X-Ray Study of Oxygen Carriers as Models of Oxyhemoproteins

Our aim is to synthesize and determine the geometric and electronic structures of cobalt and iron-dioxygen complexes that act as models of the active sites in the naturally occurring blood pigments hemoglobin and myoglobin. Our synthetic complexes have identical equatorial ligands and different N-axial bases, allowing a systematic modulation of the geometric and electronic structures of the M-O₂ groups. X-ray diffraction is used to determine their geometric structures, whereas FT-IR and electronic spectroscopy are used to probe their electronic structures. Such information is essential to obtained a full understanding of the nature of the metal-dioxygen group, which is necessary if we are to understand the mechanism of dioxygen transport in biological organisms.

1. Metal-dioxygen complex synthesis
   In order to accurately characterize the geometric and electronic structures of metal-dioxygen groups in heme models, high-quality, air-stable crystals of these complexes must be obtainable. We have synthesized several series of cobalt Schiff-base complexes that reversibly absorb dioxgen in solution and from which crystals suitable for X-ray structure and spectroscopic analyses can be obtained. The molecular architectures of these air-stable complexes are relatively simple compared to those of the myriad varieties of exotic synthetic iron porphyrins and other cobalt complexes reported in the literature, which are very intractable to crystallize. Incorporated in the ligand structures are tert-butyl or tert-amyl groups, instead of 'straps,' picket fences,' 'caps,' etc. Besides structural simplicity, another reason for the relative success in obtaining crystals has been the insertion of a 1,2-diaminocyclohexyl ring in the diamino bridges of the equatorial ligands, which, because of its enhanced flexibility allows the cobalt complexes and N-bases to react with less steric repulsion, facilitating oxygenation and crystallization of complexes.




	ORTEP drawing of the molecular structure of Co(3-t-BuSalchxn)(1-methylimidazole)(O2)•CH3CN at 120 K. The O-O bond length, 1.311(1) Å, is the most precise yet determined. Notice the C-H···O hydrogen bond between the solvent molecule CH3CN, and the terminal oxygen atom of bound O2. Click for larger image.
	We have been very successful in obtaining high-quality crystals of cobalt-dioxygen complexes utilizing trans (±)-1,2-diaminocyclohexane as a diamine bridge. Shown above is the general structure of these complexes.




2. Hydrogen-bonding Interactions
   Hydrogen-bonding interactions between Fe-bound O₂ , NO, and CO and distal histidine amino acid residues in hemoproteins is currently a 'hot' topic, as these and other polar interactions are believed to be important in stabilizing the Fe(II)-O₂ group against spontaneous autoxidation of Fe(II) to its physiologically inative Fe(III) met form, and in regulating O₂ and CO binding. To study hydrogen-bonding interactions in our complexes, we modulate the polarity of the Co-O₂ groups by changing the positions and substitutents on the N-axial bases and note any changes in intermolecular distances. Our preliminary X-ray results indicate that shorter Co-N_ax bonds result in shorter C-H···O₂ contacts. Variations in hydrogen-bonding strength are also being examined by shifts in O₂ stretching frequencies.

Arrangement of proximal His F8 and distal His E7, Val E11, and Phe CD1 residues in oxymyoglobin. The H-bond between the terminal O and N_e of His E7 is shown.
(Click for larger image.)

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