Preparation, Reactivity and Peptide Labelling Properties of (η⁶‐Arene)ruthenium(II) Complexes with Pendant Carboxylate Groups

Abstract (η 6 ‐Arene)ruthenium( II ) complexes of the type [{[η 6 ‐C 6 H 5 (CH 2 ) n COOH]Ru(µ‐Cl)Cl} 2 ] ( 2a , n = 1; 3 , n = 3) with tethered carboxylate groups can be obtained by dehydrogenation of the appropriate cyclohexadiene with RuCl 3 ·3H 2 O. Formation of a κ O ‐coordinated chelate in weakly acidic solution is observed by means of a 1 H NMR titration for both [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(aq)](OTf) 2 ( 3a′ ) and [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(phen)(aq)](OTf) 2 ( 5′ ). Sandwich complexes of the type [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(η 6 ‐amino acid)](OTf) 2 [amino acid = AcpheOH ( 6 ), ActyrOEt ( 7 ), ActrpOH ( 8 )] can be prepared by treating [{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru(acetone) 3 ](OTf) 2 with the appropriate aromatic bioligand in CF 3 COOH ( 6 / 8 ) or CH 2 Cl 2 ( 7 ). Chemospecific η 6 ‐labelling of the C ‐terminal indole function is observed for the peptide HphetrpOH in the analogous complex 9 . Quantitative formation of 8 can also be achieved in aqueous solution in the presence of a 3:1 excess of the {η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}Ru II fragment. This can also be employed for the N ‐terminal labelling of amino acids and peptides in its sandwich complex [(η 6 ‐C 6 Me 6 )Ru{η 6 ‐C 6 H 5 (CH 2 ) 3 COOH}](OTf) 2 ( 10 ). Coupling reactions by the carbodiimide method with EDC afford water‐stable complexes of the type [(η 6 ‐C 6 Me 6 )Ru{η 6 ‐C 6 H 5 (CH 2 ) 3 C(O)R}](OTf) 2 [R = trpOMe ( 11 ), pheOMe ( 12 ), glyglyOEt ( 13 )] in good yields. X‐ray structures of [(η 6 ‐C 6 H 5 CH 2 COOC 2 H 5 )RuCl(phen)](OTf) ( 4b′ ) and 10 are reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)