Adventures in Physical Chemistry

Abstract

My research has included chemical physics, electron and NMR spectroscopy, membrane biophysics, and immunology. This research was curiosity driven as well as problem and technique oriented. A theoretical equation was developed for relating nuclear hyperfine splittings to electron spin distributions in free radicals. Another equation was developed to relate NMR spectra to chemical reaction rates. Early evidence for the liquid-like properties of cell membranes was obtained through the use of paramagnetic probes (spin labels). Spin labels were used in measurements of lateral as well as transverse diffusion of phospholipids in bilayer membranes. Liquid-liquid phase separations were discovered in monolayer membranes containing phospholipids and cholesterol. In the area of immunology, it was shown that antigenic peptides bind to reconstituted class II MHC molecules in membranes and trigger specific T-helper cells.

Role of zero-point vibrational corrections to carbon hyperfine coupling constants in organic π radicals

“…Despite the fact that electron paramagnetic resonance (EPR) spectroscopy for a long time has been instrumental in analyzing spin density distributions in organic π radicals, [1][2][3][4][5][6] it is not until quite recently that first principles theories have been developed, having an accuracy that allow them to be useful for interpreting experimental spectra of such radicals. [7][8][9][10][11][12][13][14][15][16][17][18] The lack of such analysis tools forced early investigations of EPR data to rely on rules-of-thumb or simple principles that relate the spin density to the measured hyperfine coupling constants (HFCCs).…”

“…One such relation is the McConnell relation that states that the spin density ρ C on the carbon of a C-H fragment in an organic π radical is linearly dependent on the isotropic hyperfine constant of hydrogen. [1][2][3] Although such relations or structure-property tools have frequently been used in the field of EPR, [4][5][6] recent advances in the quantum chemical modeling of HFCCs in organic radicals [7][8][9][10][11][12][13][14][15][16][17][18] offer an alternative way for exploring the physical origin of these constants.…”

Rapid Release of Retinal from a Cone Visual Pigment following Photoactivation

“…The visual pigments determine the spectral sensitivity of a particular photoreceptor and share roughly 50% amino acid sequence identity [7]. The X-ray structures of rhodopsin [8] and related photobleaching conformations [9-12] have permitted a unique opportunity to understand the activation of GPCRs through the combination of computational and a large repertoire of experimental approaches (recently reviewed [13]).…”

“…Crystallography, UV/visible, ESR and FTIR spectroscopy have led to a model of the photoactivation pathway in which the steric strain of all-trans retinal drives movement of extracellular loop EL2, transmembrane helices H5-H6 and the disruption of ionic interactions in the transmembrane bundle, termed the ionic lock [13]. This framework has been applied to other members of the GPCR class [18], and thus forms a unifying principle for the activation of these proteins by ligands.…”

“…A primary focus has been the amino acids in the environment of the retinal-Schiff base linkage [13], particularly in comparative studies between chicken rhodopsin and a green-sensitive cone pigment [37]. The Schiff base has been extensively studied in rhodopsin, where it has been shown to have multiple functions, including Suppression of constitutive activity of opsin, Facilitation of regeneration Stabilization of Schiff base linkage and photosimoerization spectral tuning as mentioned above and role in determination of photointermediate lifetime [21] These studies identified a single amino acid (Rho E122 , using bovine rhodopsin numbering) that influences the rate of meta II decay and lifetime of the light-activated conformation R*.…”