Effects of Specific Inhibitors for CaMK1D on a Primary Neuron Model for Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. Despite extensive research and targeting of the main molecular components of the disease, beta-amyloid (Aβ) and tau, there are currently no treatments that alter the progression of the disease. Here, we examine the effects of two specific kinase inhibitors for calcium/calmodulin-dependent protein kinase type 1D (CaMK1D) on Aβ-mediated toxicity, using mouse primary cortical neurons. Tau hyperphosphorylation and cell death were used as AD indicators. These specific inhibitors were found to prevent Aβ induced tau hyperphosphorylation in culture, but were not able to protect cells from Aβ induced toxicity. While inhibitors were able to alter AD pathology in cell culture, they were insufficient to prevent cell death. With further research and development, these inhibitors could contribute to a multi-drug strategy to combat AD.     

Synthesis and structural characterization of copper(II) and vanadium(V) complexes of pyridyl/pyrimidyl–pyrazole derived Schiff base ligands – Metal specific adjustment of ligand binding mode

Two mononuclear copper(II) complexes [Cu(L₁)ClO₄] (1), [Cu(L₂)ClO₄] (3) and two mononuclear vanadium(V) complexes [{VO(L₁)(OCH₃)(CH₃OH)}{VO(L₁)(OCH₃)}] (2) and [VO(L₂) (OCH₃)(CH₃OH)] (4) have been synthesized using two Schiff base ligands HL₁ [N′-(2-hydroxybenzylidene)-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazide] and HL₂ [1-(4,6-dimethylpyrimidin-2-yl)-N′-(2-hydroxybenzylidene)-5-methyl-1H-pyrazole-3-carbohydrazide]. These two similar ligands HL₁ and HL₂ in their ‘ketoimine’ form function as mononegative NNNO tetradentate ones towards the Cu(II) centre forming square planar part of the square pyramidal geometry. Where as the same ligands in their ‘imineol’ form behave as binegative ONO tridentate ones to form their V(V) analogues. In the asymmetric unit of 2, there are two independent V(V) complex molecules differing in their conformations as well as in coordination environment – octahedral V(V) in ‘unit A’ is hexa-coordinated while that in ‘unit B’ being penta-coordinated is square pyramidal. Vanadium atom in 4 is in octahedral geometry with NO₅ chromophore. The ligands HL₁ and HL₂ have been synthesized for the first time in our laboratory and characterized by X-ray crystallography and spectroscopy. The complexes (1, 2 and 4) are also characterized by X-ray crystallography, spectroscopic and electrochemical studies.     

Tunnelling Dynamics of Kicked Systems: A Route to Tunnelling Control

The effects of discontinuously time-varying perturbations on the dynamics of a particle moving in harmonic, symmetric double well and symmetric triple well potentials, are investigated both classically and quantum mechanically. The quantum dynamics is followed using the time-dependent Fourier grid Hamiltonian (TDFGH) method while the classical dynamics is analyzed within the framework of classical Hamiltonian mechanics. Depending on the spatial symmetry of the perturbation and the characteristic features of the reversal time , different types of ‘phase space’ structures are observed in each of the potentials. For symmetric double and triple well potentials, quantum dynamics reveals that complete destruction of tunnelling (CDT) can be achieved in the presence of a time-dependent spatially asymmetric perturbing field that is continuous in time. Any discontinuity in time-variation of the perturbation may induce over the barrier transition. The relevance of these results in the context of (i) tunnelling control and (ii) quantum computing with 3-state or 2-state quantum registers is briefly discussed.     

Vanadium(IV)-oxo Corrole Catalyzed Selective Oxidative Cleavage of Alkenes to Aldehydes

A practical and efficient protocol for oxidative cleavage of olefinic bonds especially in arylated olefins has been demonstrated. Herein, an oxo[5,10,15-tris(4-nitrophenyl)corrolato]vanadium (IV) complex (cat.), has been successfully synthesized and the existence of two tautomeric forms of this complex in solution has been established. Oxo[5,10,15-tris(4-nitrophenyl)corrolato]vanadium (IV) (cat.) in the presence of H₂O₂ cleaves olefinic bonds to yield the corresponding aldehyde compounds. In general, a high valent, oxo-(porphyrinoid)-metal complex catalyzes the epoxide formation reactions, however, in the present case, we have observed the exclusive formation of aldehydes. The reaction offered aryl aldehydes with good yields and excellent selectivity. A mechanism was also proposed for these catalysis reactions.