II) complex with the unusual aminoglycoside antibiotic hygromycin B.
The aminoglycosidic antibiotic hygromycin B presents a peculiar chemical structure, characterized by two sugar rings joined via a spiro connection. The Cu(ii) complex of hygromycin B in water solution was characterized by (1)H-NMR, UV-Vis, EPR and CD spectroscopy, combined with potentiometric measurements. The spin-lattice relaxation enhancements were interpreted by the Solomon-Bloembergen-Morgan theory, allowing us to calculate copper-proton distances that were used to build a model of the complex by molecular mechanics and dynamics calculations. The fidelity of the proposed molecular model was checked by ROESY maps. Moreover DNA damage by the Cu(ii)-hygromycin B system was also investigated, showing single and double strand scissions exerted by the complex at concentrations in the range 1-5 mM. Addition of either hydrogen peroxide or ascorbic acid to each sample resulted in the shift of the cleavage potency towards lower concentrations of the complex.
Gaggelli
Elena
E
Department of Chemistry, University of Siena, Via Aldo Moro, 53100, Siena, Italy.
Gaggelli
Nicola
N
Molteni
Elena
E
Valensin
Gianni
G
Balenci
Duccio
D
Wrońska
Magdalena
M
Szczepanik
Wojciech
W
Nagaj
Justyna
J
Skała
Jacek
J
Jeżowska-Bojczuk
Małgorzata
M
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004249:DNA Damage; D006863:Hydrogen-Ion Concentration; D006921:Hygromycin B / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011199:Potentiometry; D011522:Protons; D012996:Solutions; D013057:Spectrum Analysis; D014867:Water / Q000737:chemistry
D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D011522:Protons; D012996:Solutions; D014867:Water; D006921:Hygromycin B; D003300:Copper