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Binary and ternary complexes of Co(II) with 1,10 – phenanthroline
and the antibiotics Norfloxacin, Ofloxacin and Enrofloxacin:
Interaction with biomembrane models
M. Ferreira, P. Gameiro
Requimte, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 4169-007 Porto.
Fluoroquinolones are antibiotics that have a large spectrum of action against Gram negative
and some Gram positive bacteria. Nowadays, one of the strategies to enhance their
pharmacological behavior is the complexation of this fluoroquinolones with divalent metal ions
since it can increase their activity and decreases their toxicity [1]. Fluoroquinolone metal
complexes can also have different lipophilicity and better interaction with the DNA [2].
Ternary complexes of quinolones (with metal and 1,10 – phenanthroline) showed an increased
activity when compared with binary complexes (with quinolone and metal) [3].The interaction
between these species and liposomes has been cited as a reference in the understanding of their
diffusion through phospholipid bilayer. [4]
In this study, the stability constants of binary complexes of Co/Norfloxacin, Co/Ofloxacin and
Co/Enrofloxacin and ternary complexes of Co/Norfloxacin/Phenanthroline,
Co/Ofloxacin/Phenanthroline and Co/Enrofloxacin /Phenanthroline, have been determined
using an automatic potentiometric system with an electrode sensible to hydrogen cation (25ºC,
I = 0,1M with NaCl and in argon atmosphere). These constants allow the drawing of the
diagrams of distribution of species over the range of pH which gives information about the
utility of these species as metalo-antibiotics. Interaction with biomembranar models, have also
been performed. The partition coefficients (Kp) of Ofloxacin, Co/Norfloxacin and
Co/Enrofloxacin with DMPC liposomes were determined by spectrofluorimetric methods
(37ºC and pH 7,4).
The results showed that the stability constants of the binary complexes are similar within the
three antibiotics and that the stability constants of ternary complexes are significantly higher
than those of the binary complexes. Interaction of the fluoroquinolones with liposomes
evidenced that Co/Enrofloxacin has the higher partition to the lipidic phase (higher Kp),
followed by Ofloxacin and Co/Norfloxacin, respectively.
References:
[1] Upadhyay, S. K., Kumar, P. and Arora, V. (2006), Complexes of quinolone drugs norfloxacin and
ciprofloxacin with alkaline earth metal perchlorates, Journal of Structural
Chemistry, 47(6), 1078-1083.
[2] Gao, F., Xie, P. Y. J. and Wang, H. (1995), Synthesis, characterization and antibacterial activity of
novel Fe(III), Co(II), and Zn(II) complexes with norfloxacin, Journal of Inorganic Biochemistry, 60, 61-
67.
[3] Saha, D. K., Sandbhor, U., Shirisha, K., Padhye, S., Deobagkar, D., Anson, C. E. and
Powell, A. K. (2004), A novel mixed-ligand antimycobacterial dimeric copper complex of ciprofloxacin
and phenanthroline, Bioorganic & Medicinal Chemistry Letters, 14, 3027- 3032.
4. Bedard, J. and Bryan, L. E. (1989), Interaction of the fluoroquinolone antimicrobial agents
Ciprofloxacin and Enoxacin with liposomes, Antimicrobial Agents and Chemotherapy, 33, 1379-1382.
348 3 rd meeting of young researchers at UP