Peptide Coupling between Amino Acids and the Carboxylic Acid of a Functionalized Chlorido-gold(I)-phosphane

Abstract

We have developed a protocol for the direct coupling between methyl ester protected amino acids and the chlorido-gold(I)-phosphane (p-HOOC(C6H4)PPh2)AuCl. By applying the EDC·HCl/NHS strategy (EDC·HCl = N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide hydrochloride, NHS = N-hydroxysuccinimide), the methyl esters of l-phenylalanine, glycine, l-leucine, l-alanine, and l-methionine are coupled with the carboxylic acid of the gold complex in moderate to good yields (62-88%). All amino acid tagged gold complexes were characterized by (1)H and (13)C NMR spectroscopy and high-resolution mass spectrometry. As corroborated by measurement of the angle of optical rotation, no racemization occurred during the reaction. The molecular structure of the leucine derivative was determined by single-crystal X-ray diffraction. In the course of developing an efficient coupling protocol, the acyl chlorides (p-Cl(O)C(C6H4)PPh2)AuX (X = Cl, Br) were also prepared and characterized.

Synthesis of Gold(I) Derivatives Bearing Alkylated 1,3,5‐Triaza‐7‐phosphaadamantane as Selective Anticancer Metallodrugs

“…In addition, a number of gold conjugates derived from amino acids or peptides have been reported. As examples, N‐heterocyclic carbene (NHC)–gold complexes,, conjugates of ferrocene coordinated to gold(I) derivatives, gold(III) dithiocarbamates,, gold(I) azides, and gold(I) thiolates, with only one example of a chloro–gold–phosphane found in the recent literature.…”

Metallostar Assemblies Based on Dithiocarbamates for Use as MRI Contrast Agents

“…Previous designs based on an organic or metal core often allow rotation about the axis of the tether and this can have a detrimental effect on the relaxivity. [3][4][5][6] Using the Evans method to determine the gadolinium concentration, 19 the relaxivity of Gd-DO3A-DTC-AuPPh3 at 0.01 MHz was found to be 11.3 and 10.3 mM −1 s −1 at 25 and 37 °C, respectively (Figure 3). As the temperature increases, the rate of internal freedom of rotation increases and this results in a reduction in the relaxivity of the complex.…”

“…Yield: 800 mg (91%). 4,44.2,43.9,43.5,30.3,30.2,30.1,29.9 (s x 8,NCH2CH2N) [AuCl(tht)] 3 (59 mg, 0.18 mmol) was dissolved in dichloromethane (10 mL) and PPh2C6H4COOH (61 mg, 0.20 mmol) was added. After stirring for 15 min, the solvent volume was reduced to ca.…”

“…2 mL under vacuum and n-pentane added to afford [AuCl(PPh2C6H4COOH)] as a colorless solid, as reported previously. 4 Yield: 87 mg (88%).…”

“…In addition, the degree to which the relaxation of water protons changes is due to the multimeric effect which stems from the increased, localized contrast agent concentration. 2 Pioneering work by Tóth, 3 Helm, 4 Parac-Vogt 5 and Desreux 6 has focused on the synthesis of molecular multimetallic gadolinium compounds, either with an organic or metalbased core. These assemblies have demonstrated impressive relaxivity in many cases.…”