Boc-S-benzyl-D-cysteine

A novel route to synthesize an organic/inorganic hybrid material containing short peptide chains attached on the surface (e.g., oligo(S-benzyl-L-cysteine)) was developed. Poly[N-(beta-aminoethylene)acrylamide] (PAEA) adsorbed onto silica particles surface (main diameter between 15 and 40 microm) was irreversibly fixed by the reaction between the accessible primary amino groups of the PAEA and 3,3',4,4'-benzophenone tetracarboxylic dianhydride (BTCDA). After the deposition of PAEA from a salt-free aqueous solution onto microporous silica particles and stabilization by a cross-linking reaction with BTCDA, five repeated coupling reactions of boc-S-benzyl-L-cysteine were performed. Changes in surface charges during the polyelectrolyte adsorption were studied by electrokinetic measurements. The cross-linking degree was a tool to control the surface charge of the PAEA/silica hybrid particles. X-ray photoelectron spectroscopy (XPS) was employed to obtain information about the amount of the adsorbed polyelectrolyte as well as the amount of the amino acid S-benzyl-L-cysteine that was covalently bound to the hybrid particle surface and polycondensed there. In the XPS spectra, the sulfur peaks (S 2p3/2, S 2p1/2, and S 2s) qualitatively and quantitatively indicated the presence of the amino acid on the hybrid material surface. After each step of coupling, the intensity of the S 2s peak was increased by a constant value. This indicates the oligopeptide growth. The novel hybrid material offers possibilities for subsequent derivatization reactions such as coupling other amino acids, peptides, obtaining hybrid ion exchange resins, and so forth.

The dimers [{(ηn-ring)MCl}2(μ-Cl)2] ((ηn-ring)M = (η5-C5Me5)Ir, (η6-p-MeC6H4iPr)Ru) react with the modified cysteines S-benzyl-l-cysteine (HL1) or S-benzyl-α-methyl-l-cysteine (HL2) affording cationic complexes of the formula [(ηn-ring)MCl(κ2N,S-HL)]Cl (1, 2) in good yield. Addition of NaHCO3 to complexes 1 and 2 gave equilibrium mixtures of neutral [(ηn-ring)MCl(κ2N,O-L)] (3, 4) and cationic [(ηn-ring)M(κ3N,O,S-L)]Cl (6Cl, 7Cl) complexes. Similar mixtures were obtained in one-pot reaction by successive addition of the modified cysteine and NaHCO3 to the above formulated dimers. Addition of the N-Boc substituted cysteine derivative S-benzyl-N-Boc-l-cysteine (HL3) and NaHCO3 to the dimers [{(ηn-ring)MCl}2(μ-Cl)2] affords the neutral compounds [(ηn-ring)MCl(κ2O,S-L3)] ((ηn-ring)M = (η5-C5Me5)Ir (5a), (η6-p-MeC6H4iPr)Ru (5b)). Complexes of the formula [(ηn-ring)MCl(κ3N,O,S-L)][SbF6] (6Sb-8Sb), in which the cysteine derivative acts as a tridentate chelate ligand, can be prepared by adding one equivalent of AgSbF6 to the solutions of compounds 5 or to the mixtures of complexes 3/6Cl and 4/7Cl. The amide proton of compounds 8aSb and 8bSb can be removed by addition of NaHCO3 affording the neutral complexes [(ηn-ring)M(κ3N,O,S-L3-H)] ((ηn-ring)M = (η5-C5Me5)Ir (9a), (η6-p-MeC6H4iPr)Ru (9b)). Complexes 9a and 9b can also be prepared by reacting the dimers [{(ηn-ring)MCl}2(μ-Cl)2] with HL3 and two equivalents of NaHCO3. The absolute configuration of the complexes has been established by spectroscopic and diffractometric means including the crystal structure determination of (RIr,RC,RS)-[(η5-C5Me5)Ir(κ3N,O,S-L1)][SbF6] (6aSb). The thermodynamic parameters associated with the epimerization at sulphur that the iridium compound [(η5-C5Me5)Ir(κ3N,O,S-L3-H)] (9a) undergoes have been determined through variable temperature 1H NMR studies.

The modified cysteine ligand, S-benzyl-α-methyl-l-cysteine (HL2), was prepared from l-cysteine hydrochloride methyl ester. The reaction of commercial S-benzyl-l-cysteine (HL1) or HL2 with the dimer, [{(η(5)-C5Me5)RhCl}2(μ-Cl)2], gives rise to the cationic complexes, [(η(5)-C5Me5)RhCl(HL)]Cl (HL = HL1 (1), HL2 (2)), in which the cysteine ligand exhibits a κ(2)N,S coordination mode. In a basic medium, HL1 or HL2 reacts with [{(η(5)-C5Me5)RhCl}2(μ-Cl)2] to afford mixtures of two epimers at the metal centre of the neutral complexes, [(η(5)-C5Me5)RhCl(κ(2)N,O-L)] (HL = HL1 (3), HL2 (4)), in which amino carboxylate adopts a κ(2)N,O mode of coordination along with variable amounts of the cationic compounds, [(η(5)-C5Me5)Rh(κ(3)N,O,S-L)]Cl (HL = HL1 (6Cl), HL2 (7Cl)), which contain κ(3)N,O,S coordinated cysteine-derived ligands. However, in a basic medium, the N-Boc substituted cysteine S-benzyl-N-Boc-l-cysteine (HL3) only yields the κ(2)O,S coordinated derivative, [(η(5)-C5Me5)RhCl(κ(2)O,S-L3)] (5), as a mixture of two diastereomers depending on the configuration of the metal centre. The bidentate chelate complexes 3-5 react with AgSbF6 to give the hexafluoroantimonates [(η(5)-C5Me5)Rh(κ(3)N,O,S-L)][SbF6] (HL = HL1 (6Sb), HL2 (7Sb), HL3 (8Sb)) with tridentate coordination. Compound 8Sb reacts with NaHCO3 to give the neutral complex [(η(5)-C5Me5)Rh(κ(3)N,O,S-L3-H)] (9), which can also be prepared by reacting the dimer [{(η(5)-C5Me5)RhCl}2(μ-Cl)2] with HL3 in the presence of two equivalents of NaHCO3. The new compounds contain up to four stereogenic centres, namely, Rh, S, N, and C. The absolute configuration of the complexes has been established by spectroscopic and diffractometric investigations, including the crystal structure determination of [(η(5)-C5Me5)RhCl(κ(2)O,S-L3)] (5), [(η(5)-C5Me5)Rh(κ(3)N,O,S-L1)][SbF6] (6Sb), [(η(5)-C5Me5)Rh(κ(3)N,O,S-L2)][SbF6] (7Sb) and [(η(5)-C5Me5)Rh(κ(3)N,O,S-L3-H)] (9). Variable temperature (1)H NMR studies reveal the existence of epimerization processes and theoretical calculations were used to discriminate their nature.