Synthesis and biological evaluation of arylphosphonium-benzoxaborole conjugates as novel anticancer agents.

Arylphosphonium-benzoxaborole conjugates have been synthesized as potential mitochondria targeting anticancer agents. The synthesized compounds have been tested for their effects on cell viability in various solid tumor cell lines including breast cancer 4T1 and MCF-7, pancreatic cancer MIAPaCa-2 and colorectal adenocarcinoma WiDr. Compound 6c is designated as a lead compound for further studies due to its enhanced effects on cell viability in the above-mentioned cell lines. Seahorse Xfe96 based metabolic assays reveal that the lead candidate 6c inhibits mitochondrial respiration in 4T1 and WiDr cell lines as evidenced by the reduction of mitochondrial ATP production and increase in proton leak. Epiflourescent microscopy experiments also illustrate that 6c causes significant mitochondrial fragmentation in 4T1 and WiDr cells, morphologically consistent with programmed cell death. Our current studies illustrate that arylphosphonium-benzoxaborole conjugates have potential to be further developed as anticancer agents.

Synthesis and evaluation of functionalized benzoboroxoles as potential anti-tuberculosis agents.

Several derivatives of aminobenzoboroxole have been prepared starting from 2-boronobenzaldehyde. All of these derivatives have been evaluated for their anti-mycobacterial activity on Mycobacterium smegmatis and cytotoxicity on breast cancer cell line MCF7. Based on these studies, all the tested molecules have been found to be generally non-toxic and benzoboroxoles with unsubstituted (primary) amines have been found to exhibit good anti-mycobacterial activity. Some of the key compounds have been evaluated for their anti-tubercular activity on Mycobacterium tuberculosis H37Rv using 7H9 and GAST media. 7-Bromo-6-aminobenzoboroxole 4 has been identified as the lead candidate compound for further development.

Tuning Up an Electronic Structure of the Subphthalocyanine Derivatives toward Electron-Transfer Process in Noncovalent Complexes with C60 and C70 Fullerenes: Experimental and Theoretical Studies.

Noncovalent π-π interactions between chloroboron subphthalocyanine (1), 2,3-subnaphthalocyanine (3), 1,4,8,11,15,18-(hexathiophenyl)subphthalocyanine (4), or 4-tert-butylphenoxyboron subphthalocyanine (2) with C60 and C70 fullerenes were studied by UV-vis and steady-state fluorescence spectroscopy, as well as mass (APCI, ESI, and CSI) spectrometry. Mass spectrometry experiments were suggestive of relatively weak interaction energies between compounds 1-4 and fullerenes. The formation of a new weak charge-transfer band in the NIR region was observed in solution only for subphthalocyanine 4 when titrated with C60 and C70 fullerenes. Molecular structures of the subphthalocyanines 2 and 4 as well as cocrystallite of 4 with C60 fullerene (4···C60) were studied using X-ray crystallography. One of the C60 fullerenes in the crystal structure of 4···C60 was found in the concave region between two subphthalocyanine cores, while the other three fullerenes are aligned above individual isoindole fragments of the aromatic subphthalocyanine. The excited-state dynamics in noncovalent assemblies were studied by transient absorption spectroscopy. The time-resolved photophysics data suggest that only electron-rich subphthalocyanine 4 can facilitate an electron-transfer to C60 or C70 fullerenes, while no electron-transfer from the photoexcited receptors 1-3 to fullerenes was observed in UV-vis and transient spectroscopy experiments. DFT calculations using the CAM-B3LYP exchange-correlation functional and the 6-31+G(d) basis set allowed an estimation of interaction energies for the noncovalent 1:1 and 1:2 (fullerene:subphthalocyanine) complexes. Theoretical data suggest that the weak (∼3.5-10.5 kcal/mol) van der Waals-type interaction energies tend to increase with an increase of the electron density at the subphthalocyanine core with compound 4 being the best platform for noncovalent interactions with fullerenes. DFT calculations also indicate that 1:2 (fullerene:subphthalocyanine) noncovalent complexes are more stable than the corresponding 1:1 assemblies.

Systematic color tuning of a family of luminescent azole-based organoboron compounds suitable for OLED applications.

A new tunable luminescent family of heterocyclic aromatic compounds containing boron has been prepared and characterized through NMR spectroscopy, mass spectrometry, absorption and fluorescence spectroscopy as well as structural study using single crystal X-ray crystallography. Spectroscopic properties of the new compounds were also studied using DFT and TDDFT computational models that showed very good agreement of the theoretical data with experimental results. Through introduction of auxochromic atoms such as sulfur and extension of the π system of the ligands it is possible to cover a large range of the visible spectrum. Activation and enhancement of the luminescence is achieved by condensation reactions that introduce the boron fragment forming stable, sublimable compounds suitable for OLED applications.

New bioactive bromotyrosine-derived alkaloid from a marine sponge Aplysinella sp.

A new bromotyrosine-derived alkaloid, (+)-aplysinillin (1), together with seven known compounds, was isolated from the crude organic extract of the marine sponge Aplysinella sp. collected from the Federated States of Micronesia. The structure of 1 was deduced by NMR and mass spectral techniques. Compounds 1-8 were evaluated for their inhibitory activity with the hyphae formation inhibition assay in Streptomyces 85E. Compounds 1 and 8 exhibited antiproliferative activities against the human breast adenocarcinoma cancer cell line MCF-7.

3H-2,1-Benzoxaborole-1-spiro-4'-(5-oxa-3a-aza-4-borapyrene).

In the title compound, C(20)H(14)BNO(2), the B atom has a tetra-hedral geometry with two short B-O and two long B-C and B-N bonds, revealing a significant difference between C(ar)-O-B and C(alk-yl)-O-B bond distances. Inter-molecular Ar-H⋯O hydrogen bonds and strong π-π inter-actions (3.368 Å) between aromatic cores of neighbouring mol-ecules result in hexa-gonal channels along the crystallographic c axis, which are potentially accessible for small mol-ecules.

A computational study of sulfur bridged cyclooctatetraenophanes.

Calculations of several thiacyclooctatetraenophanes predicted, as part of their overall geometry, substantial flattening of the cyclooctatetraene (COT) structures relative to the tub conformation generally associated with the COT molecule. The COT structures were approximately parallel to each other and the interplanar distances were predicted to be within 2.787-2.803 angstrom at the DFT/UB3YLP level of calculation. DFT/UB3LYP optimized geometries afforded significant delocalization of the COT structures in each of the thiacyclooctatetraenophanes. Hartree-Fock (HF) methods and the semi-empirical Austin Model 1 (AM1) method deviated significantly from the DFT/UB3LYP optimized geometries. Cyclooctatetraenes can undergo reversible sizing by oxidation and reduction reactions to form the aromatic dication and aromatic dianion, respectively, which could then be used to prepare molecular backbones for polymeric organometallic molecular wires. The number of bridges and the introduction of the sulfur atom have been investigated to provide disparate synthetic routes.

Double- and triple-consecutive O-insertion into tert-butyl and triarylmethyl structures.

[reaction: see text] The concecutive Criegee rearrangement reactions were studied for tert-butyl trifluoroacetate, triarylcarbinols, and benzophenone ketales with trifluoroperacetic acid (TFPAA) in trifluoroacetic acid (TFA). The formation of methyl acetate and methyl trifluoroacetate indicates that the consecutive double-O-insertion process has taken place for tert-butyl trifluoroacetate. The intermediate dimethoxymethylcarbonium ion was detected below 5 degrees C. A consecutive triple-O-insertion process has been observed for triarylmethanols and benzophenone ketals. A new high yield method of corresponding diaryl carbonates synthesis was developed.