Pattern-based recognition for the rapid determination of identity, concentration, and enantiomeric excess of subtly different threo diols.

A pattern-based recognition approach for the rapid determination of the identity, concentration, and enantiomeric excess of chiral vicinal diols, specifically threo diols, has been developed. A diverse enantioselective sensor array was generated using three chiral boronic acid receptors and three pH indicators. The optical response produced by the sensor array was analyzed by two pattern-recognition algorithms: principal component analysis and artificial neural networks. Principal component analysis demonstrated good chemoselective and enantioselective separation of the analytes, and an artificial neural network was used to accurately determine the concentrations and enantiomeric excesses of five unknown samples with an average absolute error of +/-0.08 mM in concentration and 3.6% in enantiomeric excess. The speed of the analysis was enhanced by using a 96-well plate format, portending applications in high-throughput screening for asymmetric-catalyst discovery. X-ray crystallography and (11)B NMR spectroscopy was utilized to study the enantioselective nature of the boronic acid host 2.

Probing intramolecular B-N interactions in ortho-aminomethyl arylboronic acids.

This work investigates the interplay between the intramolecular B-N dative bonding and solvent insertion in various ortho-methylamino arylboronic acids in protic media. (11)B NMR experiments were conducted to study the effect that the degree of substitution of the amine group has on B-N bonding versus solvent insertion. It was found that there is a slight increase in the amount of B-N dative bonding on going from a tertiary to a secondary to a primary amine group, but that solvent insertion dominates in all cases of the boronate esters. A X-ray crystal structure gives further insight into the structure of the solvent-inserted boronate esters, showing that the inserted solvent has its hydrogen primarily on the amine. Lastly, studies of the use of boronate esters as receptors for simple alcohols and carboxylic acids are described.

Structural characterization of a rigidified threading bisintercalator.

NMR spectroscopy was used to explore the sequence-specific interaction of DNA with a new threading bisintercalator (C1) consisting of two intercalating 1,4,5,8-naphthalenetetracarboxylic diimide (NDI) units connected by a rigid, tricyclic spiro linker. A structural model of C1 complexed to d(CGGTACCG)(2) was calculated using distance constraints obtained from solution NMR data. The model was also supported by the results from residual dipolar coupling (RDC) measurements obtained using Pf1-phage as a cosolvent. According to the model, the central cyclohexane ring of the linker connecting the two NDI units lies flat in the minor groove of DNA. Linker length, hydrogen bonding, steric, and hydrophobic factors all appear to contribute to the observed sequence specificity of binding. These results serve to illustrate the versatility of threading polyintercalation given that, in a previous study, a ligand consisiting of two NDI units joined by a flexible peptide linker was shown to bind sequence specifically within the major groove of this same sequence of DNA.

A structural investigation of the N-B interaction in an o-(N,N-dialkylaminomethyl)arylboronate system.

o-(Pyrrolidinylmethyl)phenylboronic acid (4) and its complexes with bifunctional substrates such as catechol, alpha-hydroxyisobutyric acid, and hydrobenzoin have been studied in detail by X-ray crystallography, (11)B NMR, and computational analysis. The N-B interactions in analogous boronic acids and esters have been extensively cited in molecular recognition and chemosensing literature. The focal point of this study was to determine the factors that are pertinent to the formation of an intramolecular N-B dative bond. Our structural study predicts that the formation of an N-B dative bond, and/or solvent insertion to afford a tetrahedral boronate anion, depends on the solvent and the complexing substrate present. Specifically, from (11)B NMR studies, complexation of 4 with electron-withdrawing and/or vicinally bifunctionalized substrates promotes both the formation of N-B dative bonds and the solvation of sp(2) boron to a tetrahedral sp(3) boronate. In the solid state, the presence of an N-B dative bond in the complex of 4 and catechol (7) depends on the solvent from which it crystallizes. From chloroform, an N-B bond was observed, whereas from methanol, a methoxylated boronate was formed, where the methoxy group is hydrogen-bonded with the neighboring tertiary ammonium ion. The structural optimization of compounds 4 and 7 using density functional theory in a simulated water continuum also predicts that complexation of 4 and catechol promotes either the formation of an N-B bond or solvolysis if 1 equiv of water is present. The conclusion from this study will help in the design of future chemosensing technologies based on o-(N,N-dialkylaminomethyl)arylboronate scaffolds that are targeting physiologically important substances such as saccharides, alpha-hydroxycarboxylates, and catecholamines.

Altering the folding patterns of naphthyl trimers.

Proteins can adopt helical and sheet-type secondary structures that depend on their primary sequence of amino acids. Nonnatural foldamers have been developed to emulate these protein structures as well as investigate various types of noncovalent interactions. Here we report a strategy to access two distinct folding topologies in aqueous solutions using the inherent recognition properties of aromatic donor/acceptor interactions. These oligomers are constructed of electron-rich 1,5-dialkoxynaphthalene (Dan) and electron-deficient 1,4,5,8-naphthalenetetracarboxylic diimide (Ndi) units. A trimer of the sequence Dan-Ndi-Dan was shown to adopt a pleated fold in solution, while its constitutional isomer, Dan-Dan-Ndi, adopted an intercalative or turn-type fold. UV-vis and NOESY spectroscopy analyses were consistent with the two different conformations. This study illustrates the designability of folding naphthyl oligomers and encourages the use of directed aromatic interactions to construct larger and more complex assemblies in water.

NMR structural analysis of a modular threading tetraintercalator bound to DNA.

The synthesis and NMR structural studies are reported for a modular threading tetraintercalator bound to DNA. The tetraintercalator design is based on 1,4,5,8-tetracarboxylic naphthalene diimide units connected through flexible peptide linkers. Aided by an overall C(2) symmetry, NMR analysis verified a threading polyintercalation mode of binding, with linkers alternating in the order minor groove, major groove, minor groove, analogous to how a snake might climb a ladder. This study represents the first NMR analysis of a threading tetraintercalator and, as such, structurally characterizes a new topology for molecules that bind to relatively long DNA sequences with extensive access to both DNA grooves.

Changing DNA grooves--a 1,4,5,8-naphthalene tetracarboxylic diimide bis-intercalator with the linker (beta-Ala)(3)-Lys in the minor groove.

We have been investigating a modular, threading DNA polyintercalator design based upon the 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) intercalating unit. Previously, we have reported the NMR analysis of a bis-intercalator-DNA complex in which the peptide linker between NDI units was found to occupy the DNA major groove (Guelev, Lee, Sorey, Hoffman, Iverson, Chem. Biol. 2001, 8, 415-425). Here we describe the NMR analysis of a complex between a related bis-intercalator known to display altered DNA sequence specificity. In this case, the linker resides in the DNA minor groove. We have thus shown that within this set of sequence specific bis-intercalators, both DNA grooves can be accessed, setting the stage for longer threading polyintercalators designed to have linkers occupying both grooves in an alternating fashion.