In the presence of Nα-acetyllysine, cross-links of aldehydic adenine nucleoside adducts with N-acetylcysteine lose an N-acetylcysteine moiety undergoing transformation into amino derivatives.

Fluvastatin (FLV) belongs to the group of compounds referred to as statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Statins act as cholesterol-lowering agents and are among the most frequently prescribed drugs. They upregulate low-density lipoprotein receptors in the liver by binding to the active site of HMG-CoA reductase, which is the key enzyme in cholesterol biosynthesis. Statins have been detected as contaminants in natural waters and are susceptible to degradation upon exposure to light. Fluvastatin is extremely sensitive to light; upon irradiation it forms a range of photoproducts. In this study the fluvastatin molar absorption coefficient and the quantum yield of the drug photodegradation were determined. The FLV photodegradation quantum yield value determined in this work (Φ = 0.13 ± 0.02) was found to be significantly larger than that previously reported in the literature. Our results also showed that the generation of singlet oxygen is not involved in the drug photodecomposition indicating that the excited triplet state of fluvastatin is not populated efficiently. Moreover, experimental methods and DFT calculations were applied to get insight into the possible mechanisms of fluvastatin primary photoproduct formation. Using the transient absorption spectroscopy technique, the transient species formed immediately after the drug excitation were followed, and the scheme for fluvastatin primary photochemistry was suggested. The primary photoproducts were identified on the basis of spectroscopic and spectrometric methods. A new mechanism for photooxygenation leading to the formation of one of the identified photoproducts (FP2) was proposed and a new approach to the formation of the other photoproduct (FP1) was provided. The theoretical mechanistic explanation of the photoproduct formation is in excellent agreement with the experimental data.

The substitution position in the etheno rings of M1Gx-A and M1MGx-dA was determined based on the comparison of data derived from NMR spectra with results obtained from computational calculations.

: Glutathione (GSH), due to the ability to capture the reactive electrophiles of exo- and endogenous origin, is expected to prevent cross-linking induced by these compounds. However, it may instead become cross-linked itself. We subjected glutathione to reactions with model α,β-unsaturated carbonyl systems resulting from the interactions of adenosine with bifunctional aldehyde products of lipid peroxidation, and identified a range of adducts and cross-linked products. We found that the S-conjugated adducts, initially formed in the typical for GSH Michael addition to α,β-unsaturated carbonyl system, unexpectedly undergo gradual degradation giving rise to the final N-conjugated products, in which formation of the peptide amino group was involved instead of the sulfhydryl functionality. This finding shows that the role of the GSH amino group in the non-enzymatic detoxification is underestimated and that reactions between cellular α,β-unsaturated carbonyl compounds, and GSH may be more complex than are presently perceived.