Ken Shimizu

A small, axially chiral diacid was designed with chiral memory based on restricted rotation. Heating a racemic sample with a chiral alkaloid led to an enantiomeric excess of up to 40% ee. The guest-induced chirality was preserved on cooling to rt, which was maintained even in the absence of guest (t(1/2) = 14y). The chiral enrichment process was also reversible, allowing the diacid to be used as a chiral switch.

A new series of molecular torsion balances were designed to measure the strength of individual Ag-π interactions in solution. The formation of a well-defined intramolecular Ag-π interaction in these model systems was verified by X-ray crystallography and 1H NMR. The strength of the intramolecular Ag-π interaction in solution was found to stabilizing in nature and quantified to be -1.34 to -2.6 kcal/mol using a double mutant cycle analysis. The Ag-π interaction was also found to be very sensitive to changes in geometry or solvent environment.

... AH Hoveyda, Dr. BM Cole, Dr. KD Shimizu. ... Da die Reaktionen durch die Dipeptid-Schiff-Basen beschleunigt wer-den[71, sollten eventuell auftretende Nebenprodukte der Ligan-den-Festphasensynthese kein ernstes Hindernis fur eine genaue Untersuchung sein, denn die ...

... Ken D. Shimizu, Bridget M. Cole, Clinton A. Krueger, Kevin W. Kuntz, Marc L. Snapper* und Amir H. Hoveyda* ... Unsere Methode weist gegenuber traditionelleren Verfahren zur Entdeckung chiraler Liganden eine Reihe von Vorteilen auf: 1) Die Suche kann auf einem festen ...

The majority of binding models that have been applied to molecularly imprinted polymers (MIPs) have been homogeneous models. MIPs, on the other hand, are heterogeneous materials containing binding sites with a wide array of binding affinities and selectivities. Demonstrated is that the binding behavior of MIPs can be accurately modeled by the heterogeneous Langmuir-Freundlich (LF) isotherm. The applicability of the LF isotherm to MIPs was demonstrated using five representative MIPs from the literature, including both homogeneous and heterogeneous MIPs. Previously, such comparisons required the use of several different binding models and analyses, including the Langmuir model, the Freundlich model, and numerical approximation techniques. In contrast, the LF model enabled direct comparisons of the binding characteristics of MIPs that have very different underlying distributions and were measured under different conditions. The binding parameters can be calculated directly using the LF fitting coefficients that yield a measure of the total number of binding sites, mean binding affinity, and heterogeneity. Alternatively, solution of the Langmuir adsorption integral for the LF model enabled direct calculation of the corresponding affinity spectrum from the LF fitting coefficients from a simple algebraic expression, yielding a measure of the number of binding sites with respect to association constant Finally, the ability of the LF isotherm to model MIPs suggests that a unimodal heterogeneous distribution is an accurate approximation of the distribution found in homogeneous and heterogeneous MIPs.

A large bis-urea macrocycle was synthesized and assembled into columnar nanotubes containing a sizable cavity. This purely organic nanotube is held together primarily by hydrogen bonding and yet shows remarkable thermal stability up to 180 degrees C in the presence and absence of acetic acid guest. This enables the nanotube to be used as reusable organic zeolite.

Chem. Commun., 2003, 1630-1631 DOI:10.1039/B303708H (Communication). The first 'two-over/two-under' (2O/2U) 2D weave structure assembled from Hg-containing 1D coordination polymer chains†. Yun-Hui Li, Cheng-Yong ...

... Convergent Functional Groups. 15. Synthetic and Structural Studies of Large and Rigid Molecular Clefts Ken D. Shimizu, Torin M. Dewey, and J. Rebek, Jr.' ... SOC. 1987, 109, 65496551. (e) Galln, A.; Andreu, D.; Echavarren, AM; Prados, P.; de Mendoza, J. J. Am. Chem. Soc. ...

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ABSTRACT Arigid molecular balance was developed based on a rigid bicyclic phencycloneframework having restricted rotation about a C(aryl)-N(imide) bond. At room temperature, the balance is inequilibrium between two distinct conformers. In the folded conformer, two arene surfaces form a well-definedface-to-face or edge-to-face intramolecular interaction. In the unfolded conformer, the arenesurfaces are rigidly held apart. Thus, the folded/unfolded ratio yields an accurate measure of theintramolecular arene-arene interaction and can be easily measured viaintegration of the 1H NMR spectra. Using this balance, we studied the relative importance ofthe solvophobic, electrostatic, and dispersion forces on the strength of thearene-arene interaction. The contributionsof each of these forces was found to be significant and of similarmagnitudes. The solvophobiceffects in particular were found to be surprisingly strong even in organicsolvents. The electrostatic trendsconsistent with the Hunter model were observed. However, these electrostatic trends did not diminish significantlyin polar organic solvent as expected.

CH-π interactions have been cited as an important contributor to carbohydrate recognition. To determine whether N-heterocycles form stronger CH-π interactions, the interactions of methyl ether groups with heterocyclic and nonheterocyclic aromatic surfaces were studied. Both experimental and computational experiments found that N-heterocyclic aromatic surfaces formed stronger interactions. This enhancement was attributed to attractive dipole-dipole interactions between the methyl ether C-O bond and the N-heterocyclic aromatic dipole.

The goal of this study was to experimentally test the additivity of the electrostatic substituent effects (SEs) for the aromatic stacking interaction. The additivity of the SEs was assessed using a small molecule model system that could adopt an offset face-to-face aromatic stacking geometry. The intramolecular interactions of these molecular torsional balances were quantitatively measured via the changes in a folded/unfolded conformational equilibrium. Five different types of substituents were examined (CH3, OCH3, Cl, CN, and NO2) that ranged from electron-donating to electron-withdrawing. The strength of the intramolecular stacking interactions was measured for 21 substituted aromatic stacking balances and 21 control balances in chloroform solution. The observed stability trends were consistent with additive SEs. Specifically, additive SE models could predict SEs with an accuracy from ±0.01 to ±0.02 kcal/mol. The additive SEs were consistent with Wheeler and Houk's direct SE model. However, the indirect or polarization SE model cannot be ruled out as it shows similar levels of additivity for two to three substituent systems, which were the number of substituents in our model system. SE additivity also has practical utility as the SEs can be accurately predicted. This should aid in the rational design and optimization of systems that utilize aromatic stacking interactions.

A series of new torsional molecular balances was designed to study the cooperativity of CH-π interaction in the solid state and in solution. The measured interaction energies correlated better to the number of participating alkyl carbons than to the number of CH-π contacts. The methyl and ethyl groups displayed additive interaction energies. However, the branched isopropyl group displayed strong positive cooperativity with higher than predicted interaction energies.

PAPER, Synthesis 2002(9): 1239-1244 DOI: 10.1055/s-2002-32539. © Georg Thieme Verlag Stuttgart · New York. Shape-Persistent and Shape-Adaptable Macrocycles Based on Restricted Rotation: Studies Building Toward 'Macromolecular Playdough'. ...

ABSTRACT Rhodamine amides are known to function as an important platform for molecular probe formation. The use of rhodamine-based probes has focused on the equilibrium between the off to on opening of the lactam form to the amide form. Herein, a series of four structurally similar rhodamine lactam derivatives is studied to show that the rate of conversion from the lactam form to the amide form can vary greatly (<1 s to >12 h) and that the rate trend is different from the trend for the absorbance measured at equilibrium. Slow or varying rates of ring opening for structurally similar rhodamine derivatives could produce inaccurate results. Rates were studied with both trifluoroacetic acid (TFA) and iron III. The rate of conversion changed depending on the structure of the substituent attached to the lactam nitrogen. Interestingly the rate of conversion varied even for compounds with similar absorbance at equilibrium. This work will help with the development of more effective rhodamine-based molecular probes.

[reaction--see text] Diimide 1 and octaimide 2 both adopt two stable conformations at room temperature as a result of restricted rotation about two C(aryl)-N(imide) single bonds, a compact "folded" and an open "unfolded" structure. Predictable ratios of folded and unfolded rotamers can be achieved by heating in solvents of appropriate polarity as measured by the Reichardt's parameter (E(T30)). On cooling to room temperature, the resulting conformational changes are "locked in" as restricted rotation is reestablished.

[reaction: see text] A new method is presented for the measurement of enantiomeric excess (ee) utilizing molecularly imprinted polymers (MIPs). The method is demonstrated to be accurate and rapid, as the ee values can be calculated from straightforward concentration measurements. The MIP-based assay can also be adapted to measure the ee of samples of differing initial concentrations.

The molecular imprinting process provides a synthetically efficient route to polymers with tailored recognition properties. However, the binding properties of the templated binding sites are often masked by the more prevalent background binding sites. Therefore, a strategy for reducing the number of background binding sites was developed and evaluated that uses functional monomer aggregation to suppress the formation of background sites. A series of imprinted and non-imprinted polymers was formed using crosslinking urea monomer and were evaluated for their ability to rebind the anionic template, tetrabutylammonium diphenyl phosphate (TBA-DPP). The urea monomer was shown to form linear hydrogen bonded aggregates in solution and in the solid state. Functional monomer aggregation in the polymerization solution was shown to dramatically reduce the numbers of background binding sites by occupying and blocking the urea recognition groups that were not bound to the template molecule. Despite the low aggregation constant of the urea monomer (3.5 M(-1) in chloroform), the number of background sites was reduced by more than 60%. We predict that this strategy of using monomers that aggregate to reduce background binding sites is a general one for MIPs and other types of polymers with tailored recognition properties. The key is to identify self-assembling monomers where the guest binding processes are stronger than the aggregation processes.

London dispersion forces have been cited as an important factor in protein folding, drug–receptor interactions, and catalyst selectivities. However, careful analysis of a model system finds that the dispersion interactions are only minor contributors to the formation of complexes in solution.

ABSTRACT We examined the influence of functional monomer dimerization on the efficiency of the molecular imprinting process. Specifically, the influence of methacrylic acid (MAA) dimerization on the binding properties of molecularly imprinted polymers (MIPs) was studied. First, the dimerization of MAA and the association between MAA and template molecular ethyl adenine-9-acetate (EA9A) were characterized in solution. Next, a series of MIPs and control nonimprinted polymers (NIPs) were made under varying conditions that systematically disrupted the monomer dimerization and templation process by the addition of polar solvents to the polymerization mixture. The results showed that even a monomer such as MAA with low dimerization constant is able to efficiently suppress the formation of background binding sites. To isolate the influence of monomer dimerization on the imprinting effect, the equilibrium processes in the prepolymerization mixture were modeled using the computer program COPASI. The simulation was able to reproduce the experimentally observed relationship between monomer dimerization and the suppression of the background sites. While monomer dimerization reduced the number of templated sites, the reduction in the number of background sites was large, leading to an overall increase in the percentage of templated sites. In addition, conditions were identified in which MAA dimerization can actually improve the imprinting efficiency as measured by the fraction of selective templated to background sites. On the basis of these studies with MAA, we predict that other functional monomers that can dimerize or aggregate should also show higher imprinting efficiencies in terms of selectivity while sacrificing some binding capacity. Both experimental and simulation results demonstrated that one must be very careful when using NIPs as control systems to characterize the imprinting effect as the suppression of background sites in the NIP can lead to differences in binding capacities of the MIP and NIP even in the absence of an imprinting effect.

A colorimetric sensor array composed of seven molecularly imprinted polymers was shown to accurately identify seven different aromatic amines. The response patterns were systematically classified using linear discriminant analysis with 94% classification accuracy. Analyses of the response patterns of the analytes to the imprinted polymer array suggest that the different selectivity patterns, although subtle, appear to arise from the imprinting process. The molecular imprinting process enabled the rapid preparation of the polymers in the array from ethylene glycol dimethacrylate and methacrylic acid (80:20) in the presence of six different template molecules plus a blank nonimprinted polymer. The response of the imprinted polymer array was coupled to a colorimetric response, using a dye displacement strategy. A benzofurazan dye was selected and shown to give an accurate measure of the binding properties of the imprinted polymer array to all seven analytes. The colorimetric response also enabled the inclusion of analytes that are not spectroscopically active and were not among the original analytes that were used as template molecules. This broadens the potential utility of the imprinted polymer sensor array strategy to a wider range of analytes and applications.

... Convergent Functional Groups. 15. Synthetic and Structural Studies of Large and Rigid Molecular Clefts Ken D. Shimizu, Torin M. Dewey, and J. Rebek, Jr.' ... SOC. 1987, 109, 65496551. (e) Galln, A.; Andreu, D.; Echavarren, AM; Prados, P.; de Mendoza, J. J. Am. Chem. Soc. ...

A molecular rotor was designed that rotates 7 orders of magnitude faster upon protonation. The quinoline rotor is based on a rigid N-arylimide framework that displays restricted rotation due to steric interaction between the quinoline nitrogen and imide carbonyls. At rt (23 °C), the rotor rotates slowly (t(1/2) = 26 min, ΔG(‡) = 22.2 kcal/mol). However, upon addition of 3.5 equiv of acid the rotor rotates rapidly (t(1/2) = 2.0 × 10(-4) s, ΔG(‡) = 12.9 kcal/mol). Mechanistic studies show that this dramatic acid catalyzed change is due to stabilization of the planar transition state by the formation of an intramolecular hydrogen bond between the protonated quinoline nitrogen (N(+)-H) and an imide carbonyl (O═C). The acid catalyzed acceleration is reversible and can be stopped by addition of base.