Novel organometallic proteins have been synthesized as a 1:1 composite of rhodium 2,6-bis(2oxazolinyl)phenyl (Rh‚Phebox) complexes with the apo-form of myoglobin, which is an oxygen-transport protein having b-type heme (iron porphyrin IX) as a natural prosthetic group. The X-ray structural analysis reveals that the Rh‚Phebox complex with phenyl substituents is included in the cavity with an almost perpendicular arrangement to that of the heme. The unique arrangement is supported by hydrogen bonding and a number of hydrophobic interactions, especially π-π interactions between the phenyl rings of the substituents and the imidazole moiety of His93, which is a ligand of the rhodium atom. Semiquantitative analysis of the composite stability by ESI mass spectroscopy clearly indicates that the stability of the composites depends on an extent of the interaction between the substituents of the Rh‚Phebox complexes and His93. Enantioselectivity for the chiral (S,S)-and (R,R)-Rh‚Phebox complexes with the phenyl substituents is also observed in terms of the difference in the stability of the composites. According to the arrangement of the amino acid residues around the Phebox ligand, the (S,S)-form has a suitable configuration to fit one of its phenyl rings into the hollow formed by Leu89, His93, and Ile99, while structural distortion will result if the (R,R)-isomer adopts an arrangement similar to that of the (S,S)isomer, which is confirmed with the enhancement of the maximal and minimal ellipticities of the circular dichroic spectrum in comparison with that of the intact (R,R)-isomer. Such structural strain would reduce the efficient π-π interaction between the ligand substituents and His93, resulting in less stability of the composite containing the (R,R)-isomer. The results obtained here demonstrate that the myoglobin cavity is capable of accommodating organometallic compounds totally different from the heme in its molecular shape and the arrangement in the cavity. The extension and application of the present method will allow us to produce artificial organometallic proteins bearing functions that are difficult to achieve with natural prosthetic groups.
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