•Eight new copper(II) coordination complexes synthesized and characterized•Copper(II) complexes possess alky-substituted 1,10-phenanthroline and 2,2′-bipyridine ligands.•Five copper(II) complexes characterized by single crystal X-ray diffraction•Three distorted tetrahedral, one distorted square pyramidal, and one dimeric complex described•Copper(II) complexes exhibit general in-vitro antitumor activity against lung tumor cells.In an effort to find alternatives to the antitumor drug cisplatin, a series of copper (II) complexes possessing alkyl-substituted polypyridyl ligands have been synthesized. Eight new complexes are reported herein: μ-dichloro-bis{2,9-di-sec-butyl-1,10-phenanthrolinechlorocopper(II)} {[(di-sec-butylphen)ClCu(μ-Cl)2CuCl(di-sec-butylphen)]}(1), 2-sec-butyl-1,10-phenanthrolinedichlorocopper(II) {[mono-sec-butylphen) CuCl2} (2), 2,9-di-n-butyl-1,10-phenanthrolinedichlorocopper(II) {[di-n-butylphen) CuCl2}(3), 2-n-butyl-1,10-phenanthrolinedichlorocopper(II) {[mono-n-butylphen) CuCl2} (4), 2,9-di-methyl-1,10-phenanthrolineaquadichlorocopper(II) {[di-methylphen) Cu(H2O)Cl2}(5), μ-dichloro-bis{6-sec-butyl-2,2′-bipyridinedichlorocopper(II)} {(mono-sec-butylbipy) ClCu(μ-Cl)2CuCl(mono-sec-butylbipy)} (6), 6,6′-di-methyl-2,2′-bipyridinedichlorocopper(II) {6,6′-di-methylbipy) CuCl2} (7), and 4,4′-dimethyl-2,2′-bipyridinedichlorocopper(II) {4,4′-di-methylbipy) CuCl2} (8). These complexes have been characterized via elemental analysis, UV–vis spectroscopy, and mass spectrometry. Single crystal X-ray diffraction experiments revealed the complexes synthesized with the di-sec-butylphen ligand (1) and mono-sec-butylbipy ligand (6) crystallized as dimers in which two copper(II) centers are bridged by two chloride ligands. Conversely, complexes 2, 7, and 8 were isolated as monomeric species possessing distorted tetrahedral geometries, and the [(di-methylphen)Cu(H2O)Cl2] (5) complex was isolated as a distorted square pyramidal monomer possessing a coordinating aqua ligand. Compounds 1–8 were evaluated for their in vitro antitumor efficacy. Compounds 1, 5, and 7 in particular were found to exhibit remarkable activity against human derived lung cancer cells, yet this class of copper(II) compounds had minimal cytotoxic effect on non-cancerous cells. In vitro control experiments indicate the activity of the copper(II) complexes most likely does not arise from the formation of CuCl2 and free polypyridyl ligand, and preliminary solution state studies suggest these compounds are generally stable in biological buffer. The results presented herein suggest further development of this class of copper-based drugs as potential anti-cancer therapies should be pursued.Treatment of lung cancer cell line A549 with of alkyl-substituted polypyridyl copper(II) complexes shows promising antiproliferative activity as well as a high degree of selectivity for cancerous cells over benign somatic cells.

In the face of mounting evidence revealing active learning approaches result in improved student learning outcomes compared to traditional passive lecturing, there is a growing need to change the way instructors teach large introductory science courses. However, a large proportion of STEM faculty continues to use traditional instructor-centered lectures in their classrooms. In an effort to create a low barrier approach for the implementation of active learning pedagogies in introductory science courses, flipped classroom modules for large enrollment general chemistry course sequence have been created. Herein is described how student response systems (clickers) and problem-based case studies have been used to increase student engagement, and how flipped classroom modules have integrated these case studies as collaborative group problem solving activities in 250–500 seat lecture halls. Preliminary evaluation efforts found the flipped classroom modules provided convenient access to learning materials that increased the use of active learning in lecture and resulted in a significant improvement in the course grade point average (GPA) compared to a non-flipped class. These results suggest this approach to implementing a flipped classroom can act as a model for integrating active learning into large enrollment introductory chemistry courses that yields successful outcomes.

Gold(III) complexes bearing bidentate ligands based on the 1,10-phenanthroline and 2,2′-bipyridine scaffolds have shown promising anticancer activity against a variety of tumor cell lines. In particular, our laboratory has previously found that a pseudo five coordinate gold(III) complex possessing the 2,9-di-sec-butyl-1,10-phenanthroline ligand {[(di-sec-butylphen)AuCl3]} exhibits antitumor activity against a panel of five different lung and head–neck tumor cell lines. However, the [(di-sec-butylphen)AuCl3] complex was determined to be less active than the free 2,9-di-sec-butyl-1,10-phenanthroline ligand. In order to determine if this class of gold(III) complexes has a distinct mechanism of initiating tumor cell death or if these gold complexes simply release the polypyridyl ligand in the intracellular environment, structural analogues of the [(di-sec-butylphen)AuCl3] complex have been synthesized and structurally characterized. These structural congeners were prepared by using mono-alkyl and di-phenyl substituted 1,10-phenanthroline ligands, di-alkyl and di-phenyl substituted 4-methyl-1,10-phenanthroline ligands, and mono-alkyl 2,2′-bipyridine ligands. The redox stability of this library of distorted square pyramidal gold(III) complexes has been studied and the in vitro antitumor activity of gold(III) complexes and corresponding polypyridyl ligands has been determined. The [(di-n-butylphen)AuCl3] and [(mono-n-butylphen)AuCl3] complexes have been found to be significantly more potent at inhibiting the growth of A549 lung tumor cells than the clinically used drug cisplatin. More importantly, these two gold(III) complexes are significantly more active than their respective free ligands, providing evidence that this class of pseudo five coordinate gold(III) complexes has a mechanism of initiating tumor cell death that is independent of the free ligand.[(di-sec-butylphen)AuCl3] was found to possess less pronounced anticancer activity than the 2,9-di-sec-butyl-1,10-phenanthroline ligand. [(di-n-butylphen)AuCl3] and [(mono-n-butylphen)AuCl3] inhibit in vitro tumor cell growth more than their respective free ligands. Therefore, this class of pseudo five coordinate gold(III) complexes likely has a different antitumor mechanism that is independent of the free ligand.

•Two unusual five-coordinate gold(III) coordination complexes have been synthesized.•[(sec-butylphen)AuCl3] was found to have lower in vitro IC50 values than cisplatin.•[(sec-butylphen)AuCl3] was found to have limited in vivo antitumor activity.•Binding studies indicate that [(sec-butylphen)AuCl3] binds to serum albumin protein.•Binding of [(sec-butylphen)AuCl3]} to BSA is stronger than observed with cisplatin.In an on-going effort to discover metallotherapeutic alternatives to the chemotherapy drug cisplatin, neutral distorted square pyramidal gold(III) coordination complexes possessing 2,9-disubstituted-1,10-phenanthroline ligands {[(Rphen)AuCl3]; R = n-butyl, sec-butyl} have been previously synthesized and characterized. A structurally analogous gold(III) complex bearing a 6,6′-di-methylbipyridine ligand ([(methylbipy)AuCl3]) has been synthesized and fully characterized to probe the effect of differing aromatic character of the ligand on solution stability and tumor cell cytotoxicity. The two compounds [(sec-butylphen)AuCl3] and [(methylbipy)AuCl3]) were subsequently assessed for their stability against the biological reductant glutathione, and it was found that the [(sec-butylphen)AuCl3] complex exhibits slightly enhanced stability compared to the [(methylbipy)AuCl3] complex and significantly higher stability than previously reported square planar gold(III) complex ions. Furthermore, these complexes were tested for cytotoxic effects against existing lung and head and neck cancer cell lines in vitro. The [(sec-butylphen)AuCl3] complex was found to be more cytotoxic than cisplatin against five different tumor cell lines, whereas [(methylbipy)AuCl3] had more limited in vitro antitumor activity. Given that [(sec-butylphen)AuCl3] had significantly higher antitumor activity, it was tested against an in vivo tumor model. It was found that this complex did not significantly reduce the growth of xenograft tumors in mice and initial model binding studies with bovine serum albumin indicate that interactions with serum albumin proteins may be the cause for the limited in vivo activity of this potential metallotherapeutic.A neutral five-coordinate gold(III) complex possessing the 2,9-di-sec-butyl-1,10-phenanthroline ligand [(sec-butylphen)AuCl3], exhibited impressive in vitro antitumor activity but limited in vivo efficacy. It was found that [(sec-butylphen)AuCl3] has significant binding to a model serum albumin protein. This provides a possible explanation for the limited in vivo activity of this gold-based chemotherapy.

Two different online homework systems were administered to students in a first-quarter general chemistry course. This study used a multiple regression model to control for the students’ academic and socioeconomic background, and it was found that students who completed the online homework activities performed significantly better on a common comprehensive final exam than students who did not participate. More specifically, it was found that students who completed a precourse assignment on an adaptive-responsive homework system (ALEKS; Assessment and Learning in Knowledge Spaces) could expect on average their final exam score to increase by over 13 points when compared to nonparticipating students. Students who completed a precourse assignment on a traditional responsive homework system (MasteringChemistry) also saw an average increase in their final exam score by roughly 8 points versus those who did not participate. Students who worked on the online homework for the entire quarter saw even greater gains in their final exam scores compared to nonparticipants. These findings suggest responsive online homework in general, and a responsive–adaptive learning system driven by knowledge space theory in particular, has a significant positive impact on student performance in the first-quarter general chemistry course.Keywords: Chemical Education Research; Computer-Based Learning; First-Year Undergraduate/General;

A gold(III) complex possessing 5,6-dimethyl-1,10-phenanthroline (5,6DMP) was synthesized and fully characterized using standard spectroscopic techniques, as well as X-ray crystallography and elemental analysis. The complex [(5,6DMP)AuCl2][BF4] (2) was found to possess a distorted square planar geometry about the gold(III) center, commonplace for d8 Au(III) cations possessing sterically un-hindered polypyridyl ligands. Compound 2 was evaluated for its potential use as an anticancer therapeutic. It was determined that the complex is stable in phosphate buffer over a 24-hour period, thought it does undergo rapid reduction in the presence of equimolar amounts of reduced glutathione (GSH) and ascorbic acid. The DNA binding and in vitro tumor cytotoxicity of the title compound 2 were also determined. It was found to undergo weak and reversible binding to calf thymus DNA, and was more cytotoxic towards a panel of human cancer cell lines than the commonly used chemotherapy agent cisplatin. Cytotoxicity experiments with the free 5,6DMP ligand indicate that the ligand has IC50 values that are slightly lower than those observed for the gold complex (2), and coupled with the fact that the ligand appears to be released from the gold(III) metal center in reducing environments, this suggests the ligand itself may play an important role in the antitumor activity of the parent gold complex.Both the gold(III) complex ion, [(5,6DMP)AuCl2]+, and the free 5,6DMP ligand are found to be more cytotoxic than cisplatin against in vitro lung and head–neck tumor cell lines. Stability experiments also indicate that the ligand is released upon the reduction of the gold(III) metal center. These results agree with previous studies involving gold(III) polypyridyl complexes, and highlight the need to determine whether the gold(III) complex or the free ligand act as the cytotoxic agent.

In an effort to develop novel gold-based chemotherapies, gold(III) coordination complexes possessing a series of di-2-pyridyl ligands were targeted as synthetic products. It was found that di-2-pyridyl ligands linked by different groups exhibited varying coordination to gold(III). Di-2-pyridyl sulfide (DPS) exhibited bidentate binding to gold(III), and formed a complex ion with a gold tetrachloride counter ion {[(DPS)AuCl2]AuCl4; compound 3}; di-2-pyridyl ether (DPO) formed a neutral monodentate coordination complex with gold(III) {[(DPO)(AuCl3)]; compound 4}; and attempts to make a gold(III) complex with di-2-pyridyl ketone (DPK) were unsuccessful, as a complex ion possessing the protonated ligand and a gold tetrachloride anion was isolated {[HDPK][AuCl4]; compound 5}. Compounds 3–5 were structurally characterized using X-ray crystallography, which confirmed the different coordination environments around the gold(III) metal centers.Graphical abstractThe synthesis of gold(III) complexes possessing three different classes of di-2-pyridyl ligands is reported. The di-2-pyridyl sulfide ligand coordinates gold(III) in a bidentate fashion, and forms a complex ion possessing a AuCl4− counterion; the di-2-pyridyl ketone ligand did not coordinate directly to the gold(III) metal center; and the di-2-pyridyl ether ligand formed a neutral complex in which the ligand binds to gold(III) in a monodentate fashion.Research highlights► Di-2-pyridyl ligands linked by different groups exhibited varying coordination to gold(III). ► Di-2-pyridyl sulfide (DPS) (3) exhibited bidentate binding to gold(III). ► Di-2-pyridyl ether (DPO) (4) formed a neutral monodentate coordination complex with gold(III). ► Attempts to make gold(III) complexes with di-2-pyridyl ketone (DPK) (5) were unsuccessful. ► The coordination environments of compounds 3–5 were confirmed by X-ray crystallography.