Assessing physical properties of amphoteric fluoroquinolones using phosphorescence spectroscopy

The self-association of fluoroquinolones (FQ) in water would play a relevant role in their translocations across lipid membranes. Triplet excited states of these drugs have been shown as reporters of FQ self-association using laser flash photolysis technique. A study using low-temperature phosphorescence technique was performed with quinolone derivatives such as enoxacin (ENX), norfloxacin (NFX), pefloxacin (PFX), ciprofloxacin (CPX, ofloxacin (OFX), nalidixic acid (NLA), pipemidic acid (PPA) and piromidic acid (PRA) to explore emission changes associated with self-associations and to shed some light on the triplet excited state energy (E_T) discrepancies described in the literature for most of these drugs. The emissions obtained at 77 K in buffered aqueous medium revealed that the amphoteric nature of the quinolones CPX, NFX, PFX, ENX, OFX and PPA must generate their self-associations because a redshift of their phosphorescence maxima is produced by FQ concentrations increases. Hence, this effect was not observed for NLA and PRA or when all quinolones were analysed using ethanol or ethylene glycol aqueous mixtures as glassed solvents. Interestingly, the presence of these organic mixtures produced a blue-shift in the phosphorescence emission maximum of each FQ. Additionally, laser flash photolysis experiments with PRA and the amphoteric quinolone PPA, compounds with the same skeleton but different peripheral substituent, confirm the expected correlations between the amphoteric nature of compounds and their self-associations in aqueous media because the excimer generation was only detected for PPA. Now, the discrepancies described in the literature for the E_T of FQs can be understood considering that changes of medium polarity or proticity as well as the temperature can considerably modify their E_T values. Thereby, low-temperature phosphorescence technique, is an effective way to detect molecular self-associations and surrounding changes in quinolones that opens the possibility to evaluate these effects in other drug families.