Title

Enhanced VCD in transition metal complexes and metalloproteins

Date of Award

2005

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

Advisor(s)

Laurence A. Nafie

Second Advisor

Teresa B. Freedman

Keywords

Transition metal, Metalloproteins, Vibrational circular dichroism

Subject Categories

Chemistry | Physical Sciences and Mathematics

Abstract

Enhanced vibrational circular dichroism (VCD) in transition metal complexes and metalloproteins bound with small ligands, VCD studies of conformational transitions in metal-bound polynucleic acids, and applications of VCD to absolute configuration and solution conformation determination are presented in this thesis. The metal complexes studied include metal-(-)-sparteine (metal = Co(II), Ni(II) and Zn(II)) complexes, and metal complexes with chiral Schiff base ligands (metal = Co(II), AI(III), Cr(III), Mn(III), Ni(II), and Zn(II)). Metal complexes with low-lying d-d transitions exhibit 10- to 100-fold enhanced VCD intensities in both the CH-stretching region and the mid-IR (800-2000 cm -1 ) region compared to the complexes without low-lying electronic states. The small-ligand-bound metalloproteins studied include cytochrome c and carboxymethylated cytochrome c bound with azide, cyanide, imidazole and pyrindine, Co(II)-substituted carbonic anhydrase bound with cyanate, and Co(II)-substituted insulin bound with azide. For cytochrome c and carboxymethylated cytochrome c bound with small ligands, anisotropy ratios on the order of 10 -3 were observed for the ligand-stretching modes, and enhanced VCD intensities were also observed in the 1600-1000 cm -1 region compared to the reduced (Fe(II)) proteins. Both the cyanate-bound Co(II)-carbonic anhydrase and the azide-bound Co(II)-insulin exhibit enhanced VCD anisotropy ratios for the ligand stretching modes, and are the first observations of VCD enhancement in non-heme metalloproteins. These studies provide more solid evidence for the argument based on vibronic coupling theory, that low-lying electronic states of the metal center in these complexes and the metal center in the active sites of the metalloproteins are the origins of the large enhanced VCD anisotropy ratio.

The conformational transitions between double, triple and single stranded forms of polynucleic acids poly(rA)·poly(rU), poly(dA)·poly(dT) and their metal bound derivatives as a function of temperature were studied using VCD. The double stranded structure of the nucleic acids were stabilized when bound with Mg 2+ or Ni 2+ , but were destabilized when bound with Cd 2+ .

The absolute configurations and solution conformations of seven selected molecules with pharmaceutical and biological interest were studied by combining VCD measurement with VCD calculation at the DFT level using Gaussian 98/03.

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