Studies of molecular interactions using physical techniques

The investigations described in this thesis concern the molecular interactions between polar solute molecules and various aromatic compounds in solution. Three different physical methods were employed. Nuclear magnetic resonance (n.m.r.) spectroscopy was used to determine the nature and strength of the interactions and the geometry of the transient complexes formed. Cryoscopic studies were used to provide information on the stoichiometry of the complexes. Dielectric constant studies were conducted in an attempt to confirm and supplement the spectroscopic investigations. The systems studied were those between nitromethane, chloroform, acetonitrile (solutes) and various methyl substituted benzenes. In the n.m.r. work the dependence of the solute chemical shift upon the compositions of the solutions was determined. From this the equilibrium quotients (K) for the formation of each complex and the shift induced in the solute proton by the aromatic in the complex were evaluated. The thermodynamic parameters for the interactions were obtained from the determination of K at several temperatures. The stoichiometries of the complexes obtained from cryoscopic studies were found to agree with those deduced from spectroscopic investigations. For most systems it is suggested that only one type of complex, of 1:1 stiochiometry, predominates except that for the acetonitrile-benzene system a 1:2 complex is formed. Two sets of dielectric studies were conducted, the first to show that the nature of the interaction is dipole-induced dipole and the second to calculate K. The equilibrium quotients obtained from spectroscopic and dielectric studies are compared. Time-averaged geometries of the complexes are proposed. The orientation of solute, with respect to the aromatic for the 1:1 complexes, appears to be the one in which the solute lies symmetrically about the aromatic six-fold axis whereas for the 1:2 complex, a sandwich structure is proposed. It is suggested that the complexes are formed through a dipole-induced dipole interaction and steric factors play some part in the complex formation.

GABA(A) alpha-1 subunit mediated desynchronization of elevated low frequency oscillations alleviates specific dysfunction in stroke:a case report

The paradoxical effects of the hypnotic imidazopyridine zolpidem, widely reported in persistent vegetative state, have been replicated recently in brain-injured and cognitively impaired patients. However, the neuronal mechanisms underlying these benefits are yet to be demonstrated. We implemented contemporary neuroimaging methods to investigate sensorimotor and cognitive improvements, observed in stroke patient JP following zolpidem administration.

Efficient 1,4-addition of enones and boronic acids catalyzed by a Ni-Zn hydroxyl double salt-intercalated anionic rhodium(III) complex

Intercalation of an in situ prepared [Rh(OH)6]3- complex into an anion exchangeable Ni-Zn layered hydroxy double salt (Rh/NiZn) was demonstrated. The resulting Rh/NiZn effectively catalyzed the 1,4-addition of diverse enones and phenylboronic acids to their corresponding β-substituted carbonyl compounds. In the case of 2-cyclohexen-1-one and phenylboronic acid, a turnover frequency (TOF) of 920 h-1 based on Rh was achieved. The [Rh(OH)6]3- complex maintained its original monomeric trivalent state within the NiZn interlayer following catalysis, attributable to a strong electrostatic interaction between the NiZn host and anionic Rh(III) complex.

The amyloid precursor protein (APP) binds the PIKfyve complex and modulates its function

Phosphoinositides are important components of eukaryotic membranes that are required for multiple forms of membrane dynamics. Phosphoinositides are involved in defining membrane identity, mediate cell signalling and control membrane trafficking events. Due to their pivotal role in membrane dynamics, phosphoinositide de-regulation contributes to various human diseases. In this review, we will focus on the newly emerging regulation of the PIKfyve complex, a phosphoinositide kinase that converts the endosomal phosphatidylinositol-3-phosphate [PI(3)P] to phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2)], a low abundance phosphoinositide of outstanding importance for neuronal integrity and function. Loss of PIKfyve function is well known to result in neurodegeneration in both mousemodels and human patients. Our recent work has surprisingly identified the amyloid precursor protein (APP), the central molecule in Alzheimer s disease aetiology, as a novel interaction partner of a subunit of the PIKfyve complex, Vac14. Furthermore, it has been shown that APP modulates PIKfyve function and PI(3,5)P2 dynamics, suggesting that the APP gene family functions as regulator of PI(3,5)P2 metabolism. The recent advances discussed in this review suggest a novel, unexpected, â-amyloid-independent mechanism for neurodegeneration in Alzheimer s disease.