A New Concept of Enhancing the Anticancer Activity of Manganese Terpyridine Complex by Oxygen-Containing Substituent Modification.

Eleven manganese 4'-substituted-2,2':6',2″-terpyridine complexes (1a-1c and 2a-2h) with three non-oxygen-containing substituents (L1a-L1c: phenyl, naphthalen-2-yl and naphthalen-1-yl, L1a-L1c) and eight oxygen-containing substituents (L2a-L2h: 4-hydroxyl-phenyl, 3-hydroxyl-phenyl, 2-hydroxyl-phenyl, 4-methoxyl-phenyl, 4-carboxyl-phenyl, 4-(methylsulfonyl)phenyl, 4-nitrophenyl and furan-2-yl) were prepared and characterized by IR, elemental analysis or single crystal X-ray diffraction. In vitro data demonstrate that all of these show higher antiproliferative activities than cisplatin against five human carcinoma cell lines: A549, Bel-7402, Eca-109, HeLa and MCF-7. Compound 2d presents the strongest antiproliferative effect against A549 and HeLa cells, with IC50 values being 0.281 µM and 0.356 µM, respectively. The lowest IC50 values against Bel-7402 (0.523 µM) Eca-109 (0.514 µM) and MCF-7 (0.356 µM) were obtained for compounds 2h, 2g and 2c, respectively. Compound 2g with a nitro group showed the best results on the whole, with relevantly low IC50 values against all the tested tumor cells. The DNA interactions with these compounds were studied by circular dichroism spectroscopic and molecular modeling methods. Spectrophotometric results revealed that the compounds have strong affinities in binding with DNA as intercalators, and the binding induces DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π-π stacking and hydrogen bonds. The anticancer activities of the compounds are correlated with their DNA binding ability, and the modification of oxygen-containing substituents significantly enhanced the anticancer activity, which could provide a new rationale for the future design of terpyridine-based metal complexes with antitumor potential.

Under Psychological Safety Climate: The Beneficial Effects of Teacher-Student Conflict.

Previous studies have mainly focused on the negative effects of teacher-student conflict; the positive effects of conflict have rarely been mentioned. This paper suggests that encouraging conflict could act as a teaching method to improve students' innovative competence. This study has two objectives: (1) to examine how various types of teacher-student conflict affects students' innovative competence and (2) to identify the mediating role of a psychological safety climate in the association between conflict and students' innovative competence. To achieve the objectives, we used evidence from 1207 university students. Multivariable logistic regression analysis revealed that conflicts were associated with students' innovative competence, and the mediation role of a psychological safety climate is significant. Specifically, the results revealed that Cognitive Conflict had significant positive effects on students' innovative competence, whereas Affective Conflict had a significant negative effect on students' innovative competence. In addition, we clarified a psychological safety climate as the boundary condition for the relationship between conflict and students' innovative competence.

Creativity: The Effectiveness of Teacher-Student Conflict.

This study examines the effectiveness of different types of teacher-student conflict in promoting students' creativity in universities. Previous studies mainly focused on the negative effects of conflict; few examined its positive effects. Teacher-student conflict in university classes can take many forms; however, there are no clear definitions of the various types of such conflict. This study classified teacher-student conflict as understanding conflict, process conflict, and relationship conflict, and we used this classification to extend prior research by revealing the beneficial impacts of teacher-student conflict on students' creativity. We empirically examined the relationship between teacher-student conflict and students' creativity. The hypotheses were supported by using data from questionnaires completed by 2009 students at 17 American universities. We then conducted a hierarchical regression analysis of the data using structural equation modeling. The findings indicate that understanding conflict and process conflict had significant positive effects on students' creativity, whereas relationship conflict had a significant negative effect on students' creativity. This study thus revealed the positive effect of teacher-student conflict in university classes and suggests encouraging conflict (understanding conflict and process conflict) as a unique teaching method to stimulate students' creativity.

Synthesis, Characterization, Photoluminescence, Molecular Docking and Bioactivity of Zinc (II) Compounds Based on Different Substituents.

Six new zinc(II) complexes were prepared by the reaction of ZnBr2 or ZnI2 with 4'-(substituted-phenyl)-2,2':6',2''-terpyridine compounds, bearing p-methylsulfonyl (L1), p-methoxy (L2) and p-methyl (L3), which were characterized by elemental analysis, FT-IR, NMR and single crystal X-ray diffraction. The antiproliferative properties against Eca-109, A549 and Bel-7402 cell lines and the cytotoxicity test on RAW-264.7 of these compounds were monitored using a CCK-8 assay, and the studies indicate that the complexes show higher antiproliferative activities than cisplatin. The interactions of these complexes with CT-DNA and proteins (BSA) were studied by UV-Vis, circular dichroism (CD) and fluorescent spectroscopy, respectively. The results indicate that the interaction of these zinc(II) complexes with CT-DNA is achieved through intercalative binding, and their strong binding affinity to BSA is fulfilled through a static quenching mechanism. The simulation of the complexes with the CT-DNA fragment and BSA was studied by using molecular docking software. It further validates that the complexes interact with DNA through intercalative binding mode and that they have a strong interaction with BSA.

Synthesis, characterization, photoluminescence, antiproliferative activity, and DNA interaction of cadmium(II) substituted 4'-phenyl-terpyridine compounds.

A series of CdCl2 complexes (1a-1f and 2a-2c) with 4'-(substituted-phenyl)-2,2':6',2″-terpyridine compounds bearing hydrogen (L1a), p-methyl (L1b), p-phenyl (L1c), p-tolyl (L1d), p-carboxyl (L1e), p-fluoro (L1f), p-hydroxyl (L2a), m-hydroxyl (L2b) or o-hydroxyl (L2c), were prepared and characterized by 1H NMR, IR, elemental analysis and single crystal X-ray diffraction. All the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The in vitro antiproliferative activities against four human carcinoma cell lines, A549, Bel-7402, Eca-109 and MCF-7, were investigated and cell viability studies indicate that the compounds have excellent results with the lowest IC50 values of 0.372 (1c), 1.003 (1c), 1.161 (1b) and 0.231 (1c) µM, respectively. The DNA interaction was studied by fluorescence titration, circular dichroism spectroscopy and molecular modeling methods. Spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalators and molecular docking studies indicate that the binding is contributed by the π…π stacking and hydrogen bonds.

Study on the substitution effects of zinc benzoate terpyridine complexes on photoluminescence, antiproliferative potential and DNA binding properties.

Six zinc(II) complexes, [Zn(OCOPh)2LR] (R = 1, 2, 3, 4, 5, 6) were synthesized by the reaction of zinc benzoate and six para-substituted 4-phenyl-terpyridine complexes and their structures were confirmed by elemental analysis, FT-IR, 1H NMR and X-ray single crystal diffraction analysis. Their photoluminescent properties in solid and in solutions of DMSO were studied. Three human cancer cell lines were used for antiproliferative potential: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109) and human breast cancer cell line (MCF-7). The results have shown that these zinc complexes have good inhibitory effects on cancer cells, which are better than that of the commonly used clinical drug cisplatin. The ability of the complexes to binding to CT-DNA was studied by UV spectroscopy and fluorescence titration, while the interaction between the complexes and CT-DNA, AT6, GC6 short-chain DNA sequences and G-quadruplex were analyzed by circular dichroism (CD). It is found that these complexes can bind to DNA, and the binding mode is mainly intercalator. The docking of the complexes with the DNA fragment was simulated using molecular docking software. All the results clearly display that the substituents at these ligands of the complexes have the substitution effects on the properties of photoluminescence, antiproliferative potential and DNA binding study.

Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction.

A series of ZnCl2 complexes (compounds 1-10) with 4'-(substituted-phenyl)-2,2':6',2''-terpyridine that bears hydrogen (L1), p-methyl (L2), p-methoxy (L3), p-phenyl (L4), p-tolyl (L5), p-hydroxyl (L6), m-hydroxyl (L7), o-hydroxyl (L8), p-carboxyl (L9), or p-methylsulfonyl (L10) were prepared and then characterized by 1H NMR, electrospray mass-spectra (ESI-MS), IR, elemental analysis, and single crystal X-ray diffraction. In vitro cytotoxicity assay was used to monitor the antiproliferative activities against tumor cells. Absorption spectroscopy, fluorescence titration, circular dichroism spectroscopy, and molecular modeling studied the DNA interactions. All of the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The cell viability studies indicate that the compounds have excellent antiproliferative activity against four human carcinoma cell lines, A549, Bel-7402, MCF-7, and Eca-109, with the lowest IC50 values of 0.33 (10), 0.66 (6), 0.37 (7), and 1.05 (7) µM, respectively. The spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalator and induce DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π…π stacking and hydrogen bonds, providing an order of nucleotide sequence binding selectivity as ATGC > ATAT > GCGC. These compounds intercalate into the base pairs of the DNA of the tumor cells to affect their replication and transcription, and the process is supposed to play an important role in the anticancer mechanism.

Synthesis, characterization, photoluminescence, anti-tumor activity, DFT calculations and molecular docking with proteins of zinc(ii) halogen substituted terpyridine compounds.

Reactions between halogen substituted terpyridine ligands F- (L1), Cl- (L2), Br- (L3) and I-4'-phenyl-terpyridine (L4) and ZnBr2 or ZnI2 led to the formation of complexes [Zn(Br)2L1] (1), [Zn(i)2L1] (2), [Zn(Br)2L2] (3), [Zn(i)2L2] (4), [Zn(Br)2L3] (5), [Zn(i)2L3] (6), [Zn(Br)2L4] (7), and [Zn(i)2L4] (8), respectively, which were characterized by elemental analysis, 1H NMR, IR and single crystal X-ray diffraction. Their photoluminescence properties, solution stabilities, hydrophilicity/lipophilicity properties and anti-proliferative activity against three cancer cell lines as well as structure-function relationships are analyzed. All the complexes, which show high solution stabilities and lipophilicity under determination conditions, reveal much higher antiproliferative activities than cisplatin against the human lung carcinoma cell line (A549), human hepatocellular carcinoma cell line (Bel-7042) and human breast cancer cell line (MCF-7) in vitro. Fluorescence spectroscopy and circular dichroic analysis reveal that the compounds have strong affinity binding with ctDNA and stack onto the base pairs of the ctDNA. The results obtained are further explained in terms of the electronic properties of the compounds by density functional theory (DFT) calculations, and it is found that the halogen anions play critical roles in the antitumor activity of these compounds. Their affinities to HSP90 proteins, ALK, EGFR and HER2 kinases and the binding sites on these proteins have been determined by computational docking analysis, and the results indicate that the only form of their binding is van der Waals forces.