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Several new thiazole derivatives linked pyrazole and/or pyridine rings were synthesized based on the versatile precursor 2-(5-acetyl-4-methyl-3-phenylthiazol-2(3H)-ylidene)acetonitrile (1). The synthesized derivatives were optimized using DFT approach in order to inspect the configurations and energies of the HOMO-LUMO orbitals. The data disclosed low energy gap (ΔEH-L), 0.99–2.54 eV, following the order 9

Two newly synthesized coumarin–palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and 1H-13C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.hi926), and pancreatic ductal adenocarcinoma (Panc-1). In order to examine the in silico inhibitory potential and estimate inhibitory constants and binding energies, molecular docking studies were performed. The inhibitory activity of C1 and C2 was investigated towards epidermal growth factor receptor (EGFR), receptor tyrosine kinase (RTK), and B-cell lymphoma 2 (BCL-2). According to the results obtained from the molecular docking simulations, the inhibitory activity of the investigated complexes towards all the investigated proteins is equivalent or superior in comparison with current therapeutical options. Moreover, because of the low binding energies and the high correlation rate with experimentally obtained results, it was shown that, out of the three, the inhibition of RTK is the most probable mechanism of the cytotoxic activity of the investigated compounds. [ABSTRACT FROM AUTHOR]

Two newly synthesized coumarin–palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and 1H-13C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.hi926), and pancreatic ductal adenocarcinoma (Panc-1). In order to examine the in silico inhibitory potential and estimate inhibitory constants and binding energies, molecular docking studies were performed. The inhibitory activity of C1 and C2 was investigated towards epidermal growth factor receptor (EGFR), receptor tyrosine kinase (RTK), and B-cell lymphoma 2 (BCL-2). According to the results obtained from the molecular docking simulations, the inhibitory activity of the investigated complexes towards all the investigated proteins is equivalent or superior in comparison with current therapeutical options. Moreover, because of the low binding energies and the high correlation rate with experimentally obtained results, it was shown that, out of the three, the inhibition of RTK is the most probable mechanism of the cytotoxic activity of the investigated compounds.

Several new thiazole derivatives linked pyrazole and/or pyridine rings were synthesized based on the versatile precursor 2-(5-acetyl-4-methyl-3-phenylthiazol-2(3 H)-ylidene)acetonitrile (1). The synthesized derivatives were optimized using DFT approach in order to inspect the configurations and energies of the HOMO-LUMO orbitals. The data disclosed low energy gap (ΔE H-L), 0.99–2.54 eV, following the order 9 < 3 = 4 ≈ 2 ≈ 8 < 5 < 1 < 7 ≈ 6. The in vitro anticancer activity of the new thiazole hybrids was tested against three cancer cell lines (HepG2, HCT-116, and MCF-7) as well as standard fibroblast cells (WI38) using Doxorubicin as a reference drug. The thiazole-pyridine hybrids 8 and 9 exhibited high cytotoxic efficacies against the MCF-7 cell line, IC 50 28.53 ± 0.39 and 25.47 ± 0.54 µM. Moreover, the synthesized hybrids were docked against the crystal structure of (PDB: 3rcd) as a representative protein for the human epidermal growth factor receptor (HER2) to approve the relationship between the in vitro cytotoxicity results and inhibitor binding interactions. The docking study showed that thiazole-pyridine hybrids 8 and 9 displayed the highest score of bindings, which was compatible with the results of the cytotoxicity results. [ABSTRACT FROM AUTHOR]

The identification of molecules whose biological activity can be properly modulated by light is a promising therapeutic approach aimed to improve drug selectivity and efficacy on the molecular target and to limit the side effects compared to traditional drugs. Recently, two photo-switchable diastereomeric benzodiazopyrrole derivatives 1RR and 1RS have been reported as microtubules targeting agents (MTAs) on human colorectal carcinoma p53 null cell line (HCT 116 p53-/-). Their IC50 was enhanced upon Light Emitting Diode (LED) irradiation at 435 nm and was related to their cis form. Here we have investigated the photo-responsive behavior of the acid derivatives of 1RR and 1RS, namely, d1RR and d1RS, in phosphate buffer solutions at different pH. The comparison of the UV spectra, acquired before and after LED irradiation, indicated that the trans→cis conversion of d1RR and d1RS is affected by the degree of ionization. The apparent rate constants were calculated from the kinetic data by means of fast UV spectroscopy and the conformers of the putative ionic species present in solution (pH range: 5.7−8.0) were modelled. Taken together, our experimental and theoretical results suggest that the photo-conversions of trans d1RR/d1RS into the corresponding cis forms and the thermal decay of cis d1RR/d1RS are dependent on the presence of diazonium form of d1RR/d1RS. Finally, a photo-reaction was detected only for d1RR after prolonged LED irradiation in acidic medium, and the resulting product was characterized by means of Liquid Chromatography coupled to High resolution Mass Spectrometry (LC-HRMS) and Nuclear Magnetic Resonance (NMR) spectroscopy.

Bimetallic clusters are of particular interest in several applications due to the unique properties they exhibit as a result of the synergistic effect of their metals. In addition, the substrate can alter the structure and stability of these clusters by means of cluster–support interactions. In this work, we study the physicochemical properties of Au–Pd/TiO 2 (110) supported clusters v i a density functional theory (DFT) calculations. The effect of surface TiO 2 (110) on the structural and energetic properties of Au–Pd clusters is relevant. The cohesion energy depends on both metal–metal and metal–support interactions. Au and Au-rich bimetallic clusters change their gas phase configuration upon adsorption. Some clusters do not fit well on the surface, resulting in decreased stability. By contrast, pure Pd and Pd-rich bimetallic clusters have the highest adsorption energies and charge polarization due to the cluster–surface interaction. These clusters exhibit elongation in the metal–metal bonds and redshifts in their vibrations. The Bader charge analysis shows that Au–Pd clusters donate charge to the surface, thus becoming positively charged. Finally, the TiO 2 (110) surface induces stiffness in the clusters, since the supported clusters do not exhibit low-frequency vibrations like their gas-phase analogs. [Display omitted] • The effect of TiO 2 (110) surface is relevant in pure Au and Au-rich bimetallic clusters. • Cohesion of supported clusters depends on metal–metal and metal–support interactions. • The TiO 2 (110) surface provides structural rigidity to the clusters. • Metal–support interaction leads to charge transfer from the surface to the cluster. [ABSTRACT FROM AUTHOR]

To find low energy SinCn structures out of hundreds to thousands of isomers we have developed a general method to search for stable isomeric structures that combines Stochastic Potential Surface Search and Pseudopotential Plane-Wave Density Functional Theory Car-Parinello Molecular Dynamics simulated annealing (PSPW-CPMD-SA). We enhanced the Sunders stochastic search method to generate random cluster structures used as seed structures for PSPW-CPMD-SA simulations. This method ensures that each SA simulation samples a different potential surface region to find the regional minimum structure. By iterations of this automated, parallel process on a high performance computer we located hundreds to more than a thousand stable isomers for each SinCn cluster. Among these, five to 10 of the lowest energy isomers were further optimized using B3LYP/cc-pVTZ method. We applied this method to SinCn (n = 4–12) clusters and found the lowest energy structures, most not previously reported. By analyzing the bonding patterns of low energy structures of each SinCn cluster, we observed that carbon segregations tend to form condensed conjugated rings while Si connects to unsaturated bonds at the periphery of the carbon segregation as single atoms or clusters when n is small and when n is large a silicon network spans over the carbon segregation region.

Two newly synthesized coumarin-palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and 1 H- 13 C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.hi926), and pancreatic ductal adenocarcinoma (Panc-1). In order to examine the in silico inhibitory potential and estimate inhibitory constants and binding energies, molecular docking studies were performed. The inhibitory activity of C1 and C2 was investigated towards epidermal growth factor receptor (EGFR), receptor tyrosine kinase (RTK), and B-cell lymphoma 2 (BCL-2). According to the results obtained from the molecular docking simulations, the inhibitory activity of the investigated complexes towards all the investigated proteins is equivalent or superior in comparison with current therapeutical options. Moreover, because of the low binding energies and the high correlation rate with experimentally obtained results, it was shown that, out of the three, the inhibition of RTK is the most probable mechanism of the cytotoxic activity of the investigated compounds.

Abstract: In this paper the comparative structural analysis of a series of compounds (methyl α-d-glucopyranoside, methyl 4,6-O-ethylidene-α-d-glucopyranoside (2), methyl 2,3-di-O-nitro-4,6-O-ethylidene-α-d-glucopyranoside and methyl 3-O-nitro-4,6-O-ethylidene-α-d-glucopyranoside) by way of synthesis leading to methyl 3-O-nitro-α-d-glucopyranoside (5) is reported. The title compound (5) is a novel d-glucosidic mononitrate having potential biological activity against cardiovascular diseases. The structural analysis was supported by single-crystal X-ray diffraction (XRD), 13C CP/MAS NMR spectroscopy and DFT calculations. In the case of 2 and 5, XRD analysis could not be performed due to the fact that 2 is highly hygroscopic and 5 forms improper crystals. However, the molecular structures of 2 and 5 were obtained on the basis of experimental (existing XRD data for similar compounds) and theoretical (DFT optimization) approaches. This showed of very good agreement with the 13C CP/MAS NMR spectral data. [Copyright &y& Elsevier]

To find low energy SinCn structures out of hundreds to thousands of isomers we have developed a general method to search for stable isomeric structures that combines Stochastic Potential Surface Search and Pseudopotential Plane-Wave Density Functional Theory Car-Parinello Molecular Dynamics simulated annealing (PSPW-CPMD-SA). We enhanced the Sunders stochastic search method to generate random cluster structures used as seed structures for PSPW-CPMD-SA simulations. This method ensures that each SA simulation samples a different potential surface region to find the regional minimum structure. By iterations of this automated, parallel process on a high performance computer we located hundreds to more than a thousand stable isomers for each SinCn cluster. Among these, five to 10 of the lowest energy isomers were further optimized using B3LYP/cc-pVTZ method. We applied this method to SinCn (n = 4-12) clusters and found the lowest energy structures, most not previously reported. By analyzing the bonding patterns of low energy structures of each SinCn cluster, we observed that carbon segregations tend to form condensed conjugated rings while Si connects to unsaturated bonds at the periphery of the carbon segregation as single atoms or clusters when n is small and when n is large a silicon network spans over the carbon segregation region. [ABSTRACT FROM AUTHOR]

The development of aggregation-induced emission enhancement (AIEE) active nanoprobes without any synthetic complication for solution-state and organic thin-film transistor (OTFT)-based sensory applications is still a challenging task. In this study, the novel pyrene-incorporated Schiff base (5-phenyl-4-((pyren-1-ylmethylene)amino)-4 H -1,2,4-triazole-3-thiol; PT2 ) with an AIEE property was synthesized via a one-pot reaction and was reported for detecting Zn 2+ and tyrosine in the solution state and OTFT. In the AIEE studies of PT2 (in CH 3 CN) at various water fractions ( f w : 0-97.5%), the existence of J -aggregation, crystalline changes, and nanofibers formation was confirmed by ultraviolet absorption/photoluminescence (UV/PL) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic-light scattering (DLS) techniques. Similarly, PT2 -based Zn 2+ detection and sensory reversibility with tyrosine were demonstrated by UV/PL studies with evidence related to crystalline/nanolevel changes in PXRD, SEM, TEM, AFM, and DLS data. Distinct decay profiles associated with the AIEE and sensory responses of PT2 were observed in time-resolved photoluminescence spectra. From the standard deviation and linear fittings of PL titrations, detection limits (LODs) of the Zn 2+ with PT2 and the tyrosine with PT2 -Zn 2+ were estimated as 0.79 and 45 nM, respectively. High-resolution mass and 1 H NMR results confirmed 2:1 and 1:1 stoichiometry and binding sites of PT2 -Zn 2+ - PT2* and tyrosine-Zn 2+ complexes. Moreover, the values of association constants determined by linear fittings were 4.205 × 10 -7 and 1.73 × 10 -8 M -2 , correspondingly. Optimization via the density functional theory disclosed the binding sites and suppression of twisted intramolecular charge transfer/photoinduced electron transfer (TICT/PET) as well as the involvement of restricted intramolecular rotation in the AIEE and PET "ON-OFF-ON" mechanisms in the Zn 2+ and tyrosine sensors. Results from the B16-F10 cellular and zebrafish imaging of AIEE, Zn 2+ , and tyrosine sensors further attested the applicability of PT2 in biological samples. Finally, the PT2 and pentacene-incorporated OTFT devices were fabricated. The devices displayed more than 90% change in drain-source current when reacted with Zn 2+ with an LOD of 5.46 μM but showed no response to tyrosine, thereby confirming the reversibility. Moreover, the OTFT devices also demonstrated Zn 2+ ion detection in tap water and lake water samples.

The identification of molecules whose biological activity can be properly modulated by light is a promising therapeutic approach aimed to improve drug selectivity and efficacy on the molecular target and to limit the side effects compared to traditional drugs. Recently, two photo-switchable diastereomeric benzodiazopyrrole derivatives 1RR and 1RS have been reported as microtubules targeting agents (MTAs) on human colorectal carcinoma p53 null cell line (HCT 116 p53-/-). Their IC50 was enhanced upon Light Emitting Diode (LED) irradiation at 435 nm and was related to their cis form. Here we have investigated the photo-responsive behavior of the acid derivatives of 1RR and 1RS, namely, d1RR and d1RS, in phosphate buffer solutions at different pH. The comparison of the UV spectra, acquired before and after LED irradiation, indicated that the trans→cis conversion of d1RR and d1RS is affected by the degree of ionization. The apparent rate constants were calculated from the kinetic data by means of fast UV spectroscopy and the conformers of the putative ionic species present in solution (pH range: 5.7–8.0) were modelled. Taken together, our experimental and theoretical results suggest that the photo-conversions of transd1RR/d1RS into the corresponding cis forms and the thermal decay of cisd1RR/d1RS are dependent on the presence of diazonium form of d1RR/d1RS. Finally, a photo-reaction was detected only for d1RR after prolonged LED irradiation in acidic medium, and the resulting product was characterized by means of Liquid Chromatography coupled to High resolution Mass Spectrometry (LC-HRMS) and Nuclear Magnetic Resonance (NMR) spectroscopy. [ABSTRACT FROM AUTHOR]