Xenobiotics in the environment: an investigation on the transformation kinetics, the environmental metabolites and their formation mechanisms.
Creators: name: Passananti, Monica
Publisher: name: Università degli Studi di Napoli Federico II
Year: 2013

description: Xenobiotics are continually introduced into the environment and it is very important to draw up an “environmental risk assessment” for these pollutants. Xenobiotics can be persistent and accumulate in the environment or undergo biotic and/or abiotic transformations leading to transformation products. The latter are known as environmental metabolites and may be more toxic and/or persistent than the parent compounds. Therefore, it is important to have information on the xenobiotic behavior in the different compartments (water, atmosphere, soil) as well as on the nature of their transformation products. The photochemical processes play an essential role in the environmental degradation of pollutants. Phototransformation studies may be used in combination with physical chemical properties and data from other studies (abiotic hydrolysis; biotransformation; adsorption/desorption) to help the assessment of the overall environmental transformations and transport of chemical pollutants. The photochemical behavior of a molecule depends on the presence of peculiar functional groups. However, given the heterogeneity and complexity of xenobiotics, it is often difficult to predict or rationalize the photochemical behavior of these molecules. In this PhD thesis the photochemical behavior of some chemical pollutants (mainly drugs and pesticides) under environmental-like conditions has been investigated. The selected xenobiotics are characterized by the presence in the molecular structure of a carbamate function or an indole moiety, two functions present in widely used bioactive compounds. In particular, direct photolysis studies have been carried out on drugs indomethacin, etodolac, loratidine and rivastigmine, on pesticides chlorpropham and phenisopham and on carbamic model compounds. Indirect photolysis of rivastigmine and nicotine have also been investigated. Moreover, for some xenobiotics photochemical experiments in soil have been performed. Direct photolysis studies have led to the determination of phototransformation kinetics, isolation and characterization of photoproducts and interpretation of the involved mechanisms. Investigation on indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has  evidenced the role of the aryl portion in the formation of ionic species prior to the decarboxylation, and the results give a further support to the general photodecarboxylation mechanism of arylalkanoic acids. The photochemical oxidative cleavage of C2-C3 bond through the intermediacy of peroxidic species has also been observed, and this supports the tendency of indoles to give self-sensitized photooxygenation. This type of reaction has also been observed for the other indolic drug examined, etodolac. Investigation on rivastigmine and its main human metabolite has evidenced a peculiar photochemical behavior. Both compounds undergo a β-cleavage of the benzylamine moiety resulting in photosolvolysis reaction, previously reported for benzyl ethers or esters. In particular, the photodegradation involves the tertiary amino site and leads mainly to ion-derived products characterized by departure of the Me2N-group. It is reported that amines bearing N-substituents that are capable of stabilizing the formed aminium radicals have lower oxidation potentials as compared to those with N-electron with¬drawing substituents as amides and carbamates.  This could account for the unreactivity of the carbamic-N function of rivastigmine as compared with the reactivity of the benzylaminic function. Loratidine is rapidly transformed either under UV-B or by sunlight exposure. In this case the reactive site is the double bond, while the carbamate moiety is unreactive. Pesticides chlorpropham and phenisopham contain a carbamate and a bis-carbamate function, respectively; in phenisopham one of the functions is similarly substituted as in chlorpropham. Neverthless, the two pesticides behave differently: the first one undergoes a nucleophilic photosubstitution of chlorine with water on the aromatic ring, while in phenisopham photo-Fries rearrangements occur involving the cleavage of the N-aryl O-aryl carbamate moiety. However investigation on model compounds evidences that N-aryl O-aryl substitution is not a sufficient condition to have a photo-induced breaking of the carbamate bond. This breaking is completely overcome in the presence of a chlorine on the aromatic ring. Moreover, substitution on the carbamic nitrogen as well as the presence of a N-substituent in the O-aryl moiety appears determinant to accelerate the photo-Fries reaction. All photochemical experiments evidence the determinant role of water. This is probably due to the fact that water can favor photoionization reactions, stabilize ionic intermediates and trap electrophilic species. Indirect photolysis investigations have been performed on rivastigmine and nicotine in Clermont-Ferrand (France) in collaboration with Laboratoire de Photochimie Moléculaire et Macromoléculaire-University Blaise Pascal. The results show that the degradation rate of both compounds depends on the HO• source (H2O2, nitrates, nitrites). Faster degradation has been observed in the presence of nitrates and nitrites and is probably due to reactions between the xenobiotics and photogenerated reactive nitrogen species. For rivastigmine the formation of nitro derivatives has been confirmed by LC-MS. Nitro compounds are often more toxic than the parent compounds, and hence for a complete environmental risk assessment the reactivity toward hydroxyl radical and also toward nitro reactive species that are naturally present in surface waters should be considered. Less satisfying has been the investigation on the photochemistry in soils. Despite the simple synthetic model soils used each compound examined behaves differently depending on the light absorption property and on the formation of saline bonds due to the presence of acidic or basic reactive sites. In addition to these factors in real soils other factors should be considered as the presence of microorganisms or xenobiotics, the type of texture, the pH, etc. In conclusion, the whole of the results give information on the photochemical behavior of different xenobiotics under environmental-like conditions. From a chemical point of view they give a deeper insight into the substituent and solvent effects in the photochemistry of some important compound classes as indoles, benzyl derivatives and carbamates. Therefore, these studies could allow to develop theoretical models for the prediction of the environmental fate of xenobiotics.