Accumulation of amyloid beta (Aβ) peptide and its aggregates in the human brain is considered as one of the hallmarks of Alzheimer's disease (AD). The polymorphic oligomers and fully grown fibrillar aggregates of Aβ exhibit different levels of neuronal toxicity. Moreover, aggregation of Aβ in the presence of redox-active metal ions like Cu(2+) is responsible for the additional trait of cellular toxicity induced by the generation of reactive oxygen species (ROS). Herein, a multifunctional peptidomimetic inhibitor (P6) has been presented, based on a naturally occurring metal chelating tripeptide (GHK) and the inhibitor of Aβ aggregation. It was shown by employing various biophysical studies that P6 interact with Aβ and prevent the formation of toxic Aβ forms like oligomeric species and fibrillar aggregates. Further, P6 successfully sequestered Cu(2+) from the Aβ-Cu(2+) complex and maintained it in a redox-dormant state to prevent the generation of ROS. P6 inhibited membrane disruption by Aβ oligomers and efficiently prevented DNA damage caused by the Aβ-Cu(2+) complex. PC12 cells were rescued from multifaceted Aβ toxicity when treated with P6, and the amount of ROS generated in cells was reduced. These attributes make P6 a potential therapeutic candidate to ameliorate the multifaceted Aβ toxicity in AD.

No abstract

No abstract

A hydrothermal reaction of Mn(OAc)(2)·4H(2)O, Co(OAc)(2)·4H(2)O and 1,2,4 benzenetricarboxylic acid at 220 °C for 24 h gives rise to a mixed metal MOF compound, [CoMn(2){C(6)H(3)(COO)(3)}(2)], I. The structure is formed by the connectivity between octahedral CoO(6) and trigonal prism MnO(6) units connected through their vertices forming a Kagome layer, which are pillared by the trimellitate. Magnetic susceptibility studies on the MOF compound indicate a canted anti-ferromagnetic behavior, due to the large antisymmetric DM interaction between the M(2+) ions (M = Mn, Co). Thermal decomposition studies indicate that the MOF compound forms a tetragonal mixed-metal spinel phase, CoMn(2)O(4), with particle sizes in the nano regime at 400 °C. The particle size of the CoMn(2)O(4) can be controlled by varying the decomposition temperature of the parent MOF compound. Magnetic studies of the CoMn(2)O(4) compound suggests that the coercivity and the ferrimagnetic ordering temperatures are dependent on the particle size.

The reaction of Cu(ClO4)(2).6H2O and 1,2-bis(4-pyridyl)ethane (bpe) in basic aqueous solution yields a 3D compound, {[Cu3(CO3)2(bpe)3].2ClO4}n (1) through the atmospheric fixation of CO2 composing Cu(CO3) kagomé layers pillared by the bpe linker that exhibit weak antiferromagnetic interaction in the kagomé layer and interlayer ferromagnetic coupling at low temperature.