Unnatural amino acids are effective as building blocks to design functional peptides from the following two points: (1) utilization of rigid unnatural amino acids for the incorporated peptides to control the conformation to appear the function, and (2) incorporation of functional and unnatural amino acids into peptides resulting in appearance of the inherent functions. As a combined strategy, molecular design of artificial metalloproteins utilizing 5'-amino-2,2'-bipyridine-5-carboxilic acid (H-5Bpy-OH) as an unnatural amino acid is proposed. The peptide containing three residues of the unnatural amino acid would fold through coordination to a metal ion. In particular, ruthenium(II) ion would yield a ruthenium tris(bipyridine) derivative as the core complex of the artificial protein, which would appear the similar photochemical functions as that of ruthenium(II) tris(bipyridine) complex. The central complex could form two isomers, fac and mer. For selective synthesis of the mer complex, which is expected as the core complex in the artificial protein, dicyclohexylamide as a bulky group is introduced at the C-terminal of the unnatural amino acid to destabilize the fac complex due to steric hindrance. Furthermore, in order to know the photochemical properties and function of the protein mimics, ruthenium(II) tris(2,2'-bipyridine) complexes bearing amide groups at 5,5' positions have been synthesized as the model complexes. As a result, the direction of amide groups (RNHCO-or RCONH-) in ruthenium complexes is found to significantly affect the emission efficiency: the former reduces the quantum yield and the latter enhances it, respectively. The ruthenium(II) tris(5,5'-diamide-2,2'-bipyridine) complexes are also found to strongly bind with various anions [e.g., halogen ions (Cl-, Br-) and acetate anion] in acetonitrile and to detect these anions through the emission spectral changes under air. The molecular design of artificial protein is expected to develop new fields among peptide, organic, inorganic, and physical chemistry.

Peptide origami. A peptide containing three residues of 5′‐amino‐2,2′‐bipyridine‐5‐carboxylic acid (5 Bpy) as an unnatural amino acid has been folded by coordination with a ruthenium(II) ion to generate an artificial metalloprotein. Four isomers were separated by HPLC and identified by MALDI‐TOF‐MS. Each isomer was further characterized by absorption, emission, and CD spectra.

The fac/mer-ratios of the iron(II) complexes with the derivatives of an unnatural amino acid, 5′-N-acetylamino-2,2′-bipyridine-5-carboxylic acid, were investigated. It was found that the amide derivatives with secondary amines selectively yielded the mer-isomers independently of the ligand structures. On the other hand, for the amides with primary amines, the ratios of the fac- and mer-complexes increased and decreased, respectively, with the increasing sizes of the substituents, suggesting stabilization of the fac-isomers by electrostatic interaction (or hydrogen bondings) between the ligands.

Novel ruthenium(II) complexes, fac/mer-[Ru(MeCO-5Bpy-R)3]2+ (H-5Bpy-OH = 5'-amino-2,2'-bipyridine-5-carboxylic acid; R = -NHtBu, -NH(cHex), -N(cHex)2), have been synthesized. The fac and mer isomers have been successfully separated using HPLC techniques, and their photophysical/electrochemical properties have been investigated. In the absorption and emission spectra of fac/mer-[Ru(MeCO-5Bpy-R)3]2+ with secondary amines (R = -N(cHex)2) in acetonitrile at room temperature, the maximum wavelengths based on the MLCT are longer than those for the amide derivatives with primary amines (R = -NHtBu, -NH(cHex)). A small solvent effect on the photophysical properties between fac- and mer-[Ru(MeCO-5Bpy-NHtBu)3]2+ has been observed. The excitation polarization spectra, giving P values reflecting the relation between the absorption and the emission oscillators, for the fac- and mer-ruthenium(II) complexes (C3 and C1 symmetry, respectively) have been measured for the first time. Almost no difference in the excitation polarization spectra between the fac and mer complexes is found, and these spectra are similar to that for [Ru(bpy)3]2+ with D3 symmetry. This finding suggests that the orientations of the absorption and emission oscillators, in the case of the ruthenium(II) tris(2,2'-bipyridine) derivatives, would not be affected by the symmetries of the complexes and that the P values for any derivatives would be similar to that for [Ru(bpy)3]2+.

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