Co-ordination of Gatifloxacin with Metal Ions and Their Analogues

Abstract

The stability constants of gatifloxacin-metal complexes have been studied potentiometrically. The stability constant of the gatifloxacin metal complexes were calculated using a potentiometric method. For this purpose potentiometric data were computed through PSEQUAD Software. Stoichiometry of the complexes was calculated by Job’s method and mole ratio at different pH ranging from 4 to 9. During the stoichiometric determination of gatifloxacin-metal complexes at different pH, 1:1 ratio of metal to ligand at lower pH and 1:2 ratio of metal to ligand at higher pH were employed. For thermodynamic parameters like ∆𝐺, ∆𝐻 and ∆𝑆 of gatifloxacin metal complexes were determined by pH titration at different temperatures (i.e. 30 ºC, 35 ºC, 40 ºC, 45 ºC and 50 ºC). The pH titration data were used for calculation of 𝑙𝑜𝑔𝛽 values by PSEQUAD computer program. Graphs were plotted for 𝑙𝑛𝛽 versus 1/𝑇. The slope of this graph represents (−∆𝐻/𝑅) and the intercept is (∆𝑆/𝑅). The changes in 𝑙𝑜𝑔𝛽 values at different temperatures were examined and enthalpy and entropy values were determined for ML and ML2 of gatifloxacin complexes. Gatifloxacin and moxifloxacin complexes were synthesized with different metal ions including Mg(II), Al(III), Ca(II), Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) and their structures were determined by spectrophtometric techniques like UV and IR. Stability studies of gatifloxacin and moxifloxacin were carried out under accelerated and long term conditions. Thermo lab stability chamber model T90008008 was used for that purpose. For accelerated stability studies, gatifloxacin and moxifloxacin were kept at 40 °C ± 2 °C at humidity RH 75% ± 5% and nil intensity of light (illuminate degree) was applied for six months. For long term stability conditions, at 30 °C ± 2 °C, humidity RH 70% ± 5% and nil intensity of light (illuminate degree) was applied for 12 months. No significant changed were observed on gatifloxacin under accelerated and long term conditions. In order to monitor the stability studies, the HPLC and spectrophotometric methods were developed as per ICH guide line. IR spectra were also obtained for identification of gatifloxacin and moxifloxacin were during stability studies. xix

In-vitro biological activities (antibacterial and antifungal) of gatifloxacin and moxifloxacin and their metal complexes were performed. It was found that the metal complexes are more active as compared to gatifloxacin and moxifloxacin.