Polyglutamine monomer structure and its implications for molecular self-assembly

Polyglutamine is a naturally occurring peptide found within several proteins in neuronal cells of the brain, and its aggregation has been implicated in several neurodegenerative diseases, including Huntington's disease. The resulting aggregates have been demonstrated to possess ~-sheet structure, and aggregation has been shown to start with a single misfolded peptide. The current project sought to computationally examine the structural tendencies of three mutant poly glutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing, and were analyzed quantitatively by various geometry- and energy-based methods. According to the results, the experimentally-observed inhibition of aggregation appears to be due to localized conformational restraint placed on the peptide backbone by inserted prolines, which in tum confines the peptide to native coil structure, discouraging transition towards the ~sheet structure required for aggregation. Such knowledge could prove quite useful to the design of future treatments for Huntington's and other related diseases.

Psychopathy and self-monitoring : additive and interactive effects on self-presentation tactics /

The purpose of this study was to determine the relative contributions of psychopathy and self-monitoring to the prediction of self-presentation tactics (behaviours that individuals use to manipulate their self-image). Psychopathy is composed of two main factors: Factor 1, which includes manipulativeness and shallow affect, and Factor 2, which includes irresponsibility and anti-social behaviours. Self-monitoring is a personality trait that distinguishes between those who adapt their behaviour to fit different social situations (high self-monitors) and those who behave as they feel regardless of social expectations (low selfmonitors). It was hypothesized that self-monitoring would moderate the relationship between psychopathy and self-presentation tactics. One hundred and forty-nine university students completed the Self-Monitoring Scale (Snyder, 1974), the Self-Report Psychopathy Scale - Version III (Paulhus et aI., in press), the Self-Presentation Tactics scale (Lee, S., et aI., 1999), the HEXACO-PI (a measure ofthe six major factors of personality; Lee, K., & Ashton, 2004), and six scenarios that were created as a supplementary measure of the selfpresentation tactics. Results of the hierarchical multiple regression analyses showed that self-monitoring did moderate the relationship between psychopathy and three of the selfpresentation tactics: apologies, disclaimers, and exemplification. Further, significant interactions were observed between Factor 1 and self-monitoring on apologies and the defensive tactics subscale, between Factor 2 and self-monitoring on self-handicapping, and between Factor 1 and Factor 2 on exemplification. Contrary to expectations, the main effect of self-monitoring was significant for the prediction of nine tactics, while psychopathy was significant for the prediction of seven tactics. This indicates that the role of these two personality traits in the explanation of self-presentation tactics tends to be additive in nature rather than interactive. In addition. Factor 2 alone did not account for a significant amount of variance in any of the tactics, while Factor 1 significantly predicted nine tactics. Results are discussed with regard to implications and possible directions for future research.

The effectiveness of a multisensory writing program in improving cursive writing ability in children with sensorimotor difficulties

It is estimated that five to ten percent of children experience sensory motor difficulties that result in various learnlng disabilitiies , among them. inabllity to output Information on paper in the appropriate manner (Ayres ,1985). The relationship between sensorimotorabillty and handwriting is well documented in the literature (Freeman,1917; Townsend , 1951; Nlkola-Ll sa, 1987). While much of the literature is inconclusive, there are findings to suggest that muitisensory handwriting programmes are an effective approach to improvlng writing abIlity in these chlldren. For a number of years, Occupational Therapists have been involved in the remediation of handwriting utllizing , amongst other approaches . multisensory programmes. While subjective assessments of effectiveness have been extremerly positive. scientIfic evaluation has been minimal . If further intervention in this area is to occur, it Is essential that the profession be able to justify the existence of such programmes . The purpose of this study was to examine what effects a multlsensory writing prog~am would have on the curslve writing ability of chlldren with sensorimotor dlfficulties. A single case with multiple baselines across be havlours design was used , with the behavlours being cursive writing abilIty of fIve distInct letter groups. The fIve groups were taught in random order, one group every two weeks , In a one-hour session. Repeated measurements of writing speed and qualIty for each letter group were made. This design was repeated over three other cases . Results of the study yielded statistical signifi cance in trend changes In specIfic letter groups for all of the chlldren following interventlon. One child achieved statistical significance In the overall change In quality , while none of the children achieved overall statistical significance In speed score changes . Teacher reports and an assessment of written language prior to and following the program suggest that Intervention may have had a positive effect on self-confidence in written output, and on the maturlty of written expression in some of the cases . Further research in this field is needed to validate the continual use of multisensory writing programmes by Occupational Theraplsts worklng with this specific population and to provide some directlon with regards to the Integration of multlsensory writing programmes within the regular academic remedial programme .

Spin labile conducting metallopolymers : a new architecture for hybrid multifunctional materials

The synthesis of 3-ethynylthienyl- (2.07), 3-ethynylterthienyl- (2.19) substituted qsal [qsalH = N-(8-quinolyl)salicylaldimine] and 3,3' -diethynyl-2,2' -bithienyl bridging bisqsal (5.06) ligands are described along with the preparation and characterization of eight cationic iron(III) complexes containing these ligands with a selection of counteranions [(2.07) with: SCN- (2.08), PF6- (2.09), and CI04- (2.10); (2.19) with PF6 - (2.20); (5.06) with: cr (5.07), SeN- (5.08), PF6- (5.09), and CI04- (5.10)]. Spin-crossover is observed in the solid state for (2.08) - (2.10) and (5.07) - (5.10), including a ve ry rare S = 5/2 to 3/2 spin-crossover in complex (2.09). The unusal reduction of complex (2.10) produces a high-spin iron(I1) complex (2.12). Six iron(II) complexes that are derived from thienyl analogues of bispicen [bispicen = bis(2-pyridylmethyl)-diamine] [2,5-thienyl substituents = H- (3.11), Phenyl- (3.12), 2- thienyl (3.13) or N-phenyl-2-pyridinalimine ligands [2,5-phenyl substituents = diphenyl (3.23), di(2-thienyl) (3.24), 4-phenyl substituent = 3-thienyl (3.25)] are reported Complexes (3.11), (3.23) and (3.25) display thermal spin-crossover in the solid state and (3.12) remains high-spin at all temperatures. Complex (3.13) rearranges to form an iron(II) complex (3.14) with temperature dependent magnetic properties be s t described as a one-dimensional ferromagnetic chain, with interchain antiferromagnetic interactions and/or ZFS dominant at low temperatures. Magnetic succeptibility and Mossbauer data for complex (3.24) display a temperature dependent mixture of spin isomers. The preparation and characterization of two cobalt(II) complexes containing 3- ethynylthienyl- (4.04) and 3-ethynylterhienyl- (4.06) substituted bipyridine ligands [(4.05): [Co(dbsqh(4.04)]; (4.07): [Co(dbsq)2(4.06)]] [dbsq = 3,5-dbsq=3,5-di-tert-butylI ,2-semiquinonate] are reported. Complexes (4.05) and (4.07) exhibit thermal valence tautomerism in the solid state and in solution. Self assembly of complex (2.10) into polymeric spheres (6.11) afforded the first spincrossover, polydisperse, micro- to nanoscale material of its kind. . Complexes (2.20), (3.24) and (4.07) also form polymers through electrochemical synthesis to produce hybrid metaUopolymer films (6.12), (6.15) and (6.16), respectively. The films have been characterized by EDX, FT-IR and UV-Vis spectroscopy. Variable-temperature magnetic susceptibility measurements demonstrate that spin lability is operative in the polymers and conductivity measurements confirm the electron transport properties. Polymer (6.15) has a persistent oxidized state that shows a significant decrease in electrical resistance.

New Building Blocks for Dual-Property Molecule-Based Magnets

Two classes of compounds have been prepared and characterized as building blocks for chiral magnets and ferromagnetic conductors. In the fIrst project, the organic framework of a pentadentate, (N302) macro cycle has been synthetically modifIed to introduce phenyl substituents into its organic framework and the synthesis of four new [Fe(In(N302)(CN)2] complexes (I) - (IV) is presented. [Molecular diagram availble in pdf] This work represents the fIrst structural and magnetic studies of a family of spin crossover macrocycles that comprise of both structural and stereo-isomers. Magnetic susceptibility and Mossbauer data for the R,R-complex (I) is consistent with both a thermal and a light induced spin crossover transition. The X-ray data supports a change in geometry accompanying the thermal spin transition, from a high spin (HS) 7 -coordinate complex at room temperature to a low spin (LS) 5-coordinate complex at 100 K. The crystal structure ofthe racemic complex (III) reveals a HS, 7-coordinate complex at 200 K that undergoes no signifIcant structural changes on cooling. In contrast, the magnetic - susceptibility and Mossbauer data collected on a powder sample of the racemic complex are consistent with a LS complex. Finally, the meso complex (IV) was prepared and its structure and magnetic properties are consistent with a 5-coordinate LS complex that remains low spin, but undergoes conformational changes on cooling in solution. The chiral [Fe(H)(N302)(CN)2] macro cycle (I), together with its Mn(H) and Fe(H) derivatives have also been exploited as building blocks for the self-assembly of chiral magnets. In the second project, a synthetic route for the preparation of tetrathiafulvalene (TTF) donors covalently attached to a diisopropyl verdazyl radical via a cross conjugated pyridyl linker IS presented. Following this strategy, four new TTF-py- (diisopropyl)verdazyl radicals have been prepared and characterized (V) - (VIII) . [Molecular diagram available in pdf] The first (2:1) charge transfer complex ofa TTF-py-(diisopropyl)verdazyl radical donor and a TCNQ acceptor has been prepared and structurally characterized. The crystal packing shows that the donor and acceptor molecules are organized in a mixed stacking arrangement consistent with its insulating behaviour. EPR and magnetic susceptibility data support intramolecular ferromagnetic interactions between the TTF and the verdazyl radicals and antiferromagnetic interactions between TTF donors within a stack. In an attempt to increase the intramolecular exchange interaction between the two radicals, a TTF-x-(diisopropyl)verdazyl radical (IX) was prepared, where the two radicals are connected ia a conjugated divinylene linker. The neutral radical donors stack in a more favourable head-to-head arrangement but the bulky isopropyl groups prevent the donor radicals from stacking close enough together to facilitate good orbital overlap. [Molecular diagram available in pdf].

Ligand design for molecule-based magnetic and/or conducting materials

Work in the area of molecule-based magnetic and/or conducting materials is presented in two projects. The first project describes the use of 4,4’-bipyridine as a scaffold for the preparation of a new family of tetracarboxamide ligands. Four new ligands I-III have been prepared and characterized and the coordination chemistry of these ligands is presented. This project was then extended to exploit 4,4’-bipyridine as a covalent linker between two N3O2 macrocyles. In this respect, three dimeric macrocycles have been prepared IV-VI. Substitution of the labile axial ligands of the Co(II) complex IV by [Fe(CN)6]4- afforded the self-assembly of the 1-D polymeric chain {[Co(N3O2)H2O]2Fe(CN)6}n•3H2O that has been structurally and magnetically characterized. Magnetic studies on the Fe(II) complexes V and VI indicate that they undergo incomplete spin crossover transitions in the solid state. Strategies for the preparation of chiral spin crossover N3O2 macrocycles are discussed and the synthesis of the novel chiral Fe(II) macrocyclic complex VII is reported. Magnetic susceptibility and Mössbauer studies reveal that this complex undergoes a gradual spin crossover in the solid state with no thermal hysteresis. Variable temperature X-ray diffraction studies on single crystals of VII reveal interesting structural changes in the coordination geometry of the macrocycle accompanying its SCO transition. The second project reports the synthesis and characterization of a new family of tetrathiafulvalene derivatives VIII – XII, where a heterocyclic chelating ligand is appended to a TTF donor via an imine linker. The coordination chemistries of these ligands with M(hfac)2.H2O (M( = Co, Ni, Mn, Cu) have been explored and the structural and magnetic properties of these complexes are described.