21 |
Design, synthesis and characterization of DNA supramolecular nanostructuresBrucale, Marco <1976> 16 May 2007 (has links)
No description available.
|
22 |
Biologically Active Compounds Via 2-Aza-1,3-DienesBandini, Elisa <1966> 16 May 2007 (has links)
No description available.
|
23 |
Sintesi stereocontrollata di pseudopeptidi e studi conformazionaliBalducci, Daniele <1975> 15 May 2007 (has links)
No description available.
|
24 |
Antiossidanti polifenolici contenenti zolfoFumo, Maria Grazia <1977> 06 July 2007 (has links)
No description available.
|
25 |
Each one teaches one: characterizing active forms of proteins by single molecule force spectroscopySandal, Massimo <1981> 03 July 2008 (has links)
This Ph.D. candidate thesis collects the research work I conducted under
the supervision of Prof.Bruno Samor´ı in 2005,2006 and 2007. Some parts of
this work included in the Part III have been begun by myself during my undergraduate
thesis in the same laboratory and then completed during the initial
part of my Ph.D. thesis: the whole results have been included for the sake of
understanding and completeness.
During my graduate studies I worked on two very different protein systems.
The theorical trait d’union between these studies, at the biological level, is
the acknowledgement that protein biophysical and structural studies must, in
many cases, take into account the dynamical states of protein conformational
equilibria and of local physico-chemical conditions where the system studied
actually performs its function. This is introducted in the introductory part
in Chapter 2. Two different examples of this are presented: the structural
significance deriving from the action of mechanical forces in vivo (Chapter 3)
and the complexity of conformational equilibria in intrinsically unstructured
proteins and amyloid formation (Chapter 4).
My experimental work investigated both these examples by using in both
cases the single molecule force spectroscopy technique (described in Chapter 5
and Chapter 6). The work conducted on angiostatin focused on the characterization
of the relationships between the mechanochemical properties and the
mechanism of action of the angiostatin protein, and most importantly their intertwining
with the further layer of complexity due to disulfide redox equilibria
(Part III). These studies were accompanied concurrently by the elaboration of
a theorical model for a novel signalling pathway that may be relevant in the
extracellular space, detailed in Chapter 7.2.
The work conducted on -synuclein (Part IV) instead brought a whole new
twist to the single molecule force spectroscopy methodology, applying it as a
structural technique to elucidate the conformational equilibria present in intrinsically
unstructured proteins. These equilibria are of utmost interest from
a biophysical point of view, but most importantly because of their direct relationship
with amyloid aggregation and, consequently, the aetiology of relevant
pathologies like Parkinson’s disease. The work characterized, for the first time,
conformational equilibria in an intrinsically unstructured protein at the single molecule level and, again for the first time, identified a monomeric folded conformation
that is correlated with conditions leading to -synuclein and, ultimately,
Parkinson’s disease.
Also, during the research work, I found myself in the need of a generalpurpose
data analysis application for single molecule force spectroscopy data
analysis that could solve some common logistic and data analysis problems that
are common in this technique. I developed an application that addresses some of
these problems, herein presented (Part V), and that aims to be publicly released
soon.
|
26 |
Computational investigation of structure and reactivity in organic and bio-organic chemistryCalvaresi, Matteo <1979> 15 April 2008 (has links)
No description available.
|
27 |
Enantioselective aminocatalysis: new reactions and new directionsCarlone, Armando <1979> 16 April 2008 (has links)
No description available.
|
28 |
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.
|
29 |
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).
|
30 |
Sintesi di peptidi e peptidomimetici attivi verso recettori di membranaSquassabia, Federico <1980> 16 April 2008 (has links)
No description available.
|
Page generated in 0.0347 seconds