Kinetic Trapping of an Out-of-Equilibrium Dynamic Library of Imines by Changing Solvent.

A well-behaved dynamic library composed of two imines and corresponding amines was subjected to the action of an activated carboxylic acid (ACA), whose decarboxylation is known to be base promoted, in different solvents, namely CD2Cl2, CD3CN, and mixtures of them. Two non-equilibrium systems are consequently obtained: i) a dissipative (CD2Cl2) and ii) an out-of-equilibrium (CD3CN) dynamic library whose composition goes back to equilibrium after a given time. In the former case, the library is fully coupled with the decarboxylation of the ACA, while in the latter, an energy ratchet operates. In the mixed solvents, the library exhibits a mediated behavior. Interestingly, in the presence of an excess of added ACA, the different behavior of the imine library in the two solvents is expected to manifest only when the excess acid is consumed.

Controlling the Conformation of 2-Dimethylaminobiphenyls by Transient Intramolecular Hydrogen Bonding.

Temporal control of molecular motions is receiving increasing attention because it is central to the development of molecular switches and motors and nanoscopic materials with life-like properties. Inspired by previous studies, here, we report that acid 12 can be used to temporally control the conformational freedom around the C-C bond connecting the two aromatic rings of the ditopic bases 4 and 5. Consistent with NMR measurements and DFT calculations, before fuel addition, the conformational motion of the two aromatic rings of both 4 and 5 mainly consists of a large amplitude torsional oscillation spanning about 260° and passing for the anti conformation (the two nitrogen atoms at opposite sides). Immediately after the addition of 12, due to the protonation of one nitrogen and consequent formation of an N-H···N intramolecular hydrogen bond, the torsional oscillation in both 4H+ and 5H+ is not only restricted to a smaller range (about 100°) but explores the previously forbidden conformational space around the syn conformation (the two nitrogen atoms at the same side). However, the new state is an out-of-equilibrium state since decarboxylation of the conjugate base of 12 takes place and, at the end of the process, the system reverts to the more conformationally mobile state.

Aliphatic Anion Exchange Ionomers with Long Spacers and No Ether Links by Ziegler-Natta Polymerization: Properties and Alkaline Stability.

In this work we report the synthesis of poly(vinylbenzylchloride-co-hexene) copolymer grafted with N,N-dimethylhexylammonium groups to study the effect of an aliphatic backbone without ether linkage on the ionomer properties. The copolymerization was achieved by the Ziegler-Natta method, employing the complex ZrCl4 (THF)2 as a catalyst. A certain degree of crosslinking with N,N,N',N'-tetramethylethylenediamine (TEMED) was introduced with the aim of avoiding excessive swelling in water. The resulting anion exchange polymers were characterized by 1H-NMR, FTIR, TGA, and ion exchange capacity (IEC) measurements. The ionomers showed good alkaline stability; after 72 h of treatment in 2 M KOH at 80 °C the remaining IEC of 76% confirms that ionomers without ether bonds are less sensitive to a SN2 attack and suggests the possibility of their use as a binder in a fuel cell electrode formulation. The ionomers were also blended with polyvinyl alcohol (PVA) and crosslinked with glutaraldehyde. The water uptake of the blend membranes was around 110% at 25 °C. The ionic conductivity at 25 °C in the OH- form was 29.5 mS/cm.

DNA Tile Self-Assembly Guided by Base Excision Repair Enzymes.

We demonstrate here the use of DNA repair enzymes to control the assembly of DNA-based structures. To do so, we employed uracil-DNA glycosylase (UDG) and formamidopyrimidine DNA glycosylase (Fpg), two enzymes involved in the base excision repair (BER) pathway. We designed two responsive nucleic acid modules containing mutated bases (deoxyuridine or 8-oxo-7,8-dihydroguanine recognized by UDG and Fpg, respectively) that, upon the enzyme repair activity, release a nucleic acid strand that induces the self-assembly of DNA tiles into tubular structures. The approach is programmable, specific and orthogonal and the two responsive modules can be used in the same solution without crosstalk. This allows to assemble structures formed by two different tiles in which the tile distribution can be accurately predicted as a function of the relative activity of each enzyme. Finally, we show that BER-enzyme inhibitors can also be used to control DNA-tile assembly in a specific and concentration-dependent manner.

Protein-Protein Communication Mediated by an Antibody-Responsive DNA Nanodevice.

We report here the rational design and optimization of an antibody-responsive, DNA-based device that enables communication between pairs of otherwise non-interacting proteins. The device is designed to recognize and bind a specific antibody and, in response, undergo a conformational change that leads to the release of a DNA strand, termed the "translator," that regulates the activity of a downstream target protein. As proof of principle, we demonstrate antibody-induced control of the proteins thrombin and Taq DNA polymerase. The resulting strategy is versatile and, in principle, can be easily adapted to control protein-protein communication in artificial regulatory networks.

Time Programmable Locking/Unlocking of the Calix[4]arene Scaffold by Means of Chemical Fuels.

In this work, we report that 2-cyano-2-phenylpropanoic acid and its p-Cl, p-CH3 and p-OCH3 derivatives can be used as chemical fuels to control the geometry of the calix[4]arene scaffold in its cone conformation. It is shown that, under the action of the fuel, the cone calix[4]arene platform assumes a "locked" shape with two opposite aromatic rings strongly convergent and the other two strongly divergent ("pinched cone" conformation). Only when the fuel is exhausted, the cone calix[4]arene scaffold returns to its resting, "unlocked" shape. Remarkably, the duration of the "locked" state can be controlled at will by varying the fuel structure or amount. A kinetic study of the process shows that the consume of the fuel is catalyzed by the "unlocked" calixarene that behaves as an autocatalyst for its own production. A mechanism is proposed for the reaction of fuel consumption.

Entropy-Based Rational Modulation of the pKa of a Synthetic pH-Dependent Nanoswitch.

The rational regulation of the pKa of an ionizable group in a synthetic device could be achieved by controlling the entropy of the linker connecting the hydrogen bond forming domains. We demonstrate this by designing a set of pH-responsive synthetic DNA-based nanoswitches that share the same hydrogen bond forming domains but differ in the length of the linker. The observed acidic constant (pKa) of these pH-dependent nanoswitches is linearly dependent on the entropic cost associated with loop formation and is gradually shifted to more basic pH values when the length of the linker domain is reduced. Through mathematical modeling and thermodynamic characterization we demonstrate that the modulation of the observed pKa is due to a purely entropic contribution. This approach represents a very versatile strategy to rationally modulate the pKa of synthetic devices in a highly predictable and accurate way.

Record Rate Enhancements for Tetrathiafulvalene Guests in the Formation of Bipyridinium- and Diazapyrenium-Based [2]Pseudorotaxanes.

The catalytic effects of guests 5-7 on the cyclization of 1 and 3 have been measured at 62 °C in MeCN. A record rate acceleration of more than 2000 times has been observed in the cyclization of the tricationic host 3 featuring large diazapyrenium π-surfaces by tetrathiafulvalene guests 6 and 7. The results emphasize the role played by extended π-surfaces in the host and the goodness of a tetrathiafulvalene core in the guest, enhanced by polyethereal side arms.

Regulating Competing Supramolecular Interactions Using Ligand Concentration.

The complexity of biomolecular systems inevitably leads to a degree of competition between the noncovalent interactions involved. However, the outcome of biological processes is generally very well-defined often due to the competition of these interactions. In contrast, specificity in synthetic supramolecular systems is usually based on the presence of a minimum set of alternative assembly pathways. While the latter might simplify the system, it prevents the selection of specific structures and thereby limits the adaptivity of the system. Therefore, artificial systems containing competing interactions are vital to stimulate the development of more adaptive and lifelike synthetic systems. Here, we present a detailed study on the self-assembly behavior of a C2v-symmetrical tritopic molecule, functionalized with three self-complementary ureidopyrimidinone (UPy) motifs. Due to a shorter linker connecting one of these UPys, two types of cycles with different stabilities can be formed, which subsequently dimerize intermolecularly via the third UPy. The UPy complementary 2,7-diamido-1,8-naphthyridine (NaPy) motif was gradually added to this mixture in order to examine its effect on the cycle distribution. As a result of the C2v-symmetry of the tritopic UPy, together with small differences in binding strength, the cycle ratio can be regulated by altering the concentration of NaPy. We show that this ratio can be increased to an extent where one type of cycle is formed almost exclusively.

Supramolecular buffering by ring-chain competition.

Recently, we reported an organocatalytic system in which buffering of the molecular catalyst by supramolecular interactions results in a robust system displaying concentration-independent catalytic activity. Here, we demonstrate the design principles of the supramolecular buffering by ring-chain competition using a combined experimental and theoretical approach. Our analysis shows that supramolecular buffering of a molecule is caused by its participation as a chain stopper in supramolecular ring-chain equilibria, and we reveal here the influence of various thermodynamic parameters. Model predictions based on independently measured equilibrium constants corroborate experimental data of several molecular systems in which buffering occurs via competition between cyclization, growth of linear chains, and end-capping by the chain-stopper. Our analysis reveals that the effective molarity is the critical parameter in optimizing the broadness of the concentration regime in which supramolecular ring-chain buffering occurs as well as the maximum concentration of the buffered molecule. To conclude, a side-by-side comparison of supramolecular ring-chain buffering, pH buffering, and molecular titration is presented.

Thermo-Programmed Synthetic DNA-Based Receptors.

Herein, we present a generalizable and versatile strategy to engineer synthetic DNA ligand-binding devices that can be programmed to load and release a specific ligand at a defined temperature. We do so by re-engineering two model DNA-based receptors: a triplex-forming bivalent DNA-based receptor that recognizes a specific DNA sequence and an ATP-binding aptamer. The temperature at which these receptors load/release their ligands can be finely modulated by controlling the entropy associated with the linker connecting the two ligand-binding domains. The availability of a set of receptors with tunable and reversible temperature dependence allows achieving complex load/release behavior such as sustained ligand release over a wide temperature range. Similar programmable thermo-responsive synthetic ligand-binding devices can be of utility in applications such as drug delivery and production of smart materials.

Molecular recognition and self-assembly special feature: Squaring cooperative binding circles.

The cooperative binding effects of viologens and pyridines to a synthetic bivalent porphyrin receptor are used as a model system to study how the magnitudes of these effects relate to the experimentally obtained values. The full thermodynamic and kinetic circles concerning both activation and inhibition of the cage of the receptor for the binding of viologens were measured and evaluated. The results strongly emphasize the apparent character of measured binding and rate constants, in which the fractional saturation of receptors with other guests is linearly expressed in these constants. The presented method can be used as a simple tool to better analyze and comprehend the experimentally observed kinetics and thermodynamics of natural and artificial cooperative systems.

Anion-Conducting Polymer Electrolyte without Ether Linkages and with Ionic Groups Grafted on Long Side Chains: Poly(Alkylene Biphenyl Butyltrimethyl Ammonium) (ABBA).

In this work we report the synthesis of the new ionomer poly(alkylene biphenyl butyltrimethyl ammonium) (ABBA) with a backbone devoid of alkaline-labile C-O-C bonds and with quaternary ammonium groups grafted on long side chains. The ionomer was achieved by metalation reaction with n-butyllithium of 2-bromobiphenyl, followed by the introduction of the long chain with 1,4-dibromobutane. The reaction steps were followed by 1H-NMR spectroscopy showing the characteristic signals of the Br-butyl chain and indicating the complete functionalization of the biphenyl moiety. The precursor was polycondensed with 1,1,1-trifluoroacetone and then quaternized using trimethylamine (TMA). After the acid catalyzed polycondensation, the stoichiometric ratio between the precursors was respected. The quaternization with TMA gave a final degree of amination of 0.83 in agreement with the thermogravimetric analysis and with the ion exchange capacity of 2.5 meq/g determined by acid-base titration. The new ionomer blended with poly(vinylalcohol) (PVA) or poly(vinylidene difluoride) (PVDF) was also characterized by water uptake (WU) and ionic conductivity measurements. The higher water uptake and ionic conductivity observed with the PVDF blend might be related to a better nanophase separation.

Putting the mechanism of the Soai reaction to the test: DFT study of the role of aldehyde and dialkylzinc structure.

Previous DFT calculations provided support to the proposal that the Soai reaction involves a mechanism in which dimer catalysts serve as templates for the reaction of two molecules of dialkylzinc with two molecules of aldehyde so as to reproduce themselves (ref 11). Here it is shown that, from the point of view of formal kinetics, this mechanism can be reduced to a general model, dubbed the extended dimer model, that has the Blackmond-Brown dimer model as a particular case. Depending on the interplay of kinetic constants, the extended dimer model can give rise to either chiral amplification or depletion. Calculations of the kinetic constants at the M05-2X/6-31G(d) level of theory were carried out in order to theoretically evaluate the effect of the second aza group in the six-membered aromatic ring of the aldehydic substrate and the effect of dialkylzinc structure. Predictions of chiral amplification or depletion are in striking agreement with experimental data thus lending support to the proposed mechanism.

Time-programmable pH: decarboxylation of nitroacetic acid allows the time-controlled rising of pH to a definite value.

In this report it is shown that nitroacetic acid 1 (O2NCH2CO2H) can be conveniently used to control the pH of a water solution over time. Time-programmable sequences of the kind pH1(high)-pH2(low)-pH3(high) can be achieved, where both the extent of the initial pH jump (pH1(high)-pH2(low)) and the time required for the subsequent pH rising (pH2(low)-pH3(high)) can be predictably controlled by a judicious choice of the absolute and relative concentrations of the reagents (acid 1 and NaOH). Successive pH1(high)-pH2(low)-pH3(high) sequences can be obtained by subsequent additions of acid 1. As a proof of concept, the method is applied to control over time the pH-dependent host-guest interaction between alpha-cyclodextrin and p-aminobenzoic acid.

Dissipative operation of pH-responsive DNA-based nanodevices.

We demonstrate here the use of 2-(4-chlorophenyl)-2-cyanopropanoic acid (CPA) and nitroacetic acid (NAA) as convenient chemical fuels to drive the dissipative operation of DNA-based nanodevices. Addition of either of the fuel acids to a water solution initially causes a rapid transient pH decrease, which is then followed by a slower pH increase. We have employed such low-to-high pH cycles to control in a dissipative way the operation of two model DNA-based nanodevices: a DNA nanoswitch undergoing time-programmable open-close-open cycles of motion, and a DNA-based receptor able to release-uptake a DNA cargo strand. The kinetics of the transient operation of both systems can be easily modulated by varying the concentration of the acid fuel added to the solution and both acid fuels show an efficient reversibility which further supports their versatility.

Nanocomposite Anion Exchange Membranes with a Conductive Semi-Interpenetrating Silica Network.

Nanocomposite anion exchange membranes were synthesized based on poly(sulfone trimethylammonium) chloride. A hybrid semi-interpenetrating silica network containing a large amount of quaternary ammonium groups was prepared by two sol-gel routes, in situ with a single precursor, N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TMSP), or ex situ mixing two precursors, TMSP and 3-(2-aminoethylamino)propyldimethoxy-methylsilane (AEAPS). The properties of these hybrid composites and their degradation after immersion in 1 M KOH at 60 °C were studied. The degradation is reduced in the composite materials with a lower decrease in the ion exchange capacity. FTIR spectra showed that a main degradation mechanism with a single precursor TMSP is the dissolution of the hybrid silica network in KOH, whereas it is stable with the mixture of TMSP/AEASP. This conclusion is in agreement with the thermogravimetric analysis. The mechanical properties show a better ductility with a single precursor and higher stiffness and strength, but less ductility, by the ex situ route. The activation energy was between 0.25 and 0.14 eV for Cl and OH ion conduction, respectively, consistent with the migration mechanism.

Mechanism of the asymmetric autocatalytic Soai reaction studied by density functional theory.

The mechanism of the Soai reaction has been thoroughly investigated at the M05-2X/6-31G(d) level of theory, by considering ten energetically distinct paths. The study indicates the fully enantioselective catalytic cycle of the homochiral dimers to be the dominant mechanism. Two other catalytic cycles are shown to both be important for correct understanding of the Soai reaction. These are the catalytic cycle of the heterochiral dimer and the non-enantioselective catalytic cycle of the homochiral dimers. The former has been proved to be not really competitive with the principal cycle, as required for the Soai reaction to manifest chiral amplification, whereas the latter, which is only slightly competitive with the principal one, nicely explains the experimental enantioselectivity observed in the reaction of 2-methylpyrimidine-5-carbaldehyde. The study has also evidenced the inadequacy of the B3LYP functional for mechanistic investigations of the Soai reaction.

Using antibodies to control DNA-templated chemical reactions.

DNA-templated synthesis takes advantage of the programmability of DNA-DNA interactions to accelerate chemical reactions under diluted conditions upon sequence-specific hybridization. While this strategy has proven advantageous for a variety of applications, including sensing and drug discovery, it has been so far limited to the use of nucleic acids as templating elements. Here, we report the rational design of DNA templated synthesis controlled by specific IgG antibodies. Our approach is based on the co-localization of reactants induced by the bivalent binding of a specific IgG antibody to two antigen-conjugated DNA templating strands that triggers a chemical reaction that would be otherwise too slow under diluted conditions. This strategy is versatile, orthogonal and adaptable to different IgG antibodies and can be employed to achieve the targeted synthesis of clinically-relevant molecules in the presence of specific IgG biomarker antibodies.

Amplification of chirality and enantioselectivity in the asymmetric autocatalytic Soai reaction.

From a kinetic analysis of the "dimer model", which is the most prominent mechanism of the Soai reaction, an equation is derived predicting the amplification of enantiomeric excess as a function of initial conditions. The role played by the enantioselectivity of the catalyst-product is also taken into account. Comparison with experimental data obtained at 0 degrees C by Soai et al. shows that the predicted enantiomeric excesses are lower than the experimental values by up to four orders of magnitude, and thus revision of the dimer model in the low-temperature regime is warranted. A kinetic analysis including the formation of tetramers is presented that fits the data at 0 degrees C and indicates that 2:2 heterochiral tetramers are more stable than homochiral and 3:1 heterochiral tetramers. A DFT study on diastereomers of barrel-like tetramers indeed shows higher stability of 2:2 heterochiral tetramers and thus lends support to the above kinetic analysis.