Transition metal clusters supported by multinucleating ligand frameworks as models of biological active sites

This dissertation describes efforts to model biological active sites with small molecule clusters. The approach used took advantage of a multinucleating ligand to control the structure and nuclearity of the product complexes, allowing the study of many different homo- and heterometallic clusters. Chapter 2 describes the synthesis of the multinucleating hexapyridyl trialkoxy ligand used throughout this thesis and the synthesis of trinuclear first row transition metal complexes supported by this framework, with an emphasis on tricopper systems as models of biological multicopper oxidases. The magnetic susceptibility of these complexes were studied, and a linear relation was found between the Cu-O(alkoxide)-Cu angles and the antiferromagnetic coupling between copper centers. The triiron(II) and trizinc(II) complexes of the ligand were also isolated and structurally characterized.

Chapter 3 describes the synthesis of a series of heterometallic tetranuclear manganese dioxido complexes with various incorporated apical redox-inactive metal cations (M = Na⁺, Ca²⁺, Sr²⁺, Zn²⁺, Y³⁺). Chapter 4 presents the synthesis of heterometallic trimanganese(IV) tetraoxido complexes structurally related to the CaMn₃ subsite of the oxygen-evolving complex (OEC) of Photosystem II. The reduction potentials of these complexes were studied, and it was found that each isostructural series displays a linear correlation between the reduction potentials and the Lewis acidities of the incorporated redox-inactive metals. The slopes of the plotted lines for both the dioxido and tetraoxido clusters are the same, suggesting a more general relationship between the electrochemical potentials of heterometallic manganese oxido clusters and their “spectator” cations. Additionally, these studies suggest that Ca²⁺ plays a role in modulating the redox potential of the OEC for water oxidation.

Chapter 5 presents studies of the effects of the redox-inactive metals on the reactivities of the heterometallic manganese complexes discussed in Chapters 3 and 4. Oxygen atom transfer from the clusters to phosphines is studied; although the reactivity is kinetically controlled in the tetraoxido clusters, the dioxido clusters with more Lewis acidic metal ions (Y³⁺ vs. Ca²⁺) appear to be more reactive. Investigations of hydrogen atom transfer and electron transfer rates are also discussed.

Appendix A describes the synthesis, and metallation reactions of a new dinucleating bis(N-heterocyclic carbene)ligand framework. Dicopper(I) and dicobalt(II) complexes of this ligand were prepared and structurally characterized. A dinickel(I) dichloride complex was synthesized, reduced, and found to activate carbon dioxide. Appendix B describes preliminary efforts to desymmetrize the manganese oxido clusters via functionalization of the basal multinucleating ligand used in the preceding sections of this dissertation. Finally, Appendix C presents some partially characterized side products and unexpected structures that were isolated throughout the course of these studies.

Control mechanisms in the human binocular oculomotor system

A study of human eye movements was made in order to elucidate the nature of the control mechanism in the binocular oculomotor system.

We first examined spontaneous eye movements during monocular and binocular fixation in order to determine the corrective roles of flicks and drifts. It was found that both types of motion correct fixational errors, although flicks are somewhat more active in this respect. Vergence error is a stimulus for correction by drifts but not by flicks, while binocular vertical discrepancy of the visual axes does not trigger corrective movements.

Second, we investigated the non-linearities of the oculomotor system by examining the eye movement responses to point targets moving in two dimensions in a subjectively unpredictable manner. Such motions consisted of hand-limited Gaussian random motion and also of the sum of several non-integrally related sinusoids. We found that there is no direct relationship between the phase and the gain of the oculomotor system. Delay of eye movements relative to target motion is determined by the necessity of generating a minimum afferent (input) signal at the retina in order to trigger corrective eye movements. The amplitude of the response is a function of the biological constraints of the efferent (output) portion of the system: for target motions of narrow bandwidth, the system responds preferentially to the highest frequency; for large bandwidth motions, the system distributes the available energy equally over all frequencies. Third, the power spectra of spontaneous eye movements were compared with the spectra of tracking eye movements for Gaussian random target motions of varying bandwidths. It was found that there is essentially no difference among the various curves. The oculomotor system tracks a target, not by increasing the mean rate of impulses along the motoneurons of the extra-ocular muscles, but rather by coordinating those spontaneous impulses which propagate along the motoneurons during stationary fixation. Thus, the system operates at full output at all times.

Fourth, we examined the relative magnitude and phase of motions of the left and the right visual axes during monocular and binocular viewing. We found that the two visual axes move vertically in perfect synchronization at all frequencies for any viewing condition. This is not true for horizontal motions: the amount of vergence noise is highest for stationary fixation and diminishes for tracking tasks as the bandwidth of the target motion increases. Furthermore, movements of the occluded eye are larger than those of the seeing eye in monocular viewing. This effect is more pronounced for horizontal motions, for stationary fixation, and for lower frequencies.

Finally, we have related our findings to previously known facts about the pertinent nerve pathways in order to postulate a model for the neurological binocular control of the visual axes.

The cost of quinine Cinchona pubescens control on Santa Cruz Island, Galapagos

We analyse the cost of controlling the invasive quinine tree Cinchona pubescens Vahl in the highlands of Santa Cruz Island, Galapagos. Control costs in ten 400 m2 plots formed the basis for estimating the cost of control over the whole island. In the plots, densities were 2100–24,000 stems/ha (stems >150 cm tall) and 55,000–138,000 stems/ha (all size classes combined). Control involved uprooting small plants, and applying of a mix of metsulfuron methyl and picloram to cut stumps or to machete cuts in the bark of larger trees. These methods are presently used by Galapagos National Park field crews to control quinine. Costs (in man hours, herbicide and US$) were related to stem density; the density of stems summed across four height classes was a better predictor of costs than density of any one size class. Regressions (on all size classes combined) formed the basis for predictive models of costs. Costs ranged from $14 to $2225 per ha depending on stem density. The amount of herbicide (active ingredient/ha) that must be applied to high density stands of quinine is higher than typical rates of application in an agricultural setting. The cost of treating all existing plants once across quinine’s known range on Santa Cruz Island (c. 11,000 ha) was estimated at c. US$1.65 million. CDF Contribution Number 1013.

Model-based control of a Rijke tube combustion instability

A Rijke tube is used to demonstrate model-based control of a combustion instability, where controller design is based on measurement of the unstable system. The Rijke tube used was of length 0.75m and had a grid-stabilised laminar flame in its lower half. A microphone was used as a sensor and a loudspeaker as an actuator for active control. The open loop transfer function (OLTF) required for controller design was that from the actuator to the sensor. This was measured experimentally by sending a signal with two components to the actuator. The first was a control component from an empirically designed controller, which was used to stabilise the system, thus eliminating the non-linear limit cycle. The second was a high bandwidth signal for identification of the OLTF. This approach to measuring the OLTF is generic and can be applied to large-scale combustors. The measured OLTF showed that only the fundamental mode of the tube was unstable; this was consistent with the OLTF predicted by a mathematical model of the tube, involving 1-D linear acoustic waves and a time delay heat release model. Based on the measured OLTF, a controller to stabilise the instability was designed using Nyquist techniques. This was implemented and was seen to result in an 80dB reduction in the microphone pressure spectrum. A robustness study was performed by adding an additional length to the top of the Rijke tobe. The controller was found to achieve control up to an increase in tube length of 19%. This compared favourably with the empirical controller, which lost control for an increase in tube length of less than 3%.

Impedance control reduces instability that arises from motor noise.

There is ample evidence that humans are able to control the endpoint impedance of their arms in response to active destabilizing force fields. However, such fields are uncommon in daily life. Here, we examine whether the CNS selectively controls the endpoint impedance of the arm in the absence of active force fields but in the presence of instability arising from task geometry and signal-dependent noise (SDN) in the neuromuscular system. Subjects were required to generate forces, in two orthogonal directions, onto four differently curved rigid objects simulated by a robotic manipulandum. The endpoint stiffness of the limb was estimated for each object curvature. With increasing curvature, the endpoint stiffness increased mainly parallel to the object surface and to a lesser extent in the orthogonal direction. Therefore, the orientation of the stiffness ellipses did not orient to the direction of instability. Simulations showed that the observed stiffness geometries and their pattern of change with instability are the result of a tradeoff between maximizing the mechanical stability and minimizing the destabilizing effects of SDN. Therefore, it would have been suboptimal to align the stiffness ellipse in the direction of instability. The time course of the changes in stiffness geometry suggests that modulation takes place both within and across trials. Our results show that an increase in stiffness relative to the increase in noise can be sufficient to reduce kinematic variability, thereby allowing stiffness control to improve stability in natural tasks.