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 10H-phenothiazine (PTZ) or the redox chromophore tris(2,2'-bipyridine)ruthenium(II) dication ([Rub3]2+, where b is 2,2'-bipyridine) have been synthesized and characterized. SeO2 oxidation (53% yield) of 4,4'-dimethyl-2,2'-bipyridine, Ag2O 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, [Rub2m-OH]2+ (PF6-)2, or [Rub2m-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.