New Class of Phosphine Oxide Donor-Based Supramolecular Coordination Complexes from an in Situ Phosphine Oxidation Reaction or Phosphine Oxide Ligands

A one-pot, multicomponent, coordination-driven self-assembly approach was used to synthesize the first examples of neutral bridging phosphine oxide donor-based supramolecular coordination complexes. The complexes were self-assembled from a <i>fac</i>-Re­(CO)₃ acceptor, an anionic bridging O donor, and a neutral soft phosphine or hard phosphine oxide donor

New Class of Phosphine Oxide Donor-Based Supramolecular Coordination Complexes from an in Situ Phosphine Oxidation Reaction or Phosphine Oxide Ligands

A one-pot, multicomponent, coordination-driven self-assembly approach was used to synthesize the first examples of neutral bridging phosphine oxide donor-based supramolecular coordination complexes. The complexes were self-assembled from a <i>fac</i>-Re­(CO)₃ acceptor, an anionic bridging O donor, and a neutral soft phosphine or hard phosphine oxide donor

NMR Spectroscopy-based Metabolomics of <i>Drosophila</i> Model of Huntington’s Disease Suggests Altered Cell Energetics

Huntington’s disease (HD) is a neurodegenerative disorder induced by aggregation of the pathological form of Huntingtin protein that has expanded polyglutamine (polyQ) repeats. In the <i>Drosophila</i> model, for instance, expression of transgenes with polyQ repeats induces HD-like pathologies, progressively correlating with the increasing lengths of these repeats. Previous studies on both animal models and clinical samples have revealed metabolite imbalances during HD progression. To further explore the physiological processes linked to metabolite imbalances during HD, we have investigated the 1D ¹H NMR spectroscopy-based metabolomics profile of <i>Drosophila</i> HD model. Using multivariate analysis (PCA and PLS-DA) of metabolites obtained from methanolic extracts of fly heads displaying retinal deformations due to polyQ overexpression, we show that the metabolite imbalance during HD is likely to affect cell energetics. Six out of the 35 metabolites analyzed, namely, nicotinamide adenine dinucleotide (NAD), lactate, pyruvate, succinate, sarcosine, and acetoin, displayed segregation with progressive severity of HD. Specifically, HD progression was seen to be associated with reduction in NAD and increase in lactate-to-pyruvate ratio. Furthermore, comparative analysis of fly HD metabolome with those of mouse HD model and HD human patients revealed comparable metabolite imbalances, suggesting altered cellular energy homeostasis. These findings thus raise the possibility of therapeutic interventions for HD via modulation of cellular energetics

Calmidazolium Chloride and Its Complex with Serum Albumin Prevent Huntingtin Exon1 Aggregation

Huntington’s disease (HD) is a genetic disorder caused by a CAG expansion mutation in <i>Huntingtin</i> gene leading to polyglutamine (polyQ) expansion in the N-terminus side of Huntingtin (Httex1) protein. Neurodegeneration in HD is linked to aggregates formed by Httex1 bearing an expanded polyQ. Initiation and elongation steps of Httex1 aggregation are potential target steps for the discovery of therapeutic molecules for HD, which is currently untreatable. Here we report Httex1 aggregation inhibition by calmidazolium chloride (CLC) by acting on the initial aggregation event. Because it is hydrophobic, CLC was adsorbed to the vial surface and could not sustain an inhibition effect for a longer duration. The use of bovine serum albumin (BSA) prevented CLC adsorption by forming a BSA–CLC complex. This complex showed improved Httex1 aggregation inhibition by interacting with the aggregation initiator, the NT₁₇ part of Httex1. Furthermore, biocompatible CLC-loaded BSA nanoparticles were made which reduced the polyQ aggregates in HD-150Q cells