Dissertation Defense: Zeus De los Santos
Candidate Name: Zeus De los Santos
Advisor: Christian Wolf, Ph.D.
Title: Development of Optical Methods for Sensing of Chiral Compounds Using Organometallic Probes
With the advent of high-throughput experimentation, hundreds of asymmetric reactions can be conducted in parallel. Traditional methods used to analyze asymmetric reaction mixtures are intrinsically serial, time-consuming and generate copious amounts of chemical waste. In recent years, chiroptical sensing with CD spectroscopy has become a popular alternative to address the growing need for automated high-speed chirality analysis. In this thesis, several chiroptical sensing assays with organometallic probes are described.
A stereodynamic ligand capable of Schiff-base formation and concomitant coordination to a Pd(II) center was developed for sensing of amines, amino alcohols and amino acids. This assay was applied in concentration, ee, and absolute configuration determination of a chiral amine produced by an asymmetric hydrogenation of an iminium salt. This analysis required only 1 mg of the crude reaction mixture and minimizes cost, labor, time and waste.
A stereodynamic biphenolate-Al(III) probe for quantitative ee, absolute configuration and concentration analysis of amino alcohols and α-hydroxy acids was introduced. The tropos biphenolate ligand contains phenylacetylene antennae for optimal recognition and amplification of the analyte chirality, producing CD/UV responses at high wavelengths. It was found that the chirality amplification process coincides with either linear or nonlinear correlations between the induced CD signals and the ee of the chiral substrate.
Three bisphosphine-Cu(I) complexes were synthesized and used for the stereochemical analysis of diamines and amino acids. Upon analyte coordination, the complexes generate distinct CD signals that allowed determination of the absolute configuration and ee of various chiral substrates at low concentrations.
Chirality sensing of amino acids, amino phosphonic acids, hydroxy acids, amino alcohols and diamines were performed through an auxiliary-free cobalt probe. Analysis of the enantiomeric composition and concentration of minute sample amounts was achieved with high accuracy by using Co(II) salts and H2O2. This method obviates the general prerequisite for chromophoric metal ligands to generate chiroptical signals through ECCD effects or through analyte-to-ligand chirality induction.
Finally, an optical method for accurate concentration, er and dr determination of amino alcohols based on a simple mix-and-measure protocol was developed. The reaction with salicylaldehyde and CuCl2 was found to produce spectroscopic signals that allow quantitative analysis of each stereoisomer of 1-amino-2-indanol through a combination of UV-Vis and CD spectroscopy signal deconvolutions. Applying linear programming methodology to optimize weighting of spectroscopic signals and parameter sweep algorithm for unbiased identification of optimal wavelength ranges, the concentration and relative amounts of each of the four stereoisomers in 20 samples of vastly different stereoisomeric compositions were determined with an averaged absolute %error of 1.7%.
Friday, November 15, 2019 at 1:00pm to 5:00pm
Regents Hall, 451
3700 O St. NW