Tsuyoshi Minami

Templated Synthesis of Glycoluril Hexamer and Monofunctionalized Cucurbit[6]uril Derivatives

We report that the p-xylylenediammonium ion (11) acts as a template in the cucurbit[n]uril forming reaction that biases the reaction toward the production of methylene bridged glycoluril hexamer (6C) and bis-nor-seco-CB[10]. Hexamer 6C is readily available on the gram scale by a one step synthetic procedure that avoids chromatography. Hexamer 6C undergoes macrocylization with (substituted) phthalaldehydes 12, 14, 15, and 18-in 9 M H(2)SO(4) or concd HCl at room temperature to deliver monofunctionalized CB[6] derivatives 13, 16, 17, and 19-that are poised for further functionalization reactions. The kinetics of the macrocyclization reaction between hexamer and formaldehyde or phthalaldehyde depends on the presence and identity of ammonium ions as templates. p-Xylylenediammonium ion (11) which barely fits inside CB[6] sized cavities acts as a negative template which slows down transformation of 6C and paraformaldehyde into CB[6]. In contrast, 11 and hexanediammonium ion (20) act as a positive template that promotes the macrocyclization reaction between 6C and 12 to deliver (±)-21 as a key intermediate along the mechanistic pathway to CB[6] derivatives. Naphthalene-CB[6] derivative 19 which contains both fluorophore and ureidyl C═O metal-ion (e.g., Eu(3+)) binding sites forms the basis for a fluorescence turn-on assay for suitable ammonium ions (e.g., hexanediammonium ion and histamine).

Supramolecular sensor for cancer-associated nitrosamines.

A supramolecular assay based on two fluorescent cucurbit[n]uril probes enables the recognition and quantification of nitrosamines, including cancer-associated nitrosamines, compounds that are difficult to recognize. The cross-reactive sensor leverages weak interactions and competition among the probe, metal, and guest, yielding high information density in the signal output (variance) and enabling the recognition of structurally similar guests.

Multianalyte Sensing of Addictive Over-the-Counter (OTC) Drugs

A supramolecular sensor array composed of two fluorescent cucurbit[n]uril-type receptors (probe 1 and probe 2) displaying complementary selectivities was tested for its ability to detect and quantify drug-related amines. The fluorimetric titration of the individual probes showed highly variable and cross-reactive analyte-dependent changes in fluorescence. An excellent ability to recognize a variety of analytes was demonstrated in qualitative as well as quantitative assays. Importantly, a successful quantitative analysis of several analytes of interest was achieved in mixtures and in human urine. The throughput and sensitivity surpass those of the current state-of-the-art methods that usually require analyte solid-phase extraction (SPE). These results open up the opportunity for new applications of cucurbit[n]uril-type receptors in sensing and pave the way for the development of simple high-throughput assays for various drugs in the near future.

Sensing of carboxylate drugs in urine by a supramolecular sensor array.

A supramolecular sensor array consisting of eight chemosensors embedded in a hydrogel matrix was used to sense carboxylate drugs. The discriminatory power of the array has been evaluated using principal component analysis and linear discriminant analysis. The eight-member sensor array has been shown to accurately identify 14 carboxylates in water with 100% classification accuracy. To demonstrate the potential for practical utility in the physiological environment, analysis of carboxylate drugs in human urine was also performed achieving 100% correct classification. In addition, the array performance in semiquantitative identification of nonsteroidal anti-inflammatory drugs has been investigated, and the results show that the sensor array is able to differentiate six typical nonsteroidal anti-inflammatory drugs at concentrations of 0.5-100 ppm. This illustrates the potential utility of the designed sensor array for diagnostic and environmental monitoring applications.

Accurate and reproducible detection of proteins in water using an extended-gate type organic transistor biosensor

In this Letter, we describe an accurate antibody detection method using a fabricated extended-gate type organic field-effect-transistor (OFET), which can be operated at below 3 V. The protein-sensing portion of the designed device is the gate electrode functionalized with streptavidin. Streptavidin possesses high molecular recognition ability for biotin, which specifically allows for the detection of biotinylated proteins. Here, we attempted to detect biotinylated immunoglobulin G (IgG) and observed a shift of threshold voltage of the OFET upon the addition of the antibody in an aqueous solution with a competing bovine serum albumin interferent. The detection limit for the biotinylated IgG was 8 nM, which indicates the potential utility of the designed device in healthcare applications.

Determination of Enantiomeric Excess in Amine Derivatives with Molecular Self‐Assemblies

We report the first fluorescence-based assay for the rapid determination of the ee value of amines, amino alcohols, and amino acid esters. The method uses the self-assembly of 2-formylphenylboronic acid with a chiral diol and a chiral amine or derivatives (of unknown chirality) to produce two diastereomeric iminoboronates that differ in their fluorescence intensity and polarization. The approach allows for the accurate determination of the ee value of chiral amines with errors of just 1-2%. We believe that this application of orthogonal dynamic covalent self-assembly in the determination of the enantioselectivity will lead to the development of high-throughput procedures for the determination of chirality.

Amine-triggered molecular capsules using dynamic boronate esterification

Boron-contained molecular capsules triggered by amines are described for the first time; when Et3N was employed as a chemical stimulus the Lewis acid Et3NH+, produced by solvolysis reaction on the boron, was found to be encapsulated in the internal cavity, whereas use of nBu3N led to the related dynamic capsule capable of accommodating several guest species including Cs+.

First supramolecular sensors for phosphonate anions

Fluorescent tripodal anion sensors with a 1,3,5-triethylbenzene core display a turn-on fluorescence response to phosphonate and phosphate anions and may be used as optical sensors. The properties of the receptors and sensors as well as their anion binding behavior were investigated both in solution and in solid state. The turn-on fluorescence response can be leveraged in sensing of phosphate anions and, most importantly, hydrolysis products of the nerve gas sarin, isopropyl methylphosphonate (IMP), and methylphosphonate (MP). The fluorescence signal amplification in the presence of anions allows for application of these molecules in a sensor microarray suitable for high-throughput screening.

Leveraging material properties in fluorescence anion sensor arrays: a general approach.

As the demand for probes suitable for sensor development increases, investigation of approaches that utilize known successful receptors gains in general importance. This study describes a two-prong approach that can be used as a guide to developing sensors from known receptors. First, the conversion of a simple receptor, calix[4]pyrrole, into a fluorescent probe to establish a ratiometric signal is described. Secondly, the sensors that employ an output from a single ratiometric calix[4]pyrrole probe are fabricated by using poly(ether-urethane) hydrogel copolymers. These hydrogels are designed to absorb, internalize and transport aqueous electrolytes. A sensor array of ten different poly(ether-urethane) matrices with varying comonomer proportions were doped with a single probe and were exposed to eight different anions: acetate, benzoate, fluoride, chloride, phosphate, pyrophosphate, hydrogen sulfide, and cyanide, eight urine samples and anti-inflammatory drugs (NSAIDs). The poly(ether-urethane) matrices comprise different proportions of anion-binding urethane moieties and different hydrophilicity given by the ratio between ethylene glycol ether and butylene glycol ether. This diversity in the hydration behavior provides different environment polarity, in which the recognition and self-assembly processes display enough diverse behavior to allow for unique response of the probe to the analytes. Furthermore, a single probe is shown to recognize eight different aqueous anions and eight urine samples when embedded in ten different polyurethanes in an array that displays 100 % classification accuracy. To demonstrate the potential of the concept for quantitative studies, an estimation of non-steroidal anti-inflammatory drugs ibuprofen and diclofenac in water and in saliva was performed. A limit of detection of 0.1 ppm and a dynamic range of 0.1-0.6 and 0.05-60 ppm was observed, respectively. Given the general difficulty of chemosensors to recognize aqueous anions, the fact that one probe recognizes eight different analytes attests to an enormous effect of the polymer environment on the recognition process. This method could be used to generate a variety of sensor arrays for various analyses including species that are difficult to recognize, such as small-molecule- and inorganic anions.

Trends in Structure and Growth of Higher Fullerenes Isomer Structure of C86 and C88

Abstract The isomer structure and stability of higher fullerenes is one of the most interesting issues which might be closely related with general question how a fullerene cage structure is formed. In the present study, the structures of the higher fullerenes with the sizes of C86 and C88 are described based on UV/Visible/nearIR absorption spectra and 13C NMR measurements in solution. For well-understanding the structure and growth of higher fullerenes, the isomer-free samples were prepared for all isomers associated with the C86, and C88 cages by means of a multiple stage high performance liquid chromatography (HPLC). As a result, five different isomers for C86 and C88 were successfully isolated and characterized. For these five different isomers studied in the present work, 13C NMR measurements in solution straightforwardly gave a conclusion that three of them possess the cage structures with a C2 molecular symmetry and two with a Cs molecular symmetry. The possible specific candidates for these five isomers will be discussed on the basis of both the present experimental results and recent theoretical predictions.