Thermostable and Monoconjugable Gold Clusters with a Dodecadentate Thioether Ligand Gripper

Abstract

The Schmid cluster, [1] [Au 55 (PPh 3 ) 12 Cl 6 ], has stimulated many different areas of technology ranging from catalysis research [2] to the concept of quantum electronics. [3,4] Monofunctionalized water-soluble derivatives of this cluster [5] have become commercially available and found numerous applications. [6][7][8][9][10][11][12][13][14] Recently, gold clusters have been employed as universal fluorescence quenchers in molecular beacons [15] and as nanoscale antennas for the reception of radio radiation in the GHz frequency region, which causes local and selective inductive heating of cluster-labeled biomolecules.[16] These applications as well as current experiments in DNA nanotechnology [17][18][19][20][21][22][23] point to the need for the increased thermostability of these gold clusters. We have shown that replacement of the monopodal triphenylphosphane ligands in such clusters with water-soluble tripodal thioethers based on 1,3,5-tris(thiomethyl)benzene leads to gold clusters with improved stability. [24] Herein, we report a new generation of biocompatible gold clusters that are surrounded by a single dodecadentate, nanoscale thioether-based "gripper". This method allows nanoparticles to be singly functionalized without the otherwise necessary step of purification of mixtures by HPLC.[ 25] We demonstrate that "gripped" clusters in oligonucleotide conjugates can survive the temperature conditions of polymerase chain reaction (PCR) and hybridization experiments.The concept behind our ligand is sketched in Figure 1. The Au 55 cluster was proposed to possess a cuboctahedral core, the surface of which is composed of eight corner-sharing triangles (111) and six squares (110).[1] Although there is an ongoing debate [26,27] about the cluster geometry, we decided to adopt this proposal as a working hypothesis. Au 55 is expected to bind four tripodal ligands provided that the binding mode of the ligands is comparable to that of the Schmid cluster, in which the 12 triphenylphosphanes most likely occupy the corners of the cuboctahedron. If the four tripodal ligands are connected by suitable linkers, a dodecadentate ligand will result. The synthesis was also designed so that the final material carries a single functional group to allow conjugation to (bio)molecules.Scheme 1 shows the synthesis of the target ligand 8. We selected a monomaleimido group as the monoconjugable unit to ensure functional comparability with the commercially available variant of the Schmid cluster. Thioether 2 was generated from trisbromide 1 as a key precursor that allowed the synthesis of 8 by a divergent-convergent route in only six steps with an overall yield of 31 %. The gold cluster was synthesized from ligand 8 by phase-transfer synthesis, as previously described for the tristhioether derived from lcysteine.[24] High-resolution transmission electron microscopy revealed a narrow size distribution of the clusters with a mean diameter of 1.4 nm, which is as expected for Au 55 particles. The cluster was conjugated with a 5'-thiol-modifi...

The relevance of shape and size of Au55 clusters

“…27 For this, the synthesis of the ligand molecule, shown in Fig. 27 For this, the synthesis of the ligand molecule, shown in Fig.…”

“…A very special kind of ligand exchange has recently been reported: the total coverage of the Au 55 nucleus by a single dodecadentate thioether. 27 For this, the synthesis of the ligand molecule, shown in Fig. 5, had first to be developed.…”

Monofunctionalized Gold Nanoparticles: Fabrication and Applications

“…This has been demonstrated by labeling of ssDNA with Au 55 clusters that were stabilized by a monofunctionalized benzylic thioether-based dendrimer. [48] Inspired by these studies from Kiedrowski et al, we investigated the potential of benzylic thioether-based oligomers and dendrimers for the stabilization of AuNPs. Already first experiments resulted in AuNPs with nar-…”

Gold Nanoparticles Stabilized by Single Tripodal Ligands

“…While rather complex and synthetically demanding dentritic ligands already displayed their ability to stabilize an entire AuNP, a more recent ligand design showed that also linear oligomers are able to stabilize an entire particle when bulky enough to sterically protect the surface of the ligand‐coated AuNP . With a series of linear oligomers of various sulfur–sulfur distances, a correlation between the size of the stabilized AuNP and both parameters, the distance between coordination points of these multivalent ligand structures and the equivalents of gold salt used has been observed .…”

“…In the past decade, the variety of ligand designs has been enlarged toward benzylic sulfide‐based oligomers due to their reversible binding to gold surfaces, enabling supramolecular approaches toward AuNP stabilization. The flexibility of the benzyl sulfide linkers enables favorable conformations of the ligands upon passivation of the AuNP and various ligand designs have been investigated, ranging from oligomeric, tripodal, and dendrimeric to even cage‐like thioether‐based ligands, most of them yielding AuNPs with narrow size distributions. Cages controlling the size of the nanoparticles were also developed for other noble metals like palladium, displaying catalytic activity .…”