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The Synthesis of Ruthenium and Rhodium Complexes with Functionalized N‐Heterocyclic Carbenes and Their Use in Solid Phase Peptide Synthesis
Author(s) -
Lemke Jessica,
MetzlerNolte Nils
Publication year - 2008
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200800366
Subject(s) - chemistry , ruthenium , carbene , peptide synthesis , peptide , rhodium , combinatorial chemistry , bioconjugation , transition metal carbene complex , metal , covalent bond , medicinal chemistry , stereochemistry , catalysis , organic chemistry , biochemistry
While N‐heterocyclic carbenes (NHCs) are ubiquitous ligands in catalysts for organic or industrial synthesis, their potential to form stable transition metal complexes has hardly been exploited in metal bioconjugates. In this work, we describe a straightforward synthesis of carboxylato‐functionalized imidazolium salts for covalent binding to peptides. Carbene complexes of Ru and Rh were prepared from these imidazolium salts using Ag 2 O, followed by transmetallation. The neuropeptide [Leu 5 ]‐enkephalin (Tyr‐Gly‐Gly‐Phe‐Leu) was chosen as a model peptide. Exploratory NMR experiments identified the Ru( p ‐cymene)Cl 2 complex of the asymmetrically substituted imidazol‐2‐ylidene 3b as the most suitable metal carbene precursor for solid phase peptide synthesis (SPPS). After optimization of the conditions for SPPS, a ruthenium‐NHC pseudoenkephalin (dichloro(η 6 ‐ p ‐cymene)[1‐methyl‐3‐(methyl‐ p ‐benzoyl‐Gly‐Gly‐Phe‐Leu‐OH)imidazol‐2‐ylidene]ruthenium(II), 12 ) was synthesized from 3b on solid phase using the 2‐Cl‐Trt resin and cleavage by 2 % TFA to yield the free carboxylic acid. Peptide 12 was fully characterized by HPLC, 1 H and 13 C NMR and ESI‐MS. Characteristic NMR signals, as well as the isotope pattern of Ru in the ESI‐MS, unequivocally confirm the formation of this metal‐carbene peptide bioconjugate.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)