Aromatic Diboronic Acids as Effective KPC/AmpC Inhibitors.

Over 30 compounds, including para-, meta-, and ortho-phenylenediboronic acids, ortho-substituted phenylboronic acids, benzenetriboronic acids, di- and triboronated thiophenes, and pyridine derivatives were investigated as potential ß-lactamase inhibitors. The highest activity against KPC-type carbapenemases was found for ortho-phenylenediboronic acid 3a, which at the concentration of 8/4 mg/L reduced carbapenems' MICs up to 16/8-fold, respectively. Checkerboard assays revealed strong synergy between carbapenems and 3a with the fractional inhibitory concentrations indices of 0.1-0.32. The nitrocefin hydrolysis test and the whole cell assay with E. coli DH5α transformant carrying blaKPC-3 proved KPC enzyme being its molecular target. para-Phenylenediboronic acids efficiently potentiated carbapenems against KPC-producers and ceftazidime against AmpC-producers, whereas meta-phenylenediboronic acids enhanced only ceftazidime activity against the latter ones. Finally, the statistical analysis confirmed that ortho-phenylenediboronic acids act synergistically with carbapenems significantly stronger than other groups. Since the obtained phenylenediboronic compounds are not toxic to MRC-5 human fibroblasts at the tested concentrations, they can be considered promising scaffolds for the future development of novel KPC/AmpC inhibitors. The complexation of KPC-2 with the most representative isomeric phenylenediboronic acids 1a, 2a, and 3a was modeled by quantum mechanics/molecular mechanics calculations. Compound 3a reached the most effective configuration enabling covalent binding to the catalytic Ser70 residue.

TADF Invariant of Host Polarity and Ultralong Fluorescence Lifetimes in a Donor-Acceptor Emitter Featuring a Hybrid Sulfone-Triarylboron Acceptor.

10H-Dibenzo[b,e][1,4]thiaborinine 5,5-dioxide (SO2B)-a high triplet (T1 =3.05 eV) strongly electron-accepting boracycle was successfully utilised in thermally activated delayed fluorescence (TADF) emitters PXZ-Dipp-SO2B and CZ-Dipp-SO2B. We demonstrate the near-complete separation of highest occupied and lowest unoccupied molecular orbitals leading to a low oscillator strength of the S1 →S0 CT transition, resulting in very long ca. 83 ns and 400 ns prompt fluorescence lifetimes for CZ-Dipp-SO2B and PXZ-Dipp-SO2B, respectively, but retaining near unity photoluminescence quantum yield. OLEDs using CZ-Dipp-SO2B as the luminescent dopant display high external quantum efficiency (EQE) of 23.3 % and maximum luminance of 18600 cd m-2 with low efficiency roll off at high brightness. For CZ-Dipp-SO2B, reverse intersystem crossing (rISC) is mediated through the vibronic coupling of two charge transfer (CT) states, without involving the triplet local excited state (3 LE), resulting in remarkable rISC rate invariance to environmental polarity and polarisability whilst giving high organic light-emitting diode (OLED) efficiency. This new form of rISC allows stable OLED performance to be achieved in different host environments.

Expedient Synthesis of Oxaboracyclic Compounds Based on Naphthalene and Biphenyl Backbone and Phase-Dependent Luminescence of their Chelate Complexes.

The approach to a series of six- and seven-membered oxaboraheterocycles based on naphthalene or biphenyl backbones was developed. The key synthetic step involved Br/Li exchange in respective potassium (bromoaryl)trifluoroborates followed by quenching with selected electrophiles (CO2 , DMF, Me2 Si(H)Cl) and hydrolytic workup. Two ring-expanded benzoxaborole congeners were obtained by an additional reduction step with LiAlH4 or NaBH4 . The obtained boracyclic compounds were characterized in detail by NMR spectroscopy and single-crystal X-ray diffraction. Specifically, biphenyl-based systems show dynamic behaviour interpreted in terms of inversion of non-planar seven-membered boraheterocycles. The acidity of the obtained compounds varies very strongly (pKa ranges from 3.1-9.6) depending on their structure. Due to the enhanced boron Lewis acidity, selected compounds were used as a basis for luminescent complexes with 8-hydroxyquinoline. A strong phase-dependent variation of emission-band maximum (480-527 nm) and photoluminescence quantum yield (10-95 %) was observed, which was rationalized in terms of specific aggregation effects.

Heteroelement Analogues of Benzoxaborole and Related Ring Expanded Systems.

The review covers the chemistry of organoboron heterocycles structurally related to benzoxaboroles where one of the carbon atoms in a boracycle or a fused benzene ring is replaced by a heteroelement such as boron, silicon, tin, nitrogen, phosphorus, or iodine. Related ring expanded systems including those based on naphthalene and biphenyl cores are also described. The information on synthetic methodology as well as the basic structural and physicochemical characteristics of these emerging heterocycles is complemented by a presentation of their potential applications in organic synthesis and medicinal chemistry, the latter aspect being mostly focused on the promising antimicrobial activity of selected compounds.

Boronate Covalent and Hybrid Organic Frameworks Featuring PIII and P=O Lewis Base Sites.

Invited for the cover of this issue is Sergiusz Lulinski and his co-workers from Warsaw University of Technology and University of Warsaw. The image depicts a journey through the interior of the porous Covalent Organic Framework containing phosphorus and boron centres with carbon dioxygen trapped inside an imagined cave. Read the full text of the article at 10.1002/chem.202001960.

Boronate Covalent and Hybrid Organic Frameworks Featuring PIII and P=O Lewis Base Sites.

Two covalent organic frameworks comprising Lewis basic PIII centers and Lewis acidic boron atoms were prepared by poly-condensation reactions of newly obtained tris(4-diisopropoxyborylphenyl)phosphine with 2,3,6,7,10,11-hexahydroxytriphenylene and 2,3,6,7-tetrahydroxy-9,10-dimethylanthracene. Obtained materials exhibit significant sorption of dihydrogen (100 cm3 g-1 at 1 bar at 77 K), methane (20 cm3 g-1 at 1 bar at 273 K) and carbon dioxide (50 cm3 g-1 at 1 bar at 273 K). They were exploited as solid-state ligands for coordination of Pd0 centers. Alternatively, in a bottom-up approach, boronated phosphine was treated with Pd2 dba3 and poly-condensated, yielding hybrid materials where the polymer networks are formed by means of covalent boronate linkages and coordination P-Pd bonds. In addition, the analogous materials based on phosphine oxide were synthesized. The DFT calculations on framework-guest interactions revealed that the behavior of adjacent boron and phosphorus/phosphine oxide centers is reminiscent of that found in Frustrated Lewis Pairs and may improve sorption of selected molecules.

Differential Sensing of Saccharides Based on an Array of Fluorinated Benzosiloxaborole Receptors.

Fluorinated benzosiloxaboroles-silicon congeners of benzoxaboroles, were synthesized and tested as molecular receptors for mono- and disaccharides. The receptors differed in the Lewis acidity of the boron center as well as in the number of potential binding sites. The calculated stability constants indicated different binding affinity of benzosiloxaborole derivatives towards selected saccharides, enabling their classification using a receptor array-based sensing. Unique fluorescence fingerprints were created on the basis of competitive interactions of the studied receptors with both Alizarin Red S (ARS) and tested saccharide molecules. Detailed chemometric analysis of the obtained fluorescence data (based on partial least squares-discriminant analysis and hierarchical clustering analysis) provided the differential sensing of common saccharides, in particular the differentiation between glucose and fructose. In addition, DFT calculations were carried out to shed light on the binding mechanism under different pH conditions.

Experimental and Theoretical Insights into Molecular and Solid-State Properties of Isomeric Bis(salicylaldehydes).

A series of five bis(salicylaldehydes), including four isomeric compounds based on a benzene scaffold and a closely related naphthalene derivative, were investigated in order to elucidate the impact of resonance effects and intramolecular hydrogen bonds (HBs) on the macroscopic properties of these systems. Density functional theory (DFT) computations revealed important differences between isomers on the molecular level, which was reflected in different charge distributions, aromatic C-C bond orders, and aromaticity characters. The consequences of these features were evidenced by the UV-vis absorption spectra: for 1,3-diformyl-4,6-dihydroxybenzene (2), the longest wavelength absorption band is observed at 285 nm, while its isomers 1,4-diformyl-2,5-dihydroxybenzene (1), 1,4-diformyl-2,3-dihydroxybenzene (3), and 1,2-diformyl-3,6-dihydroxybenzene (4) are characterized by absorption in the visible range (379-407 nm). The specificity of 2 results from simultaneous lowering and elevation of HOMO and LUMO energy levels, respectively. We have found that the HOMO/LUMO energy variations follow trends observed in isomeric dihydroxybenzenes (HOMO) and phthalaldehydes (LUMO), and these effects operate separately to some extent. Furthermore, theoretical calculations indicate that the UV-vis spectral properties of bis(salicylaldehydes) are directly transferable to the corresponding bis(salicylaldimines) and their boron complexes. Finally, the influence of structural and molecular stabilization effects was analyzed by means of X-ray structural analysis and periodic DFT computations.

Highly Fluorescent Red-Light Emitting Bis(boranils) Based on Naphthalene Backbone.

Ten bis(boranils) differently substituted at the boron atom and iminophenyl groups were synthesized from 1,5-dihydroxynaphthalene-2,6-dicarboxaldehyde using a simple one-pot protocol. Their photophysical properties can be easily tuned in a wide range by the variation of substituents. Their absorption and emission spectral bands are significantly red-shifted (λmax = 495-590 nm, λem = 533-683 nm) when compared with simple boranils, whereas fluorescence quantum yields are strongly improved to reach 83%. The attachment of pendant NO2 and NEt2 groups at the opposite positions of the π-conjugated bis(boranil) scaffold resulted in the formation of an unprecedented system featuring push-pull architecture.

Tuning of the colour and chemical stability of model boranils: a strong effect of structural modifications.

A series of diarylborinic complexes with salicydeneaniline ligands bearing various functional groups at the 6-position have been synthesized in high yields by applying a straightforward one-pot multicomponent protocol. UV-Vis measurements revealed the influence of electronic character of substituents on the observed maximum of emission (λem). This has been confirmed by a relatively strong linear correlation (R(2) = 0.92) of λem with Hammett σp(+) constants. Such a correlation was investigated using a QTAIM analysis of the charge density distribution. Absorption and emission bands for the obtained systems span between 390-437 nm and between 506-590 nm, respectively, with quantum yields reaching 17%. Time-dependent UV-Vis absorption measurements revealed that diphenylborinic salicydeneaniline complexes undergo slow degradation in solution under ambient conditions. In contrast, the use of a naphthalene-based chromophore or the introduction of fluorinated phenyl groups at the boron atom resulted in stable systems.

Charge transfer properties of two polymorphs of luminescent (2-fluoro-3-pyridyl)(2,2'-biphenyl)borinic 8-oxyquinolinate.

Single crystal X-ray structures of two polymorphs of (2-fluoro-3-pyridyl)(2,2'-biphenyl)borinic 8-oxyquinolinate: orthorhombic (space group Pca21), and triclinic (space group P1̄) have been established and analysed. A fast rate of crystallization results in the orthorhombic polymorph, whereas slow crystallization gives the triclinic polymorph. Physicochemical and theoretical results prove that both polymorphs form similar crystals with very similar geometry of molecules. The main differences between both forms are intermolecular interactions and their impact on the charge transporting properties of both polymorphs which was evaluated through Marcus theory. The orthorhombic polymorph is a slightly more effective electron and hole transporting material than the other polymorph. In both forms the CH···π interactions contributed the most to the CT properties. Small changes in the molecular geometry of moieties in both polymorphs affect their molecular energies significantly.

Exploiting thiol-functionalized benzosiloxaboroles for achieving diverse substitution patterns - synthesis, characterization and biological evaluation of promising antibacterial agents.

Benzosiloxaboroles are an emerging class of medicinal agents possessing promising antimicrobial activity. Herein, the expedient synthesis of two novel thiol-functionalized benzosiloxaboroles 1e and 2e is reported. The presence of the SH group allowed for diverse structural modifications involving the thiol-Michael addition, oxidation, as well as nucleophilic substitution giving rise to a series of 27 new benzosiloxaboroles containing various polar functional groups, e.g., carbonyl, ester, amide, imide, nitrile, sulfonyl and sulfonamide, and pendant heterocyclic rings. The activity of the obtained compounds against selected bacterial and yeast strains, including multidrug-resistant clinical strains, was investigated. Compounds 6, 12, 20 and 22-24 show high activity against Staphylococcus aureus, including both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains, with MIC values in the range of 1.56-12.5 µg mL-1, while their cytotoxicity is relatively low. The in vitro assay performed with 2-(phenylsulfonyl)ethylthio derivative 20 revealed that, in contrast to the majority of known antibacterial oxaboroles, the plausible mechanism of antibacterial action, involving inhibition of the leucyl-tRNA synthetase enzyme, is not responsible for the antibacterial activity. Structural bioinformatic analysis involving molecular dynamics simulations provided a possible explanation for this finding.

Heteroleptic (2-fluoro-3-pyridyl)arylborinic 8-oxyquinolinates for the potential application in organic light-emitting devices.

A one-pot protocol has been developed to obtain a series of luminescent heteroleptic diarylborinic complexes bearing the 2-fluoro-3-pyridyl and another aryl group attached to the boron atom chelated with a simple or functionalized 8-oxyquinolinato ligand. The tetrahedral geometry around the boron atom in all compounds has been established by the (11)B NMR spectroscopy and/or X-ray diffraction technique. In the solution, the obtained complexes have emission maxima ranging from 502 to 525 nm at room temperature. The quantum yield of emission significantly depends on the type and position of the substituents in the 8-oxyquinolinato ligands and aryl rings. An interpretation of the experimental UV-vis absorption and emission spectral data is supported by theoretical calculations of the frontier molecular orbitals. Marcus theory was used to theoretically evaluate charge-transport properties of the obtained complexes.

2-Meth-oxy-3-(tri-methyl-sil-yl)phenyl-boronic acid.

The mol-ecular structure of the title compound, C10H17BO3Si, features an intra-molecular O-H⋯O hydrogen bond; the boronic group group has an exo-endo conformation. In the crystal, the mol-ecules inter-act with each other by O-H⋯O hydrogen bonds, producing centrosymmetric dimers that are linked by weak π-π stacking inter-actions featuring specific short B⋯C contacts [e.g. 3.372 (2) Å], forming an infinite columnar structure aligned along the a-axis direction.

Highly electron-deficient 3,6-diaza-9-borafluorene scaffolds for the construction of luminescent chelate complexes.

The synthesis and characterization of two fluorinated 3,6-diaza-9-hydroxy-9-borafluorene oxonium acids featuring improved hydrolytic stability and the strong electron-deficient character of the diazaborafluorene core is reported. These boracycles served as precursors of fluorescent spiro-type complexes with (O,N)-chelating ligands which revealed specific properties such as delayed emission, white light emission in the solid state and photocatalytic performance in singlet oxygen-mediated oxidation reactions.

Design of a D3h-symmetry prismatic tris-(ferrocene-1,1'-diyl) molecular cage bearing boronate ester linkages.

This paper presents a simple, highly selective, and efficient (isolated yield of 68%) synthesis of a novel D3h-symmetry prismatic tris-(ferrocene-1,1'-diyl) organic cage (FcB-cage) by incorporating a boronate ester as a linkage motif. 1,1'-Diboronated derivatives of ferrocene and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) were used as the starting materials. The synthesized cage was comprehensively characterized by spectroscopic and microscopic methods, powder X-ray diffraction, thermogravimetry and voltammetry. Cyclic voltammetry analysis revealed the electronic communication between the ferrocene units of the FcB-cage. In addition, to better understand the mechanism behind the synthesis of such a cage, as well as its geometric properties, we performed DFT calculations.

Oxazoline scaffold in synthesis of benzosiloxaboroles and related ring-expanded heterocycles: diverse reactivity, structural peculiarities and antimicrobial activity.

Two isomeric benzosiloxaborole derivatives 3a and 5a bearing fluorine and 4,4-dimethyl-2-oxazolin-2-yl substituents attached to the aromatic rings were obtained. Both compounds were prone to hydrolytic cleavage of the oxazoline ring after initial protonation or methylation of the nitrogen atom. The derivative 3c featuring N-methylammoniumalkyl ester functionality was successfully subjected to N-sulfonylation and N-acylation reactions to give respective derivatives which demonstrates its potential for modular synthesis of structurally extended benzosiloxaboroles. Compound 5c bearing N-ammoniumalkyl ester underwent conversion to a unique macrocyclic dimer due to siloxaborole ring opening. Furthermore, an unexpected 4-electron reduction of the oxazoline ring occurred during an attempted synthesis of 5a. The reaction gave rise to an unprecedented 7-membered heterocyclic system 4a comprising a relatively stable B-O-B-O-Si linkage and stabilized by an intramolecular N-B coordination. It could be cleaved to derivative 4c bearing BOH and SiMe2OH groups which acts as a pseudo-diol as demonstrated by formation of an adduct with Tavaborole. Apart from the multinuclear NMR spectroscopy characterization, crystal structures of the obtained products were determined in many cases by X-ray diffraction. Investigation of biological activity of the obtained compounds revealed that derivatives 3e and 3f with pendant N-methyl arylsulfonamide groups exhibit high activity against Gram-positive cocci such as methicillin-sensitive Staphylococcus aureus ATCC 6538P, methicillin-resistant S. aureus (MRSA) ATCC 43300 as well as the MRSA clinical strains, with MIC values in the range of 3.12-6.25 mg L-1. These two compounds also showed activity against Enterococcus faecalis ATCC 29212 and Enterococcus faecium ATCC 6057 (with MICs of 25-50 mg L-1). The results of the antimicrobial activity and cytotoxicity studies indicate that 3e and 3f can be considered as potential antibacterial agents, especially against S. aureus MRSA.

(2,4-Dipropoxyphen-yl)boronic acid.

In the crystal, the title compound, C(12)H(19)BO(4), exists as a centrosymmetric O-H⋯O hydrogen-bonded dimer. Dimers are linked via C-H⋯O hydrogen bonds, generating an infinite zigzag chain oriented parallel to [1[Formula: see text]1]. The chains are assembled, giving sheets aligned parallel to (21[Formula: see text]) and inter-connected by weak C-H⋯π inter-actions, producing a three-dimensional network.

Ammonia-triphenyl-borane.

The asymmetric unit of the title compound, C(18)H(18)BN or (C(6)H(5))(3)B·NH(3), comprises two crystallographically independent but virtually identical mol-ecules. Mol-ecules of one type are linked with each other by N-H⋯π inter-actions, generating an infinite column aligned along the b-axis direction. The columns of different types of mol-ecules are inter-connected by C-H⋯π inter-actions, producing a three-dimensional array.

On the nature of the B...N interaction and the conformational flexibility of arylboronic azaesters.

It is shown that the structural and physicochemical properties of arylboronic azaesters result from the properties of the key B-N bond. This bond is different in arylboronic azaesters from typical single/double/triple B-N bonds present in other boron-nitrogen compounds. By studying a model example, 6-tert-butyl-2-(3',5'-difluorophenyl)-(N-B)-1,3,6,2-dioxazaborocane, it is proved that the molecule adopts the closed form in the solid state with the BN bond length equal to 1.7646(3) Å. This represents the longest B-N bond length for an arylboronic ester reported in literature. According to the results of experimental charge density studies and QTAIM analysis, the BN bond/contact shows good separation of the respective atomic basins and significant flexibility. The source function and NBO analyses indicate an evident involvement of the oxygen atoms in the creation of the B-N bonding. According to our DFT calculations the isolated model molecule exists in the open conformer. The constrained energy scans reveal an E(d(B-N)) potential energy surface which depends strongly on the nature of the substituents at the nitrogen and aromatic carbon atoms. It appears that an appropriate substitution can produce either conformer. A dipole moment analysis provides a good insight into the reactivity properties of the compound in solution. The opening of the azaester cage is associated with a breaking of the B-N bond, thus decreasing the magnitude of the dipole moment. The existence of the open conformer is confirmed by multi-temperature NMR studies. When decreasing the temperature of the measurements the (1)H and (11)B NMR spectra show features corresponding to the open form of the model arylboronic azaester.