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

Abstract

Boc‐l‐Lysine derivatives and lysine‐containing peptides bearing the electron donor 10 H‐phenothiazine (PTZ) or the redox chromophore tris(2,2′‐bipyridine)ruthenium(II) dication ([Rub 3,]2H, where b is 2,2‐bipyridine) have been synthesized and characterized. SeO 2 oxidation (53% yield) of 4,4′‐dimethyl‐2,2′‐bipyridine, Ag 2:O oxidation (85% yield) of the monoaldehyde, complexation (96% yield) of 4′‐methyl‐2,2′‐bipyridine‐4‐carboxylic acid (m‐OH) with Rub 2 Cl 2:. activation (81% yield) of the acid [Rub 2 m‐OH]2+ (PF 6−)2, and condensation (83% yield) of the succinimido ester [Rub 2 m‐OSu]2+ (PF 6−)2 with Boc‐Lys furnished the protected redox‐chromophore module [Boc‐Lys(Rub 2 m)‐OH]2+(PF 6−)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)‐OCH 3, and [Rub 2 m‐NHCH 3]2+ (PF 6−)2:. Activation (91% yield) of 3‐(10 H‐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. CH 3 CO‐Ala‐Lys(PTZpn)‐Ala‐OH and [Rub 2 m‐Ala‐Lys(PTZpn)‐Ala‐OH]2 (PF 6−)2. The electrochemical properties of these redox amino acids and peptides were similar to those of PTZpn‐OH, [Rub 2 m‐OH]2+(PF 6)2. or [Rub 2 m‐NHCH 3]2+ (PF 6−)2. Lys(PTZpn). [Lys(Rub 2 m)]2+ (PF 6)2:. and other redox modules may be useful for engineering light‐harvesting proteins, photovoltaic cells, and other molecular electronic devices.