Quantitative study on a simple electrochemical dsDNA-pregabalin biosensor; multi-spectroscopic, molecular docking and modelling studies.

Pregabalin (PGB) is a γ-aminobutyric acid (GABA) alkylated analog prescribed to treat neuropathic pain, fibromyalgia, and postherpetic neuralgia. Using analytical, spectroscopic methods and molecular docking and molecular dynamics (MD) simulations, a detailed experimental and theoretical investigation was conducted into the binding process and interactions between PGB and double-stranded fish sperm deoxyribonucleic acid (dsDNA). It was evident from the collected experimental results that PGB binds with ds-DNA. PGB attaches to dsDNA via minor groove binding, as demonstrated by the results of electrochemical studies, UV-Vis absorption spectroscopy, and replacement study with ethidium bromide and Hoechst-32588. PGB's binding constant (Kb) with dsDNA, as determined by the Benesi-Hildebrand plot, is 2.41×104 ± 0.30 at 298 K. The fluorescence investigation indicates that PGB and dsDNA have a binding stoichiometry (n) of 1.21 ± 0.09. Molecular docking simulations were used in the research to computational determination of the interactions between PGB and dsDNA. The findings demonstrated that minor groove binding was the mechanism by which PGB interacted with dsDNA. Based on the electrochemically responsive PGB-dsDNA biosensor, we developed a technique for low-concentration detection of PGB utilizing differential pulse voltammetry (DPV). The voltammetric analysis of the peak current decrease in the deoxyadenosine oxidation signals resulting from the association between PGB and dsDNA enabled a sensitive estimation of PGB in pH 4.80 acetate buffer. The deoxyguanosine oxidation signals exhibited a linear relationship between 2 and 16 µM PGB. The values for the limit of detection (LOD) and limit of quantitation (LOQ) were 0.57 µM and 1.91 µM, respectively.

Imidazole-Derived Alkyl and Aryl Ethers: Synthesis, Characterization, In Vitro Anticancer and Antioxidant Activities, Carbonic Anhydrase I-II Inhibition Properties, and In Silico Studies.

Imidazole derivatives display extensive applications in pharmaceutical chemistry and have been investigated as bioactive compounds for medicinal chemistry. In this study, besides the starting materials (3a-c and 4a-c), synthesis, characterization, and biological activity studies were conducted on a total of 18 compounds, nine of which are known and the other nine are original. The compounds investigated in the study are a series of alkyl (7-15) and aryl (16-24) ether derivatives bearing substituted phenyl and imidazole rings, which were characterized using various methods including 1H NMR, 13C NMR, FT-IR analysis, elemental analysis, and mass spectroscopy. Computer-aided drug design studies have been carried out to predict the biological activities of compounds. Besides DFT calculations, the binding affinities of the compounds to EGFR, VEGFR2, FGFR1, HSP90, hCA I, and hCA II were investigated. Additionally, drug-likeness and ADME analyses were performed on the compounds. Anticancer, antioxidant, and enzyme inhibition activity tests were performed in biological activity studies on the synthesized compounds. Among the synthesized compounds, compounds 17 and 19-24 generally exhibited inhibition profiles against the widespread cytosolic hCA I isozyme with IC50 values ranging from 4.13 to 15.67 nM and cytosolic hCA II isozyme with IC50 values ranging from 5.65 to 14.84 nM. L929 (mouse fibroblast cell line) was used as the control healthy cell line, and MCF7 (breast cancer), C6 (rat glioblastoma), and HT-29 (colon cancer) cells were used in cell culture studies as cancer cell lines. Before the study on cancer cells, all compounds were examined on healthy cells, and their cytotoxicity was determined. As a result of these data, studies continued with six compounds determined to be nontoxic. On cancerous cells, it was determined that compounds 3a, 3b, 4a, 4b, 4c, and 7 had cytotoxic effects on both colon cancer and brain tumors. It was found that compound 3b had a more toxic effect than cisplatin on the glioma cell line with an IC50 value of 10.721 ± 0.38 µM, and compound 3a had a more toxic effect on the colon cancer cell line with an IC50 value of 20.88 ± 1.02 µM. However, it was determined that the same compounds did not have a statistically significant effect on breast cancer. Flow cytometry studies also showed that when the IC50 dose of compound 3b was applied to the C6 cell line, the cells tended to early and late apoptosis. Additionally, it has been shown by flow cytometry that the cell cycle stops in the G0/G1 phase. A similar effect was observed in the colon cancer cell line with compound 3a. Compound 3b caused early and late apoptosis of the colon cancer cell line with the applied IC50 dose and stopped the cell cycle in the G0/G1 phase. Finally, the FRAP method studied all synthesized compounds' antioxidant effects. According to the measured antioxidant power results, it was determined that no compound had a more effective reducing power than vitamin E.

Development and Fabrication of a Molecularly Imprinted Polymer-Based Electroanalytical Sensor for the Determination of Acyclovir.

Acyclovir (ACV), a synthetic nucleoside derivative of purine, is one of the most potent antiviral medications recommended in the specific management of varicella-zoster and herpes simplex viruses. The molecularly imprinted polymer (MIP) was utilized to create an effective and specific electrochemical sensor using a straightforward photopolymerization process to determine ACV. The polymeric thin coating was developed using the template molecule ACV, a functional monomer acrylamide, a basic monomer 2-hydroxyethyl methacrylate, a cross-linker ethylene glycol dimethacrylate, and a photoinitiator 2-hydroxy-2-methyl propiophenone on the exterior of the glassy carbon electrode (GCE). Scanning electron microscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, electrochemical impedance spectroscopy, and cyclic voltammetry were employed for the purpose of characterizing the constructed sensor (AM-ACV@MIP/GCE). Differential pulse voltammetry and a 5 mM ferrocyanide/ferricyanide ([Fe(CN)6]3-/4-) redox reagent were used to detect the ACV binding to the specific cavities on MIP. The study involves density functional theory (DFT) calculations, which were conducted to investigate template-functional monomer interactions thoroughly, calculate template-functional monomer interaction energies, and determine the optimal template/functional monomer ratio. DFT calculations were performed using Becke's three-parameter hybrid functional with the Lee-Yang-Parr correlation functional (B3LYP) method and 6-31G(d,p) basis set. The sensor exhibits linear performance throughout the concentration region 1 × 10-11 to 1 × 10-10 M, and the limit of detection and limit of quantification were 7.15 × 10-13 M and 2.38 × 10-12 M, respectively. For the electrochemical study of ACV, the sensor demonstrated high accuracy, precision, robustness, and a short detection time. Furthermore, the developed electrochemical sensor exhibited exceptional recovery in tablet dosage form and commercial human blood samples, with recoveries of 99.40 and 100.44%, respectively. The findings showed that the AM-ACV@MIP/GCE sensor would effectively be used to directly assess pharmaceuticals from actual specimens and would particularly detect ACV compared to structurally similar pharmaceutical compounds.

Quantification of mirtazapine in tablets via DNA binding mechanism; development of a new HPLC method.

Atypical antidepressant mirtazapine (MIR) is mostly prescribed for the management of major depressive disorder. The identification of MIR in pharmaceutical dosage forms was made possible by developing a novel, quick, sensitive high-performance liquid chromatography (HPLC) approach that was verified in accordance with ICH recommendations. In the first part of this study, HPLC investigations were optimized with regard to variables including pH, working column, mobile phase, temperature, and flow rate. The limit of detection (LOD) was 0.013 ppm, the limit of quantification (LOQ) was 0.044 ppm, and the linear range was computed as 0.5-15 ppm (R2 = 0.9998). The recovery investigation assessed the method's accuracy, which was shown to range between 98.82 and 100.97 %. In the second part, by using UV-vis spectroscopy, HPLC, thermal denaturation, and viscosity measurements, the mechanism of binding interaction of MIR with double-stranded fish sperm deoxyribonucleic acid (dsDNA) has been thoroughly studied. The DNA binding constants (Kb) were determined using UV-Vis absorption and HPLC methods. To investigate the interactions of MIR with dsDNA, molecular docking calculations and additionally, molecular dynamics simulations were performed. Results showed that MIR is located in the minor groove of dsDNA, and in addition to hydrogen bonding, electrostatic interaction is also formed between the aromatic ring of MIR and phosphate oxygen of dsDNA. Finally, a binding characterization study using MIR tablets was also conducted in order to assess the interaction mechanism of the DNA with the drug using the validated analytical procedure developed for the MIR molecule.

DFT, molecular docking and molecular dynamics simulation studies on some recent natural products revealing their EGFR tyrosine kinase inhibition potential.

Phytochemicals are important chemical compounds in pharmaceutical chemistry. These natural compounds have interesting biological activities, including anticancer, as well as many other functions. EGFR (epidermal growth factor receptor) tyrosine kinase inhibition is emerging as one of the accepted methods in the treatment of cancer. On the other hand, computer-aided drug design has become an increasingly important field of study due to its many important advantages such as efficient use of time and other resources. In this study, fourteen phytochemicals which have triterpenoid structure and have recently entered the literature were investigated computationally for their potential as EGFR tyrosine kinase inhibitors. In the study, DFT (density functional theory) calculations, molecular docking, molecular dynamics simulations, binding free energy calculations with the use of MM-PBSA (molecular mechanics Poisson-Boltzmann Surface Area) method, and ADMET predictions were performed. The obtained results were compared to the results obtained for reference drug Gefitinib. Results showed that the investigated natural compounds are promising structures for EGFR tyrosine kinase inhibition.Communicated by Ramaswamy H. Sarma.

Controlled synthesis and computational analysis of gold nanostars for the treatment of Fusarium oxysporum.

Fusarium oxysporum (F. oxysporum) is linked to the widespread fusarium wilt in plants affecting the quality and yield of food crops. Management of fusarium wilt by synthetic fertilizers poses safety concerns. Safer-by-design nanomaterials synthesized with a greener approach can meet the needs of commercial antifungal drug resistance. Herein, a simple aqueous reduction method has been adopted for the synthesis of anisotropic gold nanostars (AuNSs) using quercetin-para aminobenzoic acid (QPABA) as both a reducing and stabilizing agent at room temperature for the treatment of F. oxysporum. QPABA was used to control the growth of Au3+ star-shaped nanoparticles at increasing concentrations in the ratio of 2 : 1 (QPABA : Au3+ ions) respectively. Transmission electron microscopy (TEM) analysis of the as-prepared gold nanoparticles confirmed the formation of nanostars with sizes of 40 ± 2 nm. The formation of anisotropic gold nanoparticles was evaluated by UV-vis characterizations which showed longitudinal surface plasmon modes at 540 and 800 nm. The gold nanoparticles exhibit excellent antifungal activity against F. oxysporum with the minimum inhibitory concentration (MIC) of 100 µg mL-1 using an agar well-diffusion assay. AuNSs proved to be efficacious in controlling F. oxysporum, as shown in the SEM analysis with a disintegrated cell membrane upon treatment. Computational analysis was performed to determine the specific binding sites on the QPABA ligand for gold ion interactions using the DFT B3LYP method, with a 6-31+G(d) basis set. Results showed that the interaction between Au3+ and QPABA at the 4 and 3 positions yielded the highest stability and formation of gold nanostars. The results suggest that the synthesized AuNSs act as a promising antifungal agent with great potential in treating frequent fungal infections that affect agricultural production.

Probing some recent natural compounds from Phellinus baumii, Colletotrichum sp. and Ligustrum lucidum as heat shock protein 90 inhibitors.

Heat shock protein 90 (HSP90) is one of the most attractive targets for research on cancer treatment, and nowadays, many studies carried out for the development of effective HSP90 inhibitors. In the current study, recently published ten natural compounds have been investigated using computer aided drug design (CADD) approach. The study consists of three parts; (1) density functional theory (DFT) calculations including geometry optimizations, vibrational analyses, and molecular electrostatic potential (MEP) map calculations, (2) molecular docking and molecular dynamics (MD) simulations, and (3) binding energy calculations. In DFT calculations, Becke three-parameter hybrid functional with Lee-Yang-Parr correlation functional (B3LYP) and 6-31 + G(d,p) basis set were used. After performing molecular docking calculations, top-scoring ligand-receptor complexes were subjected to MD simulations for 100 ns to investigate the stability of the ligand-receptor complexes and the interactions in more detail. Finally, in binding energy calculations molecular mechanics with Poisson-Boltzmann surface area (MM-PBSA) method was used. The results showed that five of the investigated ten natural compounds have higher binding affinity to HSP90α than that of reference drug Geldanamycin, and could be promising compounds for future studies.Communicated by Ramaswamy H. Sarma.

Identification of a 3-(5-methyl-2-thiazolylamino)phthalide as a new minor groove agent.

A new 3-(5-methyl-2-thiazolylamino)phthalide molecule, 3-((5-methylthiazol-2-yl)amino)isobenzofuran-1(3H)-one, was synthesized and characterized experimentally by FT-IR, NMR, UV-Vis, and single-crystal X-ray analysis and theoretically by quantum chemical calculations. The single-crystal X-ray studies revealed that the compound crystallizes in the monoclinic space group P-21/c with unit-cell parameters a = 8.0550(6) Å, b = 6.1386(3) Å, c = 23.3228(18) Å, ß = 97.724(6)° and Z = 4. Optimized geometries and the vibrational frequencies were studied at the density functional theory (DFT) level by using the hybrid functional B3LYP with a 6-311 G (d,p) basis set. The title compound was evaluated for its anti-quorum sensing (anti-QS) activity on Chromobacterium violaceum 12472 and additionally for its antibacterial activity against Staphylococcus aureus 29213, Staphylococcus epidermidis 12228, Pseudomonas aeruginosa 27853, Escherichia coli 25922, and Proteus mirabilis 14153. The lowest MIC value was 0.24 µg/mL for S. aureus 29213 and the highest MIC value was 30.75 µg/mL for E. coli 25922. While anti-bacterial activity was observed in those other than the S. epidermidis and P. Mirabilis, anti-QS activity wasn't detected. Investigations on dsDNA binding affinity indicate that the title compound binds to dsDNA via the groove binding mode. Molecular docking calculations and molecular dynamics simulations results showed also that the title compound prefers binding to the minor groove of dsDNA and remains stable in the minor groove throughout the molecular dynamics simulation.Communicated by Ramaswamy H. Sarma.

In-silico investigation of some recent natural compounds for their potential use against SARS-CoV-2: a DFT, molecular docking and molecular dynamics study.

Since its first appearance in December 2019, SARS-CoV-2 has infected many people all over the world, causing serious health problems in many people and causing many deaths, but no specific drug has been developed yet. SARS-CoV-2 main protease (SARS-CoV-2 Mpro) has an important role in viral replication and transcription, so inhibition of this enzyme is proposed to be an attractive route for the treatment of COVID-19. Natural compounds have been used in the treatment of many diseases throughout the history. In this study, it was aimed to investigate SARS-CoV-2 Mpro inhibition abilities, thus the therapeutic potentials of some novel phytochemicals which have recently been entered the literature. For this purpose, eleven novel phytochemicals obtained from various natural resources have been investigated for their potential antiviral activity against SARS-CoV-2 with the use of in silico methods. In the first part of the study, DFT (density functional theory) calculations were performed on the investigated compounds. In this part, geometry optimizations, vibrational analyses, and MEP (molecular electrostatic potential) map calculations were performed. In the second part, molecular docking calculations and then molecular dynamics (MD) simulations were performed to investigate how these natural compounds interact with SARS-CoV-2 Mpro which is a promising target for COVID-19 treatments. In this part, MM-PBSA (molecular mechanics with Poisson-Boltzmann surface area) calculations were also performed to determine the binding free energies of the investigated compounds. Results showed that most of the investigated compounds interacted with SARS-CoV-2 Mpro effectively and can be promising structures for drug development studies for COVID-19.Communicated by Ramaswamy H. Sarma.

DFT, molecular docking and molecular dynamics simulation studies on some newly introduced natural products for their potential use against SARS-CoV-2.

Throughout the history, natural products always give new paths to develop new drugs. As with many other diseases, natural compounds can be helpful in the treatment of COVID-19. SARS-CoV-2 main protease enzyme has an important role in viral replication and transcription. Therefore, inhibiting this enzyme may be helpful in the treatment of COVID-19. In this study, it is aimed to investigate eight natural compounds which have recently entered the literature, computationally for their potential use against SARS-CoV-2. For this purpose, first, density functional theory (DFT) calculations were performed on the investigated compounds, and energy minimizations, geometry optimizations, vibrational analyses, molecular electrostatic potential map calculations were carried out. After DFT calculations, geometry optimized structures were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (pdb id: 5r80) and top-scoring ligand-receptor complexes were obtained. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand-receptor complexes to investigate the stability of the ligand-receptor complexes and the interactions between ligands and receptor in more detail. Additionally, in this part of the study, binding free energies are calculated with the use of molecular mechanics with Poisson-Boltzmann surface area (MM-PBSA) method. Results showed that, all ligand-receptor complexes remain stable during the MD simulations and most of the investigated compounds but especially two of them showed considerably high binding affinity to SARS-CoV-2 main protease. Finally, in the study, ADME (adsorption, desorption, metabolism, excretion) predictions and drug-likeness analyses were performed on the investigated compounds.

Mechanism of Interactions of dsDNA Binding with Apigenin and Its Sulfamate Derivatives Using Multispectroscopic, Voltammetric, and Molecular Docking Studies.

DNA binding investigations are critical for designing better pharmaceutical compounds since the binding of a compound to dsDNA in the minor groove is critical in drug discovery. Although only one in vitro study on the DNA binding mode of apigenin (APG) has been conducted, there have been no electrochemical and theoretical studies reported. We hereby report the mechanism of binding interaction of APG and a new class of sulfonamide-modified flavonoids, apigenin disulfonamide (ADSAM) and apigenin trisulfonamide (ATSAM), with deoxyribonucleic acid (DNA). This study was conducted using multispectroscopic instrumentation techniques, which include UV-vis absorption, thermal denaturation, fluorescence, and Fourier transform infrared (FTIR) spectroscopy, and electrochemical and viscosity measurement methods. Also, molecular docking studies were conducted at room temperature under physiological conditions (pH 7.4). The molecular docking studies showed that, in all cases, the lowest energy docking poses bind to the minor groove of DNA and the apigenin-DNA complex was stabilized by several hydrogen bonds. Also, π-sulfur interactions played a role in the stabilization of the ADSAM-DNA and ATSAM-DNA complexes. The binding affinities of the lowest energy docking pose (schematic diagram of table of content (TOC)) of APG-DNA, ADSAM-DNA, and ATSAM-DNA complexes were found to be -8.2, -8.5, and -8.4 kcal mol-1, respectively. The electrochemical binding constants K b were determined to be (1.05 × 105) ± 0.04, (0.47 × 105) ± 0.02, and (8.13 × 105) ± 0.03 for APG, ADSAM, and ATSAM, respectively (all of the tests were run in triplicate and expressed as the mean and standard deviation (SD)). The K b constants calculated for APG, ADSAM, and ATSAM are in harmony for all techniques. As a result of the incorporation of dimethylsulfamate groups into the APG structure, in the ADSAM-dsDNA and ATSAM-dsDNA complexes, in addition to hydrogen bonds, π-sulfur interactions have also contributed to the stabilization of the ligand-DNA complexes. This work provides new insights that could lead to the development of prospective drugs and vaccines.

Determination of preferred walking speed on treadmill may lead to high oxygen cost on treadmill walking.

The energy consumption of walking relates to the intensity of physical effort and can be affected by the alterations in walking speed. Therefore, walking speed can be accepted as a crucial, determinant of energy consumption measurement for a walking test. We aimed to investigate the differences in preferred walking speed (PWS) determined both on overground and on a treadmill and, to measure walking energy expenditure and spatio-temporal parameters of gait on a treadmill at both, speeds. Participants (n=26) walked on a treadmill at two pre-determined speeds for 7 min while, indirect calorimetry measurements were being performed. Spatio-temporal parameters were collected, by video-taping during each walking session on a treadmill. The average overground preferred walking speed (O-PWS) was 85.96+/-12.82 m/min and the average treadmill preferred walking speed (T-PWS), was 71.15+/-13.85 m/min. Although T-PWS was lower, oxygen cost was statistically higher when, treadmill walking at T-PWS (0.158+/-0.02 ml/kg/m) than when the treadmill walking at O-PWS, (0.1480+/-0.02 ml/kg/m). Cadence (127+/-9.13 steps/min), stride (134.02+/-14.09 cm) and step length (67.02+/-6.90 cm) on the treadmill walking at O-PWS were significantly higher than cadence (119+/-10 steps/min), stride (117.96+/-14.38 cm) and step length (59.13+/-7.02 cm) on the treadmill walking at TPWS. In conclusion, walking on treadmill using O-PWS is more efficient than walking on treadmill using TPWS, in walking tests. Since using T-PWS for treadmill walking tests overestimates the oxygen cost of walking, O-PWS should be used for oxygen consumption measurement during treadmill walking tests.

2-(1H-Benzimidazol-1-yl)-1-(2-furyl)ethanone O-propyloxime.

In the mol-ecule of the title compound, C(16)H(17)N(3)O(2), the planar benzimidazole ring system [maximum deviation = 0.013 (1) Å] is oriented at a dihedral angle of 75.32 (4)° with respect to the furan ring. An intra-molecular C-H⋯O inter-action results in the formation of a planar six-membered ring [maximum deviation = 0.019 (15) Å], which is oriented at a dihedral angle of 1.91 (3)° with respect to the adjacent furan ring. In the crystal structure, inter-molecular C-H⋯N inter-actions link the mol-ecules into centrosymmetric R(2) (2)(18) dimers. In addition, the structure is stabilized by π-π contacts between the imidazole rings [centroid-centroid distance = 3.5307 (8) Å] and weak C-H⋯π inter-actions.

2-(1H-Benzimidazol-1-yl)-1-(2-fur-yl)ethanone O-isopropyl-oxime.

In the mol-ecule of the title compound, C(16)H(17)N(3)O(2), the planar benzimidazole ring system [maximum deviation = 0.015 (2) Å] is oriented at a dihedral angle of 72.17 (4)° with respect to the furan ring. An intra-molecular C-H⋯O inter-action results in the formation of a six-membered ring having an envelope conformation. In the crystal structure, inter-molecular C-H⋯N inter-actions link the mol-ecules into centrosymmetric R(2) (2)(18) dimers.

2-(1H-Benzimidazol-1-yl)-1-(2-fur-yl)ethanone O-ethyl-oxime.

In the mol-ecule of the title compound, C(15)H(15)N(3)O(2), the planar benzimidazole ring system [maximum deviation = 0.023 (2) Å] is oriented at a dihedral angle of 74.21 (5)° with respect to the furan ring. In the crystal structure, inter-molecular C-H⋯N inter-actions link the mol-ecules into centrosymmetric R(2) (2)(18) dimers. In addition, the structure is stabilized by π-π contacts between parallel imidazole rings [centroid-centroid distance = 3.726 (1) Å] and a weak C-H⋯π inter-action.

2-(1H-Benzimidazol-1-yl)-1-phenyl-ethanone.

In the mol-ecule of the title compound, C(15)H(12)N(2)O, the planar benzimidazole system is oriented at a dihedral angle of 80.43 (5)° with respect to the phenyl ring. In the crystal structure, non-classical inter-molecular C-H⋯N and C-H⋯O hydrogen bonds link the mol-ecules into layers parallel to the ab plane.

1-[2-(2,6-Dichloro-benz-yloxy)-2-(2-fur-yl)eth-yl]-1H-benzimidazole.

In the mol-ecule of the title compound, C(20)H(16)Cl(2)N(2)O(2), the planar benzimidazole ring system is oriented with respect to the furan and dichloro-benzene rings at dihedral angles of 53.39 (6) and 31.04 (5)°, respectively. In the crystal structure, inter-molecular C-H⋯Cl hydrogen bonds link the mol-ecules into centrosymmetric R(2) (2)(8) dimers. These dimers are connected via a C-H⋯π contact between the benzimidazole and the furan rings, and π-π contacts between the benz-imidazole and dichloro-benzene ring systems [centroid-centroid distances = 3.505 (1), 3.567 (1), 3.505 (1) and 3.567 (1) Å].

1-[2-(4-Fluoro-benz-yloxy)-2-phenyl-ethyl]-1H-benzimidazole.

The asymmetric unit of the title compound, C(22)H(19)FN(2)O, contains two independent mol-ecules. The planar benzimidazole ring systems are oriented with respect to the phen-yl/fluoro-benzene rings at dihedral angles of 31.10 (4)/45.17 (5) and 45.52 (5)/68.63 (5)°, respectively, for the two mol-ecules. In the crystal structure, inter-molecular C-H⋯N and inter-molecular C-H⋯N and C-H⋯F hydrogen bonds link the mol-ecules into a three-dimensional network. There are C-H⋯π contacts between the benzimidazole and fluoro-benzene rings and a π-π contact between the benzimidazole and phenyl ring systems [centroid-centroid distance = 4.575 (1) Å].

1-[2-(3,4-Dichloro-benz-yloxy)-2-phenyl-ethyl]-1H-benzimidazole.

In the mol-ecule of the title compound, C(22)H(18)Cl(2)N(2)O, the planar benzimidazole ring system is oriented with respect to the phenyl and dichloro-benzene rings at dihedral angles of 12.73 (3) and 36.57 (4)°, respectively. The dihedral angle between the dichloro-benzene and phenyl rings is 29.95 (6)°. There are C-H⋯π contacts between the benzimidazole and dichloro-benzene rings, between the benzimidazole and phenyl rings, and between a methylene group and the dichlorobenzene ring.

1-{2-Phenyl-2-[4-(trifluoro-meth-yl)-benzyl-oxy]eth-yl}-1H-benzimidazole.

The asymmetric unit of the crystal structure of the title compound, C(23)H(19)F(3)N(2)O, contains two independent mol-ecules. In the two mol-ecules the planar benzimidazole ring systems are oriented with respect to the phen-yl/trifluoro-methyl-benzene rings at dihedral angles of 9.62 (6)/78.63 (7) and 2.53 (8)/83.83 (9)°. In the crystal structure, inter-molecular C-H⋯N hydrogen bonds link the mol-ecules into R(2) (2)(6) dimers. The mol-ecules are elongated along [001] and stacked along the b axis.