Synthesis and properties of new macrocyclic derivates

2017 - 2018This PhD thesis is concerned with the design, synthesis and the characterization of new macrocyclic derivatives. Development of new macrocyclic compounds is a particularly interesting because they can involve like building block in Supramolecular chemistry and Nanochemistry. In the first place, I studied the supramolecular properties of different derivatives of the resorcin[6]arenes. Crystal of Resorcin[6]arene was obtained and it reveals that in the solid state the resorcin[6]arene assembles in a twin molecular capsule able to host toluene and ethyl acetate solvent molecules. Subsequently, I have reported the first example of resorcin[6]arene-based cavitand. Sulfate bridges play a double role, both, as structural element for the preorganization of the larger resorcin[6]arene macrocycle and as functional supramolecular interacting groups. Finally, I develop a new multivalent systems resorcin[n]arene based for inhibition of glycosidases and mannosidase that are involved in the malignant transformation of cells. These derivatives were synthetized starting to a pyrrolidine-based iminosugar and resorcinarenes compounds through CuAAS cycloaddition. Biological essays showed that all the resorcinarene derivatives have a good inhibitory activity towards mannosidase enzymes. In second instance, I synthetized new Cycloparaphenylenes (CPP) derivatives to molecular recognition and optoelectronic application. Particularly about molecular recognition field, I reported the synthesis of a [8]CPP derivative incorporating an electron-rich 1,4-dimethoxybenzene ring. This is the first example of substituted CPP derivative reported in literature able to recognize pyridinium guests. Owing to the presence of the 1,4-dimethoxybenzene ring a fine-tuning of the binding abilities toward pyridinium guests was obtained with respect to the native [8]CPP macrocycle. Hybrid Calixarene-CPP derivative that combine the supramolecular features of both the hosts was synthetized and studied in molecular recognition of Na+, Li+ and K+. This derivative shows a noncommon Li+ selectivity due to a more favorable interaction between the cation and the aromatic rings of the CPP bridge. Synthesis of incorporate the 9,10-diphenyl anthracene - [8]CPP derivative was performed and were studied optical and electronical features to obtain the first example of a CPP-based emitter in photon upconversion in the presence of the of octaethylporphyrin Pd(II) complex as a sensitizer, thus widening the application fields of this class of compounds. Finally, [8]CPP and [10]CPP was tested to produce Luminescent Solar Concentrators (LSCs). The high Stokes shift of the CPP macrocycles, enables the preparation of slabs in which a low reabsorption was observed. The results here obtained show clearly the photophysical performances of the CPPbased LSC closely matches with that of the lanthanide chelates based LSC, of interest for applications in colorless LSC. [edited by Author]XXXI cicl

Optical spectra of solids obtained by time-dependent density-functional theory with the jellium-with-gap model exchange-correlation kernel

Within the framework of ab initio time-dependent density-functional theory (TD-DFT), we propose a static approximation to the exchange-correlation kernel based on the jellium-with-gap model. This kernel accounts for electron-hole interactions and it is able to address both strongly bound excitons and weak excitonic effects. TD-DFT absorption spectra of several bulk materials (both semiconductor and insulators) are reproduced in very good agreement with the experiments and with a low computational cost.Comment: 5 pages, 3 figures, 1 tabl

Many-body effects on excitons properties in GaN/AlGaN quantum wells

The many-body effects on excitons properties in GaN/AlGaN quantum wells are theoretically investigated by using a Green's function model and the electron and hole wave functions calculated either in the envelope function approximation or in the frame of a self-consistent tight-binding model. We show that the built-in field induced by the piezoelectric and spontaneous polarization charge causes a reduction of the exciton binding energy and of the absorption coefficient well below the values expected for the quantum well with flat band. At high carrier concentrations, the many-body screening prevails over the screening of the built-in electric field, causing complete exciton bleaching at typical densities of the order of 1012 cm−2

Metabolic Aspects of Anthracycline Cardiotoxicity

Heart failure (HF) is increasingly recognized as the major complication of chemotherapy regimens. Despite the development of modern targeted therapies such as monoclonal antibodies, doxorubicin (DOXO), one of the most cardiotoxic anticancer agents, still remains the treatment of choice for several solid and hematological tumors. The insurgence of cardiotoxicity represents the major limitation to the clinical use of this potent anticancer drug. At the molecular level, cardiac side effects of DOXO have been associated to mitochondrial dysfunction, DNA damage, impairment of iron metabolism, apoptosis, and autophagy dysregulation. On these bases, the antioxidant and iron chelator molecule, dexrazoxane, currently represents the unique FDA-approved cardioprotectant for patients treated with anthracyclines.A less explored area of research concerns the impact of DOXO on cardiac metabolism. Recent metabolomic studies highlight the possibility that cardiac metabolic alterations may critically contribute to the development of DOXO cardiotoxicity. Among these, the impairment of oxidative phosphorylation and the persistent activation of glycolysis, which are commonly observed in response to DOXO treatment, may undermine the ability of cardiomyocytes to meet the energy demand, eventually leading to energetic failure. Moreover, increasing evidence links DOXO cardiotoxicity to imbalanced insulin signaling and to cardiac insulin resistance. Although anti-diabetic drugs, such as empagliflozin and metformin, have shown interesting cardioprotective effects in vitro and in vivo in different models of heart failure, their mechanism of action is unclear, and their use for the treatment of DOXO cardiotoxicity is still unexplored.This review article aims at summarizing current evidence of the metabolic derangements induced by DOXO and at providing speculations on how key players of cardiac metabolism could be pharmacologically targeted to prevent or cure DOXO cardiomyopathy

Heterogeneous enhancement pattern in DCE-MRI reveals the morphology of normal lymph nodes: an experimental study

Purpose: To investigate the heterogeneous enhancement pattern in normal lymph nodes of healthy mice by different albumin-binding contrast agents. Methods: The enhancement of normal lymph nodes was assessed in mice by dynamic contrast-enhanced MRI (DCE-MRI) after the administration of two contrast agents characterized by different albumin-binding properties: gadopentetate dimeglumine (Gd-DTPA) and gadobenate dimeglumine (Gd-BOPTA). To take into account potential heterogeneities of the contrast uptake in the lymph nodes, k-means cluster analysis was performed on DCE-MRI data. Cluster spatial distribution was visually assessed. Statistical comparison among clusters and contrast agents was performed on semiquantitative parameters (AUC, wash-in rate, and wash-out rate) and on the relative size of the segmented clusters. Results: Cluster analysis of DCE-MRI data revealed at least two main clusters, localized in the outer portion and in the inner portion of each lymph node. With both contrast agents, AUC (p < 0.01) and wash-in (p < 0.05) rates were greater in the inner cluster, which also showed a steeper wash-out rate than the outer cluster (Gd-BOPTA, p < 0.01; Gd-DTPA, p=0.056). The size of the outer cluster was greater than that of the inner cluster by Gd-DTPA (p < 0.05) and Gd-BOPTA (p < 0.01). The enhancement pattern of Gd-DTPA was not significantly different from the enhancement pattern of Gd-BOPTA. Conclusion: DCE-MRI in normal lymph nodes shows a characteristic heterogeneous pattern, discriminating the periphery and the central portion of the lymph nodes. Such a pattern deserves to be investigated as a diagnostic marker for lymph node staging

Study on the Influence of Chirality in the Threading of Calix[6]arene Hosts with Dialkylammonium Axles

The influence of chirality in calixarene threading has been studied by exploiting the “superweak anion approach”. In particular, the formation of chiral pseudo[2]rotaxanes bearing a classical stereogenic center in their axle and/or wheel components has been considered. Two kind of pseudo[2]rotaxane stereoadducts, the “endo-chiral” and “exo-chiral” ones, having the stereogenic center of a cationic axle inside or outside, respectively, the calix-cavity of a chiral calixarene were preferentially formed with specifically designed chiral axles by a fine exploitation of the so-called “endo-alkyl rule” and a newly defined “endo-α-methyl-benzyl rule” (threading of a hexaalkoxycalix[6]arene with a directional (α-methyl-benzyl)benzylammonium axle occurs with an endo-α-methyl-benzyl preference). The obtained pseudorotaxanes were studied in solution by 1D and 2D NMR, and in the gas-phase by means of the enantiomer-labeled (EL) mass spectrometry method, by combining enantiopure hosts with pseudoracemates of one deuterated and one unlabeled chiral axle enantiomer. In both instances, there was not a clear enantiodiscrimination in the threading process with the studied host/guest systems. Possible rationales are given to explain the scarce reciprocal influence between the guest and host chiral centers

Enhanced fluorescence by metal nanospheres on metal substrates

We investigate the metal enhanced fluorescence by silver nanospheres on a thin silver substrate. Experimental measurements for core/shell colloidal nanocrystals embedded in a polymer matrix show a fluorescence enhancement factor of about 9. We apply the discrete dipole approximation method to describe the local-field enhancement factor (LFEF). We find that the observed fluorescence enhancement is related to the broad LFEF profile induced by the substrate

Chirality Transfer in a Calixarene-Based Directional Pseudorotaxane Complex

Hexamethoxycalix[6]arene 3 forms a directional pseudorotaxane complex with the chiral axle (S)-(alpha-methyl-benzyl)benzylammonium 2(+). Between the two (endo-chiral)-2(+)@3 and (exo-chiral)-2(+)@3 pseudorotaxane stereoisomers, the former is preferentially formed. This result confirms the validity of the "endo-alpha-methyl-benzyl rule", previously reported by us. DFT calculations suggest that C-H horizontal ellipsis pi interactions between the methyl group of 2(+) and the calixarene aromatic rings, determine the stereoselectivity of the threading process toward the "endo-alpha-methyl-benzyl preference". An amplification of optical rotation is observed upon formation of the pseudorotaxane complex (endo-chiral)-2(+)@3 with respect to free axle 2(+). Thus, the specifical rotation of the 1:1 mixture of chiral 2(+)center dot B(ArF)(4)(-) salt and achiral 3 was augmented upon formation of the pseudorotaxane and DFT calculations were used to rationalize this result

Spontaneous polarization and piezoelectric field in G a N / A l 0.15 Ga 0.85 N quantum wells: Impact on the optical spectra

We have investigated the effects of the built-in electric field in ${\mathrm{G}\mathrm{a}\mathrm{N}/\mathrm{A}\mathrm{l}}_{0.15}{\mathrm{Ga}}_{0.85}\mathrm{N}$ quantum wells by photoluminescence spectroscopy. The fundamental electron heavy-hole transition redshifts well below the GaN bulk gap for well widths larger than 3 nm for the specific quantum wells investigated and exhibits a concomitant reduction of the intensity with increasing well thickness. The experimental data are quantitatively explained by means of a self-consistent tight-binding model that includes screening (either dielectric or by free-carriers), piezoelectric field and spontaneous polarization field. The impact of the built-in field on the exciton stability is discussed in detail. We demonstrate that the exciton binding energy is substantially reduced by the built-in field, well below the values expected from the quantum size effect in the flat band condition