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.

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.

Anhydride Post-Synthetic Modification in a Hierarchical Metal-Organic Framework.

Metal-organic frameworks (MOFs) are important porous materials. Post-synthetic modification (PSM) of MOFs via the pendant groups or secondary functional groups of organic linkers has been widely used to introduce new or enhance existing properties of MOFs for various practical applications. In this work, we have constructed, for the first time, a novel platform for PSM of MOFs by introducing an anhydride functional group into a hierarchically porous MOF (MIL-121) as an effective anchor. We have demonstrated that the combination of the high reactivity of anhydride and hierarchical porosity makes this protocol particularly novel and important, as it led to excellent opportunities of incorporating not only a wide variety of organic molecules with different sizes and chemical nature but also the noble metal complexes in MOFs. Specifically, we show that the anhydride group decorated in the MOF exhibits a high reactivity toward covalently binding 10 different guest molecules including alcohols, amines, thiols, and noble metal (Pt(II)/Pt(IV)) complexes, whereas the hierarchical pores created in the MOF allow the incorporation of guest species varying in size from methanol to larger molecules such as polyaromatic amines. This novel approach provides the community with a new avenue to prepare MOF-based materials for targeted applications. To illustrate this point, we furnish an example of using this new platform to prepare a Pt-based electrocatalyst which shows excellent catalytic activity toward the oxygen reduction reaction (ORR), a pivotal half-reaction in hydrogen-oxygen fuel cells and other energy storage and conversion devices.

Investigation of Au SAMs Photoclick Derivatization by PM-IRRAS.

In this work, we present a clean one-step process for modifying headgroups of self-assembled monolayers (SAMs) on gold using photo-enabled click chemistry. A thiolated, cyclopropenone-caged strained alkyne precursor was first functionalized onto a flat gold substrate through self-assembly. Exposure of the cyclopropenone SAM to UVA light initiated the efficient photochemical decarbonylation of the cyclopropenone moiety, revealing the strained alkyne capable of undergoing the interfacial strain-promoted alkyne-azide cycloaddition (SPAAC). Irradiated SAMs were derivatized with a series of model azides with varied hydrophobicity to demonstrate the generality of this chemical system for the modification and fine-tuning of the surface chemistry on gold substrates. SAMs were characterized at each step with polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) to confirm the successful functionalization and reactivity. Furthermore, to showcase the compatibility of this approach with biochemical applications, cyclopropenone SAMs were irradiated and modified with azide-bearing cell adhesion peptides to promote human fibroblast cell adhesion, and then imaged by live-cell fluorescence microscopy. Thus, the "photoclick" methodology reported here represents an improved, versatile, catalyst-free protocol that allows for a high degree of control over the modification of material surfaces, with applicability in materials science as well as biochemistry.

Nitrone-Modified Gold Nanoparticles: Synthesis, Characterization, and Their Potential as 18F-Labeled Positron Emission Tomography Probes via I-SPANC.

A novel bioorthogonal gold nanoparticle (AuNP) template displaying interfacial nitrone functional groups for bioorthogonal interfacial strain-promoted alkyne-nitrone cycloaddition reactions has been synthesized. These nitrone-AuNPs were characterized in detail using 1H nuclear magnetic resonance spectroscopy, transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy, and a nanoparticle raw formula was calculated. The ability to control the conjugation of molecules of interest at the molecular level onto the nitrone-AuNP template allowed us to create a novel methodology for the synthesis of AuNP-based radiolabeled probes.

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.

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.

Dual-Bioorthogonal Molecular Tool: "Click-to-Release" and "Double-Click" Reactivity on Small Molecules and Material Surfaces.

The development of reactive moieties that enable molecular control of bond-forming and bond-breaking reactions within complex media is highly important in materials and biomaterials research as it provides opportunities to carefully manipulate small molecules and material surfaces in a reliable manner. Despite recent advances in the realization of new ligation strategies and "click-and-release" systems, there has been little development of multifunctional moieties that feature a broad range of chemical capabilities. To address this challenge, we designed a molecular tool that can utilize four well-defined bioorthogonal chemistries interchangeably for the attachment, replacement, and release of molecules within a system: the Staudinger-Bertozzi ligation (SBL), perfluoroaryl azide Staudinger reaction (PFAA-SR), strain-promoted alkyne-azide cycloaddition (SPAAC), and strain-promoted alkyne-nitrone cycloaddition (SPANC). We demonstrate "click-to-release" and "double-click" reactivity on small molecules and gold nanoparticles (AuNPs) as a model material substrate. As a proof of concept for material derivatization, we employed 5 nm AuNPs-functionalized with a Rhodamine B derivative and biotin through the double-click strategy-and showed their potential as a pretargeted delivery nanocarrier. This multifunctional molecular tool enables the design and production of molecular and material systems with unique, modular, and tunable dynamic properties that can be altered under mild and bioorthogonal conditions.

Dialkynylborane Complexes of Formazanate Ligands: Synthesis, Electronic Properties, and Reactivity.

Dialkynylborane complexes of N-donor ligands have received significant attention because of their application in biological imaging, as light-harvesting materials, and as the functional component of organic photovoltaics. Despite these advances, relatively few types of N-donor ligands have been explored in this context. To this end, we prepared a series of dialkynylborane complexes of formazanate ligands and explored their electronic properties and reactivity. In doing so, we demonstrated that (1) the nature of the alkynyl substituents has little influence over the UV-vis absorption properties of the title complexes, but does affect the potentials at which they are electrochemically oxidized and reduced, (2) dialkynylborane formazanate complexes can be converted to stable radical anions by chemical reduction with cobaltocene derivatives, and (3) copper-assisted alkyne-azide cycloaddition chemistry at the alkynyl substituents directly bound to boron can be used to elaborate structural diversity. These conclusions are likely to lead to the development of, and provide guiding principles for the design of, future examples of functional molecular materials based on boron complexes of N-donor ligands.

Loading across the Periodic Table: Introducing 14 Different Metal Ions To Enhance Metal-Organic Framework Performance.

Loading metal guests within metal-organic frameworks (MOFs) via secondary functional groups is a promising route for introducing or enhancing MOF performance in various applications. In this work, 14 metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ba2+, Zn2+, Co2+, Mn2+, Ag+, Cd2+, La3+, In3+, and Pb2+) have been successfully introduced within the MIL-121 MOF using a cost-efficient route involving free carboxylic groups on the linker. The local and long-range structure of the metal-loaded MOFs is characterized using multinuclear solid-state NMR and X-ray diffraction methods. Li/Mg/Ca-loaded MIL-121 and Ag nanoparticle-loaded MIL-121 exhibit enhanced H2 and CO2 adsorption; Ag nanoparticle-loaded MIL-121 also demonstrates remarkable catalytic activity in the reduction of 4-nitrophenol.

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.

"Shine & Click" Photo-Induced Interfacial Unmasking of Strained Alkynes on Small Water-Soluble Gold Nanoparticles.

In this study, we report the design, synthesis, and characterization of small 3 nm water soluble gold nanoparticles (AuNPs) that feature cyclopropenone-masked strained alkyne moieties capable of undergoing interfacial strain-promoted cycloaddition (i-SPAAC) with azides after exposure to UV-A light. A strained alkyne precursor was incorporated onto AuNPs by direct ligand exchange of a thiol-modified cyclopropenone-masked dibenzocyclooctyne (photoDIBO) ligand. These photoDIBO-AuNPs were characterized by 1 H NMR, IR, and UV/Vis spectroscopy, as well as transmission electron microscopy (TEM) and thermogravimetric analysis (TGA), and the extent of modification was quantified. Upon irradiation with UV-A light, photoDIBO-AuNPs underwent efficient and quantitative regeneration of the parent strained alkyne by photochemical decarbonylation to afford DIBO-derivatized AuNPs. DIBO-AuNPs were found to react cleanly and rapidly (k=5.3×10-2 m-1 s-1 ) by an interfacial strain-promoted alkyne-azide cycloadditon (i-SPAAC) with benzyl azide, which served as a simple model system. Furthermore, DIBO-AuNPs were reacted with various azides and a nitrone (interfacial strain-promoted alkyne-nitrone cycloaddition, i-SPANC) to showcase the generality of this approach for the facile modification of AuNP surfaces and their properties. The cyclopropenone-based photo-triggered click chemistry at the interface of water-soluble AuNPs offers exciting opportunities for the atom-by-atom control and assembly of functional materials for applications in materials and biomaterials science as well as in chemical biology.

Insights on the Application of the Retro Michael-Type Addition on Maleimide-Functionalized Gold Nanoparticles in Biology and Nanomedicine.

The glutathione-mediated retro Michael-type addition reaction is demonstrated to take place at the interface of small water-soluble maleimide-functionalized gold nanoparticles (Maleimide-AuNP). The retro Michael-type addition reaction can be blocked by hydrolyzing the Michael addition thioether adduct at the nanoparticle's interface under reaction conditions that do not cause AuNP decomposition. This procedure "locks" the molecule of interest onto the Maleimide-AuNP template for potential uses in medical imaging and bioconjugation, ensuring no loss of the molecular cargo from the nanocarrier. On the other hand, the glutathione-mediated retro Michael-type addition reaction can be exploited for delivering a molecular payload. As a proof of concept, a fluorogenic molecular cargo was incorporated onto a Maleimide-AuNP and delivered via the glutathione-mediated retro Michael-type addition reaction.

A nanoaggregate-on-mirror platform for molecular and biomolecular detection by surface-enhanced Raman spectroscopy.

A nanoaggregate-on-mirror (NAOM) structure has been developed for molecular and biomolecular detection using surface-enhanced Raman spectroscopy (SERS). The smooth surface of the gold mirror allows for simple and homogeneous functionalization, while the introduction of the nanoaggregates enhances the Raman signal of the molecule(s) in the vicinity of the aggregate-mirror junction. This is evidenced by functionalizing the gold mirror with 4-nitrothiophenol, and the further addition of gold nanoaggregates promotes local SERS activity only in the areas with the nanoaggregates. The application of the NAOM platform for biomolecular detection is highlighted using glucose and H2O2 as molecules of interest. In both cases, the gold mirror is functionalized with 4-mercaptophenylboronic acid (4-MPBA). Upon exposure to glucose, the boronic acid moiety of 4-MPBA forms a cyclic boronate ester. Once the nanoaggregates are added to the surface, detection of glucose is possible without the use of an enzyme. This method of indirect detection provides a limit of detection of 0.05 mM, along with a linear range of detection from 0.1 to 15 mM for glucose, encompassing the physiological range of blood glucose concentration. The detection of H2O2 is achieved with optical inspection and SERS. The H2O2 interferes with the coating of the gold mirror, enabling qualitative detection by visual inspection. Simultaneously, the H2O2 reacts with the boronic acid to form a phenol, a change that is detected by SERS.

Gold nanosponges (AuNS): a versatile nanostructure for surface-enhanced Raman spectroscopic detection of small molecules and biomolecules.

Prepared by simple pour and mix chemistry, gold nanosponges (AuNS) are versatile structures for surface-enhanced Raman spectroscopy (SERS). An investigation into the enhancement is performed by relating the nanostructure's morphology to the SERS signal. The potential of the AuNS in SERS-based molecular and biomolecular detection is introduced.

Small gold nanoparticles for interfacial Staudinger-Bertozzi ligation.

Small gold nanoparticles (AuNPs) that possess interfacial methyl-2-(diphenylphosphino)benzoate moieties have been successfully synthesized (Staudinger-AuNPs) and characterized by multi-nuclear MR spectroscopy, transmission electron microscopy (TEM), UV-Vis spectroscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS). In particular, XPS was remarkably sensitive for characterization of the novel nanomaterial, and in furnishing proof of its interfacial reactivity. These Staudinger-AuNPs were found to be stable to the oxidation of the phosphine center. The reaction with benzyl azide in a Staudinger-Bertozzi ligation, as a model system, was investigated using (31)P NMR spectroscopy. This demonstrated that the interfacial reaction was clean and quantitative. To showcase the potential utility of these Staudinger-AuNPs in bioorganic chemistry, a AuNP bioconjugate was prepared by reacting the Staudinger-AuNPs with a novel azide-labeled CRGDK peptide. The CRGDK peptide could be covalently attached to the AuNP efficiently, chemoselectively, and with a high loading.

Expanding the scope of strained-alkyne chemistry: a protection-deprotection strategy via the formation of a dicobalt-hexacarbonyl complex.

A protection-deprotection strategy for strained alkynes used for bioorthogonal chemistry is reported. A strained alkyne can be protected with dicobalt-octacarbonyl and we demonstrate for the first time that a strained alkyne can be re-formed and isolated under mild reaction conditions for further bioorthogonal reactivity. The protection-deprotection strategy herein reported will expand the versatility of strained alkynes for the preparation of substrates in chemical biology and materials applications.

Thermodynamic and kinetic origins of Au25(0) nanocluster electrochemiluminescence.

Au clusters with protecting organothiolate ligands and core diameters less than 2 nm are molecule-like structures, suitable for catalysis, optoelectronics and biology applications. The spectroscopy and electrochemistry of Au25(0) (Au25[(SCH2CH2Ph)18], SCH2CH2Ph = 2-phenylethanethiol) allowed us to construct a Latimer-type diagram for the first time, which revealed a rich photoelectrochemistry of the cluster and the unique relationship to its various oxidation states and corresponding excited states. The occurrence of cluster electrochemiluminescence (ECL) was examined in the presence of tri-n-propylamine (TPrA) as a co-reactant and was discovered to be in the near-infrared (NIR) region with peak wavelengths of 860, 865, and 960 nm, emitted by Au25(+*), Au25(0*), and Au25(-*), respectively. The light emissions, with an efficiency up to 103% relative to that of the efficient Ru(bpy)3(2+)/TPrA system, depended on the kinetics of the reactions between the electrogenerated TPrA radical and Au25(z) (z = 2+, 1+, 1-, and 2-) in the vicinity of the electrode or the bulk Au25(0). These thermodynamic and kinetic origins were further explored by means of spooling ECL and photoluminescence spectroscopy during a sweep of the potential or at a constant potential applied to the working electrode. NIR-ECL emissions of the cluster can be tuned in wavelength and intensity by adjusting the applied potential and TPrA concentration based on the above discoveries.

Dissociative electron transfer to diphenyl-substituted bicyclic endoperoxides: the effect of molecular structure on the reactivity of distonic radical anions and determination of thermochemical parameters.

The heterogeneous electron transfer reduction of the bicyclic endoperoxide 1,4-diphenyl-2,3-dioxabicyclo[2.2.1]hept-5-ene (4) was investigated in N,N-dimethylformamide at a glassy carbon electrode. The endoperoxide reacts by a concerted dissociative ET mechanism resulting in reduction of the O-O bond with an observed peak potential of -1.4 V at 0.2 V s-1. The major product (90% yield) resulting from the heterogeneous bulk electrolysis of 4 at -1.4 V with a rotating disk glassy carbon electrode is 1,4-diphenyl-cyclopent-2-ene-cis-1,3-diol with a consumption of 1.73 electrons per mole. In contrast, 1,4-diphenyl-2,3-dioxabicyclo[2.2.2]oct-5-ene (1), undergoes a two-electron reduction mechanism in quantitative yield. This difference in product yield between 1 and 4 is suggestive of a radical-anion mechanism, as observed with 1,4-diphenyl-2,3-dioxabicyclo-[2.2.2] octane (2) and 1,4-diphenyl-2,3-dioxabicyclo[2.2.1]heptane (3). Convolution potential sweep voltammetry is used to determine unknown thermochemical parameters of 4, including the O-O bond dissociation energy and the standard reduction potential and a comparison is made to the previously studied bicyclic endoperoxides 1-3 with respect to the effect of molecular structure on the reactivity of distonic radical anions.