hemical and Stereochemical applications of paramagnetic lanthaipe Chelate complexes
Creators: name: Armitage, Ian MacLeod
Publisher: name: University of British Columbia
Year: 2011

description: Paramagnetic substances can produce two principal effects on the high resolution nuclear magnetic resonance (n.m.r.) spectra of any substrate molecule that will associate with them in solution. First of all the unpaired electrons can cause changes in nuclear relaxation times and secondly, paramagnetic substances produce changes in chemical shifts as a result of a pseudocontact or contact interaction or both. This thesis describes some ways in which the chemical shift changes induced by paramagnetic chelate complexes of some lanthanide metals can be used to study the chemical and stereochemical properties of organic molecules. The predominance (for protons at least) of the pseudo-contact interaction coupled with the rapid reversible equilibrium between lanthanide complex and organic substrate accounts for the unique suitability of these reagents for the present study. In Chapter I, the ¹H n.m.r. spectra of a series of 1,2:5,6-di-0_-isopropylidene-α-D-hexofuranose systems have been studied in solution with tris(dipivaloylmethane)-(dpm)-derivatives of europium, thulium and praseodymium. All three reagents were found to induce large stereospecific ¹H chemical shifts in the carbohydrate spectra. Eu(dpm)₃ was particularly suitable; producing the optimum shift to line broadening ratio. The induced shifts were found to vary linearly with the amount of added lanthanide reagent thus facilitating the recovery of the "normal" chemical shift data. Some experimental optimizations for the use of these lanthanide shift reagents to induce chemical shift dispersion, with the minimal amount of broadening and hence the maximal number of measurable coupling constants, have been discussed. The utility of lanthanide shift reagents to assist in assigning ¹³C n.m.r. spectra has also been discussed. The model system, 2,2-dimethyl-l-propanol was used for this study. In Chapter II, a detailed theoretical analysis of the equilibrium which exists between a lanthanide shift reagent, L, and a substance, S, is presented and tested on several suitable substrate molecules interacting with a variety of lanthanide shift reagents. Using this novel approach, it was possible to completely characterize the lanthanide-substrate equilibrium in terms of three parameters: the equilibrium binding constant, K[sub B]; the bound chemical shift, Δ[sub B] , for each proton of a substrate; the solution stoichiometry, a n. Subsequent use of this knowledge was applied to studies of complex stability and to determination of molecular structure. The dependence of K[sub B], Δ[sub B] and n on the basicity of the donor group, the lanthanide reagent, the intramolecular steric hindrance at the substrate donor atom and the organic solvent has been thoroughly described. Substrates used for these studies included a variety of amines, alcohols and ketones and the organic solvents consisted of carbon tetrachloride, benzene and chloroform. Lanthanide shift reagents consisted of the tris(dipivaloylmethane) derivative of europium thulium and praseodymium for which typical K[sub B] -values were &lt;100 liter mole⁻¹ and the tris(2,2-dimethyl-6,6,7,7,8,8,8-heptafluoro-3,5-octanedionato)-europium(III), [Eu(fod)₃], complex for which corresponding K[sub B]-values were increased by at least 10-fold. Perhaps the most important parameter to be unambiguously determined is the "bound" chemical shift for each proton of an organic substrate bound to a lanthanide shift reagent. This parameter reflects the stereospecific nature of the induced chemical shifts and can be used to determine the geometry of the lanthanide-substrate complex and thus presumably the conformation of the substrate itself. In Chapter III, the potential use of lanthanide shift reagents in the determination of complex conformation has been rigorously investigated using a series of detailed computer programs which have been listed in the Appendices. Particular emphasis (from both a chemical and a mathematical point of view) is placed on the importance of internal rotation to the success of this approach to molecular conformations in solution. A variety of new models for free or hindered internal rotation is proposed and tested on four organic substrates (both alcohols and amines) which are rigid except at the point of attachment to the lanthanide. The studies presented are successful in arriving at well-defined and chemically reasonable substrate conformations.