The mononuclear blue complex [Ru(III)L] (1) where L represents the trianion of 1,4,7-tris(4-tert-butyl-2-mercaptobenzyl)-1,4,7-triazacyclononane has been synthesized by the reaction of H(3)L.3HPF(6) with [Ru(II)Cl(2)(dmso)(4)] in refluxing CH(3)OH in the presence of air. Chemical or electrochemical oxidation of 1 generates [Ru(II)(2)(L-L)](PF(6))(4) (2), a dinuclear species containing two Ru(II) ions and a neutral tris(disulfide) ligand L-L. The reaction of 1 with 1 equiv of [Ru(II)Cl(2)(dmso)(4)] produces the trinuclear species [LRuRuRuL](PF(6))(2) (3) in low yield. Complexes 2 and 3 have been structurally characterized by X-ray crystallography: [Ru(II)(2)(L-L)](BPh(4))(4).10CH(3)CN, C(194)H(218)B(4)N(16)Ru(2)S(6), crystallizes in the monoclinic space group C2/c with a = 28.734(5) Å, b = 16.347(3) Å, c = 37.986(7) Å, beta = 102.35(2) degrees, and Z = 4 whereas [LRuRuRuL](PF(6))(2).H(2)O, C(78)H(110)F(12)N(6)OP(2)Ru(3)S(6), crystallizes in the monoclinic space group P2(1)/n with a = 18.755(4) Å, b = 22.278(4) Å, c = 21.920(4) Å, beta = 91.69(3) Å, and Z = 4. The electro- and spectroelectrochemistry of 1-3 have been studied in detail as have their electronic structures by (1)H NMR, EPR, UV-vis, IR, and Raman spectroscopy.

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A method for attaching organometallics to the C-terminus of amino acids via a Pd-catalyzed two-step procedure is presented. Boc-protected enantiomerically pure amino acids 1 (a Phe, b Leu, c Met, d Ser) are reacted with 1,1-diethylpropargylamine to yield alkynyl amino acids 2. After reaction with (p-iodoanilido)ferrocene carboxylic acid 3 in the presence of 5 mol % PdCl2(PPh3)2/CuI ferrocene amino acids 4 are obtained in ca. 80% yield. The reaction does not require anhydrous conditions and tolerates functional groups such as amides, alcohols (Ser, 4d) or thioethers (Met, 4c). A complete characterization by multinuclear NMR (including 15N) is carried out. Cyclic voltammetry shows a reversible wave at about +190 mV (vs Fc/Fc+) independent of the nature of the attached amino acid. In the solid state, 2a forms a left-handed helix along the crystallographic c axis which is stabilized by hydrogen bonds as revealed by a single-crystal X-ray structure determination. A comparison of IR data in solution and the solid state suggests that hydrogen bonding is also important for the solid-state structures of ferrocene amino acids 4 but does not play a role in solution. The use of this methodology for peptide chemistry is demonstrated by labeling the dipeptide Boc-Met-Phe-OH at the C-terminus and the tripeptide Boc-Phe-Glu-Leu-OMe with ferrocene. The alkyne anchoring group in the tripeptide is introduced at the Cγ(Glu) atom at an early stage of the peptide synthesis and is not affected by subsequent deprotection and coupling reactions.

This work describes a Pd‐catalyzed coupling of ferrocene alkyne derivatives to iodo amino acids. Ferrocene carboxylic acid propargyl amides were easily obtained in high yield. The crystal structures of the propargyl amine derivative 3 and the 1,1‐diethylpropargylamine derivative 4 have been determined by X‐ray diffraction. Pd‐catalyzed coupling to p‐iodoanilide amino acids gave the corresponding ferrocene‐labeled amino acid derivatives, which were easily purified by diethyl ether extraction in the case of the 1,1‐diethyl derivatives 8. The coupling reaction did not require anhydrous solvents and tolerated a variety of functional groups present in peptides such as alcohols (8a, Ser), thioethers (8d, Met), disulfide bonds (cystine, 12) esters (as in the N‐labeled Leu derivative 10) and of course amides. A minor by‐product of the coupling reaction, namely the homo‐dimer bis(ferrocene carboxylic acid propargylamide) 9, was identified in the crude reaction mixtures by mass spectrometry and independently synthesized by oxidative coupling (Glaser and Eglington) of 3. All new compounds were completely characterized spectroscopically, including 15N‐ and 2D NMR spectroscopy, Mössbauer spectroscopy and electrochemistry. This work introduces a versatile procedure for a selective functionalization of amino acids with organometallics at the C‐terminus which is expected to be of general applicability to peptide chemistry.

The reaction of Co(2)(CO)(8) with alkyne-containing amino acids [1a: phenylalanine (Phe) and 1b: methionine (Met)], two suitably alkyne-functionalized derivatives of the neuropeptide enkephalin (Enk) [3: Ac-Enk-Prop and 5: Ac-Enk(Pgl)-NH(2) (Ac--Acetyl; Pgl--propargylglycine; Prop--propargylamine)], a thymine Peptide Nucleic Acid (T-PNA) monomer (7), and a PNA-like monomer (9) derivative gave the respective dicobalthexacarbonyl bioconjugates in very good yields. Two different sites for labeling of the biomolecules were successfully used: The organometallic moiety was reacted with the C-terminus of alkyne-containing amino acids, peptide or PNA thymine monomers, and alternatively the organometallic compound was complexed to an internal site in the peptide or PNA. To this end, a simple glycine was replaced by propargylglycine in peptides, and a new alkyne-containing PNA-like monomer, in which an alkyne chain replaces the nucleobase, was used for PNA chemistry. For the synthesis of the two alkyne-containing enkephalin derivatives 3 and 5, two different resins, namely sulfamylbutyryl and Rink amid, were used as they allow to selectively insert, on the solid phase, an alkyne moiety at the C-terminus and on a side-chain of a peptide sequence, respectively. The identity and constitution of all cobalt complexes were confirmed by different analytical methods (IR, FAB, ESI-MS, and NMR). Most notably, IR spectroscopy shows intensive bands in the 2100-2000 cm(-1) region because of the Co(2)(CO)(6) moiety. In both (1)H NMR spectra of the dicobalthexacarbonyl PNA monomer derivatives 8 and 10, all signals are doubled because of the cis-trans isomerism about the central amide bond. The X-ray structure of a dicobalthexacarbonyl phenylalanine derivative (2a) confirms the proposed composition of the bioconjugates and shows that, as anticipated, the alkyne group of 2a is no longer linear upon complexation in comparison to the alkyne group of the bioconjugate precursor 1a, as indicated by a C-C[triple bond]C angle of about 143 degrees in 2a. Moreover, the C[triple bond]C bond of 1a was elongated by about 0.15 A upon Co(2) coordination.