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.