Search

This paper describes a surface analysis technique that uses the "EGaIn junction" to measure tunneling current densities (J(V), amps/cm2) through self-assembled monolayers (SAMs) terminated in a chelating group and incorporating different transition metal ions. Comparisons of J(V) measurements between bare chelating groups and chelates are used to characterize the composition of the SAM and infer the dissociation constant (Kd, mol/L), as well as kinetic rate constants (koff, L/mol·s; kon, 1/s) of the reversible chelate-metal reaction. To demonstrate the concept, SAMs of 11-(4-methyl-2,2'-bipyrid-4'-yl (bpy))undecanethiol (HS(CH2)11bpy) were incubated within ethanol solutions of metal salts. After rinsing and drying the surface, measurements of current as a function of incubation time and concentration in solution are used to infer koff, kon, and Kd. X-ray photoelectron spectroscopy (XPS) provides an independent measure of surface composition to confirm inferences from J(V) measurements. Our experiments establish that (i) bound metal ions are stable to the rinsing step as long as the rinsing time, τrinse ≪ 1 k o f f ; (ii) the bound metal ions increase the current density at the negative bias and reduce the rectification observed with free bpy terminal groups; (iii) the current density as a function of the concentration of metal ions in solution follows a sigmoidal curve; and (iv) the values of Kd measured using J(V) are comparable to those measured using XPS, but larger than those measured in solution. The EGaIn junction, thus, provides a new tool for the analysis of the composition of the surfaces that undergo reversible chemical reactions with species in solution.

This paper demonstrates that the molecular conformation (in addition to the composition and structure) of molecules making up self-assembled monolayers (SAMs) influences the rates of charge tunneling (CT) through them, in molecular junctions of the form AuTS/S(CH2)2CONR1R2//Ga2O3/EGaIn, where R1 and R2 are alkyl chains of different length. The lengths of chains R1 and R2 were selected to influence the conformations and conformational homogeneity of the molecules in the monolayer. The conformations of the molecules influence the thickness of the monolayer (i.e. tunneling barrier width) and their rectification ratios at ±1.0 V. When R1 = H, the molecules are well ordered and exist predominantly in trans-extended conformations. When R1 is an alkyl group (e.g., R1 ≠ H), however, their conformations can no longer be all-trans-extended, and the molecules adopt more gauche dihedral angles. This change in the type of conformation decreases the conformational order and influences the rates of tunneling. When R1 = R2, the rates of CT decrease (up to 6.3×), relative to rates of CT observed through SAMs having the same total chain lengths, or thicknesses, when R1 = H. When R1 ≠ H ≠ R2, there is a weaker correlation (relative to that when R1 = H or R1 = R2) between current density and chain length or monolayer thickness, and in some cases the rates of CT through SAMs made from molecules with different R2 groups are different, even when the thicknesses of the SAMs (as determined by XPS) are the same. These results indicate that the thickness of a monolayer composed of insulating, amide-containing alkanethiols does not solely determine the rate of CT, and rates of charge tunneling are influenced by the conformation of the molecules making up the junction.

This Article describes the relationship between molecular structure, and the rectification of tunneling current, in tunneling junctions based on self-assembled monolayers (SAMs). Molecular dipoles from simple organic functional groups (amide, urea, and thiourea) were introduced into junctions with the structure AgTS/S(CH2)nR(CH2)mCH3//Ga2O3/EGaIn. Here, R is an n-alkyl fragment (−CH2−)2 or 3, an amide group (either −CONH– or −NHCO−), a urea group (−NHCONH−), or a thiourea group (−NHCSNH−). The amide, urea, or thiourea groups introduce a localized electric dipole moment into the SAM and change the polarizability of that section of the SAM, but do not produce large, electronically delocalized groups or change other aspects of the tunneling barrier. This local change in electronic properties correlates with a statistically significant, but not large, rectification of current (r+) at ±1.0 V (up to r+ ≈ 20). The results of this work demonstrate that the simplest form of rectification of current at ±1.0 V, in E...

The nature of the processes at the origin of life that selected specific classes of molecules for broad incorporation into cells is controversial. Among those classes selected were polyisoprenoids and their derivatives. This paper tests the hypothesis that polyisoprenoids were early contributors to membranes in part because they (or their derivatives) could facilitate charge transport by quantum tunneling. It measures charge transport across self-assembled monolayers (SAMs) of carboxyl-terminated monoterpenoids (O2 C(C9 HX)) and alkanoates (O2 C(C7 HX)) with different degrees of unsaturation, supported on silver (AgTS ) bottom electrodes, with Ga2 O3 /EGaIn top electrodes. Measurements of current density of SAMs of linear length-matched hydrocarbons-both saturated and unsaturated-show that completely unsaturated molecules transport charge faster than those that are completely saturated by approximately a factor of ten. This increase in relative rates of charge transport correlates with the number of carbon-carbon double bonds, but not with the extent of conjugation. These results suggest that polyisoprenoids-even fully unsaturated-are not sufficiently good tunneling conductors for their conductivity to have favored them as building blocks in the prebiotic world.

How simple chemical reactions self-assembled into complex, robust networks at the origin of life is unknown. This general problem-self-assembly of dissipative molecular networks-is also important in understanding the growth of complexity from simplicity in molecular and biomolecular systems. Here, we describe how heterogeneity in the composition of a small network of oscillatory organic reactions can sustain (rather than stop) these oscillations, when homogeneity in their composition does not. Specifically, multiple reactants in an amide-forming network sustain oscillation when the environment (here, the space velocity) changes, while homogeneous networks-those with fewer reactants-do not. Remarkably, a mixture of two reactants of different structure-neither of which produces oscillations individually-oscillates when combined. These results demonstrate that molecular heterogeneity present in mixtures of reactants can promote rather than suppress complex behaviors.

This paper addresses the mechanism for rectification in molecular tunneling junctions based on alkanethiolates terminated by a bipyridine group complexed with a metal ion, that is, having the structure Au

International audience; This paper describes charge transport by tunneling across self-assembled monolayers (SAMs) of thiol-terminated derivatives of oligo(ethylene glycol) (HS(CH2CH2O)nCH3; HS(EG)nCH3); these SAMs are positioned between gold bottom electrodes and Ga2O3/EGaIn top electrodes. Comparison of the attenuation factor (β of the simplified Simmons equation) across these SAMs with the corresponding value obtained with length-matched SAMs of oligophenyls (HS(Ph)nH) and n-alkanethiols (HS(CH2)nH) demonstrates that SAMs of oligo(ethylene glycol) have values of β (β(EG)n = 0.29 ± 0.02 natom(-1) and β = 0.24 ± 0.01 Å(-1)) indistinguishable from values for SAMs of oligophenyls (β(Ph)n = 0.28 ± 0.03 Å(-1)), and significantly lower than those of SAMs of n-alkanethiolates (β(CH2)n = 0.94 ± 0.02 natom(-1) and 0.77 ± 0.03 Å(-1)). There are two possible origins for this low value of β. The more probable involves hole tunneling by superexchange, which rationalizes the weak dependence of the rate of charge transport on the length of the molecules of HS(EG)nCH3 using interactions among the high-energy, occupied orbitals associated with the lone-pair electrons on oxygen. Based on this mechanism, SAMs of oligo(ethylene glycol)s are good conductors (by hole tunneling) but good insulators (by electron and/or hole drift conduction). This observation suggests SAMs derived from these or electronically similar molecules are a new class of electronic materials. A second but less probable mechanism for this unexpectedly low value of β for SAMs of S(EG)nCH3 rests on the possibility of disorder in the SAM and a systematic discrepancy between different estimates of the thickness of these SAMs.

Magneto-Archimedes levitation (MagLev) enables the separation of powdered mixtures of illicit drugs (cocaine, methamphetamine, heroin, fentanyl, and its analogues), adulterants, and diluents based on density, and allows the presumptive identification of individual components. Small samples (mass

All matter has density. The recorded uses of density to characterize matter date back to as early as ca. 250 BC, when Archimedes was believed to have solved "The Puzzle of The King's Crown" using density.[1] Today, measurements of density are used to separate and characterize a range of materials (including cells and organisms), and their chemical and/or physical changes in time and space. This Review describes a density-based technique-magnetic levitation (which we call "MagLev" for simplicity)-developed and used to solve problems in the fields of chemistry, materials science, and biochemistry. MagLev has two principal characteristics-simplicity, and applicability to a wide range of materials-that make it useful for a number of applications (for example, characterization of materials, quality control of manufactured plastic parts, self-assembly of objects in 3D, separation of different types of biological cells, and bioanalyses). Its simplicity and breadth of applications also enable its use in low-resource settings (for example-in economically developing regions-in evaluating water/food quality, and in diagnosing disease).

An untethered, entirely soft robot is designed to operate autonomously by combining microfluidic logic and hydrogen peroxide as an on-board fuel supply. Soft robotics have so far necessarily included some 'hard' or metallic elements, in particular in the form of batteries or wiring, to connect them to an external power source. Additionally, external wiring tethering them to a power source places limits on the autonomy of such robots. Now Jennifer Lewis and colleagues have combined a 3D-printed soft polymeric robot with microfluidic logic and hydrogen peroxide as an onboard fuel to produce an eight-armed robot — an 'octobot' — that actuates its arms, without the incorporation of any hard structures. The hydrogen peroxide decomposes in the presence of a platinum catalyst to produce oxygen and a volumetric expansion that fills bladders embedded within the arms of the octobot. The design of the fuel reservoirs, microfluidic channels and vents to release the gas means that two sets of arms actuate cyclically. Soft robots possess many attributes that are difficult, if not impossible, to achieve with conventional robots composed of rigid materials1,2. Yet, despite recent advances, soft robots must still be tethered to hard robotic control systems and power sources3,4,5,6,7,8,9,10. New strategies for creating completely soft robots, including soft analogues of these crucial components, are needed to realize their full potential. Here we report the untethered operation of a robot composed solely of soft materials. The robot is controlled with microfluidic logic11 that autonomously regulates fluid flow and, hence, catalytic decomposition of an on-board monopropellant fuel supply. Gas generated from the fuel decomposition inflates fluidic networks downstream of the reaction sites, resulting in actuation12. The body and microfluidic logic of the robot are fabricated using moulding and soft lithography, respectively, and the pneumatic actuator networks, on-board fuel reservoirs and catalytic reaction chambers needed for movement are patterned within the body via a multi-material, embedded 3D printing technique13,14. The fluidic and elastomeric architectures required for function span several orders of magnitude from the microscale to the macroscale. Our integrated design and rapid fabrication approach enables the programmable assembly of multiple materials within this architecture, laying the foundation for completely soft, autonomous robots.

Magnetic levitation (MagLev) of diamagnetic or weakly paramagnetic materials suspended in a paramagnetic solution in a magnetic field gradient provides a simple method to measure the density of small samples of solids or liquids. One major limitation of this method, thus far, has been an inability to measure or manipulate materials outside of a narrow range of densities (0.8 g/cm(3)ρ2.3 g/cm(3)) that are close in density to the suspending, aqueous medium. This paper explores a simple method-"tilted MagLev"-to increase the range of densities that can be levitated magnetically. Tilting the MagLev device relative to the gravitational vector enables the magnetic force to be decreased (relative to the magnetic force) along the axis of measurement. This approach enables many practical measurements over the entire range of densities observed in matter at ambient conditions-from air bubbles (ρ ≈ 0) to osmium and iridium (ρ ≈ 23 g/cm(3)). The ability to levitate, simultaneously, objects with a broad range of different densities provides an operationally simple method that may find application to forensic science (e.g., for identifying the composition of miscellaneous objects or powders), industrial manufacturing (e.g., for quality control of parts), or resource-limited settings (e.g., for identifying and separating small particles of metals and alloys).

This work describes the autocatalytic copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction between tripropargylamine and 2-azidoethanol in the presence of Cu(II) salts. The product of this reaction, tris-(hydroxyethyltriazolylmethyl)amine (N(C3N3)3), accelerates the cycloaddition reaction (and thus its own production) by two mechanisms: (i) by coordinating Cu(II) and promoting its reduction to Cu(I) and (ii) by enhancing the catalytic reactivity of Cu(I) in the cycloaddition step. Because of the cooperation of these two processes, a rate enhancement of >400× is observed over the course of the reaction. The kinetic profile of the autocatalysis can be controlled by using different azides and alkynes or ligands (e.g., ammonia) for Cu(II). When carried out in a layer of 1% agarose gel, and initiated by ascorbic acid, this autocatalytic reaction generates an autocatalytic front. This system is prototypical of autocatalytic reactions where the formation of a product, which acts as a ligand for a catalyt...

This work describes the development of an integrated analytical system that enables high-throughput density measurements of diamagnetic particles (including cells) using magnetic levitation (MagLev), 96-well plates, and a flatbed scanner. MagLev is a simple and useful technique with which to carry out density-based analysis and separation of a broad range of diamagnetic materials with different physical forms (e.g., liquids, solids, gels, pastes, gums, etc.); one major limitation, however, is the capacity to perform high-throughput density measurements. This work addresses this limitation by (i) re-engineering the shape of the magnetic fields so that the MagLev system is compatible with 96-well plates, and (ii) integrating a flatbed scanner (and simple optical components) to carry out imaging of the samples that levitate in the system. The resulting system is compatible with both biological samples (human erythrocytes) and nonbiological samples (simple liquids and solids, such as 3-chlorotoluene, cholesterol crystals, glass beads, copper powder, and polymer beads). The high-throughput capacity of this integrated MagLev system will enable new applications in chemistry (e.g., analysis and separation of materials) and biochemistry (e.g., cellular responses under environmental stresses) in a simple and label-free format on the basis of a universal property of all matter, i.e., density.

Using curiosity as the starting point for careful observation of nature and society is a nontrivial skill, and a starting point for new intellectual endeavors and adventures. It is one essential contributor to creativity in science, and a start in forcing new ideas into inflexible professional orthodoxies.

Charge transport through junctions consisting of insulating molecular units is a quantum phenomenon that cannot be described adequately by classical circuit laws. This paper explores tunneling current densities in self-assembled monolayer (SAM)-based junctions with the structure Ag(TS)/O2C-R1-R2-H//Ga2O3/EGaIn, where Ag(TS) is template-stripped silver and EGaIn is the eutectic alloy of gallium and indium; R1 and R2 refer to two classes of insulating molecular units-(CH2)n and (C6H4)m-that are connected in series and have different tunneling decay constants in the Simmons equation. These junctions can be analyzed as a form of series-tunneling junctions based on the observation that permuting the order of R1 and R2 in the junction does not alter the overall rate of charge transport. By using the Ag/O2C interface, this system decouples the highest occupied molecular orbital (HOMO, which is localized on the carboxylate group) from strong interactions with the R1 and R2 units. The differences in rates of tunneling are thus determined by the electronic structure of the groups R1 and R2; these differences are not influenced by the order of R1 and R2 in the SAM. In an electrical potential model that rationalizes this observation, R1 and R2 contribute independently to the height of the barrier. This model explicitly assumes that contributions to rates of tunneling from the Ag(TS)/O2C and H//Ga2O3 interfaces are constant across the series examined. The current density of these series-tunneling junctions can be described by J(V) = J0(V) exp(-β1d1 - β2d2), where J(V) is the current density (A/cm(2)) at applied voltage V and βi and di are the parameters describing the attenuation of the tunneling current through a rectangular tunneling barrier, with width d and a height related to the attenuation factor β.

This paper describes the influence of the substitution of fluorine for hydrogen on the rate of charge transport by hole tunneling through junctions of the form Ag(TS)O2C(CH2)n(CF2)(m)T//Ga2O3/EGaIn, where T is methyl (CH3) or trifluoromethyl (CF3). Alkanoate-based self-assembled monolayers (SAMs) having perfluorinated groups (R(F)) show current densities that are lower (by factors of 20-30) than those of the homologous hydrocarbons (R(H)), while the attenuation factors of the simplified Simmons equation for methylene (β = (1.05 ± 0.02)n(CH2)(-1)) and difluoromethylene (β = (1.15 ± 0.02)n(CF2)(-1)) are similar (although the value for (CF2)n is statistically significantly larger). A comparative study focusing on the terminal fluorine substituents in SAMs of ω-tolyl- and -phenyl-alkanoates suggests that the C-F//Ga2O3 interface is responsible for the lower tunneling currents for CF3. The decrease in the rate of charge transport in SAMs with R(F) groups (relative to homologous R(H) groups) is plausibly due to an increase in the height of the tunneling barrier at the T//Ga2O3 interface, and/or to weak van der Waals interactions at that interface.

This work describes the development of magnetic levitation (MagLev) to characterize the kinetics of free-radical polymerization of water-insoluble, low-molecular-weight monomers that show a large change in density upon polymerization. Maglev measures density, and certain classes of monomers show a large change in density when monomers covalently join in polymer chains. MagLev characterized both the thermal polymerization of methacrylate-based monomers and the photopolymerization of methyl methacrylate and made it possible to determine the orders of reaction and the Arrhenius activation energy of polymerization. MagLev also made it possible to monitor polymerization in the presence of solids (aramid fibers, and carbon fibers, and glass fibers). MagLev offers a new analytical technique to materials and polymer scientists that complements other methods (even those based on density, such as dilatometry), and will be useful in investigating polymerizations, evaluating inhibition of polymerizations, and studying polymerization in the presence of included solid materials (e.g., for composite materials).

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim This study uses mutants of human carbonic anhydrase (HCAII) to examine how changes in the organization of water within a binding pocket can alter the thermodynamics of protein–ligand association. Results from calorimetric, crystallographic, and theoretical analyses suggest that most mutations strengthen networks of water-mediated hydrogen bonds and reduce binding affinity by increasing the enthalpic cost and, to a lesser extent, the entropic benefit of rearranging those networks during binding. The organization of water within a binding pocket can thus determine whether the hydrophobic interactions in which it engages are enthalpy-driven or entropy-driven. Our findings highlight a possible asymmetry in protein–ligand association by suggesting that, within the confines of the binding pocket of HCAII, binding events associated with enthalpically favorable rearrangements of water are stronger than those associated with entropically favorable ones.

This paper compares rates of charge transport across self-assembled monolayers (SAMs) of n-alkanethiolates having odd and even numbers of carbon atoms (nodd and neven) using junctions with the structure M(TS)/SAM//Ga2O3/EGaIn (M = Au or Ag). Measurements of current density, J(V), across SAMs of n-alkanethiolates on Au(TS) and Ag(TS) demonstrated a statistically significant odd-even effect on Au(TS), but not on Ag(TS), that could be detected using this technique. Statistical analysis showed the values of tunneling current density across SAMs of n-alkanethiolates on Au(TS) with nodd and neven belonging to two separate sets, and while there is a significant difference between the values of injection current density, J0, for these two series (log|J0Au,even| = 4.0 ± 0.3 and log|J0Au,odd| = 4.5 ± 0.3), the values of tunneling decay constant, β, for nodd and neven alkyl chains are indistinguishable (βAu,even = 0.73 ± 0.02 Å(-1), and βAu,odd= 0.74 ± 0.02 Å(-1)). A comparison of electrical characteristics across junctions of n-alkanethiolate SAMs on gold and silver electrodes yields indistinguishable values of β and J0 and indicates that a change that substantially alters the tilt angle of the alkyl chain (and, therefore, the thickness of the SAM) has no influence on the injection current density across SAMs of n-alkanethiolates.

This paper describes a physical-organic study of the effect of uncharged, polar, functional groups on the rate of charge transport by tunneling across self-assembled monolayer (SAM)-based large-area junctions of the form Ag(TS)S(CH2)(n)M(CH2)(m)T//Ga2O3/EGaIn. Here Ag(TS) is a template-stripped silver substrate, -M- and -T are "middle" and "terminal" functional groups, and EGaIn is eutectic gallium-indium alloy. Twelve uncharged polar groups (-T = CN, CO2CH3, CF3, OCH3, N(CH3)2, CON(CH3)2, SCH3, SO2CH3, Br, P(O)(OEt)2, NHCOCH3, OSi(OCH3)3), having permanent dipole moments in the range 0.5 < μ < 4.5, were incorporated into the SAM. A comparison of the electrical characteristics of these junctions with those of junctions formed from n-alkanethiolates led to the conclusion that the rates of charge tunneling are insensitive to the replacement of terminal alkyl groups with the terminal polar groups in this set. The current densities measured in this work suggest that the tunneling decay parameter and injection current for SAMs terminated in nonpolar n-alkyl groups, and polar groups selected from common polar organic groups, are statistically indistinguishable.

Analysis of rates of tunneling across self-assembled monolayers (SAMs) of n-alkanethiolates SCn (with n = number of carbon atoms) incorporated in junctions having structure Ag(TS)-SAM//Ga2O3/EGaIn leads to a value for the injection tunnel current density J0 (i.e., the current flowing through an ideal junction with n = 0) of 10(3.6±0.3) A·cm(-2) (V = +0.5 V). This estimation of J0 does not involve an extrapolation in length, because it was possible to measure current densities across SAMs over the range of lengths n = 1-18. This value of J0 is estimated under the assumption that values of the geometrical contact area equal the values of the effective electrical contact area. Detailed experimental analysis, however, indicates that the roughness of the Ga2O3 layer, and that of the Ag(TS)-SAM, determine values of the effective electrical contact area that are ~10(-4) the corresponding values of the geometrical contact area. Conversion of the values of geometrical contact area into the corresponding values of effective electrical contact area results in J0(+0.5 V) = 10(7.6±0.8) A·cm(-2), which is compatible with values reported for junctions using top-electrodes of evaporated Au, and graphene, and also comparable with values of J0 estimated from tunneling through single molecules. For these EGaIn-based junctions, the value of the tunneling decay factor β (β = 0.75 ± 0.02 Å(-1); β = 0.92 ± 0.02 nC(-1)) falls within the consensus range across different types of junctions (β = 0.73-0.89 Å(-1); β = 0.9-1.1 nC(-1)). A comparison of the characteristics of conical Ga2O3/EGaIn tips with the characteristics of other top-electrodes suggests that the EGaIn-based electrodes provide a particularly attractive technology for physical-organic studies of charge transport across SAMs.

MagLev offers four advantages:1) it separates multiple populations in a single step, 2) itquantifies the density of each population, 3) it is applicable tosmall crystals (100 mm size), and 4) it provides seed crystalsfor large-scale crystallization. We used MagLev to separatemixtures of polymorphs of four compounds: 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) 1, sulfa-thiazole 2, carbamazepine 3, and trans-cinnamic acid 4(Scheme 1).A survey of the Cambridge Structural Database indicatesthat 3.1–3.5% of the compounds submitted crystallize indifferent polymorphic forms.

A few-component network of biologically relevant, organic reactions displays bistability and oscillations, without an enzymatic catalyst. Dissipative chemical reaction networks are systems that operate away from equilibrium and exhibit features such as continuous regeneration of components and autonomous regulation. The biological cell is one such out-of-equilibrium chemical network. Until now it has not been possible to recreate this type of dynamic behavior using simple organic molecules relevant to prebiotic Earth. Now, George Whitesides and colleagues demonstrate a few-component system of interacting organic species that, combined into a reaction network, displays autocatalytic and oscillatory features. All of the organic components are relatively simple and do not require enzymatic catalysis to react. Networks of organic chemical reactions are important in life and probably played a central part in its origin1,2,3. Network dynamics regulate cell division4,5,6, circadian rhythms7, nerve impulses8 and chemotaxis9, and guide the development of organisms10. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics11 such as spontaneous pattern formation, bistability and periodic oscillations12,13,14, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate–thioester exchange, thiolate–disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes15 and DNA16,17) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov–Zhabotinskii-type reactions)18,19, the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving chemical systems.

This paper describes the interaction between ubiquitin (UBI) and three sodium n-alkyl sulfates (SCnS) that have the same charge (Z = −1), but different hydrophobicity (n = 10, 12 and 14). Increasing the hydrophobicity of the n-alkyl sulfate resulted in: (i) an increase in the number of distinct intermediates (that is, complexes of UBI and surfactant) that form along the pathway of unfolding; (ii) a decrease in the minimum concentrations of surfactant at which intermediates begin to form (i.e., a more negative ΔGbinding of surfactant for UBI), and (iii) an increase in the number of surfactant molecules (p) bound to UBI in each intermediate or complex. These results demonstrate that small changes in the hydrophobicity of a surfactant can significantly alter the binding interactions with a folded or unfolded cytosolic protein.

This paper describes physical-organic studies of charge transport by tunneling through self-assembled monolayers (SAMs), based on systematic variations of the structure of the molecules constituting the SAM. Replacing a -CH(2)CH(2)- group with a -CONH- group changes the dipole moment and polarizability of a portion of the molecule and has, in principle, the potential to change the rate of charge transport through the SAM. In practice, this substitution produces no significant change in the rate of charge transport across junctions of the structure Ag(TS)-S(CH(2))(m)X(CH(2))(n)H//Ga(2)O(3)/EGaIn (TS = template stripped, X = -CH(2)CH(2)- or -CONH-, and EGaIn = eutectic alloy of gallium and indium). Incorporation of the amide group does, however, increase the yields of working (non-shorting) junctions (when compared to n-alkanethiolates of the same length). These results suggest that synthetic schemes that combine a thiol group on one end of a molecule with a group, R, to be tested, on the other (e.g., HS~CONH~R) using an amide-based coupling provide practical routes to molecules useful in studies of molecular electronics.

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]

This paper describes a synthetic dimer of carbonic anhydrase, and a series of bivalent sulfonamide ligands with different lengths (25 to 69 Å between the ends of the fully extended ligands), as a model system to use in examining the binding of bivalent antibodies to antigens. Assays based on analytical ultracentrifugation and fluorescence binding indicate that this system forms cyclic, noncovalent complexes with a stoichiometry of one bivalent ligand to one dimer. This dimer binds the series of bivalent ligands with low picomolar avidities (K(d)(avidity) = 3-40 pM). A structurally analogous monovalent ligand binds to one active site of the dimer with K(d)(mono) = 16 nM. The bivalent association is thus significantly stronger (K(d)(mono)/K(d)(avidity) ranging from ~500 to 5000 unitless) than the monovalent association. We infer from these results, and by comparison of these results to previous studies, that bivalency in antibodies can lead to associations much tighter than monovalent associations (although the observed bivalent association is much weaker than predicted from the simplest level of theory: predicted K(d)(avidity) of ~0.002 pM and K(d)(mono)/K(d)(avidity) ~ 8 × 10(6) unitless).

A previous study, using capillary electrophoresis (CE) [J. Am. Chem. Soc. 2008, 130, 17384-17393], reported that six discrete complexes of ubiquitin (UBI) and sodium dodecyl sulfate (SDS) form at different concentrations of SDS along the pathway to unfolding of UBI in solutions of SDS. One complex (which formed between 0.8 and 1.8 mM SDS) consisted of native UBI associated with approximately 11 molecules of SDS. The current study used CE and (15)N/(13)C-(1)H heteronuclear single quantum coherence (HSQC) NMR spectroscopy to identify residues in folded UBI that associate specifically with SDS at 0.8-1.8 mM SDS, and to correlate these associations with established biophysical and structural properties of this well-characterized protein. The ability of the surface charge and hydrophobicity of folded UBI to affect the association with SDS (at concentrations below the CMC) was studied, using CE, by converting lys-ε-NH(3)(+) to lys-ε-NHCOCH(3) groups. According to CE, the acetylation of lysine residues inhibited the binding of 11 SDS ([SDS]2 mM) and decreased the number of complexes of composition UBI-(NHAc)(8)·SDS(n) that formed on the pathway of unfolding of UBI-(NHAc)(8) in SDS. A comparison of (15)N-(1)H HSQC spectra at 0 mM and 1 mM SDS with calculated electrostatic surface potentials of folded UBI (e.g., solutions to the nonlinear Poisson-Boltzmann (PB) equation) suggested, however, that SDS binds preferentially to native UBI at hydrophobic residues that are formally neutral (i.e., Leu and Ile), but that have positive electrostatic surface potential (as predicted from solutions to nonlinear PB equations); SDS did not uniformly interact with residues that have formal positive charge (e.g., Lys or Arg). Cationic functional groups, therefore, promote the binding of SDS to folded UBI because these groups exert long-range effects on the positive electrostatic surface potential (which extend beyond their own van der Waals radii, as predicted from PB theory), and not because cationic groups are necessarily the site of ionic interactions with sulfate groups. Moreover, SDS associated with residues in native UBI without regard to their location in α-helix or β-sheet structure (although residues in hydrogen-bonded loops did not bind SDS). No correlation was observed between the association of an amino acid with SDS and the solvent accessibility of the residue or its rate of amide H/D exchange. This study establishes a few (of perhaps several) factors that control the simultaneous molecular recognition of multiple anionic amphiphiles by a folded cytosolic protein.

This paper describes the performance of junctions based on self-assembled monolayers (SAMs) as the functional element of a half-wave rectifier (a simple circuit that converts, or rectifies, an alternating current (AC) signal to a direct current (DC) signal). Junctions with SAMs of 11-(ferrocenyl)-1-undecanethiol or 11-(biferrocenyl)-1-undecanethiol on ultraflat, template-stripped Ag (Ag(TS)) bottom electrodes, and contacted by top electrodes of eutectic indium-gallium (EGaIn), rectified AC signals, while similar junctions based on SAMs of 1-undecanethiol-SAMs lacking the ferrocenyl terminal group-did not. SAMs in these AC circuits (operating at 50 Hz) remain stable over a larger window of applied bias than in DC circuits. AC measurements, therefore, can investigate charge transport in SAM-based junctions at magnitudes of bias inaccessible to DC measurements. For junctions with SAMs of alkanethiols, combining the results from AC and DC measurements identifies two regimes of bias with different mechanisms of charge transport: (i) low bias (|V|1.3 V), at which direct tunneling dominates, and (ii) high bias (|V|1.3 V), at which Fowler-Nordheim (FN) tunneling dominates. For junctions with SAMs terminated by Fc moieties, the transition to FN tunneling occurs at |V| ≈ 2.0 V. Furthermore, at sufficient forward bias (V0.5 V), hopping makes a significant contribution to charge transport and occurs in series with direct tunneling (V ≲ 2.0 V) until FN tunneling activates (V ≳ 2.0 V). Thus, for Fc-terminated SAMs at forward bias, three regimes are apparent: (i) direct tunneling (V = 0-0.5 V), (ii) hopping plus direct tunneling (V ≈ 0.5-2.0 V), and (iii) FN tunneling (V ≳ 2.0 V). Since hopping does not occur at reverse bias, only two regimes are present over the measured range of reverse bias. This difference in the mechanisms of charge transport at forward and reverse bias for junctions with Fc moieties resulted in large rectification ratios (R100) and enabled half-wave rectification.

The hydrophobic effect, the free-energetically favorable association of nonpolar solutes in water, makes a dominant contribution to binding of many systems of ligands and proteins. The objective of this study was to examine the hydrophobic effect in biomolecular recognition using two chemically different but structurally similar hydrophobic groups, aliphatic hydrocarbons and aliphatic fluorocarbons, and to determine whether the hydrophobicity of the two groups could be distinguished by thermodynamic and biostructural analysis. This paper uses isothermal titration calorimetry (ITC) to examine the thermodynamics of binding of benzenesulfonamides substituted in the para position with alkyl and fluoroalkyl chains (H(2)NSO(2)C(6)H(4)-CONHCH(2)(CX(2))(n)CX(3), n = 0-4, X = H, F) to human carbonic anhydrase II (HCA II). Both alkyl and fluoroalkyl substituents contribute favorably to the enthalpy and the entropy of binding; these contributions increase as the length of chain of the hydrophobic substituent increases. Crystallography of the protein-ligand complexes indicates that the benzenesulfonamide groups of all ligands examined bind with similar geometry, that the tail groups associate with the hydrophobic wall of HCA II (which is made up of the side chains of residues Phe131, Val135, Pro202, and Leu204), and that the structure of the protein is indistinguishable for all but one of the complexes (the longest member of the fluoroalkyl series). Analysis of the thermodynamics of binding as a function of structure is compatible with the hypothesis that hydrophobic binding of both alkyl and fluoroalkyl chains to hydrophobic surface of carbonic anhydrase is due primarily to the release of nonoptimally hydrogen-bonded water molecules that hydrate the binding cavity (including the hydrophobic wall) of HCA II and to the release of water molecules that surround the hydrophobic chain of the ligands. This study defines the balance of enthalpic and entropic contributions to the hydrophobic effect in this representative system of protein and ligand: hydrophobic interactions, here, seem to comprise approximately equal contributions from enthalpy (plausibly from strengthening networks of hydrogen bonds among molecules of water) and entropy (from release of water from configurationally restricted positions).

This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (

This paper proposes a mechanism for the rectification of current by self-assembled monolayers (SAMs) of alkanethiolates with Fc head groups (SC(11)Fc) in SAM-based tunneling junctions with ultra-flat Ag bottom electrodes and liquid metal (Ga(2)O(3)/EGaIn) top electrodes. A systematic physical-organic study based on statistically large numbers of data (N = 300-1000) reached the conclusion that only one energetically accessible molecular orbital (the HOMO of the Fc) is necessary to obtain large rectification ratios R ≈ 1.0 × 10(2) (R = |J(-V)|/|J(V)| at ±1 V). Values of R are log-normally distributed, with a log-standard deviation of 3.0. The HOMO level has to be positioned spatially asymmetrically inside the junctions (in these experiments, in contact with the Ga(2)O(3)/EGaIn top electrode, and separated from the Ag electrode by the SC(11) moiety) and energetically below the Fermi levels of both electrodes to achieve rectification. The HOMO follows the potential of the Fermi level of the Ga(2)O(3)/EGaIn electrode; it overlaps energetically with both Fermi levels of the electrodes only in one direction of bias.

Uniform amplification of a mixture of phage clones is central to the selection of peptides and proteins presented on the coat proteins of phage (phage display).[1,2] Uniform amplification cannot be achieved when phage having different rates of growth compete with each other in a common solution. Here we describe a method for uniform amplification of individual phage clones, from a mixture of clones possessing different growth characteristics. We use a microfluidic droplet generator[3] to separate individual clones from a mixture of slowly growing (S) and rapidly growing (R) M13 filamentous phage into droplets of growth media (ca. 200 µm in diameter) containing E. coli. At sufficiently low concentrations of phage, each droplet contains one or no phage particles. Different phage cannot compete for bacterial hosts when isolated in different droplets, and the relative number of S and R clones present at the start is preserved after amplification. Because amplification of phage clones depends on the size of the droplets in which they reside, the use of droplets of uniform size is essential for the success of this process.

This paper describes a new system for non-electronic communication that can transmit alphanumeric information encoded as pulses of light, over intervals of hours. The objective of this research was to design “infofuses” that improved the previously described systems in three ways: 1) they could transmit information for hours instead of seconds, 2) they could transmit long messages, and 3) they resisted accidental extinction. These characteristics improve the functionality and potential for practical use of infofuses, and make themmore convenient to use as a test bed for a new approach to fusing chemistry and information—“infochemistry”. We consider the elements of a system for manipulating information that comprises seven steps: 1) generating the message (either by writing it, or by collecting it from a sensor), 2) encoding the information in a form that a device can transmit, 3) transmitting the information, 4) receiving the information, 5) decoding the information, 6) interpreting the decoded information, 7) acting on this information. Here, we focus on steps (2) and (3). To simplify the problem, we assume that reception and decoding will be accomplished optically and electronically, and that there are no constraints (that we must consider) on the complexity, cost, or performance of the systems that accomplish these functions. We also assume that generating the message involves a separate set of issues which may or may not be primarily chemical. Systems based on infochemistry combine the storage and transmission of encoded information with four attractive features of chemistry: 1) high energy density; 2) autonomous generation of power that can be used for both sensing and for transmission; 3) no requirement for batteries; 4) facile coupling with certain kinds of chemical sensing. We have described two infochemical systems that do not require external electrical power (they use only chemical interactions or reactions) to transmit alphanumeric information. The first system—which we call an “infofuse”—is based on a strip of flammable polymer (nitrocellulose). In this system, patterns of spots of thermally emissive salts encode information. The second—which we call a “droplet shutter”—is a microfluidic device that capitalizes on the high stability of operation of a flow-focusing nozzle to generate bubbles and droplets. In this system, windows in an opaque mask encode information. The combination of optically transparent droplets and windows serve as optical shutters. A third system—a frequency-agile microdroplet-based laser—requires electrical power to operate the pump laser, and is intended for different applications. In our previous design of infofuses, information was encoded as patterns of ions (Li, Rb, Cs) on a strip of nitrocellulose. Ignition of one end of a nitrocellulose strip initiated propagation of a flame-front (at T 1000 8C) at 2– 3 cms . As this moving hot zone reached each spot containing added metal ions, it caused the emission of light at wavelengths characteristic of the thermal emission of the corresponding atomic species. The pattern of emissive salts, ordered in space, therefore, became a sequence of pulses of light at characteristic wavelengths, ordered in time. We have described infofuses that used three thermal emitters (the perchlorate or nitrate salts of Li, Rb, and Cs, with Na as an internal standard for intensity) to encode and transmit alphanumeric messages. Because each of these three ions can either be present or absent in a particular spot, there are seven unique combinations (2 1; we have chosen not to use 0,0,0 to avoid ambiguities between a pulse and a space between pulses). Seven unique pulses allow an encoding scheme that assigned alphanumeric characters to combinations of two (7= 49) sequential optical pulses. The infofuses fabricated according to this design demonstrated the principle of a successful strategy for coupling chemistry with the encoding and transmitting of chemical information, but suffered from a number of weaknesses. Two were of primary concern to us: 1) While burning, the flame-front had to remain far (> 1– 2 mm) from surfaces, so that the heat transfer from the flame to the surface did not cool and extinguish the flame. When the flame-front of nitrocellulose infofuses with dimensions we used (1–3 mm wide, ca. 100 mm thick) came close (< 1–2 mm) to any solid surface, their rate of propagation decreased, and the flame frequently extinguished. This characteristic required that the burning infofuses have a vertical orientation, and be out of contact with solid surfaces; these restrictions limited the practical applicability of these infofuses. 2) The rapid propagation of the flame-front (ca. 3 cms ) precluded times of transmission longer than about 1 min (an infofuse on which the flame propagated at this rate would require a length of 2.6 km to transmit continuous or repetitive messages for 24 h). Here we describe a new experimental platform for infofuses that addresses these weaknesses by using a “dualspeed” arrangement (Figure 1), in which a fuse that burns slowly and continuously (a “SlowFuse”) and that does not transmit information, intermittently ignites fuses (strips of nitrocellulose) that burn quickly and transmit information [*] Dr. C. Kim, Dr. S. W. Thomas, III, Prof. G. M. Whitesides Department of Chemistry and Chemical Biology Harvard University 12 Oxford Street, Cambridge, MA 02138 (USA) E-mail: gwhitesides@gmwgroup.harvard.edu

In complete control: The magnitude of current rectification in well-defined supramolecular tunneling junctions can be controlled by changing the terminal functionality (red spheres) of dendrimers (gray spheres) immobilized on a supramolecular platform (see picture). Junctions containing biferrocene and ferrocene end groups showed larger rectification ratios than junctions containing adamantyl end groups.

This Article compares the ability of self-assembled monolayers (SAMs) of alkanethiolates with ferrocene (Fc) head groups (SC(11)Fc), and SAMs of alkanethiolates lacking the Fc moiety (SC(10)CH(3) and SC(14)CH(3)), to conduct charge. Ultraflat surfaces of template-stripped silver (Ag(TS)) supported these SAMs, and a eutectic alloy of gallium and indium (EGaIn), covered with a skin of gallium oxide (presumably Ga(2)O(3)), formed electrical top-contacts with them. EGaIn is a liquid at room temperature, but its spontaneously formed surface oxide skin gives it apparent non-Newtonian properties and allows it to be molded into conically shaped tips; these tips formed soft electrical contacts with SAMs and formed stable SAM-based tunneling junctions in high (70-90%) yields. Measurements of current density, J, versus applied voltage, V, showed that tunneling junctions composed of SAMs of SC(11)Fc rectify current with a rectification ratio R approximately 1.0 x 10(2) (R = |J(-V)|/|J(V)| at +/-1 V and with a log-standard deviation of 3.0). In contrast, junctions lacking the Fc moiety, that is, junctions composed of SAMs of SC(n-1)CH(3) (with n = 11 or 15 and presenting terminal CH(3) groups), showed only slight rectification (R = 1.5 (1.4) and 2.1 (2.5), respectively). A statistical analysis of large numbers (N = 300-1000) of data gave detailed information about the spread in values and the statistical significance of the rectification ratios and demonstrated the ability of the experimental techniques described here to generate SAM-based junctions in high yield useful in physical-organic studies.

This article describes a new procedure for generating and transmitting a message--a sequence of optical pulses--by aligning a mask (an opaque sheet containing transparent "windows") below a microfluidic channel in which flows an opaque continuous fluid containing transparent droplets. The optical mask encodes the message as a unique sequence of windows that can transmit or block light; the flow of transparent droplets in the channel converts this message into a sequence of optical pulses. The properties of the windows on the mask (e.g., their size, wavelength of transmittance, orientation of polarization) determine the information carried in these optical pulses (e.g., intensity, color, polarization). The structure of a transmitted signal depends on the number and spacing of droplets in the channel. Fourier transformation can deconvolve superimposed signals created by the flow of multiple droplets into the message that a single droplet would transmit. The research described in this contribution explores a new field at the intersection of chemistry, materials science, and information technology: infochemistry.

This paper describes an analytical system that uses magnetic levitation to measure densities of solids and water-immiscible organic liquids with accuracies ranging from +/-0.0002 to +/-0.02 g/cm(3), depending on the type of experiment. The technique is compatible with densities of 0.8-3 g/cm(3) and is applicable to samples with volumes of 1 pL to 1 mL; the samples can be either spherical or irregular in shape. The method employs two permanent NdFeB magnets positioned with like poles facing one another--with the axis between the poles aligned with the gravitational field--and a container filled with paramagnetic medium (e.g., MnCl(2) dissolved in water) placed between these magnets. Density measurements are obtained by placing the sample into the container and measuring the position of the sample relative to the bottom magnet. The balance of magnetic and gravitational forces determines the vertical position of the sample within the device; knowing this position makes it possible to calculate the density of the sample.

This paper describes a method for the purification of monoclonal antibodies (rat anti-2,4-dinitrophenyl IgG: IgG(DNP); and mouse antidigoxin IgG: IgG(Dgn)) from ascites fluid. This procedure (for IgG(DNP)) has three steps: (i) precipitation of proteins heavier than immunoglobulins with ammonium sulfate; (ii) formation of cyclic complexes of IgG(DNP) by causing it to bind to synthetic multivalent haptens containing multiple DNP groups; (iii) selective precipitation of these dimers, trimers, and higher oligomers of the target antibody, followed by regeneration of the free antibody. This procedure separates the targeted antibody from a mixture of antibodies, as well as from other proteins and globulins in a biological fluid. This method is applicable to antibodies with a wide range of monovalent binding constants (0.1 microM to 0.1 nM). The multivalent ligands we used (derivatives of DNP and digoxin) isolated IgG(DNP) and IgG(Dgn) from ascites fluid in yields of >80% and with >95% purity. This technique has two advantages over conventional chromatographic methods for purifying antibodies: (i) it is selective for antibodies with two active Fab binding sites (both sites are required to form the cyclic complexes) over antibodies with one or zero active Fab binding sites; (ii) it does not require chromatographic separation. It has the disadvantage that the structure of the hapten must be compatible with the synthesis of bi- and/or trivalent analogues.

This paper describes a study of the generation and flow of photocurrent through junctions containing three-dimensional arrays of colloidal CdSe quantum dots (QDs) of either a single size or multiple sizes. The electrodes were indium tin oxide (ITO) covered with a thin layer of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and a eutectic alloy of Ga and In (EGaIn). We measured the current-voltage characteristics of the junctions in the dark and under illumination, with various sources and wavelengths of excitation, and their photocurrent action spectra. Size-selective photoexcitation of the arrays of multiple sizes of QDs helped to determine (i) the location of the interface at which photoinduced separation of charge occurred, (ii) whether the energy absorbed by the QDs was redistributed before separation of charge, and (iii) the dependence of the photovoltage on the locations of various sizes of QDs within the junction. This research is a step toward the use of QDs for harvesting light and for transporting energy and charge in devicessfor example, solar cells and photodetectorssthat operate at zero bias.

This paper describes the synthesis of the trivalent hapten molecule 1, containing three 2,4-dinitrophenyl (2,4-DNP) groups, and the use of this molecule to aggregate three molecules of anti-2,4-DNP IgG into a complex with 3:2 stoichiometry (IgG312). The equilibrium product IgG312 was generated in approximately 90% yield upon mixing IgG and 1; during incubation, thermodynamically unstable, high-molecular-weight aggregates (104 nm in diameter) form first and convert subsequently to IgG312. The thermodynamics and the kinetics of the formation of aggregates were studied using size-exclusion high-performance liquid chromatography (SE-HPLC), dynamic light scattering (DLS), and analytical ultracentrifugation (AUC). An analytical model based on multiple species in equilibrium was developed and used to interpret the SE-HPLC data. The aggregate IgG312 was more stable thermodynamically and kinetically than monomeric aggregates of this IgG with monomeric derivatives of 2,4-DNP; this stability suggests potential applications of these aggregates in biotechnology.

This paper describes the fabrication and characterization of ionic electrets-materials that bear a long-lived electrostatic charge because of an imbalance between the number of cationic and anionic charges in the material. Crosslinked polystyrene microspheres that contain covalently bound ions and mobile counterions transfer some of their mobile ions in air, in the absence of bulk liquid, to another material upon contact. According to the ion-transfer model of contact electrification, this selective transfer of mobile ions yields microspheres that have a net electrostatic charge. A tool that operates on the principle of electrostatic induction measures the charge on individual microspheres (50-450 microm in diameter). Microspheres with a variety of covalently bound ionic functional groups (tetraalkylammonium, alkyltriphenylphosphonium, alkylsulfonate, and arylsulfonate) acquire charges consistent with this ion-transfer mechanism. The charge on a microsphere is proportional to its surface area (ca. 1 elementary charge per 2000 nm2) and close to the theoretical limit imposed by the dielectric breakdown of air. The charge density in an atmosphere of SF6 is more than twice that in an atmosphere of N2. These observations suggest that the charge density of these ionic electret microspheres is limited by the dielectric breakdown of the surrounding gas. Functionalizing the surfaces of glass or silicon with covalently bound ions and mobile counterions generates ionic electrets from these inorganic substrates. Soft lithography can pattern charge on a planar silicon surface (with oxide) and on the surface of 250-mum glass microspheres.

Current methods of monitoring breathing require cumbersome, inconvenient, and often expensive devices; this requirement sets practical limitations on the frequency and duration of measurements. This article describes a paper-based moisture sensor that uses the hygroscopic character of paper (i.e. the ability of paper to adsorb water reversibly from the surrounding environment) to measure patterns and rate of respiration by converting the changes in humidity caused by cycles of inhalation and exhalation to electrical signals. The changing level of humidity that occurs in a cycle causes a corresponding change in the ionic conductivity of the sensor, which can be measured electrically. By combining the paper sensor with conventional electronics, data concerning respiration can be transmitted to a nearby smartphone or tablet computer for post-processing, and subsequently to a cloud server. This means of sensing provides a new, practical method of recording and analyzing patterns of breathing.

This paper uses the binding pocket of human carbonic anhydrase II (HCAII, EC 4.2.1.1) as a tool to examine the properties of Hofmeister anions that determine (i) where, and how strongly, they associate with concavities on the surfaces of proteins and (ii) how, upon binding, they alter the structure of water within those concavities. Results from X-ray crystallography and isothermal titration calorimetry show that most anions associate with the binding pocket of HCAII by forming inner-sphere ion pairs with the Zn(2+) cofactor. In these ion pairs, the free energy of anion–Zn(2+) association is inversely proportional to the free energetic cost of anion dehydration; this relationship is consistent with the mechanism of ion pair formation suggested by the “law of matching water affinities”. Iodide and bromide anions also associate with a hydrophobic declivity in the wall of the binding pocket. Molecular dynamics simulations suggest that anions, upon associating with Zn(2+), trigger rearrangements of water that extend up to 8 Å away from their surfaces. These findings expand the range of interactions previously thought to occur between ions and proteins by suggesting that (i) weakly hydrated anions can bind complementarily shaped hydrophobic declivities, and that (ii) ion-induced rearrangements of water within protein concavities can (in contrast with similar rearrangements in bulk water) extend well beyond the first hydration shells of the ions that trigger them. This study paints a picture of Hofmeister anions as a set of structurally varied ligands that differ in size, shape, and affinity for water and, thus, in their ability to bind to—and to alter the charge and hydration structure of—polar, nonpolar, and topographically complex concavities on the surfaces of proteins.

This work examines charge transport (CT) through self-assembled monolayers (SAMs) of oligoglycines having an N-terminal cysteine group that anchors the molecule to a gold substrate, and demonstrate that CT is rapid (relative to SAMs of n-alkanethiolates). Comparisons of rates of charge transport-using junctions with the structure Au(TS)/SAM//Ga2O3/EGaIn (across these SAMs of oligoglycines, and across SAMs of a number of structurally and electronically related molecules) established that rates of charge tunneling along SAMs of oligoglycines are comparable to that along SAMs of oligophenyl groups (of comparable length). The mechanism of tunneling in oligoglycines is compatible with superexchange, and involves interactions among high-energy occupied orbitals in multiple, consecutive amide bonds, which may by separated by one to three methylene groups. This mechanistic conclusion is supported by density functional theory (DFT).

Almost all proteins contain charged amino acids. While the function in catalysis or binding of individual charges in the active site can often be identified, it is less clear how to assign function to charges beyond this region. Are they necessary for solubility? For reasons other than solubility? Can manipulating these charges change the properties of proteins? A combination of capillary electrophoresis (CE) and protein charge ladders makes it possible to study the roles of charged residues on the surface of proteins outside the active site. This method involves chemical modification of those residues to generate a large number of derivatives of the protein that differ in charge. CE separates those derivatives into groups with the same number of modified charged groups. By studying the influence of charge on the properties of proteins using charge ladders, it is possible to estimate the net charge and hydrodynamic radius and to infer the role of charged residues in ligand binding and protein folding.

This paper describes a systematic study of the thermodynamics of association of bovine carbonic anhydrase II (BCA) and para-substituted benzenesulfonamides with chains of oligoglycine, oligosarcosine, and oligoethylene glycol of lengths of one to five residues. For all three of these series of ligands, the enthalpy of binding became less favorable, and the entropy less unfavorable, as the chain length of the ligands increased. The dependence on chain length of the enthalpy was almost perfectly compensated by that of the entropy; this compensation resulted in dissociation constants that were independent of chain length for the three series of ligands. Changes in heat capacity were independent of chain length for the three series and revealed that the amount of molecular surface area buried upon protein-ligand complexation did not increase with increasing chain length. Taken together, these data refute a model in which the chains of the ligands interact hydrophobically with the surface of BCA. To explain the data, a model is proposed based on decreasing "tightness" of the protein-ligand interface as the chain length of the ligand increases. This decreasing tightness, as the chain length increases, is reflected in a less favorable enthalpy (due to fewer van der Waals contacts) and a less unfavorable entropy (due to greater mobility of the chain) of binding for ligands with long chains than for those with short chains. Thus, this study demonstrates a surprising example of enthalpy/entropy compensation in a well-defined system. Understanding this compensation is integral to the rational design of high-affinity ligands for proteins.

This study compares the folding of two polypeptides--bovine carbonic anhydrase (BCA) and peracetylated BCA (BCA-Ac(18))--having the same sequence of amino acids but differing by 18 formal units of charge, from a solution containing denaturing concentrations of sodium dodecyl sulfate (SDS). Acetylation of BCA with acetic anhydride converts all 18 lysine-epsilon-NH(3)(+) groups to lysine-epsilon-NHCOCH(3) groups and generates BCA-Ac(18). Both BCA and BCA-Ac(18) are catalytically active, and circular dichroism spectroscopy (CD) suggests that they have similar secondary and tertiary structures. SDS at concentrations above approximately 10 mM denatured both proteins. When the SDS was removed by dialysis, both proteins were regenerated in native form. This study suggests that large differences in the net charge of the polypeptide have no significant influence on the structure, the ability to refold, or the rate of refolding of this protein from solutions containing SDS. This study reinforces the idea that charged residues on the surface of BCA do not guide protein folding and raises the broader question of why proteins have charged residues on their surface, outside of the region of the active site.