Nathan D. Shapiro

A bonding model for gold(I) carbene complexes

The last decade has witnessed dramatic growth in the number of reactions catalyzed by electrophilic gold complexes. While proposed mechanisms often invoke the intermediacy of gold-stabilized cationic species, the nature of bonding in these intermediates remains unclear. Herein, we propose that the carbon-gold bond in these intermediates is comprised of varying degrees of both σ and π-bonding; however, the overall bond order is generally less than or equal to unity. The bonding in a given gold-stabilized intermediate, and the position of this intermediate on a continuum ranging from gold-stabilized singlet carbene to gold-coordinated carbocation, is dictated by the carbene substituents and the ancillary ligand. Experiments show that the correlation between bonding and reactivity is reflected in the yield of gold-catalyzed cyclopropanation reactions.

Gold-Catalyzed [3+3]-Annulation of Azomethine Imines with Propargyl Esters

The gold-catalyzed [3+3]-cycloaddition reaction of propargyl esters and azomethine imines has been developed. The reaction provides a rapid entry into a wide range of substituted tetrahydropyridazine derivatives from simple starting materials. A stepwise mechanism involving addition of the 1,3-dipole to a gold-carbenoid intermediate is proposed.

Synthesis of Azepines by a Gold-Catalyzed Intermolecular [4 + 3]-Annulation

A convenient gold(III)-catalyzed synthesis of azepines from the intermolecular annulation of propargyl esters and alpha,beta-unsaturated imines is reported (19 examples, 55-95% yield). This formal [4 + 3]-cycloaddition reaction is proposed to proceed via a stepwise process involving intramolecular trapping of an allyl-gold intermediate.

Asymmetric additions to dienes catalysed by a dithiophosphoric acid

Chiral Brønsted acids (proton donors) have been shown to facilitate a broad range of asymmetric chemical transformations under catalytic conditions without requiring additional toxic or expensive metals. Although the catalysts developed thus far are remarkably effective at activating polarized functional groups, it is not clear whether organic Brønsted acids can be used to catalyse highly enantioselective transformations of unactivated carbon–carbon multiple bonds. This deficiency persists despite the fact that racemic acid-catalysed ‘Markovnikov’ additions to alkenes are well known chemical transformations. Here we show that chiral dithiophosphoric acids can catalyse the intramolecular hydroamination and hydroarylation of dienes and allenes to generate heterocyclic products in exceptional yield and enantiomeric excess. We present a mechanistic hypothesis that involves the addition of the acid catalyst to the diene, followed by nucleophilic displacement of the resulting dithiophosphate intermediate; we also report mass spectroscopic and deuterium labelling studies in support of the proposed mechanism. The catalysts and concepts revealed in this study should prove applicable to other asymmetric functionalizations of unsaturated systems.

Synthesis and structural characterization of isolable phosphine coinage metal π-complexes

The chemical community has recently witnessed a dramatic increase in the application of cationic gold(I)-phosphine complexes as homogeneous catalysts for organic synthesis. The majority of gold(I)-catalyzed reactions rely on nucleophilic additions to carbon–carbon multiple bonds, which have been activated by coordination to a cationic gold(I) catalyst. However, structural evidence for coordination of cationic gold(I) complexes to alkynes has been limited. Here, we report the crystal structure of a gold(I)-phosphine η2-coordinated alkyne. Related Ag(I) and Cu(I) complexes have been synthesized for comparison. The crystallization of these complexes was enabled by tethering a labile alkyne ligand to a strongly coordinating triarylphosphine. This approach also proved applicable to crystallization of the first gold(I)-phosphine η2-coordinated alkene.

The SAM, Not the Electrodes, Dominates Charge Transport in Metal-Monolayer//Ga2O3/Gallium–Indium Eutectic Junctions

The liquid-metal eutectic of gallium and indium (EGaIn) is a useful electrode for making soft electrical contacts to self-assembled monolayers (SAMs). This electrode has, however, one feature whose effect on charge transport has been incompletely understood: a thin (approximately 0.7 nm) film-consisting primarily of Ga(2)O(3)-that covers its surface when in contact with air. SAMs that rectify current have been measured using this electrode in Ag(TS)-SAM//Ga(2)O(3)/EGaIn (where Ag(TS) = template-stripped Ag surface) junctions. This paper organizes evidence, both published and unpublished, showing that the molecular structure of the SAM (specifically, the presence of an accessible molecular orbital asymmetrically located within the SAM), not the difference between the electrodes or the characteristics of the Ga(2)O(3) film, causes the observed rectification. By examining and ruling out potential mechanisms of rectification that rely either on the Ga(2)O(3) film or on the asymmetry of the electrodes, this paper demonstrates that the structure of the SAM dominates charge transport through Ag(TS)-SAM//Ga(2)O(3)/EGaIn junctions, and that the electrical characteristics of the Ga(2)O(3) film have a negligible effect on these measurements.

The rate of charge tunneling through self-assembled monolayers is insensitive to many functional group substitutions.

At its conception, the field of molecular electronics promised to provide the ability to engineer the rate of charge transport, by design of the molecular structure of electronic junctions.[1] The hypothesis was that the electronic and geometrical structure of molecules in a junction would have a significant and predictable effect on the rate and mechanism of charge transport through their influence on the energetic topography of the tunneling barrier. Here we show the preparation and electrical characterization of junctions (Figure 1) of the structure AgTS/S(CH2)4CONH(CH2)2R//Ga2O3/EGaIn (AgTS = template-stripped silver surface[2]; R = tail group; EGaIn = eutectic gallium and indium alloy; Ga2O3 = a passivating metal oxide film on the surface of the EGaIn[3–5]) including a range of common aliphatic, aromatic, and heteroaromatic organic tail groups. We demonstrate that the rate of charge transport across these self-assembled monolayers (SAMs) is surprisingly insensitive to changes in the structure of the organic molecules of which they are composed. This study is based on a physical-organic design: that is, the information it provides comes from comparisons of rates of tunneling across related structures, rather than from the interpretation of the absolute values of single measurements. Figure 1 A) Schematic description of tunneling junction consisting of a template-stripped Ag bottom-electrode supporting a SAM, and contacted by a Ga2O3/EGaIn top-electrode. B) A schematic of one junction. C) The numbering system based on non-hydrogen atoms in ... Targets for shaping the tunneling barriers of molecular junctions have included electron–donor–bridge–acceptor molecules,[1a,6] molecular quantum dot systems,[7] aromatic molecules,[8] and complex organic molecules with multiple functional groups.[9] Many of these studies ostensibly shaping the tunneling barriers of molecular junctions have, however, been difficult to interpret because, when they were carried out, there were no experimental systems that generated well-characterized, statistically validated data. This paper characterizes the rates of charge transport by tunneling across a series of molecules—arrayed in SAMs—containing a common head group and body (HS(CH2)4CONH(CH2)2-) and structurally varied tail groups (-R); these molecules are assembled in junctions of the structure AgTS/SAM//Ga2O3/EGaIn. Over a range of common aliphatic, aromatic, and heteroaromatic organic tail groups, changing the structure of R does not significantly influence the rate of tunneling. In making these measurements, we utilize C12 and C18 alkanethiols as calibration standards to allow comparison with results from other types of junctions. Limited studies[4,5,10–15] of charge transport using a range of junctions have described the relation between molecular structure and the rate of tunneling. For example, Venkataraman et al.[14] reported that the rate of charge transport through a series of diaminobenzenes depends on the alignment of the metal Fermi level to the closest molecular orbital. Chiechi and Solomon et al.[15] compared the rate of charge transport through three different anthracene derivatives of approximately the same thickness, and concluded that conjugation influences the rate of charge transport. Studies exploring the correlation between molecular structure and charge transport based on systematic physical–organic measurements of the rate of charge transport over a wide range of structures are sparse. This paper describes tunneling rates through SAMs of molecules with a variety of molecular structures including aromatic, heterocyclic, and aliphatic moieties. We have previously examined ferrocene-terminated SAMs[4] and SAMs comprising odd-and even-numbered n-alkanethiolates.[5]

Aqueous Multiphase Systems of Polymers and Surfactants Provide Self-Assembling Step-Gradients in Density

This Communication demonstrates the generation of over 300 phase-separated systems-ranging from two to six phases-from mixtures of aqueous solutions of polymers and surfactants. These aqueous multiphase systems (MuPSs) form self-assembling, thermodynamically stable step-gradients in density using a common solvent, water. The steps in density between phases of a MuPS can be very small (Δρ ≈ 0.001 g/cm(3)), do not change over time, and can be tuned by the addition of co-solutes. We use two sets of similar objects, glass beads and pellets of different formulations of Nylon, to demonstrate the ability of MuPSs to separate mixtures of objects by differences in density. The stable interfaces between phases facilitate the convenient collection of species after separation. These results suggest that the stable, sharp step-gradients in density provided by MuPSs can enable new classes of fractionations and separations based on density.

Paramagnetic Ionic Liquids for Measurements of Density Using Magnetic Levitation

Paramagnetic ionic liquids (PILs) provide new capabilities to measurements of density using magnetic levitation (MagLev). In a typical measurement, a diamagnetic object of unknown density is placed in a container containing a PIL. The container is placed between two magnets (typically NdFeB, oriented with like poles facing). The density of the diamagnetic object can be determined by measuring its position in the magnetic field along the vertical axis (levitation height, h), either as an absolute value or relative to internal standards of known density. For density measurements by MagLev, PILs have three advantages over solutions of paramagnetic salts in aqueous or organic solutions: (i) negligible vapor pressures; (ii) low melting points; (iii) high thermal stabilities. In addition, the densities, magnetic susceptibilities, glass transition temperatures, thermal decomposition temperatures, viscosities, and hydrophobicities of PILs can be tuned over broad ranges by choosing the cation-anion pair. The low melting points and high thermal stabilities of PILs provide large liquidus windows for density measurements. This paper demonstrates applications and advantages of PILs in density-based analyses using MagLev.

Measuring Binding of Protein to Gel-Bound Ligands Using Magnetic Levitation

This paper describes the use of magnetic levitation (MagLev) to measure the association of proteins and ligands. The method starts with diamagnetic gel beads that are functionalized covalently with small molecules (putative ligands). Binding of protein to the ligands within the bead causes a change in the density of the bead. When these beads are suspended in a paramagnetic aqueous buffer and placed between the poles of two NbFeB magnets with like poles facing, the changes in the density of the bead on binding of protein result in changes in the levitation height of the bead that can be used to quantify the amount of protein bound. This paper uses a reaction-diffusion model to examine the physical principles that determine the values of rate and equilibrium constants measured by this system, using the well-defined model system of carbonic anhydrase and aryl sulfonamides. By tuning the experimental protocol, the method is capable of quantifying either the concentration of protein in a solution, or the binding affinities of a protein to several resin-bound small molecules simultaneously. Since this method requires no electricity and only a single piece of inexpensive equipment, it may find use in situations where portability and low cost are important, such as in bioanalysis in resource-limited settings, point-of-care diagnosis, veterinary medicine, and plant pathology. It still has several practical disadvantages. Most notably, the method requires relatively long assay times and cannot be applied to large proteins (>70 kDa), including antibodies. The design and synthesis of beads with improved characteristics (e.g., larger pore size) has the potential to resolve these problems.