Agnieszka Adamczyk-Woźniak

Lewis acidity and sugar receptor activity of 3-amino-substituted benzoxaboroles and their ortho-aminomethylphenylboronic acid analogues

The pKas as well as apparent binding constants of several 3-amino-substituted benzoxaboroles with alizarin red S (ARS) and some biologically important sugars have been evaluated and compared with that of the parent aminomethylphenylboronic acids. The investigated benzoxaboroles reveal lower acidity than the corresponding boronic acids. All the studied boronic compounds display the usual order of apparent binding constant values with glucose, galactose and fructose. The X-ray structure of the model catechol ester of the morpholinylmethylphenylboronic acid has been determined. The molecules are monomeric zwitterions with a tetracoordinated boron atom. The intermolecular interactions have been described with the aid of the Hirshfeld surface analysis.

Influence of the substituents on the structure and properties of benzoxaboroles.

Benzoxaboroles possessing aryl substituents in the oxaborole ring were synthesized, and their structures were determined by single-crystal X-ray diffraction. Structures in the solid state are centrosymmetric dimers with two intermolecular hydrogen bonds. These compounds were investigated using a combination of the spectroscopic and the computational approach, comparing their properties with the unsubstituted compound. Investigated compounds were characterized by (1)H, (13)C, and (11)B NMR spectroscopy in solution. Assignment of (1)H and (13)C signals was made on the basis of HSQC and HMBC spectra. The molecular structure of 1,3-dihydro-1-hydroxy-3-phenyl-2,1-benzoxaborole was calculated by the density functional (B3LYP) method with the extended 6-311++G(d,p) basis set. The calculated geometrical parameters were compared with experimental X-ray data, and the differences between experimental and calculated values were found to be of the order of experiment standard deviation, confirming a good description by this level of theory. The harmonic frequencies, potential energy distribution (PED), and IR intensities of this compound and its deuterated analogue were calculated with the B3LYP method. The assignment of the experimental spectra was made on the basis of the calculated PED. The consequence of dimer formation is the splitting of the vibrational modes into symmetric and antisymmetric vibrations. The structure modification resulting from the hydrogen bonded dimers formation is presented.

Amination-reduction reaction as simple protocol for potential boronic molecular receptors. Insight in supramolecular structure directed by weak interactions

The synthesis of the potential molecular receptors in the amination-reduction reaction has been investigated within the model system comprising (2-formylphenyl)boronic acid and morpholine. The 3-amine substituted benzoxaborole was identified to be the intermediate of the synthesis and the unsubstituted benzoxaborole as the by-product resulting from reduction of the starting material. The insight into the reactivity of the starting materials as well as the intermediate benzoxaborole enabled significant rise in the yield of 2-(aminomethyl) phenylboronic acids synthesis. The solid state structure of 2-(piperidylmethyl)phenylboronic acid has been re-determined, and the description of the molecule and the crystal is given. The supramolecular layer structure directed by the weak C-H…O and C-H…π interactions was identified and scrutinized based on the geometry and Hirshfeld surface analyses

Organoboron compounds as Lewis acid receptors of fluoride ions in polymeric membranes

Newly synthesized organoboron compounds - 4-octyloxyphenylboronic acid (OPBA) and pinacol ester of 2,4,6-trifluorophenylboronic acid (PE-PBA) - were applied as Lewis acid receptors of fluoride anions. Despite enhanced selectivity, the polymer membrane electrodes containing the lipophilic receptor OPBA exhibited non-Nernstian slopes of the responses toward fluoride ions in acidic conditions. Such behavior was explained by the lability of the B-O bond in the boronic acids, and the OH(-)/F(-) exchange at higher fluoride content in the sample solution. In consequence, the stoichiometry of the OPBA-fluoride complexes in the membrane could vary during the calibration, changing the equilibrium concentration of the primary anion in membrane and providing super-Nernstian responses. The proposed mechanism was supported by (19)F NMR studies, which indicated that the fluoride complexation proceeds more effectively in acidic solution leading mainly to PhBF(3)(-) species. Finally, the performances of the membranes based on the phenylboronic acid pinacol ester, with a more stable B-O bond, were tested. As it was expected, Nernstian fluoride responses were recorded for such membranes with worsened fluoride selectivity.

Glucose-Responsive Hybrid Nanoassemblies in Aqueous Solutions: Ordered Phenylboronic Acid within Intermixed Poly(4-hydroxystyrene)-block-poly(ethylene oxide) Block Copolymer.

Coassembly behavior of the double hydrophilic block copolymer poly(4-hydroxystyrene)-block-poly(ethylene oxide) (PHOS-PEO) with three amphiphilic phenylboronic acids (PBA) differing in hydrophobicity, 4-dodecyloxyphenylboronic acid (C12), 4-octyloxyphenylboronic acid (C8), and 4-isobutoxyphenylboronic acid (i-Bu) was studied in alkaline aqueous solutions and in mixtures of NaOHaq/THF by spin-echo (1)H NMR spectroscopy, dynamic and electrophoretic light scattering, and SAXS. The study reveals that only the coassembly of C12 with PHOS-PEO provides spherical nanoparticles with intermixed PHOS and PEO blocks, containing densely packed C12 micelles. NMR measurements have shown that spatial proximity of PHOS-PEO and C12 leads to the formation of ester bonds between -OH of PHOS block and hydroxyl groups of -B(OH)2. Due to the presence of PBA moieties, the release of compounds with 1,2- or 1,3-dihydroxy groups loaded in the coassembled PHOS-PEO/PBA nanoparticles by covalent binding to PBA can be triggered by addition of a surplus of glucose that bind to PBA competitively. The latter feature has been confirmed by fluorescence measurements using Alizarin Red as a model compound. Nanoparticles were proved to exhibit swelling in response to glucose as detected by light scattering.

5-Fluoro-1,3-dihydro-2,1-benzoxaborol-1-ol.

In the crystal structure of the title compound, C7H6BFO2, a broad-spectrum antifungal drug (AN2690), the planar [maximum deviation 0.035 (1) Å] molecules form centrosymmetric R 2 2(8) dimers via strong O—H⋯O hydrogen bonds. The dimers are arranged into layers by weak intermolecular C—H⋯O and C—H⋯F hydrogen bonds. The symmetry of this two-dimensional supramolecular assembly can be described by the layer group p and topologically classified as a simple uninodal four-connected two-dimensional network of a (4.4.4.4.6.6) topology. Further weak C—H⋯O interactions build up the three-dimensional structure.

The influence of fluorine position on the properties of fluorobenzoxaboroles.

5-Fluoro-2,1-benzoxaborol-1(3H)-ol, a potent antifungal drug also known as Tavaborole or AN2690, has been compared with its three isomers in terms of its activity against several fungi as well as pKa and multinuclear NMR characterization. The molecular and crystal structure of 6-fluoro-2,1-benzoxaborol-1(3H)-ol was determined and compared with that of AN2690.

Piperazine derivatives of boronic acids – potential bifunctional biologically active compounds

The combination of a piperazine and boronic groups within one molecule can result in a totally novel biological activity. A series of benzyl piperazine derivatives of boronic acids have been obtained by the facile and effective method based on the amination-reduction reaction of 2-formylphenylboronic acid with N-substituted piperazines. The molecular and crystal structures of six novel derivatives have been investigated, along with Hirshfeld surface analysis and hydrogen bond energy estimation. The studied compounds display several structural features that make them promising candidates as biologically active compounds.

Influence of fluorine substituents on the properties of phenylboronic compounds

Abstract Rapid development of research on the chemistry of boronic acids is connected with their applications in organic synthesis, analytical chemistry, materials’ chemistry, biology and medicine. In many applications Lewis acidity of boron atoms plays an important role. Special group of arylboronic acids are fluoro-substituted compounds, in which the electron withdrawing character of fluorine atoms influences their properties. The present paper deals with fluoro-substituted boronic acids and their derivatives: esters, benzoxaboroles and boroxines. Properties of these compounds, i.e. acidity, hydrolytic stability, structures in crystals and in solution as well as spectroscopic properties are discussed. In the next part examples of important applications are given.

Spectroscopic insight into supramolecular assemblies of boric acid derivatives and β-cyclodextrin

Interactions of select boric acid derivatives with β-cyclodextrin were investigated. All products were obtained employing the grinding-induced mechanochemical approach. It was found that phenylboronic acid, benzoxaborole and boric acid form non-covalent, hydrogen bonding-based systems with β-cyclodextrin, whereas catechol and pinacol esters of phenylboronic acid as well as ferroceneboronic acid form host-guest inclusion complexes. The interactions were probed using spectroscopic methods: 1H NMR, 1H-1H ROESY NMR, 1H DOSY NMR, FT-IR. Association constant values were evaluated by 1H DOSY NMR. The highest association constant was found for boric acid (117.5 ± 2.5 M-1), whilst the lowest for benzoxaborole (14.8 ± 0.3 M-1). The study shows the influence of boron compound structure on the nature of the assembly formed with β-cyclodextrin, laying up the basis for future work with such supramolecular systems.