Organic Chemistry is recognized as a course that presents many difficulties and conceptual challenges for students. To combat the high failure rates and poor student attitudes associated with this challenging course, we implemented a "flipped" model for the first-semester, largeenrollment, Organic Chemistry course. In this flipped course, lectures were replaced by short videos, which were delivered via a course management system, and class time was reserved for problem solving and other active learning activities. We assessed the impact of the flipped course on course grades and failure rate compared to historical course data. The results showed that there was a statistically significant improvement in A and B grades and a decrease in failure/withdrawal rates for the flipped course. We also assessed students' attitudes toward the course using a valid and reliable instrument, the Attitude toward the Subject of Chemistry Inventory Version 2 (ASCIv2). The results showed a statistically significant increase in students' emotional satisfaction and intellectual accessibility for the flipped course compared to those for traditional lecture courses. The flipped format of the course provided students with increased access to course material, which increased time for in-class group learning and discussion. We believe that this aspect of the course format led to a reduction in cognitive load, thereby increasing students' emotional satisfaction and intellectual accessibility in the course. Our results demonstrate that the flipped course model can be adopted for challenging, large-enrollment courses.

General chemistry is the first undergraduate course in which students further develop their understanding of fundamental chemical concepts. Many of these fundamental topics highlight the numerous conceptual interconnections present in chemistry. However, many students possess incoherent knowledge structures regarding these topics. Therefore, effective assessments are needed to identify these interconnections. The use of concept-mapping and think-aloud interviews to investigate the knowledge structures of undergraduate organic chemistry students' regarding bonding concepts is the focus of this research study. Herein, we spotlight the bonding concepts of electronegativity and polar covalent bonds. In essence, the study found that understanding of electronegativity was weak among students with low concept map scores (LS students) compared to students with high concept map scores (HS students). Additionally, several common misconceptions of electronegativity were revealed through student interviews. An examination of LS student interviews further revealed that a lack of understanding of electronegativity led to a misunderstanding of polar covalent bonding. The think-aloud interviews were a reflection of the connections students made with the concepts of electronegativity and polar covalent bonding in their concept maps. Implications for the chemistry curriculum are also presented.

Solid tumors generally grow under hypoxic conditions, a pathophysiological change, which activates the expression of genes responsible for malignant, aggressive, and treatment-refractory properties. Hypoxia inducible factor (HIF) is the chief transcription factor regulating hypoxia-driven gene expression. Therefore, the HIF pathway has become a critical target for cancer therapeutics development. We screened a privileged library of about 10,000 natural-product-like compounds using a cell-based assay for HIF-dependent transcriptional activity and identified several arylsulfonamide HIF pathway inhibitors. Among these compounds, the most potent ones showed an IC50 of ~0.5 μM in the hypoxia-responsive element (HRE)-luciferase reporter system. Further studies are needed to fully elucidate the mechanism of action of this class of compounds and their structure-activity relationship.

Hypoxia, a reduction in partial oxygen pressure, is a salient property of solid tumors. Hypoxia drives malignant progression and metastasis in tumors and participates in tumor resistance to radio- and chemotherapies. Hypoxia activates the hypoxia-inducible factor (HIF) family of transcription factors, which induce target genes that regulate adaptive biological processes such as anaerobic metabolism, cell motility and angiogenesis. Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance. Consequently, HIF-1 has become an important therapeutic target for inhibition by small molecules. Herein, we describe the design and synthesis of small molecules that inhibit the HIF-1 signaling pathway. Many of these compounds exhibit inhibitory activity in the nanomolar range. Separate mechanistic studies indicate that these inhibitors do not alter HIF-1 levels, but interfere with the HIF-1α/HIF-1β/p300/CBP complex formation by interacting with p300 and CBP.

Chemistry education research has sought to understand why students struggle in organic chemistry courses. Beyond the volume and difficulty of the material taught in this course, there are also affective factors, such as attitude toward chemistry, that can influence how students perform. Studies have documented cases in which students of underrepresented minority backgrounds in science fields have less positive attitudes than their majority peers. Thus, in this study, we investigated whether the significant positive attitude gains found in a flipped classroom compared to a traditional lecture course extended to the Black female students in the sample when compared to the rest of their peers. Our study employs measurement invariance testing, which reveals whether an instrument's internal structure holds for different groups, to support valid comparisons. The study documents that Black female students began the course with lower attitude scores than their peers. Results of this study indicate that, while Black female students experience similar attitude gains to the rest of their peers in the flipped classroom, initial attitude differences are not completely erased by this single experience. Our study also uses structural equation modeling to describe the relationship between attitude and achievement in this flipped organic chemistry classroom. The attitude− achievement relationship was successfully modeled by a reciprocal causation framework in which emotional satisfaction had a small but significant and positive relationship with subsequent achievement measures. In light of the observed relationship between attitude and achievement, this finding suggests that continued research into both attitudinal and achievement factors for students from populations underrepresented in the sciences is warranted.

Students can perceive the laboratory environment in a variety of ways that can affect what they take away from the laboratory course. This qualitative study characterizes undergraduate students’ perspectives of a project-based Organic Chemistry laboratory using the theoretical framework of phenomenography. Eighteen participants were interviewed in a semi-structured format to collect their perspectives of the Organic Chemistry lab. Eight qualitatively different ways in which students perceived the lab were uncovered and an outcome space was derived. The findings of this work are intended to inform the design of the undergraduate laboratory curriculum in chemistry that facilitate better student learning. Implications and suggestions for design of laboratory courses based on the results of this work are also presented.

The interaction of CXCR4 with CXCL12 (SDF-1) plays a critical role in cancer metastasis by facilitating the homing of tumor cells to metastatic sites. Based on our previously published work on CXCR4 antagonists, we have synthesized a series of aryl sulfonamides that inhibit the CXCR4/CXCL12 interaction. Analog bioactivities were assessed with binding affinity and Matrigel invasion assays. Computer modeling was employed to evaluate a selection of the new analogs docked into the CXCR4 X-ray structure and to rationalize discrepancies between the affinity and Matrigel in vitro assays. A lead compound 5a displays subnanomolar potency in the binding affinity assay (IC50 = 8.0 nM) and the Matrigel invasion assay (100% blockade of invasion at 10 nM). These data demonstrate that benzenesulfonamides are a unique class of CXCR4 antagonists with high potency.

CXCR4 inhibitors are promising agents for the treatment of cancer metastasis and inflammation. A series of novel tertiary amine derivatives targeting CXCR4 were designed, synthesized, and evaluated. The central benzene ring linker and side chains were modified and optimized to study the structure-activity relationship. Seven compounds displayed much more potent activity than the reference drug, AMD3100, in both the binding affinity assay and the blocking of Matrigel invasion functional assay. These compounds exhibited effective concentration ranging from 1 to 100 nM in the binding affinity assay and inhibited invasion from 65.3% to 100% compared to AMD3100 at 100 nM. Compound IIn showed a 50% suppressive effect against carrageenan-induced paw inflammation in a mouse model, which was as effective as the peptidic antagonist, TN14003 (48%). These data demonstrate that symmetrical bis-tertiary amines are unique CXCR4 inhibitors with high potency.