Investigation of a new bis(carboxylate)triazole-based anchoring ligand for dye-sensitised solar cell chromophore complexes

A novel anchoring ligand for dye-sensitised solar cell chromophoric complexes, 1-(2,2’-bipyrid-4-yl)-1,2,3-triazole-4,5-dicarboxylic acid (dctzbpy), is described. The new dye complexes [Ru(bpy)2(dctzbpy)][PF6]2 (AS16), [Ir(ppy)2(dctzbpy)][PF6] (AS17) and [Re(dctzbpy)(CO)3Cl] (AS18) were prepared in a two stage procedure with intermediate isolation of their diester analogues, AS16-Et2, AS17-Et2 and AS18-Et2 respectively. Electrochemical analysis of AS16-Et2, AS17-Et2 and AS18-Et2 reveal reduction potentials in the range -1.50 to -1.59 V (vs Fc+/Fc) which is cathodically shifted with respect to that of the model complex [Ru(bpy)2(dcbH2)]2+ (1) (Ered = -1.34 V, dcbH2 = 2,2’-bipyridyl-4,4’dicarboxylic acid). This therefore demonstrates that the LUMO of the complex is correctly positioned for favourable electron transfer into the TiO2 conduction band upon photoexcitation. The higher energy LUMOs for AS16 to AS18 and a larger HOMO-LUMO gap result in blue-shifted absorption spectra and hence reduced light harvesting efficiency relative to their dcbH2 analogues. Preliminary tests on TiO2 n-type and NiO p-type DSSCs have been carried out. In the cases of the Ir(III) and Re(I) based dyes AS17 and AS18 these show inferior performance to their dcbH2 analogues. However, the Ru(II) dye AS16 (η = 0.61 %) exhibits significantly greater efficiency than 1 (η = 0.1 %). In a p-type cell AS16 shows the highest photovoltaic efficiency (η = 0.028 %), almost three times that of cells incorporating the benchmark dye coumarin C343

Inhibition of the photochromic behaviour of a 3,3-diphenyl-3H-pyrano[3,2-f]quinoline ligand by coordination to Ag(I) ions

The synthesis and characterisation of a photoresponsive 3,3-diphenyl-3H-pyrano[3,2-f]quinoline ligand which contains both quinoline and thiazole N-donor moieties is described. This ligand acts as a bidentate N-donor ligand and the solid-state structure of a Ag(I) complex is reported. Whereas the free ligand exhibits typical photochromic behaviour, coordination with Ag(I) results in complete inhibition of the photochromic response. However, excitation wavelength dependent emission spectra demonstrated an increase in fluorescence response of the new Ag(I) complex

Epitope-engineered human hematopoietic stem cells are shielded from CD123-targeted immunotherapy

Targeted eradication of transformed or otherwise dysregulated cells using monoclonal antibodies (mAb), antibody-drug conjugates (ADC), T cell engagers (TCE), or chimeric antigen receptor (CAR) cells is very effective for hematologic diseases. Unlike the breakthrough progress achieved for B cell malignancies, there is a pressing need to find suitable antigens for myeloid malignancies. CD123, the interleukin-3 (IL-3) receptor alpha-chain, is highly expressed in various hematological malignancies, including acute myeloid leukemia (AML). However, shared CD123 expression on healthy hematopoietic stem and progenitor cells (HSPCs) bears the risk for myelotoxicity. We demonstrate that epitope-engineered HSPCs were shielded from CD123-targeted immunotherapy but remained functional, while CD123-deficient HSPCs displayed a competitive disadvantage. Transplantation of genome-edited HSPCs could enable tumor-selective targeted immunotherapy while rebuilding a fully functional hematopoietic system. We envision that this approach is broadly applicable to other targets and cells, could render hitherto undruggable targets accessible to immunotherapy, and will allow continued posttransplant therapy, for instance, to treat minimal residual disease (MRD)

The role of copper(II) in the aggregation of human amylin

Amylin is the 37-residue peptide hormone produced by the islet β-cells in the pancreas and the formation of amylin aggregates is strongly associated with β-cells degeneration in type 2 diabetes, as demonstrated by more than 95% of patients exhibiting amylin amyloid upon autopsy. It is widely recognized that metal ions such as copper(II) have been implicated in the aggregation process of amyloidogenic peptides such as Aβ and α-synuclein and there is evidence that also amylin self-assembly is largely affected by copper(II). For this reason, in this work, the role of copper(II) in the aggregation of amylin has been investigated by several different experimental approaches. Mass spectrometric investigations show that copper(II) induces significant changes in the amylin structure which decrease the protein fibrillogenesis as observed by ThT measurements. Accordingly, solid-state NMR experiments together with computational analysis carried out on a model amylin fragment confirmed the non fibrillogenic nature of the copper(II) induced aggregated structure. Finally, the presence of copper(II) is also shown to have a major influence on amylin proneness to be degraded by proteases and cytotoxicity studies on different cell cultures are reported

Mitochondria-localising DNA-binding biscyclometalated phenyltriazole iridium(III) dipyridophenazene complexes: syntheses and cellular imaging properties

Two new biscyclometalated complexes [Ir(ptzR)2(dppz)]+ (dppz = dipyridophenazene; ptzRH = 4-phenyl-1-benzyl-1,2,3-triazole (1+) and 4-phenyl-1-propyl-1,2,3-triazole (2+)) have been prepared. The hexafluorophosphate salts of these complexes have been fully characterized and, in one case, the X-ray structure of a nitrate salt was obtained. The DNA binding properties of the chloride salts of the complexes were investigated, as well as their cellular uptake by A2780 and MCF7 cell lines. Both complexes display an increase in the intensity of phosphorescence upon titration with duplex DNA, indicating the intercalation of the dppz ligand and, given that they are monocations, the complexes exhibit appreciable DNA binding affinity. Optical microscopy studies reveal that both complexes are taken up by live cancer cell lines displaying cytosol based luminescence. Colocalization studies with commercial probes show high Pearson coefficients with mitotracker dyes confirming that the new complexes specifically localize on mitochondria

Molecular mechanism of Abeta recognition and neuroprotection by the glycoconjugate beta-sheet-breaker peptide Ac-LPFFD-Th

Inhibition of amyloid formation may represent a promising therapeutic approach for the treatment of neurodegenerative diseases. To this regard, peptide-based inhibitors of Abeta aggregation have been widely investigated with a particular emphasis to those derived from original amyloid sequences. The experimental work described in the present PhD Thesis aims at outlining the molecular mechanisms underlying the antifibrillogenic and neuroprotective action exhibited by a new class of trehalose conjugated pentapeptides. Trehalose (Th), a non-reducing disaccharide of alpha-(D)glucose, has been demonstrated to be effective in preventing the aggregation of several proteins. We figured out that the development of hybrid compounds may provide new molecules with improved properties that might sinergically increase the potency of their single moieties. Since it has been demonstrated that Abeta oligomers are the toxic species, it becomes a priority to counteract the Abeta self-assembly because of its doubly dangerous effect associated with oligomers generation and removal of the neurotrophic monomeric form of Abeta1-42 peptide. Starting from the well-known neuroprotective action of the LPFFD peptide, (C. Soto, Nat Med. 1998) we investigated whether the Ac-LPFFD-Th peptide would act as an Abeta monomer-stabilizer thus exerting a neuroprotective activity. In support of this hypothesis, time-resolved proteolysis and ESI-MS experiments, performed during my PhD experimental work, showed a direct interaction between these beta-breaker peptides and Abeta monomers. In this work, the C-terminal trehalose conjugated Ac-LPFFD-Th derivative ability to recognize and bind low molecular weight aggregated forms of Abeta has been investigated by means of different biophysical techniques, including Th-T fluorescence, DLS, ESI-MS and NMR. Furthermore, biological assays on murine cortical primary neuronal cultures were performed in order to clarify and further characterize the mechanism of cytoprotection exhibited by the Ac-LPFFD-Th. In this PhD thesis, we demonstrated that Ac-LPFFD-Th modifies the aggregation features of Abeta and protects neurons from Abeta oligomers toxic insult

A remark on voters'rationality in Besley and Coate model of representative democracy

Voting games are characterized by the emergence of dominated strategies, that would be iteratively deleted by rational players. In this note we show, via an example, how applying iterated dominance restricts the set of equilibrium outcomes in Besley and Coate (1997) citizencandidate model of representative democracy

LQG Control OVer Multi-channel TCP-like Erasure Networs With Probabilistic Packet Acknowledgements

info:eu-repo/semantics/publishe

On the effect of packet acknowledgment on the stability and performance of networked control systems

This work concerns discrete-time Linear Quadratic Gaussian (LQG) optimal control of a remote plant that communicates with the control unit by means of a packets dropping channel. Namely, the output measurements are sent to the control unit through an unreliable network and the actions decided by the control unit are sent to the plant actuator via the same network. Sensor and control packets may be randomly lost according to a Bernoulli process. In this work we focus on the importance of acknowledgments in the communication between the control unit and the actuators. In the literature two extreme cases have been considered: either guaranteed acknowledgment or complete lack of it. Although very common in practice, the case where the acknowledgment packets can be lost has not been dealt with a sufficient level of detail. In this work we focus on such a case by assuming that also the acknowledgment packets can be lost according to a Bernoulli process. We can show how the partial loss of acknowledgements yields a non classical information pattern [1], making the optimal control law a nonlinear function of the information tion set. For the special case each observation packet contains the complete state information, we can prove linearity of the optimal controller. Furthermore, we can compute the control law in closed form and show that the stability range increases monotonically with the arrival rate of the acknowledgement packets.info:eu-repo/semantics/publishe