The exploration of gas-phase stereospecific interactions in the mass spectrometer
Abstract
Gas-phase stereospecific interactions were investigated using tandem mass spectrometry and the kinetic method, a sensitive linear free energy method of treating mass spectrometric results that are converted into thermochemical data. Enantiospecific interactions were created through the formation of a metal complex chelated with a chiral analyte and two chiral references to form a trimeric cluster ion. The chiral purity of the trimeric cluster ion was probed as a result of dissociation by collisional activation and the results obtained were treated by the kinetic method. Chiral and isomeric recognition were achieved for various systems: drugs, peptides, and amino acids. Enantioselectivity was improved with the addition of a fixed non-dissociating ligand in the trimeric cluster ion of various positional tetrapeptide complexes. The enantioselectivity determined by the single ratio version of the kinetic method, was compared to that determined by the fixed-ligand version of the kinetic method. The changes in enantioselectivity were judged against changes in the transition metal cations and positional tetrapeptides. Quantitative improvements in MS based chiral methods were also shown, where two new methodologies, the vernier method and the standard addition method, were developed to (1) determine the chirality of enantiomericlly pure samples more accurately and (2) to get quantitative data from a non-linear calibration plot, respectively. In a different study, comparisons between two instrumental techniques, MS and chromatography, as well as two ionization techniques, DESI and ESI, for the chiral purity determination of pharmaceutical drug candidates were made. The evaluation of method validation parameters in addition to DESI ionization demonstrated the promise of MS as a high-throughput technique for pharmaceutical applications.
Degree
Ph.D.
Advisors
Cooks, Purdue University.
Subject Area
Analytical chemistry
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.