Synthesis, Photophysical and Electronic Properties of a D-π-A Julolidine-like Pyrenyl-o-Carborane.

We synthesized 2-(1-1,2-dicarbadodecaboranyl(12))-6,6,12,12-tetramethyl-7,8,11,12-tetrahydro-6H,10H-phenaleno[1,9-fg]pyrido[3,2,1-ij]quinoline (4) a julolidine-like pyrenyl-o-carborane, with pyrene substituted at the 2,7-positions on the HOMO/LUMO nodal plane. Using solid state molecular structures, photophysical data, cyclic voltammetry, DFT and LR-TDDFT calculations, we compare o-carborane and B(mes)2 (mes = 2,4,6-Me3C6H2) as acceptor groups. Whereas the π-acceptor strength of B(mes)2 is sufficient to drop the pyrene LUMO+1 below the LUMO, the carborane does not do this. We confirm the π-donor strength of the julolidine-like moiety, however, which raises the pyrene HOMO-1 above the HOMO. In contrast to the analogous pyrene-2-yl-o-carborane, 2-(1-1,2-dicarbadodecaboranyl(12))-pyrene VI, which exhibits dual fluorescence, because the rate of internal conversion between locally-excited (LE) and charge transfer (CT) (from the pyrene to the carborane) states is faster than the radiative decay rate, leading to a thermodynamic equilibrium between the 2 states, 4 shows only single fluorescence, as the CT state involving the carborane as the acceptor moiety in not kinetically accessible, so a more localized CT emission involving the julolidine-like pyrene moiety is observed.

Phosphine-catalyzed 1,2-cis-diboration of 1,3-butadiynes.

Trialkyl phosphines PMe3 and PEt3 catalyze the 1,2-cis-diboration of 1,3-butadiynes to give 1,2-diboryl enynes. The products were utilized to synthesize 1,1,2,4-tetraaryl enynes using a Suzuki-Miyaura protocol and can readily undergo proto-deborylation.

Twisted [C2O5]2--groups in Ba[C2O5] pyrocarbonate.

The inorganic pyrocarbonate salt Ba[C2O5] contains twisted pyrocarbonate anions ([C2O5]2-), an atomic arrangement previously not observed in other pyrocarbonates. This unexpected additional structural degree of freedom points towards an enlarged chemical variability in this novel group of compounds. Ba[C2O5] was synthesized in a laser-heated diamond anvil cell at 30(2) GPa by heating a mixture of Ba[CO3] + CO2 to ≈ 1500(200) K. Its crystal structure was solved from single crystal synchrotron X-ray diffraction data and confirmed by density functional theory-based calculations. The two planar [CO3]2--groups of the [C2O5]2--anion are strongly twisted around the bridging oxygen atom. Ba[C2O5] has been observed in the pressure range of 5-30 GPa, where its symmetry is P6/m with Z = 12.

Photocatalyzed Borylcyclopropanation of Alkenes with a (Diborylmethyl)iodide Reagent.

Cyclopropane skeletons play a prominent role in the development of organic synthesis and pharmaceutical chemistry. Herein, we report the design and synthesis of a stable, multifunctional (diborylmethyl)iodide reagent (CHI(Bpin)2 ) for the photoinduced cyclopropanation of alkenes, providing an array of 1,2-substituted cyclopropylboronates in good yields. This α-haloboronic ester can be readily synthesized on a multigram scale from commercially available starting materials. Furthermore, the protocol displays high chemo- and diastereoselectivity, excellent functional-group tolerance, and allows for late-stage borylcyclopropanation of complex molecules. Mechanistic studies reveal that the borylcyclopropanation proceeds through a radical addition/polar cyclization pathway mediated by the photocatalyst fac-Ir(ppy)3 and visible light.

Regioselective Iridium-Catalyzed C8-H Borylation of 4-Quinolones via Transient O-Borylated Quinolines.

The quinolone-quinoline tautomerization is harnessed to effect the regioselective C8-borylation of biologically important 4-quinolones by using [Ir(OMe)(cod)]2 as the catalyst precursor, the silica-supported monodentate phosphine Si-SMAP as the ligand, and B2 pin2 as the boron source. Initially, O-borylation of the quinoline tautomer takes place. Critically, the newly formed 4-(pinBO)-quinolines then undergo N-directed selective Ir-catalyzed borylation at C8. Hydrolysis of the OBpin moiety on workup returns the system to the quinolone tautomer. The C8-borylated quinolines were converted to their corresponding potassium trifluoroborate (BF3 K) salts and to their C8-chlorinated quinolone derivatives. The two-step C-H borylation-chlorination reaction sequence resulted in various C8-Cl quinolones in good yields. Conversion to C8-OH-, C8-NH2 -, and C8-Ar-substituted quinolones was also feasible by using this methodology.

The Radical Anion and Dianion of Benzo[3,4]cyclobuta[1,2-b]phenazine.

We present the reduction of two azaacenes (a benzo-[3,4]cyclobuta[1,2-b]phenazine and a benzo[3,4]cyclobuta[1,2-b]naphtho[2,3-i]phenazine derivative), featuring a single cyclobutadiene unit, to their radical anions and dianions. The reduced species were produced using potassium naphthalenide in the presence of 18-crown-6 in THF. Crystal structures of the reduced representatives were obtained and their optoelectronic properties evaluated. Charging these 4n Hückel systems gives dianionic 4n + 2 π-electron systems with increased antiaromaticity, according to NICS(1.7)zz calculations, featuring unusually red-shifted absorption spectra.

Backbone-controlled LUMO energy induces intramolecular C-H activation in ortho-bis-9-borafluorene-substituted phenyl and o-carboranyl compounds leading to novel 9,10-diboraanthracene derivatives.

The choice of backbone linker for two ortho-bis-(9-borafluorene)s has a great influence on the LUMO located at the boron centers and, therefore, the reactivity of the respective compounds. Herein, we report the room temperature rearrangement of 1,2-bis-(9-borafluorenyl)-ortho-carborane, C2B10H10-1,2-[B(C12H8)]2 ([2a]) featuring o-carborane as the inorganic three-dimensional backbone and the synthesis of 1,2-bis-(9-borafluorenyl)benzene, C6H4-1,2-[B(C12H8)]2 (2b), its phenylene analog. DFT calculations on the transition state for the rearrangement support an intramolecular C-H bond activation process via an SEAr-like mechanism in [2a], and predicted that the same rearrangement would take place in 2b, but at elevated temperatures, which indeed proved to be the case. The rearrangement gives access to 3a and 3b as dibora-benzo[a]fluoroanthene isomers, a form of diboron polycyclic aromatic hydrocarbon (PAH) that had yet to be explored. The isolated compounds 2b, 3a, and 3b were fully characterized by NMR, HRMS, cyclic voltammetry (CV), single-crystal X-ray diffraction analysis, and photophysical measurements, supported by DFT and TD-DFT calculations.

Electrophilic C-H Borylation of Aza[5]helicenes Leading to Bowl-Shaped Quasi-[7]Circulenes with Switchable Dynamics.

The intrinsic relationship between helicenes and circulenes is of fundamental interest and importance in molecular engineering. Herein, electrophilic borylation of phenanthroline-derived aza[5]helicenes is presented, resulting in the incorporation of a boryl unit into two termini of helicenes to afford quasi-[7]circulenes. Their bowl-shaped structures were determined by X-ray diffraction. UV-vis absorption and fluorescence spectroscopy, as well as electrochemical measurements and DFT calculations, gave insight into their electronic properties. Variable-temperature NMR studies and DFT calculations revealed bowl-to-bowl inversion at room temperature and bowl-to-helix equilibria at elevated temperature, highlighting the important role of B ← N bond strength in tuning their dynamic properties.

Mixed-ligand complexes of copper(ii) with thienoyltrifluoroacetonate and nitrogen containing ligands: synthesis, structures, antimicrobial activity, cytotoxicity, Hirshfeld surface analysis and DFT studies.

Mixed-ligand complexes of copper(ii) with thienoyltrifluoroacetonate (TTA-H), 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), and tetramethylethylenediamine (tmen), associated with counter ions such as Cl-, and NO3 - have been synthesized and characterized by molar conductance measurements, elemental analysis, mass spectrometry, IR and UV-Vis spectroscopy, antimicrobial activity, cytotoxicity assay studies, and single-crystal X-ray diffraction. The UV-Vis spectra and crystal structures are consistent with the adoption of square pyramidal geometry for all of the complexes except [Cu(TTA)tmen]NO3 and [Cu(TTA)2tmen] which have square planar and octahedral geometries, respectively. Conductance measurements of the mixed-ligand complexes indicated that they were all non-electrolytes, with the ligands and anions being coordinated to Cu except [Cu(TTA)tmen]NO3 which is a 1 : 1 electrolyte. All of the complexes were moderately active on all the fungi tested (Candida albicans, Aspergillus niger, Penicillium notatum, Rhizopus stolonifer) except [Cu(TTA)bipyCl] which showed increased activity in Candida albicans and Aspergillus niger. All of the compounds tested showed LC50 values greater than 100 with [Cu(TTA)(phen)NO3] being the least toxic of the compounds. Molecular geometries of the complexes were optimized at the PBE1PBE/def2SVP and PBE1PBE/6-311g(d,p) level of theory and the results were compared with the single-crystal X-ray diffraction data. Electronic properties such as HOMO, LUMO, HOMO-LUMO gaps and global reactivity descriptors are reported at the PBE1PBE/6-311g(d,p) level of theory. Hirshfeld surface analysis was carried out to investigate the cooperative non-covalent supramolecular interactions within the various complexes.

The Radical Anion, Dianion and Electron Transport Properties of Tetraiodotetraazapentacene.

Tetraiodotetraazapentacene I4 TAP, the last missing derivative in the series of halogenated silylated tetraazapentacenes, was synthesized via condensation chemistry from a TIPS-ethynylated diaminobenzothiadiazol in three steps. Single and double reduction furnished its air-stable monoanion and relatively air-stable dianion, both of which were characterized by crystallography. All three species are structurally and spectroscopically compared to non-halogenated TAP and Br4 TAP. I4 TAP is an n-channel material in thin-film transistors with average electron mobilities exceeding 1 cm2 (Vs)-1 .

Iridium-Catalyzed Borylation of 6-Fluoroquinolines: Access to 6-Fluoroquinolones.

The Ir-catalyzed C-H borylation of fluoroquinolines has been realized. The quinoline boronic ester formed undergoes a range of important transformations of relevance to medicinal chemistry. Judicious choice of the substituent at C4 on the quinoline facilitated the unmasking of a fluoroquinolone─the core structure of many antibiotics.

Electron-Rich EDOT Linkers in Tetracationic bis-Triarylborane Chromophores: Influence on Water Stability, Biomacromolecule Sensing, and Photoinduced Cytotoxicity.

Three novel tetracationic bis-triarylboranes with 3,4-ethylenedioxythiophene (EDOT) linkers, and their neutral precursors, showed significant red-shifted absorption and emission compared to their thiophene-containing analogues, with one of the EDOT-derivatives emitting in the NIR region. Only the EDOT-linked trixylylborane tetracation was stable in aqueous solution, indicating that direct attachment of a thiophene or even 3-methylthiophene to the boron atom is insufficient to provide hydrolytic stability in aqueous solution. Further comparative analysis of the EDOT-linked trixylylborane tetracation and its bis-thiophene analogue revealed efficient photo-induced singlet oxygen production, with the consequent biological implications. Thus, both analogues bind strongly to ds-DNA and BSA, very efficiently enter living human cells, accumulate in several different cytoplasmic organelles with no toxic effect but, under intense visible light irradiation, they exhibit almost instantaneous and very strong cytotoxic effects, presumably attributed to singlet oxygen production. Thus, both compounds are intriguing theranostic agents, whose intracellular and probably intra-tissue location can be monitored by strong fluorescence, allowing switching on of the strong bioactivity by well-focused visible light.

Thermodynamic equilibrium between locally excited and charge-transfer states through thermally activated charge transfer in 1-(pyren-2'-yl)-o-carborane.

Reversible conversion between excited-states plays an important role in many photophysical phenomena. Using 1-(pyren-2'-yl)-o-carborane as a model, we studied the photoinduced reversible charge-transfer (CT) process and the thermodynamic equilibrium between the locally-excited (LE) state and CT state, by combining steady state, time-resolved, and temperature-dependent fluorescence spectroscopy, fs- and ns-transient absorption, and DFT and LR-TDDFT calculations. Our results show that the energy gaps and energy barriers between the LE, CT, and a non-emissive 'mixed' state of 1-(pyren-2'-yl)-o-carborane are very small, and all three excited states are accessible at room temperature. The internal-conversion and reverse internal-conversion between LE and CT states are significantly faster than the radiative decay, and the two states have the same lifetimes and are in thermodynamic equilibrium.

Copper-Catalyzed Borylation of Acyl Chlorides with an Alkoxy Diboron Reagent: A Facile Route to Acylboron Compounds.

Herein, the copper-catalyzed borylation of readily available acyl chlorides with bis(pinacolato)diboron, (B2 pin2 ) or bis(neopentane glycolato)diboron (B2 neop2 ) is reported, which provides stable potassium acyltrifluoroborates (KATs) in good yields from the acylboronate esters. A variety of functional groups are tolerated under the mild reaction conditions (room temperature) and substrates containing different carbon-skeletons, such as aryl, heteroaryl and primary, secondary, tertiary alkyl are applicable. Acyl N-methyliminodiacetic acid (MIDA) boronates can also been accessed by modification of the workup procedures. This process is scalable and also amenable to the late-stage conversion of carboxylic acid-containing drugs into their acylboron analogues, which have been challenging to prepare previously. A catalytic mechanism is proposed based on in situ monitoring of the reaction between p-toluoyl chloride and an NHC-copper(I) boryl complex as well as the isolation of an unusual lithium acylBpinOBpin compound as a key intermediate.

Methyl Viologens of Bis-(4'-Pyridylethynyl)Arenes - Structures, Photophysical and Electrochemical Studies, and their Potential Application in Biology.

A series of bis-(4'-pyridylethynyl)arenes (arene=benzene, tetrafluorobenzene, and anthracene) were synthesized and their bis-N-methylpyridinium compounds were investigated as a class of π-extended methyl viologens. Their structures were determined by single crystal X-ray diffraction, and their photophysical and electrochemical properties (cyclic voltammetry), as well as their interactions with DNA/RNA were investigated. The dications showed bathochromic shifts in emission compared to the neutral compounds. The neutral compounds showed very small Stokes shifts, which are a little larger for the dications. All of the compounds showed very short fluorescence lifetimes (<4 ns). The neutral compound with an anthracene core has a quantum yield of almost unity. With stronger acceptors, the analogous bis-N-methylpyridinium compound showed a larger two-photon absorption cross-section than its neutral precursor. All of the dicationic compounds interact with DNA/RNA; while the compounds with benzene and tetrafluorobenzene cores bind in the grooves, the one with an anthracene core intercalates as a consequence of its large, condensed aromatic linker moiety, and it aggregates within the polynucleotide when in excess over DNA/RNA. Moreover, all cationic compounds showed highly specific CD spectra upon binding to ds-DNA/RNA, attributed to the rare case of forcing the planar, achiral molecule into a chiral rotamer, and negligible toxicity toward human cell lines at ≤10 µM concentrations. The anthracene-analogue exhibited intracellular accumulation within lysosomes, preventing its interaction with cellular DNA/RNA. However, cytotoxicity was evident at 1 µM concentration upon exposure to light, due to singlet oxygen generation within cells. These multi-faceted features, in combination with its two-photon absorption properties, suggest it to be a promising lead compound for development of novel light-activated theranostic agents.

Aggregation-Induced Dual Phosphorescence from (o-Bromophenyl)-Bis(2,6-Dimethylphenyl)Borane at Room Temperature.

Designing highly efficient purely organic phosphors at room temperature remains a challenge because of fast non-radiative processes and slow intersystem crossing (ISC) rates. The majority of them emit only single component phosphorescence. Herein, we have prepared 3 isomers (o, m, p-bromophenyl)-bis(2,6-dimethylphenyl)boranes. Among the 3 isomers (o-, m- and p-BrTAB) synthesized, the ortho-one is the only one which shows dual phosphorescence, with a short lifetime of 0.8 ms and a long lifetime of 234 ms in the crystalline state at room temperature. Based on theoretical calculations and crystal structure analysis of o-BrTAB, the short lifetime component is ascribed to the T1 M state of the monomer which emits the higher energy phosphorescence. The long-lived, lower energy phosphorescence emission is attributed to the T1 A state of an aggregate, with multiple intermolecular interactions existing in crystalline o-BrTAB inhibiting nonradiative decay and stabilizing the triplet states efficiently.

Rocaglates as Antivirals: Comparing the Effects on Viral Resistance, Anti-Coronaviral Activity, RNA-Clamping on eIF4A and Immune Cell Toxicity.

Rocaglates are potent broad-spectrum antiviral compounds with a promising safety profile. They inhibit viral protein synthesis for different RNA viruses by clamping the 5'-UTRs of mRNAs onto the surface of the RNA helicase eIF4A. Apart from the natural rocaglate silvestrol, synthetic rocaglates like zotatifin or CR-1-31-B have been developed. Here, we compared the effects of rocaglates on viral 5'-UTR-mediated reporter gene expression and binding to an eIF4A-polypurine complex. Furthermore, we analyzed the cytotoxicity of rocaglates on several human immune cells and compared their antiviral activities in coronavirus-infected cells. Finally, the potential for developing viral resistance was evaluated by passaging human coronavirus 229E (HCoV-229E) in the presence of increasing concentrations of rocaglates in MRC-5 cells. Importantly, no decrease in rocaglate-sensitivity was observed, suggesting that virus escape mutants are unlikely to emerge if the host factor eIF4A is targeted. In summary, all three rocaglates are promising antivirals with differences in cytotoxicity against human immune cells, RNA-clamping efficiency, and antiviral activity. In detail, zotatifin showed reduced RNA-clamping efficiency and antiviral activity compared to silvestrol and CR-1-31-B, but was less cytotoxic for immune cells. Our results underline the potential of rocaglates as broad-spectrum antivirals with no indications for the emergence of escape mutations in HCoV-229E.

Pure Boric Acid Does Not Show Room-Temperature Phosphorescence (RTP).

Boric acid (BA) has been used as a transparent glass matrix for optical materials for over 100 years. However, recently, apparent room-temperature phosphorescence (RTP) from BA (crystalline and powder states) was reported (Zheng et al., Angew. Chem. Int. Ed. 2021, 60, 9500) when irradiated at 280 nm under ambient conditions. We suspected that RTP from their BA sample was induced by an unidentified impurity. Our experimental results show that pure BA synthesized from B(OMe)3 does not luminesce in the solid state when irradiated at 250-400 nm, while commercial BA indeed (faintly) luminesces. Our theoretical calculations show that neither individual BA molecules nor aggregates would absorb light at >175 nm, and we observe no absorption of solid pure BA experimentally at >200 nm. Therefore, it is not possible for pure BA to be excited at >250 nm even in the solid state. Thus, pure BA does not display RTP, whereas trace impurities can induce RTP.

Selective, Transition Metal-free 1,2-Diboration of Alkyl Halides, Tosylates, and Alcohols.

Defunctionalization of readily available feedstocks to provide alkenes for the synthesis of multifunctional molecules represents an extremely useful process in organic synthesis. Herein, we describe a transition metal-free, simple and efficient strategy to access alkyl 1,2-bis(boronate esters) via regio- and diastereoselective diboration of secondary and tertiary alkyl halides (Br, Cl, I), tosylates, and alcohols. Control experiments demonstrated that the key to this high reactivity and selectivity is the addition of a combination of potassium iodide and N,N-dimethylacetamide (DMA). The practicality and industrial potential of this transformation are demonstrated by its operational simplicity, wide functional group tolerance, and the late-stage modification of complex molecules. From a drug discovery perspective, this synthetic method offers control of the position of diversification and diastereoselectivity in complex ring scaffolds, which would be especially useful in a lead optimization program.

Base-Mediated Radical Borylation of Alkyl Sulfones.

A practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal-free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2 neop2 ), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late-stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates.