Molecular recognition in a uradinyl-functionalized stable radical

Stable radical 2-(6-uradinyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl (1) binds to hydrogen-bonding complement 2,6-di(propylamido)pyridine (DAP) in chloroform with Ka=220 M(-1) at 33 degrees C; ESI-MS shows not only 1:DAP complementary dyad formation, but also 1:(DAP)2 formation at higher concentrations of DAP.     

Selective co-aggregation of gold nanoparticles functionalised with complementary hydrogen-bonding groups

Molecular recognition between two species of Au55 clusters bearing complementary hydrogen-bonding groups provides a facile route to accomplish solution-based assembly of two-component nanoparticle aggregates.     

Creation of a pair of stereochemically complementary biocatalysts

N-Acetylneuraminic acid lyase (NAL) exhibits poor facial selectivity during carbon-carbon formation, and as such, its utility as a catalyst for use in synthetic chemistry is limited. For example, the NAL-catalyzed condensation between pyruvate and (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dipropylbutyramide yields ca. 3:1 mixtures of diastereomeric products under either kinetic or thermodynamic control. Engineering the stereochemical course of NAL-catalyzed reactions could remove this limitation. We used directed evolution to create a pair of stereochemically complementary variant NALs for the synthesis of sialic acid mimetics. The E192N variant, a highly efficient catalyst for aldol reactions of (2R,3S)-2,3-dihydroxy-4-oxo-N,N-dialkylbutyramides, was chosen as a starting point. Initially, error-prone PCR identified residues in the active site of NAL that contributed to the stereochemical control of an aldolase-catalyzed reaction. Subsequently, an intense structure-guided program of saturation and site-directed mutagenesis was used to identify a complementary pair of variants, E192N/T167G and E192N/T167V/S208V, which were approximately 50-fold selective toward the cleavage of the alternative 4S- and 4R-configured condensation products, respectively. It was shown that wild-type NAL could not be used for the highly stereoselective synthesis of a 6-dipropylamide sialic acid mimetic because the 4S-configured product was only approximately 3-fold kinetically favored and only approximately 3-fold thermodynamically favored over the alternative 4R-configured product. However, the complementary 4R- and 4S-selective variants allowed the highly (>98:<2) diastereoselective synthesis of both 4S- and 4R-configured products under kinetic control from the same starting materials. Conversion of an essentially nonselective aldolase into a pair of complementary biocatalysts will be of enormous interest to synthetic chemists. Furthermore, since residues identified as critical for stereoselectivity are conserved among members of the NAL superfamily, the approach might be extended to the evolution of other useful biocatalysts for the stereoselective synthesis of biologically active molecules.     

Molecular basis of the recognition process: hydrogen-bonding patterns in the guanine primary recognition site of ribonuclease T1

Investigation of the intrinsic H-bonding pattern of the guanine complex with a sizable segment (from Asn43 to Glu46) of the primary recognition site (PRS) in RNase T1 at the B3LYP/6-311G(d,p) level of theory enables the electronic density characteristics of the H-bonding patterns of the guanine-PRS complexes to be identified. The perfect H-bonding pattern in the guanine recognition site is achieved through the guanine complex interactions with the large segment of the PRS. Two significant short H-bonds, O epsilon 1...HN1 and O epsilon 2...HN2, have been identified. The similar short H-bond distances found in the anionic GC- base pair and in this study suggest that the short hydrogen-bond distances may be characteristic of the multiple H-bonded anionic nucleobases. The H-bonding energy distribution, the geometric analysis of the H-bonding pattern, and the electron structure characteristics of the H-bonds in the guanine PRS of RNase T1 all suggest that the O epsilon 1...HN1 and O epsilon 2...HN2 side-chain H-bonds dominate the binding at the guanine recognition site of RNase T1. Also, the geometry evidence, the electron structure characteristics, and the properties of the bond critical points of the H-bonds reveal that the side-chain H-bonding and the main-chain H-bonding are mutually intensifying. Thus the positive cooperativity between Asn43 to Tyr45 and Glu46 is proposed.     

Abundant polymorphism in a system with multiple hydrogen-bonding opportunities: oxalyl dihydrazide

To date, only one crystal structure has been reported in the literature for oxalyl dihydrazide [H(2)N.NH.CO.CO.NH.NH(2)]. In the present paper, we report the discovery of four new polymorphs of oxalyl dihydrazide, obtained by crystallization from solution under different conditions, including the use of different crystallization solvents. All polymorphs have the trans-trans-trans conformation of the N-N-C-C-N-N backbone, but the positions of the hydrogen atoms of the NH(2) groups relative to this backbone differ between the different polymorphs through variation of the torsion angle around each NH-NH(2) bond. The different polymorphs display a range of different hydrogen-bonding arrangements, constructed from different types of hydrogen-bonded array. The existence of several different potential hydrogen-bond donor and hydrogen-bond acceptor groups in the oxalyl dihydrazide molecule, together with the fact that the N-H bonds of the NH(2) groups adopt different orientations with respect to the molecular plane, leads to several possible geometric permutations for hydrogen-bonding arrangements in the solid state. It would not be surprising if even more polymorphs of oxalyl dihydrazide are discovered in the future.     

A heterodifunctionalised ferrocene derivative that self-assembles in solution through complementary hydrogen-bonding interactions

A heterodifunctionalised ferrocene, containing a carboxylic acid and an amidopyridine unit, self-assembles in organic solvents through complementary hydrogen bonds.     

Improved complementary polymer pair system: switching for enzyme activity by PEGylated polymers

The development of technology for on/off switching of enzyme activity is expected to expand the applications of enzyme in a wide range of research fields. We have previously developed a complementary polymer pair system (CPPS) that enables the activity of several enzymes to be controlled by a pair of oppositely charged polymers. However, it failed to control the activity of large and unstable α-amylase because the aggregation of the complex between anionic α-amylase and cationic poly(allylamine) (PAA) induced irreversible denaturation of the enzyme. To address this issue, we herein designed and synthesized a cationic copolymer with a poly(ethylene glycol) backbone, poly(N,N-diethylaminoethyl methacrylate)-block-poly(ethylene glycol) (PEAMA-b-PEG). In contrast to PAA, α-amylase and β-galactosidase were inactivated by PEAMA-b-PEG with the formation of soluble complexes. The enzyme/PEAMA-b-PEG complexes were then successfully recovered from the complex by the addition of anionic poly(acrylic acid) (PAAc). Thus, dispersion of the complex by PEG segment in PEAMA-b-PEG clearly plays a crucial role for regulating the activities of these enzymes, suggesting that PEGylated charged polymer is a new candidate for CPPS for large and unstable enzymes.     

Molecular recognition studies with a simple dipyrrinone

We present our investigations of 2-ethyl-3-methyl-(10H)-dipyrrin-1-one, its self-association, and anion binding properties. This receptor is easily accessible in a facile single step synthesis with a straightforward workup. An examination of the concentration dependence of the dipyrrinone NH chemical shifts in CDCl₃ and (CDCl₂)₂ over the temperature range from −20 °C to 100 °C determined the self-association constant to be 3850 M⁻¹. Molecular recognition studies have shown that it has a preference for guests with an OH moiety, such as hydrogen sulfate (HSO₄⁻) and carboxylic acids (RCO₂H).     

D3h-symmetrical hydrogen-bonding unit as a saccharide recognition and self-assembling module

A D(3h)-symmetrical triresorcinol module 1,3,5-tris(2,6-dihydroxy-4-pentylphenyl)benzene ( 3) was investigated in terms of its hydrogen-bonding ability for glycoside recognition and self-association. When 3 was treated with glycoside, corresponding changes were induced in (1)H NMR, UV, and CD spectra. The titration experiments indicated the participation of not only a 1:1 but also a 1:2 association of a glucosamine derivative guest. Self-association of 3 caused gelation with CDCl(3), and was studied by (1)H NMR and X-ray analysis.     

Magnetic field effects and radical pair mechanisms in enzymes: a reappraisal of the horseradish peroxidase system

Reinvestigation by stopped-flow spectrophotometry of the previously observed influence of a static magnetic field on the horseradish peroxidase (HRP)-catalyzed reduction of hydrogen peroxide by Taraban et al. (J. Am. Chem. Soc. 1997, 119, 5768) did not reproduce the originally observed effects. No magnetic field effect was observed for static fields of up to 75 mT. Field-induced changes in both k1 and k2 reported in the original work were found to produce equal and opposite effects on the shape of the observed kinetic decay of the 418 nm spectroscopic signal as a result of the difference in the relative absorbances of Native HRP and Compound II.     

Molecular recognition in a thermoplastic elastomer

Selective incorporation of bisurea guests in thermoplastic elastomers with poly(tetrahydrofuran) soft blocks and bisurea containing hard blocks is observed when the distances between the urea groups of host and guest match. The incorporation leads to significant modulation of mechanical properties. With bisurea-functionalized dyes as guests, a strong difference in extractability by detergent solution was shown between dyes differing by just one methylene unit between urea groups. Upon elongation of elastomer films, strong differences in alignability of matching and nonmatching dyes were observed.     

Hydroxyl group recognition by hydrogen-bonding donor and acceptor sites embedded in a layered metal-organic framework

One of the dominant types of interactions between host and guest molecules is hydrogen-bonding, and these interactions can work selectively for a guest molecule. Here, we demonstrate a metal-organic framework (MOF) having both hydrogen-bonding donor and acceptor sites that are quite effective for selective sorption. The MOF selectively interacts with hydroxylic guests in contrast to aprotic hydrogen-bonding guests and shows a sorption selectivity for protic H(2)O, MeOH, and EtOH guests. Notably, this is the first compound that shows complete selectivity in adsorption not for MeCN and MeCHO but for EtOH, which has similar fundamental properties except for its proticity.     

Spin evolution of radical pair with radical containing two groups of equivalent magnetic nuclei

Analytical solution is obtained for time-resolved magnetic field effects (TR-MFE) on recombination fluorescence of radical-ion pair (RIP) containing radical ion with two groups of magnetically equivalent nuclei. The present theoretical approach is applied to three experimental systems: RIPs containing radical cations of 2,3-dimethylbutane, 2,2,6,6-tetramethylpiperidine, or diisopropylamine and radical anion of p-terphenyl-d14 in nonpolar alkane solutions. Good agreement between theory and experiment is found for all the three systems, hyperfine coupling constants of radical cations are obtained by fitting the experimental TR-MFE traces. The potential of the TR-MFE technique for studying radical ions with nonequivalent nuclei is discussed in detail. The wide applicability of the theoretical model and the experimental technique make them useful for studying short-lived radical species that are often beyond the reach of the conventional electron paramagnetic resonance spectroscopy.     

Ligand self-assembling through complementary hydrogen-bonding in the coordination sphere of a transition metal center: the 6-diphenylphosphanylpyridin-2(1H)-one system

Motivated by previous findings which had shown that transition metal catalysts based on the 6-diphenylphosphanylpyridone ligand (6-DPPon, 2) display properties as a self-assembling bidentate ligand-metal complex, we have performed a thorough study on the bonding situation of this ligand, alone and in the coordination sphere of a late transition metal. Thus, combining a number of spectroscopic methods (UV-vis, IR, NMR, X-ray), we gained insights into the unique structural characteristics of 2. These experimental studies were corroborated by DFT calculations, which were in all cases in good agreement with the experimental results. The free ligand 2 prefers to exist as the pyridone tautomer 2A and dimerizes to the pyridone-pyridone dimer 4A in solution as well as in the crystal state. The corresponding hydroxypyridine tautomer 2B is energetically slightly disfavored (ca. 0.9 kcal/mol within the up-conformer relevant for metal coordination); hence, hydrogen bond formation within the complex may easily compensate this small energy penalty. Coordination properties of 2 were studied in the coordination sphere of a platinum(II) center. As a model complex, [Cl(2)Pt(6-DPPon)(2)] (11) was prepared and investigated. All experimental and theoretical methods used prove the existence of a hydrogen-bonding interligand network in solution as well as in the crystal state of 11 between one 6-DPPon ligand existing as the pyridone tautomer 2A and the other ligand occupying the complementary hydroxypyridine form 2B. Dynamic proton NMR allowed to determine the barrier for interligand hydrogen bond breaking and, in combination with theory, enabled us to determine the enthalpic stabilization through hydrogen-bonding to contribute 14-15 kcal/mol.     

Supramolecular adducts of mesocyclic diamines with various carboxylic acids: Charge-assisted hydrogen-bonding in molecular recognition

Aggregation of saturated mesocyclic diamine 1,4-diazacycloheptane (dach) or piperazine (pipz) and diversiform carboxylic acids with mono- or di-carboxyls yields a series of novel binary supramolecular adducts via two-point molecular recognition. All the supramolecular assemblies were obtained by solvent evaporation method from different media. X-ray single-crystal diffraction analyses reveal that these supramolecular moieties present 1D chain motif, 2D flat, corrugated sheet structures and 3D CdSO₄, pillar-layered networks through carboxylate-amide N–H⋯O, as well as its proton transfer form N⁺–H⋯O⁻, carboxyl head to tail O–H⋯O, and extended hydrogen-bonding interactions. Their compositions and structures were also confirmed by Fourier transform infrared (FT-IR) spectroscopy. Thermal stability of these binary crystalline adducts has been investigated by thermogravimetric analysis (TGA), suggesting similar thermal stabilities.     

Molecular recognition of mono- and disaccharides through interaction with p-iodophenylboronic acid in capillary electrophoresis with a chemiluminescence detection system

Molecular recognition of mono- and disaccharides was performed making use of the interaction between their diol groups and p-iodophenylboronic acid in capillary electrophoresis (CE) with a chemiluminescence (CL) detection system. p-Iodophenylboronic acid acted as an enhancer for luminol-horseradish peroxidase-hydrogen peroxide CL reaction. p-Iodophenylboronic acid was injected as a sample into the present system to give a CL peak on the electropherogram. The CL intensities were examined using running buffers including mono- and disaccharides. The CL intensities with 1-methyl-D-glucoside, D-saccharose, D-maltose, D-glucose, and D-fructose decreased in this order. The decrease in CL intensity was based on the formation by p-iodophenylboronic acid of cyclic esters with mono- and disaccharides, particularly with those including cis-diol groups. That is, the decrease in CL intensity affected the specific complexation between p-iodophenylboronic acids and saccharides, leading to the molecular recognition of saccharides. We also report separation of a mixture of p-iodophenol and p-iodophenylboronic acid as well as estimation of the apparent binding constant between p-iodophenylboronic acid and saccharides taking advantage of their molecular recognition behavior.     

Microfluidic chip-based cell electrophoresis with multipoint laser-induced fluorescence detection system

In this work, the electrophoretic mobility (EPM) measurement of individual cells was investigated by a simple on-chip electrophoresis system with LIF multipoint detection. The system enabled the characterization of cell electrophoresis behavior as well as the fluorescence signal from individual cells simultaneously. The measurement yielded the electropherograms of a large number of cells labeled with dye, in which the migration time and migration distance could be obtained easily. The EPM has been demonstrated to be different between the K562 cells and K562 cells treated with anticancer drug arsenic trioxide (As2O3). The K562 cells were found to exhibit a lower EPM compared to the cells after drug addition with different concentration. In this preliminary study, over 300 cells could be analyzed within 2 h, demonstrated a much higher analysis throughput compared with traditional methods. The established system is simple and fast, which is expected to be a promising method for evaluating cell surface properties and to be useful in clinical and pharmaceutical applications.     

Intermolecular interactions in heteromolecular crystals of tetrazine derivatives with azoles

Heteromolecular crystal structures formed by symmetrically and unsymmetrically 3,6-disubstituted tetrazine derivatives with NH donor azoles are investigated. The main crystal motifs and the intermolecular interactions responsible for their formation are identified.