Graphene, a material made exclusively of sp(2) carbon atoms with its π electrons delocalized over the entire 2D network, is somewhat chemically inert. Covalent functionalization can enhance graphene's properties including opening its band gap, tuning conductivity, and improving solubility and stability. Covalent functionalization of pristine graphene typically requires reactive species that can form covalent adducts with the sp(2) carbon structures in graphene. In this Account, we describe graphene functionalization reactions using reactive intermediates of radicals, nitrenes, carbenes, and arynes. These reactive species covalently modify graphene through free radical addition, CH insertion, or cycloaddition reactions. Free radical additions are among the most common reaction, and these radicals can be generated from diazonium salts and benzoyl peroxide. Electron transfer from graphene to aryl diazonium ion or photoactivation of benzoyl peroxide yields aryl radicals that subsequently add to graphene to form covalent adducts. Nitrenes, electron-deficient species generated by thermal or photochemical activation of organic azides, can functionalize graphene very efficiently. Because perfluorophenyl nitrenes show enhanced bimolecular reactions compared with alkyl or phenyl nitrenes, perfluorophenyl azides are especially effective. Carbenes are used less frequently than nitrenes, but they undergo CH insertion and C═C cycloaddition reactions with graphene. In addition, arynes can serve as a dienophile in a Diels-Alder type reaction with graphene. Further study is needed to understand and exploit the chemistry of graphene. The generation of highly reactive intermediates in these reactions leads to side products that complicate the product composition and analysis. Fundamental questions remain about the reactivity and regioselectivity of graphene. The differences in the basal plane and the undercoordinated edges of graphene and the zigzag versus arm-chair configurations warrant comprehensive studies. The availability of well-defined pristine graphene starting materials in large quantities remains a key obstacle to the advancement of synthetic graphene chemistry.

ConspectusA major challenge in materials science is the ongoing search for coupling agents that are readily synthesized, capable of versatile chemistry, able to easily functionalize materials and surfaces, and efficient in covalently linking organic and inorganic entities. A decade ago, we began a research program investigating perfluorophenylazides (PFPAs) as the coupling agents in surface functionalization and nanomaterial synthesis. The p-substituted PFPAs are attractive heterobifunctional coupling agents because of their two distinct and synthetically distinguishable reactive centers: (i) the fluorinated phenylazide, which is capable of forming stable covalent adducts, and (ii) the functional group R, which can be tailored through synthesis.Two approaches have been undertaken for material synthesis and surface functionalization. The first method involves synthesizing PFPA bearing the first molecule or material with a functional linker R, and then attaching the resulting PFPA to the second material by activating the azido group. In the second approach, the material surface is first functionalized with PFPA via functional center R, and coupling of the second molecule or material is achieved with the surface azido groups. In this Account, we review the design and protocols of the two approaches, providing examples in which PFPA derivatives were successfully used in material surface functionalization, ligand conjugation, and the synthesis of hybrid nanomaterials.The methods developed have proved to be general and versatile, and they are applicable to a wide range of materials (especially those that lack reactive functional groups or are difficult to derivatize) and to various substrates of polymers, oxides, carbon materials, and metal films. The coupling chemistry can be initiated by light, heat, and electrons. Patterned structures can be generated by selectively activating the areas of interest. Furthermore, the process is easy to perform, and light activation occurs in minutes, greatly facilitating the efficiency of the reaction. PFPAs indeed demonstrate many benefits as versatile surface coupling agents and offer opportunities for further exploration.

Covalent functionalization of pristine graphene poses considerable challenges due to the lack of reactive functional groups. Herein, we report a simple and general method to covalently functionalize pristine graphene with well-defined chemical functionalities. It is a solution-based process where solvent-exfoliated graphene was treated with perfluorophenylazide (PFPA) by photochemical or thermal activation. Graphene with well-defined chemical functionalities was synthesized and the resulting materials were soluble in organic solvents or water depending on the nature of the functional group on PFPA. KeywordsGraphene; Azides; Covalent functionalization; Photochemistry Graphene, a material having a two-dimensional atomic layer of sp 2 carbon, has emerged as a nanoscale material with a wide range of unique properties. [1][2][3] In order to realize the many potential applications that graphene can offer, the availability of graphene with well-defined and controllable surface and interface properties is of critical importance. Despite the numerous studies on the properties and potentials of graphene, robust methods for producing chemically functionalized graphene are still lacking. 4,5 The most common method for the covalent functionalization of graphene employs graphene oxide (GO), 6 which is prepared by treating graphite particles with strong acids. 7 The oxidation process produces various oxygen-containing species, the nature and density of which are difficult to control.Covalent functionalization of pristine graphene poses considerable challenges due to its lack of reactive functional groups. Herein, we report a simple and general method for the covalent functionalization of pristine graphene. The approach is based on perfluorophenylazide (PFPA), 8,9 which upon photochemical or thermal activation, is converted to the highly reactive singlet perfluorophenylnitrene that can subsequently undergo C=C addition reactions with the sp 2 C network in graphene to form the aziridine adduct. We have confirmed the covalent bond formation between PFPA and graphene using X-ray photoelectron spectroscopy. 10,11 By controlling the functional group on the PFPA (Scheme 1), graphene with well-defined chemical functionalities can be prepared in a single step using a simple solution-based process.* To whom correspondence should be addressed. yanm@pdx.edu. PFPAs bearing alkyl (1), ethylene oxide (2), and perfluoroalkyl groups (3) (Scheme 1) were synthesized and used in this study (see Supporting Information for detailed synthesis and characterization of the compounds). These functional groups were chosen to impact the solubility and surface energy of the resulting graphene. Pristine graphene was prepared by exfoliating graphite in o-dichlorobenzene (DCB), a procedure that has been shown to produce graphene flakes in high yield. 12 Sonication of graphite in DCB followed by centrifugation gave a well-dispersed graphene solution, which was collected and used in the subsequent reactions. These graphene flakes consisted primarily of ...

The sensitive optoelectronic properties of metal nanoparticles make nanoparticle-based materials a powerful tool to study fundamental biorecognition processes. Here we present a new and versatile method for coupling underivatized carbohydrates to gold nanoparticles (Au NPs) via the photochemically induced reaction of perfluorophenylazide (PFPA). A one-pot procedure was developed where Au NPs were synthesized and functionalized with PFPA by a ligand-exchange reaction. Carbohydrates were subsequently immobilized on the NPs by a fast light activation. The coupling reaction was efficient, resulting in high coupling yield as well as high ligand surface coverage. A colorimetric system based on the carbohydrate-modified Au NPs was used for the sensitive detection of carbohydrate-protein interactions. Binding and cross-reactivity studies were carried out between carbohydrate-functionalized Au NPs and lectins. Results showed that the surfacebound carbohydrates not only retained their binding affinities towards the corresponding lectin, but also exhibited affinity ranking consistent with that of the free ligands in solution.

Glyconanomaterials, nanomaterials carrying multiple carbohydrate ligands, provide an excellent platform for sensitive protein recognition. Using nanomaterials as the scaffold, multivalent interactions between glycan ligands and proteins have been demonstrated. However, the quantitative analysis of the binding affinity of these glyconanomaterials has been lacking. In this article, we report a new method to measure the binding affinity of glyconanoparticle (GNP)-protein interactions based on a fluorescent competition binding assay, which yielded the apparent dissociation constant (Kd) of GNPs with the interacting protein. Au nanoparticles conjugated with underivatized mono-, oligo-, poly-saccharides were synthesized using our recently developed photocoupling chemistry. The affinities of these GNPs with lectins were measured and were several orders of magnitude higher than the corresponding free ligands with lectins. The effect of ligand display on the binding affinity of GNPs was furthermore studied where GNPs of varying linker type, spacer length, ligand density, and nanoparticle size were prepared and Kd values determined. The long spacer linker containing hydrocarbon and ethylene oxide units gave the highest binding affinity as well as assay sensitivity. The binding affinity increased with ligand density in general, showing a drastic increase in affinity at low ligand density. In addition, the affinity enhancement was more pronounced on smaller NPs than the larger ones. These results not only demonstrate that the binding affinity of GNPs is highly influenced by how the ligands are presented on the nanoparticles, but also pave the way for tailor-made glyconanomaterials with tunable affinity by way of ligand display.

The reactivities of enamines and predistorted (strained) dipolarophiles toward perfluoroaryl azides (PFAAs) were explored experimentally and computationally. Kinetic analyses indicate that PFAAs undergo (3 + 2) cycloadditions with enamines up to 4 orders of magnitude faster than phenyl azide reacts with these dipolarophiles. DFT calculations were used to identify the origin of this rate acceleration. Orbital interactions between the cycloaddends are larger due to the relatively low-lying LUMO of PFAAs. The triazolines resulting from PFAA–enamine cycloadditions rearrange to amidines at room temperature, while (3 + 2) cycloadditions of enamines and phenyl azide yield stable, isolable triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC also show increased reactivity toward PFAAs over phenyl azide but are slower than enamine–azide cycloadditions.

We present a simple and efficient method to covalently immobilize graphene on silicon wafers using perfluorophenylazide (PFPA) as the coupling agent. Graphene sheets were covalently attached to PFPA-functionalized wafer surface by a simple heat treatment under ambient conditions. The formation of single and multiple layers of graphene were confirmed by Raman spectroscopy, and optical and atomic force microscopy. Evidence of covalent bond formation between graphene and PFPA decorated silicon wafer was given by X-ray photoelectron spectroscopy and sonication treatment.Graphene, a two-dimensional atomic thin layer of carbon nanostructure, has emerged as a unique nanoscale material with promising applications in electronics due to its stable crystal structure, optical transparency, and its exceptional electronic properties of high electron mobility and high saturation velocity for both electrons and holes [1][2][3][4][5][6][7] . However, realization of these potentials has been severely hampered by the availability of large-scale and stable graphene structures that are needed for electronic device fabrication. Furthermore, graphene films with well-defined and controllable surface and interface properties are important for both fundamental studies and practical applications of the material. 8,9 Among various reported preparation methods, 10-17 mechanical cleavage of highly oriented pyrolytic graphite (HOPG) remains to be the most popular and successful in producing single or few layers of graphene sheets. 18 The earliest approach involves the use of a Scotch tape to peel multiple layers of graphene from HOPG, and transfer the sheets to a substrate by pressing followed by releasing. The films obtained in this manner contain different numbers of graphene layers, and the percentage of single graphene sheets varies from sample to sample. An improved version of the mechanical cleavage technique involves applying external pressure to press HOPG on the substrate and thus physically transferring the material from HOPG to the substrate. 19,20 Chou and coworkers used the pillars on a stamp fabricated by nanoimprinting to cut and exfoliate graphene islands from HOPG, and then transferred the films from the stamp to the device active areas on a substrate. 19 Padture et al. fabricated a graphite stamp by etching into HOPG using the technique of photolithography. The HOPG stamp was then pressed onto a silicon wafer creating arrays of multi-layered graphene sheets on the substrate surface. 20 The graphene sheets deposited by these transferring methods are physisorbed on the substrate and can be easily removed by solvent wash (with isopropanol or acetone) or sonication. 21 Here, we report a method to covalently attach graphene to silicon wafers using perfluorophenylazides (PFPA) as the coupling agent. Upon photochemical or thermal activation, the azido group gives the highly reactive singlet perfluorophenylnitrene that can subsequently undergo C-H insertion and/or C=C addition reactions with the neighboring molecules (Scheme...

We report a fast Staudinger reaction between perfluoroaryl azides (PFAAs) and aryl phosphines, occurring readily under ambient conditions. A rate constant as high as 18 M−1 s−1 was obtained between methyl 4-azido-2,3,5,6-tetrafluorobenzoate and methyl 2-(diphenylphosphanyl)benzoate in CD3CN/D2O. In addition, the iminophosphorane product was stable toward hydrolysis and aza-phosphonium ylide reactions. The PFAA-Staudinger reaction proved to be an excellent bioothorgonal reaction. PFAA-derivatized mannose and galactose were successfully transformed into cell surface glycans and efficiently labeled with phosphine-derivatized fluorescent bovine serum albumin.