A new insight into the oxidative mechanism of caffeine and related methylxanthines in aprotic medium: May caffeine be really considered as an antioxidant?

Background: Antioxidant properties have been recently suggested for caffeine that seems showing protective effects against damages caused by oxidative stress. In particular, a HO% scavenging activity has been ascribed to caffeine. Even if the oxidation of caffeine has been widely studied, the antioxidant mechanism is still far to be understood. Methods: The electrochemical behavior of caffeine, theobromine and theophylline was studied in aprotic medium by cyclic voltammetry and electrolysis in UV–vis cell; a computational analysis of the molecular structures based on the Density Functional Theory was performed; the reactivity of all substrates towards lead dioxide, superoxide and galvinoxyl radical was followed by UV–vis spectrophotometry. Results: Results supported the mono-electronic oxidation of the C4]C5 bond for all substrates at high oxidation potentials, the electron-transfer process leading to a radical cation or a neutral radical according to the starting methylxanthine N7-substituted (caffeine and theobromine) or N7-unsubstituted (theophylline), respectively. A different following chemical fate might be predicted for the radical cation or the neutral radical. No interaction was evidenced towards the tested reactive oxygen species. Conclusions: No reactivity via H-atom transfer was evidenced for all studied compounds, suggesting that an antiradical activity should be excluded. Some reactivity only with strong oxidants could be predicted via electron- transfer. The acclaimed HO% scavenging activity should be interpreted in these terms. The study suggested that CAF might be hardly considered an antioxidant. General significance: Beyond the experimental methods used, the discussion of the present results might provide food for thought to the wide audience working on antioxidants

Xanthine scaffold: available synthesis routes to deliver diversity by derivatization

The functionalization of the skeletal systems of heterocycles represents a significant goal for the development of new compounds. The heterocyclic molecule xanthine (3,7-dihydro-1Hpurine- 2,6-dione) is a purine base with a bicyclic ring skeleton and four different nitrogen atoms, three of them are -NH groups. The principal derivatives are the well known natural methylxanthines (e.g., caffeine, theophylline and theobromine) that have prominent physiological effects at a very low dose. The natural methylated xanthines, theophylline, theobromine and caffeine, are present in different plants such as the tea, cocoa and coffee species. For this reason natural xanthines can be considered as bio-based and renewable starting materials; their use in organic synthesis is strongly recommended in order to carry out sustainable chemistry. Essentially, the xanthine scaffold led to the preparation of numerous compounds very attractive in the pharmaceutical field, and these drugs are commercialized for a wide range of biological activities. The scope of this mini-review is to consider the use of natural xanthines as starting material in chemical transformations carried out in organic solvents, without the intent to be exhaustive of all the synthetically chemical applications. More information on the chemical and electrochemical reactivity of this structural core in an organic solvent can be useful for the scientific community. The effectiveness of natural xanthines can be improved by modifying the structures of these already biologically active compounds

A Simplified Framework for Historic Cities to Define Strategies Aimed at Implementing Resilience Skills: The Case of Lisbon Downtown

The concepts of resistance to unforeseen disasters and rapid post-disaster recovery of historic cities are necessary due to the earthquakes that have profoundly influenced their evolution. The improvement of this property strongly depends on the effectiveness of the preventive tools. In this work, an operational framework for the resilience assessment of a historical city characterized by high cultural and historical elements is developed, which corresponds to the main contribution of this research. The research includes multicriteria analysis based on the in-depth knowledge of the city’s historical development, the study of the effects of past earthquakes, structural vulnerability analysis of pombalino buildings, architectural types and socio-economic aspects. The aim is to obtain the necessary elements to guide an aware plan for improving resilience and the reduction of vulnerability through a GIS tool aimed at preventing and defining urban intervention priorities. The framework proposed is applied to Lisbon downtown

Environmental aspects of internal migration in Tanzania

In recent years, the issue of the nexus of climate change and human migration has attracted a growing amount of interest among scholars and policy makers. Using individual-level data from the Tanzania National Panel Survey conducted in 2008\u20132009, we examine the roles played by droughts or floods, crop diseases, and severe water shortages in inter-district migration in Tanzania. Findings reveal that droughts or floods and crop diseases are associated with an overall decrease in the likelihood of inter-district mobility, providing support for the \u201cenvironmental scarcity\u201d hypothesis. Yet migration becomes a likely response to droughts and floods among individuals with no education suggesting mobility is a key livelihood strategy among those most disadvantaged. Future examination of domestic migration-environment processes at the individual-level is critical for informed policy and programs

WO3 and Ionic Liquids: A Synergic Pair for Pollutant Gas Sensing and Desulfurization

This review deals with the notable results obtained by the synergy between ionic liquids (ILs) and WO3 in the field of pollutant gas sensing and sulfur removal pretreatment of fuels. Starting from the known characteristics of tungsten trioxide as catalytic material, many authors have proposed the use of ionic liquids in order to both direct WO3 production towards controllable nanostructures (nanorods, nanospheres, etc.) and to modify the metal oxide structure (incorporating ILs) in order to increase the gas adsorption ability and, thus, the catalytic eciency. Moreover, ionic liquids are able to highly disperse WO3 in composites, thus enhancing the contact surface and the catalytic ability of WO3 in both hydrodesulfurization (HDS) and oxidative desulfurization (ODS) of liquid fuels. In particular, the use of ILs in composite synthesis can direct the hydrogenation process (HDS) towards sulfur compounds rather than towards olefins, thus preserving the octane number of the fuel while highly reducing the sulfur content and, thus, the possibility of air pollution with sulfur oxides. A similar performance enhancement was obtained in ODS, where the high dispersion of WO3 (due to the use of ILs during the synthesis) allows for noteworthy results at very low temperatures (50 C)

Reaction of Electrogenerated Cyanomethyl Anion with Cyclohexylisocyanate: Synthesis of N-(cyclohexylcarbamoyl) acetamide. An Unexpected Product

The contamination with water of the cathodic ACN-Et4NBF4 solution gave us the opportunity to investigate alkyl isocyanate reactivity toward electrogenerated anions. The cathodic reduction of a ACN-Et4NBF4 solution led to the formation of both hydroxide and cyanomethyl anions. The reaction of the catholyte with cyclohexylisocyanate led to the exclusive formation of acetamidated product, with no traces of cyanomethylated one. On the contrary, when reacting with benzaldehyde only the cyanomethylated was isolated. Considering that the acetamidated product of benzaldehyde is reported to be unstable (thus its formation cannot be excluded), various experiments were carried out in order to understand the anomalous reactivity of cyclohexylisocyanate. Moreover, computational analysis allowed to state the higher stability of acetamidated product with respect to the cyanomethylated one. The possibility of a concerted reaction, instead of acetamide anion formation prior to the reaction, is still an open question

Organic electrochemistry: Synthesis and functionalization of β-lactams in the twenty-first century

Organic electrochemistry is a technique that allows for the heterogeneous redox reactions avoiding both the use of stoichiometric amounts of redox reagents and the resulting formation of stoichiometric by-pro- ducts. In fact, the redox reagent in these reactions is the electron, which is naturally eco-friendly and pro- duces no side compounds. It is therefore quite obvious that electrochemistry can be classified as a “green” tech- nology. The use of this methodology in the synthesis of β-lactams is not a novelty, but the growing interest in this class of biologically active compounds, due to the dis- covery of new fields of application (after a moment of decrease in interest due to antibiotic resistance) has been a stimulus for the search for more efficient electro- chemical ways to synthesize and transform β-lactams. Thus, this review deals with the twenty-first-century applications of electroorganic technique to the chemistry of β-lactams, by analyzing first the syntheses classified by the type of reactions (cyclization, cycloaddition, etc.) and then by manipulating the β-lactam structure, using it as a synthon. Lastly, the importance of this technique is demonstrated by a study of a pilot plant scale reduction of a cephalosporanic acid derivative to a commercially important antibiotic

Guaifenesin-Ketamine-Xylazine Infusion to Maintain Anesthesia in Mules Undergoing Field Castration

Many minor and surgical procedures can be performed in the field under sedation or general anaesthesia. Numerous drug combinations have been used for sedation, induction and maintenance. The purpose of this study was to determine if the combination of guaifenesin, ketamine and xylazine, commonly referred to as “triple drip”, produce safe and satisfactory total intravenous anaesthesia in mules undergoing field castration, premedicated with xylazine and induced with thiopental. Eight healthy adult intact male mules, aged 4 to 6 years and weighing 380 to 490, were anesthetized to performe field castration. Before anaesthesia a 14-gauge, 13–cm catheter was placed percutaneously in the external jugular vein. Mules were premedicated with 1.3 mg/kg xylazine IV and anaesthesia was then inducted with 6 mg/kg IV thiopental within 10 min after premedication, when the animals were at least moderately sedated. Additional xylazine was administered when the mules were inadequately sedated. Sedation was considered good when lowering of the head, drooping of the lower lip and drooping of the ears were present using a 4-point sedation score. Once the mules were recumbent, the infusion of guaifenesin (50 mg/ml) - ketamine (20 mg/ml) - xylazine (0.5 mg/ml) (GKX) was started to maintain general anaesthesia, approximately 1ml/kg/hr (based on monitoring eye signs, muscle relaxation of the neck, respiratory rate and pattern, and the responses to surgical stimulation. The spermatic cord of each testis was infiltrated with 5 ml of lidocaine to achieve local anaesthesia before the scrotum skin incision. The open technique of castration was applied to all mules for postoperative drainage. During anaesthesia heart rate (HR), respiratory rate RR), rectal temperature (RT) and hemoglobin saturation with oxygen (SpO2) were measured every 5 minutes. Times to sternal recumbency, lateral recumbency and standing were recorded. The data recorded were statistically analysed using simple one-way analysis of variance (ANOVA) and a pvalue>0.05 was considered significant. The qualities of anaesthesia were evaluated using induction, maintenance and recovery scores. The resultes suggest that the premedication using 1.3 mg/kg IV xylazine for mules undergoing thiopental anaesthesia was satisfactory and only one animal needed a supplemental dose of xylazine (0.3 mg/kg IV) to induce better sedation. The total IV amount of thiopental for induction was sufficient to achieve lateral recumbency in all animals. Furthermore, GKX provided adequate surgical plane of general anaesthesia to performe castration in all mules, without responses to the manuality or significant modification of HH, RR, RT, and SpO2 in comparison with the basal values and to maintain a satisfactory muscle relaxation. Recovery from anaesthesia was uneventful, smooth and clinically acceptable in all mules

An insight into the reactivity of the electrogenerated radical cation of caffeine

Controlled potential electrolyses of caffeine (CAF) were carried out at a Pt electrode in undried acetonitrile (ACN) and ACN-H2O and the products of the anodic oxidation were analyzed by HPLC-PDA-ESI-MS/MS. A higher current efficiency occurred in ACN-H2O, but an analogous chromatographic outline was found in both media, evidencing a reactive pathway of the electrogenerated radical cation CAF•+ with water, added or in trace, as nucleophile. No dimeric forms were evidenced, excluding any coupling reactions. Neither was 1,3,7-trimethyluric acid found, reported in the literature as the main oxidative route for CAF in water. Four main chromatographic peaks were evidenced, assigned to four proposed structures on the base of chromatographic and spectral data: a 4,5-diol derivative and an oxazolidin-2-one derivative were assigned as principal oxidation products, supporting a mechanism proposed in a previous work for the primary anodic oxidation of the methylxanthines olefinic C4 = C 5 bond. Two highly polar degradation products were also tentatively assigned, that seemed generating along two different pathways, one opening the imidazolic moiety and another one opening the purinic one

Impact of dealcoholization by osmotic distillation on metabolic profile, phenolic content, and antioxidant capacity of low alcoholic craft beers with different malt compositions

Beer antioxidants originate mainly from malts, classified as colored, caramel, and roasted, according to the malting process. This study aimed to characterize, in terms of phenolic antioxidants, three types of Pale Ale craft beers brewed using increasing percentage of dark malt (0, 5, and 15% Caraamber malt, called PA100, PA95, PA85, respectively) and to evaluate the impact of dealcoholization by osmotic distillation (OD) on the same antioxidants. All the alcoholic (PA, 6.2-6.8 vol %) and low alcoholic (LA-PA, 1 vol %) beers were analyzed by HPLC-ESI-MS/MS, total phenolic content (TPC), and antioxidant activity (AA): similar phenolic profiles were evidenced and 43 compounds identified or tentatively identified. Some differences were found among PA100, PA95, and PA85: PA85 was richer in free phenolic compounds (10.55 mg/L) and had a higher TPC (463.7 GAE mg/L) and AA (852.1 TE mg/L). LA-PA beers showed the same phenolic profile and similar TPC and AA compared to PA beers; however, there were some differences regarding LA-PA85 (5.91 mg/L). Dealcoholization by OD seemed to weakly affect the phenolic fraction. ESI-MS/MS infusion experiments evidenced oligosaccharides, small organic acids, and amino acids, whose presence was confirmed and quantitated by NMR: besides ethanol and other alcohols, weak to strong loss of low-molecular-weight metabolites was evidenced in LA-PA beers