Oxidative addition of amino acids and other biologically interesting molecules to an iridium metal center

The oxidative addition of amino acids and other biologically interesting molecules to iridium{(I) complexes was studied and the reactivity of the resulting hydrido chelate complexes was investigated. Oxidative addition of amino acids to [Ir(COD)(PMe₃)₃]Cl resulted in the formation of meridional tris trimethylphosphine Ir(III) hydride complexes, with the amino acid chelated to the metal center forming 5 membered rings. The majority of the naturally occurring amino acids were studied as potential oxidative addition reactants. The amino acids with reactive side chains did not form clean products. The amino acids without reactive side chains did form clean products which were characterized by ¹H NMR, ³¹P NMR, ¹³C NMR spectroscopy, C,H analyses, and single crystal X-ray diffraction. The studies went on to investigate other 𝛂 amino acid compounds and attempts were made to form 6 membered ring complexes with 𝛃 amino acids. The reactivity of these complexes was also studied. A number of reaction conditions were used in attempts to induce the iridium amino acid complexes and various unsaturates, but the stability of the 5 membered ring system did not allow for insertion of unsaturates. An attempt was made to synthesize coordinately unsaturated complexes of iridium with amino acids. A variety of reactions were tried with the coordinately unsaturated compound, [Ir(COD)(DMPE)]Cl, but amino acid products were not produced in these reactions. Rather, an interesting rearrangement product of [Ir(COD)(DMPE)]Cl was formed and the crystal structure of [Ir (µ¹, µ³ - COD)DMPE]Cl complex was solved. Other attempts to induce reactivity of hydrido amino acid - Ir complexes involved synthesizing N-methyl amino acid complexes. The treatment of [Ir(COD)(PMe₃)₃]Cl with N-methylphenylalanine or N-methylglycine formed the respective chelate hydrido complexes. The reactivity studies of these complexes were negative. The insertion of an unsaturate was observed with 2-amino-4- pentenoic acid. This compound is an a-amino acid with a tethered olefin and when treated with Ir(COD)(PMe₃)₃]Cl binds through three sites (O, N, C) to the metal center. The Ir-C bond formed supports the fact that the olefin has inserted into the Ir-H bond. The crystal structure of this complex was solved. Several amino acid iridium complexes were tested for biological activity in NCI cancer and HIV assays. The complexes had no activity against cancer, but the phenylalanine complex did show moderate activity against HIV. The results prompted studies with other biologically interesting molecules and a number of sulfur containing compounds were studied. The formation of 4 membered ring systems was observed resulting from reactions of thiourea and analogs with [Ir(COD)(PMe₃)₃]Cl. These compounds are to be studied for their reactivity with unsaturates.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Department dc:contributor.department

Chemistry

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

1993

Author dc:creator

• Roy, Christopher P.

Chair dc:contributor.committeechair

• Merola, Joseph S.

Committee members dc:contributor.committeemember

• Hanson, Brian E.
• Dillard, John G.
• Anderson, Mark R.
• Gibson, Harry W.

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

etd-12222005-090634

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/40448