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Magnetic hysteresis and large coercivity in bisbenzimidazole radical-bridged dilanthanide complexes.Chemical Science May 2023A judicious combination of radical ligands innate to diffuse spin orbitals with paramagnetic metal ions elicits strong magnetic exchange coupling which leads to...
A judicious combination of radical ligands innate to diffuse spin orbitals with paramagnetic metal ions elicits strong magnetic exchange coupling which leads to properties important for future technologies. This metal-radical approach aids in effective magnetic communication of especially lanthanide ions as their 4f orbitals are contracted and not readily accessible. Notably, a high spin density on the donor atoms of the radical is required for strong coupling. Such molecules are extremely rare owing to high reactivity rendering their isolation challenging. Herein, we present two unprecedented series of bisbenzimidazole-based dilanthanide complexes [(Cp*Ln)(-Bbim)] (1-Ln = Gd, Tb, Dy, Bbim = 2,2'-bisbenzimidazole) and [K(crypt-222)][(Cp*Ln)(μ-Bbim˙)] -(2-Ln = Gd, Tb, Dy), where the latter contains the first Bbim˙ radical matched with any paramagnetic metal ion. The magnetic exchange constant for 2-Gd of = -1.96(2) cm suggests strong antiferromagnetic Gd-radical coupling, whereas the lanthanides in 1-Gd are essentially uncoupled. calculations on 2-Tb and 2-Dy uncovered coupling strengths of -4.8 and -1.8 cm. 1-Dy features open hysteresis loops with a coercive field of of 0.11 T where the single-molecule magnetism can be attributed to the single-ion effect due to lack of coupling. Excitingly, pairing the effective magnetic coupling with the strong magnetic anisotropy of Dy results in magnetic hysteresis with a blocking temperature of 5.5 K and coercive field of 0.54 T, ranking 2-Dy as the second best dinuclear single-molecule magnet containing an organic radical bridge. A Bbim species is formed electrochemically hinting at the accessibility of Bbim-based redox-active materials.
PubMed: 37265712
DOI: 10.1039/d3sc01562a -
Isolation of the elusive bisbenzimidazole Bbim˙ radical anion and its employment in a metal complex.Chemical Science May 2022The discovery of singular organic radical ligands is a formidable challenge due to high reactivity arising from the unpaired electron. Matching radical ligands with...
The discovery of singular organic radical ligands is a formidable challenge due to high reactivity arising from the unpaired electron. Matching radical ligands with metal ions to engender magnetic coupling is crucial for eliciting preeminent physical properties such as conductivity and magnetism that are crucial for future technologies. The metal-radical approach is especially important for the lanthanide ions exhibiting deeply buried 4f-orbitals. The radicals must possess a high spin density on the donor atoms to promote strong coupling. Combining diamagnetic Y ( = 1/2) with organic radicals allows for invaluable insight into the electronic structure and spin-density distribution. This approach is hitherto underutilized, possibly owing to the challenging synthesis and purification of such molecules. Herein, evidence of an unprecedented bisbenzimidazole radical anion (Bbim˙) along with its metalation in the form of an yttrium complex, [K(crypt-222)][(Cp*Y)(μ-Bbim˙)] is provided. Access of Bbim˙ was feasible through double-coordination to the Lewis acidic metal ion and subsequent one-electron reduction, which is remarkable as Bbim was explicitly stated to be redox-inactive in closed-shell complexes. Two molecules containing Bbim (1) and Bbim˙ (2), respectively, were thoroughly investigated by X-ray crystallography, NMR and UV/Vis spectroscopy. Electrochemical studies unfolded a quasi-reversible feature and emphasize the role of the metal centre for the Bbim redox-activity as neither the free ligand nor the Bbim complex led to analogous CV results. Excitingly, a strong delocalization of the electron density through the Bbim˙ ligand was revealed temperature-dependent EPR spectroscopy and confirmed through DFT calculations and magnetometry, rendering Bbim˙ an ideal candidate for single-molecule magnet design.
PubMed: 35685798
DOI: 10.1039/d1sc07245e -
ACS Omega Dec 2022A facile synthesis of benzimidazoles was described by a one-pot process containing acylation-cyclization of -arylamidoxime. This method provided an alternative synthesis...
A facile synthesis of benzimidazoles was described by a one-pot process containing acylation-cyclization of -arylamidoxime. This method provided an alternative synthesis of benzimidazoles with a certain diversity of substituted groups in acceptable yields (up to 96%). More importantly, the construction of bis-benzimidazole (), the key intermediate for making telmisartan, was achieved by adopting this method that enabled avoiding the undesired nitration with nitric/sulfuric acid and the cyclization in polyphosphoric acid in the existing operations.
PubMed: 36530318
DOI: 10.1021/acsomega.2c06554 -
Polymers Mar 2023A series of aliphatic polybenzimidazoles (PBIs) with methylene groups of varying length were synthesized by the high-temperature polycondensation of...
A series of aliphatic polybenzimidazoles (PBIs) with methylene groups of varying length were synthesized by the high-temperature polycondensation of 3,3'-diaminobenzidine (DAB) and the corresponding aliphatic dicarboxylic acid in Eaton's reagent. The influence of the length of the methylene chain on PBIs' properties was investigated by solution viscometry, thermogravimetric analysis, mechanical testing and dynamic mechanical analysis. All PBIs exhibited high mechanical strength (up to 129.3 ± 7.1 MPa), glass transition temperature (≥200 °C) and thermal decomposition temperature (≥460 °C). Moreover, all of the synthesized aliphatic PBIs possess a shape-memory effect, which is a result of the presence of soft aliphatic segments and rigid -benzimidazole groups in the macromolecules, as well as strong intermolecular hydrogen bonds that serve as non-covalent crosslinks. Among the studied polymers, the PBI based on DAB and dodecanedioic acid has high adequate mechanical and thermal properties and demonstrates the highest shape-fixity ratio and shape-recovery ratio of 99.6% and 95.6%, respectively. Because of these properties, aliphatic PBIs have great potential to be used as high-temperature materials for application in different high-tech fields, including the aerospace industry and structural component industries.
PubMed: 36987180
DOI: 10.3390/polym15061399 -
Scientific Reports Jun 2021At present, nuclear condensation and fragmentation have been estimated also using Hoechst probes in fluorescence microscopy and flow cytometry. However, none of the...
At present, nuclear condensation and fragmentation have been estimated also using Hoechst probes in fluorescence microscopy and flow cytometry. However, none of the methods used the Hoechst probes for quantitative spectrofluorometric assessment. Therefore, the aim of the present study was to develop a spectrofluorometric assay for detection of nuclear condensation and fragmentation in the intact cells. We used human hepatoma HepG2 and renal HK-2 cells cultured in 96-well plates treated with potent apoptotic inducers (i.e. cisplatin, staurosporine, camptothecin) for 6-48 h. Afterwards, the cells were incubated with Hoechst 33258 (2 µg/mL) and the increase of fluorescence after binding of the dye to DNA was measured. The developed spectrofluorometric assay was capable to detect nuclear changes caused by all tested apoptotic inducers. Then, we compared the outcomes of the spectrofluorometric assay with other methods detecting cell impairment and apoptosis (i.e. WST-1 and glutathione tests, TUNEL, DNA ladder, caspase activity, PARP-1 and JNKs expressions). We found that our developed spectrofluorometric assay provided results of the same sensitivity as the TUNEL assay but with the advantages of being fast processing, low-cost and a high throughput. Because nuclear condensation and fragmentation can be typical markers of cell death, especially in apoptosis, we suppose that the spectrofluorometric assay could become a routinely used method for characterizing cell death processes.
Topics: Antineoplastic Agents; Apoptosis; Bisbenzimidazole; Camptothecin; Cell Death; Cell Line; Cell Nucleus; Cisplatin; DNA Fragmentation; Flow Cytometry; Hep G2 Cells; Humans; Microscopy, Fluorescence; Reproducibility of Results; Spectrometry, Fluorescence; Staurosporine
PubMed: 34099803
DOI: 10.1038/s41598-021-91380-3 -
Scientific Reports Oct 2019Bisbenzimidazoles with terminal alkynyl linkers, selective inhibitors of bacterial topoisomerase I, have been evaluated using bacterial cytological profiling (BCP) to...
Bisbenzimidazoles with terminal alkynyl linkers, selective inhibitors of bacterial topoisomerase I, have been evaluated using bacterial cytological profiling (BCP) to ascertain their mechanism of action and screened for synergism to improve Gram-negative bacterial coverage. Principal component analysis of high throughput fluorescence images suggests a dual-mechanism of action affecting DNA synthesis and cell membrane integrity. Fluorescence microscopy of bacteria challenged with two of the alkynyl-benzimidazoles revealed changes in the cellular ultrastructure that differed from topoisomerase II inhibitors including induction of spheroplasts and membrane lysis. The cytoskeleton recruitment enzyme inhibitor A22 in combination with one of the alkynyl-benzimidazoles was synergistic against Acinetobacter baumannii and Escherichia coli. Gram-positive coverage remained unchanged in the A22-alkynyl bisbenzimidazole combination. Efflux inhibitors were not synergistic, suggesting that the Gram-negative outer membrane was a significant barrier for alkynyl-bisbenzimidazole uptake. Time-kill assays demonstrated the A22-bisbenzimidazole combination had a similar growth inhibition curve to that of norfloxacin in E.coli. Bisbenzimidazoles with terminal alkynyl linkers likely impede bacterial growth by compromising cell membrane integrity and by interfering with DNA synthesis against Gram-positive pathogens and in the synergistic combination against Gram-negative pathogens including E. coli and multidrug-resistant A. baumanii.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bisbenzimidazole; Cell Membrane; Drug Synergism; Escherichia coli; Topoisomerase I Inhibitors
PubMed: 31578425
DOI: 10.1038/s41598-019-48898-4 -
The Journal of General Virology Dec 2021The shortcomings of current anti-human cytomegalovirus (HCMV) drugs has stimulated a search for anti-HCMV compounds with novel targets. We screened collections of...
The shortcomings of current anti-human cytomegalovirus (HCMV) drugs has stimulated a search for anti-HCMV compounds with novel targets. We screened collections of bioactive compounds and identified a range of compounds with the potential to inhibit HCMV replication. Of these compounds, we selected bisbenzimide compound RO-90-7501 for further study. We generated analogues of RO-90-7501 and found that one compound, MRT00210423, had increased anti-HCMV activity compared to RO-90-7501. Using a combination of compound analogues, microscopy and biochemical assays we found RO-90-7501 and MRT00210423 interacted with DNA. In single molecule microscopy experiments we found RO-90-7501, but not MRT00210423, was able to compact DNA, suggesting that compaction of DNA was non-obligatory for anti-HCMV effects. Using bioinformatics analysis, we found that there were many putative bisbenzimide binding sites in the HCMV DNA genome. However, using western blotting, quantitative PCR and electron microscopy, we found that at a concentration able to inhibit HCMV replication our compounds had little or no effect on production of certain HCMV proteins or DNA synthesis, but did have a notable inhibitory effect on HCMV capsid production. We reasoned that these effects may have involved binding of our compounds to the HCMV genome and/or host cell chromatin. Therefore, our data expand our understanding of compounds with anti-HCMV activity and suggest targeting of DNA with bisbenzimide compounds may be a useful anti-HCMV strategy.
Topics: Antiviral Agents; Binding Sites; Bisbenzimidazole; Capsid; Cell Line; Cytomegalovirus; DNA; DNA Replication; Humans; Molecular Structure; Viral Load; Virus Replication
PubMed: 34882533
DOI: 10.1099/jgv.0.001702 -
Royal Society Open Science Sep 2022In this study, a series of 14 Cu (II), Zn (II), Ni (II) and Ag (I) complexes containing bis-benzimidazole derivatives were successfully designed and synthesized from...
In this study, a series of 14 Cu (II), Zn (II), Ni (II) and Ag (I) complexes containing bis-benzimidazole derivatives were successfully designed and synthesized from 2-(1-benzimidazole-2-yl)-phenol derivatives and corresponding metal salt solutions. The compound structures were identified by FT-IR, H-NMR, powder X-ray diffraction and ESI-MS analyses, and the presence of the metal in the complexes was confirmed by ultraviolet-visible spectroscopy and ICP optical emission spectrometry. Electronic structure calculations were also carried out to describe the detailed structures in addition to the electronic absorption spectra of the ligands. The cytotoxic activity of the complexes was evaluated against three human cancer cell lines: lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cells. All complexes inhibited anti-proliferative cancer cells better than free ligands, especially Zn (II) and Ag (I) complexes, which are most sensitive to MDA-MB-231 cells. In addition, showing the growth inhibition of three cancer cell lines with IC < 10.4 µM, complexes , and could be considered potential multi-targeted anti-cancer agents.
PubMed: 36147940
DOI: 10.1098/rsos.220659 -
Frontiers of Optoelectronics Apr 2023Single perylene diimide (PDI) used as a non-fullerene acceptor (NFA) in organic solar cells (OSCs) is enticing because of its low cost and excellent stability. To...
Single perylene diimide (PDI) used as a non-fullerene acceptor (NFA) in organic solar cells (OSCs) is enticing because of its low cost and excellent stability. To improve the photovoltaic performance, it is vital to narrow the bandgap and regulate the stacking behavior. To address this challenge, we synthesize soluble perylenetetracarboxylic bisbenzimidazole (PTCBI) molecules with a bulky side chain at the bay region, by replacing the widely used "swallow tail" type alkyl chains at the imide position of PDI molecules with a planar benzimidazole structure. Compared with PDI molecules, PTCBI molecules exhibit red-shifted UV-vis absorption spectra with larger extinction coefficient, and one magnitude higher electron mobility. Finally, OSCs based on one soluble PTCBI-type NFA, namely MAS-7, exhibit a champion power conversion efficiency (PCE) of 4.34%, which is significantly higher than that of the corresponding PDI-based OSCs and is the highest PCE of PTCBI-based OSCs reported. These results highlight the potential of soluble PTCBI derivatives as NFAs in OSCs.
PubMed: 37087536
DOI: 10.1007/s12200-023-00063-6 -
Communications Biology Feb 2023Type IA topoisomerases maintain DNA topology by cleaving ssDNA and relaxing negative supercoils. The inhibition of its activity in bacteria prevents the relaxation of...
Type IA topoisomerases maintain DNA topology by cleaving ssDNA and relaxing negative supercoils. The inhibition of its activity in bacteria prevents the relaxation of negative supercoils, which in turn impedes DNA metabolic processes leading to cell death. Using this hypothesis, two bisbenzimidazoles, PPEF and BPVF are synthesized, selectively inhibiting bacterial TopoIA and TopoIII. PPEF stabilizes the topoisomerase and topoisomerase-ssDNA complex, acts as an interfacial inhibitor. PPEF display high efficacy against ~455 multi-drug resistant gram positive and negative bacteria. To understand molecular mechanism of inhibition of TopoIA and PPEF, accelerated MD simulation is carried out, and results suggested that PPEF binds, stabilizes the closed conformation of TopoIA with -6Kcal/mol binding energy and destabilizes the binding of ssDNA. The TopoIA gate dynamics model can be used as a tool to screen TopoIA inhibitors as therapeutic candidates. PPEF and BPVF cause cellular filamentation and DNA fragmentation leading to bacterial cell death. PPEF and BPVF show potent efficacy against systemic and neutropenic mouse models harboring E. coli, VRSA, and MRSA infection without cellular toxicity.
Topics: Animals; Mice; Escherichia coli; DNA Topoisomerases, Type I; Bisbenzimidazole; DNA; DNA, Single-Stranded
PubMed: 36807602
DOI: 10.1038/s42003-023-04412-1