Linking Chemistry to Community: Integration of Culturally Responsive Teaching into General Chemistry I Laboratory in a Remote Setting.

The COVID-19 pandemic redefined how chemistry laboratories were taught. It also introduced a racial health disparity for Black and Brown people. The General Chemistry I laboratory curriculum at a Historically Black College and University (HBCU) in Baltimore, MD, was redesigned to meet student needs during this challenging time. While surrounded by civil unrest and uncertainty, we wanted to reach our underrepresented students in a way that they felt seen and heard. "The Mystery of Mr. Johnson" series was designed to reinforce the role chemistry can serve in advancing equity in their community. This interconnected series of three experiments (Solutions, Titration, Spectroscopy) developed chemistry laboratory skills which were applied to diabetes, a COVID-19 comorbidity, and health disparity highly prevalent in Baltimore. "The Mystery of Mr. Johnson" series provided opportunities for students to gain exposure to the role of chemistry in addressing a health disparity that impacts their community. The culminating project was a public service announcement to communicate lifestyle changes and the prevalence of diabetes in the black community.

Microwave-Assisted Synthesis of Organometallic Rhenium (I) Pentylcarbonato Complexes: New Synthon for Carboxylato, Sulfonato and Chlorido Complexes.

Tricarbonylrhenium(I)(α-diimine) complexes are of importance because of their strong cytotoxic and fluorescence properties. Syntheses of such complexes were achieved through a two-step process. First, the pentylcarbonato complexes, fac-(CO)3(α-diimine)ReOC(O)OC5H11 were synthesized through a microwave-assisted reaction of Re2(CO)10, α-diimine, 1-pentanol and CO2 in a few hours. Second, the pentylcarbonato complexes are treated with carboxylic, sulfonic and halo acids to obtain the corresponding carboxylato, sulfonato and halido complexes. This is the first example of conversion of Re2(CO)10 into a rhenium carbonyl complex through microwave-assisted reaction.

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents.

Microtubule stabilizing agents, such as paclitaxel, docetaxel, and cabazitaxel have been among the most used chemotherapeutic agents in the last decades for the treatment of a wide range of cancers in the clinic. One of the concerns that limit their use in clinical practice is their intrinsic and acquired drug resistance, which is common to most anti-cancer chemotherapeutics. Taccalonolides are a new class of microtubule stabilizers isolated from the roots of a few species in the genus of Tacca. In early studies, taccalonolides demonstrated different effects on interphase and mitotic microtubules from those of paclitaxel and laulimalide suggesting a unique mechanism of action. This prompts the exploration of new taccalonolides with various functionalities through the identification of minor constituents of natural origin and semi-synthesis. The experiments on the new highly potent taccalonolides indicated that taccalonolides possessed a unique mechanism of covalently binding to the microtubule. An X-ray diffraction analysis of a crystal of taccalonolides AJ binding to tubulin indicated that the covalent binding site is at ß-tubulin D226. Taccalonolides circumvent all three mechanisms of taxane drug resistance both in vitro and in vivo. To improve the activity, the structure modification through semi-synthesis was conducted and the structure-activity relationships (SARs) was analyzed based on natural and semi-synthetical taccalonolides. The C22-C23 epoxide can significantly increase the antiproliferation potency of taccalonolides due to the covalent link of C22 and the carboxylic group of D226. Great progress has been seen in the last few years in the understanding of the mechanism of this class of microtube-stabilizing agents. This review summarizes the structure diversity, structure-activity relationships (SARs), mechanism of action, and in vivo activities of taccalonolides.

The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines.

PURPOSE: Because of the scarcity of suitable brain cancer drugs, researchers are frantically trying to discover novel and highly potent drugs free of side effects and drug-resistance. Rhenium compounds are known to be nontoxic and exhibit no drug resistance. For that reason, we have developed a series of novel rhenium acetylsalicylato (RAC or ASP) complexes to test their cytotoxicity on brain cancer cells. Also we have attempted to explore the DNAbinding properties of these compounds because many drugs either directly or indirectly bind to DNA. METHODS: We have treated the RAC series compounds on human astrocytoma brain cancer cell lines and rat normal brain astrocyte cells and determined the efficacy of these complexes through in vitro cytotoxicity assay. We carried out the DNA-binding study through UV titrations of a RAC compound with DNA. Also we attempted to determine the planarity of the polypyridyl ligands of the RAC series compounds using DFT calculations. RESULTS: RAC6 is more potent than any other RAC series compounds on HTB-12 human astrocytoma cancer cells as well as on Glioblastoma Multiforme D54 cell lines. In fact, The IC-50 value of RAC6 on HTB-12 cancer cells is approximately 2 µM. As expected, the RAC series compounds were not active on normal cells. The DFT calculations on the RAC series compounds were done and suggest that the polypyridyl ligands in the complexes are planar. The UV-titrations of RAC9 with DNA were carried out. It suggests that RAC9 and possibly all RAC series compounds bind to minor grooves of the DNA. CONCLUSION: Because of the very low activity of RAC6 on normal cells and low lC50 value of on astrocytoma (HTB-12) cell lines, it is possible that RAC6 and its derivatives may potentially find application in the treatment of brain cancers. The DFT calculations and UV titrations suggest that RAC series compounds either bind to DNA intercalatively or minor grooves of the DNA or both. However, it is highly premature to make any definite statement in the absence of other techniques.

Unprecedented anticancer activities of organorhenium sulfonato and carboxylato complexes against hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells.

Cisplatin and other metal-based drugs often display side effects and tumor resistance after prolonged use. Because rhenium-based anticancer complexes are often less toxic, a novel series of organorhenium complexes were synthesized of the types: XRe(CO)3Z (X = α-diimines and Z = p-toluenesulfonate, 1-naphthalenesulfonate, 2-naphthalenesulfonate, picolinate, nicotinate, aspirinate, naproxenate, flufenamate, ibuprofenate, mefenamate, tolfenamate, N-acetyl-tryptophanate), and their biological properties were examined. Specifically, in hormone-dependent MCF-7 and hormone-independent triple-negative MDA-MB-231 breast cancer cells, the p-toluenesulfonato, 1-naphthalenesulfonato, 2-naphthalenesulfonato, picolinato, nicotinato, acetylsalicylato, flufenamato, ibuprofenato, mefenamato, and N-acetyl-tryptophanato complexes were found to be far more potent than conventional drug cisplatin. DNA-binding studies were performed in each case via UV-Vis titrations, cyclic voltammetry, gel electrophoresis, and viscosity, which suggest DNA partial intercalation interaction, and the structure-activity relationship studies suggest that the anticancer activities increase with the increasing lipophilicities of the compounds, roughly consistent with their DNA-binding activities.

Microwave-assisted synthesis of rhodamine derivatives.

The microwave synthesis of 12 rhodamine-derived imines is described. The present work involves condensation of rhodamine hydrazide with various aromatic aldehydes in ethanol under microwave irradiation. The results obtained indicate that, unlike classical heating, microwave irradiation results in higher yields, shorter reaction time, mild reaction condition and simple work-up procedure. The structures of synthesized compounds were confirmed by 1H-NMR, 13C-NMR, FT-IR and high-resolution mass spectra data.

Anticancer Properties of Novel Rhenium Pentylcarbanato Compounds against MDA-MB-468(HTB-132) Triple Node Negative Human Breast Cancer Cell Lines.

AIM: To study the efficacy of novel rhenium compounds to treat triple node negative breast cancer. PLACE AND DURATION: Six (6) novel rhenium pentycarbanato compounds (PC1-6) were synthesized and triple node negative breast cancer cell lines HTB-132 and Balb/c mouse kidney cell lines were treated with each of them for 48 hours. The results were analyzed by a common trypan blue cell death assay system and statistically analyzed. PLACE AND DURATION: The compounds were synthesized, analyzed and evaluated at the Department of Chemistryof Morgan State University, Baltimore, Maryland and the Pharmaceutical Sciences Department of Elizabeth City State University campus of the University of North Carolina system. METHODOLOGY: The novel rhenium compounds were synthesized from one-pot reactions of Re2(CO)10 with the corresponding α-diimine ligands in 1-pentanol.The compounds were characterized spectroscopically. The cell lines were cultured by standard cell culture procedure and treated with each of the six compounds in DMSO for 48 hours with a negative control and a DMSO vehicular control along with a cisplatin positive control.The cytotoxicity was evaluated by standard trypan blue assay and the results were statistically analyzed. RESULTS: The trypan blueassay reveals that these compounds have significant cytotoxicity against MDA-MB-468 (HTB-132) triple node negative breast cancer cell lines and are less nephrotoxic than cisplatin. CONCLUSION: The novel rhenium compounds PC 1-6 can potentially find applications in the treatment of highly malignant triple node negative breast cancer.

DNA-binding and cytotoxic efficacy studies of organorhenium pentylcarbonate compounds.

Seven organorhenium pentylcarbonate compounds (PC1-PC7) have been synthesized. DNA-binding studies of the PC-series compounds using electronic spectroscopy and gel electrophoresis suggest that the compounds presumably bind to DNA in an intercalative mode. The intrinsic binding constants for PC4, PC6, and PC7 were found to be 1.6 × 10(4), 3.9 × 10(4), and 4.2 × 10(4) M(-1), respectively. The X-ray structure determinations and density functional theory calculations indicate that the polypyridyl ligands in the compounds are nearly planar facilitating DNA binding through an intercalation mechanism. Cytotoxicity studies of 10 µM pentylcarbonate compounds against HTB-12 human astrocytoma brain cancer cells were studied for 48 h. It was observed that each of the pentylcarbonate compounds is active against the cancer cells. However, under analogous conditions, CRL-2005 rat astrocyte normal brain cells are not affected significantly.

Synthesis of quaternary heterocyclic salts.

The microwave synthesis of twenty quaternary ammonium salts is described. The syntheses feature comparable yields to conventional synthetic methods reported in the current literature with reduced reaction times and the absence of solvent or minimal solvent.

The effect of novel rhenium compounds on lymphosarcoma, PC-3 prostate and myeloid leukemia cancer cell lines and an investigation on the DNA binding properties of one of these compounds through electronic spectroscopy.

Despite the tremendous success of cisplatin and other platinum-based anticancer drugs, severe toxicity and resistance to tumors limit their applications. It is believed that the coordination (formation of covalent bond) of the metal (platinum) to the nitrogen bases of DNA cause the ruptures of the cancer as well as normal cells. A search for anticancer drugs with different modes of action resulted in the synthesis of variety of novel compounds. Many of them are in clinical trials now. Recently we synthesized a series of novel rhenium pentylcarbonato compounds (PC1-PC6). The rhenium atom in each compound is coordinated (bonded) to a planar polypyridyl aromatic ligand, thereby forcing each compound to intercalate between the DNA bases. We have investigated the DNA binding properties of one of the PC-series of compounds (PC6) using electronic spectroscopy. The UV absorption titration of PC6 with DNA shows hypochromic effect with concomitant bathochromic shift of the charge transfer band at 290 nm. These results suggest that the compound PC6 binds to DNA through intercalation. It is therefore likely that the other PC-series of compounds will behave in a similar manner. Thus it is expected that these compounds will exhibit negligible or no side effect. We have observed that the PC-series of compounds are strong cytotoxic agents against lymphosarcoma (average GI50 ≈ 2±2.6 µM), PC-3 prostate (average GI50 ≈ 3±2.8 µM) and myeloid leukemia (average GI50 ≈ 3±2.8 µM) cancer cell lines. The average GI50 values of the PC-series of compounds are 2-3 less than the corresponding GI50 values of cisplatin. Also each of the PC-series of compounds exhibits less toxicity than cisplatin in the glomerular mesangial cells.

Microwave synthesis of cyanine dyes.

Heptamethine cyanine dyes are a class of near infrared (NIR) dyes that have captured the interest of the scientific community. Although applications that utilize NIR fluorescence technology are rapidly expanding, progress is limited by the lack of availability and cost of suitable compounds that can be utilized as labels and/or probes. Herein, we report the use of microwave assisted organic synthesis of five NIR cyanine dyes in yields ranging from 64-83% with a significant reduction in solvent use. Spectra characteristics including absorbance and emission spectra, molar absorptivity, quantum yield, fluorescence lifetime, and redox potentials were determined for each synthesized NIR cyanine dye.

1-(5-Carboxy-pent-yl)-2,3,3-trimethyl-3H-indol-1-ium bromide monohydrate.

In the title compound, C(17)H(24)NO(2) (+)·Br(-)·H(2)O, the pentyl group chain in the cation extends nearly perpendicular [N-C-C-C = -64.4 (3)°] to the mean plane of the indole ring with the carboxyl end group twisted such that the dihedral angle between the mean planes of the indole and carb-oxy groups measures 43.2 (4)°. Both ions in the salt form inter-molecular hydrogen bonds (O-H⋯Br and O-H⋯O) with the water mol-ecule. As a result of the Br⋯H-O-H⋯Br inter-actions, a zigzag chain is formed in the c-axis direction. The crystal packing is influenced by the collective action of the O-H⋯O and O-H⋯Br inter-molecular inter-actions as well as π-π stacking inter-molecular inter-actions between adjacent benzyl rings of the indole group [centroid-centroid distance = 3.721 (13) Å] and inter-molecular C-H⋯π inter-actions between a methyl hydrogen and the benzyl ring of the indole group. The O-H⋯Br inter-actions form a distorted tetra-hedral array about the central Br atom. A MOPAC AM1 calculation provides support to these observations.

Microwave synthesis of quaternary ammonium salts.

The microwave synthesis of several quaternary ammonium salts is described. The synthesis provides comparable or better yields than published methods with reduced reaction times and in the absence of solvent.

Microwave synthesis of near infrared heptamethine cyanine dye.

Cyanine dyes are an interesting class of near infrared (NIR) dyes that have captured the interest of the scientific community. The NIR cyanine dye of interest, heptamethine cyanine dye NIR-1, exhibits characteristics that satisfy the qualifications as an acceptor in a Fluorescence Resonance Energy Transfer (FRET) biosensor [Wher, 1976]. Applications of FRET systems include structure determination and conformation of proteins [Hammer et al., 2002], receptor/ligand interactions [Hammer et al., 2002], and the cellular exposure to environmental toxins [Schwartz and Ulfelder, 1992]. This research stems from an interdepartmental collaboration to develop a NIR FRET biosensor, with significant advantages over the existing systems. A critical component of this endeavor is the development of an efficient environmentally conscious synthesis of novel NIR cyanine dyes utilizing microwave technology. Herein, we report the microwave synthesis of NIR-1. 2,3,3-Trimethyl-1-ethyl-3H-indolium iodide (I) synthesis is advantageous over the reported synthesis due to the significantly reduced reaction time of 450 s from 15 h and a decrease in the amount of iodoethane from 5 eq. to 3 eq. The condensation of heterocyclic salt I and bisaldehyde II has been accomplished in 220 s in 85% yield in the microwave oven; benzene has been eliminated from the condensation reaction procedure. Spectral characteristics of NIR-1 were determined and compared to commercially available NIR-1. A significant absence of asymmetry at the broad peak associated with the maximum absorbance wavelength, a slight increase in quantum yield (+ approximately .02) and the blue shift of the maximum absorbance wavelength (- approximately 5 nm) was observed.