Irena Škorić

Photolytic degradation of norfloxacin, enrofloxacin and ciprofloxacin in various aqueous media

The photolytic degradation of norfloxacin, enrofloxacin and ciprofloxacin, fluoroquinolone antibacterials widely used in human and veterinary medicine, was investigated under simulated solar irradiation in different water matrices (river water and synthetic wastewater similar by composition to wastewater of pharmaceutical industry). The results showed that investigated fluoroquinolones degrade very quickly and photodegradation followed pseudo first order kinetics. The slowest photodegradation rate was observed in river water for all three fluoroquinolones. In the case of pharmaceutical mixture irradiation, no significant differences in rate constants were observed compared to single-component experiments. The structures of photodegradation products were determined and photodegradation pathways were suggested. Two main processes occurred primary from enrofloxacin depending on pH values: (I) cyclopropane ring cleavage at pH 4 and (II) oxidative photodegradation at pH 8. The structures of the photoproducts E-1 to E-6 are unknown and have not been reported for this fluoroquinolone. For ciprofloxacin two main processes were also identified depending on experimental conditions. Under acidic conditions (pH 4), reactions involved rather the quinolone ring (cleavage of the cyclopropane ring and fluorine solvolysis), while at pH 8 the side-chain reactions took place. The photodegradation pathway of norfloxacin somewhat differed from the previous two. There was no significant dependence on reaction conditions and there were no two different pathways. Determination and identification of photodegradation products were performed by liquid chromatography-mass spectrometry (LC-MS/MS). The obtained results are of importance for assessing the environmental fate of fluoroquinolones in aqueous media.

Photophysics of Push–Pull Distyrylfurans, Thiophenes and Pyridines by Fast and Ultrafast Techniques

Time-resolved transient absorption and fluorescence spectroscopy with nano- and femtosecond time resolution were used to investigate the deactivation pathways of the excited states of distyrylfuran, thiophene and pyridine derivatives in several organic solvents of different polarity in detail. The rate constant of the main decay processes (fluorescence, singlet-triplet intersystem crossing, isomerisation and internal conversion) are strongly affected by the nature [locally excited (LE) or charge transfer (CT)] and selective position of the lowest excited singlet states. In particular, the heteroaromatic central ring significantly enhances the intramolecular charge-transfer process, which is operative even in a non-polar solvent. Both the thiophene and pyridine moieties enhance the S1 →T1 rate with respect to the furan one. This is due to the heavy-atom effect (thiophene compounds) and to the (1) (π,π)*→(3) (n,π)* transition (pyridine compounds), which enhance the spin-orbit coupling. Moreover, the solvent polarity also plays a significant role in the photophysical properties of these push-pull compounds: in fact, a particularly fast (1) LE*→(1) CT* process was found for dimethylamino derivatives in the most polar solvents (time constant, τ≤400 fs), while it takes place in tens of picoseconds in non-polar solvents. It was also shown that the CT character of the lowest excited singlet state decreased by replacing the dimethylamino side group with a methoxy one. The latter causes a decrease in the emissive decay and an enhancement of triplet-state formation. The photoisomerisation mechanism (singlet/triplet) is also discussed.

Photochemical dimerization of styrylnaphthofurans-II

Irradiation of styrylnaphthofurans (3a, 3b) [10-1 M] (benzene) under anaerobic conditions gives mainly dimeric products (65-70%): [2+2] ethene-ethene cycloaddition products (9a, 9b, 10a, 10b, and 11a, 11b) (40-44%) and [2+2] ethene-furan cycloaddition products (12a, 12b) (20-22%). Minor quantities of electrocyclization products (7a, 7b) (3.5-4.5%) and dihydrocyclization products (8a, 8b) (3-4.5%) are also isolated. The structures of the products are based on 1H and 13C NMR spectra, applying COSY, LR COSY, APT, HETCOR and NOESY techniques.

Thermal reaction of [3,4]-benzo-8-substituted-3Z,5Z,7E-octatetraenes and quantum-chemical study of the (8π,6π)-electrocyclisation

The first example of thermal (8π,6π)-electrocyclisation of 1,3,5,7-octatetraene with one double bond embedded in an aromatic moiety is described. By this process, [3,4]-benzo-8-substituted octatetraene derivatives, the cis,trans-1-(o-vinylphenyl)-4-(R = Me, Ph, 2-furyl)buta-1,3-dienes were transformed to a new endo-7-(R = Me, Ph, 2-furyl) and exo-7-(R = Me)-2,3-benzobicyclo[4.2.0]octa-2,4-dienes. Mechanism of reaction was also studied by DFT quantum-chemical calculations. The M06/6-311+G(d,p)//M06/6-31+G(d,p) calculations indicate that formation of the single endo-isomer in the case of phenyl and 2-furyl substituents is determined by higher activation barriers for exo-6π-electrocyclisation than for 8π-cycloreversion.

Kinetics and degradation pathways of photolytic and photocatalytic oxidation of the anthelmintic drug praziquantel

In this study, an anthelmintic drug, praziquantel(PZQ), was degraded using the direct photolysis, photocatalysis, and oxidation processes including UV radiation, TiO2 film, and hydrogen peroxide. The photolytic degradation with predominant wavelengths of 185/254nm (UV-C) proved to be more efficient with a half-life of 3.13min compared to the radiation of 365nm (UV-A) where the degradation did not occur. In order to enhance the rate of PZQ photolytic degradation, H2O2 was added, which resulted in two to three times higher degradation rates. In the photocatalytic degradation, TiO2 film was used as catalyst. The degradation was ten times faster in the photocatalytic experiments where UV-C light (k=0.2390min-1) was used than in those with UV-A (k=0.0201min-1). Comparing the results from all performed experiments it can be concluded that the UV-C/TiO2/H2O2 process yielded the highest degradation rate and complete degradation of PZQ was obtained in less than 7min. The degradation of PZQ followed the first order kinetics in all the experiments. The photo degradation was inhibited in the presence of methanol. The degradation pathways and the structural formulae of five degradation products (m/z 273, 269, 189, 147, 132) were proposed based on the liquid chromatography tandem mass spectrometry analysis.

Synthesis, Photochemistry, and Photophysics of Butadiene Derivatives: Influence of the Methyl Group on the Molecular Structure and Photoinduced Behavior

Novel butadiene derivatives display diverse photochemistry and photophysics. Excitation of 2-methyl-1-(o-vinylphenyl)-4-phenylbutadiene leads to the dihydronaphthalene derivative, whereas photolysis of the corresponding model o-methyl analogue results in the formation of the naphthalene-like derivative, deviating from the nonmethylated analogue of the prior starting compound and producing benzobi- and -tricyclic compounds. The effect of the methyl substituents is even more dramatic in the case of the dibutadienes. The parent unsubstituted compound undergoes photoinduced intramolecular cycloaddition giving benzobicyclo[3.2.1]octadiene, whereas the photochemical reaction of the corresponding dimethylated derivative shows only geometrical isomerization due to the steric effect of the substituents. Methyl groups on the butadiene backbones reduce the extent of conjugation, causing a blue-shift of the characteristic absorption band. The fluorescence efficiency is dramatically decreased, as a consequence of nonplanarity and reduced rigidity of the molecules due to the crowding by the methyl and phenyl groups together. Four molecules of very similar structures show dramatically different photoinduced behavior, revealing how changes of the nature and position of the substituents are valuable in understanding the photophysics and photochemistry of these types of compounds.

Identification of Degradation Products of Praziquantel during the Mechanochemical Activation

Graphical abstract Figure. No caption available. HighlightsPraziquantel, BCS II class drug, is mechanochemically activated in vibrational mill.Cogrinding process with povidone and crospovidone gives several degradation products.Degradation products depend on the polymer type rather than the process conditions.Two of the main degradation products are identified.Structure are proposed on the basis of GC–MS, UPLC‐MS and 1H NMR. ABSTRACT Praziquantel (PZQ) is an inexpensive, low toxicity BCS II class anthelmintic drug used for the treatment of neglected tropical diseases. In earlier papers a mechanochemical activation has been used to induce physical transformations on the drug which would ameliorate its solubility and hence its bioavailability and a systematic study of the effects of varying temperature, frequency and time of milling on drug melting enthalpy and drug recovery was given. In this communication, the focus is on the degradation products that are formed during this mechanical treatment of Praziquantel. In the cogrinding process with povidone and crospovidone several degradation products are formed. Different degradation products are formed, which depend on the type of polymer rather than the process conditions. Two of the most prominent degradation products were identified and their structure proposed on the basis of information obtained from GC–MS, UPLC‐MS and 1H NMR techniques.