Synthesis and characterization of dicobalthexacarbonyl-alkyne derivatives of amino acids, peptides, and peptide nucleic acid (PNA) monomers.

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.

Redox Chemistry of (1,4,7-Tris(4-tert-butyl-2-mercaptobenzyl)-1,4,7- triazacyclononane)ruthenium(III), [Ru(III)L]: Synthesis and Characterization of [Ru(II)(2)(L-L)](BPh(4))(4).10CH(3)CN and [LRuRuRuL](PF(6))(2).H(2)O.

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.

Synthesis and characterisation of hetero-bimetallic organometallic phenylalanine and PNA monomer derivatives.

The rational, sequential synthesis of two hetero-bimetallic derivatives of the amino acid phenylalanine and one thymine (T) peptide nucleic acid (PNA) monomer is reported. Ferrocene carboxylic acid and (eta-ethene)bis(triphenylphosphine)platinum(0) were successfully reacted with propargylamide amino acid (1a and 1b) or a T PNA monomer derivative (6) to give the expected three bimetallic compounds 4a, 4b and 9 in good yield. An enzymatic route using cross-linked enzyme crystals (CLEC) of subtilopeptidase A in organic solvents gave the ferrocene carboxylate phenylalanine propargylamide precursor (Fc-CO-Phe-NH-CH(2)-CCH, 3a) in comparable yield and purity to the traditional deprotection-peptide coupling sequence. (31)P NMR spectra of these bioorganometallics showed two doublets with (195)Pt satellites corresponding to two chemically different (31)P atoms. Interestingly, in the case of the T PNA monomer derivative 9, these signals were also doubled in a 60 : 40 ratio as a consequence of the existence of two slowly interconverting isomers in solution. Furthermore, the single-crystal X-ray structures of 3a and the hetero-bimetallic phenylalanine derivative 4b were determined, showing the presence of the two organometallics moieties separated by ca. 8.5 A in 4b as well as illustrating the stability of such compounds.