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Fotofisica e fotochimica di sistemi organici coniugati di interesse biologico e tecnologicoConti, Irene <1976> 15 April 2008 (has links)
No description available.
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Enantioselective aminocatalysis: new reactions and new directionsCarlone, Armando <1979> 16 April 2008 (has links)
No description available.
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Sviluppo di biosensori: modifiche di superfici elettrodiche e sistemi di immobilizzazione enzimaticaMignani, Adriana <1977> 16 April 2008 (has links)
An amperometric glucose biosensor was developed using an anionic clay matrix (LDH) as
enzyme support. The enzyme glucose oxidase (GOx) was immobilized on a layered double
hydroxide Ni/Al-NO3 LDH during the electrosynthesis, which was followed by crosslinking
with glutaraldehyde (GA) vapours or with GA and bovine serum albumin (GABSA)
to avoid the enzyme release.
The electrochemical reaction was carried out potentiostatically, at -0.9V vs. SCE, using a
rotating disc Pt electrode to assure homogeneity of the electrodeposition suspension,
containing GOx, Ni(NO3)2 and Al(NO3)3 in 0.3 M KNO3. The mechanism responsible of the
LDH electrodeposition involves the precipitation of the LDH due to the increase of pH at
the surface of the electrode, following the cathodic reduction of nitrates.
The Pt surface modified with the Ni/Al-NO3 LDH shows a much reduced noise, giving rise
to a better signal to noise ratio for the currents relative to H2O2 oxidation, and a linear range
for H2O2 determination wider than the one observed for bare Pt electrodes.
We pointed out the performances of the biosensor in terms of sensitivity to glucose,
calculated from the slope of the linear part of the calibration curve for enzimatically
produced H2O2; the sensitivity was dependent on parameters related to the electrodeposition
in addition to working conditions. In order to optimise the glucose biosensor performances,
with a reduced number of experimental runs, we applied an experimental design.
A first screening was performed considering the following variables: deposition time (30 -
120 s), enzyme concentration (0.5 - 3.0 mg/mL), Ni/Al molar ratio (3:1 or 2:1) of the
electrodeposition solution at a total metals concentration of 0.03 M and pH of the working
buffer solution (5.5-7.0).
On the basis of the results from this screening, a full factorial design was carried out, taking
into account only enzyme concentration and Ni/Al molar ratio of the electrosynthesis
solution.
A full factorial design was performed to study linear interactions between factors and their
quadratic effects and the optimal setup was evaluated by the isoresponse curves. The
significant factors were: enzyme concentration (linear and quadratic terms) and the
interaction between enzyme concentration and Ni/Al molar ratio.
Since the major obstacle for application of amperometric glucose biosensors is the
interference signal resulting from other electro-oxidizable species present in the real
matrices, such as ascorbate (AA), the use of different permselective membranes on Pt-LDHGOx
modified electrode was discussed with the aim of improving biosensor selectivity and
stability.
Conventional membranes obtained using Nafion, glutaraldehyde (GA) vapours, GA-BSA
were tested together with more innovative materials like palladium hexacyanoferrate
(PdHCF) and titania hydrogels.
Particular attention has been devoted to hydrogels, because they possess some attractive
features, which are generally considered to favour biosensor materials biocompatibility and,
consequently, the functional enzyme stability. The Pt-LDH-GOx-PdHCF hydrogel
biosensor presented an anti-interferant ability so that to be applied for an accurate glucose
analysis in blood. To further improve the biosensor selectivity, protective membranes
containing horseradish peroxidase (HRP) were also investigated with the aim of oxidising
the interferants before they reach the electrode surface. In such a case glucose determination
was also accomplished in real matrices with high AA content.
Furthermore, the application of a LDH containing nickel in the oxidised state was
performed not only as a support for the enzyme, but also as anti-interferant sistem.
The result is very promising and it could be the starting point for further applications in the
field of amperometric biosensors; the study could be extended to other oxidase enzymes.
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Synthesis, multiscale-multiphase characterization and applications of thiophene-based biohybridsAlesi, Silvia <1980> 15 April 2008 (has links)
Biohybrid derivatives of π-conjugated materials are emerging as powerful tools to study biological events through the (opto)electronic variations of the π-conjugated moieties, as well as to direct and govern the self-assembly properties of the organic materials through the organization principles of the bio component. So far, very few examples of thiophene-based biohybrids have been reported.
The aim of this Ph. D thesis has been the development of oligothiophene-oligonucleotide hybrid derivatives as tools, on one side, to detect DNA hybridisation events and, on the other, as model compounds to investigate thiophene-nucleobase interactions in the solid state.
To obtain oligothiophene bioconjugates with the required high level of purity, we first developed new synthetic ecofriendly protocols for the synthesis of thiophene oligomers. Our innovative heterogeneous Suzuki coupling methodology, carried out in EtOH/water or isopropanol under microwave irradiation, allowed us to obtain alkyl substituted oligothiophenes and thiophene based co-oligomers in high yields and very short reaction times, free from residual metals and with improved film forming properties. These methodologies were subsequently applied in the synthesis of oligothiophene-oligonucleotide conjugates.
Oligothiophene-5-labeled deoxyuridines were synthesized and incorporated into 19-meric oligonucletide sequences. We showed that the oligothiophene-labeled oligonucletide sequences obtained can be used as probes to detect a single nucleotide polymorphism (SNP) in complementary DNA target sequences. In fact, all the probes showed marked variations in emission intensity upon hybridization with a complementary target sequence. The observed variations in emitted light were comparable or even superior to those reported in similar studies, showing that the biohybrids can potentially be useful to develop biosensors for the detection of DNA mismatches.
Finally, water-soluble, photoluminescent and electroactive dinucleotide-hybrid derivatives of quaterthiophene and quinquethiophene were synthesized. By means of a combination of spectroscopy and microscopy techniques, electrical characterizations, microfluidic measurements and theoretical calculations, we were able to demonstrate that the self-assembly modalities of the biohybrids in thin films are driven by the interplay of intra and intermolecular interactions in which the π-stacking between the oligothiophene and nucleotide bases plays a major role.
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Organocatalytic asymmetric mannich-type reactions: an easy approach to optically active amine derivativesFini, Francesco <1979> 15 April 2008 (has links)
The topics I came across during the period I spent as a Ph.D. student are mainly two. The first concerns
new organocatalytic protocols for Mannich-type reactions mediated by Cinchona alkaloids derivatives
(Scheme I, left); the second topic, instead, regards the study of a new approach towards the enantioselective
total synthesis of Aspirochlorine, a potent gliotoxin that recent studies indicate as a highly selective and
active agent against fungi (Scheme I, right).
At the beginning of 2005 I had the chance to join the group of Prof. Alfredo Ricci at the Department of
Organic Chemistry of the University of Bologna, starting my PhD studies. During the first period I started to
study a new homogeneous organocatalytic aza-Henry reaction by means of Cinchona alkaloid derivatives as
chiral base catalysts with good results. Soon after we introduced a new protocol which allowed the in situ
synthesis of N-carbamoyl imines, scarcely stable, moisture sensitive compounds. For this purpose we used
α-amido sulfones, bench stable white crystalline solids, as imine precursors (Scheme II).
In particular we were able to obtain the aza-Henry adducts, by using chiral phase transfer catalysis, with a
broad range of substituents as R-group and excellent results, unprecedented for Mannich-type
transformations (Scheme II).
With the optimised protocol in hand we have extended the methodology to the other Mannich-type
reactions. We applied the new method to the Mannich, Strecker and Pudovik (hydrophosphonylation of
imines) reactions with very good results in terms of enantioselections and yields, broadening the usefulness
of this novel protocol.
The Mannich reaction was certainly the most extensively studied work in this thesis (Scheme III).
Initially we developed the reaction with α-amido sulfones as imine precursors and non-commercially
available malonates with excellent results in terms of yields and enantioselections.3 In this particular case we
recorded 1 mol% of catalyst loading, very low for organocatalytic processes. Then we thought to develop a
new Mannich reaction by using simpler malonates, such as dimethyl malonate.4 With new optimised
condition the reaction provided slightly lower enantioselections than the previous protocol, but the Mannich
adducts were very versatile for the obtainment of β3-amino acids. Furthermore we performed the first
addition of cyclic β-ketoester to α-amido sulfones obtaining the corresponding products in good yield with
high level of diastereomeric and enantiomeric excess (Scheme III).
Further studies were done about the Strecker reaction mediated by Cinchona alkaloid phase-transfer
quaternary ammonium salt derivatives, using acetone cyanohydrin, a relatively harmless cyanide source
(Scheme IV). The reaction proceeded very well providing the corresponding α-amino nitriles in good yields
and enantiomeric excesses.
Finally, we developed two new complementary methodologies for the hydrophosphonylation of imines
(Scheme V). As a result of the low stability of the products derived from aromatic imines, we performed the
reactions in mild homogeneous basic condition by using quinine as a chiral base catalyst giving the α-aryl-α-amido phosphonic acid esters as products (Scheme V, top).6 On the other hand, we performed the addition of
dialkyl phosphite to aliphatic imines by using chiral Cinchona alkaloid phase transfer quaternary ammonium
salt derivatives using our methodology based on α-amido sulfones (Scheme V, bottom). The results were
good for both procedures covering a broad range of α-amino phosphonic acid ester.
During the second year Ph.D. studies, I spent six months in the group of Prof. Steven V. Ley, at the
Department of Chemistry of the University of Cambridge, in United Kingdom. During this fruitful period I
have been involved in a project concerning the enantioselective synthesis of Aspirochlorine. We provided a
new route for the synthesis of a key intermediate, reducing the number of steps and increasing the overall
yield. Then we introduced a new enantioselective spirocyclisation for the synthesis of a chiral building block
for the completion of the synthesis (Scheme VI).
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Sintesi di peptidi e peptidomimetici attivi verso recettori di membranaSquassabia, Federico <1980> 16 April 2008 (has links)
No description available.
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Messa a punto di procedure per la semi-sintesi di composti ad attività antitumorale partendo da prodotti naturali. Studi di struttura-attivitàSamorì, Cristian <1976> 16 April 2008 (has links)
Camptothecin, (CPT) is a pentacyclic alkaloid isolated for the first time from the
Chinese tree Camptotheca acuminata, and which has soon attracted the attention of
medicinal chemists and pharmacologists due to its promising anti-cancer activity
against the most aggressive histo-types. So far, most of the synthesized camptothecin
analogues are A and B ring modified compounds, which have been prepared via
synthetic or semi-synthetic routes. To the best of our knowledge, a very limited number
of C, D, or E ring modified analogues of CPT have been reported; moreover, the few
derivatives known from the literature showed a reduced or no biological activity.
This dissertation presents synthetic studies on camptothecin new derivatives along with
the development of a new and general semi-synthetic methodology to obtain a large
variety of analogues.
We report here the semi-synthesis of a new family of 5-substituted CPT's, along with
their biological activity evaluation, which will be compared with reference compounds.
The use of carrier-linked prodrugs has emerged as a useful strategy to overcome some
of the drawbacks related with the use of the parent drug, such as low solubility,
membrane permeability properties, low oral absorption, instability, toxicity, and nontargeting.
Herein we report CPT-prodrugs synthesized via ring opening of the lactone
moiety as 17-O-acyl camptothecin tripartate conjugates, which bear a polyamine side
chain with different architectures, as the carriers.
Moreover, we found that the replacement of the oxygen atom with sulphur on the
piridone D-ring, dramatically improves the potency of the novel 16a-thio-camptothecin
derivatives, opening new possibilities in the modelling of this class of compounds.
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Structure determination of proteins and peptides in solution: simulation, chirality and NMR studiesPietropaolo, Adriana <1981> 16 April 2008 (has links)
The study of protein fold is a central problem in life science, leading in the
last years to several attempts for improving our knowledge of the protein
structures. In this thesis this challenging problem is tackled by means of
molecular dynamics, chirality and NMR studies.
In the last decades, many algorithms were designed for the protein secondary
structure assignment, which reveals the local protein shape adopted by segments of amino acids. In this regard, the use of local chirality for the protein
secondary structure assignment was demonstreted, trying to correlate as well
the propensity of a given amino acid for a particular secondary structure.
The protein fold can be studied also by Nuclear Magnetic Resonance (NMR)
investigations, finding the average structure adopted from a protein. In this
context, the effect of Residual Dipolar Couplings (RDCs) in the structure refinement was shown, revealing a strong improvement of structure resolution.
A wide extent of this thesis is devoted to the study of avian prion protein.
Prion protein is the main responsible of a vast class of neurodegenerative
diseases, known as Bovine Spongiform Encephalopathy (BSE), present in
mammals, but not in avian species and it is caused from the conversion of
cellular prion protein to the pathogenic misfolded isoform, accumulating in
the brain in form of amiloyd plaques. In particular, the N-terminal region,
namely the initial part of the protein, is quite different between mammal
and avian species but both of them contain multimeric sequences called Repeats, octameric in mammals and hexameric in avians. However, such repeat
regions show differences in the contained amino acids, in particular only
avian hexarepeats contain tyrosine residues. The chirality analysis of avian
prion protein configurations obtained from molecular dynamics reveals a high
stiffness of the avian protein, which tends to preserve its regular secondary
structure. This is due to the presence of prolines, histidines and especially tyrosines, which form a hydrogen bond network in the hexarepeat region, only
possible in the avian protein, and thus probably hampering the aggregation.
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Synthetic and mechanistic investigation of new radical processes: reaction of organic azides with group-XIII Lewis acidsBencivenni, Giorgio <1978> 15 April 2008 (has links)
Dichloroindium hydride revealed to be a valid alternative to tributyltin hydride for radical
reduction of organic (alkyl, aryl, acyl, solfonyl) azides. The new approach entails mild reaction
conditions and provides high yields of the corresponding amines and amides, also showing high
degrees of selectivity. The system dichloroindium hydride / azides can be utilised in fivemembered
ring closures of g-azidonitriles, as a new source of aminyl radicals for the attractive
synthesis of interesting amidine compounds in the absence of both toxic reagents and tedious
purification procedures. Allylindium dichloride seems a good substitute for dichloroindium
hydride for generation of indium centred radicals under photolytic conditions, since it allows
allylation of electrophilic azides (e.g. phenylsulfonyl azide) and halogen or ester δ-substituted
azides, the latter through a 1,5-H transfer rearrangement mechanism. Evidences of the radical
nature of the reactions mechanism were provided by ESR spectroscopy, furthermore the same
technique, allowed to discover that the reaction of azides with indium trichloride and other group
XIII Lewis acids, in particular gallium trichloride, gives rise to strongly coloured, persistent
paramagnetic species, whose structure is consistent with the radical cation of the head-to-tail
dimer of the aniline corresponding to the starting azide.
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Asymmetric synthesis of benzylic and heterobenzylic amines / Sintesi asimmetrica di ammine benziliche ed eterobenzilicheGualandi, Andrea <1978> 16 April 2008 (has links)
C2-Symmetrical, enantiopure 2,6-di[1-(1-aziridinyl)alkyl]pyridines (DIAZAPs) were prepared by a high-yielding, three-step sequence starting from 2,6-pyridinedicarbaldehyde and (S)-valinol or (S)-phenylglycinol. The new compounds were tested as ligands in palladium-catalyzed allylation of carbanions in different solvents. Almost quantitative yield and up to 99% enantiomeric excess were obtained in the reactions of the enolates derived from malonate, phenyl- and benzylmalonate dimethyl esters with 1,3-diphenyl-2-propenyl ethyl carbonate.
Asymmetric synthesis of 2-(2-pyridyl)aziridines from chiral 2-pyridineimines bearing a stereogenic center at the nitrogen atom was development. The envisioned route involves the addition of chloromethyllithium to the imine derived from 2-pyridinealdehyde and (S)-valinol, protected as O-trimethylsilyl ether. The analogous reaction performed on the imine derived from (S)-valine methyl ester gave the product containing the aziridine ring as well as the α-chloro ketone group coming from the attack of chloromethyllithium to the ester function. Other stereogenic alkyl substituents at nitrogen gave less satisfactory results. Moreover, the aziridination protocol did not work on other aromatic imines, e.g. 3-pyridineimine and benzaldimine, which are not capable of bidentate chelation. The N-substituent could not be removed, but aziridine underwent ring-opening by attack of nitrogen, sulfur, and oxygen nucleophiles. Complete or prevalent regioselectivity was obtained using cerium trichloride heptahydrate as a catalyst. In some cases, the N-substituent could be removed by an oxidative protocol.
The addition of organometallic (lithium, magnesium, zinc) reagents to 2-pyrroleimines derived from (S)-valinol and (S)-phenylglycinol gave the N-substituted-1-(2-pyrrolyl)alkylamines with high yields and diastereoselectivities. The (S,S)-diastereomers were useful intermediates for the preparation of enantiopure 1-[1-(2-pyrrolyl)alkyl]aziridines by routine cyclization of the β-aminoalcohol moiety and of (S)-N-benzoyl 1-[1-(2-pyrrolyl)alkyl]amines and their N-substituted derivatives by oxidative cleavage of the chiral auxiliary.
1-Allyl-2-pyrroleimines obtained from (S)-phenylglycinol and (S)-valinol underwent highly diastereoselective addition of allylmetal reagents, used in excess amounts, to give the corresponding secondary amines with concomitant allyl to 1-propenyl isomerisation of the 1-pyrrole substituent. Protection of the 2-aminoalcohol moiety as oxazolidinone, amide or Boc derivate followed by ring closing metathesis of the alkene groups gave the unsaturated bicyclic compound, whose hydrogenation afforded the indolizidine derivative as a mixture of separable diastereomers. The absolute configuration of the main diastereomer was assessed by X-ray crystallographic analysis.
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