This journal is © The Royal Society of Chemistry 2017 Chem. Soc. Rev.

Cite this:DOI: 10.1039/c7cs00023e

New trends in the functionalization ofmetallic gold: from organosulfur ligandsto N-heterocyclic carbenes

Sabrina Engel,† Eva-Corinna Fritz† and Bart Jan Ravoo*

In this Tutorial Review, we describe the development of new ligands for functionalizing and stabilizing

metallic gold in the form of planar gold surfaces and gold nanoparticles (NPs). Starting from the state-

of-the-art of organosulfur ligands, we describe the gold–sulfur bond formation and the nature of the

resulting interface. In addition, we explain methods to prepare ordered monolayers on planar surfaces

and stable ligand shells around NPs, illustrating important pioneering studies and examples of current

research. Moreover, we highlight recent advancement in functionalizing gold by N-heterocyclic carbenes

(NHCs), a promising alternative ligand class regarding stability and variable design strategies. We discuss

the chemistry of the carbene–gold bond and report on advantages of this new ligand. Additionally,

selected examples of current research illustrate the formation of ultra-stable self-assembled monolayers

of NHCs on gold surfaces as well as the preparation of NHC-stabilized gold NPs.

Key learning points(1) Organosulfur-based self-assembled monolayers on planar gold surfaces: preparation, adsorption processes and interfacial properties.(2) Organosulfur-stabilized gold NPs: modern design strategies of ligand shells provide functional NPs for diverse applications.(3) N-Heterocyclic carbenes: promising new ligand class for metallic gold-based nanosystems and gold–carbene bond characteristics.(4) N-Heterocyclic carbene-based self-assembled monolayers on planar gold surfaces: from the basics of NHC-based surface modification to the formation ofultra-stable monolayers.(5) N-Heterocyclic carbene-stabilized gold NPs: general synthetic procedures and innovative NP systems.

IntroductionThe noble metal gold is the most extensively studied metal inthe field of nanotechnology due to its unique properties andwidespread applications.1 Gold is stable against oxidation reac-tions with atmospheric oxygen and withstands reactions withmost chemicals allowing one to handle samples and performexperiments under atmospheric conditions. Moreover, gold isparticularly interesting due to its compatibility with biomoleculesresulting in a broad range of applications in the area of bio-medicine, including sensing, imaging or cancer therapy.2,3 Cells,for instance, can adsorb onto gold surfaces without adverseeffects. Furthermore, the catalytic activity of gold as well as itselectronic and optical properties offer a diverse potential in thearea of nanomaterial research.4

Although quite expensive, gold is commercially available andcan be easily converted into thin planar films of different crystalsurface structures ((111), (110) and (100)) or colloidal particles insolution. Gold-coated surfaces can be readily prepared by physicalvapor deposition (PVD), sputtering or electrodeposition andare simple to pattern by photolithography, micromachining orchemical etching. Moreover, planar gold surfaces are applicableas substrates for analytical methods such as surface plasmonresonance (SPR) spectroscopy and quartz crystal microbalancewith dissipation monitoring (QCM-D).1,2

Gold nanoparticles (AuNPs) with a size of 1–100 nm areamong the most common colloids. The large surface area-to-volume ratio of nanoscale particles results in a huge amount ofcoordinatively unsaturated surface atoms, leading to entirely newphysical characteristics and a significant increase in reactivitycompared to flat surfaces. For instance, unique optical propertiesof AuNPs are caused by their interaction with light.5–7 Irradiationinduces polarization of the free conduction band electrons,resulting in a collective coherent oscillation of the electrondensity relative to the positive metallic lattice. The oscillation

Organic Chemistry Institute and Center for Soft Nanoscience,

Westfalische Wilhelms-Universitat Munster, Corrensstrasse 40, 48149 Munster,

Germany. E-mail: b.j.ravoo@uni-muenster.de

† Both authors contributed equally to this work.

Received 12th January 2017

DOI: 10.1039/c7cs00023e

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amplitude reaches a maximum at a defined frequency, theso-called surface plasmon resonance (SPR), which stronglydepends on the electron density, effective mass of the electronsas well as particle shape and size.5

AuNPs must be stabilized by ligands to overcome the highsurface energy and attractive van der Waals interactions betweenthe metal cores, which would otherwise cause an irreversibleaggregation. Stabilization can be achieved by electrostatic repul-sion, steric hindrance or a combination of both. Moreover, thenature of the ligand can affect the shape, size and size distribu-tion of the particles within the synthesis process and influencethe resulting nanomaterial’s properties.4,8

A variety of ligands have been employed to functionalizemetallic gold; particularly organosulfur-based compounds likethiols, sulfides or disulfides are versatile candidates because oftheir strong affinity to gold and high packing density. Therefore,they have been widely applied to immobilize inorganic, organicand biological materials9 on gold surfaces and NPs. The prepara-tion of self-assembled monolayers (SAMs) on planar gold surfaces

and the wet chemical synthesis of organosulfur-stabilized AuNPsare well-established methods in bottom-up nanofabrication.8,10

Nevertheless, the gold–sulfur bond is not completely inert, andthe oxidative and thermal stability of thiol-functionalized AuNPsand SAMs is far from perfect demanding for alternative ligands.Recently, N-heterocyclic carbenes (NHCs) have emerged as sur-face ligands due to their capability to form strong carbene–metalbonds and flexibility to attach diverse functional groups atdifferent molecular positions in simple synthesis procedures,yielding a broad variety of ligands, which are in contrast tomost commonly used linear organosulfur ligands.4

In this Tutorial Review we compare the properties andadvantages of organosulfur and NHC ligands, focusing on thefunctionalization and stabilization of planar gold surfacesand AuNPs. Using selected examples from current research,we highlight differences between these two ligand types andillustrate the prospects of NHCs in the field of gold-basednanotechnology.

Organosulfur ligands on metallic goldGeneral aspects of the gold…sulfur bond and adsorptionprocesses

The chemistry of the interaction between thiols and gold appearssimple, but is still not entirely understood.1 Preparative function-alization of gold is not complicated, because no oxide layer needsto be removed before usage. Instead, it is the detailed under-standing of the gold–sulfur bond and the physical arrangementof the sulfur atom on top of the gold lattice which is still in focusof today’s research. However, it is generally accepted that thecovalent interaction between gold and sulfur requires the for-mation of a gold–thiolate bond.11 In 2014, Zhang and coworkersdemonstrated that the adsorption process of a thiol on planargold begins with physisorption.12 In the following chemisorption,the sulfur–hydrogen bond is cleaved, resulting in the generationof a thiyl radical, which subsequently forms the gold–sulfurbond. Experimental evidence of the hydrogen atom dissociation

Eva-Corinna Fritz

Eva-Corinna Fritz (born in 1987in Wiesbaden, Germany) studiedchemistry at the University ofMunster, where she obtained herMSc degree in 2012. For her PhD,she joined the group of Prof. BartJan Ravoo and investigated thepreparation functional nanoscalesystems incorporating gold. In2016, she defended her PhD thesisentitled ‘‘Strategies to functionalizeaddressable gold surfaces – Fromsupramolecular polymer brushesand bimetallic surfaces to con-trolled nanoparticle aggregation’’.

Bart Jan Ravoo

Bart Jan Ravoo (born in 1970in Enschede, The Netherlands)obtained his MSc and PhD degreesfrom the University of Groningen.He was a Newman scholar atUniversity College Dublin and anassistant professor at the Universityof Twente. Since 2007 he has beena professor at the WestfalischeWilhems-Universitat Munster,where he is in charge of the‘‘Synthesis of Nanoscale Systems’’group. His research focuseson biomimetic supramolecular

chemistry and surface functionalization by molecular self-assembly.He co-initiated the Center for Soft Nanoscience (SoN) in Munster.

Sabrina Engel

Sabrina Engel (born in 1991 inOstercappeln, Germany) receivedher MSc degree in chemistry fromthe University of Munster in 2015.During her MSc thesis she workedon nanoparticle functionalizationstrategies by use of host–guestchemistry. Currently, she is a PhDstudent under the supervision ofProf. Bart Jan Ravoo supported bya FCI fellowship. Her researchinterests are focused on the supra-molecular functionalization ofstimuli-responsive nanoparticlesfor application in biomedicineand catalysis.

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the monodentate adsorbates (75–86% surface density), whereasbidentate BMTBM yielded a rather loosely packed structurewith a relative packing density of 43%, based on the fact thattwo sulfur head groups of BMTBM occupy more space on thesurface compared to a single sulfur head group of the monodentateadsorbate. Nevertheless, solution-phase thermal desorption studiesindicate remarkably higher thermal stability for the monolayergenerated from BMTBM than for monodentate thiol SAMs. Afterheating up for 1 h at 90 1C, a fraction of B 75% of the BMTBMmonolayer survived, while less than 20% of MBM and MTBMremained on the gold surface.

Gold nanoparticles functionalized with organosulfur ligands

Functionalization of AuNP ligand shells can be performedanalogous to the strategies to functionalize SAMs describedabove. A functional ligand can be (1) equipped with the desiredfunctional group before the particle synthesis; (2) immobilizedon the particle surface in the course of an exchange reaction;or (3) immobilized within the ligand shell in a post-syntheticcovalent or non-covalent modification.27,28

In 2015, Kay and coworkers reported for the first timethe application of dynamic covalent hydrazone chemistry toreversibly and quantitatively modify a functional ligand shellon AuNPs.29 In general, a combined functionalization of NPs by apost-synthetic exchange reaction of pre-functionalized ligandsis advantageous, because the NP synthesis is not limited by thefunctionalization reaction conditions. Therefore, a symmetricdisulfide was equipped with a tetraethylene glycol undecyl chain,which was functionalized with a fluorinated hydrazine at thechain end (Fig. 7, red). Alkyl chains ensured a highly organizedmonolayer due to the maximization of van der Waals inter-actions, while ethylene glycol chains provided polar solventcompatibility and steric flexibility of the reactive chain ends.A thermodynamically controlled dynamic hydrazine exchangewas achieved under acidic conditions and in the presence of analdehyde. First, a reversible and complete exchange by a trifluori-nated aldehyde (Fig. 7, dark blue) was investigated, whereas theligand exchange and the resulting composition of the ligand shellwere characterized in situ and monitored in real-time by 19F-NMRspectroscopy. To demonstrate the potential of this approach toprepare tailor-made nanomaterials, tunable solubility of AuNPs

was obtained by using aldehydes of different polarity (Fig. 7,green: apolar, light blue: polar). Based on the fine-tuning of theextent of the exchange reaction in combination with a variationof the nature of the aldehyde added, a continuum of particlesolubility was realized.

Kubik and coworkers designed a clever synthesis procedurefor water soluble AuNPs protected by a mixed ligand shell con-sisting of three different adsorbate molecules, which were appliedto recognize dipeptides.30 Diffusion-ordered NMR spectroscopy(DOSY NMR) revealed a significantly higher efficiency of peptidebinding for a combination of three orthogonal functional groupscompared to mono- or difunctionalized AuNPs. To investigate therecognition process, three fairly different thiol-based ligandswere selected (Fig. 8), which allow a cooperative action in bindingpeptides and do not interact with each other, preventing anintramolecular conformational collapse of the receptor or anintermolecular self-aggregation. Thiols Q and C, with the quater-nary ammonium ion function and the crown ether moiety, areimportant for binding to the C- and N-terminal ends of unpro-tected peptides, respectively. The trimethylalkyl ammoniumgroup of Q is also necessary to provide water solubility, whereasthe phenyl group of thiol P is relevant to induce a selective recogni-tion for peptides with aromatic side chains. First, dioctylamine-protected AuNPs were prepared and by performing a ligandexchange reaction with the functionalized thiols the weaklybound amine ligand was replaced, which allowed simple con-trol over the ratio of the three ligands. The exact ligand ratiowas determined by decomposing the particles, releasing theligands with iodine and measuring 1H-NMR in the presence ofan internal standard. DOSY NMR showed the highest affinitybetween peptides and AuNPs for the combination of all threeligands, and furthermore demonstrated a favored binding tothe aromatic Gly–Phe peptide.

The work of Simon and coworkers demonstrates the positiveeffect of multivalency on the stability of hollow gold nanospheres(HAuNSs) and nanorods (AuNRs) by use of mono-, bi- and tri-dentate polyethylene glycol (PEG) thiol-based ligands.31 Therefore,citrate-stabilized HAuNSs were synthesized via sacrificial galvanicreplacement reaction and cetyltrimethylammonium bromide

Fig. 6 Surface-initiated polymerization of PMMA on gold surfacesinitiated by SAMs consisting of MBM (left), MTBM (middle) and BMTBM(right). The diagram shows the film thickness of generated PMMA polymerbrushes as a function of the reaction temperature.26 Reprinted from ref. 26with permission from ACS Publications.

Fig. 7 Schematic representation of the dynamic covalent hydrazoneexchange to reversibly modify the ligand shell of AuNPs (top). Molecularstructures of the hydrazine-functionalized alkyl thiolates as starting ligandsand the dynamic covalent aldehyde-based building blocks of differentsolubility (bottom).29 Reprinted from ref. 29 with permission from Wiley.

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avidin using EDC/NHS coupling. Biotin–FITC binding experi-ments revealed that each AuNP-Zwit is able to bind nine avidinmolecules on the surface. These AuNP–avidin conjugates canbe lyophilized and redispersed without losing their activity,offering the possibility of transportation as powders for futuretherapeutic formulations or to further functionalize AuNPs withany biotin-labeled biomacromolecules.

In 2015, Prins and coworkers developed a sophisticated con-cept to prepare transient signals from functionalized NPs poweredby adenosine triphosphate (ATP), corresponding to a temporalregulation of a supramolecular process.33 One main characteristicof that concept is the imitation of biological signal transductionpathways. The developed supramolecular system is based on thenon-covalent interaction between a fluorescent oligoanion anda pre-functionalized cationic surface of AuNPs, whereby thesignal of the system corresponds to the fluorescence signal. Thestabilizing cationic ligand consists of a long alkyl thiol, which isterminated by a metal complex (Fig. 11a). In a bound state of

the oligoanion (A) to the AuNP, the fluorescence is quenchedbecause of the close proximity to the gold surface. Upon theaddition of ATP as a competitive binding partner, the oligoanionwas displaced resulting in the appearance of a fluorescencesignal (Fig. 11b). The generation of an ATP driven fluorescencetransient signal was obtained in the presence of a highly efficientenzyme responsible for the decomposition of ATP. Displacingthe oligoanion by the stronger binding ATP resulted in a fast andtransient increase of the fluorescence signal. However, enzymaticdecomposition of ATP caused a decay of the signal, whereasthe decay rate correlated with the concentration of the enzyme(Fig. 11, box). A concentration-dependent activation of two differentsignal transduction pathways was realized by using an additionalfluorescent dipeptide, which has a lower affinity towards thecationic surface. Based on two different binding affinities,the signal transduction was regulated by the concentration ofadded ATP and the consequent potential of displacing thefluorescent transducer. While the oligoanion-mediated signal

Fig. 10 Chemical structure of the zwitterionic carboxybetaine ligand and scheme of the conjugation of the functionalized AuNPs with biomolecules(biotin-functionalized horseradish peroxidase). High colloidal stability was demonstrated by successive freeze drying cycles and increasing ionicstrengths.32 Reprinted from ref. 32 with permission from ACS Publications.

Fig. 11 AuNP-based supramolecular system imitating biological signal transduction pathways. (a) Molecular structures of the functional alkyl thiol aswell as the signal transducer oligoanion A and the signal regulating nucleotide; (b) schematic representation of the fluorescent signal transduction bydisplacement (top) and of the generation of a transient signal (box).33 Reproduced from ref. 33 with permission from Nature Publishing Group.

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General aspects of the gold…carbene bond and adsorptionprocesses

Due to the fact that this research field is still in its infancy, notall details of the NHCs binding to gold surfaces are completelyunderstood. Nonetheless, in 2015 Johnson and coworkers pub-lished a review on carbene ligands in surface chemistry describingthe state-of-the-art of carbenes as ligands for the functionalizationof metal NPs and surfaces. For a discussion of the metal–carbenebond including orbital interactions as well as a general overviewof synthetic procedures for NHC-stabilized NPs and surfaces, thereader is referred to this comprehensive article.34 In contrast,the present Tutorial Review will concentrate on the noble metalgold and, in this context, on the newest findings regarding thegold–NHC bond formation and absorption processes of NHCson gold surfaces.

In 2016, Richeter and coworkers investigated the reactivityof small and large AuNPs towards NHCs and the mode of NHCgrafting by use of experimental and theoretical approaches.37

Today, it is well-known that the stability of NHC-coated AuNPsdepends on the molecular structure of NHCs and on theirsynthesis. Small and flexible NHCs with methyl groups or longalkyl chains as N-substituents can minimize steric repulsion withthe AuNP surfaces. Further functionalization of the backbonewith long alkyl chains or aromatic rings can cause additionalstabilizing interactions between the ligands, resulting in stableNHC-functionalized AuNPs.38 Chemical reduction, thermolysisor ligand exchange reactions are the main synthesis strategies,whereby until now imidazol-2-ylidenes are the most used NHCs.In contrast, Richeter and coworkers used benzimidazol-2-ylidenesas NHC ligands to achieve further stabilization through p–pinteractions and prepared NHC-capped AuNPs by use of aligand exchange starting from di-n-dodecylthioether-stabilizedAuNPs. Three different NHCs were examined with methyl (NHCa),n-hexyl (NHCb) or benzyl (NHCc) groups at the nitrogen atoms(Fig. 13a). Regarding the synthesis, thioether-stabilized AuNPswere mixed with the corresponding benzimidazolium salts andNaOtBu was added to deprotonate and generate the carbenespecies in situ. Transmission electron microscopic (TEM) analysisshowed a shrinking of the average particle size, whereby thesmallest NHC-capped AuNPs were obtained in the case of NHCaand the biggest ones by use of NHCb. X-ray diffraction (XRD)and 13C solid state NMR measurements suggest that etching of

the AuNPs occurs in consequence of the formation of bis(NHC)AuI complexes. This process is stronger for NHC ligands, whichare not able to stabilize AuNPs sufficiently, leading to smallerparticles like in the case of NHCa. NHCb appears to be the beststabilizing ligand, probably due to the enhanced presence ofinter-NHC interactions between the long alkyl chains attachedto the nitrogen atoms. To analyze the reactivity of large AuNPstowards NHCa, DFT calculations were performed consideringplanar Au(111) surfaces, the most stable surface type and pre-dominant in large AuNPs, revealing that the binding angle is quiteflexible and is dependent on the surface coverage. Nevertheless,a perpendicular binding geometry is favored (Fig. 13b). In thisway, optimal Au–C orbital overlap is obtained and intermolecularinteractions between the methyl groups are ideal. The modelingalso pointed out that the grafting of NHCa onto a gold adatom,which is a low coordinated reactive gold atom pulled out of thesurface, is the most energetically favored binding mode. This canbe explained by the absence of steric hindrance between themethyl groups and the surface. The binding energy of thisorientation is�63.55 kcal mol�1 with an Au–C bond distance of2.03 Å, which is similar to distances measured for NHC–AuI

complexes. In comparison, the di-n-dodecylthioether ligandshows a significant weaker binding energy (�14.36 kcal mol�1)and a much longer Au–S bond distance of 2.60 Å favoring thereplacement of the ligand in the exchange reaction.

To analyze the binding behavior of NHCs on small AuNPs,well-defined Au38 gold clusters with a size of B 1 nm were modeled(Fig. 13c). Modeling considered two central atoms surroundedby an ellipsoidal 21 gold frame forming a C3-symmetric Au23

core, whereas the remaining 15 gold atoms were located on thetriangular faces of the Au23 core. Natural bonding orbital (NBO)analysis revealed a separation of the bare cluster into two groupsof different charges. Atoms of the Au23 core were partiallynegatively charged, whereas the remaining atoms had a partialpositive charge. During the binding process of a single NHCaligand to one gold atom, the C3-symmetry of the cluster wasbroken and gold atoms moved closer to each other. Dependingon the location of the NHCa, binding energies between �19.51and �34.41 kcal mol�1 were reached, whereas the bindingstrength was higher for NHCa attached to the least coordinatedgold atom, which is in good agreement with the adatom theoryfor flat Au(111) surfaces. Bond lengths varied between 2.08 and

Fig. 13 Structure of investigated NHCs and representation of NHC binding to gold. (a) Benzimidazol-2-ylidenes with three different N-substituents;(b) grafting model of NHCa on planar Au(111) showing a perpendicular binding behavior; (c) most stable equilibrium structure of NHCa binding to themodeled Au38 cluster.37 Reproduced from ref. 37 with permission from Wiley.

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2.10 Å and the NHC ligand preferred to bind in an ‘‘on-top’’position on a tetrahedron formed by four gold atoms, wherebyno binding angle was energetically favored. During the bindingprocess a charge transfer from NHCa to the Au23 core wasobserved based on the electron–donor character of NHCs. Dueto the binding of nine NHCa ligands, the cluster was completelycovered and the metallic core of the cluster had a large negativecharge (�2.57 |e|), which led to increased coulomb repulsionbetween the gold atoms resulting in larger Au–Au distances(2.67–12.27 Å compared to 2.79–11.96 Å) within the cluster.

The work of Richeter and coworkers demonstrates that thebinding behavior of NHCs to AuNPs is independent of theparticle size, because both models (planar Au(111) vs. Au38 cluster)yielded comparable results. The strong gold–carbene bond com-petes with the gold–gold bond resulting in a restructuring ofthe Au surface, leading to the formation of surface defects likeAu adatoms. As a consequence, mono-NHC–Au fragments can beeasily released from the surface and a reaction with the remainingNHC ligands in solution can occur, yielding bis(NHC) AuI com-plexes. Thus, an etching of the AuNPs occurs, which decreases theparticle size. However, by means of a sophisticated NHC design,stabilizing ligand–ligand interactions can be generated at theAuNP surface (e.g. in the case of NHCb) to suppress the etchingprocess and to yield stable AuNPs.

Fuchs, Glorius and coworkers used scanning tunnelingmicroscopy (STM) to further examine the mobility of differentNHC ligands on planar gold surfaces, which is necessary forthe formation of well-ordered intact SAMs.39 For this purpose,NHC precursors with a carboxylate functionality were used and

immobilized on the gold surface by physical vapor deposition(PVD) under ultrahigh vacuum conditions. A heating processinduced the release of CO2, whereby the resulting NHCs coulddirectly bind to the surface without generating any impurities.In this work, three imidazol-2-ylidene CO2 adducts with differentsteric and electronic properties were chosen (IMes, IPr, and IMe)and analyzed by STM. STM images of the carbene IMes showeddisordered ellipsoidal shapes, indicating the inability of IMesmolecules to rotate freely on the surface due to unordered anddifferently oriented surface binding. In contrast, deposition ofIPr on Au(111) resulted in a highly ordered hexagonally packedSAM of circular shape proving the ability for a free molecularNHC rotation around a single carbene–gold bond on the surface.At a low surface coverage (up to 0.01 monolayer), IPr ligandswere detected along the edges of the Au(111) step and elbowpositions of the 22 � O3 reconstructed Au(111) surface. Islandsof IPr were visible for an increased coverage (4 0.05 monolayer),which were preferably formed at face-centered-cubic (fcc) stackingregions and easily split into smaller units and recombinedwithin following movement processes. On reaching the satura-tion coverage, the mobility of IPr within the SAM remained high,and the herringbone structure of the Au(111) substrate under-neath combined with the hexagonal-close-packed (hcp) structureof IPr was imaged (Fig. 14a). In the case of IMe, similar processeswere detected at low coverage rates. However, at the saturationcoverage a centered rectangular close-packed structure was imaged,presumably as a consequence of the different substituents atthe nitrogen atoms. Although NHCs are strongly bound to thegold surface, the formed islands and SAMs exhibit relatively

Fig. 14 STM measurements of the NHC-functionalized Au surface and simulations of the adatom formation. (a) Submonolayer STM image indicating thepreference of IPr to occupy the fcc regions and elbow positions of the Au(111) herringbone reconstruction; (b and c) successive STM measurements taken atthe same area showing the high mobility of IPr–Au islands; (d and e) DFT optimized structures of IMe on Au(111) without and with adatom attendance;(f) CP-MD simulation of the Au adatom formation in the presence of IMe.39 Reproduced from ref. 39 with permission from Nature Publishing Group.

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exhibit the same (electro-)chemical resistance as the ultra-stableNHC SAMs reported previously. Furthermore, it is possible togenerate NHC films in vacuo directly from the solid by connect-ing a solid doser to an UHV chamber and heating to 325 K. Theexceptional thermal stability was proven via temperature pro-grammed desorption (TPD) measurements, resulting in a Tmax =605 K for the loss of the NHC from the surface, which is about125 K higher compared to simple thiols. Based on this value, aNHC–Au bond strength of 158 � 10 kJ mol�1 was determined(compared to 126 kJ mol�1 for thiol films). High-resolutionelectron energy loss spectroscopy (HREELS) revealed a perpendi-cular binding of the NHC to Au(111) and STM proved a highuniformity of the films prepared in vacuo with a low pit andisland density and an adsorbate-modified herringbone recon-struction. Films generated in methanol exhibit larger amountsof pitting and islanding, but are still of high quality. The filmswere further analyzed by electrochemical methods investigatingthe surface coverage (3.92 � 0.12 molecules per nm2) and theaverage electron transfer rate KET (9.1 s�1, similar to compar-able thiol film). To demonstrate that these NHC films outper-form thiol SAMs, the group developed a NHC sensor chip forSPR-based biosensing (Fig. 17). SPR chips were functionalizedwith alkylated NHC (3d) SAMs and were checked against com-mercially available thiol-based hydrophobic association chips(HPA). These sensor chips were treated with phosphatidylcholinevesicles to form supported hybrid bilayers, which are usually usedto investigate receptor–analyte interactions. SPR and scanningelectron microscopic (SEM) measurements showed that the NHC-functionalized sensor chip provided a better vesicle fusion dueto greater spacing of NHCs, allowing an easier interdigitation

of phosphatidylcholine. The formation of a functional hybridbilayer was further proved by adsorption studies with variousconcentrations of the peptide melittin that is able to interactwith these bilayers. By use of the NHC chip, stronger and morereliable binding curves were obtained, whereas by applying theHPA chip less reproducible responses were reached. Additionally,the nonspecific adsorption of bovine serum albumin (BSA) wasexamined, which is a hint for the quality of the hybrid bilayers asit only adsorbs at defects. Different buffers and pH values weretested and in all cases except one, the amount of adsorbed BSAwas higher for HPA chips, again pointing out the superior qualityof supported lipid bilayers on NHC-based sensor chips, especiallyat pH extremes. This opens up the possibility for consistentprotein sensing in more extreme environments with a higherreproducibility and at the same time lower levels of nonspecificbinding. Furthermore, NHC chips possess higher thermal (65 1Cin air for 24 h) and long-term stability (9 months) in contrast tocommercial thiol-based SPR sensor chips. In sum, NHCs are onthe march in surface chemistry and possess the potential toreplace thiol-based SAMs in various applications.

Gold nanoparticles functionalized with N-heterocyclic carbenes

In 2009, Chechik and coworkers were the first to prepare NHC-functionalized AuNPs via ligand exchange of didodecyl sulfide(DDS)-protected AuNPs. However, the NPs formed insolubleprecipitates after some hours.43 Shortly afterwards, Tilley andVignolle published for the first time the synthesis of redispersibleNHC-stabilized AuNPs with long alkyl chains as N-substituentsby reduction of NHC–AuI-complexes.44 Since then differentstrategies to functionalize AuNPs with various NHC ligands

Fig. 17 SPR-based biosensing with NHC-functionalized chips compared to HPA chips. (a) Sensor chip design; (b) hybrid bilayer formation monitored by SPR;(c) SEM images of bilayer formation indicating vesicle formation on HPA chips; (d) quantitative melittin sensing; (e) unspecific BSA adsorption depending onbuffer and pH.42 Reprinted from ref. 42 with permission from Nature Publishing Group.

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have been developed (see the comprehensive review by Johnsonand coworkers34).

Pileni and coworkers carried out stability tests proving theenhanced oxygen resistance of NHC-functionalized gold nano-crystals (AuNCs) compared to dodecanethiol (DDT)-stabilizedAuNCs by treating these NP species with oxygen plasma andmolecular oxygen.45 DDT-stabilized AuNCs of different sizes(DDT@AuNC1–5) were prepared from various precursors by useof three different synthesis procedures. NHC-functionalizedNCs (L1–L5@AuNC) were obtained by deprotonation of differentbenzimidazolium chloroaurate salts with sodium hydride inCH2Cl2/toluene and subsequent reduction with aqueous NaBH4

solution. NHCs differ in the length of alkyl chains and in thechain position, influencing the buried volume of NHCs that hasan effect on the particle size. To investigate the oxygen plasmatreatment, AuNCs were dissolved, immobilized on TEM grids andimaged before (initial status see Fig. 18A–D) and after exposure tooxygen plasma for 80 s focusing on the particle morphology.Under the selected conditions all DDT-coated AuNCs showcoalescence and agglomeration of nanocrystals (Fig. 18E and F),independent of the synthesis strategy or particle size, which ledto the conclusion that the DDT ligands have been partiallydesorbed from the gold surface during plasma treatment. Incontrast, no changes in the integrity and 2D assembly weredetected for all types of NHC-functionalized AuNCs; even after120 s exposure time L1–L5@AuNC remained structurally unaffected.These results demonstrate the enhanced oxygen stability ofNHC-functionalized AuNCs compared to DDT-capped AuNCs.To investigate the influence of molecular oxygen, the synthe-sized AuNCs were dried and exposed to molecular oxygen for1 week. NMR analysis of redispersed DDT-functionalizedAuNCs showed a large decrease of free DDT ligand and DDT

bound to the surface of the AuNCs as well as the formation of thecorresponding disulfide, indicating a low resistance to molecularoxygen. In contrast, the NMR spectra of NHC-capped AuNCsbefore and after oxygen treatment were nearly unchanged. Massspectrometry revealed a small amount of the cationic bis-carbene[(NHC)2Au]+ complex. Further studies are necessary to determinewhether this NHC complex remains bound to the AuNC surfaceand thereby favors the stabilization.

An interesting example of water soluble NHC-functionalizedAuNPs that are electrostatically stabilized, addressable for apH-stimulus and hence switchable between aggregated anddissolved state was published by Glorius, Ravoo and coworkersin 2015.46 Four NHCs with negatively charged groups (sulfonateand carboxylate) and scaffolds with several steric demands wereconsidered (Fig. 19) and NHC@AuNPs were synthesized vialigand exchange combined with phase transfer. Starting fromthe precursor imidazolium salt, NHCs were generated in situ bydeprotonation and a biphasic system was obtained by adding asolution of DDS-protected AuNPs. The phase transfer (apolar topolar phase) of AuNPs indicated the successful displacement ofneutral DDS by the negatively charged NHC. The obtainedNHCs@AuNPs decreased significantly in size during ligandexchange (from B 9 nm to 4–5 nm, depending on the NHC)leading to a relatively high polydispersity. The reason for this isthe dissociation of NHC–AuI-complexes from the NP surface,resulting in the erosion of AuNPs. After purification no further sizechanges were noted, and in contrast high long-term stability for atleast three months in aqueous solution due to the strong electro-static stabilization (zeta potential between �30 and �50 mV) wasobserved. Regarding the pH responsiveness, at pH 4 AuNPsfunctionalized with sulfonated ligands remained stable, whereascarboxylate-capped species aggregated, caused by the loss of

Fig. 18 TEM images of AuNCs stabilized with DDT (left) or NHC (right) before (t = 0 s, upper section) and after treatment with oxygen plasma (t = 80–120 s,lower section). (A) DDT@AuNC1 generated from [(Et2Bimy)AuCl]; (B) DDT@AuNC4 generated from [(PPh3)AuCl]; (C) L3@AuNC; (D) L4@AuNC; (E–H) thesame TEM grid areas after oxygen plasma exposure.45 Reprinted from ref. 45 with permission from ACS Publications.

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Chem. Soc. Rev. This journal is© The Royal Society of Chemistry 2017

the gold–gold bonding, leading to a restructuring of the AuNPsurface combined with an increased number of defects withimproved kinetics for CO2 reduction.

Song and coworkers developed a hybrid nanocompositesystem consisting of NHC-functionalized conducting polymers(CPs) and AuNPs, which was formed by concurrent dispropor-tionation and oxidative polymerization, and possessed a highactivity for the catalytic reduction of 4-nitrophenol.50 A bithiophene-functionalized NHC–Au(I) complex (BT-NHC–AuCl, Fig. 21) wastreated with silver triflate (AgOTf) to remove chloride and promotethe disproportionation of Au(I) to Au(III) and Au(0). The presenceof Au(III) species led to oxidative polymerization of the thiophenemoieties combined with the growth of AuNPs, which catalyze thedisproportionation reaction. By adding the coordinating ligand2,20-bipyridine the disproportionation and hence the formation ofthe NHC-CP/AuNPs hybrid composite was suppressed. PowderXRD measurements reinforced the existence of AuNPs in thehybrid materials and the reduction of Au(III) during the oxidativepolymerization, and TEM images revealed the presence of sphe-rical well-dispersed AuNPs with an average size of 3.6 � 1.1 nm(Fig. 21a). Further experiments confirmed the role of the NHCfunctionality in the hybrid nanocomposite formation. First, aBr-NHC–AuCl complex was added to a separate electroactivemonomer (bithiophene, BT) to induce a NHC–Au interaction.Well-dispersed AuNPs with an average size of 5.3 � 1.4 nm wereobserved within the polymer. In the other case, a Me2S–AuClcomplex was added to BT to analyze the hybrid nanocompositeformation without a NHC–Au interaction, leading to the genera-tion of large, aggregated AuNPs (10 � 4.2 nm, Fig. 21c). Thus, themetal–ligand interaction between the NHC group and gold isimportant for the dispersion of AuNPs in the NHC-CP/AuNPhybrid nanocomposite. Finally, via UV/vis spectroscopy a highcatalytic activity of the designed system was observed at roomtemperature for the reduction of 4-nitrophenol to 4-aminophenolin aqueous solution after adding NaBH4.

ConclusionBased on the outstanding properties of gold, including its highstability, ease of use, unique spectral properties and biocom-patibility, this noble metal is a key material in nanotechnology.It is crucial to stabilize and functionalize AuNPs and planar goldsurfaces with suitable ligands, providing the desired properties todevelop innovative nanomaterials. SAMs and ligand shells con-sisting of organosulfur-based compounds can be regarded as‘‘the golden standard’’ for gold surface modification. They arefrequently used due to their convenient handling and simplepreparation in a monodisperse and size-controlled manner. Theirresistance towards challenging chemical environments can beimproved by taking advantage of the chelate effect of multivalentligands. Regarding the achievement of finely tuned surfaceproperties or to serve complex applications, mixed ligand shellsor SAMs play a central role. However, under extreme conditionsthe stability of the gold–sulfur bond has reached its limitations,and new ligand designs are required. Within the last few years,

NHCs have emerged as an alternative ligand class to function-alize gold surfaces and NPs due to their strong gold–carbenebond and diverse design strategies. By varying the chemicalstructure of NHCs, the molecular order of SAMs and stability ofAuNPs can be adjusted, leading to entirely new applications andproperties, in some examples yielding ultra-stable monolayerssuperior to organosulfur-based SAMs under extreme conditions.Additionally, NHC ligands can feature a higher resistance towardsoxygen, enable biomedical applications or provide a high catalyticactivity suitable for electrocatalysis. Hence, NHCs are on themarch in gold surface chemistry. We expect that intelligentstrategies to prevent AuNP etching and methods to quickly screenNHC designs will be implemented, so that this ligand class hasthe potential to be a strong competitor for organo-sulfur ligandsin the future.

AcknowledgementsWe thank the Fonds der Chemischen Industrie (FCI) for adoctoral fellowship to S. E. This work was supported by theDeutsche Forschungsgemeinschaft (DFG SFB 858).

Notes and references1 J. C. Love, L. A. Estroff, J. K. Kriebel, R. G. Nuzzo and G. M.

Whitesides, Chem. Rev., 2005, 105, 1103–1170.2 E. Boisselier and D. Astruc, Chem. Soc. Rev., 2009, 38, 1759–1782.3 K. Saha, S. S. Agasti, C. Kim, X. Li and V. M. Rotello, Chem.

Rev., 2012, 112, 2739–2779.4 S. Roland, X. Ling and M.-P. Pileni, Langmuir, 2016, 32,

7683–7696.5 P. K. Jain, X. Huang, I. H. El-Sayed and M. A. El-Sayed,

Acc. Chem. Res., 2008, 41, 1578–1586.6 P. Mulvaney, Langmuir, 1996, 12, 788–800.7 R. Sardar, A. M. Funston, P. Mulvaney and R. W. Murray,

Langmuir, 2009, 25, 13840–13851.8 M.-C. Daniel and D. Astruc, Chem. Rev., 2004, 104, 293–346.9 D. A. Giljohann, D. S. Seferos, W. L. Daniel, M. D. Massich,

P. C. Patel and C. A. Mirkin, Angew. Chem., Int. Ed., 2010, 49,3280–3294.

10 M. Grzelczak, J. Perez-Juste, P. Mulvaney and L. M. Liz-Marzan,Chem. Soc. Rev., 2008, 37, 1783–1791.

11 H. Hakkinen, Nat. Chem., 2012, 4, 443–455.12 Y. Xue, X. Li and W. Zhang, Nat. Commun., 2014, 5, 4348,

DOI: 10.1038/ncomms5348.13 T. Burgi, Nanoscale, 2015, 7, 15553–15567.14 P. D. Jadzinsky, G. Calero, C. J. Ackerson, D. A. Bushnell and

R. D. Kornberg, Science, 2007, 318, 430–433.15 O. Voznyy, J. J. Dubowski, J. T. Yates Jr. and P. Maksymovych,

J. Am. Chem. Soc., 2009, 131, 12989–12993.16 G. E. Poirier, Chem. Rev., 1997, 97, 1117–1128.17 C. Vericat, M. E. Vela, G. Benitez, P. Carro and R. C. Salvarezza,

Chem. Soc. Rev., 2010, 39, 1805–1834.18 D. J. Lavrich, S. M. Wetterer, S. L. Bernasek and G. Scoles,

J. Phys. Chem. B, 1998, 102, 3456–3465.

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