Controlling the Structure, Properties and Surface Reactivity of Clickable Azide-Functionalized Au25 (SR)18 Nanocluster Platforms Through Regioisomeric Ligand Modifications.

To fine-tune structure-property correlations of thiolate-protected gold nanoclusters through post-assembly surface modifications, we report the synthesis of the o, m, and p regioisomeric forms of the anionic azide-functionalized [Au25 (SCH2 CH2 -C6 H4 -N3 )18 ]1- platform. They can undergo cluster-surface strain-promoted alkyne-azide cycloaddition (CS-SPAAC) chemistry with complementary strained-alkynes. Although their optical properties are similar, the electrochemical properties appear to correlate with the position of the azido group. The ability to conduct CS-SPAAC chemistry without altering the parent nanocluster structure is different as the isomeric form of the surface ligand is changed, with the [Au25 (SCH2 CH2 -p-C6 H4 -N3 )18 ]1- isomer having the highest reaction rates, while the [Au25 (SCH2 CH2 -o-C6 H4 -N3 )18 ]1- isomer is not stable following CS-SPAAC. Single-crystal X-ray diffraction provide the molecular structure of the neutral forms of the three regioisomeric clusters, [Au25 (SCH2 CH2 -o/m/p-C6 H4 -N3 ]0 , which illustrates correlated structural features of the central core as the position of the azido moiety is changed.

Golden Opportunity: A Clickable Azide-Functionalized [Au25(SR)18]- Nanocluster Platform for Interfacial Surface Modifications.

Ultrasmall atomically precise monolayer-protected gold thiolate nanoclusters are an intensely researched nanomaterial framework, but there is a lack of a system that can be directly synthesized and undergo interfacial surface chemistry. We report an [Au25(SCH2CH2-p-C6H4-N3)18]- nanocluster platform with azide moieties appended onto each surface ligand. The structure of this surface reactive cluster has been confirmed by single-crystal X-ray crystallography, mass spectrometry and ultraviolet visible, infrared and nuclear magnetic resonance spectroscopies. We show that all surface azide moieties are amenable to cluster-surface strain-promoted alkyne-azide cycloaddition chemistry with a strained cyclooctyne, opening this as a new platform to allow functional, postassembly surface modifications to this very prominent nanocluster.

NHC Ligated Group 11 Metal-Arylthiolates Containing an Azide Functionality Amenable to "Click" Reaction Chemistry.

The reaction of N-heterocyclic carbene (NHC) Group 11 metal complexes, [(NHC)M-X] (X = chloride, acetate), with the new azide-modified arylthiol 1-HSCH2-2,5-Me2-4-N3CH2-C6H2, 1 (for M = Au; X = Cl), or 1-Me3SiSCH2-2,5-Me2-4-N3CH2-C6H2, 2 (for M = Cu, X = Cl; M = Ag, X = OAc), affords the "clickable" NHC-metal thiolates [( iPr2-bimy)Au-(1-SCH2-2,5-Me2-4-N3CH2-C6H2)], 5; [(IPr)Au-(1-SCH2-2,5-Me2-4-N3CH2-C6H2)], 6; [(IPr)Ag-(1-SCH2-2,5-Me2-4-N3CH2-C6H2)], 7; and [(IPr)Cu-(1-SCH2-2,5-Me2-4-N3CH2-C6H2)], 8 ( iPr2-bimy = 1,3-di-isopropylbenzimidazol-2-ylidene, IPr = 1,3-bis(2,6-di-iso-propylphenyl)imidazol-2-ylidene). Single-crystal X-ray analysis of all metal complexes show that they are two-coordinate, nearly linear, with a terminally bonded thiolate ligand possessing an accessible azide (-N3) moiety. The strain-promoted alkyne-azide cycloaddition (SPAAC) reaction of complex 6 with bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH) and dibenzocyclooctyne-amine (DBCO-NH2) illustrated the reactivity of the azide moiety toward strain-promoted cycloaddition. The rate of the SPAAC reaction between complex 6 and BCN-OH was determined via 1H NMR spectroscopy under second order conditions, and was compared to that of BCN-OH with PhCH2N3.

Fluorogenic Gold Nanoparticle (AuNP) Substrate: A Model for the Controlled Release of Molecules from AuNP Nanocarriers via Interfacial Staudinger-Bertozzi Ligation.

The ability to regulate small-molecule release from metallic nanoparticle substrates offers unprecedented opportunities for nanocarrier-based imaging, sensing, and drug-delivery applications. Herein we report a novel and highly specific release methodology off gold nanoparticle (AuNP) surfaces based on the bioorthogonal Staudinger-Bertozzi ligation. A thiol ligand bearing the molecular cargo, a Rhodamine B dye derivative, was synthesized and used to modify small water-soluble 5 nm AuNPs. Upon incorporation into the AuNP monolayer, we observed efficient quenching of the dye emission, resulting in a very low level of fluorescence emission that provided the baseline from which cargo release was monitored. We examined the ability of these AuNPs to react with azide molecules via Staudinger-Bertozzi ligation on the nanoparticle surface by monitoring the fluorescence emission after the introduction of an organic azide. We observed an immediate increase in emission intensity upon azide addition, which corresponded to the release of the dye into the bulk solution. The 31P NMR spectrum of the AuNP product also agrees with the formation of the ligation product. Thus this system represents a novel and highly specific release methodology off AuNP surfaces that can have potential applications in drug delivery, sensing, and materials science.

Towards the design of self-sorting nanomaterials through kinetically directed chemoselective control over interfacial surface chemistry.

A gold nanoparticle platform is described in which post-synthesis surface modifications can be conducted using kinetically-tunable strain-promoted cycloaddition chemistry, which is dependent on the electronic properties of the complementary dipolar species. This permits chemoselective reactivity with one reactive dipole over another less reactive dipole, providing exciting opportinities for kinetically-directed self-sorting strategies.

Highly Electron-Deficient Pyridinium-Nitrones for Rapid and Tunable Inverse-Electron-Demand Strain-Promoted Alkyne-Nitrone Cycloaddition.

Highly accelerated inverse-electron-demand strain-promoted alkyne-nitrone cycloaddition (IED SPANC) between a stable cyclooctyne (bicyclo[6.1.0]nonyne (BCN)) and nitrones delocalized into a Cα-pyridinium functionality is reported, with the most electron-deficient "pyridinium-nitrone" displaying among the most rapid cycloadditions to BCN that is currently reported. Density functional theory (DFT) and X-ray crystallography are explored to rationalize the effects of N- and Cα-substituent modifications at the nitrone on IED SPANC reaction kinetics and the overall rapid reactivity of pyridinium-delocalized nitrones.