32 research outputs found
Taking advantage of Co(ii) induced enhanced VCD for the fast and sensitive determination of enantiomeric excess
Co(II) induces a large VCD signal enhancement, which overcomes the low sensitivity of VCD and opens new perspectives in quantitative VCD. We used a stereodynamic system, where the analyte determines the chirality of the Co(II) coordination sphere. The strong VCD signals stand out the baseline, which allows for their rapid and accurate quantitation. This lends itself to the first general method for the ee determination of α-amino acids based on vibrational circular dichroism and constitutes a model for the design of sensitive quantitative assays based on VCD
Stabilized Arylzinc Iodides in Negishi Acylative Cross-Coupling: A Modular Synthesis of Chalcones
Abstract: Stabilized arylzinc iodides, synthesized by direct insertion of zinc into the corresponding
halides, were used as nucleophiles into an acylative Negishi coupling reaction to synthesize chalcones.
The reaction conditions were optimized to afford optimal results on a model reaction and then applied
to synthesize nine compounds. Esters, chlorides, electron-rich, electron-poor and sterically hindered
substrates are well tolerated and even heteroaryl derivatives can be synthesized
Experimental and guided theoretical investigation of complex reaction mechanisms in a prins reaction of glyoxylic acid and isobutene
(Chemical Equation Presented) A laboratory experiment was designed for undergraduate students, in which the outcome of an easy single-step organic synthesis with well-defined conditions was not elucidated until the end of the exercise. In class, students predict and discuss the possible products using their knowledge of reaction mechanisms. In the laboratory, they learn how to carry out a reaction safely with gaseous isobutene, and to isolate and identify the two main products. The class and the laboratory components are completed in 10 h, including laboratory time of 6 to 7 h, divided in two sessions. The class-component could also be implemented independently as a theoretical exercise in a "virtual experiment" simply by presenting the methods and results to students using a guided-inquiry approach, appropriate for a standard 3 h undergraduate class. The finding that the simple reaction leads to a largely unexpected product, together with open discussions with students covering several theoretical aspects applicable to this reaction, helps to promote critical thinking and to provide an effective educational tool to better understand the process of scientific research in chemistry
Zinc-selective inhibition of the promiscuous bacterial amide-hydrolase DapE: implications of metal heterogeneity for evolution and antibiotic drug design
The development of resistance to virtually all current antibiotics makes the discovery of new antimicrobial compounds with novel protein targets an urgent challenge. The dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) is an essential metallo-enzyme for growth and proliferation in many bacteria, acting in the desuccinylation of N-succinyl-l,l-diaminopimelic acid (SDAP) in a late stage of the anabolic pathway towards both lysine and a crucial building block of the peptidoglycan cell wall. l-Captopril, which has been shown to exhibit very promising inhibitory activity in vitro against DapE and has attractive drug-like properties, nevertheless does not target DapE in bacteria effectively. Here we show that l-captopril targets only the Zn(2+)-metallo-isoform of the enzyme, whereas the Mn(2+)-enzyme, which is also a physiologically relevant isoform in bacteria, is not inhibited. Our finding provides a rationale for the failure of this promising lead-compound to exhibit any significant antibiotic activity in bacteria and underlines the importance of addressing metallo-isoform heterogeneity in future drug design. Moreover, to our knowledge, this is the first example of metallo-isoform heterogeneity in vivo that provides an evolutionary advantage to bacteria upon drug-challenge
A LC-QTOF Method for the Determination of PEGDE Residues in Dermal Fillers
Hyaluronic acid is one of the most important ingredients in dermal fillers, where it is often cross-linked to gain more favorable rheological properties and to improve the implant duration. Poly(ethylene glycol) diglycidyl ether (PEGDE) has been recently introduced as a crosslinker because of its very similar chemical reactivity with the most-used crosslinker BDDE, while giving special rheological properties. Monitoring the amount of the crosslinker residues in the final device is always necessary, but in the case of PEGDE, no methods are available in literature. Here, we present an HPLC-QTOF method, validated according to the guidelines of the International Council on Harmonization, which enables the efficient routine examination of the PEGDE content in HA hydrogels
Preparazione di bifenoli naturali funzionalizzati con unitĂ fotosensibili reversibili
Il lavoro di ricerca ha voluto
investigare la funzionalizzazione di bifenili naturali al fine di una loro applicazione nel campo
dei materiali organici fotosensibili reversibili, appartenenti alla classe delle molecole
switches
De Novo Design of secondary structures: Synthesis and conformational studies
Chemists have long sought to extrapolate the power of
biological catalysis and recognition to synthetic systems.
These efforts have focused largely on low molecular
weight catalysts and receptors; however, biological
systems themselves rely almost exclusively on polymers,
proteins and RNA, to perform complex chemical
functions. Proteins and RNA are unique in their ability to
adopt compact, well-ordered conformations, and specific
folding provides precise spatial orientation of the
functional groups that comprise the “active site”. These
features suggest that identification of new polymer
backbones with discrete and predictable folding
propensities (“foldamers”) will provide a basis for design
of molecular machines with unique capabilities. The
foldamer approach complements current efforts to design
unnatural properties into polypeptides and
polynucleotides.
The aim of this thesis is the synthesis and
conformational studies of new classes of foldamers, using
a peptidomimetic approach. Moreover their attitude to be
utilized as ionophores, catalysts, and nanobiomaterials
were analyzed in solution and in the solid state.
This thesis is divided in thematically chapters that are
reported below.
It begins with a very general introduction (page 4) which
is useful, but not strictly necessary, to the expert reader.
It is worth mentioning that paragraph I.3 (page 22) is the
starting point of this work and paragraph I.5 (page 32) isrequired to better understand the results of chapters 4
and 5.
In chapter 1 (page 39) is reported the synthesis and
conformational analysis of a novel class of foldamers
containing (S)-β3-homophenylglycine [(S)-β3-hPhg] and D-
4-carboxy-oxazolidin-2-one (D-Oxd) residues in alternate
order is reported. The experimental conformational
analysis performed in solution by IR, 1HNMR, and CD
spectroscopy unambiguously proved that these oligomers
fold into ordered structures with increasing sequence
length. Theoretical calculations employing ab initio MO
theory suggest a helix with 11-membered hydrogenbonded
rings as the preferred secondary structure type.
The novel structures enrich the field of peptidic foldamers
and might be useful in the mimicry of native peptides.
In chapter 2 cyclo-(L-Ala-D-Oxd)3 and cyclo-(L-Ala-DOxd)
4 were prepared in the liquid phase with good overall
yields and were utilized for bivalent ions chelation (Ca2+,
Mg2+, Cu2+, Zn2+ and Hg2+); their chelation skill was
analyzed with ESI-MS, CD and 1HNMR techniques and
the best results were obtained with cyclo-(L-Ala-D-Oxd)3
and Mg2+ or Ca2+.
Chapter 3 describes an application of oligopeptides as
catalysts for aldol reactions. Paragraph 3.1 concerns the
use of prolinamides as catalysts of the cross aldol
addition of hydroxyacetone to aromatic aldeydes, whereas
paragraphs 3.2 and 3.3 are about the catalyzed aldol
addition of acetone to isatins. By means of DFT and AIM
calculations, the steric and stereoelectronic effects that
control the enantioselectivity in the cross-aldol addition
of acetone to isatin catalysed by L-proline have been
studied, also in the presence of small quantities of water.
In chapter 4 is reported the synthesis and the analysis of
a new fiber-like material, obtained from the selfaggregation
of the dipeptide Boc-L-Phe-D-Oxd-OBn,
which spontaneously forms uniform fibers consisting of
parallel infinite linear chains arising from singleintermolecular N-H···O=C hydrogen bonds. This is the
absolute borderline case of a parallel β-sheet structure.
Longer oligomers of the same series with general formula
Boc-(L-Phe-D-Oxd)n-OBn (where n = 2-5), are described
in chapter 5. Their properties in solution and in the solid
state were analyzed, in correlation with their attitude to
form intramolecular hydrogen bond.
In chapter 6 is reported the synthesis of imidazolidin-2-
one-4-carboxylate and (tetrahydro)-pyrimidin-2-one-5-
carboxylate, via an efficient modification of the Hofmann
rearrangement. The reaction affords the desired
compounds from protected asparagine or glutamine in
good to high yield, using PhI(OAc)2 as source of iodine(III)
Foldamers based on oxazolidin-2-ones
Foldamers are artificial molecules capable of organization into well defined secondary structures such as helixes, β sheets and turns. The essential requirement for an oligomer to qualify for inclusion in the foldamer family is to possess a well defined, repetitive secondary structure, imparted by conformational restrictions imposed by the monomeric unit. These compounds may be composed of subunits of any kind, but most of them contain unusual amino acids and/or aromatic units. We describe the synthesis, the conformation analysis and the physical properties (in the solid state) of pseudopeptide foldamers containing imido-type functions, obtained by coupling the nitrogen of a 4-carboxy oxazolidin-2-one unit with the carboxylic acid moiety of the next unit, which may be another 4-carboxy oxazolidin-2-one or an amino acid. Such an imido-type function is characterized by a nitrogen atom connected both to an endocyclic and to an exocyclic carbonyl group, and tends always to adopt the trans conformation. As a consequence of this remarkable property, which causes local constraint, these imido-type oligomers are forced to fold in ordered conformations. In combination with interactions of other kinds (H bond, apolar interactions, etc.), these lead to the formation of supramolecular materials. The synthetic approach is highly tuneable with endless variations, so materials with required properties may be prepared "on demand", simply by changing the design and the synthesis. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Formation of gels in the presence of metal ions
A small library of stereoisomeric pseudopeptides able to make gels in different solvents has been prepared and their attitude to make gels in the presence of several metal ions was evaluated. Four benzyl esters and four carboxylic acids, all containing a moiety of azelaic acid (a long chain dicarboxylic acid) coupled with four different pseudopeptide moieties sharing the same skeleton (a phenyl group one atom apart from the oxazolidin-2-one carboxylic group), were synthesized in solution, by standard coupling reaction. The tendency of these pseudopeptides to form gels was evaluated using the inversion test of 10 mM solutions of pure compounds and of stoichiometric mixtures of pseudopeptides and metal ions. To obtain additional information on the molecular association, the gel samples were left dry in the air to form xerogels that were further analyzed using SEM and XRD. The formation of gel containing Zn(II) or Cu(II) ions gave good results in term of incorporation of the metal ions, while the presence of Cu(I), Al(III) and Mg(II) gave less satisfactory results. This outcome is a first insight in the formation of stable LMWGs formed by stoichiometric mixtures of pseudopeptides and metal ions. Further studies will be carried out to develop similar compounds of pharmacological interest. © 2011 Springer-Verlag