99 research outputs found

    UV-A light treatment for controlling enzymatic browning of fresh-cut fruits

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    Enzymatic browning is critical in the preservation of the quality and the shelf-life of fresh-cut fruits. Non-thermal technologies such as UV radiation are emerging for controlling polyphenol oxidase (PPO) activity, the main agent responsible for browning. After determining the best operational conditions of a UV LED illuminator (2.43\ub710-3 Wm-2 irradiance), the anti-browning effect of UV-A light (390 nm) treatment at 25 \ub0C over increasing time periods up to 60 min was assessed on fresh-cut apples (Golden Delicious, Granny Smith, Fuji) and pears (Abate F\ue9tel, Decana). Colour variation (\u394E) and its percent reduction (%R\u394E) were measured using a colorimeter and the greatest effect was observed in apples which showed higher %R\u394E values than pears (58% vs 25% after 60 min exposure, respectively). Moreover electrophoretic and zymographic techniques demonstrated the inhibitory effect of UV-A irradiation on PPO activity. Anti-browning was found to be related to irradiance, exposure time and the fruit cultivar. Overall this study confirmed UV-A LED technology as an eco-friendly alternative to traditional approaches for reducing browning of minimally processed products. Industrial relevance: Treatment of fresh-cut products with UV-A LED is not only easy and inexpensive to produce but also presents few hazards for humans. Moreover, the use of LED light sources brings many advantages such as energy savings, device durability, low environmental impact, high luminous efficiency and little thermal effect. UV-A LED technology has great potential to meet the demands of the food industry in the processing of fresh-cut fruits and vegetables. In addition it could also be considered a pre-treatment of fruits and vegetables being processed for the production of snacks

    Antioxidant Properties of Soybean Oil Supplemented with Ginger and Turmeric Powders

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    Soybean oil has been supplemented with 10% (w/w) of ginger and turmeric powders derived from commercial products (GC—commercial ginger and TC—commercial turmeric), freeze-dried rhizomes (freeze-dried ginger (GR) and freeze-dried turmeric rhizome—TR) and peels (freeze-dried ginger peel (GP) and freeze-dried turmeric peel—TP) for developing a functional seasoning with great lipid stability for human consumption. The exhausted ginger and turmeric powders were also recovered and recycled two times to promote a more sustainable process. The antioxidant activity and oxidative stability of oil samples were evaluated respectively by spectrophotometric and Rancimat methods. Folin–Ciocalteu assay and HPLC analysis were also performed to quantify total polyphenols, ginger-derived 6-gingerol and 6-shogaol, and turmeric-derived curcumin. Their antioxidant activity as well as oxidative stability, which non-linearly decreased over cycles because of a strongly reduced phenolic extractability, linearly increased with increasing phenolic yields. Hence, ginger and turmeric can be proposed as healthy spices containing bioactive compounds to control lipid oxidation and improve oil stability. Moreover, the valorization of peels as eco-friendly source of natural antioxidants is a valid strategy for providing added-value to these agro-food wastes

    Co-fermentation of onion and whey: a promising synbiotic combination

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    Juice from three different onion varieties was mixed with sweet whey and used as growth 18 substrate for four lactic acid bacteria strains, isolated from agri-food by-products, to 19 evaluate the possibility to exploit such substrates, known to be reach in bioactive 20 molecules, as fermented drinks for human consumption. Results show good growth 21 performance for Lactobacillus fabifermentans, L. plantarum and Streptococcus 22 macedonicus. On the contrary S. thermophilus did not grow in the mixture while S. 23 macedonicus did not develop in pure onion juice. After 48 h the overall sugar content 24 decreased significantly. In particular, glucose was not utilized while inulin was completely 25 preserved. Moreover, MS/MS analysis revealed the presence of the rare trisaccharide 26 lactosucrose. 27 In the light of these considerations, the formulation obtained may be considered a potential 28 synbiotic product with pleasant taste and beneficial effects for consumers and also an eco-29 friendly solution to convert an agro-food by-product into value added products

    Innovative technologies and bioactive compounds for the control of polyphenol oxidase

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    The enzymatic browning and melanogenesis are associated respectively with the most of qualitative and economical losses during post-harvest processing in agro-food industry and human skin disorders in cosmetic field. The main responsible is tyrosinase or polyphenol oxidase (PPO, EC 1.14.18.1), a copper-containing oxidoreductase that catalyses two different enzymatic reactions involving polyphenolic substrates and oxygen and producing dark pigments. Recently, the research of new eco-friendly systems for controlling PPO activity is focused on innovative non-thermal technologies and bioactive compounds to replace the conventional thermal treatments and traditional additives. All of these have critical points related not only to organoleptic and nutritional qualities of agro-food products and stability in cosmetic formulations but also to human health after topical, oral or parenteral exposure. In this regards, the goal of this study is to evaluate, by in vitro and in vivo assays, the anti-browning performances of a UV-A LED technology (first contribution) and two natural extracts obtained from agro-food by-products such as citrus hydrosols (CIHs; second contribution) and agricultural wastes like vineyard pruning residues (VPRs; third contribution). In the first contribution, after fixing the optimal operational conditions of a UV LED illuminator prototype (2.43·10-3 Wm-2 irradiance) in accordance with number of LED diodes, voltage, and distance from sample, the UV-A light (390 nm) treatment at 25 °C over increasing time periods up to 60 min was applied on fresh-cut apples (Golden Delicious, Granny Smith, and Fuji) and pears (Abate FĂ©tel and Decana). The total colour change (ΔE) and its percent reduction (%RΔE) were measured using a colorimeter and the greatest performances were observed in apples with higher %RΔE values than pears (58.3% vs. 25.5% on average after 60 min exposure, respectively). Moreover electrophoretic and zymographic techniques on the commercial mushroom tyrosinase (TYR) and PPO extracted from irradiated Golden Delicious apple slices confirmed the inhibitory effects of UV-A light on PPO activity. The anti-browning effectiveness of UV-A LED technology was related to irradiance, exposure time, and fruit type and cultivar. In the second contribution, three kinds of hydrosols, which have been obtained by subjecting citron, lemon, and orange peels to steam distillation (CH, LH, and, OH respectively), were spectrophotometrically assessed for anti-TYR activity in the presence of (+)–epicatechin and L-DOPA as the model phenolic substrates of plant enzymatic browning and human skin melanogenesis, respectively. All of the CIHs showed a mixed-type inhibition at varying levels in the 21.8–68.9 % range, depending on substrate type and concentration. The gas chromatography analysis (GC) of their terpene contents indicated that some known TYR inhibitors including myrcene, sabinene, geraniol and citral were present in CIHs. The third contribution investigate the anti-browning and antioxidant potentials of some grape juices obtained by cold-pressing the berries collected from the VPRs of Barbera (B) and Merlot (M) cultivars during 2013 (1) and 2014 (2) seasons. Among the VPRs, Merlot wastes spectrophotometrically exhibited a greater uncompetitive inhibition towards TYR activity than those of Barbera (68.2% and 67.8% for M1 and M2, respectively; 56.3% and 58.8% for B1 and B2, respectively), in the presence of catechol substrate, as confirmed also by gel diffusion assay. The zymographic techniques on the isoforms isolated from TYR and some plant PPOs (Fuji and Golden Delicious apples; Abate FĂ©tel pears; Bintje potatoes) as well as in vivo trials on several fresh-cut fruits (Fuji, Golden Delicious, Granny Smith apples; Abate and Decana pears) vegetables (Bintje potatoes; eggplants), and dried apple slices (Golden Delicious) demonstrated that the inhibitory performances were related mainly to enzyme source. In this regards, this chemical treatment with VPRs was not effective on pear PPO. However, the VPRs showed not only anti-browning but also whitening and antioxidant capacities that were associated mainly with their high organic acids and epigallocatechin gallate (EGCG) contents detected by HPLC analysis. Overall this research confirms that the inhibitory effectiveness is a function of PPO source and inhibitor type and dose. The UV-A LED technology, CIHs, and VPRs are eco-friendly, safe, and inexpensive systems for effectively inhibiting PPO activity, thus preserving the enzymatic browning in agro-food and cosmetic industries. Moreover, these natural extracts, whose anti-browning performances depends mainly on their bioactive compounds contents, suggest a possible recycling use with high value added of these agro-food by-products

    Valorization of onion extracts as anti-browning agents

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    The enzymatic browning, whose main responsible is polyphenol oxidase (PPO, EC 1.14.18.1), is involved in the phenolic oxidation and colour alteration of minimally-processed fruits and vegetables. Currently, the research of new strategies to inactivate PPO is moving towards replacing synthetic additives such as organic acids and sulphites with natural inhibitors. The present study is focused on investigating the anti-browning performance of juices and distillates obtained from three onion varieties (white, yellow, and red) and Borettana onion wastes (inner layers). Their inhibitory activity on a commercial mushroom tyrosinase and some plant PPOs has been evaluated by spectrophotometric and electrophoretic analysis. The in vivo trials has been also carried out by monitoring over time at room temperature the colour change on potato slices under accelerated browning conditions. The effectiveness of onion samples in limiting enzymatic browning was affected by not only the enzyme source but also inhibitor type. Although distillates had higher anti-PPO capacity as confirmed by in vitro assays, juices showed better in vivo effectiveness. Hence, onions and their wastes can be valorised as a natural source of anti-browning agents to control PPO activity thus preserving sensory, antioxidant and nutritional properties of agro-food products

    Identification of most relevant variables and processes to assess the environmental impacts of remediation technologies along their life cycles: Focus on the waste management scenarios

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    The application of Life Cycle Assessment (LCA) to remediation technologies is still not a consolidated practice and it is especially lacking in the assessment of the environmental impacts associated to the management of the waste produced during remediation. This study aims at addressing these methodological gaps by identifying the typologies of waste typically generated during the remediation of a contaminated site and classifying them according to the European Waste Catalogue (EWC) codes. Thereafter, the following steps are: (i) the identification of the waste management scenarios (WMSs) applicable to the identified waste typologies, (ii) the selection of Life Cycle Assessment processes that can be used to assess the impacts of the different WMSs and (iii) the quantification and comparison of the environmental impacts caused by the different WMSs applied considering hazardousness levels to which the same waste may belong in relation to its contamination levels and characteristics: inert, non-hazardous and hazardous waste (Waste Framework Directive 2008/98/EC). As results, a matrix reporting the classes and typologies of waste, their EWC codes, their different WMSs and the suitable LCA processes from the Ecoinvent database that can be applied to each EWC within a specific WMS, has been developed. Additionally, the comparative assessment of the impacts caused by the Ecoinvent processes applicable to the same waste typology within the same WMS has been performed to support the selection of the most appropriate WMS case by case

    The Relationship between Life Course Socioeconomic Conditions and Objective and Subjective Memory in Older Age.

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    While objective memory performance in older adults was primarily shown to be affected by education as indicator of life course socioeconomic conditions, other life course socioeconomic conditions seem to relate to subjective memory complaints. However, studies differ in which life course stages were investigated. Moreover, studies have explored these effects in an isolated way, but have not yet investigated their unique effect when considering several stages of the life course simultaneously. This study, therefore, examined the respective influence of socioeconomic conditions from childhood up to late-life on prospective memory (PM) performance as an objective indicator of everyday memory as well as on subjective memory complaints (SMC) in older age using structural equation modeling. Data came from two waves of the Vivre-Leben-Vivere aging study (n=993, Mage=80.56). The results indicate that only socioeconomic conditions in adulthood significantly predicted late-life PM performance. PM performance was also predicted by age and self-rated health. In contrast, SMC in older age were not predicted by socioeconomic conditions at any stage of the life course but were predicted by level of depression. In line with the cognitive reserve hypothesis, present results highlight the significance of education and occupation (adulthood socioeconomic conditions) for cognitive functioning in later life

    Innovative technologies and bioactive compounds for the control of polyphenol oxidase

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    The enzymatic browning and melanogenesis are associated respectively with the most of qualitative and economical losses during post-harvest processing in agro-food industry and human skin disorders in cosmetic field. The main responsible is tyrosinase or polyphenol oxidase (PPO, EC 1.14.18.1), a copper-containing oxidoreductase that catalyses two different enzymatic reactions involving polyphenolic substrates and oxygen and producing dark pigments. Recently, the research of new eco-friendly systems for controlling PPO activity is focused on innovative non-thermal technologies and bioactive compounds to replace the conventional thermal treatments and traditional additives. All of these have critical points related not only to organoleptic and nutritional qualities of agro-food products and stability in cosmetic formulations but also to human health after topical, oral or parenteral exposure. In this regards, the goal of this study is to evaluate, by in vitro and in vivo assays, the anti-browning performances of a UV-A LED technology (first contribution) and two natural extracts obtained from agro-food by-products such as citrus hydrosols (CIHs; second contribution) and agricultural wastes like vineyard pruning residues (VPRs; third contribution). In the first contribution, after fixing the optimal operational conditions of a UV LED illuminator prototype (2.43·10-3 Wm-2 irradiance) in accordance with number of LED diodes, voltage, and distance from sample, the UV-A light (390 nm) treatment at 25 °C over increasing time periods up to 60 min was applied on fresh-cut apples (Golden Delicious, Granny Smith, and Fuji) and pears (Abate FĂ©tel and Decana). The total colour change (ΔE) and its percent reduction (%RΔE) were measured using a colorimeter and the greatest performances were observed in apples with higher %RΔE values than pears (58.3% vs. 25.5% on average after 60 min exposure, respectively). Moreover electrophoretic and zymographic techniques on the commercial mushroom tyrosinase (TYR) and PPO extracted from irradiated Golden Delicious apple slices confirmed the inhibitory effects of UV-A light on PPO activity. The anti-browning effectiveness of UV-A LED technology was related to irradiance, exposure time, and fruit type and cultivar. In the second contribution, three kinds of hydrosols, which have been obtained by subjecting citron, lemon, and orange peels to steam distillation (CH, LH, and, OH respectively), were spectrophotometrically assessed for anti-TYR activity in the presence of (+)–epicatechin and L-DOPA as the model phenolic substrates of plant enzymatic browning and human skin melanogenesis, respectively. All of the CIHs showed a mixed-type inhibition at varying levels in the 21.8–68.9 % range, depending on substrate type and concentration. The gas chromatography analysis (GC) of their terpene contents indicated that some known TYR inhibitors including myrcene, sabinene, geraniol and citral were present in CIHs. The third contribution investigate the anti-browning and antioxidant potentials of some grape juices obtained by cold-pressing the berries collected from the VPRs of Barbera (B) and Merlot (M) cultivars during 2013 (1) and 2014 (2) seasons. Among the VPRs, Merlot wastes spectrophotometrically exhibited a greater uncompetitive inhibition towards TYR activity than those of Barbera (68.2% and 67.8% for M1 and M2, respectively; 56.3% and 58.8% for B1 and B2, respectively), in the presence of catechol substrate, as confirmed also by gel diffusion assay. The zymographic techniques on the isoforms isolated from TYR and some plant PPOs (Fuji and Golden Delicious apples; Abate FĂ©tel pears; Bintje potatoes) as well as in vivo trials on several fresh-cut fruits (Fuji, Golden Delicious, Granny Smith apples; Abate and Decana pears) vegetables (Bintje potatoes; eggplants), and dried apple slices (Golden Delicious) demonstrated that the inhibitory performances were related mainly to enzyme source. In this regards, this chemical treatment with VPRs was not effective on pear PPO. However, the VPRs showed not only anti-browning but also whitening and antioxidant capacities that were associated mainly with their high organic acids and epigallocatechin gallate (EGCG) contents detected by HPLC analysis. Overall this research confirms that the inhibitory effectiveness is a function of PPO source and inhibitor type and dose. The UV-A LED technology, CIHs, and VPRs are eco-friendly, safe, and inexpensive systems for effectively inhibiting PPO activity, thus preserving the enzymatic browning in agro-food and cosmetic industries. Moreover, these natural extracts, whose anti-browning performances depends mainly on their bioactive compounds contents, suggest a possible recycling use with high value added of these agro-food by-products.L’imbrunimento enzimatico dei prodotti agro-alimentari in post-raccolta e le problematiche associate alla melanogenesi nel settore cosmetico comportano consistenti perdite qualitative ed economiche. Il principale responsabile di entrambi questi fenomeni Ăš la tirosinasi o polifenol ossidasi (PPO, EC 1.14.18.1), una ossido riduttasi contenente un ione rame all’interno del sito attivo, che catalizza due differenti reazioni enzimatiche di ossidazione di substrati polifenolici e quindi rende possibile la successiva formazione di composti scuri. Negli ultimi anni, lo studio di nuovi sistemi ecocompatibili per il controllo dell’attivitĂ  enzimatica si Ăš focalizzato sulle tecnologie non-termiche e sugli inibitori di origine naturale da proporre in alternativa ai convenzionali trattamenti termici ed ai tradizionali additivi chimici. Un impulso alla ricerca in questa direzione Ăš stato dato dalla dimostrazione del loro impatto negativo non solo sulla qualitĂ  organolettica e nutrizionale dei prodotti agro-alimentari e sulla stabilitĂ  delle formulazioni cosmetiche, ma anche sulla sicurezza in seguito ad ingestione o contatto. Partendo da questi presupposti il progetto di ricerca alla base di questa tesi di dottorato vuole valutare, attraverso saggi in vitro e in vivo, l’efficacia anti-imbrunimento di tre possibili sistemi alternativi: una tecnologia UV-A basata su fonte di luce a LED (primo contributo) e due estratti naturali ottenuti da sottoprodotti agro-industriali, gli idrosol degli agrumi (CHIs; secondo contributo) e gli scarti di potatura del vigneto (VPRs; terzo contributo). Nel primo contributo, il trattamento basato su luce UV-A, alla lunghezza d’onda di 390 nm, Ăš stato applicato, a temperature ambiente, in intervalli fino un’ora complessiva, su fette di mela (Golden Delicious, Granny Smith, Fuji) e pera (Abate FĂ©tel, Decana), utilizzando un prototipo di illuminatore a LED, dove alcuni parametrici fisici, quali numero di diodi, voltaggio e distanza dal campione, sono stati impostati in modo tale da garantire il massimo irraggiamento (2.43·10-3 Wm-2). La variazione totale di colore (ΔE) e la sua riduzione percentuale (%RΔE) sono state misurate utilizzando un colorimetro; le mele trattate mostravano una maggiore percentuale di riduzione del colore rispetto alle pere (rispettivamente 58.3% e 25.5% in media, dopo un irraggiamento di 60 minuti). Le ottime potenzialitĂ  inibitorie del trattamento con luce UV-A nei confronti dell’attivitĂ  PPO sono state confermate anche dalle prove elettroforetiche e zimografiche eseguite su una tirosinasi commerciale di origine fungina (TYR) e sulla PPO estratta dalle fette di mela Golden Delicious dopo l’irraggiamento. Sulla base dei risultati ottenuti, l’efficacia anti-imbrunimento di questa tecnologia non termica, basata su luce UV-A con fonte a LED dipende non solo da tempo e intensitĂ  di irraggiamento, ma anche da tipo e cultivar di frutti utilizzati. Nel secondo contributo, l’inibizione tirosinasica da parte di tre diversi tipi d’idrosol, co-prodotti durante distillazione in corrente di vapore delle bucce di cedro, arancia e limone (CH, LH, OH, rispettivamente), Ăš stata determinata spettrofotometricamente, utilizzando (+)–epicatechina e L-DOPA come substrati fenolici rappresentanti, rispettivamente, l’imbrunimento enzimatico delle piante e la melanogenesi della pelle. Tutti gli idrosol di agrumi testati mostravano un’inibizione enzimatica di tipo misto (tra 21.8 e 68.9 %), in base al tipo e alla concentrazione di substrato fenolico utilizzato. L’analisi gas cromatografica (GC) degli idrosol di agrumi ha permesso di individuare tra i terpeni alcuni noti inibitori dell’enzima TYR, quali mircene, sabinene, geraniolo e citrale. Il terzo contributo esamina le potenzialitĂ  anti-imbrunimento e antiossidante di alcuni centrifugati di bacche d’uva provenienti dagli scarti di potatura del vigneto di due diverse cultivar, Barbera (B) e Merlot (M), durante le stagioni di vendemmia dell’anno 2013 (1) e 2014 (2). Tra gli scarti di diradamento, quelli di Merlot inibivano maggiormente l’attivitĂ  dell’enzima commerciale TYR, quantificata allo spettrofotometro in presenza del substrato catecolo, rispetto a quelli di Barbera (68.2% e 67.8% per M1 e M2, rispettivamente; 56.3% and 58.8% per B1 e B2, rispettivamente) mostrando un’inibizione di tipo acompetitiva; i risultati spettrofotometrici sono stati confermati anche dai test su piastra. Le tecniche zimografiche applicate sulle isoforme enzimatiche isolate da TYR e da alcune PPO vegetali (mele Fuji e Golden Delicious; pere Abate FĂ©te; patate Bintje) cosĂŹ come le prove in vivo, condotte su diverse fette di frutta (mele Fuji, Golden Delicious e Granny Smith; pere Abate e Decana) verdura (patate Bintje; melanzane) e su fette essiccate di mela Golden Delicious, hanno dimostrato che il grado d’inibizione dipende principalmente dall’origine dell’enzima. Infatti, questo trattamento chimico non si Ăš rivelato efficace nei confronti della PPO di pera. Tuttavia, lo studio effettuato sugli scarti di potatura di vigneto ha messo in luce le loro potenzialitĂ  non solo come agenti anti-imbrunimento, ma anche come sbiancanti e antiossidanti; le loro molteplici proprietĂ  possono essere correlate al loro alto contenuto in acidi organici ed epigallocatechin gallato (EGCG). Nel complesso, questa ricerca dimostra come l’efficacia inibitoria sia legata principalmente non solo all’origine della PPO, ma anche alla dose e al tipo di inibitore applicato. La tecnologia UV-A con fonte a LED, gli idrosol di agrumi e gli scarti di potatura del vigneto rappresentano sistemi sicuri, economici ed a basso impatto ambientale per controllare l’imbrunimento enzimatico nel settore agro-alimentare e cosmetico. Inoltre, questi estratti naturali, ricchi in composti bioattivi con forti proprietĂ  inibitorie, suggeriscono un possibile impiego alternativo che potrebbe conferire un interessante valore aggiunto a questi sottoprodotti della filiera agro-industriale

    Liability of Private Legal Persons Under International Criminal Law

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    The primary objective of the present thesis is to understand from a theoretic point of view whether private legal persons, such as multinational corporations, may be held liable for participation in crimes under international law. This question – which addresses an issue of utmost importance in the current academic debate at international level – challenges the main principles of both international and criminal law. Indeed, as to public international law, a recognition of some form of direct responsibility of private legal persons requires a preliminary understanding of the consequences this might have on the principles of exclusive sovereignty and equality of States and of individual liability under international criminal law. This requires an evaluation of whether the traditional interpretation of these principles is consistent with the current status of the sources of law. With regard to criminal law, the extension of criminal liability, from natural persons only, to juristic persons requires a reconsideration of the fundamental principles concerning attribution, culpability and causation, in order to adapt them to the specific nature of such entities. Indeed, some additional reflections on the issue of participation and modes of liability would be required as well. Consequently, the present work will be divided in two parts. The objective of Part I will be to clarify, from the point of view of international law, whether private legal persons might be directly responsible for crimes. Thus, the first step will be to distinguish this issue from that of responsibility of public legal entities. Then, the analysis will focus on the history of the concept of corporate responsibility as it has evolved since the times of the Nuremberg trials. Ultimately, an overview of the more recent sources of international law addressing this issue will be given, including a comparative analysis of States’ domestic practice from different legal families. Thus, it will be possible to conclude whether corporate responsibility already amounts either to an international custom or at least to a general principle of law. Part II will address the question whether corporate liability at international level should be criminal in its nature, by means of distinguishing the main features of criminal, civil and administrative liability. Once this preliminary question will be answered, the core aim of the second part will be that of determining what the substantive elements for making corporate entities criminally liable should be. This will involve the very concepts of criminal act, mens rea, causation, and punishment. The related criticalities will be addressed, in the attempt to find workable solutions from both a practical and theoretical point of view. Ultimately, such findings will be compared with the current status of the doctrine of modes of liability under international criminal law, in order to ascertain whether corporate liability would be consistent with this regime and what changes this may entail de jure condendo. To face this challenge, the present work will strongly rely on the huge amount of contributes by some of the most highly qualified scholars to the current debate concerning the issue. The academic contribute to this subject is indeed extremely important in order to keep alive the attention on the topic, as this is one of the main ways to put States under pressure and urging them to take some further step towards an exhaustive regulation of corporate criminal liability. Indeed, this is how civil society may contribute in transnational law-making. The enforcement of legal remedies, by States as well as by regional and international organizations, may be influenced through an horizontal process, made of initiatives by a number of non-governmental organizations and other private subjects. Indeed, in an historical moment in which the very concept of territory is losing its previous importance in the field of legal regulation of individual behaviours, the need to go beyond national standards and look for international cooperation is increasingly important even in the field of criminal law

    Synthesis, characterization, reactivity and biological evaluation of octahedral Pt(IV) prodrugs with active axial ligands

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    Platinum(II) complexes are very important drugs in anticancer chemotherapy. Although few Pt(II) complexes have been approved for the clinical use, in recent years attention has been paid to Pt(IV) complexes as prodrugs, which generally exhibit higher chemical inertness than their Pt(II) counterparts and undergo fewer side reactions with biomolecules. These complexes can be in vivo reduced in the hypoxic and reducing environment of the tumor so that the octahedral Pt(IV) complexes are transformed into their active square-planar Pt(II) metabolites by loss of the axial ligands (activation by reduction). The choice of the ligands is essential to modulate lipophilicity and redox properties of the Pt(IV) prodrugs: they can be biologically active molecules themselves (synthesizing, in this way, bifunctional prodrugs) or linker between the Pt core and a vector for drug targeting and delivery (DTD) methods. The works of this thesis is composed by three projects about three different topics of the modern research on platinum anticancer drug development. The first project involves the development of a new way for the oxidation of Pt(II) complexes with N-chlorosuccinimide as oxidant in ethylene glycol and the study of the stability and reactivity toward different reactions (esterification, synthesis of carbamates and CuAAC click chemistry reaction) of the resulting axially unsymmetric Pt(IV) complexes. The second project, inspired by the philosophy of the active drug targeting and delivery strategy, is aimed to evaluate the effect of the anchoring site of glutamine and glutamine-like to the platinum complex on the cellular recognition by means of antiproliferative activity and cellular uptake tests. The third project is focused on the bifunctional drug concept and is structured in the synthesis, characterization and evaluation of the antiproliferative activity of cisplatin- and [PtCl2(1R,2R-cyclohexanediamine)]- based Pt(IV) complexes bearing clofibric and perillic acid as bioactive axial ligands
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