Dr. Tanay Kesharwani

Benzofuran is an important backbone for molecules that make up several pharmaceuticals, herbicides/pesticides, and organo-electronics. An environmentally benign dimethyl(methylthio)sulfonium tetrafluoroborate salt was used as an electrophile to induce cyclization of o-alkynyl anisoles to form 2,3-disubstituted benzofurans. The cyclization is performed at ambient reaction conditions, only takes 12 hours to get excellent yields, and shows a high tolerance for various substituted alkynes. Also, a trimethyl group obtained after the cyclization reactions allows for a cascade cyclization, and an alkyne is used in the reaction to create a thieno[3,2-b]benzofuran core structure.

Electrostatic interactions between oppositely charged entities play a key role in pre-organizing substrates and stabilizing transition states of reactions in enzymes. The use of electrostatic interactions to pre-organize ions in nanoconfined pores, however, has not been investigated to its full potential. Herein, we describe how carboxylate anions can be pre-organized at the behest of their electrostatic interactions with K+ cations in nanoconfined tunnels present in γ-cyclodextrin metal-organic frameworks, i.e., CD-MOFs. Several carboxylate anions, which are all much smaller than the cavities of the tunnels, were visualized by X-ray crystallography when nanoconfined in CD-MOFs, despite the large voids present in the tunnels. These anions were found to be aligned within a planar array defined by four K+ cations, positioned around the periphery of the tunnels. The strong electrostatic interactions between the carboxylate anions and the K+ cations dictate the orientation of the anions and override the influence of other possible noncovalent bonding interactions between them and the tunnels. Consequently, the aligned pairs of γ-cyclodextrin rings constituting the tunnels become distorted, resulting in their lower symmetry and fewer disordered carboxylate anions in the solid-state. Our findings offer a transformative strategy for controlling the packing and orientation of ions in nanoconfined environments.

Antimicrobial Resistance (AMR) is the next impending health crisis knocking at our doors and the biggest challenge in fighting AMR infections is the scarcity of novel and effective antibiotics. The objective of this study is to evaluate novel class of compounds called benzothiophenes for their potential antimicrobial activity. Previous studies have indicated great promise of benzothiophene derivatives as an important biological core structure. Benzo[b]thiophene core structure is present in several FDA-approved drugs, such as raloxifene, zileuton, and sertaconazole. In this study, the novel benzothiophene derivatives were synthesized using common organic synthesis methods such as Sonogashira coupling and electrophilic cyclization reactions. Proton nuclear magnetic resonance (1H-NMR), carbon nuclear magnetic resonance (13C-NMR), gas chromatography-mass spectroscopy (GC-MS), and high-performance liquid chromatography (HPLC) were used to determine compound identity and purity. The compounds were tested against gram positive bacteria (S. aureus, M. luteus, and E. faecalis), gram-negative bacteria (E. coli, and P. aeruginosa) and fungi such as C. albicans and C. tropicalis, via a broth microdilution susceptibility assay in a 96-well plate. Briefly, varying concentrations of the compound were incubated with the cells. After incubation, the plates were read using a plate reader to determine the absorbance and minimum inhibitory concentration (MIC) values. The low MIC values for the benzo[b]thiophene derivative compounds signify a promising antimicrobial activity. Further biological studies were performed to determine the toxicity of the compounds to human cell lines. Preliminary results showed that addition of some groups increased the antibacterial activity of the benzo[b]thiophene derivatives while addition of other groups decreased the activity of the compounds. In conclusion, this project will help to identify more potent benzo[b]thiophene derivatives with broader efficacy against both bacteria and fungi. This research accomplishes crucial steps toward developing potent benzo[b]thiophenes as a possible clinical candidate as an antimicrobial drug.

Billions of years of evolution have honed nature’s extraordinary capacity in promoting site-selective functionalization of C(sp3)–H bonds in complex molecules. Central to this incredible proficiency is the effect of confinement incurred by enzymes’ active sites, which pre-organize substrates in desired co-conformations prior to their selective transformations. The fact that C(sp3)–H bonds with negligible stereoelectronic differences can be differentiated at an Ångström level during enzymatic catalysis means that precise control of site selectivities in C(sp3)–H functionalization can in principle be achieved by tailoring the cavity sizes, geometries, and stereoelectronic environments of artificial receptors. Given the importance of late-stage functionalization in drug development, there is every reason to believe that confinement, among other strategies, will become an increasingly important tool for tackling challenges in the selective editing of C(sp3)–H bonds in complex settings.

Covalent organic frameworks (COFs) have unique features, including intrinsic porosity, crystallinity, and tunability, making them desirable materials for diverse applications ranging from environmental remediation to energy harvesting. Among these applications, COFs are extensively studied for their photocatalytic hydrogen evolution by converting solar energy into clean and renewable fuel via water splitting. COFs have several advantages over conventional inorganic catalysts, such as tunable band structures, high surface areas, and low cost. However, the research in this field is still in the early stages, and COFs still face some challenges, such as low charge carrier mobility, high exciton binding energy, and poor stability. To overcome these challenges, various design strategies relying on a mechanistic approach have been developed to design and modify COFs for enhanced photocatalytic performance. These include extending the p-conjugation, incorporating heteroatoms or metal complexes, and donor-acceptor (D-A) configuration, which ultimately improves the light absorption charge separation of COFs. Additionally, blending COFs with other functional materials, such as inorganic-organic semiconductors, can create synergistic effects to boost photocatalytic activity. In this review, the design aspects of the fabrication of COFs as effective photocatalysts have been reported.

Near-infrared (NIR) light is known to have outstanding optical penetration in biological tissues and to be non-invasive to cells compared with visible light. These characteristics make NIR-specific light optimal for numerous biological applications, such as the sensing of biomolecules or in theranostics. Over the years, significant progress has been achieved in the synthesis of fluorescent cyclophanes for sensing, bioimaging, and making optoelectronic materials. The preparation of NIR-emissive porphyrin-free cyclophanes is, however, still challenging. In an attempt for fluorescence emissions to reach into the NIR spectral region, employing organic tetracationic cyclophanes, we have inserted two 9,10-divinylanthracene units between two of the pyridinium units in cyclobis­(paraquat-p-phenylene). Steady-state absorption, fluorescence, and transient-absorption spectroscopies reveal the deep-red and NIR photoluminescence of this cyclophane. This tetracationic cyclophane is highly soluble in water and has been employed successfully as a probe for live-cell imaging in a breast cancer cell line (MCF-7).

This paper describes the synthesis of several halogenated S and Se heterocycles and tests their biological activity by measuring the effects on the myeloid leukemia cell line, PLB-985 cells. We report that select compounds exhibit significant increases in mitochondria membrane potential and increased oxidative stress in PLB-985 cells. In addition, several compounds caused cytotoxicity at high cell densities. Our results contribute to the foundational knowledge of different S and Se containing compounds and their possible impacts on human cells.

A stable dimethyl(thiodimethyl)sulfonium tetrafluoroborate saltwas employed for the electrophilic cyclization reaction ofo-alkynyl thioanisoles forthe synthesis of 2,3-disubstituted benzo[b]thiophenes. The reaction describedherein works well with various substituted alkynes in excellent yields, and avaluable thiomethyl group was introduced with ease. The reaction utilizesmoderate reaction conditions and ambient temperature while tolerating variousfunctionalities. To elucidate the mechanism, electrophilic addition reactions usingthe dimethyl(thiodimethyl)sulfonium tetrafluoroborate salt with diphenylacetylenewas demonstrated.

In this study, a new environmentally benign iodine-mediated one-pot iodocyclization/alkylation strategy for the synthesis of benzo[b]thiophene derivatives starting from 2-alkynylthioanisoles was developed. The synthesis of a diverse population of 2,3-disubstituted benzo[b]thiophenes was achieved in high yields by employing moderate reaction conditions using 1,3-dicarbonyl substrates as the nucleophile and various substituted propargyl alcohols as both the cyclization precursor and the alkylating agent. This method resulted in the formation of a series of complex structures obtained in a single step. Additionally, a strategy was devised for the one pot iodocyclization/oxidation of propargyl alcohols into carbonyl functionalized benzo[b]thiophene structures. These green one-pot reaction processes were designed to reduce wastes and byproducts while generating a complex substitution pattern on the benzo[b]thiophene structure. The reported methodologies may be used to synthesize more functionalized benzo[b]thiophene structures that can be used in both biomedical and organic electronic applications.

Nuclear magnetic resonance (NMR) spectroscopy has become a cornerstone tool for studying a variety of molecular features in advanced chemistry laboratories. In this experiment, students prepare a pyrrole-beta-amide via a one-pot, three-step synthesis and use NMR spectroscopy to confirm its molecular structure. In addition, variable temperature (VT) H-1 NMR spectroscopy is used to study the dynamic amide bond, a functional group with restricted rotation about the C-N bond. The VT NMR data allow the students to determine the coalescence temperature associated with the slow equilibrium at room temperature and the corresponding energy barrier (Delta G(double dagger)) for the restricted rotation about the C-N bond.