Vibrational spectroscopic characterization of fluoroquinolones.
Quinolones are important gyrase inhibitors. Even though they are used as active agents in many antibiotics, the detailed mechanism of action on a molecular level is so far not known. It is of greatest interest to shed light on this drug-target interaction to provide useful information in the fight against growing resistances and obtain new insights for the development of new powerful drugs. To reach this goal, on a first step it is essential to understand the structural characteristics of the drugs and the effects that are caused by the environment in detail. In this work we report on Raman spectroscopical investigations of a variety of gyrase inhibitors (nalidixic acid, oxolinic acid, cinoxacin, flumequine, norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, enoxacin, sarafloxacin and moxifloxacin) by means of micro-Raman spectroscopy excited with various excitation wavelengths, both in the off-resonance region (532, 633, 830 and 1064 nm) and in the resonance region (resonance Raman spectroscopy at 244, 257 and 275 nm). Furthermore DFT calculations were performed to assign the vibrational modes, as well as for an identification of intramolecular hydrogen bonding motifs. The effect of small changes in the drug environment was studied by adding successively small amounts of water until physiological low concentrations of the drugs in aqueous solution were obtained. At these low concentrations resonance Raman spectroscopy proved to be a useful and sensitive technique. Supplementary information was obtained from IR and UV/vis spectroscopy.
Neugebauer
U
U
Institut für Physikalische Chemie der Universität Jena, Helmholtzweg 4, D-07743 Jena, Germany.
Szeghalmi
A
A
Schmitt
M
M
Kiefer
W
W
Popp
J
J
Holzgrabe
U
U
D001372:Aza Compounds / Q000737:chemistry; D002937:Cinoxacin / Q000737:chemistry; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000737:chemistry; D027081:DNA Gyrase / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D015365:Enoxacin / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D024841:Fluoroquinolones / Q000737:chemistry*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D008958:Models, Molecular; D008962:Models, Theoretical; D000077266:Moxifloxacin; D009268:Nalidixic Acid / Q000737:chemistry; D009643:Norfloxacin / Q000737:chemistry; D015242:Ofloxacin / Q000737:chemistry; D010093:Oxolinic Acid / Q000737:chemistry; D011804:Quinolines / Q000737:chemistry; D015363:Quinolones / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013696:Temperature; D014466:Ultraviolet Rays; D014732:Vibration; D014867:Water / Q000737:chemistry
D001372:Aza Compounds; D004269:DNA, Bacterial; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D011804:Quinolines; D015363:Quinolones; D014867:Water; D015365:Enoxacin; D009268:Nalidixic Acid; D002939:Ciprofloxacin; D015242:Ofloxacin; D027081:DNA Gyrase; D010093:Oxolinic Acid; C053091:lomefloxacin; D002937:Cinoxacin; D009643:Norfloxacin; C047224:sarafloxacin; D000077266:Moxifloxacin; C012976:flumequine