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2-Formylphenylboronic acids display many interesting features, not only from synthetic but also from an application as well as structural points of view. 5-Trifluoromethyl-2-formyl phenylboronic acid has been synthesized and characterized in terms of its structure and properties. The presence of an electron-withdrawing substituent results in a considerable rise in the acidity in comparison with its analogues. In some solutions, the title compound isomerizes with formation of the corresponding 3-hydroxybenzoxaborole. Taking into account the probable mechanism of antifungal action of benzoxaboroles, which blocks the cytoplasmic leucyl-tRNA synthetase (LeuRS) of the microorganism, docking studies with the active site of the enzymes have been carried out. It showed possible binding of the cyclic isomer into the binding pocket of Candida albicans LeuRS, similar to that of the recently approved benzoxaborole antifungal drug (AN2690, Tavaborole, Kerydin). In case of Escherichia coli LeuRS, the opened isomer displays a much higher inhibition constant in comparison with the cyclic one. The antimicrobial activity of the title compound was also investigated in vitro, showing moderate action against Candida albicans. The compound reveals higher activity against Aspergillus niger as well as bacteria such as Escherichia coli and Bacillus cereus. In case of Bacillus cereus, the determined Minimum Inhibitory Concentration (MIC) value is lower than that of AN2690 (Tavaborole). The results confirm potential of 2-formylphenylboronic acids as antibacterial agents and give a hint of their possible mechanism of action.

Benzoxaboroles emerged recently as molecules of high medicinal potential with Kerydin® (Tavaborole) and Eucrisa® (Crisaborole) currently in clinical practice as antifungal and anti-inflammatory drugs, respectively. Over a dozen of 3-amino benzoxaboroles, including Tavaborole’s derivatives, have been synthetized and characterized in terms of their activity against Candida albicans as a model pathogenic fungus. The studied compounds broaden considerably the structural diversity of reported benzoxaboroles, enabling determination of the influence of the introduction of a heterocyclic amine, a fluorine substituent as well as the formyl group on antifungal activity of those compounds. The determined zones of the growth inhibition of examined microorganism indicate high diffusion of majority of the studied compounds within the applied media as well as their reasonable activity. The Minimum Inhibitory Concentration (MIC) values show that the introduction of an amine substituent in position “3” of the benzoxaborole heterocyclic ring results in a considerable drop in activity in comparison with Tavaborole (AN2690) as well as unsubstituted benzoxaborole (AN2679). In all studied cases the presence of a fluorine substituent at position para to the boron atom results in lower MIC values (higher activity). Interestingly, introduction of a fluorine substituent in the more distant piperazine phenyl ring does not influence MIC values. As determined by X-ray studies, introduction of a formyl group in proximity of the boron atom results in a considerable change of the boronic group geometry. The presence of a formyl group next to the benzoxaborole unit is also detrimental for activity against Candida albicans.

Isomeric isobutoxy phenylboronic acids (ortho-, meta-, para-) were synthesized and their properties such as pK a and thermal stability have been compared. Molecular and crystal structures of the para isomer were determined by single crystal XRD methods. DSC and TGA measurements have been Scheme 1. Formation of boroxines on dehydration of phenylboronic acids.[a]

(13)C nuclear spin relaxation processes in seven cyclodextrins (from six-membered alpha to twelve-membered eta) were investigated in (2)H(2)O solution at multiple magnetic fields. Detailed analysis of (13)C longitudinal relaxation in laboratory and rotating frames and (13)C{(1)H} nuclear Overhauser enhancement in these molecules yielded their rotational diffusion tensors and a semiquantitative picture of their internal dynamics.

Three isomers of (trifluoromethoxy)phenylboronic acids were studied in the context of their physicochemical, structural, antimicrobial and spectroscopic properties. They were characterized by 1H, 13C, 11B and 19F NMR spectroscopy. The acidity of all the isomers was evaluated by both spectrophotometric and potentiometric titrations. The introduction of the -OCF3 group influences the acidity, depending, however, on the position of a substituent, with the ortho isomer being the least acidic. Molecular and crystal structures of ortho and para isomers were determined by the single crystal XRD method. Hydrogen bonded dimers are the basic structural motives of the investigated molecules in the solid state. In the case of the ortho isomer, intramolecular hydrogen bond with the -OCF3 group is additionally formed, weaker, however, than that in the analogous -OCH3 derivative, which has been determined by both X-Ray measurements as well as theoretical DFT calculations. Docking studies showed possible interactions of the investigated compounds with LeuRS of Escherichia coli. Finally, the antibacterial potency of studied boronic acids in vitro were evaluated against Escherichia coli and Bacillus cereus.

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