Synthesis of redox derivatives of lysine and related peptides containing phenothiazine or tris(2,2′‐bipyridine)ruthenium(II)

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Abstract
Boc-l-Lysine derivatives and lysine-containing peptides bearing the electron donor 10H-phenothiazine (PTZ) or the redox chromophore tris(2,2′-bipyridine)ruthenium(II) dication ([Rub3,]2H, where b is 2,2-bipyridine) have been synthesized and characterized. SeO2 oxidation (53% yield) of 4,4′-dimethyl-2,2′-bipyridine, Ag2:O oxidation (85% yield) of the monoaldehyde, complexation (96% yield) of 4′-methyl-2,2′-bipyridine-4-carboxylic acid (m-OH) with Rub2Cl2:. activation (81% yield) of the acid [Rub2m-OH]2+ (PF6−)2, and condensation (83% yield) of the succinimido ester [Rub2m-OSu]2+ (PF6−)2 with Boc-Lys furnished the protected redox-chromophore module [Boc-Lys(Rub2m)-OH]2+(PF6−)2 in 29% overall yield over five steps. The first two steps constitute the first practical synthesis of the monocarboxylic acid m-OH (45% overall yield). Also prepared were m-OSu, Boc-Lys(m)-OH, Boc-Lys(m)-OCH3, and [Rub2m-NHCH3]2+ (PF6−)2:. Activation (91% yield) of 3-(10H-phenothiazine-10)propanoic acid (PTZpn-OH) and condensation (92% yield) of the succinimido ester PTZpn-OSu with Boc-Lys furnished the protected electron-donor module Boc-Lys(PTZpn)-OH (84% overall yield). The latter was used in solid-phase syntheses of two redox tripeptides. CH3CO-Ala-Lys(PTZpn)-Ala-OH and [Rub2m-Ala-Lys(PTZpn)-Ala-OH]2 (PF6−)2. The electrochemical properties of these redox amino acids and peptides were similar to those of PTZpn-OH, [Rub2 m-OH]2+(PF6)2. or [Rub2 m-NHCH3]2+ (PF6−)2. Lys(PTZpn). [Lys(Rub2m)]2+ (PF6)2:. and other redox modules may be useful for engineering light-harvesting proteins, photovoltaic cells, and other molecular electronic devices.